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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093
PMCID: PMC4892127


Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.1

Extracellular volume associates with outcomes more strongly than native or post-contrast myocardial T1


Objectives: Myocardial fibrosis in noninfarcted myocardium is emerging as a principal phenotype of vulnerability to adverse events such as mortality and hospitalization for heart failure (HHF), but its optimal noninvasive measurement remains uncertain despite consistently robust histologic validation data for extracellular volume fraction (ECV). We therefore compared ECV, native T1, post contrast T1, the gadolinium contrast partition coefficient (lambda), and the presence of nonischemic scar in their associations with mortality and HHF outcomes.

Method: To quantify of myocardial fibrosis, we performed T1 mapping (MOLLI) in basal and mid short axis slices with cardiovascular magnetic resonance (CMR) before contrast and 12-30 minutes post contrast bolus in 1185 consecutive patients without amyloidosis, hypertrophic or stress cardiomyopathy. We assessed associations with outcomes using Kaplan-Meier plots and chi square values from univariable Cox regression models. All standard T1 mapping parameters were obtained: native and post contrast myocardial T1, the partition coefficient lambda, and ECV. ECV = (1-hematocrit) · [ΔR1myocardium]/[ΔR1bloodpool], where R1 = 1/T1 Late gadolinium enhancement imaging with phase sensitive reconstruction identified nonischemic scar.

Results: Over a median of 1.7 years, 111 individuals experienced events after CMR: 55 HHF events and 74 deaths. ECV yielded better separation of Kaplan-Meier curves in a dose dependent fashion (Figure) and also stronger associations with the combined endpoint of death or HHF. The ECV chi square (77.3, p < 0.001) was at least twice as large as the Native T1 chi square (37.5, p < 0.001), the lambda chi square (34.8, p < 0.001) and nonischemic scar (chi square = 20.5, p<0.001). Post-contrast T1 was not associated with outcomes, even when adjusting further for time after contrast bolus, renal function, and patient weight (chi square <3, p >0.10).

Conclusion: Analogous to histologic previously published validation data, quantitative ECV myocardial fibrosis measures associated with outcomes far stronger than other surrogate measures outcome measures such as native T1, post contrast T1 and nonischemic scar on LGE images. These data suggest that ECV is the noninvasive metric of choice to measure myocardial fibrosis.

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Figure. Kaplan-Meier Plots for T1 mapping parameters.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.2

Cardiac Magnetic Resonance measured Extracellular Volume Independently Predicts Adverse Outcome in Heart Failure with Preserved Ejection Fraction


Background: Cardiac magnetic resonance (CMR) T1 mapping allows accurate non-invasive quantification of extracellular matrix volume (ECV). Accumulation of extracellular matrix (ECM) is a key pathophysiological mechanism in heart failure with preserved ejection fraction (HFpEF). HFpEF accounts for approximately 50% of all HF cases and is associated with a poor prognosis. However, the prognostic relevance and hemodynamic consequences of CMR-ECV in HFpEF are unknown.

Materials and Methods: Between January 2011 and August 2015 we prospectively enrolled 108 HFpEF patients. All patients underwent CMR T1 mapping for ECV measurement, using the Modified Look-Locker Inversion recovery (MOLLI) sequence. Right heart catheterization was performed in 92 (85%) patients.

Results: The study cohort was prospectively followed for up to three years, during which 33 (30.6%) had a cardiac event (hospitalization and/or death for cardiac reason). Patients with ECV ≥27.6% had more events (p = 0.011), higher NT-proBNP levels (p = 0.018), larger right atria (p = 0.025) compared to patients with ECV <27.6%. By univariable Cox analysis ECV ≥ 27.6% (p = 0.040), presence of pleural effusion (p = 0.001), NYHA class III or IV (p = 0.005), NT-proBNP (p = 0.001), systolic pulmonary artery pressure (sPAP) (p = <0.001), diastolic PAP (p = 0.001), mean PAP (p = <0.001), stroke volume (p = 0.041), venous oxygen saturation (SvO2) (p = 0.028), transpulmonary gradient (p = <0.001), diastolic pressure gradient (p = 0.002), pulmonary pulse pressure (p = <0.001) and pulmonary vascular resistance (PVR) (p = <0.001) were significantly associated with outcome. By multivariable Cox analysis only ECV ≥27.6% (p = 0.049), presence of pleural effusion (p = 0.001), NYHA class III or IV (p = 0.012), NT-proBNP (p = 0.036) and PVR (p = <0.001) remained significant predictors of cardiac events. ECV significantly correlated with clinical, CMR and hemodynamic parameters: 6MWD (R = -0.272, p = 0.006), NYHA class (R = 0.220, p = 0.023), NT-proBNP (R = 0.362, p = <0.001), pulmonary artery diameter (R = 0.262, p = 0.006), right atrial volume (P = 0.299, p = 0.002), mean right atrial pressure (P = 0.246, p = 0.020), SvO2 (P = -0.241, p = 0.023) and stroke index (P = -0.234, p = 0.030).

Conclusions: CMR-ECV independently predicts outcome in HFpEF and is correlated with severity of symptoms as well as exercise capacity. Reduction of ECV may therefore be a promising therapeutic target.

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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.3

Cardiac MRI Under Percussive Ventilation: A New Promising Technique


Background: High-resolution 3D cardiac MR is in general based on respiratory compensation techniques to allow for long acquisitions extending beyond a breath-hold. Such compensation mechanisms are, however, not always accurate. High frequency percussive ventilation (PV) administers small volumes of air, so-called “percussions”, with adjustable pressures and at high frequencies, thereby potentially replacing spontaneous breathing and allowing for a long period of apnea.

Aim: To implement the PV technique in a MR environment and to test its potential for 3D high-resolution coronary MRA during long periods of apnea without the need to apply respiratory compensation techniques.

Material and Methods: PV was delivered by Transrespirator® (Percussionaire® Corporation,Idaho,USA), which was adapted to be MRI compatible by integrating tubes allowing its installation outside the MRI room. One metallic component of the Phasitron was replaced by a MRI-compatible part. The phasitron represents an open circuit in order to protect from the risk of baro-trauma. The entire system is pneumatic, works without electronics, is not influenced by electromagnetic forces, and it ventilates non-invasively without sedation. One volunteer (38 y) and one patient (55 y) with a thymic lesion underwent a MRI (1.5T Aera,Siemens,Germany) under percussive ventilation (PV-MRI). Participants were trained to maintain their breath during 3 preliminary sessions before undergoing the PV-MRI. During PV-MRI, the apnea periods ended at the discretion of the participant. Heart rate and O2 saturation were monitored during the whole MRI. The breathing cycle amplitude reduction was monitored by using a conventional MR navigator. Turbo-SE, VIBE, and coronary MRA (3D cartesian/radial SSFP, isotropic resolution: 1.15mm3/1.3mm3) were performed without contrast medium during 3 sets of PV apnea on inspiration.

Results: PV-MRI was well tolerated in both cases. Mean apnea duration was 10.5 min (range 8.5-12.0 min) in the healthy volunteer and 5.8 min (range 5.0-6.2 min) in the patient. The coronary arteries were well visualized by the 3D-SSFP sequence as shown in Fig. 1A/B. With this technique, lung volumes were “frozen” in full inspiration and pulmonary vessels were also well visualized with PV-MRI (Fig. 1C).

Conclusion: PV is feasible and well tolerated in the MRI environment and allows for apnea durations of up to 10 minutes. Coronary MRA yielded high-resolution images of the coronary arteries without the need to apply any respiratory compensation. Larger series are needed to evaluate the potential of PV-MRI.

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Figure 1. A/B/C: 30/8.5/20-mm thick MIP of a 3D-SSFP acquisition without respiratory compensation acquired during a 6.2 minutes apnea with PV.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.4

Histological Validation of Cardiac Magnetic Resonance for the Evaluation of Myocardial Fibrosis after Heart Transplantation in Children


Objectives: Diffuse fibrosis may impact myocardial function in children after heart transplantation (HTx). Quantification of diffuse myocardial fibrosis with cardiac magnetic resonance (CMR) is increasingly applied to patients with heart disease and has been shown to correspond well to fibrosis degrees by histology. However, comparisons with histological fibrosis burdens in children are lacking. The aim of this study was to correlate CMR markers of fibrosis to the gold standard of myocardial biopsy.

Methods: 17 patients (9.7 ± 6.3 years; 8 girls) after HTx were prospectively enrolled. Twenty endomyocardial biopsy (EMB) procedures (with 5 myocardial samples each) and CMRs were performed on the same day, at a median of 2.2 years post HTx, 0.02-12.6 years). EMB was done as per institutional post HTx protocol. All 100 specimens were stained with picrosirius red. The degree of fibrosis (%fibrosis) was calculated as ratio of fibrosis area to total myocardial area. Endocardium and scars at previous biopsy sites were excluded from analysis.

Native and post-contrast T1 values were measured within the interventricular septum (IVS) on a mid-ventricular short axis slice, using a modified look-locker inversion recovery approach (MOLLI). Extracellular volume (ECV) was calculated from pre- and post-contrast T1 times and the patients' hematocrit. Native T1 and ECV were correlated with %fibrosis.

Results: Mean %fibrosis was 10.0 ± 3.4%. Mean septal native T1 values were 1008 ± 32ms. Mean ECV within the IVS was 0.30 ± 0.03. %fibrosis and showed a moderate correlation with T1 (r = 0.53, p < 0.05) and with ECV (r = 0.46, p < 0.05), respectively.

Conclusions: Fibrosis markers by CMR correlate with histological degrees of fibrosis on EMBs in children after HTx. The agreement between CMR and histology may have been impacted by of inflammation and edema during rejection on T1 and ECV measurements. Further, poor the EMBs may be an imperfect representation of the septal myocardium, especially when taken from previous biopsy sites. Overall, this study suggests that native T1 and CMR can be utilized as markers of diffuse myocardial fibrosis in children.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.5

First Pass Perfusion Reserve Index in Paediatric Patients with Arterial Switch for Transposition of Great Arteries


Background: Arterial switch operation is the treatment of choice for correction of transposition of the great arteries (TGA). Coronary anatomy is the most impacting early prognostic factor after surgery. We previously described potential mechanisms of late coronary complications according to coronary position after surgical transfer. As systematic screening protocol is not worldwide defined, data about late coronary outcome are lacking. Noninvasive first pass perfusion with cardiac magnetic resonance (cMRI) is sensitive technique for evaluation of myocardial perfusion in ischemic heart disease.

Objectives: Here we aimed to apply a comprehensive cMRI protocol in children and adolescents to assess coronary artery complications in late follow up after arterial switch operation for TGA.

Methods: Between 2010 and 2014, 66 patients were prospectively enrolled (median age 13.9± 5.5 years) into two groups according to the presence (9/66)or absence (57/66) of coronary arteries abnormalities at previous computer tomography or angiography screening at 5 ± 2 years. Coronary position and anatomy were analysed as previously described. Semi-quantitative evaluation of myocardial perfusion was performed by the analysis of myocardial First-Pass perfusion images at rest and during adenosine infusion and the segmental perfusion reserve index (PRI) was calculated. Late gadolinium enhancement (LGE) was also studied.

Results: Eleven patients (11/66= 16%) had perfusion defects (PRI < 1.5). In 9/11 perfusion defects were in anterior-anteroseptal or anterolateral segments vs 2/11 in inferior-inferoseptal-inferolateral segments. In 16 (16/66 = 24%) patients left coronary artery was reimplanted in clock position 11 or 12. Interestingly, these patients with left coronary in position 11-12 had more frequent perfusion defects than other patients (7 vs 2, p = 0.004). Moreover, considering only the myocardial segments irrigated by left coronary artery, semiquantitative perfusion defects were found only in patients with left coronary artery in position 11 and 12 (7 vs 0, p = 0.0002). These patients had significantly lower PRI in myocardial segments irrigated by left coronary artery myocardial than other patients (2.0 ± 1 vs 2.7 ± 1, p < 0.05). LGE was positive in 2 cases. No patients with decreased PRI had LGE. All patients with decreased PRI were asymptomatic and did not show echocardiographic or functional signs of myocardial ischemia.

Conclusion: cMRI can provide a useful tool for detecting asymptomatic myocardial perfusion delay. PRI analysis results confirm the presence of a high-risk group of patients. Clinical implication of early detection of perfusion delay should be investigated.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.6

Myocardial Fibrosis is Prevalent in Obstructive Sleep Apnea and Associated with Hospitalization for Heart Failure or Death


Background: Myocardial fibrosis may be prevalent and mediate increased rates of hospitalization for heart failure (HHF) and mortality in patients with obstructive sleep apnea (OSA). We quantified myocardial fibrosis by extracellular volume fraction (ECV) and examined associations between these outcomes. Since myocardial fibrosis is reversible, this data may inform disease mechanisms and potential targets for therapy in OSA that remain uncertain.

Methods: We enrolled 1,094 consecutive referred patients for cardiovascular magnetic resonance (CMR) without amyloidosis, congenital heart disease, stress cardiomyopathy, or hypertrophic cardiomyopathy and 16 healthy controls. We quantified ECV in noninfarcted myocardium and tracked outcomes prospectively, including a subgroup of 176 patients with available polysomnography. For survival analyses, the logrank test compared Kaplan-Meier curves, and multivariable Cox regression models measured associations with outcomes.

Results: Myocardial fibrosis was prevalent in OSA, where 97 of 324 (30%) patients exhibited elevated ECV > =30%. While patients with OSA exhibited higher ECV compared to healthy controls (27.6% (IQR 25.2-30.5) versus 24.1% (IQR 23.1%-25.7%, p = <0.001)), ECV in OSA was not significantly higher compared to patients with known or suspected heart disease referred for CMR (p = 0.45). OSA disease severity measured by apnea-hypopnea index (AHI) was weakly correlated with left ventricular mass index (R2 = 0.03, p = 0.01), systolic blood pressure (R2 = 0.03, p = 0.049), and diastolic blood pressure (R2 = 0.034 p = 0.04). AHI was not significantly associated with ECV, end-diastolic volume index, ejection fraction, B-type Natriuretic Peptide, Glomerular Filtration Rate (GFR), or HHF/mortality events (p < =0.09 for all).

Over a median follow-up of 2.3 years (IQR 1.2-3.2 years) there were 62 HHF events and 108 deaths after CMR in 147 individuals. There was no difference in rates of HHF or death (p = 0.15) in patients with or without OSA (Figure 1). Yet, in OSA patients, myocardial fibrosis was significantly associated with increased event rates (Figure 2) adjusting for age, GFR, myocardial infarction size, ejection fraction (HR 1.6 95%CI 1.2-2.2 for every 5% increase in ECV, p = 0.003).

Conclusions: Myocardial fibrosis is prevalent in OSA and associated with HHF or death. Quantifying myocardial fibrosis in OSA patients may improve cardiovascular risk stratification and provide a phenotype for targeted therapeutic intervention.

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Figure 1.

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Figure 2.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.25

Myocardial substrates underlyng early ventricular arrhythmias in st-elevation acute myocardial infarction: the role of cardiac magnetic resonance


Background: Is well note that scar detected by Cardiac Magnetic Resonance (CMR) is a predictor of late and no early ventricular arrhythmias due to re-entry mechanism. Recent studies suggested that myocardium salvaged may represent a substrate for early one. CMR is able to individualize myocardial area at risk and salvaged myocardium.

Aims: Analyze if substrates detected by CMR are able to predict arrhythmias in patients with ST-segment elevation myocardial infarction.

Methods: We enrolled consecutive patients presenting acute coronary syndrome with persistent ST-segment elevation and treated by primary PCI within 12 hours after symptoms onset and who underwent a complete CMR protocol including edema and LGE sequences within 10 days from admission. We excluded patients with late myocardial infarction (>12 h), pre-infarction angina and poor image quality and not eligible for CMR. All patients were monitored to detect early (<48 hours) major ventricular arrhytmias as ventricular fibrillation (VF) and susteined ventricular tachycardia (SVT).

Results: 30 patients (75% male, median age 63 y.o.) were enrolled. During first 48 hours 8 patients had at least one major arrhythmias (3 SVT, 3 VF pre PCI and 3 VF post PCI). The overall population were divided into two groups in according with the presence (8) or absence (22) of arrhythmias. Time pain-to-balloon (233 vs 170 minutes), Troponin I peak (72 vs 97 ug/L) and culprit lesion were not different between the two groups. The arrhythmic one had a quite normal left ventricle ejection fraction compared to the non arrhythmic one (55% vs 49%, p = 0.045). The presence and the global amount of edema, myocardial necrosis (LGE), microvascular obstruction and haemmoragic area were not difference into the two groups. The only parameter that demonstrate a significant association with the presence of early ventricular major arrhythmias was salvaged myocardium (21% vs 5%, p = 0.035). An amount of 10% salvaged myocardium was the critical substrate mass to determine the presence early ventricular arrhythmias (specificity 77%, sensitivity 75%).

Conclusion: From our data not area at risk but a critical mass of salvaged myocardium was associated with the presence of major early ventricular arrhythmias. Probabily due to an heterogenic substrate related to peri-infarct region.

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Figure 1.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.2

Cardiac magnetic resonance predicts atrial fibrillation occurrence in patients with hypertrophic cardiomyopathy


Objectives: Patients with hypertrophic cardiomyopathy (HCM) are known to be more prone to atrial fibrillation (AF). We sought to identify predictors of AF onset in HCM patients with the use of cardiac magnetic resonance (CMR).

Methods: We prospectively enrolled 259 patients with HCM, no prior history of atrial arrhythmia, and no AF episode on a 24-hour Holter performed at inclusion. 165 patients (63%) underwent CMR using Cine SSFP and Late gadolinium enhanced (LGE) imaging (3D IR FLASH). On the left ventricle (LV), maximal wall thickness, LV volumes and ejection function (EF) were measured. LGE images were analyzed to detect LV fibrosis, and LGE patterns were categorized as either ischemic-like or non-ischemic, the latter being further characterized as either midwall patchy LGE in hypertrophied segments or focal LGE on LV-RV junctions. In addition left atrial (LA) dimensions and volumes (maximum, pre-A and minimum volumes) were measured and used to compute the following functional parameters: LA total ejection fraction (EF), conduit fraction, active emptying fraction, and expansion index. Patients were followed clinically and with 24-hour Holter recordings every 6 months. Univariable and multivariable regression analyses were performed to identify clinical and imaging predictors of AF occurrence.

Results: During a mean follow up of 27 ± 11 months 31 patients (12%) developed AF. In the CMR group AF was detected in 19 patients (12%). Characteristics in patients with vs. without AF occurrence are shown in the Table. Sequential Cox multivariable analysis, after elimination of potential multicollinearity, identified CMR independent predictors of AF occurrence: LA diameter (HR = 1.09, 95%CI: 1.01-1.16, P = 0.02), LA EF (HR = 0.94, 95%CI: 0.90-0.99, P = 0.008) and LV LGE (HR = 4.53, 95%CI: 1.02-20.06, P = 0.046). Among clinical characteristics, age was the only independent predictor (HR = 1.03, 95%CI: 1.00-1.06, P = 0.03). Univariable analysis documented LGE at RV-LV junctions as the pattern with the closest relationship with AF (71% in pts with AF occurrence vs. 37% without, P = 0.006).

Conclusion: LA size, LA emptying function and LV fibrosis on CMR are independent predictors of AF occurrence in patients with HCM. The mechanisms linking the ventricular HCM phenotype to AF should be analyzed in future studies.

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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.3

T1 and T2 mapping cardiovascular magnetic resonance to monitor inflammatory activity in patients with myocarditis


Background: Myocarditis is a heterogeneous disease with a large spectrum of possible clinical courses ranging from complete healing to end stage heart failure. Thus, there is a need for reliable tools to monitor disease activity and to identify patients with persistent inflammation who are at risk for an adverse outcome. T1 and T2 mapping are emerging cardiovascular magnetic resonance (CMR) tools for quantitative tissue characterization in myocarditis. This study evaluated the use of T1 and T2 mapping CMR to monitor disease activity during a 12-month follow-up period after first manifestation of myocarditis.

Methods: This study included 37 patients with the first clinical manifestation of rigorously defined acute myocarditis, who underwent CMR at 1.5 Tesla at baseline (BL) in the acute phase, after 3 months (FU-I, n = 27) and after 12 months (FU-II, n = 16). T1 and T2 mapping CMR were performed in addition to a conventional CMR myocarditis protocol. T1 quantification was performed on three short axes using a modified Look-Locker inversion-recovery (MOLLI) variant before and 15 minutes after administration of 0.075 mmol/kg Gadolinium-BOPTA. T2 quantification was performed using a free-breathing, navigator-gated gradient- and spin-echo hybrid sequence (GRASE). Maps were generated using a dedicated plug-in for the OsiriX software to calculate myocardial T2, native/post-contrast T1 and extracellular-volume-fraction (ECV) values.

Results: Median left ventricular ejection fraction (LVEF) improved from 56 (32-67) % at BL to 63 (49-68) % at FU-I (p < 0.01). Median global myocardial T2 significantly decreased from 61 (57-64) ms at BL to 58 (55-63) ms at FU-I (p < 0.05). Similarly, median global myocardial native T1 decreased from 1100 (1070-1135) ms at BL to 1059 (1039-1113) ms at FU-I (p < 0.05). Furthermore, global myocardial ECV was significantly lower at FU-I with 26 (24-30) % compared to 29 (26-32) % at BL (p < 0.05). However, there were no further significant changes in LVEF, global myocardial T2, native T1 and ECV during the further course from FU-I to FU-II.

Conclusion: T1 and T2 mapping CMR techniques offer novel insights into the course of myocardial inflammation in myocarditis. Our findings suggest that the major decrease of inflammatory activity in myocarditis occurs within the first 3 months after first clinical manifestation. T1 and T2 mapping techniques have great potential for monitoring disease activity in myocarditis.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.4

Impact of electronic coaching on cardiovascular risk reduction in a high-risk primary prevention population – A cardiovascular magnetic resonance sub-study


Background: Cardiovascular disease (CVD) remains one of the main causes of mortality globally. Innovative techniques are required to tackle the anticipated rise in CVD due to rising obesity, diabetes and an ageing population. Personalized electronic (e-) coaching utilizes platforms such as the internet and email to help motivate healthy living. Cardiovascular magnetic resonance (CMR) imaging offers a range of powerful imaging parameters that can be used as outcome measures in clinical trials at reduced cost and follow-up duration and can inform performance of larger scale randomized controlled trails (RCT).

Aims: The aim of the study was to assess the clinical effectiveness of e-coaching in a high risk, asymptomatic primary prevention cohort using surrogate markers of left ventricular (LV) mass and pulse wave velocity.

Methods: Between July 2013 and November 2015 we conducted a single center RCT of 402 participants, comparing e-coaching in addition to standard of care (SOC) vs. SOC alone. E-coaching included a personalized webpage with heart health advice for each subject based on their individual lifestyle and risk factors, progress charts with goals and achievements and email reminders with tips. The SOC consisted of face-to-face advice on risk factor and medication based on ESC and NICE guidelines.

Estimated 10-year CVD risk of 10% or more was required with no prior history of CVD. In the sub-study CMR (Philips 1.5T) along with Vicorder device based carotid-femoral pulse wave velocity (PWV) and CVD risk assessment was performed at baseline and 6 month follow-up in the first 100 participants (1:1 allocation based on treatment arm) consenting to CMR and with no scanning contraindications.

Results: Average age was 65.8 years in the e-coaching and 64.1 in the SOC group. See table 1 for other baseline data. Compared to baseline both groups showed reduction in LV mass (e-coach -2.01g vs. -1.27g, p= 0.74, figure 1) and PWV (e-coach -0.30 m/s vs. -0.77m/s, p= 0.08). Findings were consistent when LV mass was indexed to body surface area. Global risk scores, body mass index, glucose and blood pressure also showed improvement but with no statistical difference between the two groups.

Conclusion: Personalized e-coaching does not show clinical effectiveness in CVD risk reduction when combined with current standard of care. Evidence of effectiveness of a potentially costly health technology is vital before recommending its widespread use in resource limited health care systems.

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Figure. Change in LV mass in the e-coaching and standard of care groups over 6 months.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.5

Anatomical and functional evaluation of postinterventional pulmonary vein stenosis by magnetic resonance imaging


Background: Pulmonary vein stenosis (PVS) after radiofrequency ablation for atrial fibrillation remains a challenge despite considerable technological advances. We aimed to evaluate anatomical and functional PVS assessment by MRA and MR perfusion imaging.

Material and Methods: 57 patients (61 studies) with a known PVS were evaluated. Patients were scanned in a 1.5T MRI scanner. All patients received a contrast-enhanced three-dimensional angiography and high-resolution k-t accelerated CMR lung perfusion was performed in 28 patients. In 50 patients previous studies (MRA or CTA) were available for comparison. Three dimensional reconstructions of the left atria were performed and pulmonary vein branches were assessed. Pulmonary perfusion deficits were correlated to PV subbranches.

Results: MRA was safe in all patients. Underlying heart rhythm did not affect image quality. In all patients with a perfusion deficit the corresponding PV subbranch could be ientified. In 3 patients without previous imaging MRA alone did not allow detect occlusion of a subbranch but a corresponding perfusion deficit existed. In one patient a perfusion deficit could be diagnosed despite PV collateralization.

Conclusions: Anatomical and functional PVS assessment by MRA and MR perfusion imaging has the potential to improve diagnosis and evaluation of long term outcome. MRA has the potential to miss occlusion of PV subbranches and can lead to inaccurate diagnoses.

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Figure. (A) First dynamic of contrast-enhanced three-dimensional cardiovascular magnetic resonance angiography of the pulmonary veins (p.a.view) showing total occlusion of the left superior PV (B) High-resolution k-t accelerated cardiovascular magnetic resonance lung perfusion imaging identified an extensive perfusion deficit of the left upper lobe (coronal orientation).

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.6

Reduced infarct-adjacent wall thickening and impaired restperfusion in the area at risk of successfully reperfused acute myocardial infarction


Background: Myocardial infarction (MI) leads to heart failure in a substantial number of patients. Investigation of the infarct-adjacent segments can offer better insights into left ventricular remodeling. Our study aims to quantify radial wall strain (WS) and myocardial blood flow (MBF) with cardiac magnetic resonance (CMR) in the infarct zone (IZ), borderzones (BZ) and remote myocardium (RM) in a large patient population in the acute phase of MI.

Methods: In this substudy of the NOMI-trial ( identifier: NCT01398384) using the placebo arm, 68 patients underwent CMR with T2-weighted, cine, dual bolus first pass perfusion, and gadolinium enhancement (LGE) imaging within 48 to 72 hours of acutely revascularized ST-elevation MI in a 1.5 tesla MR scanner. TIMI 2-3 flow was achieved in all patients after PCI. Corresponding basal and midventricular SAX slices of the CMR acquisitions were aligned and divided into 12 corresponding equiangular (30°) segments. WS was measured as the percentage of radial wall thickening, absolute MBF was quantified using Fermi deconvolution. Values for the IZ were calculated as the mean of segments with LGE. The infarct-adjacent 30 degree segments were defined as BZ-inAAR or BZ-outAAR, depending on their location resp. in- or outside the area at risk on T2-weighted imaging. Values for the RM were calculated as the mean of the remaining segments. Apical slices seldomly included more than one myocardial zone and were excluded from analysis.

Results: One hundred thirty six slices were analyzed. WS was impaired to a similar extent in BZ-inAAR (28.5%, 12.0-49.5) and BZ-outAAR (29.0%, 10.7-46.2, p = 0.141) compared to RM (49.5%, 34.9-59.7, p < 0.003), and even more in the IZ (15.1%, 1.6-29.5, p < 0.003). MBF was impaired in the BZ-inAAR and IZ only (0.39 ml/g/min, 0.33-0.53 and 0.30 ml/g/min, 0.22-0.41 resp.), compared to BZ-outAAR and RM (0.49 ml/g/min, 0.35-0.62 and 0.44 ml/g/min, 0.34-0.59 resp., p < 0.003).

Conclusions: WS is impaired in the infarct-adjacent segments regardless of perfusion, so probably as a result of geometric tethering. Myocardial restperfusion in the area at risk is still reduced in successfully revascularized acute MI.

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Figure. WS is presented on the left, MBF on the right. WS is decreased to a similar extent in both borderzones(left), although perfusion is normal in the BZ-outAAR, whereas MBF in the BZ-inAAR is significantly impaired (right). * = p < 0.003, ns = not significant.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.30

Correlation between circulating microRNA 29 and diffuse myocardial fibrosis, assessed by T1 mapping, in patients affected by non ischemic dilative cardiomyopathy


Background: Myocardial fibrosis is a fundamental process in the development of myocardial dysfunction in cardiomyopathies, leading to myocardial remodeling and poor outcome. Circulating microRNAs could prove to be novel biomarkers for cardiovascular diseases. In particular, miR-29 is the best-characterized direct regulator of extracellular matrix protein synthesis. Recently, it has been associated with diffuse myocardial fibrosis in hypertrophic cardiomyopathy (HCM).

Aim of the Study: To assess the correlation between microRNA 29a and diffuse interstitial myocardial fibrosis in patients affected by non-ischemic dilative cardiomyopathy (NIDCM).

Methods: Eleven consecutive patients who were referred for screening to Policlinico San Donato, Cardiac Imaging Unit, were prospectively enrolled. All patients underwent CMR, performed with LGE quantification to detect regional fibrosis and T1 mapping for diffuse fibrosis. Peripheral blood samples were taken before CMR exam to obtain hematocrit, useful for extracellular volume

(ECV) calculation. Plasma samples (10 min centrifugation at 400 g followed by a further 10 min at 600 g) were stored at −80 °C for RNA isolation.

Results: Patients affected by NIDCM were 42% males (57,8 ± 13,5 years old), Left Ventricular End Diastolic Volume (LVEDV index ml/m2) was 112,7 ± 15, Left ventricular mass index was 104 ± 9,2, mean LV Ejection Fraction was 36,9 ±13,3, LGE % was 3,7± 7,7. No significant difference was found in microRNA 29a levels between DCM and controls (n = 42) (1,10± 0,7 vs 1,25 ± 0,94, p:ns). In DCM patients, an inverse correlation between microRNA29a and left ventricular stroke volume (SV) was found (Rho = -0,711, p:0,021). Mean septum ECV was 0,33 ± 0,03. No correlation was found between microRNA29a levels and macroscopic fibrosis, as assessed by LGE percentage. However, we found a strong inverse correlation, in DCM patients, between microRNA 29 and ECV (Rho = -0,672, p:0,047), and a tendency of negative correlation with blood T1 mapping post (Rho = -0,594, p:0,092).

Conclusions: For the first time it has been reported a strong negative correlation between microRNA-29 a and ECV in NIDCM patients, probably reflecting its role as a negative regulator of genes encoding collagens and extracellular matrix proteins. This finding suggests that microRNA-29a could be a circulating biomarker for early detection of diffuse myocardial fibrosis, as assessed by T1 mapping. A larger sample size is needed to confirm our data and to determinate the role of this biomarker in DCM patients.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.8

Association of Smoking with Myocardial Injury and Clinical Outcome in Patients Undergoing Mechanical Reperfusion for ST-Elevation Myocardial Infarction


Aims: There is evidence suggesting a positive effect of cigarette smoking on myocardial tissue reperfusion and clinical outcomes in patients with myocardial infarction (“smoker's paradox”). We aimed to evaluate the relationship of smoking with cardiac magnetic resonance (CMR)-determined myocardial salvage and damage as well as clinical outcome in patients undergoing primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction (STEMI).

Methods and Results: This multicenter study included 727 consecutive STEMI patients reperfused within 12 hours after symptom onset. CMR imaging parameters (area-at-risk [AAR], infarct size [IS], myocardial salvage index [MSI], microvascular obstruction [MVO]) and intramyocardial haemorrhage [IMH] were compared according to admission smoking status. Major adverse cardiac events (MACE) rates at 12 months after infarction were compared between groups. Three hundred and thirty-nine (46.6%) patients were current smokers. There was no difference in the extent of AAR (35 [24-47] vs. 37 [27-49] % of left ventricular volume [LV], p = 0.10), IS (16 [8-25] vs. 17 [10-26] %LV, p = 0.21), MSI (53 [29-70] vs. 52 [34-71], p = 0.47), MVO (0 [0-1.7] vs. 0 [0-1.6] %LV, p = 0.91), or in the frequency of IMH (42% vs. 39%. p = 0.58) between smokers and non-smokers. Smokers had lower MACE (3.8% vs. 8.2%, p = 0.01) rate. However, adjustment for differences in baseline risk factors, attenuated the association of smoking with MACE markedly (HR = 0.71, 95% CI 0.36 to 1.38, p = 0.31).

Conclusion: Smoking is not associated with PPCI efficacy (myocardial salvage) or irreversible myocardial damage in patients with STEMI. The lower MACE rate of smokers was entirely explained by differences in baseline risk characteristics, thus challenging the existence of a “smoker's paradox”.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.9

Assessing the risk of late cardiotoxicity in low risk breast cancer survivors receiving contemporary anthracycline treatment: a 6 year 100 patient study


Background: Chemotherapy cures patients with cancer but anthracyclines (AC) are cardiotoxic. In clinical practice left ventricle ejection fraction (EF) changes are used to detect cardiotoxicity. However, routine surveillance should not be limited to assess EF alone due to EF limitation.

Objectives: To explore the late cardiac effects of AC using advanced cardiac imaging and biomarkers in low-risk breast cancer survivors.

Methods: 132 women from a former study of AC (intermediate dose – mean dose 399 ± 85.4 mg/m2) breast cancer therapy were traced. After exclusions (died, recurrent disease, pregnancy, did not wish to attend), 98 attended. These had been selectively recruited to have no cardiovascular risk factors and no previous radio/chemo-therap. All subjects underwent baseline pre-chemotherapy cardiac magnetic resonance (CMR) imaging. Subjects were compared with an age-matched control group of healthy volunteers (HV, n = 34) at follow-up. All underwent resting ECG, blood biomarkers, advanced echocardiography and CMR structure, function (with the original 2005 protocol) and T1 mapping (MOLLI) for ECV quantification.

Results: 98 women attended for follow up (age 55 ± 8.5 years, mean 6 years post AC treatment), and no participants reported cardiac symptoms or fulfilled criteria for cardiotoxicity. Across the AC group, EF fell by -3.7 ± 4.2% (range from -13 to +8%) over 6 years follow-up, although all measurements remained within the normal range. Patients with higher dose of AC (≥450mg/m2) had greater EF reduction compare to lower doses (4.6 ± 3.7% versus 2.7 ± 4.4%, p = 0.030). There were no differences in standard CMR parameters between the AC and HV groups, except the LA was larger in the AC group. Native myocardial T1 was greater in AC (1052 ± 30 vs 1037 ± 31 msec, p = 0.012). Mean ECV calculations were similar (0.28 ± 0.029 vs 0.28 ± 0.029, p = 0.803), however, values were slightly higher when left (vs right) radiotherapy had been performed (0.29 ± 0.030 vs 0.28 ± 0.023, p = 0.017). Echocardiography found lower systolic and diastolic myocardial velocities and global longitudinal strain parameters - but within the normal reference range - with greatest reductions in the AC group who had experienced an EF drop ≥5% by CMR.

Conclusion: Chemotherapy with AC causes a small non-clinical reduction in the cardiac function (however measured) with a dose-response relationship, as does left sided radiotherapy. These changes are however small and may be missed by EF measurements alone.

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Figure. Left: AC subjects exposed to higher anthracycline doses shower greater EF reduction compared with low dose. Centre: myocardial native T1 was higher in the AC patients. Right: No statistically differences in the myocardial ECV mean values were observed.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.10

Risk stratification in sarcoidosis: Incidence of cardiac sarcoidosis in individuals diagnosed with extra-cardiac disease by cardiovascular magnetic resonance


Introduction: Cardiac death is the leading cause of mortality in patients with sarcoidosis. In those with extra-cardiac sarcoidosis diagnosis, little is known of the incidence of cardiac sarcoidosis (CS). Myocardial infiltration of cardiac sarcoidosis is a marker in risk stratification of these patients. Late gadolinium enhancement (LGE) by cardiovascular magnetic resonance (CMR) imaging has the ability to identify the myocardial infiltration of cardiac sarcoidosis (CS). We therefore investigated the incidence of CS in patients with extra-cardiac sarcoidosis without cardiac manifestations using LGE-CMR.

Methods: 72 patients with clinically and radiologically diagnosed pulmonary sarcoidosis, without signs or symptoms of cardiovascular involvement, were enrolled over a three-year period. LGE-CMR was performed on all patients. The presence of LGE in the left ventricular myocardium was considered diagnostic for CS. Patients were classified as CS or non-CS based on the LGE-CMR findings.

Results: Mean age was 51 ± 19 years, with a female predominance (61%). CS was detected in 19 patients (23%). When compared to those patients without LGE, patients with CS had higher rates of previously documented non-sustained ventricular tachycardia (22% vs. 5%), a greater prevalence of an abnormal ECG (52% vs. 18%) and a higher heart rate during CMR (82bpm vs. 72bpm).

Conclusion: CMR should be considered as an adjunct to conventional diagnostic workup in all patients with pulmonary sarcoidosis. Long-term follow-up of consecutive patients with isolated CS is needed to determine the natural history and rates of ventricular arrhythmias.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.11

Patterns of late gadolinium enhancement in Brugada syndrome

Rachel Bastiaenen, PhD,1,2 Andrew T. Cox, MRCP,1,2 Yanushi Wijeyeratne, MRCP,1,2 Nicholas Colbeck, MBBS,1 Nadia Pakroo, MBBS,1 Hammad Ahmed, MBBS,1 Nick Bunce, MD,2 Lisa Anderson, MD,1,2 Sanjay Prasad, MD,1,2 Sanjay Sharma, MD,1,2 and Elijah R. Behr, MD1,2


Background: There is increasing evidence to suggest that the Brugada ECG pattern is a marker of subtle structural heart disease. We characterised a cohort of patients with Brugada syndrome (BrS) using cardiac magnetic resonance (CMR) late gadolinium enhancement techniques.

Methods: BrS was diagnosed according to international guidelines. CMR data from 78 BrS patients (44 + /-15 years; 64% male) was compared with data from 78 normal controls (42 + /-14 years; 64% male).

Results: Right ventricular (RV) ejection fraction was lower (61 + /-8% vs 64 + /-5%; p = 0.004) and RV end-systolic volume was greater (31 + /-10ml/m2 vs 28 + /-6ml/m2; p = 0.015) in BrS patients compared with normal controls, but these values remained within the normal range. Overall LGE was demonstrated in 8% BrS patients (midwall LGE in 5%) and no normal controls (p = 0.028; figure 1). In BrS patients with midwall LGE there were no other features of cardiomyopathy at the time of CMR but further genetic testing has revealed a desmoplakin mutation in one patient and evolution of T wave inversion throughout all the precordial ECG leads during two year follow-up in another. Both of these are major criteria for arrhythmogenic right ventricular cardiomyopathy (ARVC), but as yet neither patient fulfills diagnostic criteria for this condition.

Conclusion: Some BrS patients demonstrate midwall LGE consistent with an underlying cardiomyopathic process. This lends further support to the presence of subtle structural abnormalities in BrS. It suggests a degree of phenotypic overlap with ARVC in some cases and may serve as an early marker for evolution of a cardiomyopathic phenotype over time.

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Figure 1. Cardiac magnetic resonance imaging in Brugada syndrome (BrS). Panels A and B demonstrate late gadolinium enhancement (LGE) in a 45 year old male patient with BrS. Patchy midwall LGE is demonstrated in the mid and apical lateral wall, basal and apical inferolateral wall of the left ventricle and mid anteroseptum. Panels C and D demonstrate midwall LGE in the mid inferoseptum of his 53 year old sister who also has BrS. Panels E and F demonstrate midwall LGE in the basal and mid septum and anteroseptum of a 40 year old man with BrS who was subsequently found to have a desmoplakin gene mutation.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.12

Detailed Left Atrial Assessment in Anderson Fabry Disease


Introduction: Left atrial (LA) function is increasingly recognised as an important marker in multiple cardiac pathologies. Left ventricular hypertrophy and diastolic dysfunction are common in Fabry Disease (FD), and histological LA abnormalities are identifiable post-mortem. The aim of this study was to assess LA function in a cohort of patients with FD, with and without left ventricular hypertrophy.

Methods: 25 genetically-confirmed patients with FD (15 without LVH, 10 with LVH, all in sinus rhythm) and 15 age and gender matched healthy volunteers (HV); FD (13 male) 46.2 ± 13.8 years, HV (7 male) 39.7 ± 14.3 years, underwent CMR at 1.5T (Avanto, Siemens AG, Erlangen, Germany). A standardised clinical CMR protocol was used in all. Biplane LA volumes were obtained from 4- and 2-chamber SSFP cine images (cmr42, Circle Cardiovascular Imaging Inc., Calgary, Canada). Mean atrial strain and strain-rate parameters were also derived from these sequences using dedicated CMR feature tracking software (Diogenes® TomTec, Germany).

Results: Results are shown in table 1. Those with LVH were older, reflecting the natural history of FD. LA volumes and volume-derived left atrial functional parameters (total, passive and active ejection fractions and LA expansion index) did not differ between LVH-negative FD patients and HVs. However those with LVH had significantly increased volumes, with reduction in total and passive ejection fractions and reduced LA expansion index, reflecting reduced conduit and reservoir functions.

Those without LVH had significantly reduced total atrial strain and early negative strain rate, reflecting reduced LA and LV compliance, respectively. Early passive strain and negative strain rate, and LA expansion index reduced further in LVH positive patients, reflecting worsening conduit and reservoir function. Strain markers of booster pump function, known to increase in hypertrophic cardiomyopathy, showed no difference between the groups.

Discussion: LA function, particularly conduit function which reflects LV compliance, is impaired in Fabry disease, even in the absence of left ventricular hypertrophy and increased LA volume. Disturbances in volumetric indices of LA function were seen only in those with LVH, and likely reflect a later stage of disease. LA strain parameters of conduit and reservoir function, however, may have a role in the detection of early cardiac involvement in Fabry Disease

Table 1.

of Left atrial function in Fabry Disease

Group A: Healthy Volunteers (n = 15)Group B: Fabry Disease, No LVH (n = 15)Group C: Fabry Disease, LVH (n = 10)p- value (Group A vs. B)p-value (Group A vs. C)p-value (Group B vs. C)
GenderMale = 7Male = 8Male = 5
Age (years)39.7 ± 14.440.1 ± 12.457.4 ± 7.9
Maximum LV Wall Thickness (mm)9.6 ± 0.910.3 ± 3.117.3 ± 6.10.43<0.00010.002
LV Ejection Fraction (%)63.8 ± 2.766.5 ± 6.268.0 ±
LA Max Volume/BSA(ml)39.3 ± 12.137.7 ± 12.949.9 ± 10.30.730.060.04
LA Min Volume/BSA(ml)16.3 ± 5.815.7 ± 5.127.6 ± 7.00.770.00070.0002
LA Pre-atrial Contraction Volume/BSA (ml)26.4 ± 8.227.0 ± 8.740.7 ± 9.60.840.00020.003
Total Ejection Fraction (%)58.8 ± 6.558.1 ± 4.044.6 ± 9.10.720.0004<0.0001
LA expansion index (%)1.48 ± 0.361.40 ± 0.230.85 ± 0.310.520.00070.0001
Total strain (%)34.86.628.25.424.45.60.0050.0020.15
Peak systolic strain rate (-1)1.31 ± 0.471.08 ± 0.271.03 ±
Passive Ejection Fraction (%)32.67.427.
Passive Strain (%)20.1 ± 6.117.4 ± 6.011.0 ±
Peak early negative strain rate (-1)-1.07 ± 0.31-0.84 ± 0.31-0.5 ±
Booster Pump
Active Ejection Fraction38.6 ± 9.141.4 ± 9.632.0 ± 8.70.420.120.04
Active Strain (%)13.8 ± 5.611.1 ± 4.213.5 ±
Peak late negative strain rate (-1)-1.0 ± 0.37-0.85 ± 0.45-0.95 ± 0.290.340.780.59
Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.13

Role of cardiac magnetic resonance in the diagnosis of ARVC/D mimics


Introduction: ARVC/D is a rare, genetic heart disease, with autosomal dominant trasmission. Diagnostic 2010 Task Force Criteria include CMR. The purpose of our study is to evaluate the role of CMR in patients with suspected ARVC/D in confirming/ruling out the diagnosis or identify mimics of ARVC/D.

Materials and Methods: Consecutive subjects referred for a clinical CMR during a 12-month period we included (N = 2481). We identified patients referred for CMR with suspected ARVC/D on the basis of symptoms and clinical presentation, family history of ARVC/D or sudden cardiac death, abnormal ECG or TTE.

Results: N = 124 patients (5% of the 12-month CMR referral cohort) were referred with suspected ARVC/D were identified. In 14% of the patients (n = 17) CMR was able to identify the final diagnosis. In addition CMR was able to establish in large part of patients a normal heart structure. N = 4 patients (3%) met criteria for ARVC/D: n = 3 major and n = 1 minor, n = 11 patients (8.8%) had disease could mimic ARVC/D “ARVC/D mimics”, n = 2 patients had evidence of previous MI and n= 70 (56%) had a normal heart structure.

Additional diagnosis identified were congenital absence of pericardium (n = 1) (Fig.1), dilated cardiomyopathy (n = 1), left ventricular non compaction cardiomyopathy (n = 1), left ventricular non compaction cardiomyopathy plus myocardial infarct (n = 1), arrhythmogenic left ventricular cardiomyopathy (ALVC, variant of ARVC/D) (n = 1), anomalous venous return (n = 1) (Fig.1), atrial septal defect with left to right shunting (n = 1) (Fig.2), asymmetric pectus excavatum (n = 1) (Fig.2), athletic heart (n = 2) and sarcoidosis (n = 1), all mimicking ARVC/D.

Conclusions: Our study demonstrates the role of CMR not only in detecting abnormalities compatible with ARVC/D but also in identifying a variety of diseases that can mimic ARVC/D.

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Figure 1. (A)(B) Congenital absence of pericardium. (A) 4-chamber view, heart is

displaced in the left side of the thorax, with apex pointing posteriorly; axial HASTE, lung interposed between the ascending aorta and the pulmonary artery (arrow) (B). (C)(D) Anomalous venous return. (C) 4-chamber view, RV dilated; (D) left upper pulmonary vein (arrow-head) on the left side of aortic arch draining upwards toward the brachiocephalic trunk.

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Figure 2. (A)(B) ASD. Large superior interatrial defect is seen with blood flowing from the left to the right (arrow-head) (C)(D) Asymmetric pectus excavatum. Right ventricle distorted by the abnormal chest morphology (arrow)

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.14

Comparison of transtlioracic ecliocardiography versus cardiac magnetic for implantable cardioverter defibrillator therapy in primary prevention strategy dilated cardiomyopathy patients


Background: Implantable cardioverter-defibriIIators(ICDs) has been proved as a valid primary prevention strategy to reduce mortaIity in patients with dilated cardiomyopathy (DCM) with reduced Ieft ventricula rejection function (LVEF) <35%. Cardiac magnetic resonance (CMR) is now considered the gold standard technique for LVEF assessment and it provides important information on tissue characterization such as late gadoIinium enhancement (LGE). Several studies have shown differences between CMR and TIE evaluation. The aim of this study is to determine whether LV evaIuation and LGE detection by CMR are superior to conventional TIE measurements for risk stratification of DCM patients evaluated for ICD impIantation in primary prevention strategy.

Methods: 270 consecutive DCM patients (Meanage 63 ± 13 yo, maIe 220 patients) referred to our Institution to be evaluated for ICD impIantation in primary prevention were enroIIed. All patients under went both the and CMR left ventricle end-diastoIic (LVEDV) and end-systoIic (LVESV) voIumes and LVE festimation. Additionally, LGE. presence was a isodetected by CMR. All patients were foIIowed-up for the major adverse cardiacevents (MACE) defined as a combined end point of ventricular tachycardia, ventricular fibrillation and sudden cardiacdeath.

Results: All patients performed both tests successfully. The mean follow-up was 850 ± 330 days. The showed a lower LVEDV (86 ± 28 vs. 131 ± 41 ml/m2) and LVEDV (57 ± 21 vs. 93 ± 40 ml/m2) and a higher LVEF (35 ± 10 vs. 31 ± 9 %) as compared to CMR (p < 0.0001). MACE occurred in 68 patients (25 %). Patients experienced MACE showed a higher LVEDV-IIE (94 ± 28 vs. 84 ± 28 ml/m2, p:0.01), LVESV-IIE (64 ± 27 vs. 55 ±23 ml/m2, p:0.003), LVEDV-CMR (141 ± 43 vs. 128 ± 41 ml/m2, p:0.01), LVESV-CMR (105 ± 42 vs. 90 ± 39 ml/m2, p:0.003), Iower LVEF-CMR (29 ± 10 vs. 32 ± 9 %, p:0.0027) and a higher LGE prevalence (67 vs. 44 %, p:0.0009) as compared to patients without MACE. At multivariate anaIysis, LVEF-CMR [HR:2.3 (1.6-3.01)] and presence of LGE [HR: 4.08 (2.15-6.02)] were independently associated with MACE (p < 0.001). In the subset of patients with LVEF-TTE > 35 %, the addition of LVEF-CMR and LGE provides anetre classification improvement (NRI) of 42 % and 26%, respectiveIy, interms of outcomes.

Conclusions: LVEF and LG Eestimation by CMR might provide additional prognostic stratification as compared to The that could identify a subset of subjects in whom ICD implantation is still indicated despite LVEF-TTE > 35%.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.1

Validation of aortic in-vitro strain measurement by Magnetic Resonance Imaging with realistic abdominal aortic aneurism phantom


Introduction: Preoperative diagnostic protocols of abdominal aortic aneurysm (AAA) are today mainly based on the measurement of the aortic maximum diameter. This measurement is insufficient because the diameter is not a discriminant variable for predicting the rupture of the aorta. Recent works show the importance of determining the wall stress both due to the aortic shape, the pressure and the blood flow. The problem is very complex and requires the implementation of sophisticated models taking into account the heterogeneity of tissues and the complexity of flow. Then it is essential to validate the capacity of existing medical imaging systems to provide reliable measurements that will be introduced in these models.

Method: The aim of this study is to verify the MRI's ability to provide reliable measurements, firstly for the deformation of the aortic wall, and secondly for the blood flow. Cine MRI acquisitions (SSFP sequence) enabled to accurately determine the geometry and deformation of the aneurysm and 4D flow MRI measurements (thanks to a 3D PC-MRI sequence) were used to quantify the velocities of the fluid. Measurements were carried out in vitro with an experimental device that simulated hemodynamic circulation on a realistic AAA phantoms in silicone that have properties closest as possible as the actual physiological conditions. The sequences were prospectively gated with the pressure signal given by a pressure sensor. The deformations of the phantom wall were then determined through solid modeling with Abaqus software in which the geometry and internal stresses determined by CFD modeling (pressure, Wall Shear Stress) were introduced (see Fig. 1). The deformations were compared with measurement made by stereovision. Moreover, blood flow estimation with MRI was compared with the fluid modelling performed with ANSYS software.

Results: The obtained deformations with MRI are close to those obtained by stereovision with relative deviations less than 15% (see Fig.2). The comparison pixel to pixel between 4D Flow IRM and CFD is difficult because the spatial discretizations are different for the both technics. However the results of the mean instantaneous velocities are very similar between the two approaches throughout the cycle. Conclusion Our approach makes it possible to validate the ability of MRI to perform deformation measurements on phantom carried out with homogeneous materials and having complex geometries in which complex flow circulate. The first results showed the performance of the MRI to provide reliable raw data that can be included in the theoretical models.

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Figure 1. The different steps of the strain calculation

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Figure 2. Maximal main strain comparison between stereovision and modelling obtained from IRM measurement

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.2

A novel method of Segment Length Tracking providing regional strain measures from standard CMR cine images in CRT candidates

A Zweerink, MD,1 CP Allaart, MD, PhD,1 L Wu, MD,1 JPA Kuijer, PhD,2 AM Beek, MD, PhD,1 P Croisille, MD, PhD,3 P Clarysse, PhD,3 AC van Rossum, MD, PhD,1 and R Nijveldt, MD, PhD1


Background: Myocardial deformation analysis, providing strain measures on a regional level throughout the left ventricle (LV), is increasingly recognized for its additional value in the selection of heart failure (HF) patients for Cardiac Resynchronization Therapy (CRT). Although Cardiovascular Magnetic Resonance (CMR) myocardial tagging (MT) is considered to be the gold standard in quantifying LV wall deformation, this specialized technique is predominantly used for scientific purposes only. CMR cine imaging, on the other hand, has become routine clinical practice in most CRT candidates. Accordingly, the purpose of this study is to evaluate the accuracy and robustness of regional strain measurements using a novel method of segment length tracking (SLT) on standard cine images in CRT candidates compared to MT.

Methods: Twenty-seven HF patients (age 65 ± 10 y, 16 men) with left bundle branch block (LBBB) underwent CMR examination with both steady-state free-precession (SSFP) cine imaging and MT imaging to determine regional strains in the septum and the lateral wall. SLT was performed by measuring segment length between two endocardial anatomic landmarks (trabeculae) throughout all phases on the mid-LV short axis cines, relative to the end-diastolic segment length (figure 1A). This measure of frame-to-frame segment length change was compared to circumferential strain measurements in the tagged mid-layer of the same short axis slice position, analyzed using inTag software (figure 1B).

Results: Regional end-systolic strain values showed excellent agreement between both methods (figure 2). End-systolic strain measures showed large variation from -18.0% in the lateral wall up to +11.7% in the septum. Over this range of 29.7%, the mean difference between both methods was -2.0 ± 6.8% with the cine analysis structurally producing slightly lower strain values compared to the tagging analysis. Reproducibility of end-systolic strain measures by SLT were excellent for both the intra-observer analysis (ICC 0.96) and the inter-observer analysis (ICC 0.92).

Conclusions: Introducing the SLT post-processing technique on standard CMR cine images offers both accurate and robust circumferential strain measures compared to the gold standard MT technique. Future studies will have to focus on the prognostic value of SLT based strain parameters in CRT candidates.

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Figure A illustrates the SLT method on cine images. Figure B illustrates the MT analysis on tagged images (same patient.) ED, end-diastolic; avo, aortic valve opening; ES, end-systolic; mvo, mitral valve opening.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.3

T1 mapping can quantify the area-at-risk and infarct size – no need for T2 mapping or conventional LGE imaging in acute STEMI at 1.5T


Background: Native T1 mapping has been shown to accurately delineate the area-at-risk (AAR) at 1.5T in dogs and at 3T in STEMI patients when compared to T2 mapping. T1 mapping-based inversion recovery (IR) synthetic late gadolinium enhancement (LGE) could also accurately quantify chronic myocardial infarct (MI) size. We evaluated whether T1 mapping could accurately quantify the AAR from the native T1 maps and the acute MI size from the post-contrast T1 mapping-based IR synthetic LGE.

Methods: CMR was performed in 22 reperfused STEMI patients on a Siemens 1.5T scanner at 2 ± 1 days. Left ventricular (LV) short axis T2 maps, native T1 (MOLLI) maps, motion-corrected, free-breathing single shot SSFP averaged PSIR LGE (FB MOCO PSIR 10 mins post Dotarem) and post contrast T1 maps (15 mins post Dotarem) were acquired. The MOLLI prototype generated 2 sets of IR images (magnitude-reconstructed IR: MagIR and phase sensitive IR: PSIR) inline at different inversion times (TI). Using CVI42 software, the images from the MagIR and PSIR sets with the optimal TI were chosen to obtain 2 sets of synthetic LGE images. Figure 1 shows an example of a patient with an anterior STEMI. MI size and AAR were quantified using 5SD and 2SD thresholds from the remote myocardium respectively and expressed as percentage of the LV.

Results: The AAR by T2 was 42.7 ± 13.0% and by T1 was 42.6 ± 13.2%, P = 0.86 with an excellent correlation (R = 0.99) and agreement (bias = 0 ± 4.6%). The MI size by FB MOCO PSIR LGE was similar to MagPSIR synthetic LGE (24.8 ± 14.7% versus 24.6 ± 14.3%, P = 0.51) but marginally higher than PSIR synthetic LGE (24.8 ± 14.7% versus 24.1 ± 14.1%, P = 0.01). There was an excellent correlation and agreement between both the FB MOCO PSIR LGE and MagPSIR synthetic LGE (R= 0.99, bias = 0 ± 2.5%) and PSIR synthetic LGE (R = 0.99, bias = 0 ± 2.4%).

Conclusions: T1 mapping allows the quantification of the AAR from the native T1 maps and MI size from the synthetic LGE images derived from the post-contrast T1 maps. Scanning time could be shortened by not doing T2 mapping or LGE.

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Figure 1.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.4

Reliability and reproducibility of trans-valvular flow measurement by 4D flow magnetic resonance imaging in acute myocardial infarct patients: two centre study


Background: 4-dimensional (4D) flow MRI has advantage over 2-dimensional PC-MRI as it allows retrospective valve tracking, multi-planar dynamic phase contrast reconstruction to estimate stroke volumes (SV) reliably with good reproducibility in healthy subjects. However, this has not been demonstrated in patients with regional wall motion abnormality. We hypothesise that the SV assessed by 4D flow MRI through the mitral valve (MV) and the aortic valve (AV) will be consistent. We also investigated mitral valve (MV) and aortic valve (AV) SV and also the inter-observer reliability for intracardiac flow in acute myocardial infarction (AMI) patients.

Methods: Fifteen patients underwent CMR at 1.5T (Ingenia CV, Philips Healthcare, Best, The Netherlands). CMR Protocol included: 2-chamber, 3-chamber, 4-chamber cines and 4D flow MRI with isotropic voxel size (3 × 3 × 3mm3), parallel imaging (SENSE 2), velocity sensitivity Venc 150cm/s in all three directions and using echo-planar imaging (EPI) to factor of 5 for read-out acceleration. Free breathing was allowed and no respiratory motion correction was used. Retrospective gating was used and 30 cardiac phases were reconstructed. Images were analysed by two assessors (MH and PG) from two sites blinded to each other. Retrospective valve tracking with measurement planes positioned perpendicular to the inflow direction on 2-, 3- and 4-chamber cines was used to calculate SV. Background correction was used from velocity sampled in the myocardium.

Results: Mean MV SV was 68 ± 15 ml (PG) and 67 ± 17 ml (MH) (p = 0.90). Mean AV SV was 70 ± 20 ml (PG) and 73 ± 14 ml (MH) (p = 0.96). Eight (53%) patients had mitral regurgitation, four (27%) had aortic regurgitation and four (27%) had tricuspid regurgitation. All regurgitation was graded as trivial/mild (MR fraction - 6.7 ± 2 %; AR fraction - 1.9 ± 4 %). SV through MV and AV did not differ (PG: intraclass correlation coefficient (ICC) was 0.94, CI 0.81–0.97 p = 0.65; MH: ICC = 0.86, CI 0.46–0.96 p = 0.35). Coefficient of variation (CV) of inter-observer variability for MV SV was 6.3% and the concordance correlation coefficient was 0.93 CI (0.81-0.97) with accuracy of 0.99. CV of inter-observer variability for AV SV was 6.4% and the concordance correlation coefficient was 0.90 CI (0.72-0.96) with accuracy of 0.98.

Conclusion: 4D flow MRI with retrospective valve tracking provides reliable assessment of transvalvular flow in AMI patients with high inter-observer agreement.

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Figure 1. Scatter diagram for MV and AV stroke volume demonstrating inter-observer reproducibility.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.5

Insights into hypertensive heart disease phenotypes: spectrum of myocyte, interstitial and vascular changes by cardiovascular MRI

Jonathan C L Rodrigues, BSc(Hons), MBChB(Hons), MRCP, FRCR,1,2 Antonio Matteo Amadu, MD,1,3 Amardeep Ghosh Dastidar, MBBS, MRCP,1,4 Gergley Szantho, MD, MRCP,1 Stephen Lyen, MBBS, FRCR,1,5 Cattleya Godsave, BSc, MBBS, MRCP,1 Laura E K Ratcliffe, BSc(Hons), MBBS, MRCP,6 Amy E Burchell, MA, BM BCh, MRCP,4,6 Emma C Hart, BSc, PhD,2,6 Mark C K Hamilton, MBChB, MRCP, FRCR,1,5 Angus K Nightingale, MA, MB BChir, FRCP, MD,4,6 Julian F R Paton, BSc(Hons), PhD,2,6 Nathan E Manghat, MBChB, MRCP, FRCR, MD,1,5 and Chiara Bucciarelli-Ducci, MD, PhD, FESC, FRCP1,4


Introduction: The European Society of Cardiology classified hypertensive heart disease (HHD) into 4 left ventricular (LV) phenotypes by indexed LV mass (LVM), mass : volume ratio (M:V) and indexed end diastolic volume (EDV) (Table 1). All forms of HHD carry varying degrees of adverse cardiovascular prognosis, but their underlying mechanisms are poorly understood. We sought to investigate the presence and extend of ultra–structural myocardial changes and variation in central aortic function using CMR relaxometry and voxel–tracking myocardial strain techniques.

Methods: 88 hypertensive patients (49 ± 14 years, 57% male, SBP: 167 ± 30mmHg, DBP: 96 ± 14 mmHg) underwent CMR (1.5T) and were compared with 29 age–and sex–matched normotensive controls (47 ± 14years, 59% male, SBP: 128 ± 12mmHg, DBP: 79 ± 10mmHg). Native and post–contrast T1–mapping was performed. Circumferential myocardial strain was calculated with voxel–tracking software. Aortic compliance and distensibility were also estimated.

Results: Please see Figure 1. At a structural level, increased LV mass in eccentric LVH and concentric LVH resulted from: i) significantly increased myocardial cell volume (eccentric LVH: 78 ± 19 vs concentric LVH: 73 ± 15 vs remodeling: 55 ± 9 respectively, P < 0.05) and ii) significantly increased interstitial volume (eccentric LVH: 33 ± 10 vs concentric LVH: 30 ± 10 vs remodeling: 19 ± 2 respectively, P < 0.05). Functionally, eccentric LVH and concentric LVH were associated with significantly impaired peak circumferential strain (eccentric LVH: –12.8 ± 4.6 vs concentric LVH: – 15.5 ± 3.1 vs remodeling: –17.1 ± 3.2 vs controls: –17.4 ± 2.6% respectively, P < 0.05), with evidence of systolic and diastolic strain rate impairment. Despite similar BP severity as LVH phenotypes, LV remodeling was not associated with significant intracellular/interstitial expansion (native T1: 1029 ± 45 vs 1024 ± 41ms, P = 0.67) or myocardial dysfunction compared to normotensive controls but was associated with reduced aortic compliance and distensibility.

Conclusions: The extent of interstitial fibrosis is different across hypertensive heart disease phenotypes. LVH, in particular eccentric LVH, is associated with significant myocardial interstitial fibrosis and systolic/diastolic strain impairment. LV remodeling is associated with normal myocardial, but abnormal aortic, function. Our results may explain the poor cardiovascular prognosis with hypertensive LVH.

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Figure 1.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.6

Myocardial partition coefficient of gadolinium: A comparison between patients with acute myocarditis, chronic infarction and healthy volunteers


Introduction: Cardiovascular magnetic resonance (CMR) imaging allows distinction of myocarditis (MC) from myocardial infarction (MI). The tissue-blood partition coefficient (PC) of gadolinium, derived from T1 measurements, may reflect tissue injury, increasing in proportion to the expansion of the extracellular volume by edema or fibrosis. In this study, we compared the PC of gadolinium in the overall myocardium, in scarred areas and in unscarred (remote) areas in healthy volunteers, in patients with acute MC and in patients with chronic MI. We also correlated the PC with the myocardial scar burden.

Methods: Healthy volunteers (10, males (53.5 %), 49.2 ± 12.3 years), chronic MI patients (19, males (94.7 %), 62.7 ± 8.0 years) and acute MC patients (15, males (80%), 46.9 ± 15.6 years) underwent late gadolinium enhancement (LGE) CMR imaging and MOLLI T1 measurements with administration of gadolinium (Gd-BOPTA) at 3T (Magnetom Skyra, Siemens Healthcare, Erlangen). T1 measurements were performed before, 5 and 15 minutes after Gd-BOPTA injection, in 3 short-axis slices, analyzing both the entire myocardium and the remote myocardium after exclusion of the scar, as defined by LGE. The PC for Gd-BOPTA was computed. The percent of LGE volume (signal intensity > 5 SD above the remote myocardium signal intensity) was used to measure the scar burden.

Results: The PC was higher in the overall left ventricular myocardium of MC patients compared to chronic MI and volunteers (0.43 ± 0.07 vs. 0.40 ± 0.05, p = 0.08 vs. 0.40 ± 0.06, p = 0.09, respectively). PC in MC scars was significantly higher than in the remote myocardium (0.60 ± 0.12 vs. 0.40 ± 0.08, p = 0.002), and significantly lower than in chronic MI scars (0.60 ± 0.12 vs. 0.85 ± 0.21, p = 0.002). There was no difference between PC in the remote myocardium of MC and chronic MI patients compared to healthy volunteers. The correlation between % volume of LGE and PC in LV was strong and significant in MC and chronic MI patients with R = 0.89, p = 0.04 and R = 0.74, p = 0.03 for MC and chronic MI patients respectively (figure 1).

Conclusion: The PC of Gd-BOPTA is significantly elevated in areas of acute and chronic myocardial injury. Based on PC results, MC may show diffuse myocardial injury while chronic MI scars correspond to focal areas with a higher degree of gadolinium uptake, suggesting denser replacement fibrosis. The longitudinal change in PC and its relation to the evolution of MC may be studied to use it as an index of disease activity

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Figure 1. Correlation between partition coefficient and LGE volume in percent of LV volume

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.8

A comparison of circumferential strain results from multiple software packages in healthy subjects


Background: Cardiovascular Magnetic Resonance (CMR) is an important modality to assess cardiac function. CMR is now the reference standard modality to assess myocardial global parameters such as cardiac mass, volume and ejection fraction but it can also assess myocardial regional deformation parameters such as strain and strain rate throughout the cardiac cycle. An accurate assessment of regional parameters could allow earlier detection of cardiac disease onset thus playing a critical role in patient management and improving quality of life. An increasing number of studies make use of feature tracking techniques as a quantitative post processing method. They derive motion deformation parameters from standard steady-state free precession sequence, which is part of routine clinical imaging protocols. The main objective of this study is to compare circumferential strain measurements obtained from different feature tracking and tagging software packages in healthy subjects.

Methods: 41 healthy subjects were prospectively enrolled to undergo CMR; one study was excluded for insufficient image quality. All images were obtained using a 1.5T Achieva Philips scanner (Best, the Netherlands) and a dedicated 32-channel cardiac coil. Steady state free precession breath hold cine images were obtained in the short axis plane (basal, mid and apical levels). Matching short axis tagged images were obtained using complementary spatial modulation of magnetization (CSPAMM), with a tag separation of 7.5 mm and a tag grid angle of 90o. Tagging is considered as the reference standard method to measure strain from CMR images.

Endocardial and epicardial boundaries of the left ventricle were drawn manually at end diastole and end systole. Strain and strain rate values were calculated semi-automatically using the following software packages: 2D Cardiac Performance Analysis, MR (TomTec Imaging Systems, Munich, Germany), CVI42 (Circle Cardiovascular Imaging Inc. Calgary, Canada) and CIM-FT (Auckland MRI Research Group, New Zealand). Tagged images were analyzed using CIMTag2D software (CIMTag2D v.8.1.2, Auckland MRI Research Group, New Zealand). All statistical analysis was done using SPSS (IBM Corporation, Armonk, New York, USA).

Results: Results of global circumferential strain and strain rate means are given in Table 1 and Table 2.

There were significant differences (P < 0.05) in most circumferential (basal, mid, apical) strains measured by Tomtec, CVI42 and CIM-FT compared to CIMTag measurements. There were also statistically significant differences for most circumferential (basal, mid, apical) strain rates measured by FT-software packages compared to CIMTag results. Strain rate results measured by Tomtec showed significant differences for 3 parameters, whilst 3 parameters showed no significant difference compared to CIMTag results. Mean strain results measured by CIMTag showed higher values in most parameters than FT-software packages results.

Figure 1 shows a box plot of the peak absolute values of the global circumferential strain for the mid short axis slice. The peak strain measured by CVI42 is more spread out compared to other software packages, which indicates more variability. Apical and basal slices showed similar trends. Moreover, apical and mid circumferential strain results measured by CIMTag were higher than those measured by FT-software packages.

Conclusions: FT- software packages showed significant differences in circumferential strain measurements when compared to CIMTag, with only a few parameters in agreement. Higher variability was observed for CVI42 compared to other software packages. There is a clear need for a reference standard method of validation, ideally based on a numerical phantom to assess the accuracy of these software packages in order to facilitate their use in a clinical setting. Currently outputs from different FT software cannot be directly compared and a need for standardization exists.

Funding: This project is funded by a Saudi scholarship to the first author.

Table 1.

Absolute value of global circumferential strain (%) measurement for different software packages. Data are presented as mean ± standard deviation (SD). Grey cells show there was a significant difference (p < 0.05) with CIMTag measurements.

ParametersCIMTagFeature Tracking
SAX-basal17.78 ± 2.1220.27 ± 5.8915.62 ± 2.9816.92 ± 2.50
SAX-mid19.49 ± 3.9816.68 ± 4.0614.22 ± 2.8415.25 ± 2.37
SAX-apical19.59 ± 5.4317.33 ± 4.1517.48 ± 4.0218.48 ± 4.48

Table 2.

Absolute value of global circumferential strain rate (s-1) measurements for the different software packages. Data are presented as mean ± standard deviation (SD). Grey cells highlight significant differences (p < 0.05) with CIMTag measurements. RP= Reverse Peak, P= Peak

ParametersCIMTagFeature Tracking
SAX-basalRP−0.76 ± 0.12−1.21 ± 0.78−0.75 ± 0.18−0.64 ± 0.12
P0.71 ± 0.151.33 ± 1.040.86 ± 0.210.55 ± 0.17
SAX-midRP−0.88 ± 0.12−0.85 ± 0.27−0.76 ± 0.18−0.65 ± 0.13
P0.76 ± 0.170.99 ± 0.340.69 ± 0.190.46 ± 0.12
SAX-apicalRP−0.93 ± 0.11−0.79 ± 0.21−1.07 ± 0.63−0.87 ± 0.32
P0.86 ± 0.210.98 ± 0.250.99 ± 0.660.61 ± 0.37

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Figure 1. Absolute peak global circumferential strain for mid-short axis slice measured by different software packages.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.1

Cardiac Involvement in Patients With Different Rheumatic Disorders


Purpose: There is much controversy about the prevalence of cardiac involvement in patients with rheumatic disorders. This is of importance, since consequences of cardiac involvement range from different treatment regimes to adverse outcomes. Consequently, our primary aim was to evaluate the prevalence of cardiac involvement in different forms of rheumatic disorders by CMR.

Methods: 297 patients underwent CMR. Cardiac involvement was defined by presence of late gadolinium enhancement (LGE). Patients with a history of myocardial infarction and/or prior revascularization procedure were excluded. Patients were further divided into 5 subgroups: (1) ANCA associated vasculitis, (2) non-ANCA associated vasculitis, (3) autoimmune connective tissue disorders, (4) arthritis, and (5) sarcoidosis.

Results: We enrolled n = 63 patients in the ANCA associated vasculitis group, 34 of them (54%) were LGE positive. LGE showed a non-ischemic pattern in 33 patients (97%), isolated ischemic LGE pattern was present in only 1 patient. The Non-ANCA associated vasculitis group consisted of 32 patients, in 7 patients (22%) LGE could be detected. LGE was non-ischemic in 6 patients (86%), isolated ischemic LGE was present in only 1 patient. In the group with connective tissue disorders 15 out of 110 patients (14%) showed LGE: Of these, 13 patients (87%) showed non-ischemic LGE, 2 patients isolated ischemic LGE, 2 patients had both non-ischemic and ischemic pattern. The Arthritis group consisted of 47 patients, in 10 of them (21%) LGE was detected. Non-ischemic LGE pattern was found in 8 patients (80%), ischemic LGE was present in 3 patients (30%), in one patient LGE-CMR revealed both LGE patterns. 45 patients were in the sarcoid group, 11 of them (24%) showed LGE: 8 patients had non-ischemic LGE (73%), 3 patients ischemic LGE (27%). Comparing prevalence of cardiac involvement in the five different rheumatic subgroups, the highest prevalence of cardiac involvement (54%) was detected in patients with ANCA-associated vasculitis. Conversely, in our cohort of autoimmune connective tissue disorders, LGE CMR revealed the lowest prevalence of cardiac involvement.

Conclusion: There is a wide variation in the prevalence of cardiac involvement in different groups with rheumatic disorders. In patients with ANCA associated vasculitis cardiac involvement seems to be common (54%), whereas patients with autoimmune connective tissue disorders seem to have a low prevalence of cardiac involvement (14%).

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.2

Gender differences in the development of cardiac complications: a multicentric prospective study in a large cohort of thalassemia major patients


Introduction: We aimed to prospectively assess if the male gender was associated with an higher risk of progressive cardiac iron accumulation, development of biventricular dysfunction and myocardial fibrosis assessed by CMR, and development of cardiac complications including heart failure (HF), arrhythmias and pulmonary hypertension (PH).

Methods: We considered 1711 TM patients (899 females, 31.09 ± 9.08 years), consecutively enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) Network. Myocardial iron overload was assessed by the multislice multiecho T2* technique. Biventricular function was quantified by cine images. Late gadolinium enhancement (LGE) images were acquired to detect myocardial fibrosis.

Results: Although having a similar risk of accumulating iron, males showed a significant higher risk of developing cardiac dysfunction, heart failure, arrhythmias and cardiac complications globally considered (Table 1). Figure 1 shows the Kaplan-Meier curves for the outcomes for which the male sex was a significant prognosticator. Until 20-30 years of follow-up (FU) the two lines (male and female sex) were almost overlapping while after they clearly diverged.

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Patients were divided in two groups based on the FU duration. A significant gender-specific difference in the frequency of ventricular dysfunction and cardiac complications appeared for patients followed for at least 20 years. So, two subgroups of patients were identified: patients followed for less than 20 years and patients followed for more than 20 years. In the first subgroup males and females had a comparable risk of developing cardiac iron overload, ventricular dysfunction and cardiac complications. Conversely, if a FU longer than 20 years was considered, males exhibited a significant higher risk of having ventricular dysfunction, heart failure, arrhythmias, and cardiac complications.

Conclusion: Females seem to tolerate iron toxicity better, possibly as an effect of reduced sensitivity to chronic oxidative stress. According to the International Guidelines, TM patients should perform a complete cardiac evaluation every year. Our study suggested that in females older than 20 years the FU may be performed every 24 months, thus reducing health care costs.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.3

Comparison of T1-mapping, T2-weighted and contrast-enhanced cine imaging at 3.0T CMR for diagnostic oedema assessment in ST-segment elevation myocardial infarction


Background: Myocardial salvage index (MSI) derived using cardiac magnetic resonance (CMR) can be used to gauge success of reperfusion strategies; it remains a strong predictor of adverse remodeling and prognosis post STEMI. However, various limitations of sequences used to typically image myocardial oedema have made it challenging to achieve reliable AAR detection in the majority in clinical trials. Optimal detection of reversible myocardial injury could improve the reliability of MSI determination and its prognostic relevance.

Objective: To compare the robustness of myocardial oedema detection using T2-weighted short-tau inversion recovery (T2w-STIR), free-breathing motion-corrected (moco) T1-mapping and contrast-enhanced steady state free precession (CE-SSFP) sequences on 3.0T CMR in patients presenting with STEMI.

Methods: Forty-five patients underwent CMR 1-5 days following presentation with STEMI. AAR was quantified using semi-automatic thresholding on T2w-STIR and short-axis CE-SSFP cine images and resulting parametric colour maps from moco-T1 Modified Look Locker Inversion Recovery (MOLLI) sequences and compared using analysis of variance (ANOVA). Pearson's correlation coefficient was used to assess correlation. Inter-sequence agreement was assessed using the Bland-Altman method, coefficient of variation (CoV) and two-way mixed-effect intra-class correlation coefficient (ICC) for absolute agreement.

Results: Patient characteristics are presented in Table 1. AAR assessed using the three methods was not significantly different (p = 0.988) with excellent correlation and good agreement, although with wide limits of agreement (see Table 2). Correlation and agreement between AAR derived using moco-MOLLI and CE-SSFP were excellent. However, the diagnostic imaging rate obtained with T2w-STIR (76%) was poor compared with CE-SSFP (87%) and highest with moco-T1-mapping (98%), p = 0.008.

Conclusions: moco-T1-mapping using MOLLI may be the more robust than T2w-STIR and CE-SSFP for detecting reversible myocardial injury and determination of MSI for the prediction of functional recovery following STEMI. The poor diagnostic imaging rate of T2w-STIR may limit its usefulness in large clinical studies. CE-SSFP maybe a useful alternative to T2w-STIR for AAR detection where T1-mapping is not available. Our findings require validation in larger multi-centre studies.

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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.4

Evaluation of Tissue Changes in Remote Noninfarcted Myocardium after Acute Myocardial Infarction using T1-mapping


Background: Following acute myocardial infarction (MI) there is an extensive inflammatory reaction in infarcted myocardium. However, less is known about the inflammatory response in noninfarcted remote regions, and its role in cardiac remodelling. The present study assesses the temporal changes in T1-relaxation parameters (as markers of edema and cellularity) of the remote myocardium after acute MI, and determines its relationship with cardiac remodelling.

Methods: In this prospective study, 42 patients with acute MI treated with primary PCI were included and underwent CMR after 4-6 days and 3 months. Cine imaging, late gadolinium enhancement, and T1-mapping (MOLLI) was performed at 1.5T. T1-maps were acquired at the level of the infarcted area, before and 8 and 25-minutes after bolus (0.2 mmol/kg) injection of a gadolinium (Gd)-based contrast. T1 relaxation times were measured in the myocardial tissue opposite of the infarcted area. Gd-clearance rate was calculated by dividing the change in T1 between the 2 post-contrast time points by the time interval. Native T1 relaxation times were corrected for heart rate variability during data acquisition and were normalized to blood T1.

Results: Native T1 values of remote myocardium had significantly decreased from baseline to follow-up (997 ± 35 msec to 986 ± 27 msec, p < 0.01)(Figure 1). There were, however, no changes from baseline to follow-up in 8-min post-contrast T1 (p = 0.48), 25-min post-contrast T1 (p = 0.16), and Gd-clearance rate (p = 0.95). At baseline, remote native T1 values significantly differed between subgroups of patients, and were higher in patients with microvascular obstruction (MVO) (p = 0.02), an anterior MI (p = 0.04), absence of ST segment resolution (STR) (0.04), and large MI size (p = 0.01)(Figure 2). In a multivariable linear regression model, remote zone native T1 values at baseline were inversely associated with left ventricular ejection fraction (LVEF) at baseline (B: -0.08, p < 0.01), but were not associated with changes in LVEF or LV volumes.

Conclusion: In remote noninfarcted myocardium, a small change in native T1, but not in post-contrast T1 or Gd-clearance rate, was observed between baseline and 3 months after acute MI. Remote native T1 values at baseline were associated with markers of reperfusion injury and were independently associated with worse LVEF post-MI.

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Figure 1. Native normalized T1 relaxation times in remote myocardium 4–6 days (base) and 3 months (FU) after MI.

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Figure 2. Differences in remote native T1 values between patients with (open squares) and without (black squares) MVO, anterior MI, no STR, and large MI.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.5

Right ventricular long axis strain – The prognostic value of a novel parameter in non-ischemic dilated cardiomyopathy using standard cardiac magnetic resonance imaging


Background: Long axis strain (LAS) has been shown to be a fast assessable parameter for the analysis of left ventricular longitudinal function in cardiac magnetic resonance (CMR). However, the prognostic value of right ventricular long axis strain (RV-LAS) using CMR is unknown. This study investigates the association of RV-LAS with outcome in patients with non-ischemic dilated cardiomyopathy (DCM).

Methods: 350 consecutive patients with DCM were prospectively included and analyzed retrospectively. RV-LAS was assessed by measuring the length between the epicardial border of the left ventricular apex and the middle of a line connecting the origins of the tricuspidal valve leaflets in enddiastole and endsystole (figure 1). Values for RV-LAS were calculated according to the strain formula.

Results: The endpoint, a combination of cardiac death, heart transplantation, cardiac decompensation or sustained ventricular arrhythmias, occurred in 85 patients during a mean follow-up period of 3.8 ± 0.1 years. The mean values of RV-LAS were significant reduced in patients with endpoint (-10.6 ± 4.4 vs. -8.3 ± 3.9, p = <0.0001). On multivariate analysis, RV-LAS remained an independent predictor of the endpoint (HR 1.1, p = 0.004). ROC analysis yielded a RV-LAS criterion of -8.9% for the endpoint. Kaplan-Meier survival curves showed a reduced outcome in patients with RV-LAS ≤-8.9% (p < 0.0001).

Conclusion: Assessment of RV-LAS in CMR is an independent predictor of outcome in patients with DCM and offers incremental information beyond standard CMR parameters including LGE.

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Figure 1. RV-LAS: The length between the epicardial border of the LV apex and the middle of a line connecting the origins of the tricuspidal valve leaflets was measured in both enddiastole and endsystole.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.6

The role of the right ventricular insertion point in heart failure patients with preserved ejection fraction: Insights from a cardiovascular magnetic resonance study


Background: In pulmonary hypertension (PH), increased afterload for the right ventricle (RV) is reported to induce fibrosis at the RV insertion point (RVIP), detectable by cardiac magnetic resonance (CMR) using late gadolinium enhancement (LGE). In contrast to LGE imaging, T1-mapping, a new CMR technique, allows quantitative assessment of myocardial native T1 times and extracellular volume (ECV). However, the role of T1-mapping of the RVIP in humans is unknown and the prognostic value has never been investigated.

Methods: We investigated 116 patients with heart failure and preserved ejection fraction (HFpEF), a patient population frequently suffering from PH, who underwent CMR including T1-mapping. Of these, 100 (86%) underwent right heart catheterization (RHC) for hemodynamic assessment. Native T1-times were measured at the anterior and inferior RVIP and ECV was calculated.

Patients were followed for 21 ± 18 months and the prognostic value of T1-mapping of the RVIPs was investigated by Cox-regression analysis.

Results: A total of 82% suffered from PH (mean pulmonary artery pressure, mPAP, ≥25mmHg). In 30%, LGE was detectable at the anterior RVIP, which was associated with higher mPAP as compared to patients without LGE (39 ± 13mmHg vs. 32 ± 9mmHg, p = 0.045), however, this was not seen for the inferior RVIP (34 ± 11mmHg vs. 31 ± 10mmHg, p = 0.118), where in 77% of patients LGE was present.

Native T1-times were 987 ± 78ms at the anterior and 1017 ± 89ms at the inferior RVIP and ECV was 32 ± 6% and 35 ± 7%, respectively. There was a significant correlation between mPAP and native T1 times as well as ECV of the anterior RVIP (r = 0.354, p < 0.001 and r = 0.248, p = 0.038) and the inferior RVIP (r = 0.248, p = 0.026 and r = 0.289, p = 0.015).

In total, 23% experienced a cardiovascular event. By Kaplan-Meier analysis, LGE was significantly associated with reduced survival when present at the anterior RVIP (log-rank, p = 0.011) but not at the inferior RVIP (log-rank, p = 0.207).

By multivariable Cox-regression, native T1-times at the anterior, but not the inferior, RVIP above the median were significantly associated with outcome (p = 0.037), even after adjusting for age, atrial fibrillation, diabetes, NT-proBNP levels, RV size and function, and presence of LGE at the anterior RVIP.

Conclusion: T1-mapping at the anterior RVIP provides new insights in the pathological processes in HFpEF patients and might detect alterations at early stages in these patients. Additionally, it is a predictor of outcome.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.7

Myocardial fibrosis associates with B-type natriuretic peptide levels and outcomes more than wall stress


Background: B-type natriuretic peptide (BNP) is a nonspecific cardiac risk marker attributed to hemodynamic wall stress that strongly associates with adverse outcomes, but whether myocardial fibrosis (MF) is more strongly associated with both BNP and risk than wall stress is uncertain. Such data might demonstrate MF as a novel etiology of BNP elevation and further promote the emerging paradigm of MF as a therapeutic target in cardiomyopathy and heart failure.

Methods: We measured MF with histologically validated extracellular volume fraction (ECV) measures in 1176 consecutive adult individuals referred for clinical cardiovascular magnetic resonance (CMR). Linear regression quantified associations with log transformed BNP. Among those at risk with elevated BNP (≥100 pg/mL), Cox regression models quantified associations with the combined endpoint of all-cause mortality or hospitalization for heart failure (HHF) using a standardized definition, blinded to ECV and wall stress data. All multivariable models (linear or Cox) adjusted for demographics, EF and volumes, body mass, renal function, atrial fibrillation, mitral regurgitation, ischemic cardiomyopathy, and myocardial infarction size.

Results: Median age was 56 years (IQR 44-66). Median ECV was 27.6 (IQR 25.5-30.7%). Both ECV and wall stress associated with log BNP (p < 0.001) in univariable linear regression models, but ECV was more strongly associated (t value 17.2 vs. 15.5). In multivariable linear regression models, ECV remained strongly associated with log BNP (t value 10.6, p < 0.001), whereas wall stress was no longer associated with log BNP (t value 0.7, p = 0.51). In 497 patients with BNP ≥ 100 pg/mL, 103 events occurred (43 HHF and 78 deaths including 16 deaths after HHF) over a median of 2.3 years. Wall stress did not associate with outcomes. In contrast, ECV was the variable most strongly associated with adverse events (HR 1.36 95%CI 1.15-1.61) for every 5% increase in multivariable Cox models.

Conclusion: Myocardial fibrosis (MF) is more strongly associated with BNP than wall stress. In those with elevated BNP, ECV was robustly associated with outcomes but wall stress was not. These data suggest that MF is a key mediator of cardiomyopathy and vulnerability. Since MF is known to be reversible, MF may be a promising therapeutic target in heart failure and cardiomyopathy.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.8

Prognostic Value of Pulmonary Blood Volume by Contrast-Enhanced Magnetic Resonance Imaging in Heart Failure Outpatients – The PROVE-HF Study

F. Ricci, MD, A. Barison, MD, PhD, G. Todiere, MD, R. Gaeta, MD, PhD, S. Galllina, MD, PhD, M. Emdin, MD, PhD, R. De Caterina, MD, PhD, and G.D. Aquaro, MD


Background: In patients with heart failure (HF) early diagnosis of subclinical congestion is key to ensure prompt and effective treatment, and to prevent recurrent hospitalizations. Pulmonary blood volume (PBV) is a novel magnetic resonance (MRI) tool for the quantitative evaluation of pulmonary congestion.

Purpose: To prospectively assess the prognostic value of PBV in a cohort of HF outpatients.

Methods: Forty-four consecutive patients (34 men, 60 ± 12 years) and 31 age- and sex-matched healthy controls underwent contrast-enhanced cardiac MR. PBV was calculated as the product of stroke volume and number of cardiac cycles for an intravenous bolus of gadolinium contrast to pass through the pulmonary circulation, as determined by first-pass perfusion imaging.

Results: As compared to healthy controls, chronic HF outpatients showed significantly higher PBV index (PBVI, 317 ± 112 vs. 379 ± 146, ml/m2, p = 0.03) and pulmonary transit time (PTT, 6.6 ± 1.8 vs. 8.4 ± 2.9 sec, p = 0.004). PBVI was significantly associated with echocardiographic indices of diastolic dysfunctioN. Namely, PBVI showed a moderate positive correlation with tissue-Doppler E/E' ratio (R2 = 0.391, P < 0.001) and systolic pulmonary artery pressure, as assessed by CW-Doppler (R2 = 0.255, P < 0.001).During a median follow-up period of 39 ± 20 months, 13 patients (29%) reached the composite end-point of cardiovascular death, HF hospitalization or sustained ventricular arrhythmias/appropriate ICD intervention. Using a cut-off point of PBVI >541 ml/m2, corresponding to 2SD above the mean of healthy controls, Kaplan-Meier event-free survival rates were significantly higher in patients below (81%) as compared with patients above (14%) this cut-off (P < 0,001). On multivariate analysis PBVI was the only independent predictor of the composite end-point (HR 8.3- 95% CI: 2.01-35.66; p = 0.004).

Conclusions: PBVI is a novel approach to quantitatively determine pulmonary intravascular blood pool and may be used to evaluate the severity of pulmonary congestion in HF patients undergoing cardiac MRI examination.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.9

Magnetic Resonance Adenosine Perfusion Imaging as Gatekeeper of Invasive Coronary


Background: Current guidelines for the diagnosis and management of patients with stable coronary artery disease (CAD) strongly support the performance of non-invasive imaging techniques for the detection of myocardial ischemia prior to revascularization procedures. This recommendation originates from the strong evidence base showing the lack of prognostic benefit from percutaneous coronary interventions (PCI) over optimal medical therapy in patients without verification of myocardial ischemia. On the other hand, it could be demonstrated that patients with functionally significant coronary artery stenoses do benefit from revascularization. Cardiac magnetic resonance imaging (CMR) has emerged to be a diagnostic modality of choice for the detection of myocardial ischemia with high sensitivity and specificity. We therefore designed this prospective and randomized trial to compare a CMR-driven vs. angiography-driven management of patients with stable CAD and pathologic stress ECG concerning major cardiac endpoints, futile angiographies and quality of life.

Methods: Consecutive patients suspicious of initial manifestation or progress of CAD were prospectively enrolled in this study. After obtainment of written consent, subjects were randomized 1:1 into two groups. Group I directly underwent coronary angiography. PCI was performed in case of ≥70% stenosis in a coronary vessel with ≥2 mm diameter. Group II underwent contrast-enhanced (Dotarem, Guerbet, France) adenosine-perfusion CMR at 3 Tesla. Patients that exhibited reversible ischemia were then sent to PCI. All patients received optimal medical therapy.

After sample size estimation and power analysis, follow-up was planned to be 3 years for every patient.

Primary endpoint was defined as cardiac death and non-fatal myocardial infarction. Secondary endpoints were number of coronary angiographies with and without PCI and change in symptoms/quality of life. Symptoms were objectified by the Seattle Angina Questionnaire (SAQ) at baseline and after each year of follow-up.

Results: After randomization, group I consisted of 101 patients, 93 of these patients were treated according to protocol. In group II, 95 out of 99 patients received the initially planned treatment. In group I, there 50 (53.8%) coronary angiographies revealed no obstructive CAD. The other 43 (46.2%) subjects were treated with PCI. In the CMR group, 68 (71.6%) patients did not exhibit reversible ischemia and were thus treated conservatively. The other 27 (28.4%) patients with reversible ischemia were sent to PCI. SAQs showed no significant baseline difference between both groups. One year results are expected in January 2016.

Conclusion: This is a randomized and prospective clinical trial with three-years follow-up period, which will prove whether a CMR-driven management of patients with stable CAD is non-inferior compared to primary coronary angiography regarding hard endpoint as myocardial death or non-fatal myocardial infarction and quality of life assessed by the SAQ. One year follow-up data will be available for presentation during the EuroCMR meeting 2016.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.10

Influence of non-invasive hemodynamic CMR parameters on maximal exercise capacity in surgically untreated patients with Ebstein's anomaly


Introduction: Ebstein's anomaly is often associated with RV dysfunction. Data on RV function in surgically untreated patients are however rare. Since a good quality of life correlates with a good exercise capacity in daily life, we investigated non-invasive quantitative data derived from cardiovascular magnetic resonance (CMR) and its impact on maximal exercise capacity in patients with surgically untreated Ebstein's anomaly.

Methods: We investigated 54 unoperated patients with Ebstein's anomaly, age 5 to 69 years (median 30 years) and examined these patients with CMR and cardiopulmonary exercise testing (CPET). We compared seventeen CMR parameters with CPET parameters. We performed univariate and multivariate analysis with the focus on the maximal exercise capacity in these patients. For the maximal exercise capacity peak oxygen uptake as the percentage of normal (peakVO2%) was selected. The following CMR volume and flow parameters were correlated to peakVO2%. Both right and left ventricular ejection fraction (RVEF and LVEF), the indexed enddiastolic and endsystolic volumes (RVEDVi, RVESVi, LVEDVi and LVESVi) as well as the indexed stroke volumes (RVSVi and LVSVi), the total normalized right and left heart volumes (volume of the atrium and the ventricle together) as well as the total right to left heart volume ratio (R/L-ratio). Indexed flow data as the antegrade (PA ante, Aorta ante) and the indexed net flow (PA netto, Aorta netto) in the pulmonary artery and the aorta as well as its normalized values on heart rate (CI-PA, CI-Aorta) were used.

Results: RVEF (r2 0.2788), PA netto (r2 0.2330), and PA ante (r2 0.1912) showed the best correlation with peakVO2% (all p < 0.001). Further significant linear correlation could also be demonstrated with CI-PA, LVEF, LVSVi, Aorta netto, RVESVi and Aorta ante. All other parameters did not show a significant correlation with peakVO2%. Multivariate analysis for RVEF and PA netto revealed a r2 of 0.4350.

Conclusions: CMR parameters reflecting cardiac function as RVEF and LVEF and flow data of cardiac forward flow best correlate to peakVO2%. The evaluation of the indexed net flow in the pulmonary artery and the overall function of the right ventricle (RVEF) best predicts the maximal exercise capacity in patients with Ebstein's anomaly.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.11

Proximal aortic stiffening in Turner patients is more pronounced in the presence of a bicuspid valve. A segmental functional MRI study


Objective: To study structural and functional segmental aortic properties in Turner syndrome (TS) patients.

Methods: Aortic abnormalities contribute to increased morbidity and mortality of women with Turner syndrome. MRI allows segmental study of aortic elastic properties.

Using MRI, we performed pulse wave velocity (PWV) and distensibility measurements of the thoracic and abdominal aorta in 55 TS-patients, aged 13 to 59 years, and in a control population (n = 31; aged 21 to 58 years). We investigated the contribution of TS on aortic stiffness in our entire cohort, in aortic valve-morphology subgroups, and in the younger and older subgroups.

Results: Compared to controls, TS patients had higher PWV of the entire aorta (F = 7.3; p = 0.009) and thoracic aorta (TA-PWV; F = 10.5; p = 0.002), but not of the abdominal aorta (F = 0.3; p = 0.619). Ascending aortic (AA) diameters (but not more distal aortic diameters) were also significantly larger (F = 4.2; p = 0.043). No differences in distensibility were found. The increase in TA-PWV and AA diameters was more pronounced in bicuspid compared to tricuspid TS patients. Similarly, bicuspid TS patients also showed a decreased proximal aortic distensibility. In exploratory analyses, the observed proximal aortic stiffening and dilatation were largely similar when comparing younger and older TS patients.

Conclusion: Turner patients exhibit a predominant stiffening and dilatation of the proximal aorta, more pronounced when their aortic valve is bicuspid. These abnormalities are present at an early age, suggesting an aortic wall disease inherent to the TS, and only limited effect of accelerated ageing in the young adult Turner patient.

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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.12

Flow pattern and vascular distensibility of the pulmonary arteries in patients after repair of tetralogy of Fallot. Insights from 4D flow CMR


Objectives: Pulmonary regurgitation is a frequent sequela after repair of tetralogy of Fallot (TOF). The regurgitant flow may lead to changes in the flow profile and in size and distensibility of the pulmonary arteries (Pas).

We sought to assess Pa flow and distensibility in TOF patients (pts) by cardiac magnetic resonance (CMR) and to correlate them with the flow patterns provided by 4D flow CMR.

Methods: 18 TOF pts (mean age 28 ± 11yrs, weight 63 ± 12 kg) and 9 control subjects (age 17 ± 7yrs, weight 63 ± 24kg) underwent CMR. 2D Phase-contrast (PC) images were acquired through-plane in the main (MPA), right (RPA) and left pulmonary artery (LPA). A 4D PC dataset was acquired covering all the great arteries. Vessel areas and quantitative flow were measured on the 2D PC images. The flow patterns in MPA, RPA and LPA were qualitatively assessed for presence of helix or vortex on the reconstructed 4D images. Flow parameters, size and distensibility of the Pas were compared between TOF pts and controls and in the TOF group between RPA and LPA with regard to helix/vortex.

Results: In TOF pts, MPA mean regurgitant fraction (RF) was 25 ± 17%. Compared to controls, both Pas were larger and distensibility was higher in LPA (p 0.048) but not in RPA. RF was greater in LPA than in RPA (29 ± 19% vs 16 ± 14%, p 0.001) and LPA area was larger than RPA area (316 ± 134 vs 257 ± 116 mm2/m2, p 0.0342). LPA net flow was lower than RPA net flow (p 0.0005). Distensibility was similar in LPA and RPA and significantly correlated with RF, regurgitant flow and minimum area in both Pas branches.

By 4D flow, vortex was observed in the LPA in 72% (13/18) of TOF pts, but not in normals. Helical flow was present in 44% (8/18) of pts and in 11% (1/9) of normals. Presence of vortex in the LPA was independent from any other parameter; LPA helix was more frequent in pts with higher distensibility (p 0.04).

RPA presented helical flow in 77% (14/18) of TOF pts and in 55% (5/9) of controls. Vortex was only detected in 11% (2/18) of TOF pts. RPA helical flow was not correlated to other parameters.

Conclusion: In pts after TOF repair, Pas size and distensibility are mainly determined by the amount of regurgitant flow and less by specific flow patterns, such as vortex or helix. Characteristic flow patterns are found in LPA and RPA, which seem to be more related to the geometry of the pulmonary bifurcation and its branches than to quantitative flow parameters.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.13

Myocardial deformation characteristics of the systemic right ventricle after atrial switch operation for transposition of the great arteries


Introduction: The atrial switch operation (Senning) has been the main surgical repair technique for d-transposition of the great arteries for many years. The Senning procedure results in a subsystemic morphologic right ventricle (RV) and a subpulmonary morphologic left ventricle (LV). This can be regarded as a model for the effects of long-term pressure overload on the RV, and of ultimately decreased afterload on the LV. We sought to determine the impact of these chronically altered loading conditions on the myocardial deformation of the RV and LV.

Methods: 26 patients after Senning (age 28.4± 7.5y) and 18 normal controls (age 22.2± 11.4y; p = 0.034) underwent cardiac magnetic resonance (CMR) imaging. 2D SSFP cine images were acquired in an horizontal long axis and in a short axis covering both ventricles and post-processed with a feature tracking software (TomTec 2D CPA). Global circumferential strain was measured on a short axis mid-ventricular slice. Global longitudinal strain was measured in a long axis, separately for each ventricle.

Results: When comparing RV in either position, subsystemic circumferential strain was higher than subpulmonary circumferential strain (-16.1± 2.9% vs. -13.1± 4.3%; p < 0.01), and subsystemic longitudinal strain was lower than subpulmonary longitudinal strain (-12.8± 3.3% vs. -18.3± 3.8%; p < 0.001). In contrast, LV global strain in subsystemic vs. subpulmonary position was similar: LV circumferential strain (-23± 13.1% vs. -20.2± 3.9%; n.s.); LV longitudinal strain (-17.5± 4.6% vs. -16.1± 5.3%; n.s.).

The subsystemic RV showed lower circumferential (-16.1± 2.9% vs. -23± 13.1%; p < 0.05) and lower longitudinal strains (-12.8± 3.3% vs. -17.5± 4.6%; p < 0.001) than the subsystemic LV. The subpulmonary LV exerted greater circumferential strains (-20.2± 3.9% vs. -13.1± 4.3%; p < 0.001) but similar longitudinal strains compared to the subpulmonary RV (-16.1± 5.3% vs. -18.3± 3.8%; n.s.).

Conclusions: In discordant ventriculo-arterial connection, the subsystemic RV adapts to the increased afterload with an increase in circumferential strain and an impaired longitudinal deformation. This may represent the effect of a positive interventricular interaction due to the shared circumferential fibers, since the LV shows higher circumferential strain than the RV even in subpulmonary position.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.14

Three-dimensional vortex formation in patients with a Fontan circulation: evaluation with 4D flow CMR


Introduction: In the normal heart, formation of ring-shaped vortex flow has been suggested to help efficient blood flow during early (E) and late (A) diastolic filling of the left ventricle (LV), while altered vortex formation can be associated with LV abnormalities and inefficient blood flow [1,2,3]. Patients with a Fontan circulation have various underlying cardiac anatomy and it is unknown how this relates to vortex formation during diastolic filling. The purpose of this study was to assess three-dimensional (3D) vortex formation in patients with a Fontan circulation with different underlying pathologies, using four-dimensional (4D) flow CMR.

Methods: 11 patients with a Fontan circulation (age 15 ± 5 years) were evaluated by 4D flow CMR. Whole-heart 4D Flow CMR scans were performed on a 3 Tesla MRI (Ingenia, Philips Healthcare) with three-directional velocity-encoding of 150 cm/s in all directions, acquired voxel size of 3 × 2.6 × 3 mm3 and 30 phases reconstructed over one cardiac cycle. 3D vortex formation was identified in the LV at E- and A-diastolic filling, using the Lambda2 (λ2)-method [2]. Vortex formation during E- and A-diastolic filling was visually assessed.

Results: Vortex flow was present in all 11 patients at peak E-filling and in 10 patients at peak A-filling. One patient (with no A-wave) had no vortex during A-filling. Table 1 shows the versatile vortex formation in these patients. Normal “ring-shaped”' vortices were present in four patients. A double vortex ring (“eight-shaped”) was present in four patients with two functional atrioventricular (AV)-valves (Figure 1a). One patient showed a large vortex ring along the ventricular septal defect (VSD) with protrusion in both ventricles (Figure 1b). Triangular vortices were present in two hypoplastic left heart syndrome (HLHS) patients (Figure 1c). Two patients showed a vortex ring with reversed septal-lateral orientation compared to other patients, which could be related to the asymmetric length of the AV-valve leaflets [3].

Conclusion: Altered 3D vortex formation is present in patients with a Fontan circulation during E- and A-filling and can be related to the different underlying pathologies. Future studies have to reveal the influence of this abnormal vortex formation on cardiac function.


1. Kilner et al. Nature 2000

2. Elbaz et al. JCMR 2014

3. Calkoen et al. JTCVS 2015

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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.16

Mitral valve prolapse: arrhythmogenic substrates by cardiac magnetic imaging


Introduction: Mitral valve prolapse (MVP) is a common valvular disorder with a benign prognosis in the vast majority of patients, but with an incidence of sudden cardiac death (SCD) twice than in the general population. Recent data support the theory that left ventricular (LV) fibrosis constitutes the substrate of SCD in MVP patients. Cardiac Magnetic Resonance (CMR) represents a noninvasive imaging modality that provides a comprehensive characterization of both the valve and the myocardium.

Aim: To assess the presence of myocardial substrates as scar in patients with MVP and arrhythmias.

Methods: We enrolled consecutive patients with MVP diagnosed by an 2D echocardiography. For each one we detect the presence of ventricular arrhythmias by a 24 hours 12-leads ECG continuous monitoring. All patients underwent complete CMR scan including post contrast sequences. Complex ventricular arrhythmias (LV-CVA) were defined as non sustained or sustained ventricular tachycardia exclusively with right bundle branch block (RBBB) morphology suggesting an origin from LV. Patients with moderate or severe mitral valve regurgitation or other cardiomyopathies were exclude.

Results: a total of 52 patients were enrolled (33 female, median age 44 years); a bileaflet MVP was found in 31 (60%). On the basis of presence of significant ventricular arrhythmias, a group of “arrhythmic MVP” (N:33) compared to “non-arrhythmic MVP” (N:19) patients were identified. No differences on ventricular volumes and function were found. On post-contrast sequences, LV LGE was identified in 36 (69%). The LGE location was at the level of papillary muscles in 28 patients (54%) and LV infero-basal segment, near posterior valve leaflet annulus, in 26 (50%). The presence of LV-LGE was associated with LV-CVA [32 (97%) vs 4 (21), p < 0.001].

Conclusions: arrhythmic MVP patients are characterized by a myocardial substrate of electrical instability detectable by CMR, such as LGE both of papillary muscle and infero-basal LV wall. This points may represent area stretched by abnormal valve excursion leading to a local fibrosis, as confirmed also by post mortem analysis. The management of MVP patients with LGE by CMR, whether drugs, catheter ablation or ICD, remains a clinical challenge requiring further studies.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.17

Increased local wall shear stress after coarctation repair is associated with descending aorta pulse wave velocity: evaluation with CMR and 4D flow


Background: Coarctation of the aorta (CoA) is a local narrowing of the descending aorta (AO), typically distal from the left subclavian artery. Curative operational treatment is available and survival in childhood is good. However, in adulthood complications including hypertension, restenosis and aneurysm formation are not uncommon. In this explorative CMR study, we sought to investigate whether an association exists between AO wall compliance (expressed in pulse wave velocity (PWV) and distensibility) and 3D wall shear stress (WSS) in the AO in children after CoA repair.

Methods: 19 patients aged 12.8 ± 3 years underwent 4D flow CMR on 3T MRI (Ingenia, Philips Healthcare). 14 patients had a bicuspid aortic valve and none of the patients had clinical indication for re-intervention. 19 healthy volunteers aged 13.2 ± 3 years were included to assess normal values of PWV. PWV was determined from high-temporal 1-directional velocity encoding, for both proximal AO (ascending AO plus aortic arch) as well as the descending AO. Distensibility was measured at the ascending AO from the lumen area distension and the brachial pulse pressure. 3D WSS was determined from 4D flow CMR using CAAS MR 4Dflow v1.0 software (Pie Medical Imaging).

Results: There was no difference in age between volunteers and patients (p = 0.901). Proximal AO PWV (4.3 ± 0.9 m/s; in controls vs 5.0 ± 1.4 m/s in patients) and descending AO PWV (4.1 ± 0.9 m/s vs 3.9 ± 0.9 m/s) were not significantly different between both groups (p = 0.499 and p = 0.538 respectively). Ascending AO distensibility and proximal AO PWV were correlated (r = -.62; p = 0.008) in patients as expected, but not in volunteers due to the narrow range in both parameters. No relationship was found between overall WSS and PWV (r = -.053 p = 0.846) in entire AO but peak WSS in the aortic arch and proximal AO PWV were correlated (r = -.550 p = 0.027). The average ratio of peak WSS near the repaired CoA to average WSS in the entire AO was 2.6 ± 0.5 and this ratio was correlated to descending AO PWV (r = .518; p = 0.04).

Conclusion: Regional AO wall compliance measured by PWV was not significantly different between young controls and patients after CoA repair. However, at the repaired site, local WSS is more than doubled in patients, and this is associated with PWV distal to the CoA site. The AO seems to be locally affected in the distal rather than proximal AO. Altered wall compliance and WSS may in part explain the long term sequela in patients after CoA repair.

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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.18

Three-dimensional wall shear stress assessed by 4Dflow CMR in bicuspid aortic valve disease


Background: Ascending aorta (AAo) aneurysms may be partially caused by altered flow patterns associated with bicuspid aortic valve (BAV). Wall shear stress (WSS) has been hypothesized as an important biomarker for aortic dilatation. Thus, specific WSS patterns could potentially explain the development of a certain phenotype in BAV patients. The aim of our study was to analyze differences in WSS patterns using 3D maps according to the BAV morphotype.

Methods: Eighty-six BAV patients with no severe valvular disease and aortic diameters under 50 mm were enrolled. Fusion phenotype was right-left (RL-BAV) in 65 patients, and right-non coronary (RN-BAV) in 21. All subjects underwent 4D Flow MRI with retrospective cardiac gating at 1.5 T. Eight double-oblique analysis planes were equally distributed in the AAo between the sinotubular junction and the origin of the brachiocephalic trunk. Peak-systolic WSS was calculated in each plane, as described by Stalder et al. 3D WSS maps were estimated by longitudinally interpolating these WSS values. Peak velocity, flow eccentricity and rotational flow were evaluated in three slices located at proximal (S2), mid (S4) and distal AAo (S8). Calculations were performed using custom Matlab software.

Results: Table 1 summarizes differences between RL-BAV and RN-BAV in peak velocity, eccentricity and rotational flow at different aortic levels. RN-BAV had higher peak velocities and rotational flow. Different BAV phenotypes presented different outflow jet direction that correlated with the distribution of WSS within the aortic wall. Thus, RN-BAV patients presented a maximum WSS from proximal left posterior-to-distal right aortic wall (figure 1b) while the maximum WSS was from left posterior-to-right anterior at proximal-medial levels in RL-BAV patients (figure 1a).

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Conclusion: Maximum AAo-WSS region varies according to the BAV morphotype. 3D WSS maps can precisely illustrate these surface variations in WSS and can be a useful tool to better understand the pathophysiology of aortic dilatation in these patients.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.19

Cardiac Amyloidosis and Aortic Stenosis – The Convergence of Two Aging Processes


Background: Senile cardiac amyloidosis (SCA), once thought to be a rare disease, has been commonly diagnosed with Cardiac MRI (CMR). Recent autopsy series in octogenarians with severe aortic stenosis who received transcatheter aortic valve replacement reported prevalence up to 30%.

Objectives: To evaluate the prevalence of SCA detected by CMR in patients with confirmed moderately-severe symptomatic aortic stenosis (AS) and its association with clinical outcomes.

Methods: 95 consecutive AS patients (85% with severe AS) who underwent CMR study (1.5T Siemens Magnetom Espree) and echocardiogram within 15 days (median 6 days, IQR 0-15) were included in the analysis. Society of Thoracic Surgery predicted risk of mortality (STS-PROM) was calculated for each patient using over 40 clinical parameters. SCA was identified when characteristic pattern involving either subendocardial or diffuse myocardial LGE was observed. Cox-proportional hazards model performed after adjusting for potential confounders to evaluate the independent prognostic role of AS + SCA.

Results: A total of 9 patients (8 males, 89%) had AS + SCA (10% prevalence). Clinical, imaging and outcomes are listed in Table 1. Patients with AS + SCA were older than those with only AS (87 ± 5 vs. 68 ± 5 years, p < 0.0001) and had higher STS-PROM (6.8 ± 4.2 vs. 3.3 ± 3.2 %, p = 0.003). Over median follow-up of 10 months (IQR: 3- 19 months), there were 28 deaths (30%) and 39 AVRs (31 surgical and 8 transcatheter). There was no difference in the percentage of AVR performed in AS + SCA vs. isolated AS (33% vs. 42%, p = 0.73). Despite adjustment for AVR (HR = 0.51, 95% CI 0.22-1.18, p = 0.11) and STS-PROM (HR = 1.16, 95% CI 1.07-1.25, p < 0.0001), presence of AS + SCA was an independent predictor of all-cause mortality (HR = 4.02, 95% CI = 1.3-12.7, p = 0.02).

Conclusion: SCA is not uncommon in octogenarians presenting with symptomatic severe AS. One year all-cause mortality in AS + SCA patients was 3 times higher than in patients with isolated severe AS (Figure 1). Whether this risk can be modulated by additional therapies, beyond AVR, requires future studies.

Table 1.

Clinical, Imaging Characteristics and Outcomes of Patients with AS + SCA

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Figure 1. Kaplan-Meier Curves Comparing All-Cause Mortality in AS vs. AS + SCA Patients

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.20

Blood T1 variability explained in healthy volunteers: an analysis on MOLLI, ShMOLLI and SASHA


Background: Native myocardial T1 is known to be affected by variables such as age, gender, heart rate and partial voluming from blood pool. Blood T1 itself has a wider variability. We aimed to investigate causes of blood T1 variability.

Methods: 77 healthy volunteers with no known cardiovascular condition underwent CMR at 1.5T (Siemens, Avanto). Mid ventricular short axis native T1 maps by MOLLI (with T1* reconstruction in addition), ShMOLLI and SASHA were acquired. Hematocrit (Hct), iron profile and lipid profile were acquired immediately prior to the scan. CVI42 (Calgary, Canada) was used for analysis of the maps. A ROI was drawn in the blood pool on the MOLLI T1 map, avoiding papillary muscles, and was copied onto the MOLLI T1*, ShMOLLI and SASHA T1 maps.

Results: Complete datasets of blood and maps were available for all 77 volunteers (mean age 49 ± 14, range 20-76, 49% males). Mean ± SD of blood T1 by MOLLI T1 was 1638 ± 78ms, MOLLI T1* 1686 ± 111ms, ShMOLLI T1 1543 ± 77ms and SASHA 1584 ± 100ms. There was a negative correlation between blood T1 and Hct (R2 0.530, coeff. -0.728, p < 0.0001). Hct, iron, HDL-cholesterol, ferritin, triglicerides (TG), LDL-cholesterol and total iron binding capacity (TIBC) resulted to be significant at univariate analysis while this was not the case for albumin and total cholesterol. The multivariate analysis performed including only the significant variables showed that Hct, iron and HDL-cholesterol are significantly correlated with blood T1 by MOLLI T1 and T1*, ShMOLLI and SASHA (Table 1).

Conclusions: In health, Hct, iron and HDL-cholesterol explain almost all (90%) of blood T1 variability with anaemia and low iron increasing T1 but with HDL reducing it.

Table 1.

Univariate and multivariate analysis for blood variables and blood T1 by MOLLI T1, MOLLI T1*, ShMOLLI and SASHA.

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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.21

Myocardial deformation on CMR predicts adverse outcomes in carcinoid heart disease - a new marker of risk


Introduction: Carcinoid heart disease (CHD) is a frequent and adverse complication of carcinoid syndrome due to right ventricular (RV) failure. Medical therapy has a 2-year survival of 20% and while surgical valve replacement is effective in improving symptoms and may increase survival, peri-operative risk remains 15-20%. Echocardiography is considered gold standard for assessing CHD and data on the role of cardiacmagnetic resonance imaging (CMR) are limited despite recognised advantages in assessment of theright heart. This study aims to assess the role of CMR in the assessment of CHD.

Methods: 50 consecutive patients with proven neuroendocrine tumours were referred with elevated NT pro-BNP to the European Centre of Excellence for Neuroendocrine Tumours in Birmingham between 2005-2015. At referral, all subjects underwent comprehensive left ventricular (LV) and RV assessment with CMR (1.5T Siemens Avanto), including deformation (Tissue Tracking, Circle cvi42), and late gadolinium enhancement (LGE).

Results: 36 patients were diagnosed with CHD and 14 without (CHD-neg). RV valve disease was universal in CHD: severe tricupid regurgitation (97%), severe pulmonary regurgitation (86%). On CMR, RV end-diastolic volume (EDV) and end-systolic volume (ESV) were increased (120 ± 30 vs. 67 ± 14 ml/m2, p < 0.01; 49 ± 20 vs. 11 ± 3ml/m2, p < 0.01) but with no difference in RVEF (60 ± 14% vs. 60 ± 9% p = 0.92). There was early evidence of ventricular-ventricular interaction, with reduction in LVEDV (53 ± 16 vs. 72 ± 16 ml/m2, p < 0.01) and LVESV (19 ± 10 vs. 28 ± 16ml/m2, p < 0.05) in CHD but no difference in LVEF (67 ± 8% vs. 63 ± 14%, p = 0.3). There was no difference in LV global longitudinal strain (GLS) or circumferential strain (GCS) between groups. RV LGE indicative of endocardial plaques was present in 6/36 (17%) but not observed in CHD-neg. Diffuse LV LGE was present 5 CHD patients. Over follow up (median 1.3 years [0.6-3.1]), 20 patients with CHD died. These patients had a lower GCS (14.8 ± 4.6% vs. 18.2 ± 4.4%, p < 0.05) and lower GLS (14.7 ± 4.7% vs. 18.3 ± 4.4%, p < 0.05) on CMR but no difference in ventricular size, EF or NT-proBNP. In a logistic regression model, LV GLS remained an independent predictor of death.

Conclusion: Significant increase in RV size and the presence of RV plaques are measurable on CMR early following referral with CHD. This is sufficient to adversely affect LV filling and global deformation, which may contribute to effort intolerance and adverse outcomes.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.22

Myocardial Perfusion Reserve and Global Longitudinal Strain in Early Rheumatoid Arthritis


Objectives: Rheumatoid arthritis (RA) is a systemic inflammatory condition associated with increased cardiovascular mortality compared with the general population. Proposed mechanisms for this increased mortality include coronary microvascular dysfunction due to immune dysregulation and systemic inflammation.

First pass myocardial perfusion CMR allows quantification of myocardial blood flow (MBF) from which myocardial perfusion reserve (MPR) can be derived. In the absence of epicardial coronary artery disease, reduced MPR represents coronary microvascular dysfunction. We therefore hypothesised MPR would be reduced in RA patients.

Additionally, we hypothesised that abnormalities in left ventricular (LV) deformation would be evident in RA patients, as LV mass has been reported to be reduced in established disease.

Methods: Twelve patients with newly diagnosed, treatment naïve RA and 12 healthy volunteers (HV) underwent CMR at 3.0T (Phillips Achieva TX). Both groups had no history of coronary artery disease or additional risk factors for this. Dual bolus resting and stress perfusion imaging was performed (0.1mmol/kg Gadolinium DTPA) and MBF values for the mid ventricular slice were estimated using Fermi constrained convolution (PMI v 0.4 [Sourbron, 2009]). MPR was calculated by dividing stress MBF by rest MBF. Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) by feature tracking were calculated using bSSFP images (CVI 42, Circle Cardiovascular Imaging, Calgary, Canada).

Results: Mean age of RA patients was 48 ± 16 and mean age of HV 47 ± 14. Of the RA patients, were 4 were male and 8 were female. Of the HV, 2 were male and 10 were female. Mean values for MPR were 1.98 ± 0.79 and 1.99 ± 0.72 (P = 0.88) for RA and HV respectively. Mean values for LVEF were 63 ± 4 and 62 ± 4% (P = 0.48) respectively for RA patients and HV. Mean values for GLS were -20.2 and -21 ± 0.4 (P= 0.396) for RA and HV respectively.

Conclusion: These preliminary findings from the CADERA trial suggest that, newly diagnosed, treatment naïve RA patients have no detectable abnormalities on perfusion CMR compared with HV. Therefore, whilst present in established RA, coronary microvascular dysfunction may not yet have developed in early RA. Additionally, no abnormalities of LV systolic function were evident in newly diagnosed RA and may be a later manifestation of the disease.

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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.42

Exercise CMR to differentiate athlete's heart from patients with early dilated cardiomyopathy


Introduction: It can be difficult to distinguish between early stage dilated cardiomyopathy (DCM) and left ventricular (LV) dilation with mildly reduced LV ejection fraction (EF) which is a relatively common observation amongst endurance athletes (EAs). This has important consequences for clearance for competitive sport participation since DCM may precipitate fatal ventricular arrhythmias.

Methods: We prospectively included 9 EAs and 9 asymptomatic patients with mild DCM (7 familial DCM and 2 partially recovered severe DCM), all LVEF 40-55% at inclusion. In all subjects beta-blockers were withheld 24 hours before evaluation. First, cardiopulmonary exercise testing was performed to determine maximal power (Pmax). Then, cardiac magnetic resonance (CMR) imaging was performed at rest and during bicycle exercise at 25%, 50% and 66% of Pmax to determine left and right ventricular (RV) end-diastolic and end-systolic volumes, from which ejection fraction (EF) was calculated.

Results: At rest, RVEF was lower in EAs than in DCM patients, whereas LVEF was similar (Figure 1A). At peak exercise, RVEF was similar in both groups. However, LVEF augmentation was observed in EAs but was attenuated in DCM patients. Receiver-operator characteristic curves demonstrated that a cut-off value of 11.2% for the increase in LVEF from rest to peak exercise (ΔLVEF) had a sensitivity of 89% and specificity of 89% to differentiate EAs from DCM patients [AUC = 0.89(0.72-1.06); P = 0.005], whereas resting LVEF (cut-off: 50.8%) was not predictive (Figure 1B).

Conclusion: Evaluation during exercise facilitates the differentiation between athlete's heart and DCM. An athlete's heart demonstrates good myocardial contractile reserve as compared to subjects with early DCM in whom LV functional reserve is reduced.

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Figure 1.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.24

Real-Time, x-mri guidance to optimise left ventricular lead placement for delivery of cardiac resynchronisation therapy


Suboptimal LV lead placement contributes to cardiac resynchronization therapy (CRT) non-response. Cardiac MR (CMR) identifying myocardial scar & dyssynchrony allows targeted LV lead placement. Currently CMR is performed prior & separate to implantation. We describe a novel guidance platform, integrated within an XMR facility enabling CMR data acquisition, processing & analysis with immediate overlay onto live fluoroscopy.

Methods and Results: Short & long axis cines & late gadolinium sequences are segmented and projected onto a 16-segment AHA model demonstrating location, transmurality & burden of myocardial fibrosis. Regional motion analysis demonstrates the latest mechanical activating segments. This process is performed seamlessly while the patient is within the XMR suite allowing segmented LV geometry/scar to be immediately co-registered with fluoroscopy. CS venography is overlaid onto the 3D-shell to identify the preferential targets for LV stimulation. This platform has been successfully used in 6 patients with no significant increase in procedure time or radiation dose compared with our historical controls (89 ± 18 vs.113 ± 28 minutes & 826 ± 191 vs. 950 ± 450 cGycm2, p = ns). Late, target segments avoiding scar were paced in all cases. Visualization of the target informed positioning of the LV lead and enabled identification of the optimal poles to use for biventricular stimulation (Figure).

Conclusion: Performing and processing CMR data in real time is feasible and may aid optimal LV lead placement for CRT delivery. This can be accomplished in a single sitting with no delay between CMR and CRT implant.

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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.25

The role of Cardiac magnetic resonance imaging in patients undergoing ablation for ventricular tachycardia- Defining the substrate and visualizing the outcome


Background: Pre- interventional Cardiac Magnetic Resonance (CMR) imaging may help to identify the underlying arrhythmogenic substrate in patients undergoing radiofrequency (RF) ablation for ventricular tachycardia (VT). However, the extent and characteristics of structural damage induced by the ablation itself and its association with acute procedural outcome remain poorly defined so far.

Methods: 17 patients (82% male, median age 57.5± 11 years, 6 with known coronary artery disease) who underwent VT ablation received CMR scans pre- and post- ablation. CMR was performed at 1.5 Tesla including cine, T2-weighted, 3D- early and late- gadolinium- enhancement (LGE)- imaging in standard cardiac geometries. LGE and microvascular obstruction (MO) were expressed as percentage of total left ventricular mass. The electrophysiological (EP) procedures were performed according to local protocols using the Carto©- Mapping- system in all cases. Non- inducibility of VTs at the end of the procedure was defined as the primary endpoint. RF ablation was performed using a 3.5 mm Thermocool catheter, flow rate 30 ml/min.

Results: In 13 patients, substrate defined as positive LGE, could be described on pre-interventional CMR imaging (11 endocardial, 1 endo- and epicardial, 1 strictly epicardial; mean LGE 22.6% ± 16). Mean left ventricular ejection fraction (LV-EF) before ablation was 45% ±11. Successful ablation was performed in all cases using a mean maximum energy of 55 ±11 Watt. Epicardial access was used in 3 patients.

On postinterventional scans, myocardial edema was visible in 9 patients. MO was present in all patients (mean MO 6 ± 2%, 7 cases with a MO >5%) Mean postinterventional LV-EF showed to significant difference to baseline (42%15, p = 0.4) and decreased in only 1 patient (MO> 5%). The extent of MO correlated significantly with the applied maximum energy (R = 0.625, p = 0.007) and the mean ablation time (R = 0.512, p = 0.036). A 100% transmural ablation lesion was observable in 4 patients.

Conclusion: Apart from reliably defining the arrhythmogenic substrate preinterventionally in patients with VTs undergoing ablation, postprocedural CMR imaging reveals acute myocardial injury in the form of edema and MO induced by the ablation itself. The extent of the lesions directly correlates with the time and the maximum power of the applied RF energy. Whether the lesion characteristics on are associated with short- and long- term outcome needs to be further assessed.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.26

Impact of cardiovascular magnetic resonance on clinical management and decision-making of out of hospital cardiac arrest survivors with inconclusive coronary angiogram


Background: Non-traumatic out of hospital cardiac arrest (OHCA) is the leading cause of death worldwide. Urgent coronary angiography is a class IB recommendation, as 2/3 of cases are secondary to acute coronary syndrome. However diagnosis and management of patients with unobstructed coronaries or unidentified culprit lesion on angiogram is challenging. We sought to assess the additive role of cardiac magnetic resonance (CMR) in patients with an inconclusive coronary angiogram and to determine the best CMR parameter in predicting clinical impact.

Methods: We analysed the CMR registry data of consecutive patients surviving non-traumatic OHCA, undergoing urgent angiogram and CMR from two tertiary cardiology centres. The study focused on the analysis of patients with an inconclusive angiogram, defined as unobstructed coronaries or coronary artery disease (CAD) without a clear culprit lesion. Clinical impact of CMR was defined as a change in diagnosis, as compared to a multi- parametric pre-CMR diagnosis, or a change in management, which could be a change in medication or the performance/avoidance of invasive procedures.

Results: Out of 174 OHCA survivors referred for CMR following urgent angiogram, we identified 110 patients (63%,84 male,mean age55 ± 17) with inconclusive angiogram: 73 patients(66%) had unobstructed coronaries and 37(34%) had CAD with no clear culprit. Diagnosis based on CMR findings was ischemic heart disease in 43 patients (39%), non-ischemic heart disease in 33 (30%), a structurally normal heart was found in 24 (22%) and non-specific findings in 10 (9%). Overall, CMR had a clinical impact in 72% of patients, determining a change in diagnosis in 25% of patients, a change in management in 30%, and a change in both in 17%. CMR led to revascularization in 20% of patients and to ICD implantation in 10%; an invasive procedure was avoided in 12% of patients. In a multivariate model including clinical and imaging parameters, the strongest predictors of the clinical impact of CMR were regional wall motion abnormality and the analysis of LGE sequences (p 0.042,95% CI 1.05-9.99; p < 0.0001,95% CI 5.46-73.7,respectively).

Conclusions: CMR had a clinical impact in more then two thirds of OHCA survivors with an inconclusive coronary angiogram. The analysis of LGE sequences was the strongest independent predictor of clinical impact following CMR. Given its additional role CMR should be incorporated in the clinical-diagnostic work-up of this group of patients.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.27

Detection of coronary stenosis at rest using Oxygenation-Sensitive Magnetic Resonance Imaging


Objective: To determine whether Oxygenation-Sensitive Magnetic Resonance Imaging (MRI) can identify functionally significant coronary artery disease (CAD) without the need for stress.

Background: In the setting of CAD, microvascular dilation has been shown to occur in post-stenotic myocardium at rest. Microvascular volume is a determinant of signal intensity with Oxygenation-Sensitive (O-S) MRI. Therefore, we postulated that O-S imaging at rest could detect microvascular heterogeneity, and thereby identify coronary stenosis without recourse to physiological or pharmacological stress.

Methods: Rest O-S images were acquired at 3 Tesla using a T2-prepared ECG-gated steady-state free precession sequence and assessed quantitatively using a resting O-S index (interquartile range of segmental O-S signal intensities/median segmental signal intensity). First-pass perfusion images were also acquired at rest and stress (intravenous adenosine, 140 µg/kg/min) and assessed quantitatively using model-independent deconvolution. A threshold resting O-S index to identify myocardial ischaemia at the patient level (as defined quantitatively as ≥1 myocardial segment with hyperaemic myocardial blood flow ≤1.6ml/min/g) was first determined in a derivation arm comprising 25 patients with known CAD and 20 healthy volunteers. To determine diagnostic performance, this threshold was then applied in a separate validation group comprising 57 patients with suspected CAD referred for diagnostic angiography.

Results: Receiver-operating characteristic curve analysis defined a threshold resting O-S index of 16.1% to identify patients with myocardial ischaemia (72% sensitivity and 78% specificity; area under the curve 0.72 ± 0.08, p = 0.0078). Application of this threshold in the validation arm of the study yielded sensitivity 88%, specificity 58% and diagnostic accuracy 75% for the identification of subjects with ischaemia, and 82%, 61%, and 75%, respectively, for identifying those with significant coronary stenosis. At the patient level, there was reasonable agreement between resting O-S imaging and both first-pass perfusion (kappa = 0.51) and quantitative coronary angiography (kappa = 0.48).

Conclusions: O-S imaging indicates the presence of microvascular heterogeneity at rest in CAD. Assessment of microvascular heterogeneity offers a potential means for identifying the anatomical and functional significance of CAD without the need for stress.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.1

Longitudinal strain assessment in dilated cardiomyopathy patients using a novel accelerated DENSE sequence


Objectives: Strain assessments are prognostically valuable in patients with dilated cardiomyopathy (DCM), particularly longitudinal strain which can be abnormal prior to the development of marked systolic functional impairment. Displacement encoding with stimulated echoes (DENSE) is an accurate and reproducible technique to measure myocardial strain, but its clinical utility is limited by long breath hold times or navigator gating which can be impractical and time consuming. We developed an accelerated DENSE sequence and sought to evaluate its utility in longitudinal strain assessment in DCM.

Methods: We modified a cine spiral DENSE sequence to selectively excite a reduced field of view thereby reducing breath hold time by 30%. 12 DCM patients (8 males, mean age 55 ±15 years) underwent a 2D cine DENSE imaging using this novel sequence in a horizontal long-axis slice and vertical long-axis slice (Siemens Skyra 3T). DCM was diagnosed based on CMR criteria of LV dilation and impaired ejection fraction according to age and gender adjusted nomograms.

Images were acquired at 3.5x3.5x8.0mm3 spatial resolution, 30ms temporal resolution and 2 direction encoding at 0.06cycles/mm. The FOV was 224mm2 with a breath hold duration of 14 RR intervals. Global longitudinal strain was extracted from the DENSE data using contour strains in a Matlab post-processing software from the University of Virginia.

Results: All patients were able to sustain the breath hold duration for the accelerated DENSE acquisition and had complete CMR assessment of myocardial strain. Mean left ventricular ejection fraction (LVEF) was 47 ± 7.8%.

Table 1 shows global peak strain and time to peak strain from horizontal and vertical long axis images for each subject. Peak longitudinal strain measurements show strong negative correlations with LVEF for both vertical (r = -0.84, p = <0.001) and horizontal (r = -0.73, p = 0.007) long axis measurements.

Figure 1 shows an example of longitudinal strain curves for a DCM patient (subject 10) with severely impaired systolic function (LVEF 36%) compared to a healthy volunteer (LVEF 68%).

Conclusion: We demonstrate the feasibility of use of a novel accelerated DENSE sequence to obtain longitudinal strain measurements in patients with DCM in a clinically acceptable breath hold duration.

Table 1.

Longitudinal strain in DCM patients. Results are shown from 2 long axis views, HLA = horizontal long axis, VLA = vertical long axis. LVEF = left ventricular ejection fraction.

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Figure 1. Longitudinal strain curves from a healthy volunteer compared to a patient with DCM (HLA = horizontal long axis, VLA = vertical long axis).

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.2

Simultaneous T1 and T2 cardiac quantification with CABIRIA: initial clinical experience


Objectives: The purpose of this study was to evaluate the performance of the cardiac balanced-SSFP inversion recovery with interleaved sampling acquisition (CABIRIA) [1] sequence on a cohort of patients with different cardiac pathologies. This sequence provides simultaneous T1 and T2 quantification. The homogeneity of its quantitative results across the different regions of the heart was assessed and the global T1 and T2 values were compared across pathologies.

Methods: A cohort of 14 subjects was included in the study. Among these, 2 had no cardiac condition, 5 suffered from myocarditis, 4 from Hypertrophic Cardiomyopathy (HCM), and 3 from Pulmonary Hypertension (PAHT). A pre-contrast short-axis CABIRIA acquisition (Resolution: 1.7x1.7x7mm^3, Flip angle: 35°, 15 acquisitions per inversion pulse, repeated 2 times) was performed in the context of a routine cardiac MR examination on a 1.5 Avanto scanner (Siemens Healthcare, Erlangen, Germany). The T1 and T2 maps were analyzed offline by means of a custom segmentation interface that divided the view into 6 segments, following the American Heart Association guidelines (see fig. 1). Each segment of each map was treated as a data point and differences across the segments were analyzed as a measure of robustness of the CABIRIA method. Differences across pathologies were also quantitative analyzed. Analysis of Variance (ANOVA) testing was used in both cases.

Results: No significant differences were found for T1 maps across the different segments (p = 0.35) and moderately significant differences were found for T2 maps (p = 0.03). Significant differences were found across diagnoses for T1 values (p < 0.001), with values of 1225 ± 121, 1108 ± 91, 1207 ± 107, and 1220 ± 88ms for normal, HCM, Myocarditis and PAHT. Nonsignificant differences were found across diagnoses for T2 values (p = 0.06), with respective values of 93 ± 28, 75 ± 21, 78 ± 23, and 81 ± 30 ms (Fig. 2).

Conclusion: The method showed a higher robustness in T1 mapping with respect to T2 mapping, which can be hypothesized as a result of magnetic field inhomogeneities across the different segments. Our findings resulted in a higher T1 values for healthy subjects with respect to other pathologies. This is somewhat surprising, but this can be due to the small number of subjects included in this control group, which also lead to a higher spread in values as depicted in Fig. 2.


1. Santini et al. Magn Reson Med, 74: 365–371, 2015

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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.3

Head-to-head comparison of acceleration algorithms in 4-dimensional flow CMR


Background: Standardisation and validation of four-dimensional (4D) flow CMR acquisition methods is lacking. Our aim was to compare three acceleration methods in 4D flow CMR: 4D segmented fast-gradient-echo with segmentation factor 2 (4D-TFE), 4D non-segmented gradient-echo with echo-planar imaging (EPI, factor 5) (4D-FFEPI) and 4D kt-BLAST accelerated TFE (factor 5; 11 training lines).

Methods: CMR was performed in two institutions (Leiden and Leeds) on identical 1.5T systems (Ingenia CV, Philips Healthcare). Methods were compared in a phantom (straight tube with 7mm diameter with stationary flow ranging between 1.07-2.48 l/min) and 15 volunteers. In the phantom setup, the 3 4D flow sequences were compared to 2-dimensional phase contrast (2D PC). In volunteers, the CMR protocol included: cines, 2D PC at the aortic valve (AV) and mitral valve (MV) and whole-heart free-breathing (no respiratory motion correction) 4D flows. Field of view, slices, phases (30), voxel size and VENC were the same for each subject. 4D-FFEPI and 4D-TFE used retrospective ECG gating while 4D kt-BLAST used prospective ECG-triggering. In volunteers, stroke volumes (SV) at MV and AV were obtained by retrospective valve tracking. In volunteers, net acquisition time for each 4D flow sequence was recorded, as well as a visual grading of image quality on a four-point scale: 0, no artefacts to 3, non-evaluable.

Results: The phantom setup showed that all 4D flows underestimated flow volumes when compared to 2D PC (4D-FFEPI -3 ± 1%; 4D-TFE -9 ± 1%; 4D kt-BLAST -10 ± 3%). In vivo validation was performed in 15 volunteers (44 ± 11yrs old and 60% male). Acquisition times are presented in Figure 1. 4D-FFEPI and 4D kt-BLAST had minimal artifacts. For 4D-TFE however, 8 AV and 5 MV assessments were non-evaluable because of phase dispersion artefacts. All methods showed significant difference between AV SV and MV SV (Table 1). Non-significant underestimation in 4D flow peak velocity was found at static positions: 4D-FFEPI: 2 ± 26 cm/s with CoV 26%, 4D-TFE: 11 ± 41 cm/s with CoV 40%, 4D kt-BLAST: 7 ± 30 cm/s with CoV 31%.

Conclusion: 4D EPI accelerated 4D flow had the shortest acquisition time, best agreement with the 2D-PC and the lowest variability. Consistency between MV and AV net forward flow was marginally but not significantly better with 4D-FFEPI (10.5%) than with 4D-TFE (11%). 4D kt-BLAST demonstrated significant underestimation of NFF and CoV was poor. 4D-TFE was most susceptible to artefacts.

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Figure 1. Time taken (in minutes) for acquisition using the three 4D Flow accelerated techniques.

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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.4

Left ventricular function and size evaluated by hybrid cardiac positron emission tomography-magnetic resonance: Intraindividual comparison of left ventricular ejection fraction and ventricular volumes derived by two modalities


Objectives: Hybrid cardiac imaging using combined positron emission tomography (PET) and magnetic resonance (MR) systems is an upcoming imaging technology, currently under evaluation for clinical use. The aim of this work is to intraindividually compare results from left ventricular function and left ventricular volumes evaluated by an integrated PET-MR system using a dual tracer protocol.

Methods: Dual tracer [13N]ammonia ([13N]NH3) (750 ± 230MBq) and 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) (310 ± 92MBq) cardiac PET-MR was performed in 13 patients for evaluation of cardiac viability in ischemic heart disease. Left ventricular ejection fraction, endiastolic volumes (EDV), and endsystolic volumes (ESV) were derived from 3 Tesla cardiac MR as well as from the simultaneously acquired [13N]NH3 and [18F]FDG PET images. MR data were calculated from short axis cine images in the endiastolic and endsystolic phase during breath hold. PET data were derived from the myocardial phase during free breathing using 16 gates in a time frame of 15 minutes for [13N]NH3 and 10 or 20 minutes for [18F]FDG.

Results: Mean values for LVEF derived from MR, [13N]NH3 PET and [18F]FDG PET were 45 ± 16%, 48 ± 17% and 46 ± 17%. Mean values for EDV were 188 ± 66ml for MR, 171 ± 85ml for [13N]NH3 PET and 159 ± 86ml for [18F]FDG PET. For ESV MR derived values were 122 ± 68ml; [13N]NH3 PET values were 101 ± 76ml and [18F]FDG PET values were 96 ± 78ml respectively. LVEF showed an excellent correlation between MR and [13N]NH3 PET (R = 0.96; mean difference 4.6%; range 0-14%) as well as between MR and [18F]FDG PET (R = 0.89; mean difference 6%; range 1-17%). In addition, significant correlations have been observed between EDV obtained from MR and by [13N]NH3 PET (R = 0.86; mean difference 39ml; range 7-106ml), and between EDV measured by MR and [18F]FDG PET (R = 0.83; mean difference 43ml; range 0-109ml). Similarly, the comparison of ESV values acquired from MR with those acquired from [13N]NH3 PET and [18F]FDG PET revealed an excellent correlation (R = 0.94; mean difference 29ml; range 7-60ml) and (R = 0.88; mean difference 32ml; range 13-82ml) respectively; all P < 0.001.

Conclusion: Left ventricular volumes and left ventricular function simultaneous derived from an integrated PET-MR do show an excellent correlation between the data derived from the MR and the PET system with slightly better results for [13N]NH3 PET compared to [18F]FDG PET when considering MR as the gold standard.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.5

Left Atrium assessed by Cardiovascular Magnetic Resonance at 1.5 and 3 Tesla – age and gender effects


Background: The impact of the left atrium (LA) for the prediction of therapeutic success as well as its impact on clinical outcome e.g. in cardiomyopathies is well known. Currently, the use of volumes and/or function is different in most trials but a standardization would be helpful to offer a uniform view on disease understanding.

Cardiovascular magnetic resonance (CMR) is a well established technique of cardiac morphology and accepted as the gold standard, but often disparaged as a very time‐consuming method.

We aim to provide LA parameters including LA ejection fraction (EF) in male and female healthy volunteers at 1.5 and 3 Tesla using a time effective approach.

Methods: We analyzed 203 healthy volunteers at 1.5 and 3 Tesla using cine‐SSFP‐imaging based on the biplanar approach. Simpsons rule was used to quantify the atria in the 2‐and 4‐chamber view excluding pulmonary veins and the left atrium appendage in LA Systole and LA Diastole (see also figure 1).

Using cvi42 we calculated mean values and standard deviation for LAEDV, LAESV, LASV, LAEF and all volumes were normalized to Body‐surface‐area (BSA) and Height (H) and subdivided by gender.

We analyzed the volunteers according to three age groups with group 1 from 20 to 39 years, group 2 from 40 to 59 years and group 3 60 years orolder to compare LA values at different ages.

Results: We included 105 male and 77 female healthy volunteers (age group 1 50 male and 26 female, age group 2 36 and 31 and group 3 19 and 20).

There was no significant difference in the absolute volumes inour volunteers between field strengths (see table 1).

There were no gender‐related differences in normalized parameter with males having a LAEDV/BSA of 33 ml/m2 and a LAESV/BSA of 12 ml/m2 and women of 34 ml/m2 and 11 ml/m2 (p > 0.6), respectively. But the absolute values were different (LAEDV and LAESV (p < 0.01) with men having larger volumes.

We found a significant decrease in LAEDV/BSA and LAEDV/H in older age with age group1 having a LAEDV/BSA of 36 ml/m2, decreasing to a LAEDV/BSA of 33 ml/m2 in age group 2 respectively of 30 ml/m2 in age group 3 (see also figure 1).

Summary: Our main findings are that LA–size decreases during the life–cycle in healthy volunteers and that normalization to body–size helps to overcome sex–related differences. There is no dependency on field strengths.

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Figure 1. Decreasing LAEDV/BSA with older age.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.6

Comparison of Free Breathing Cardiac MRI Radial technique to the Standard Multi breath-hold cine SSFP CMR technique for the assessment of LV Volumes and Function


Background: Cardiac MRI (CMRI) is generally accepted as the gold standard for left ventricular (LV) volumes and function assessment. Standard cine SSFP sequences require prolonged, repeated breath holds and therefore may be challenging, particularly for debilitated, pediatric and elderly patients. The compressed sensing, Radial cine (RC) k‐space acquisition technique can provide a good image quality without the need for breath holding. The purpose of this study was to compare volume and function results between free breathing RC technique and the standard multi–breath-hold cine SSFP technique.

Methods: 24 patients who underwent clinically indicated cardiac MRI (CMRI) were included in the study. In all patients both standard cine and radial cine sequences were performed. The images were analyzed using CMR42 semiautomatic tool of the CVI42 software, version 5.0.0 for both LV and RV end diastolic volume (EDV), end systolic volume (ESV) and ejection fraction (EF) and myocardial mass for LV. The RC and the standard breath-hold SSFP techniques were compared using Pearson correlation and Bland-Altman analyses. Values of p < 0.05 were considered statistically significant.

Results: The average age was 45.7 ± 18, there were 15 males and 9 females. Results of Pearson correlations and Bland-Altman analyses (P values for all correlations were <0.05) are summarized in the table below.

Conclusions: The results demonstrate the feasibility of applying the RC compressed sensing strategy to evaluate LV and RV volume and function with high accuracy in a variety of patients, without the need for breath holding, in considerably shorter scan times.

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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.7

Self-navigated free-breathing isotropic 3D whole heart phase sensitive inversion recovery magnetic resonance without navigator for detection of myocardial infarction


Background: Cardiac magnetic resonance (CMR) is considered as gold standard for detection of scar after myocardial infarction. Navigator techniques allow acquisition of 3D scar information however have limited scan efficiency. This study evaluates the accuracy of a self-navigated isotropic free-breathing 3D whole-heart CMR acquisition technique with integrated, contrast independent iterative approach to 1D self navigation with phase sensitive inversion recovery (3DSN-PSIR) to detect myocardial scar tissue.

Methods: Patients presenting with chronic myocardial infarction detected by late gadolinium enhancement on standard 2D phase sensitive inversion recovery sequences (2D-PSIR) underwent a CMR exam with 3DSN-PSIR on a 1.5T clinical MRI scanner (MAGNETOM Aera, Siemens Healthcare, Germany). Data acquisition was performed 15 minutes after administration of 0.2mmol/kg of Gadobutrol in free-breathing during the most quiescent systolic phase with a prototype ECG-triggered and segmented respiratory self-navigated 3D radial trajectory implementing an inversion-recovery (IR) prepared acquisition, a reference scan, and a phase-sensitive reconstruction. Imaging parameters were: TR/TE 2.9/1.45ms, FOV 220mm3, resolution 1.4mm3, RF excitation angles 115°(IR) and 8°(reference), bandwidth 900 Hzx/px, fat saturation, inversion time (TI) 250-320ms. A total of about 14000 radial readouts were acquired for each 3DSN-PSIR with 100% respiratory efficiency. Short axis slices were reconstructed from 3DSN-PSIR datasets to yield the same slice thickness (10mm) as the 2D-PSIR images. Scar tissue was segmented both on 2D-PSIR and the reconstructed 3DSN-PSIR slices.

Results: Six patients were included (patient characteristics see table). 3DSN-PSIR successfully corrected for respiratory motion in all acquisitions. All scars visualized by 2D-PSIR could be identified by 3DSN-PSIR (example see figure). 3D and 2D scar volume did not differ: 3D: 59 ± 28ml vs. 2D: 47 ± 18ml, p = 0.07. Bland Altman-analyses and correlations showed a good agreement of quantification of scar volume obtained by 3DSN-PSIR compared to standard 2D-PSIR: 8.9 ± 6.6ml, r = 0.99, p < 0.001, intraobserver -3.2 ± 9.6 ml, r = 0.94, p= 0.005; interobserver -11.2 ± 14.7 ml, r = 0.88, p = 0.032.

Conclusions: These preliminary data show that detection of myocardial scar by 3DSN-PSIR is feasible and shows a good agreement with standard 2D-PSIR. This technique should be investigated in future larger studies.

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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.8

Assessment of Right Ventricular Strain Using Myocardial Deformation Recovery Semi Automated Technique: Initial Experience and Normal Values


Objective: Assessment of Right Ventricluar (RV) strain by cardiac magnetic resonance (CMR) imaging may add prognostic information, beyond global RV function in patients with pulmonary hypertension, right sided valvular pulmonary tricuspid regurgitation, and complex congenital heart disease. Currently echocardiography is the main modality to assess RV strain and is limited to RV free wall.

Methods: Dedicated RV Myocardial Strain Software: Myocardial deformation recovery from the cine MRI first involves constructing a deformable model based on the endocardial and the epicardial tracing in the reference frame, assuming the myocardium is nearly incompressible. In each of the subsequent frames the displacements of the control points of the model are determined using feature tracking method with the incompressible model constraint. Using this method, not only the myocardial boundaries, but the entire myocardial tissue is tracked. CMR of 37 patients without known cardiac pathology and preserved biventricular function were analyzed retrospectively.

Strain analysis: Horizontal long axis was used for calculation of longitudinal strain (fig 1). Short axis at the base, mid and apex of the RV was used to calculate circumferential strain (fig 2). Intraventricular septum was not included in the strain calculation. Endocardial and epicardial contours were drawn in the phase with most distinct myocardium boundaries; RV trabeculations were carefully excluded. The software automatically propagated contours throughout all phases. Longitudinal (Ell) and circumferential strain (Ecc) was computed.

Results: The age range was 4-72 years with an average of 31 (± 20.69). Analysis time per patient was < 5 minutes. Average Ell was -21.92 (± 3.42). Average Ecc for basal, mid and apical segments were as follows: -10.60 (±3.42), -10.94 (± 3.68), -11.84 (±3.28). There was no significant difference between the basal, mid and apical levels. The intraclass correlation coefficient (ICC) was 0.785 for Ell, and 0.877, 0.943, and 0.902 respectively for the Ecc at the base, mid, and apical levels. There was no correlation between age and strain.

Conclusion: Rapid analysis of RV Ell and Ecc can be accomplished with excellent intraobserver variability. Further studies are needed to determine performance and utility of this dedicated RV Deformation Recovery Strain software in the clinical settings.

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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.9

Tissue tracking myocardial deformation analysis and prediction of left ventricular remodeling in acute myocardial infarction


Background: The novel tissue tracking analysis software (TT) for cardiac magnetic resonance (CMR) allows the study of myocardial deformation parameters based on routinely acquired CMR sequences. It was our purpose to evaluate the feasibility of this technique in ST-elevation acute myocardial infarction (STEMI) patients and its ability to predict left ventricular remodeling.

Methods: A total of 100 STEMI patients were prospectively studied with a 1.5 T CMR scan within 3-5 days of successful primary percutaneous intervention. Routine SSFP sequences from 3 long-axis and a stack of short-axis slices were analyzed with TT (CVI42, Circle Cardiovascular Imaging Inc.) and peak systolic global longitudinal, circumferential and radial strain values were studied and correlated with basal ejection fraction and infarct size as determined with late gadolinium enhancement imaging. Follow-up CMR was performed at 6-months to assess left ventricular volumes. Left ventricular remodeling was defined as a 20% or greater increase in left ventricular end-diastolic volume (LVEDV).

Results: During follow-up, 27 patients presented with left ventricular remodeling (mean increase in LVEDV 36 ± 12%, minimum 22%, maximum 78%). Patients with left ventricular remodeling presented lower basal left ventricular ejection fraction and higher relative infarct size and microvascular obstruction mass, as well as worse global longitudinal, circumferential and radial strain (table 1). Global peak systolic circumferential strain was the best predictor of left ventricular remodeling with a sensitivity of 70% and a specificity of 74% for a cut-off value of -15.9% (AUC 0.7).

Conclusions: CMR myocardial deformation analysis with the TT software provides a new tool for evaluation of STEMI patients and prediction of left ventricular remodeling. Global peak systolic circumferential strain was the strongest predictor with a cut-off value of -15.9%.

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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.10

Investigating strategies for optimal 31P MRS clinical cardiac at 3T: Initial Results


Background: The metabolic information obtained from 31P MR cardiac spectra has been demonstrated to be useful in the failing heart [1], in patients with Dilated Cardiomyopathy (DCM) [2]. However technological and physiological challenges prevent wider clinical use of the technique. Prohibitively expensive high field MR scanners, requiring specialist hardware and post-processing knowledge are required to obtain adequate signal to noise (SNR) to quantify the Phosphocreatine (PCr) and Adenosine Tri-phosphate (ATP) signals. Respiratory and cardiac motion is known to degrade spectral quality. Two approaches often employed to mitigate motion effects involve positioning patients prone and ECG gating; which prolongs scan times (> 30 mins.) Lying prone for long periods is not well tolerated by cardiac patients.

Objective: We investigated a number of strategies to optimise 31P spectral acquisition both ECG gated and un- gated to obtain myocardial spectra from healthy subjects using a 1H-31P cardiac surface coil on a 3T Siemens Trio MRI scanner.

Methods: Following coil spatial coil sensitivity testing using a 31P 2-D Chemical Shift Imaging (CSI) free induction decay (FID) sequence gated and un-gated ECG, free breathing, nuclear Overhauser enhanced (nOe), cardiac was used to acquire 31P spectra in un-combined mode from five healthy subjects with parameters [TR/TE: 440/2.3ms FA: 90]. Additionally an in-house PCr-optimised sequence, with saturation bands [TR/TE: 500/2.3ms FA: 45] was used to acquire spectra from a single volunteer. Finally, the impact of nOe on spectral quality was also investigated. Spectra were acquired in the prone position with fitting and quantification carried out using Siemens software. Approval was obtained from the local research ethics committee.

Results: Figure 1 shows the voxel site in the anterior myocardium from which spectra were obtained in under 14 minutes from the simple loop coil. Figures 2 and 3 show the impact of PCr flip angle and TR optimisation in the same volunteer. An increase in PCr integral of more than 10% was obtained, although ATP resonances were diminished. The application of nOe the increased PCr integral by 61%.

Discussion and Conclusion: With careful patient positioning, utilising nOe, quantifiable free-breathing, non ECG-gated spectra were obtained from a simple loop coil in under 14 minutes. The default settings (combined spectra) rendered PCr and ATP peaks unobservable. Similarly, ATP spectral peaks acquired without nOe were also unquantifiable.

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Figure 1. IV septal voxel site

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Figure 2. 31P spectrum from loop coil

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Figure 3. Flip Angle optimised spectrum

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.11

Quantitative Criteria for the Diagnosis of the Congenital Absence of Pericardium by Cardiac Magnetic Resonance


Background: Congenital absence of the left ventricular pericardium (LCAP) is a rare and poorly known cardiac malformation. Diagnosis of LCAP is usually performed by Cardiac Magnetic Resonance (CMR) using only qualitative criteria. The aim of the present study was to establish quantitative criteria for the accurate diagnosis of LCAP on CMR.

Methods: We enrolled 9 consecutive patients affected by LCAP (mean age 26 ± 8 years, 7 males), 13 healthy controls, 13 patients with dilated cardiomyopathy (DCM), 12 patients with hypertrophic cardiomyopathy (HCM) and 13 patients with right ventricular overload (RVO). All patients underwent CMR. For each patients we measured left and right ventricular volumes, mass, atrium, end-diastolic and end-systolic longitudinal diameters (DLD, SLD) and transverse diameters (DTD, DTS) the whole heart volume change (WHVC), and the cardio-vertebral angle (CVA).

The whole-heart volume was measured in end-systole and end-diastole and difference. Whole-heart volume change (WHVC), was expressed in percentage of the end-diastolic volume. The cardio-vertebral angle (CVA) was also measured in the end-diastolic phase of the long axis cine stack as the angle identified between a line directed from the anterior margin of vertebral body to cardiac apex and the major axis of vertebral body

Results: LCAP had higher left ventricular and right ventricular DLD and SLD than all the other groups. Yet, much greater significant difference was found for the WHVC and CVA.

The WHVC was significantly higher in LCAP (21.9 ± 5.4), compared to healthy subject (8.6 ± 2.4, p < 0.001), DCM (7.1 ± 1.8, p < 0.001), HCM (9.3 ± 2.4, p < 0.001) and RVO (8 ± 2.4, p < 0.001). CVA was significantly lower in LCAP (104 ± 14°) than healthy controls (140 ± 11°, p < 0.001), DCM (139 ± 5°,p < 0.001), HCM (150 ± 6°, p < 0.001) and RVO (131 ± 8°, p<0.001).

The sensitivity and specificity of DLD and SLD of both ventricles, WHVC and CVA have been evaluated at ROC curves analysis.

WHVC had the highest sensitivity and specificity to diagnose LCAP using a threshold of >13% Statistical analysis demonstrated the statistical equivalence of interobserver and intraobserver WHVC measurements.

Conclusions: In LCAP the systo-diastolic WHVC is an optimal quantitative criteria to identify the patient with LCAP, beside the standard qualitative features and the indirect morphologic signs on CMR imagines or as a replacement when these are doubts.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.12

Widespread tissue injury during acute myocardial infarction: evidence from advanced CMR relaxometry


Objective: In patients with ST elevation myocardial infarction (STEMI), myocardial tissue injury is not restricted to the territory supplied by the culprit artery but it affects also the remote myocardium supplied by unaffected arteries.(1) The aim was to investigate the T1 characteristics in infarcted and remote myocardium comparing it with normal healthy volunteers.

Methods: 30 patients (mean age 61 ± 10years and 70% males) with STEMI and successful revascularisation by percutaneous coronary intervention (PPCI) and 20 healthy volunteers (with no previous medical history), were included. Each patient underwent clinical CMR at 1.5 T, T1 mapping (MOLLI) pre and post contrast within 48hours after PPCI. The healthy volunteers underwent native T1 mapping only, as no contrast was given. The pre and post contrast T1 values and ECV were evaluated in each of the 16 AHA myocardial segments.

Results: Out of 480 myocardial segments in STEMI patients, 143 were affected and the rest were unaffected or remote (no regional wall motion abnormality, no oedema and no late gadolinium enhancement). The mean native T1 and the mean ECV of the remote myocardium was significantly lower compared to infarcted myocardium (1054 ± 65msec vs 1153 ± 85ms, p < 0.0001 and 0.32 ± 0.06 vs 0.46 ± 0.11ms, p < 0.0001 respectively). However when compared to 320 normal myocardial segments from healthy volunteers, the mean native T1 in the remote myocardium was significantly higher (1054 ± 65msec vs 1028 ± 48msec, p < 0.0001). The mean ECV of the remote myocardium was also higher than normal reference standard (0.32 ± 0.06 vs 0.25 ± 0.04). (2)

Conclusions: This is the first study looking at the impact of STEMI on remote myocardium via non-invasive tissue characterisation by advanced CMR relaxometry technique. Our study highlights that in STEMI the remote myocardium is also affected when compared to normal healthy myocardium. Albeit the myocardial tissue injury in the infarcted territory is significantly greater than remote myocardium. These findings may have significant future implications in the treatment of STEMI, including targeting the remote myocardial inflammation.


1. Abbate A, Bonanno E, Mauriello A, et al. Widespread myocardial inflammation and infarct-related artery patency. Circulation. 2004;110(1):46-50.

2. Dabir D, Child N, Kalra Aet al. Reference values for healthy human myocardium using a T1 mapping methodology: results from the International T1 Multicenter cardiovascular magnetic resonance study. J Cardiovasc Magn Reson. 2014;16:69.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.13

Computed tomography coronary angiography verSus sTRess cArdiac magneTic rEsonance for the manaGement of sYmptomatic revascularized patients: a cost effectiveness study (STRATEGY study)


Background: Computed tomography coronary angiography (CTCA) and stress cardiac magnetic resonance (stress-CMR) are both suitable for diagnosing obstructive coronary artery disease (CAD) in symptomatic patients for chest pain with previous history of revascularization. However, the evaluation of performance of non-invasive tests has to take in account the subsequent diagnostic, testing and medical procedures derived, clinical outcomes and cumulative costs and radiation exposure rather than their diagnostic accuracy alone. The aim of this study is to compare the clinical and economic outcomes of using anatomical (CTCA) versus a functional strategy (stress-CMR) in revascularized symptomatic patients for chest pain.

Methods and Materials: four hundred revascularized symptomatic patients for chest pain were addressed to CTCA (n: 200, mean age 68 +- yo, male 168) or stress-CMR (n:200, mean age 66 +- 9 yo, male 177) and followed-up in terms of downstream non invasive tests, invasive coronary angiography (ICA) and revascularization procedure, medical costs for CAD management, cumulative effective radiation dose and major adverse cardiac events (MACEs) defined as composite endpoints of non fatal myocardial infarction and cardiac death.

Results: all patients performed both tests successfully. The mean follow-up for CTCA and stress-CMR groups were similar (772 + -398 vs 794 + -345 days, p:ns). Compared with stress CMR strategy, CCTA was associated with an increased likelihood of subsequent mean number of further non-invasive tests (1.04 vs. 0.81, p < 0.01), cardiac catheterization (40% vs. 30%, p< 0.05). No differences were found in terms of subsequent percutaneous coronary interventions (PCI) (30% vs. 26%, p:0,37) but stress-CMR group was associated with a favorable trend of PCI/ICA rate (86% vs.75%, p:0.08) and MACEs (4% vs. 8.5%, p:0.06). Moreover, CTCA strategy showed a higher mean cost per patient [2329.46 vs. 2617.47 Euro (-11%), p < 0.05] and a lower mean effective radiation dose [22 vs. 4.4 mSv (-80% 10 yop), p < 0.01].

Conclusions: despite similar on risk profiles, revascularized patients initially evaluated with CTCA after PCI had more downstream non invasive and invasive testng, higher CAD-related spending and effective radiation exposure as compared to patients evaluated with stress-CMR with comparable MACEs.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.14

Comparison of low- versus high-dose of gadobutrol for late gadolinium enhancement imaging at 1.5 Tesla: a clinical feasibility study


Background: Gadolinium-based contrast agent (GBCA) enhanced imaging forms the basis of contemporary cardiac magnetic resonance (CMR) imaging. There is a continuous drive to reduce doses due to possible accumulation of GBCA in human tissue and rare but potentially severe side-effects. Gadobutrol represents a second-generation macrocyclic, non-ionic GBCA, with favorable physicochemical properties resulting in a high relaxivity allowing for possible dose reduction.

Aim: To assess intra- and inter-reader comparability of late gadolinium enhancement (LGE) imaging and image quality of 0.1 mmol/kg versus 0.2 mmol/kg gadobutrol dose in a cohort of consecutive patients.

Materials and Methods: Thirty-two consecutive patients (22 males and 10 females; median age, 57.5 years, range 19-87 years) with an indication for LGE CMR imaging at 1.5 Tesla were prospectively enrolled. LGE left ventricular short axis images were acquired 5 minutes after 0.1 mmol/kg of gadobutrol administration (“low-dose”). Then, additional 0.1 mmol/kg gadobutrol were administered, LGE short axis imaging was repeated 10 minutes after administration (“high-dose”). A four-point scale was used to grade visual signal intensity, image quality, scar-to-myocardium and scar-to-blood contrast.

Results: From the initial 32 patients enrolled in the study, 3 were excluded for artifacts. Global scar detection showed no statistical difference between readers (p = 0.06), doses (p = 1) and their interaction (p = 1). When LGE positive segments were divided in ischaemic and non-ischaemic, segmental extension showed no statistically significant difference between readers (p = 0.35), doses (p = 0.13) or their combined effect (p = 0.39). Transmurality of ischaemic segments showed no significant difference as well between readers (p = 0.62), doses (p = 0.17) or their combined effect (p = 0.4). Signal intensity, image quality and scar-to-myocardium contrast were rated similar for dose (p = 0.20), reader (p = 0.30) or their interaction (p = 0.20). Scar-to-blood contrast showed no differences between readers (p = 0.06) but was significantly higher with the low-dose (p < 0.05).

Conclusions: Low-dose gadobutrol LGE imaging may represent a cost effective, safe and tolerable alternative to high-dose. Our results showed nearly identical results between readers for the detection of enhancement, image quality and signal intensity with a better delineation between scar and blood when compared to 0.2 mmol/kg body weight gadobutrol.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.15

Multi-parametric Cardiac Magnetic Resonance for Prediction of Cardiac Complications in Thalassemia Intermedia: a Prospective Multicenter Study


Introduction: Cardiovascular Magnetic Resonance (CMR) has an established role in managing and predicting prognosis of patients with Thalassemia Major (TM). Thalassemia Intermedia (TI) is a milder variant of thalassemia showing a different clinical and prognostic profile; pulmonary hypertension (PH) is a more common complication.

We prospectively determined the predictive value of CMR parameters, including measurement of right ventricular mass, for cardiac complications in TI.

Methods: We considered 342 TI patients enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) Network; about half of them (178/302, 58.9%) were transfusion-dependent. Myocardial and liver iron overload were measured by T2* multiecho technique. Atrial dimensions, left and right ventricular mass and systolic function were quantified by cine images. Late gadolinium enhancement (LGE) images were acquired to detect myocardial fibrosis [6].

Results: Twenty-three patients were excluded because a cardiac complication was present at the time of first CMR, so we prospectively followed 319 patients (mean age at first scan 38.02 ± 11.69 years, 165 females).

Mean follow-up time was 52.24 ± 24.87 months. Cardiac events were recorded in 22 patients (6.9%): heart failure (HF) in 1 patient, arrhythmias in 12 patients, pulmonary hypertension (PH) in 7 patients and myocardial infarction (MI) in 2 patients. Due to the low number of events, only arrhythmias, PH and cardiac complications globally considered were taken as cardiac outcomes for univariate and multivariate analysis.

In the multivariate analysis RV hypertrophy was the only independent predictive factor for arrhythmias (HR = 33.83, 95% CI = 6.07-188.74, P < 0.0001) and PH (HR = 73.33, 95% CI = 10.00-537.57, P < 0.0001). RV hypertrophy (HR = 24.12, 95% CI = 5.09-114.12, P < 0.0001) and myocardial fibrosis by LGE (HR = 6.59, 95% CI = 1.33-32.67, P = 0.021) were independent prognostic factors for cardiac complications in the multivariate analysis. The Figures display the Kaplan–Meier curves showing the impact of the independent predictive factors on each outcome.

Conclusions: For the first time we studied the prognostic value of RV mass as part of multiparametric CMR imaging in a population of TI patients. RV hypertrophy identified patients at high risk for arrhythmias and PH. Both RV hypertrophy and fibrosis were independent predictive factor for cardiac complications. Measurement of RV mass should be part of the multi-parametric CMR study of TI patients.

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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.16

Prognostic value of Cardiovascular Magnetic Resonance derived indexes of myocardial fibrosis in heart transplant recipients


Background: The myocardium of transplanted hearts is characterized by interstitial inflammation and damage followed by death of myocytes. These lesions result in replacement and interstitial fibrosis which in the long term can impair ventricular function.The aim of the present study was to assess the association of tissue characterization using cardiovascular magnetic resonance (CMR) parameters with cardiovascular adverse events in patients who survived the first year after orthotopic cardiac transplantation (HTx).

Methods and Results: We studied 70 subjects age 48 ± 13 year, 19 F. Average time from HTx 6.5 ± 6 yrs. Myocardial T1 was determined using MOLLI protocol at 1.5 tesla consisting of 3 inversion blocks generating 3-3-5 single-shot True-FISP images. Pre- and post-Gadolinium (GD) injection short-axis T1 maps were acquired within single-breathholds. The myocardial T1 mapping values (ms) were drawn from AHA 16 regions of the left ventricle. Myocardial T1 mapping values pre- and post-GD were normalized to the T1 of blood and haematocrit to calculate the Extra Cellular Volume fraction (ECV). Late gadolinium enhancement was quantified as relative percentage of the total left ventricular mass (LGE%). A composite of major adverse cardiovascular events: cardiovascular death, hospital admission for congestive heart failure, arrhythmias, coronary revascularization (MACE) were recorded during the follow-up period after CMR median 1.73 years. Data are reported as mean ± SD. Twelve MACE were recorded (2 deaths). Patients with MACE had a higher pre-contrast T1: 1047 ±75 vs 989 ± 57 msec, p = 0.004, higher LGE%: 9 ± 10 vs 2.7 ± 3.6, p = <0.001 and higher ECV: 34 ± 0.03% vs 29 ± 0.03%, p = 0.0001. ROC curves selected thresholds of 1016 msec (Sensitivity 67; Specificity 72) for pre-contrast T1 mapping, 30% (Sensitivity 83; Specificity 59) for ECV and 2.77% (Sensitivity 83; Specificity 68) for LGE% to discriminate patients with MACE. Kaplan-Meier survival curves demonstrated that pre-contrast T1 > 1016 msec (logrank test: p = 0.04), ECV >30% (logrank test: p = 0.02) and LGE% > 2.77% (logrank test: p = 0.0007) were associated with an increased risk of sustaining an index event during follow up.

Conclusions: CMR derived indexes of fibrosis can help to stratify HTx patients with increased risk of MACE and CV death.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.17

The role of CMR in the acute phase of hospitalization: changing paradigms


Background: Cardiac Magnetic Resonance (CMR) is an invaluable tool in the assessment of ischaemic and non-ischaemic heart disease. The incremental value of CMR in chronic cardiac conditions has already been demonstrated. However, there is limited evidence evaluating the impact of CMR in the acute hospitalised cardiac patients. We sought to evaluate the impact of CMR on the diagnosis and clinical decision-making in acute hospitalised patients.

Methods: We evaluated the 1 year registry data of 2481 consecutive scans (Jan 2014-Dec2014) at a large tertiary cardiothoracic center and identified 283 patients refered for inpatient CMR scan. CMR protocol included short axis and long axis cines, T2 weighted oedema sequences, early and late gadolinium enhancement(LGE) images. Definitions for “significant clinical impact” of CMR included change in pre-CMR diagnosis, influence on hospitalization period, change in medication, as well as influence on decision making for invasive medical procedures such as CABG, angiography and ICD implantation.

Results: Of the 283 patients, 8 (2.8%) were excluded due to poor image quality and/or incomplete scans, leaving a sample of 275 patients (66% male, mean age 59yrs, with mean ejection fraction of 46% ± 19. Patients were referred to CMR for further assessessment of ischemic heart disease, cardiomyopathy or congenital heart disease.

Overall, CMR had a significant clinical impact on 68% of the patients. This included a completely new diagnosis in 27% of the patients, change in management in 31% and a total of 10% of patients had both a new diagnosis and a change in management. CMR results led to invasive procedures on 27%, avoided invasive procedures on 16%, and had an influence on hospital discharge on 15% of the patients. 84% of the patients had echocardiography prior to CMR. CMR confirmed the echo diagnosis in 11%, complemented the echo findings by additing significant new information in 41% and changed the echo diagnosis in 30% of the cases.

In a multivariable model that included clinical and imaging parameters, age and presence of LGE were the only independent predictor of “significant clinical impact” (LGE p-value .007, OR 2.782, CI 1.328-5.828)

Conclusions: CMR had a significant impact in patient's diagnosis and management in 68% of acutely hospitalised patients. The presence of LGE was the only independent predictor of significant clinical impact following CMR.

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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.18

Preoperative CMR-based score predict ventricular response after surgical left ventricular reconstruction in ischemic heart failure patients


Objectives: Left ventricular (LV) remodeling is a complex process following acute myocardial infarction (MI) and leading to a dilated and distorted LV cavity. Surgical LV reconstruction (SVR) aims to reduce LV end-diastolic volume by excluding scar tissue and to restore a more physiological LV geometry, thereby improving LV function and clinical status. However, factors determining outcome are still not completely understood. Cardiac magnetic resonance (CMR) is the gold standard imaging technique to show necrotic myocardium (scar tissue) in vivo and to quantify LV function. Based on the observation that the total amount and the regional distribution of scar tissue could affect postoperative reverse remodeling, we suggest a new score including preoperative CMR parameters assumed to affect LV function (CMR score) in order to predict postoperative outcome.

Methods: Patients with previous MI eligible for SVR were studied by contrast-enhanced CMR before and six months after surgery. The CMR protocol included standard sequences for anatomical and functional evaluation of the ventricles and post-contrast sequences for late gadolinium enhancement (LGE) evaluation. The CMR score includes the following preoperative CMR parameters: LV end-diastolic volume, LV end-systolic volume, RV end-systolic volume, LV diastolic sphericity index, LV mass and wall thickness, LGE mass and distribution.

Results: We studied 18 patients (mean age 65 ± 10 years, 16 males). CMR score showed an inverse, significant statistical correlation with LV ejection fraction (LVEF) (rho = -0.60, p value = 0.009) and with right ventricular ejection fraction (RVEF) at 6-month follow-up (rho = -0.67, p value = 0.002) (see Figure).

Conclusion: Our preliminary data suggest that anatomical and functional variables from preoperative CMR could predict the effect of SVR on LV and RV function. CMR analysis of LGE mass and distribution could play a role in determining postoperative cardiac function. This study suggests the clinical usefulness of CMR score that, however, needs to be validated in a larger population.

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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.19

Excellent response rate to cardiac resynchronization therapy guided with magnetic resonance imaging


Objectives: Cardiac resynchronization therapy (CRT) is a well-established method for patients with drug refractory symptoms of heart failure. However, there is still substantial number of non-responders to CRT. We aimed to prove that cardiac magnetic resonance (CMR) can accurately identify the target segment for CRT implantation and therefore increase the response rate.

Methods: The study population consisted of 45 patients (age 63 ± 12y, 71% males) undergoing CRT implantation. All patients underwent 2D echocardiography (ECHO) including strain analysis on Vivid E9 (GE Healthcare) and CMR on Siemens Trio 3T scanner including tagging sequence with strain analysis (inTag Sofware). The target segment for lead implantation was defined as the latest site of mechanical contraction (both ECHO and CMR) with < 25% myocardial scar determined by the late gadolinium enhancement (CMR). CRT implantation was guided by CMR results only. We aimed to achieve the lead/ target segment exact concordance. All patients were followed up including repeat ECHO and clinical assessment. Responders were defined as LV end-systolic diameter reduction > 10% together with NYHA class improvement ≥ 1 at 12 months follow-up.

Results: The average length of the follow up was 20 ± 7 months with 11.1% death rate and 8.9% rate of hospitalizations for heart failure. Symptoms at baseline were NYHA II in 40% and NYHA III in 60%. Left bundle branch block (LBBB) (Strauss criteria) was present in 88.9%, mean QRS duration was 165 ± 14 ms. CMR derived mean LV EF was 24 ± 9%, end-diastolic volume 219 ± 58 ml, end-systolic volume 169 ± 59 ml. Image quality for target segment detection was suboptimal in 2 patients (4.4%) in CMR study. The response rate was 100% in the subgroup of 18 patients with LBBB and the exact concordance of the lead position/target segment assessed by CMR. The response rate was 59% in 22 patients with LBBB and discordant lead position/target segment. There were 5 patients without LBBB with the response rate 0%, independent of the lead position/target segment concordance. The response rate was 81% in patients with LBBB and concordant lead/target segment assessed retrospectively by ECHO and 69% in patients with LBBB and discordant lead/target segment (ECHO). Fig 1,2

Conclusions: CMR enables detection of the site of latest LV mechanical activation in 95.6%. Successful trans-venous targeted lead placement results in excellent response rate, but remains challenging and surgical placement might be an option.

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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.20

The ECG as a predictor of arrhythmogenic substrate on Cardiac Magnetic Resonance Imaging in patients undergoing ablation for premature ventricular contractions


Background: The most likely origin of premature ventricular contractions (PVC) may be deduced from surface ECG analysis during pre-procedural planning of an electophysiological (EP) procedure. Apart from purely benign forms of increased ventricular ectopy, myocardial substrate (e.g. regional fibrosis) may be present in certain cases which will significantly impact the invasive treatment approach. Cardiac magnetic resonance imaging (CMR) can reliably identify fibrotic target lesions and, hence, may assist in adequate patient selection and procedural planning.

Methods: 48 patients (60% male, median age 56 ± 14.8, median PVC count 18748 ± 13175) referred for radiofrequency (RF) ablation of PVCs at our institution who underwent CMR before EP study were included in the analysis. A 12 lead electrocardiogramm (ECG) documentation of PVCs was available in all patients. CMR was performed at 1.5Tesla using cine, T1/T2-weighted and 3D-delayed enhancement imaging in standard cardiac geometries. RF ablation was performed according to local protocols using a 3-D-mapping tool (Carto®) and a 3.5 mm Thermocool catheter, flow rate 30 ml/min.

Results: On surface ECG right bundle branch block (RBBB) morphology was present in 50% of patients. Fibrotic substrate on CMR was present in 11 patients. In univariate analysis, RBBB morphology on surface ECG significantly predicted the presence of substrate (p = 0.01). Multiple PVC morphologies (≥2) were present in 6 patients and also predicted substrate on CMR (p = 0.006) Patients with substrate showed no significant difference with regard to baseline characteristics including known structural heart disease or left ventricular ejection fraction (43% ± 13 vs. 50% ± 11, p = 0.09). CMR-identified ventricular substrate was verified to represent the site of origin of the clinical PVCs during EP study in all patients. Succesful RF ablation of the clinical PVC (reduction of PVC burden >95%) was achieved in 93.8% of all cases.

Mean ablation time was signifiantly longer and the mean maximum applied energy was higher in patients with ventricular substrate (1479 ± 971s vs. 722 ± 744s, p = 0.012 and 50 ± 7Watt vs. 43 ± 10 Watt, p = 0.04 respectively).

Conclusion: ECG morphology of PVCs is a significant predictor of the presence of myocardial subtrate on CMR imaging. In patients with RBBB morphology and/or multiple PVC patterns CMR should be performed routinely before ablation in order to guide the electrophysiological procedure and improve success rate.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.21

Comparison of T1-mapping at 3.0T CMR and angiographic APPROACH score for area at risk assessment in ST-segment elevation myocardial infarction


Background: Myocardial salvage index (MSI) derived using cardiac magnetic resonance (CMR) is a strong independent predictor of adverse remodeling and prognosis post STEMI. It is typically imaged using a T2-weight short tau inversion recovery sequence, which is susceptible to an array of artifacts limiting its usefulness to evaluate MSI as a reliable surrogate marker of myocardial injury. T1-mapping has recently come to the fore as a viable alternative but it requires acquisition of, often time consuming, additional images and post-processing. Optimal detection of reversible myocardial injury could improve the reliability of MSI determination and its prognostic relevance.

Objective: To compare the robustness of myocardial oedema detection using free-breathing motion-corrected (moco) T1-mapping on 3.0T CMR and the validated ‘APPROACH’ angiographic area at risk (AAR) score in patients presenting with STEMI.

Methods: Forty-five patients underwent CMR 1-5 days following presentation with STEMI. AAR was quantified using resulting parametric colour maps from moco-T1 Modified Look Locker Inversion Recovery (MOLLI) sequences and compared to the AAR derived in a core-lab using the APPROACH score in a using analysis of variance (ANOVA). Pearson's correlation coefficient was used to assess correlation. Inter-sequence agreement was assessed using the Bland-Altman method, coefficient of variation (CoV) and two-way mixed-effect intra-class correlation coefficient (ICC) for absolute agreement.

Results: Patient characteristics are presented in Table 1. AAR assessed using the two methods was significantly different (p = 0.02) with moderate to poor correlation and agreement (see Table 2). However, the diagnostic imaging rate obtained with both techniques was excellent

Conclusions: moco-T1-mapping using MOLLI at 3.0T CMR and angiographic APPROACH score are not inter-changeable for detecting reversible myocardial injury and determination of MSI for the prediction of functional recovery following STEMI. Further work is required to assess the test-retest repeatability and overall reliability of each technique.

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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.22

Pathological correlates of left bundle branch disease in patients with non-ischemic cardiomyopathy: a cardiovascular magnetic resonance study


Background: The pathological correlates of intraventricular conduction delays in patients with non-ischemic cardiomyopathy (NICM) have been scarcely investigated.

Aim: To assess left ventricular (LV) structural, functional and tissue abnormalities associated with left-system intraventricular conduction delay, either left anterior hemiblock (LAHB) or complete left bundle branch block (LBBB), in a cohort of NICM patients submitted to cardiovascular magnetic resonance (CMR).

Materials and Methods: Twelve lead electrocardiogram and CMR were performed in 196 consecutive patients with NICM. The presence and extent of myocardial fibrosis was evaluated with late gadolinium enhancement (LGE) technique. The presence of left-bundle disease (LBD) including LBBB or LAHB, right-bundle branch block, aspecific conduction delay and normal intraventricular conduction (nIVC) was recorded.

Results: Compared to nIVC patients, those with LBD were older (66 vs 59.5 years, p = 0.001), had greater LV volumes (p = 0.035 for end-diastolic and p = 0.009 for end-systolic volume) and mass (92 vs 85 g/m2, p = 0.034), and showed lower LV ejection-fraction (33 vs 40%, p = 0.008). LGE was observed more commonly in LBD than nIVC patients and was more often located in the septum (all P < 0.001). At multivariate analysis, septal LGE (but not fibrosis in other LV regions) was independently associated with a higher likelihood of LBD (OR 6.1, 95% CI 2.9 to 12.7, P < 0.001), even after correction for LV volumes, mass and ejection fraction.

Conclusions: In NICM, the presence of LBD is associated with worse LV remodeling and dysfunction than nIVC. Septal fibrosis yielded a 6-fold greater likelihood of LBD independently of the degree of LV dilatation and systolic dysfunction.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.23

Myocardial remodelling and fibrosis in nonischaemic dilated cardiomyopathy: insights from cardiovascular magnetic resonance


Background: In nonischaemic dilated cardiomyopathy (DCM), myocardial fibrosis can be detected by cardiovascular magnetic resonance (CMR) as late gadolinium enhancement (LGE) and has been associated with worse prognosis. We investigated whether LGE is associated with left ventricular (LV) reverse remodelling in DCM.

Methods: Ninety-seven DCM patients (age 56 ± 14 years, 62 male) with LV ejection fraction ≤50% were enrolled and underwent baseline CMR; patients with ischaemic, valvular, congenital heart disease, other cardiomyopathies or contraindications to CMR were excluded. After a median 29-month follow-up (interquartile range 16-46) on optimal medical therapy, all patients underwent a second CMR; patients who died, underwent device implantation or declined a second CMR, were also excluded from the study. LGE was quantified on post-contrast CMR images as percentage of LV mass. LV reverse remodelling was defined as a decrease >10% of LV end-systolic volume at follow-up.

Results: Mean LV ejection fraction was 37 ± 10% at baseline, 44 ± 12% at follow-up. LGE was present in 56 (58%) patients at baseline (median 6% of LV mass, interquartile range 3-11%), without significant differences at follow-up (median 7%, interquartile range 4-11%, p = NS). Patients experiencing LV reverse remodelling during follow-up (n = 53, 55%) presented a baseline worse LV ejection fraction (34 ± 11%) than patients not experiencing LV reverse remodelling (41 ± 8%, p < 0.01), greater LV end-diastolic volume (125 ± 38 vs. 112 ± 26 ml/m2, p = 0.05), worse right ventricular ejection fraction (54 ± 13% vs. 59 ± 10%, p = 0.03), but significantly less fibrosis (median 5% of LV mass, interquartile range 2-9% vs. median 9%, interquartile range 3-15%, p < 0.01); no age or gender differences were observed (p = NS). Multivariate regression analysis showed that LGE extent at baseline CMR was a negative predictor of LV reverse remodelling (p < 0.01), even after correction for age, New York Heart Association class, LV volumes and systolic function.

Conclusions: In DCM patients, LGE extent was a negative independent predictor of LV reverse during follow-up, irrespective of the initial clinical status and the severity of ventricular dysfunction.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.24

The association between fibrosis and contractile dysfunction in hypertrophic cardiomyopathy assessed by cardiovascular magnetic resonance


Introduction: At present the diagnosis of hypertrophic cardiomyopathy (HCM) is made when a segment measures ≥15mm using cardiac imaging. Using cardiovascular magnetic resonance (CMR) extracellular volume (ECV) mapping techniques it is possible to detect early phenotypic manifestation of HCM, such as extracellular matrix expansion, which can occur before overt hypertrophy. It is unknown whether strain impairment occurs early in the disease process when there is ECV expansion with overt hypertrophy.

Methods: 50 patients with HCM underwent CMR studies at 3.0T including cine imaging in multiple planes, T1 mapping for calculation of ECV and late gadolinium enhancement (LGE) imaging. For each segment of the American Heart Association (AHA) model of each subject segment thickness, the presence of LGE and strain by feature tracking were measured.

Results: Circumferential strain by feature tracking (Ecc-FT) was lower in segments with ECV expansion (-17.0 ± 10.3 vs -19.9 ± 8.4%, N = 783 P < 0.001). However in segments <15mm Ecc-FT was not significantly different between those with and without ECV expansion (-19.7 ± 9.2 vs -20.6 ± 7.9%, N = 684, P = 0.43). In segments <15mm Ecc-FT was significantly lower in those with LGE (-12.9 ± 8.2 vs -20.9 ± 8.1%, N = 684, P < 0.001).

There were significant correlations between Ecc-FT and both segment thickness and ECV (Rs = 0.616 and 0.176, P < 0.001 for both). However on multivariable linear regression only segment thickness had a significant association with Ecc-FT (beta = -0.54, p < 0.001).

Conclusion: Regional strain impairment is predominantly associated with the degree of hypertrophy and replacement fibrosis assessed by the presence of LGE. In non-hypertrophied segments strain is not significantly impaired by the presence of interstitial fibrosis detected by ECV expansion on T1 mapping. Therefore the presence of interstitial fibrosis may be a more useful method than impairment of strain of identifying HCM in subjects with borderline LV hypertrophy.

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Figure. (A) Gross hypertrophy (>15mm) in the septum. (B) FT strain map of the same slice, shown in systole. Colour scale ranges from akinetic (red) to >20% strain (blue). (C) LGE imaging showing replacement fibrosis in inferoseptum (white arrow). (D) ECV map ranging from 0 (blue) to 100% (red). Note the replacement fibrosis (black arrow) and the non-hypertrophied anterior and anterolateral walls have marked ECV expansion (35-45%) yet have normal radial strain on FT imaging.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.25

Persistent myocardial inflammation due to intramyocardial haemorrhage in reperfused STEMI as a precursor to adverse LV remodelling - insights from multi-parametric mapping


Background: Microvascular obstruction (MVO) and intramyocardial haemorrhage (IMH) still occur in reperfused ST-segment elevation myocardial infarction (STEMI) patients and are associated with adverse left ventricular (LV) remodelling and worse clinical outcomes. We aimed to use T1, T2 and T2* mapping to understand the changes occurring in the myocardial infarct (MI) zone and the remote myocardium in reperfused STEMI patients with and without adverse (LV) remodelling.

Methods: 40 reperfused STEMI patients underwent a CMR at 4 ± 2 days and at 5 ± 2 months post PPCI on a Siemens 1.5T scanner. Native T1 (MOLLI), T2, T2* and post contrast T1 maps were acquired. Co-registered and motion-corrected automated ECV maps were generated offline. 20 matched healthy volunteers served as controls. IMH and chronic iron deposition were defined as a hypointense core with T2* < 20ms. Adverse LV remodelling was defined as ≥20% increase in LV end-diastolic volume.

Results: 26 out of 40 patients (65%) had MVO. Figure 1 shows an example of the multi-parametric maps of an inferior STEMI with MVO and IMH and chronic iron deposit on the follow-up scan (arrows). The T2* in the MI zone in patients with IMH was 13 ± 3ms compared to 30 ± 6ms in those without (P < 0.001). All patients with adverse LV remodelling (8/40, 20%) had MVO with IMH. 87% of patients with IMH on the acute scans developed chronic iron deposition and displayed higher T2 values in the surrounding infarct zone compared with those without at follow-up (T2: 61 ± 4ms versus 53 ± 4ms, P = 0.001). ECV in remote myocardium (ECVRemote) was higher on the acute scan when compared to control (27.9 ± 2.1% versus 26.4 ± 2.1%, P = 0.01), but this difference was non-significant at follow-up (27.0 ± 2.1% versus 26.4 ± 2.1%, P = 0.30). In the 8 patients with adverse LV remodelling, the ECVRemote was higher on both the acute and follow-up scan when compared to those without adverse LV remodelling (acute scan: 29.5 ± 1.4% vs. 27.4 ± 2.0%; P = 0.01; follow-up scan 28.6 ± 1.5% vs. 26.6 ± 2.1%; P = 0.02). There was no difference in T2 values in the remote myocardium in these patients.

Conclusions: Most patients with IMH developed chronic iron deposition. This is associated with persistent inflammation on T2 mapping and adverse LV remodelling. Adverse LV remodelling is associated with remote ECV expansion. IMH - either acutely or chronically–is a potential therapeutic target to prevent inflammation and subsequent adverse LV remodelling.

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Figure 1

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.26

Semiquantitative analysis of low and high b value DWI for detecting myocardial edema in acute myocarditis


Objectives: Evaluate the clinical feasibility and accuracy of semiquantitative analysis of DWI with low and high b value in patients with acute myocarditis compared to T2 STIR.

Methods: 20 patients with confirmed acute myocarditis and 17 control subjects were submitted to cardiac MRI. The cardiac MRI protocol included short-axis black blood T2 STIR, delayed enhancement and DWI. MRI studies were performed using a 3 Tesla and 1,5T Magnet.

We performed a whole cardiac SSh EPI DWI sequence including three b values (0, 50 and 300 mm2/s) with cardiac trigger, acquired in diastole and apnea.

Semiquantitative analysis of the signal intensity (SI) and ADC map by plotting ROIs on areas of inflamed myocardium showing high signal intensity on both b50 and b300 mm2/s (SIb300; ADCb300) and in those regions with high signal intensity on b50 mm2/s that loss signal at b300 mm2/s (SIb50; ADCb50). The ratio of signal intensity of T2 STIR myocardium vs pectoral muscle (T2 Ratio), SI and ADCb50 Ratio (SIb50/SIpectoral; ADCb50/ADCpectoral), SI and ADCb300 Ratio (SIb300/SIpectoral; ADCb300/ADCpectoral) were obtained.

Results: Significant differences between patients with acute myocarditis in comparison to normal controls were found in T2 Ratio (2.40 ± 0.674 vs. 1.74 ± 0.29: p < 0.001), SIb300 (803.55 ± 640.29 vs. 891.17 ± 220.9; p: 0.018) and SIb300 Ratio (2.59 ± 1.61 vs. 1.43 ± 0.69; p < 0.001). SIb50 and ADC based measurements did not show significant differences among both groups.

ROC curves revealed a high area under the curve of T2 Ratio (0.874; p < 0.001); SIb300 (0.725; p: 0.020) and SIb300 Ratio (0.828; p < 0.001).

Conclusion: DWI (SIb300 and SIb300 Ratio) detect myocardial edema in a similar manner to T2 STIR and with excellent interobserver agreement.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.27

Value of Cardiac MRI In Detecting Coronary Artery Disease In Newly Diagnosed Systolic Dysfunction


Introduction: Coronary angiography (CA) is systematically realized in case of newly diagnosed systolic dysfunction (SyD) but 75-80% are normal. Subendocardial enhancement in Cardiac-MRI (CMR) is known as highly specific for ischemic disease, and its value to diagnose Coronary Artery Disease (CAD) has been suggested in small series.

Objective: Determine the value of CMR in detecting CAD for patients with SyD (left ventricular ejection fraction LVEF ≤45%) without obvious etiology.

Methods- From 2009 to 2015, 305 patients were retrospectively included with newly diagnosed LVEF ≤45% unexplained by clinical, electrical and echographic evaluation. A Coronary Angiography (CA) and CMR had to be performed within 3 months. 40 CMR and 40 CA were re-interpreted to evaluate the fiability of the interpretations. 4 groups were defined, depending on CAD diagnosed or not by CA (« CA+ or –») or CMR (« CMR+ or - »).

Results: CA was normal for 247 (81%) patients and identified 58 (19%) ischemic heart diseases; CMR showed a late subendocardial enhancement in 85 (28%) patients. 20 (6,5%) patients were revascularized. Most of CMR and CA were concordant: 215 (70%) patients « CA- and CMR- » and 56 (18%) patients « CA+ and CMR+ ». 2 (0,7%) patients were « CA+ but CMR- »; none were revascularized. 32 (10%) patients were « CA- but CMR+ »; for most of them, diagnosis of MINOCA (Myocardial Infarction and Non-Obstructive Coronary Arteries) was withheld: reperfused acute myocardial infarction, coronary spasm … Sensibility of CMR compared to CA was 97%, with a good concordance in terms of coronary territory too; specificity was 87%. Sensibility of CA compared to CMR was 64% and specificity 99%. For 84 (28%) patients CMR allowed another diagnosis: myocarditis, LV non-compaction, Tako-Tsubo …

Conclusions: CMR detected 97% of significant CAD at CA in patients with newly diagnosed LVEF ≤ 45%, and recognized a lot of MINOCA not diagnosed by CA. Every patients revascularized had late gadolinium enhancement. Thus, in this indication, CMR seems more and more interchangeable with CA.

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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.28

Usefulness of cardiac magnetic resonance in tuberous sclerosis complex


Objective: Tuberous sclerosis complex (TSC) is a rare autosomal dominant inherited syndrome, which may affect many organs, most commonly brain, kidneys, lungs and heart. The most common cardiac manifestation is the rhabdomyoma, a benign tumour that usually undergoes spontaneous regression in the first years of life. The aim of this study was to review the cardiac magnetic resonance (CMR) findings in TSC adult patients.

Methods: TSC adult patients referred to CMR between April 2012 and January 2015 were analysed. Five patients were referred, but in one patient CMR could not be done due to claustrophobia. A transthoracic echocardiography (TTE) was performed before CMR (1.5T Avanto Dot, Siemens, Erlangen and Signa LX 9.1, General Electric, Milwakee). The CMR protocol included the following sequences: b-steady-state free precession (b-SSFP) cine sequence, T1 black-blood turbo spin-echo (BB-TSE), T1 BB-TSE with fat saturation (fat-sat), myocardial perfusion with a saturation-recovery turbo field-echo sequence and late gadolinium-enhancement sequence (LGE).

Results: Mean age was 36,6 ± 11,9 years and 4/5 were female. All patients had brain involvement, with medical history of epilepsy in 4/5. Renal involvement with angiomyolipomas was present in 3/5. No patient had cardiovascular symptoms. Intermittent preexcitation in the electrocardiogram was present in one patient but without history of tachycardia. Echocardiography and CMR findings are summarized in the table. In 3/4 patients, CMR showed at least one intramyocardial area of hypointensity in b-SSFP and hyperintensity in T1 BB-TSE with a marked signal decrease in T1 BB-TSE fat-sat (figure). In the echocardiography these areas presented as rather hyperechogenic (figure). Finally, global and segmental functions were normal and no pathological enhancements were found.

Conclusion: Adult patients with TSC may have myocardial fatty infiltrates probably due to a rhabdomyoma regression. CMR is very useful in TSC because it provides a better characterization of cardiac disease.

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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.29

Papillary muscles offer further insight into hypertrophied hearts: a cardiovascular magnetic resonance study


Background: The aetiology of left ventricular hypertrophy (LVH) is often difficult to determine. The left ventricular papillary muscles (LVPM) sometimes appear differentially hypertrophied, particularly in Fabry disease (FD) where storage appears detectable by cardiovascular magnetic resonance (CMR) T1 mapping.

Aim: To characterise LVPM mass across a range of heart diseases with LVH, and to gain further insight into the mechanisms of LVPM hypertrophy in FD using T1 mapping.

Methods: 538 cases were retrospectively recruited from research CMR cohorts: 125 FD, 85 hypertrophic cardiomyopathy (HCM), 67 amyloid, 82 aortic stenosis (AS), 40 hypertension, and 79 controls. LVPM contribution to total LVM was measured using manual contouring on CMR short axis cine images. T1 values (septal and LVPM) were measured using ShMOLLI sequences in FD and controls.

Results: LVPM contribution to LVM was the highest in the LVH + ve FD group and significantly increased compared to all other groups (FD: 13 ± 3%, HCM 10 ± 3%, amyloid 8 ± 2%, AS 7 ± 3%, hypertension 7 ± 2%, controls 7 ± 1%; p < 0.001). LVH + ve HCM also had significantly increased LVPM. In the LVH-ve cohorts, only FD had significantly increased LVPM (11 ± 3%; p < 0.001).

In FD there was relative concordance in septal and LVPM T1 values. LVH + ve FD: when the septal T1 was low, LVPM T1 was low in 90%. LVH-ve FD: when the septal T1 was normal, the LVPM T1 was normal in 70% (indicating no detectable storage), and when the septal T1 was low, 75% had a low LVPM T1 (indicating storage). Despite these findings, LVPM contribution to LVM was similar between the low septal T1 and normal septal T1 groups in LVH-ve FD (11 ± 3% vs 10 ± 3%, p = 0.08).

Conclusion: Disproportionate hypertrophy of LVPMs in LVH + ve hearts is seen in Fabry and HCM. This phenomenon also occurs in LVH-ve FD. Low T1 is not always present in FD LVPM hypertrophy, implicating other pathological mechanisms.

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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.137

Diagnostic and clinical implications of CMR timing (early versus late) in patients with troponin positive acute coronary syndromes and unobstructed coronary arteries


Background: 7-15% of patients with acute coronary syndrome (ACS) have unobstructed coronary arteries. In these patients cardiac magnetic resonance (CMR) can identify different underlying aetiologies.

Aim: To evaluate the diagnostic and decision making implications of CMR timing (early versus late) in patients with ACS and unobstructed coronary arteries.

Methods: Registry data on 204 consecutive patients (mean age 55yrs, 51% males) with troponin positive ACS and unobstructed coronary arteries, referred for a CMR (Sept 2011-Jul 2014) were evaluated. An “early” CMR (<2weeks from presentation) was performed in 98 patients and 106 patients underwent a “late” (>2weeks from presentation) comprehensive CMR scan. Table 1. “Significant clinical impact” was predefined as change in diagnosis/management. Propensity matching was performed between early and late CMR groups to minimise any selection bias due to the differences in clinical characteristics.

Results: Overall, a cause for the troponin rise was found in 70% of patients and CMR had a significant clinical impact in 66%, including leading to change in the final diagnosis in 54%. In a multivariable model that included clinical and imaging parameters, presence of late gadolinium enhancement (LGE) and age were the only independent predictors of “significant clinical impact” (LGE OR 2.3, p = 0.02). Table 2. In a propensity score analysis, 58 pair of patients was matched for early and late CMR. The diagnostic pick up rate in the “early” was significantly higher than “late” group (88% vs 50% p < 0.0001). Myocarditis (33%) was the most common diagnosis in the “early” group, whereas myocardial infarction (MI) (22%) was most prevalent in the matched “late” group. The prevalence of MI was not different in the “early” and “late group (22% vs 26% respectively, p = 0.83). The clinical impact also improved significantly in the early group compared to the propensity score matched late group. (76% vs 51%, p = 0.01).

Conclusion: In a large cohort of patients with troponin positive ACS and unobstructed coronary arteries CMR was able to establish a final diagnosis in overall 70%. CMR made a significant additive clinical impact on management and diagnosis in 66% of patients, with LGE being the best independent predictor of impact. Moreover, the diagnostic value as well as the clinical impact of CMR improved significantly when carried out within 2 weeks from presentation.

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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.1

Evaluation of right ventricular transverse strain and strain rate in patients with acute ST-segment elevation myocardial infarction: a cardiac magnetic resonance feature tracking study


Background: Impaired right ventricular (RV) systolic function after acute ST-segment elevation myocardial infarction (STEMI) is associated with poor clinical outcomes. CMR feature tracking technique enables quantification of myocardial deformation and becomes promising method. The aim of this study was to evaluate longitudinal and transverse strain and strain rate of RV free wall in patients with acute isolated left ventricular STEMI using CMR feature tracking.

Methods: A total of 38 participants (mean age 59 ± 10.8 years; 60% male) were recruited into the study and underwent CMR at 1.5 Tesla (Siemens Magnetom Aera). TomTec 2D Cardiac Performance Analysis software was used to analyze mean and segmental longitudinal and transverse strain and strain rate of the RV free wall. Patients with RV myocardial infarction (LGE of RV myocardium) were excluded.

Results: RV free wall longitudinal strain and strain rate parameters did not reach statistical significance. Patients with acute STEMI demonstrated lower mean RV free wall transverse strain (12.40 ± 8.10% vs 21.70 ± 7.32%, p = 0.0001) and strain rate (1.08 ± 0.33 s-1 vs 1.51 ± 0.38 s-1, p = 0.001) than controls. We also performed segmental analysis. Transverse strain was significantly impaired in the basal (15.52 ± 8.81% vs 24.52 ± 11.29%, p = 0.03), mid (11.16 ± 8.34% vs 18,21 ± 7.57%, p = 0.02) and apical (10.52 ± 11.53% vs 22.37 ± 10.33%, p = 0.001) segments of RV free wall in patients with STEMI comparing with controls. Transverse strain rate was lower in the basal (0.97 ± 0.44 s-1 vs 1.51 ± 0.43 s-1, p = 0.001) and mid (0.91 ± 0.31 s-1 vs 1.36 ± 0.41 s-1, p = 0.01) segments in STEMI group. There was no difference between groups for apical transverse strain rate of RV free wall.

Conclusions: This study demonstrates that transverse strain and strain rate of RV free wall are impaired in patients with acute isolated left ventricular STEMI while longitudinal RV systolic function remains normal.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.2

Cardiac resynchronization in ischemic heart failure patients: a comparison between therapy guided by cardiac magnetic resonance imaging and 2D-speckle tracking echocardiography


Aims and Objectives: In heart failure (HF) patients, cardiac resynchronization therapy (CRT) has beneficial effects on symptoms, left ventricular (LV) systolic function and survival. In ischemic HF patients non-response rate to CRT is higher as compared to non-ischemic HF patients. Aim of study was to explore role of late gadolinium enhancement cardiac MRI (LGE-CMR) and 2D-speckle tracking echocardiography to guide CRT implantation in ischemic HF patients.

Methods and Materials: 90 ischemic HF patients were divided in 2 groups. Group 1: 30 patients undergone to LGE-CMR and 2D-speckle tracking echocardiography at baseline. Scar transmurality was assessed on LGE-CMR images using 17-segment model. Transmural scar was defined as having >50% of thickness in any of 17 segments. Viable segment was defined when scar tissue was < 51% of its thickness. From 2D-speckle tracking echocardiography was derived global longitudinal strain bulls eye of time to peak longitudinal strain. Target zone for LV lead placement was defined most delayed viable segment based on information derived from LGE-CMR and 2D-speckle tracking echocardiography. Group 2: 60 patients were implanted according current clinical practice with LV lead preferably placed in (postero-)lateral vein without any imaging information. Response to CRT was defined as reduction of LV end-systolic volume ≥15% at 6 months follow-up.

Results: Baseline characteristic were not different between the two study groups. Response rate to CRT was significantly higher in group 1 (73% vs 52%, p = 0.045).

Conclusions: LGE-CMR together with 2D-speckle tracking echocardiography are important tools to guide CRT implantation in ischemic HF patients in order to improve response rate to CRT.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.3

Cardiac magnetic resonance versus bisphosphonate scintigraphy for diagnosis of cardiac amyloidosis


Background: Cardiac amyloidosis (CA) is a disease still under-diagnosed, requiring a multidisciplinary approach. Cardiac magnetic resonance (CMR) imaging, with late gadolinium enhancement (LGE) and bisphosphonates scintigraphy (BS) represent two valuable tools for CA diagnosis. Currently, no comparison has been performed between LGE CMR and single photon emission computed tomography (SPECT) findings.

Aim: To compare SPECT global and regional radiotracer myocardial uptake and LGE distribution in patients with transthyretin-related CA (TTR-CA) or light-chain cardiac amyloidosis (AL-CA). To assess CMR and BS feasibility in patients with CA and to test diagnostic accuracy of hydro-methylene-bisphosphonates in CA.

Results: Eighty-two patients with clinical suspicion of CA underwent BS between 2011-2015. CMR was not performed in 35 of them (43%). Twenty-five patients (30%) were excluded because of CMR-related contraindications (implanted with CMR incompatible devices, claustrophobia, advanced chronic kidney disease). Forty-six patients (57%) underwent both CMR and BS representing study population. TTR-CA and AL-CA groups did not show statistical differences in terms of biventricular volumes, masses and myocardial thickness. Moreover, no differences were noted in terms of LGE presence with the exception of LGE apex-to-base gradient that was observed in 26% of TTR-CA and in no AL-CA patient (p < 0.05).

With regard to BS specificity and sensitivity CA generic diagnosis was 100% and 66% respectively, whereas CMR presented 100% specificity and sensitivity. When a specific diagnosis of TTR-CA was considered, BS specificity and sensitivity was 100% and 95% respectively, while CMR specificity and sensitivity was 67% and 100% respectively. SPECT semi-quantitative evaluation, assessed as number of beats per voxel per minute (bvm) > 9851 allowed to identify segments likely comprising amyloid deposits with 87% specificity and sensitivity. Comparison between SPECT and CMR showed a 93% concordance for the left ventricle (p < 0.0001) and 84% concordance (p < 0.005) for the right ventricle.

Conclusions: Combined CMR and SPECT use allows exploiting CMR accuracy for CA diagnosis and SPECT diagnostic accuracy for TTR-CA detection. SPECT and CMR segmental comparison of cardiac amyloid is highly concordant for both ventricles in TTR-CA.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.4

Strain relaxation index, a novel tagged MRI-derived diastolic function parameter, is impaired in metabolic syndrome


Background: Strain relaxation index (SRI) is a recently described diastolic function parameter derived from tagged magnetic resonance imaging (MRI) that independently predicts heart failure. Subclinical structural and functional cardiac changes in patients with metabolic syndrome (MetS) are being increasingly recognized and are associated with increased insulin resistance.

Objective: To evaluate the association between tagged-MRI derived left ventricular diastolic functional parameters and insulin resistance, across the continuum from MetS to type 2 diabetes mellitus (T2DM).

Methods: This cross-sectional study included 1,558 subjects from the Multi-Ethnic Study of Atherosclerosis (MESA) baseline examination who underwent diastolic function analysis by tagged-MRI. Diastolic parameters were early diastolic strain rate (EDSR), peak torsion recoil rate (pTRR) and SRI (defined as the difference between post-systolic and systolic times of the strain peaks, divided by the EDSR peak). Insulin resistance was determined by homeostatic model assessment of insulin resistance (HOMA-IR). Subgroups were defined assuming categories of increasing insulin resistance (IR): 1) no MetS and no T2DM; 2) presence of MetS without T2DM; 3) presence of T2DM. Multivariate linear regression was used to determine the relationship of MetS and IR categories with diastolic function, including age, gender and ethnicity as co-variates.

Results: The final population included 53% males, mean age of 65.5 ± 9.7 years. Subgroups 1, 2 and 3 were comprised by 937 (60%), 407 (26%) and 214 (14%) subjects respectively. HOMA-IR increased from subgroup 1 (1.8 ± 0.9) toward subgroup 2 (3.0 ± 1.8) and subgroup 3 (6.5 ± 27.5), p for trend <0.001. Significant decrease in EDSR and pTRR and an increase in SRI, meaning worse diastolic function, were found across the groups (Table 1). In the multivariate regression analysis, MetS was associated with worse SRI (β-coefficient = 0.263; 95% CI 0.086-0.441), but not with EDSR and pTRR. Considering subgroup 1 as reference, MetS without T2DM was associated with worse SRI (β-coefficient = 0.274; 95% CI 0.074-0.474), and a tendency to impaired SRI in diabetic patients was found (β-coefficient = 0.215; 95% CI: -0.040;0.471).

Conclusion: MetS was associated with worse left ventricular diastolic function, assessed by SRI. Our findings highlight the significant changes observed in patients with impaired glucose homeostasis, even without the presence of T2DM.

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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.5

Global Longitudinal Strain Predicts Chronic Myocardial Infarction in Patients with Normal Ejection Fraction


Objective: Chronic myocardial infarction (MI) detected by late gadolinium enhancement (LGE) is associated with significant mortality and morbidity [1]. Limited subendocardial infarction may not lead to reduction in ejection fraction (EF) and a regional wall motion abnormality (RWMA) may not be evident.

Global longitudinal strain (GLS) is impaired independently of EF in a number of conditions, enabling early detection of disease. Strain imaging predicts final infarct size in MI and is superior to LVEF in predicting morbidity and mortality [2]. We hypothesised that subjects with chronic MI but normal EF would have impaired GLS compared to healthy volunteers.

Methods: Twenty patients with chronic MI (defined as subendocardial hyperenhancement on LGE) and normal LVEF and 20 healthy volunteers underwent CMR at either 1.5T or 3.0T (Philips Achieva TX). Standard bSSFP cine images were used to calculate LV dimensions and GLS by feature tracking (CVI 42, Circle Cardiovascular Imaging Calgary, Canada). LGE imaging was performed in all patients (0.2mmol/kg Gadolinium DTPA).

Results: Patients were matched for age (59.78 ± 12 vs 59.59 ± 5.4 p = 0.95) and for ejection fraction (see figure A) (60.4 ± 3.8 vs 62.2 ± 3.5 p= 0.11). Visual evidence of RWMA was present in 13/20 (65%) of chronic MI patients and 0/20 healthy volunteers. GLS (see figure A) was significantly lower in patients with chronic MI than in those without (-16.07 ± 3.9 vs -19.79 ± 2.3 p= 0.001).

Conclusion: GLS is impaired in patients with chronic MI but normal LVEF. GLS identifies abnormalities in LV systolic contraction not apparent with LVEF alone. It may reveal chronic MI in patients with contraindications to gadolinium-based contrast or prognostication of this subset of chronic MI patients. GLS could be used to detect chronic MI by alternative imaging modalities.


1. EB S, JJ C, Sigurdsson S, et al. Prevalence and prognosis of unrecognized myocardial infarction determined by cardiac magnetic resonance in older adults. JAMA 2012;308:890–6.

2. Antoni ML, Mollema S a., Delgado V, et al. Prognostic importance of strain and strain rate after acute myocardial infarction. Eur Heart J 2010;31:1640–7. doi:10.1093/eurheartj/ehq105

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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.6

Optimal Dose Of Dobutamine During Low-Dose Dobutamine Stress Echocardiography In Correctly Identify Viable Segments On Cardiovascular Magnetic Resonance


Background: Partial thickness late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) and biphasic response on low-dose dobutamine stress echocardiography (DSE) can predict viable myocardium. However little is known about the optimal dose of dobutamine during low dose DSE at which biphasic response first appear to correctly identify viable segments on CMR.

Objective: This study aims to look at the ability of different doses of dobutamine during low-dose DSE to correctly identify viable segments on CMR by late gadolinium enhancement.

Method: Patients with chronic left ventricular dysfunction scheduled for elective revascularization were prospectively selected. They underwent DSE using incremental doses of 2.5mcg/kg, 5mcg/kg, 7.5mcg/kg, 10mcg/kg, 15mcg/kg and 20mcg/kg. Blood pressure (BP), ECG and heart rate were continuously monitored. This was followed by late gadolinium study using standard viability protocol on 1.5T CMR. Number of thickening and non-thickening segments visualized at each stage of DSE were compared to the number of segments with LGE on CMR based on 16-segment model. Data was analyzed using SPSS.

Result: 80 myocardial segments were analyzed. Number of thickening segments were highest at 7.5mcg/kg of dobutamine. After 7.5mcg/kg of dobutamine, there was a negative association between systolic BP, diastolic BP and heart rate with increasing dobutamine doses. In CMR, 44 segments had less than 50% thickness subendocardial LGE and 41 segments had more than 50% thickness of subendocardial LGE. At baseline, the mean sensitivity of DSE to correctly identify number of viable segments on CMR was 25% with a specificity of 79%. With incremental dose of dobutamine, the sensitivity and specificity increased, reaching its highest at 7.5mcg/kg of dobutamine (sensitivity and specificity 80%). At 10mcg/kg of dobutamine onwards, the sensitivity and specificity dropped to lowest level of 52% and 45% respectively at 20mcg/kg of dobutamine.

Conclusion: At 7.5mcg/kg of dobutamine, biphasic response is best demonstrated and has the highest sensitivity and specificity to correctly identify viable segments on CMR. Higher dobutamine doses may precipitate haemodynamic compromise in patients with critical CAD.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.7

Absolute wall thickening and left ventricular ejection fraction–a unifying theory of myocardial contraction and heart failure?

Dr Jonathan Rodrigues, BSc(Hons), MBChB(Hons), MRCP, FRCR,1,2 Mr Ben Rooms,3 Miss Katie Hyde,3 Mr Stephen Rohan, BSc(Hons),3 Dr Amardeep Ghosh Dastidar, MBChB, MRCP,1 Dr Mark Hamilton, MBChB, MRCP, FRCR,1 Dr Chiara Bucciarelli‐Ducci, MD, PhD, FRCP, FESC,1 Dr Angus Nightingale, MA, MB BChir,FRCP, MD,4 Professor Julian Paton, BSc(Hons), PhD,4 Dr Nathan Manghat, MBChB, MRCP, FRCR, MD,1 and Professor David MacIver, MBBS, MD, FRCP5,6


Introduction: No single well–established hypothesis for the mechanisms of heart failure exists. Left ventricular ejection fraction (LVEF) is widely used to dichotomise heart failure into reduced and preserved LVEF cohorts, with the latter often believed to be due to diastolic dysfunction. Mathematical modeling has demonstrated that LVEF is determined by myocardial shortening and end–diastolic wall thickness (EDWT). We hypothesized that a common myocardial mechanism occurs in heart failure regardless of cause and we aimed to quantify the relationship of absolute wall thickening (AWT) on LVEF across a range of global cardiac pathologies with varying degrees of EDWT using cardiac magnetic resonance (CMR).

Methods: 183 subjects underwent CMR at 1.5T, including 53 with idiopathic dilated cardiomyopathy (DCM), 36 with amyloid cardiomyopathy, 55 with hypertension (HTN) and 39 controls. Ventricular volumes and LVEF were calculated. EDWT and end–systole wall thickness (ESWT) were measured in basal and mid myocardial segments from long axis cines. AWT was defined as (ESWT–EDWT). Relative AWT (rAWT) was (AWT/ED LV internal diameter). Longitudinal strain was estimated from modified 6–point mean mitral annular plane systolic excursion. Circumferential strain was estimated using an established equation.

Results: Please see Table 1. The study included subjects with normal (controls: 64 ± 7% and HTN: 66 ± 8%), moderately reduced (Amyloid: 49 ± 16%) and severely reduced (DCM: 30 ± 11%) LVEF. There were significant differences in indexed EDV (controls: 77 ± 18ml/m2, DCM: 133 ± 27ml/m2, HTN: 85 ± 16ml/m2 and amyloid: 86 ± 34ml/m2, P < 0.0001) and EDWT (controls: 8 ± 1mm, DCM: 8 ± 1mm, HTN: 11 ± 3mm and amyloid: 14 ± 3mm, P < 0.0001) between subgroups. There was weak positive correlation between EDWT and LVEF (R = 0.185, P < 0.05)(Figure 1A). Reduced longitudinal (R = –0.457, P < 0.0001) and circumferential strain (R = –0.710, P < 0.0001) were associated with significantly reduced AWT. AWT was strongly related to LVEF (R = 0.812, P < 0.0001). Changes in rAWT accounted for 77% of LVEF variability across the cohort (R2 = 0.766)(Figure 1B).

Conclusion: We demonstrate, for the first time, that LVEF is determined by changes in rAWT across a range of global LV diseases of varying EDWT and EDV. AWT depends on EDWT and the degree of longitudinal and circumferential strain. Our findings offer a potentially unifying mechanism for changes in LVEF and refine our understating of heart failure with preserved and reduced LVEF.

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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.8

Transient St Elevation in Acs Like Myocarditis


Background: Chest pain in acute myocarditis is common and generally associated with some ST elevation and rise of myocardial damage markers. In some patients further chest pain recurs hours or days after initial symptom, sometimes but not invariably associated with pericarditis; some previous reports suggest that coronary vasospasm may be a clinically relevant occurence in acute myocarditis cases.

Methods: We prospectively collected pertinent data in all ACS like myocarditis patients that had a CMR scan performed in between 2 weeks after symptom onset. EKG was continuously monitored for at least the first 72 hours post admission.

Results: 25 patients, mean age 46 years, were collected. Among these, 2 had recurrence of chest pain during the first 48 hours, with concomitant transient ST elevation > 2mm, both persisting for a few minutes, resembling variant angina. Coronary angiography (in the absence of chest pain) did not show any luminal defect nor irregularities of vessel walls; myocardial markers were rised and CMR showed non coronary late Gadolinium enhancement (LGE) pattern with mid wall-epicardial localisation; overall left ventricular systolic function was normal. T2 sequences and LGE failed to show any pericardial inflammation.

Our study put together with previous data suggests coronary vasospasm as a mechanism of recurrent chest pain in patients with myocarditis.

Conclusions: coronary vasospasm could be a not uncommon, clinically relevant event in acute myocarditis patients with ACS like pattern.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.9

Patients after Fontan with a “total cavopulmonary connection” Fontan modification develop more collateral flow compared to “old-fashioned” Fontan modifications


Objectives: Fontan palliation has evolved over time. Among many modifications creation of “total cavopulmonary connection (TCPC) ” Fontan such as intracardiac tunnel or extracardiac conduit has been proposed as a superior alternative to “old-fashioned” Fontan modifications such as RA-PA, or RA-RV tunneling. Collateral flow is a well-known residuum in patients with Fontan. However, no studies have examined collateral flow between different types of Fontan modifications. So the aim of this study was to compare collateral flow of patients with a TCPC to collateral flow of patients with “old-fashioned” Fontan modifications.

Methods: We conducted a retrospective study on patients with any type of Fontan, who underwent a routine clinical CMR at our institution over a 6-year period with collateral flow quantification. The entire cohort was divided into two groups: 32 patients with TCPC, (median age 15(2-60)yrs.); 7 patients with “old-fashioned” Fontan modifications, (median age 31(21- 35)yrs.). Patients with a fenestration were excluded. We determined collateral flow by using the commonly used equation: flow volume aorta ascendens–(flow volume superior vena cava + flow volume inferior vena cava)

Results: Collateral flow was larger in patients with a TCPC compared to patients with “old-fashioned” Fontan modifications [median 0.6((-0.1)-1.7) vs. 0.2((-0.04)-0.5) L/min/m2, p < 0.006]. Additionally, cardiac index measured as the flow volume in the aorta ascendens was also larger in patients with a TCPC compared to patients with “old-fashioned” Fontan modifications [median 3.2(2.2-4.9) vs. (2.6(1.9-3.3) L/min/m2, p < 0.01].

Conclusions: Patients years after any type of Fontan modifications have substantial collateral flow. However, patients with a TCPC have significantly more collateral flow compared to patients with “old-fashioned” Fontan modifications. This leads to a significantly higher work load of the heart as demonstrated by the larger cardiac index of patients with a TCPC compared to patients with “old-fashioned” Fontan modifications. We suggest that the larger collateral flow in TCPC may be due to different flow characteristics in the superior vena cava compared to “old-fashioned” Fontan modifications.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.10

A MRI–derived 3D patient specific model for fibrosis quantification in atrial fibrillation


Introduction: Atrial fibrillation (AF) is the most common type of arrhythmia and the mechanisms that sustain it are not yet clearly identified. Catheter ablation is a promising therapy for AF. However, to achieve durable restoration of sinus rhythm, multiple procedures may be required. Early studies have suggested both extensive atrial tissue fibrosis and association between scar gaps and pulmonary vein (PV) reconnection sites as possible causes of the poor outcomes of the AF catheter ablation. In this study, in order to assist the electrophysiologist in patient selection and ablation procedure planning, we developed a 3D patient–specific left atrium (LA) model integrating anatomical and structural information derived from magnetic resonance angiography (MRA) and delayed–enhanced MR imaging (DE–MRI).

Materials and Methods: Thirty–five patients with paroxysmal AF were enrolled in the study and MRA and DE–MRI images were acquired. A patient–specific anatomical model was derived by MRA data, applying an edge–based level set approach guided by a phase–based edge detector (figure A, upper panels). A multimodality affine registration based on mutual information was then applied to register MRA into the spatial domain of DE–MRI (figure A, bottom panels). Once affine registration parameters were obtained, the corresponding intensity gray level information derived from the DE–MRI was overlapped on the registered 3D surface LA model, allowing the 3D visualization of LA fibrosis location and extent (figure B). In order to obtain a qualitative validation, the 3D LA models were compared with voltage maps reconstructed during the ablation procedures.

Results: The 3D patient specific model obtained through MRA segmentation and registration of DE–MRI data was feasible in all patients. Time required for the analysis was about 30 min for each patient. An example of the qualitative comparison between high enhanced regions in the 3D LA model with fibrosis information and the low voltage areas in the electroanatomical map is shown in figure C.

Conclusion: Preliminary qualitative validation of the 3D LA model including structural information seems a promising tool for a correct fibrosis localization and quantification. Next steps include assessment of the proposed tool to quantify scar location and extent for patient selection and catheter ablation planning.

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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.11

Scar burden and survival in patients with ischemic cardiomyopathy and poor LV ejection fraction


Background: It is unclear whether in patients with ischemic cardiomyopathy and low EF (EF < 40%) late revascularization might be beneficial. We investigated the prognosis in a cohort of patients with ischemic cardiomyopathy and EF < 40% following late revascularization (LR) compared to a cohort of patients receiving optimal medical therapy alone (MED). We also investigated whether scar burden associates with prognosis in these 2 groups.

Methods: Patients with ischemic cardiomyopathy and low EF, defined as <40%, who underwent CMR in a single institution were prospectively followed up since 2003. 25 consecutive patients who underwent LR and 25 consecutive patients who had MED are reported here. Patient demographics, CMR characteristics and scar burden calculated using the 5SD and FWHM methods (CMR 42, Circle CI) were analyzed by blinded observers.

Results: Patient demographics and CMR results including scar burden are shown in table 1.

There was no difference in survival between LR and MED (p = 0.62) as shown in the Kaplan Meier survival curve in figure 2. Scar burden did not associate with prognosis in either the LR (FWHM p = 0.983; 5SD p = 0.572) or the MED group (FWHM p = 0.952, 5SD p = 0.896). In the LR no other variables were significant. However in the MED NYHA Class was significantly associated with prognosis with higher NYHA conferring worse survival (HR = 3.2, p = 0.011, 95% CI 1.3-7.9, per 1 category increase in NYHA)

Conclusion: LR did not offer a prognostic benefit in patients with ischemic cardiomyopathy and low EF. Scar burden did not associate with prognosis in either LR or MED group. In the MED group, patients with worse NYHA had worse prognosis, but this was not seen in the LR group.

Table 1.

Patient demographics at the time of CMR and CMR parameters including scar burden quantification. There were no significant differences between the patients who subsequently underwent

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Figure 1. Kaplan Meier survival curve of patients who underwent Late revascularization (Late Revasc) or medical therapy alone (No Revasc), indicating that there is no significant survival benefit in survival between the two groups.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.12

Relation of inflammatory markers with myocardial and microvascular injury in patients with reperfused ST- elevation myocardial infarction


Background: In patients with acute ST-elevation myocardial infarction (STEMI), elevated concentrations of inflammatory markers are correlated with worse clinical outcome. The aim of this study was to comprehensively investigate the relationship of circulating markers of inflammation with myocardial and microvascular damage after STEMI.

Methods: In 111 consecutive STEMI patients, blood samples were obtained on admission and from day 1 to day 4 after primary percutaneous coronary intervention (PPCI) and analyzed for high-sensitivity C-reactive protein (hs-CRP), white blood cell count (WBCc) and fibrinogen. Cardiac magnetic resonance imaging was performed within the first week and 4 months after PPCI for assessment of myocardial function and damage.

Results: Peak concentrations of hs-CRP (20.5[9.6-44.4]mg/L), WBCc (12.4[10.5-15.3]G/L) and fibrinogen (3640[3150-4550]mg/L) showed significant correlations with both infarct size (r = 0.31 to 0.41; p < 0.01) and left ventricular (LV) ejection fraction (r = -0.29 to -0.39; p< 0.01) assessed in the acute as well as chronic stage following STEMI. Furthermore, peak concentrations of these inflammatory markers were significantly higher in patients with microvascular obstruction (MVO) compared to patients without MVO (p ≤ 0.01). C-statistics revealed that the prognostic values of all three biomarkers for the prediction of large chronic infarct size (>8% of LV myocardial mass) were moderate without significant differences (area under the curve (AUC): hs-CRP = 0.73 (95%CI 0.63-0.82), WBCc = 0.67 (95%CI 0.56-0.78) and fibrinogen = 0.70 (95%CI 0.59-0.80); all p > 0.12). Combination of inflammatory markers did not significantly increase the AUC (p > 0.05).

Conclusion: In STEMI patients treated with PPCI, increased levels of hs-CRP, WBCc and fibrinogen are associated with decreased LV function and more pronounced myocardial damage at baseline and 4 months after infarction.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.13

Equivalence of segmented conventional and fast single-shot late gadolinium enhancement (LGE) techniques for


Background: Segmented single-slice/single-breath-hold 2D phase-sensitive inversion recovery (2D-PSIR) sequences are the gold standard for evaluation of myocardial fibrosis. Aim of this study was to assess the accuracy of single-shot LGE sequences to detect and quantify myocardial fibrosis in patients with ischemic and non-ischemic etiology of LGE.

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Methods: Patients with chronic myocardial infarction/coronary artery disease (CAD; n = 121), myocarditis (n = 35) and hypertrophic cardiomyopathy (HCM) (n = 20) were prospectively enrolled. Image studies were performed on 1.5T Siemens Magnetom Avanto fit. After administration of contrast agent (gadoteridol 0.2mmol/kg for CAD and HCM, gadopentetate dimeglumin 0.2mmol/kg for myocarditis), LGE images were acquired ECG-gated in short axis slices (slice thickness 7mm, gap 0mm) using 4 different LGE sequences (Figure 1): (1) conventional segmented 2D phasesensitive inversion recovery in single-slice/single-breath-hold technique (TR 744ms, TE 5.17ms, Flip Angle 30°), (2) single-breath-hold 3D-IR sequence (TR 924ms, TE 1.06ms, Flip Angle 50°), (3) 3D-SSFP sequence in breath-hold and (4) non-breath-hold technique (TR 700ms, TE 1.05ms, Flip Angle 65°). For all techniques, inversion time was individually adjusted to null the remote myocardium. LGE was quantitatively assessed using a semi-automated threshold method: positive LGE was defined as signal intensity 6 standard deviations (SD) above signal intensity of remote myocardium for CAD and 3 SD for myocarditis/HCM. Differences in size of LGE-positive areas (in gram) were analyzed using Bland-Altman-Analysis.

Results: There was no significant difference in size of LGE-positive areas between the segmented 2D-PSIR and 3D-IR, 3DSSFP LGE sequence (Table 1A), independent of the underlying etiology. Comparing breath-holding to free-breathing technique in the 3D-SSFP LGE sequence, scar size in patients with CAD is smaller in free-breathing sequence (mean difference 0.44g, p = 0.01), whereas no differences were found in HCM (Table 1B).

Acquisition times were significantly shorter for 3D-IR (23.3 s ± 7.4 s) and 3D-SSFP (22.1 s ± 7.0 s) as compared to 2D-PSIR (365.2 s ± 94.9 s).

Conclusions: Fast 3D-SSFP, 3D-IR and conventional segmented 2D-PSIR sequences are equivalent techniques for the assessment of myocardial fibrosis, independent of an ischemic or non-ischemic etiology. In CAD, free-breathing 3DSSFP technique results in slightly smaller infarction size compared to acquisition in single breath-hold.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.14

Cardiac Mri Appearances of Tuberculosis - A Review of Varied Presentations in India


Objective: Pictorial representation of different types of presentation of cardiac tuberculosis on cardiac MRI seen in our institute.

Introduction: Cardiovascular tuberculosis is a relatively infrequent condition in European society but is commonly seen in the Indian subcontinent. Classical presentation is with pericardial involvement with some cases showing myocardial involvement. Cardiac MRI is extremely useful in assessing patients with suspected cardiac tuberculosis as echocardiography is often non diagnostic. It can also be used in following up of patients to assess response to therapy.

Methods and Materials: Retrospective review of all the cardiac MR examinations performed in our institute during the period of January 2014 to December 2015. All patients with proven tuberculosis were included and analysed.

Results: In our institute, Cardiac Tuberculosis on CMR was seen in the following major patterns:

1. Mass like presentation in both atria.

2. Pericarditis- Calcific and non calcific

3. Myocarditis

Conclusion: Although cardiac tuberculosis is a rare disease, the recognition of this entity and its varied presentation is important for diagnosis, management and follow up. As this being one of the treatable condition.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.15

Atheroma burden, cardiac remodelling and epicardial fat: A comparison between healthy South Asian and European adults using Whole Body Cardiovascular MR


Objectives: South Asians (SAs) have a higher risk of coronary artery disease, congestive cardiac failure and stroke, but paradoxically lower prevalence of peripheral arterial disease (PAD) than Western Europeans (WEs). The aim of this study was thus to evaluate early changes in systemic atherosclerotic burden and cardiac remodelling in healthy South Asians compared with Western Europeans using whole body cardiovascular MRI (WB-CVMR).

Methods: 19 SA and 38 age, gender and BMI matched WE were recruited. All were ≥40 years, free from cardiovascular disease (CVD) and with a 10-year risk of CVD <20% as assessed by the ATPIII risk score. WB-CVMR was performed which comprised a whole body angiogram (WBA) and cardiac magnetic resonance (CMR). These were performed on a 3T MRI (Tim Trio, Seimens, Germany) scanner using whole body coils following dual phase injection of gadoteric acid (Guerbet, France). A standardized atherosclerotic score (SAS) was calculated from the WBA, while indexed left ventricular mass and volumes, and indexed epicardial and thoracic fat volumes were calculated from the CMR.

Results: SAs exhibited a significantly lower iliofemoral atheroma burden (regional SAS 0.0 ± 0.0 vs 1.9 ± 6.9, p = 0.048) and a trend towards lower overall atheroma burden (WB SAS 0.7 ± 0.8 vs 1.8 ± 2.3, p = 0.1). They had significantly lower indexed left ventricular mass (46.9 ± 11.8 vs 56.9 ± 13.4ml/m2, p = 0.008), end diastolic volume (63.9 ± 10.4 vs 75.2 ± 11.4ml/m2, p = 0.001), end systolic volume (20.5 ± 6.1 vs 24.6 ± 6.8ml/m2, p = 0.03) and stroke volume (43.4 ± 6.6 vs 50.6 ± 7.9ml/m2, p = 0.001), but with no significant difference in ejection fraction, mass-volume ratio or global functioning index. These differences persisted after accounting for CVD risk factors. Despite smaller heart volumes the volume of epicardial fat deposition was similar between the two groups (2.6 ± 1.4 vs. 2.7 ± 1.7 cm2/m2, p = 0.8).

Conclusions: South Asians have a lower peripheral atherosclerotic burden and smaller hearts than Western Europeans even in a healthy low-intermadiate risk population. Thus the paradoxical high risk of CVD compared with PVD risk may be due to an adverse cardiac haemodynamic status incurred by the smaller heart rather than atherosclerosis.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.16

Symptomatic Ventricular Arrhythmias: Diagnostic Yield of Cardiac Magnetic Resonance


Objectives: To assess the diagnostic yield of cardiac magnetic resonance (CMR) in patients with ventricular arrhythmias.

Methods: From 2014 to 2015, consecutive patients referred to our institution for the management of symptomatic non-sustained ventricular tachycardia (NSVT), sustained ventricular tachycardia (SVT), ventricular fibrillation (VF) or aborted sudden cardiac death (SCD) were prospectively included. A complete diagnostic work-up was performed including clinical symptoms, personal and family history, ECG and/or Holter, echocardiography, and at the discretion of the referring cardiologist exercise testing and coronary angiography. CMR was performed in all patients, including cine SSFP and late gadolinium enhancement (LGE) imaging (breath-holded 3D IR FLASH). The diagnostic yield of CMR was assessed by comparing diagnoses obtained with vs. without CMR information, as defined by 2 observers in consensus, non-CMR diagnoses being blinded from CMR results.

Results: 217 consecutive patients (age 54 ± 17 years, 55 women) were included (69[32%] NSVT, 123[57%] SVT, 25[12%] VF or SCD). Dominant clinical symptoms were palpitation in 75(35%), lightheadedness in 39(18%), syncope in 35(16%), chest pain in 25(12%), SCD in 25(12%), dyspnea in 15(7%), and cardiogenic shock in 3(2%). The diagnostic work-up comprised exercise testing in 180(83%), and coronary angiography in 137(63%). Diagnoses without CMR information were no structural heart disease (SHD) in 123(57%), ischemic in 57(27%), non-ischemic dilated cardiomyopathy (DCM) in 15(7%), post-inflammatory in 3(1%), arrhythmogenic right ventricular cardiomyopathy (ARVC) in 9(4%), hypertrophic cardiomyopathy in 4(2%), and other in 6(3%). In the whole population CMR led to a modification of diagnosis in 40/217(18%). The diagnostic yield of CMR was higher in patients with no SHD as per pre-CMR assessment (diagnostic change in 32/123[26%]) than in patients with SHD (diagnostic change in 8/94[9%]). Modifications in diagnosis were influenced by LGE imaging in 36/40(90%), and by cine imaging in 4/40(10%). When including CMR information, novel diagnoses included post-inflammatory scar in 20(50% of all diagnostic changes), ischemic in 6(15%), no SHD in 3(8%), ARVC in 3(8%), DCM in 2(5%), and other in 6(15%).

Conclusions: The incremental value of CMR in the diagnostic management of patients with ventricular arrhythmias (NSVT, SVT and SCD) is high, particularly in those with no known SHD as per pre-CMR assessment.

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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.17

CMR assessment of aortic stiffness in asymptomatic low risk patients with type 2 diabetes mellitus


Introduction: Arterial Stiffness (AS) is a non-invasive marker of cardiovascular disease which results in a reduction in aortic distensibility (AD) and an increase in pulse wave velocity (PWV). Previous studies have demonstrated increased AS is associated with adverse outcomes. Advanced age and type 2 diabetes mellitus (T2DM) are associated with increased AS however the influence of other risk factors in T2DM and how they interact is not known. We hypothesised that poor control of diabetes and higher ambulatory blood pressure (ABP) would be associated with increased arterial stiffness.

Methods: We recruited 80 asymptomatic patients with type 2 diabetes from primary care who were not taking any antihypertensive medication and 10 healthy controls. All subjects underwent assessment of risk factors, 24 hour ABP and CMR at 3.0T with Philips Achieva system. CMR protocol included cine aortic imaging planned at the level of the main pulmonary artery and retrospectively gated, velocity encoded phase-contrast cines.

AD was calculated from an average of contours drawn on the ascending and descending aorta. PWV was derived from velocity-time curves and the distance between the ascending and descending aorta using the transit-time method.

Results: AD was lower (2.04 ± 1.02 10-3mmHg-1 vs 3.18 ± 1.32 10-3mmHg-1, P = 0.005) however the difference in PWV was not significant (7.81 ± 2.77 m/s vs 6.97 ± 1.93 m/s, P = 0.38) in T2DM than in controls.

In subjects with T2DM there were significant negative correlations between AD and age (R = -0.64, P < 0.001), duration of diabetes (R = -0.23, P = 0.045) and mean systolic ABP (R = -0.26, P = 0.02). PWV had a significant correlation with increasing age (R = 0.50, P < 0.001) and duration of diabetes (R = 0.31, P = 0.01). There was no significant association between AS and total cholesterol, smoking, hsCRP or the presence of persistent microalbuminuria.

Conclusion: In this cohort of low risk, asymptomatic patients with T2DM there was evidence of increased aortic stiffness compared to controls. In these patients aortic stiffness was influenced primarily by age, duration of T2DM and systolic ABP.

Table showing AD and PWV of 10 healthy controls and 80 patients with T2DM.

ControlT2DMP value
Ascending aorta AD, 10-3mmHg-12.95±1.811.90±1.190.06
Descending aorta AD, 10-3mmHg-13.42±1.132.19±1.040.002
Average AD, 10-3mmHg-13.19±1.322.04±1.020.005
Aortic PWV, m/s6.98±1.937.81±2.770.38
Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.18

Shock index as a predictor of myocardial damage and clinical outcome in ST-elevation myocardial infarction


Background: Data on the prognostic value of the shock index in patients with ST-elevation myocardial infarction (STEMI) are scarce. Furthermore, the relationship of shock index with myocardial damage is unknown. Aim of this study was therefore to evaluate the association of the shock index with markers of myocardial damage and clinical outcome in patients with reperfused STEMI.

Methods and Results: This multicenter study analyzed 791 patients. Patients were categorized in 2 groups according to admission shock index (optimized cut-off = 0.62). Infarct severity was determined by cardiac magnetic resonance imaging. Major adverse cardiac events (MACE) were defined as a composite of death, reinfarction and new congestive heart failure within 12 months. Patients with elevated admission shock index (n = 321 [40.6%]) had a significantly larger area-at-risk (37.6 [27.8-50.4]% of left ventricular volume [LV] vs. 34.3 [24.5-46.0]%LV, p = 0.02), larger infarct size (19.5 [10.7-28.0]%LV vs. 14.9 [7.7-22.3]%LV, p < 0.001), lower myocardial salvage index (46.2 [27.9-64.5] vs. 53.5 [36.5-75.2], p < 0.001), and a larger extent of microvascular obstruction (0.3 [0.0-2.2]%LV vs. 0.0 [0.0-1.4]%LV, p = 0.01). An elevated shock index was associated with reduced MACE-free survival (p < 0.001). Furthermore, admission shock index was identified as independent predictor of MACE (hazard ratio = 2.92 [1.24-4.22], p < 0.01).

Conclusion: STEMI patients with an elevated admission shock index had more pronounced myocardial and microvascular damage. Moreover, shock index was independently associated with MACE at 12 months after STEMI.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.19

Combined biomarker testing for the prediction of microvascular obstruction after primary percutaneous coronary intervention for acute ST-segment elevation myocardial infarction


Background: Microvascular obstruction (MVO) as detected by cardiac magnetic resonance (CMR) imaging indicates microvascular destruction with subsequent adverse clinical outcome after reperfused ST-segment elevation myocardial infarction (STEMI). The predictive value of different biomarkers for the occurrence of MVO is insufficiently studied. This study compared the prognostic value of admission and peak concentrations of routinely available biomarkers for the detection of MVO after reperfused STEMI.

Methods: One hundred and twenty-eight STEMI patients undergoing primary percutaneous coronary intervention (PPCI) were enrolled in this single-center, prospective, observational study. CMR was performed within the first week after infarction to assess infarct characteristics, including MVO. Admission and peak concentrations of high-sensitivity cardiac troponin T (hs-cTnT), creatine kinase (CK), N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), lactate dehydrogenase (LDH), aspartate transaminase (AST) and alanine transaminase (ALT) were measured.

Results: MVO was detected in 69 patients (54%). Peak concentrations of hs-cTnT, CK, hs-CRP, LDH, AST and ALT showed similar prognostic value for the prediction of MVO (area under the curve (AUC) = 0.77, 0.77, 0.68, 0.79, 0.78 and 0.73, all p > 0.050), whereas the prognostic utility of peak NT-proBNP was lower (AUC = 0.64). Combination of these biomarkers did not result in higher predictive value as compared to hs-cTnT alone (p = 0.349).

Conclusion: hs-cTnT, CK, hs-CRP, LDH, AST and ALT peak concentrations provided similar prognostic value for the prediction of MVO, whereas the prognostic utility of NT-proBNP was lower. Combining these biomarkers could not further improve prognostic utility compared to hs-cTnT alone.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.20

A novel oscillometric technique compared with cardiac magnetic resonance for the assessment of aortic pulse wave velocity in ST-segment elevation myocardial infarction


Background: Pulse wave velocity (PWV) is the proposed gold-standard for the assessment of aortic elastic properties. A recently developed oscillometric device, which allows for non-invasive and cost-effective measurement of aortic PWV, showed a moderate to good agreement with cardiac magnetic resonance imaging (CMR) in healthy volunteers. Now we compared the two methods in patients presenting with ST-segment elevation myocardial infarction (STEMI).

Methods: We assessed aortic PWV in 60 mechanically reperfused STEMI patients using two different methods. The oscillometric method (PWVOSC) is based on mathematical transformation of brachial pressure waveforms, oscillometrically determined using a common cuff (Mobil-O-Graph, I.E.M. Stolberg, Germany). Phase-contrast CMR imaging (1.5 Tesla scanner, Siemens, Erlangen, Germany) at the level of the ascending and abdominal aorta was performed to determine PWVCMR with the use of the transit time method.

Results: The mean age of the study population was 57 ± 11 years; 11 (19%) were female. Median PWVOSC was 7.4 m/s (IQR 6.8 - 8.9 m/s) and median PWVCMR was 6.3 m/s (IQR 5.7 - 8.2 m/s) (p < 0.001). A strong correlation was detected between both methods (r = 0.724, p < 0.001). Bland-Altman analysis revealed a bias of 0.62 m/s (upper and lower limit of agreement: 3.84 m/s and -2.61 m/s). The coefficient of variation between both methods was 21%.

Conclusion: In mechanically reperfused STEMI patients, aortic PWV assessed non-invasively by transformation of brachial pressure waveforms showed an acceptable agreement with the CMR-derived transit time method.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.21

Aorto-pulmonary collaterals evaluated by CMR is associated to reduced “effective” cardiac index late after Fontan palliation


Objective: Aorto-pulmonary collaterals (APCs) are frequent in patients with uni-ventricular heart (UVH). Their clinical significance remains controversial and the mechanism that leads to their formation are poor known. Cardiac output (CO) in a Fontan circulation is decreased compare to normal population. Quantitative assessment of APCs blood flow and evaluation of cardiac output (CO) and cardiac (CI) using cardiac magnetic resonance (CMR) has been already validated.

Aim: to evaluate the factors associated to APCs flow (QAPCs) assessed by CMR in patients late after Fontan palliation and their impact on “effective” CI and on clinical outcome.

Methods: Form our CMR database we identified all patients with Fontan intervention who underwent CMR. Patients with a complete set of flow measurements allowing calculation of APC flow were included. QAPCs was calculated as (left pulmonary veins flow + right pulmonary veins flow) - (right pulmonary artery flow + left pulmonary artery flow), assessed by means of through-plane phase-contrast.Values were normalized to body surface area. Effective CI was calculated as (QAo flow- QAPCs)/BSA. Medical and surgical history and clinical status were recorded.

Results: Sixty-five patients post Fontan palliation were included in the study (36 M, age: 19 ± 10). Follow-up from Fontan palliation at CMR study was 12 ± 7 years, range: 1-31 years. Median QAPCs was 734 ml/min/m2 (range 106-3000), corresponding to a median 22% (4-73) of systemic blood flow. QAPCs didn't correlate neither with age at CMR study and at Fontan palliation neither with rest O2 sat, ventricular volumes, ejection fraction and mass. QAPCs was not associated to systemic ventricular type (right, left or 2 complex ventricles), atrial arrhythmias, atrio-ventricular valve regurgitation. Meanwhile QAPCs correlates with indexed aortic flow, r= 0.6, P< 0.001 but inversely correlates with effective CI, r= -0.39, P = 0.001. QAPCs correlate inversely also with left pulmonary artery area (r= -0.37 P= 0. 07).

Conclusions: New CMR techniques allow reliable quantification of QAPCs. After Fontan palliation QAPCs has a wide range and is associated to reduced left pulmonary artery area. From our data increase of APC flow is associated to further reduction of effective systemic blood flow. Further studies are needed to better define the clinical impact of APC and the indication of its embolization.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.22

Evaluation of pulmonary transit time and Pulmonary Blood Volume with first-pass perfusion CMR imaging in adult with repaired Congenital Heart disease


Background: Management of Adults With Repaired Congenital Heart Disease is still challenging. Heart failure secondary to residual anatomical sequels as well arrhythmic events are not rare in this population. Pulmonary transit time (PTT) is significantly prolonged in patients with acquired heart disease and heart failure. Cardiac magnetic resonance (CMR) has emerged as an accurate tool to quantify PTT of intravenous contrast agents and Pulmonary blood volume (PBV). The aim of this study was to assess PTT and PBV in adults with Repaired cono-truncal heart defect, to determine if they reflect conventional indexes of ventricular dysfunction and to assess their association to adverse cardiac event.

Methods: twenty-seven patients with repaired cono-truncal anomalies, mainly Tetralogy of Fallot (n = 19), 16 men (31 ± 11 years) and 13 age-and sex-matched healthy controls underwent CMR examination comprehensive of first-pass perfusion. PBV was calculated as the product of stroke volume and number of cardiac cycles for an intravenous bolus of gadolinium contrast to pass through the pulmonary circulation, as determined by cardiac-gated first-pass perfusion imaging. Twenty-one patients underwent also a cardio-pulmonary test (CPT). PTT and indexed PBV (PBVi) correlated to conventional indexes of ventricular function. Cardiac event before the study or during follow up as well as subsequent re-operation were reported.

Results: PTT correlates inversely with LVEF (r= -0.46,P= 0.01), with LVESV (R= 0.48; P = 0.01) and with VECO2 slope at CPT (r= 0.5, P = 0.02); PBVI correlates with LVESV (R= 0.38; P = 0.04) and with VECO2 slope at CPT (r= 0.49, P = 0.02). Using a cut-off of PTT >10.3 sec, corresponding to 2SD above the mean of healthy controls, six patients above it have lower LVEF in comparison with those with PTT≤ 10.3 (median 48%, range 37-57% vs median 57%, range 37-73%) and experienced more cardiac events before CMR (p = 0.04) and during follow-up (p = 0.03). The occurrence of cardiac events and/or reinterventions during the follow-up was associated to higher PBVi (342 ± 104 sec vs 148 ± 144, P = 0.01).

Conclusions: pulmonary intravascular blood pool (PBVi) and the time it flows through (PTT), can be assessed non invasively by means of contrast-enhanced MR. Both PTT and PBVi were associated to cardiac event at study and at follow-up in our group of adult with repaired cono-truncal anomalies. Further studies in a larger population are warranted to assess its prognostic value.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.23

Prognostic value of the cardiac magnetic resonance as a predictor of improvement in ventricular function after TakoTsubo syndrome


Introduction: Tako-Tsubo syndrome (TTS) is a reversible cardiomyopathy defined by criteria established by the Mayo Clinic and by the Japanese Society, which are echocardiographic, electrocardiographic and analytical criteria, having excluded coronary disease, pheochromocytoma or myocarditis. The resolution of the wall motion abnormalities could take days or even months. Cardiac magnetic resonance imaging (CMR) can help to predict the degree of recovery of ventricular function on the basis of the findings of the baseline study on the income.

Methods: The objective was to analyze the value of the CMR as a predictor of the degree of improvement in ventricular function (LVEF) in the follow-up. All patients (P) were included from January 2009 to April 2015 with the diagnostic code 429.83 (TS, ICD-9 - MC) who held a CMR in income.

Results: We included 25 P that met the diagnostic criteria of STK of the Mayo Clinic and who had performed a CMR during hospitalization. The average age was 69.6 years, 92% were women and 56% presented stress as a trigger. The majority of the cases were presented with killip class I (48%). 12% had a history of ischemic heart disease. Of these 25 P, 52% of them presented a normal CMR (Group 1). The remaining 48% (Group 2) presented some alteration in tissue characterization (8% edema, 28% enhancement transmural/ subendocardial, 12% subepicardial). The average initial LVEF in Group 1 was 34% and in Group 2, 45%, with statistically significant difference (p = 0.005). The average recovery of ventricular function (assessed with echocardiogram) in Group 1 was 25 points, while in Group 2 it was 13 points, this difference being statistically significant (p = 0.008). With respect to enzyme elevation, Tpn T US or CK, there were no significant differences (p = 0.621, and p = 0.269 respectively).

Conclusions: In this serie of 25 P with Tako-Tsubo Cardiomyopathy according to criteria of Mayo Clinic, the CMR allows to classify them into 2 groups, those with alterations in tissue characterization and those without, being the last group the one that present a more decreased income LVEF, although with a greater degree of recovery. These findings would reclassify up to 40% of patients (10 patients) in other diagnoses such as myocarditis or ischemic disease in the presence of coronary arteries without significant lesions, and must be considered as a new diagnostic criterion in future classifications.

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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.24

Diagnostic performance of ECG detection of left atrial enlargement in patients with arterial hypertension relative to the cardiac magnetic resonance gold-standard: impact of obesity


Introduction: Guidelines on the management of arterial hypertension suggest that an electrocardiogram (ECG) be routinely performed. ECG may demonstrate evidence of left atrial enlargement (LAE), which has adverse prognostic implications. We sought to determine the accuracy of 5 ECG criteria of LAE in a hypertensive cohort relative to cardiac magnetic resonance (CMR) and to investigate the confounding effect of obesity.

Methods: Consecutive referrals for CMR (1.5T) from a tertiary hypertension clinic were reviewed. Patients with any concomitant cardiac pathology were excluded. ECGs were assessed, blinded to the CMR data, for: 1) P wave >110ms, 2) P mitrale (notched P wave with inter-peak duration >40ms), 3) P wave axis <30°, 4) Area of negative P terminal force in lead V1 (NPTF-V1) > 40ms·mm and 5) Positive P terminal force in aVL (PPTF-aVL) >0.5mm. Maximal LA volume index (LAVI), excluding LA appendage and pulmonary vein confluence, was measured by the biplane area-length method (previously validated against LA short axis cine stack). LAE was defined as ≥55ml/m2 (>2 standard deviations above published references values). Sensitivity, specificity, positive predictive value, negative predictive value and accuracy were calculated. Area under the receiver operator curve analysis was performed.

Results: 130 patients were included (age: 51.4 ± 15.1 years, 47% male, 51% obese, systolic blood pressure: 171 ± 29mmHg, diastolic blood pressure: 97 ± 15mmHg). The prevalence of LAE by CMR was 26% and by ECG varied from 1% (P mitrale) to 27% (P axis < 30o), and was 46% when ≥1 ECG LAE criteria were present (Table 1). There was no significant difference in mean LAVI when ≥1 ECG LAE criterion was present compared to when no ECG LAE criteria were present (47 ± 15 vs 50 ± 15 ml/m2, P = 0.235). All the individual ECG LAE criteria were more specific than sensitive (Table 1), with specificities ranging from 70% (P axis <30o) to 99% (P mitrale). Obesity attenuated the specificity of most of the individual ECG LAE criteria (Table 2). Obesity correlated with significant lower specificity (48% vs 65%, P < 0.05) and a trend towards lower sensitivity (59% vs 43%, P = 0.119) when ≥1 ECG criteria of LAE were present.

Conclusion: Individual ECG criteria of LAE in hypertension are specific, but not sensitive, for identifying anatomical LAE, relative to CMR. LAE in hypertension should not be excluded on the basis of the ECG, particularly in obese subjects.

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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.25

Utility of cardiac magnetic resonance imaging for diagnosis of cardiac sarcoidosis and prediction of therapeutic effects in patients with complete heart block and implanted magnetic resonance-conditional pacemaker: A multicenter study


Aims: Complete heart block (CHB) is a serious consequence of cardiac sarcoidosis (CS), requiring early diagnosis and effective anti-inflammatory treatment. This study aimed to survey the prevalence of CS in CHB patients implanted with magnetic resonance-conditional pacemaker (MRCP) and to evaluate whether cardiac MR (CMR) findings could predict responders to corticosteroid therapy.

Methods and Results: Fifty CHB patients implanted with MRCP were enrolled in this study. CMR was performed to detect delayed enhancement (DE) as a sign of myocardial fibrosis and increased T2-weighted signal (T2-WS) as a sign of myocardial edema. We defined CS based on both histological diagnosis of extra-cardiac sarcoidosis and positive findings on CMR. Eight (16%) of the 50 patients diagnosed with CS.All of the CS patients were female, and the incidence of CS in females aged 40-69 years was 63% (5 of 8 patients). In the CS group, angiotensin-converting enzyme levels were significantly higher (18.1 ± 4.1 U/L vs. 13.5 ± 4.7 U/L, p = 0.014) and the left ventricular ejection fraction was significantly lower (57 ± 7 % vs. 62 ± 6 %, p = 0.048) in the CS group than in the idiopathic CHB group. Overall, 5 of 8 CS patients recovered from CHB after corticosteroid therapy; before corticosteroid therapy, all these patients exhibited smaller area of DE and increased T2-WS, and showed normal wall motion and thickness in the interventricular septum.

Conclusions: CS was diagnosed in 63% of female, middle-aged patients with CHB requiring pacemaker implantation. The extent of cardiac involvement detected by CMR might predict the response to corticosteroid therapy.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.26

Cardiac magnetic resonance late gadolinium enhancement in patients with genetic dilated cardiomyopathy


Introduction: Dilated cardiomyopathy (DCM) has an estimated prevalence of 1:2500 in adult population, with genetic etiology explaining 30-50% of “idiopathic” cases. Genetic causality is difficult to identify because of the scarcity of distinctive red flags. In recent years, cardiac magnetic resonance (CMR) has emerged as a valuable imaging modality in this field. However, it's utility in diagnosing genetic DCM remains largely unknown. In this work we aimed to describe CMR findings in genetically characterized DCM patients.

Methods: We included patients with idiopathic and familial DCM, that underwent a comprehensive CMR with a 3-T scanner (Siemens, Erlangen, Germany), as part of the diagnostic work-up. Left ventricular (LV) volumes, ejection fraction (LVEF) and mass were measured using dedicated software (ARGUS Software™, Siemens Healthcare Global). LV late gadolinium enhancement (LGE) presence, pattern and location were assessed; extensive fibrosis was defined as LGE in ≥ 3 LV segments.

Molecular analysis included the search of mutations in LMNA/C, MYH7, MYBPC3, TNNT2, ACTC1, TPM1, CSRP3, TCAP, SGCD, PLN, MYL2, MYL3, TNNI3, TAZ and LBD3 genes. Pathogenicity was assessed by comparisons with mutations previously described, functional tests and segregations studies.

Results: We analyzed 73 patients, 46.6% with familial DCM, 52.8% men, with mean LVEF of 34 ± 11% and LV end-diastolic volume of 128 ± 34mL. We identified 18 genetic variants in 17 distinct patients. Eleven patients presented variants with pathogenicity criteria.

Comparing patients with or without genetic variants, we observed no difference in CMR parameters. Focusing on patients with mutations in MYBPC3, TNNT2 and MYH7 genes, we found only a trend toward an association of MYH7 mutations with LGE (p = 0.057)–with a significant predilection for septum involvement (p = 0.042), and with the presence of non-compaction (p = 0.057). There was no relationship between the remaining CMR variables.

Conclusion: LGE might have some utility in the clinical recognition of patients with genetic DCM, namely those with MYH7 mutations, although additional studies are warranted to confirm these findings. Nevertheless, the exclusion of other causes of LV dysfunction and the use of more recent CMR tools, as interstitial fibrosis assessment, support the continued exploration of this technique in the evaluation of genetic/familial DCM patients.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.27

2.Left ventricular hypertrophy in hypertensive patients–comparison of Cardiac Magnetic Resonance and Echocardiographic analysis of morphological and functional LV-parameters



Aim: The aim of this research is to present usefulness of Cardiac Magnetic Resonance (CMR) to assess left ventricular hypertrophy in hypertensive patients and comparison of echocardiographic and Cardio MR results.

Material and Methods: We analysed a group consisting of 48 hypertensive patients, with suspected left ventricular hypertrophy. Cardio MR was performed by 1,5 Tesla Scanner.

We assessed left ventricular parameters such as: Ejection Fraction, End-Diastolic Volume and End-Systolic Volume. We also assessed left ventricular diameters as well as left ventricular posterior wall and interventricular septum thickness. We also calculated left ventricular mass (LVM) and left ventricular mass index (LVMI).

Results: In most cases (66,7%) patients had significant hypertrophy of the left ventricle. They also had higher LVM than the normal. We affirmed statistically significant changes of left ventricular's morphological parameters and LVM.

The significant correlation was found between posterior wall diameter and LVM, as well as between interventricular septum and LVM. The significant correlation was found between posterior wall diameter and left ventricular Ejection Fraction and End-Systolic Volume.

To compare Echocardiography analysis with CMR we have to conclude that LV mass and Ejection Fraction measured by CMR is usually less than echocardiographic LV mass and EF, but EDV and ESV is usually more than in Echocardiography.

Conclusion: In conclusion we can say that CMR is an effective method to detect LVH in hypertensive patients. There are significant differences between CMR and Echocardiographic results of LVH parameters.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.28

Is Angiographic Perfusion Score assessed in patients with acute myocardial infarction correlated with Cardiac Magnetic Resonance infarct size and N-terminal pro-brain natriuretic peptide in 6-month follow-up



Aim: Aim of the study was to analyze the correlation between Angiographic Perfusion Score (APS) and Cardio MR infarct size and left ventricular function parameters in 6 month follow-up.

Material and Methods: APS proposed as a simple, angiographic score linking epicardial and myocardial perfusion parameters before and after percutaneous coronary intervention (PPCI) is a predictor of shortterm outcome in patients with ST-segment elevation myocardial infarction (STEMI) treated with PCI.

In a cohort of 68 patients with STEMI treated with PCI APS was calculated for infarct-related artery based on angiographic parameters and was defined as the sum of the TIMI flow grade and the TMPG before and after PCI (range of points from 0 to 12). Full perfusion was defined as APS ≥ 10.

All patients received trombolytics.

Cardiac magnetic resonance (CMR) parameters and N-terminal pro-brain natriuretic peptide (NT pro-BNP) were assessed at 6 months.

Results: Median APS was 7.5 points. APS ≥ 10 was present in 42% of patients. The significant correlation was found between APS and: CMR infarct size, CMR LV ejection fraction, LV end-diastolic volume index, LV end-systolic volume index, NT pro-BNP. Patients with APS ≥ 10 had significantly lower infarct size, LV volumes, higher EF and lower NT pro-BNP.

Conclusion: APS assessed in patients with STEMI treated with PCI is a good predictor of infarct size and left ventricular function in 6-month follow-up. There was a significant correlation of APS and CMR parameters and NT pro-BNP after 6 months.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.29

Cardiac Magnetic Resonance Patterns of Left Ventricular Diastolic Function In Hypertrophic Cardiomyopathy


Purpose: Assessment of diastolic function with cardiac magnetic resonance (CMR) is challenging and underused, probably based on the belief that it requires complex calculations and special software. Although some diastolic function parameters are easy to obtain with routine cine CMR, information on their significance is currently lacking. The purpose of this study was to compare the diastolic function parameters obtained with CMR in a cohort of patients with hypertrophic cardiomyopathy (HCM) with those seen in a control healthy group.

Methods: A total of 31 patients with HCM and 23 healthy control group subjects with good quality CMR imaging studies, were analyzed. Diastolic function by CMR was obtained with left ventricle (LV) automatic segmentation of routine cine CMR images by tracing endocardial and epicardial borders of LV in short axis views. Time-volume curves were obtained and the following diastolic function parameters were calculated: Peak Filling Rate (PFR), time to PFR and diastolic volume recovery (proportion of diastole required to recover 80% stroke volume) (DVR80). Groups were compared by parametric and non-parametric tests depending on the normal distribution of the samples. A ROC curve was obtained to identify the best cutoff values for diastolic dysfunction.

Results: LV filling curves were successfully obtained in all patients analyzed. Mean age in HCM group was 65 ± 11.6 years old and median age in healthy group was 33 (IQR: 14) years. LV mass was higher in patients with HCM (186.9 ±70.45 gr vs 108.22 ±39.37 gr; p < 0.001). PFR was lower in HCM group compared to control group (400 IQR: 300 vs 600 IQR: 300 ml/sec; p = 0.001). Diastolic filling intervals were significantly prolonged in patients with HCM: tPFR (223 IQR: 169 vs 158 IQR: 63 msec; p = 0.008); DVR80 (83 IQR: 12 vs 57 IQR: 15%; p < 0.001). DVR80 was the parameter that obtained a higher area under the ROC curve (AUC = 0.89 ± 0.04; p < 0.001). A cutoff value of 69.5% DVR80 identified the presence of diastolic dysfunction with 84% sensitivity and 87% specificity.

Conclusions: All CMR simple markers of diastolic dysfunction are significantly affected in patients with HCM. DVR80 was the most sensitive and specific parameter of diastolic dysfunction in these patients.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.30

Impact of platelet volume on thrombus burden and tissue reperfusion in patients with STEMI treated with primary angioplasty: MRI study


Objective: Mean platelet volume (MPV), one of the indices of platelet reactivity has been shown to be related to impaired angiographic reperfusion in ST-segment elevation myocardial infarction (STEMI) patients treated with primary angioplasty. However data regarding MPV and its association with tissue level reperfusion in the setting of STEMI are limited. We aimed to investigate whether MPV on admission is associated with microvascular obstruction (MVO) assessed by cardiac magnetic resonance imaging (MRI) in STEMI patients with high thrombus burden of infarct related artery (IRA).

Methods: Based on SMART MRI study, out of 70 eligible patients, cardiac MRI was not performed in 5 patients because of patient's refusal, and in 5 patients due to chronic renal insufficiency. Thus, cardiac MRI was performed in 60 patients 10 ± 6 days after index STEMI, and MVO and IS were available in only 37 patients. All patients underwent thrombectomy and primary angioplasty for STEMI. MRI MVO and infarct size (IS) were measured 8 min after gadolinium injection with late enhancement sequences and were analyzed quantitatively at a blinded core laboratory. Thrombus burden of IRA were evaluated by angiography and by optical computed tomography after thrombectomy. Patients were grouped into two as with (n = 14, 38%) and without MRI MVO. Admission MPV and residual platelet reactivity (RPR, assessed by light transmittance aggregometry) after 60 mg prasugrel loading dose, were measured and compared between two groups.

Results: Admission MPV was similar in patients with and without MVO (11.4 ± 1.0 fL vs. 11.0 ± 0.9 fL respectively, p = 0.214) as well as RPR (ADP 10 µmol, 36.0% ± 18.3% vs. 32.6% ± 14.3%, p = .529). A significant Spearman's correlation was found between MPV and thrombus burden of IRA (p = 0.036), but not between MPV and MVO (p = 0.141). After multivariate analysis, including age, MPV, RPR, IS and door-to-balloon time, the only significant predictor of MVO was the severity of IS as peak creatine kinase (p = 0.003), but not the MPV.

Conclusions: in setting of contemporary primary angioplasty for STEMI using thrombectomy and high-potency antiplatelet drug prasugrel, the MPV on admission is associated with high thrombus burden of IRA but it doesn't seem able to influence tissue reperfusion evaluated by MRI.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.31

Right ventricle systolic function assessment and its prognostic implications in cardiac amyloidosis


Background: Cardiac involvement in amyloidosis is due to extracellular deposition of misfolded proteins, leading to a restrictive cardiomyopathy. From well-built evidence we know that left ventricle systolic dysfunction (LVSD) is associated with a dismal prognosis. Nonetheless, the prognosis impact of right ventricle systolic dysfunction in this subset is less clear.

Methods: From 2012 to 2014, consecutive patients with a diagnosis of cardiac amyloidosis, who had a complete transthoracic echocardiographic (TTE) and cardiac magnetic resonance study (CMR), within 2 months, were retrospectively analyzed. Left and right ventricle systolic function was determined by both imaging modalities. TTE measurements included left ventricle ejection fraction (LVEF), left ventricle global longitudinal strain (LVGLS), right ventricle ejection fraction (RVEF) and right ventricle global longitudinal strain (RVGLS). By CMR left and right ventricle ejection fraction (CMR LVEF and RVEF, respectively) were determined. Prognostic outcome was defined by a composite endpoint of cardiac mortality and hospital readmission.

Results: 18 patients presented a complete echocardiographic study. Of those, 8 patients also had a contemporary CMR study (50% females, mean age 70.6 ± 10.9 yo). Primary amyloidosis was diagnosed in 50% and 62.5% were in NYHA class ≥III. By TTE, mean LVEF was 57.1 ± 14.3%, LVGLS was -9.1 ± 4.4%, RVEF was 57.1 ± 16.7% and RVGLS -13.7 ± 9.4%. By CMR, mean LVEF and RVEF was 55.1 ± 16.2% and 46.6 ± 17.9%, respectively. Mean follow-up time was 15.4 ± 15.1 months and the composite endpoint occurred in 62.5% of patients. In this cohort, patient with adverse events presented a significantly lower RVEF (46.4 ± 6.6 vs 69 ± 4.2%, p = 0.007) and worst RVGLS (-6.5 ± 3.2 vs -20.8 ± 0.7%, p = 0.007) by TTE and lower RVEF (37.3 ± 10.3 vs 70.5 ± 2.1%, p = 0.013) by CMR. Patients with adverse outcomes presented lower LVEF and worst LVGLS, by TTE and lower LVEF by CMR, although it did not achieved statistical significance (55.0 ± 12.2 vs 56.0 ± 25.4%, -7.3 ± 2.4 vs -14.4 ± 6.2%, 53.4 ± 11.9 vs 71 ± 12.7%, all p > 0.05).

Conclusions: In our cohort, a right ventricle systolic dysfunction measured by TTE and CMR conferred a dismal prognosis in cardiac amyloidosis patients. This finding heightens the importance of consider this sometimes overlooked tool in the routine evaluation of these patients.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.32

Cardiac MRI - an important tool in the evaluation of multsystemic inflamatory diseases. An Erdheim-Chester Disease case report


Introduction: It has been found by MRI and CT studies that cardiac involvement in multisystemic disease occurs more often than expected, in different forms, and that cardiovascular manifestations are underdiagnosed. Cardiovascular involvement in multisystemic disease as in the Erdheim-Chester disease (ECD) is seen in the majority of patients and is associated with a reduced response to treatment and an overall poor prognosis. The prognosis of ECD remains poor, with mortality rates of 60% at 32 months after diagnosis, mainly due to cardiopulmonary causes.

Case Report: A 49-year-old man, affected by ECD, was referred to our department for a correct assessment of the degree of cardiac involvement through cardiac magnetic resonance imaging (MRI). The patient presented with a medical history of bone, retroperitoneal involvement and with heart failure symptoms. The final diagnosis of ECD was confirmed by proximal right tibia biopsy which showed the presence of infiltrated foamy histiocytes, CD 68 + CD1a -.

The MRI study at the admission showed diffusely thickened pericardium with strong enhancement of the pericardial layers after gadolinium administration with nodular delayed enhancement involving the epicardium. Real-time CMR in cardiac short-axis during free breathing showed increased ventricular coupling with inspiratory septal inversion and increased right-sided septal motion at onset of expiration. Analysis with Argus software from short axis SSFP cine images demonstrated reduced left ventricular ejection fraction (LVEF 47%) with reduced stroke volume (36 ml) and reduced ejection fraction of the right ventricle (RVEF 35%).

Cardiac MRI 6 months after treatment with INTERFERON demonstrated the normalization of the ejection fraction of the left ventricle and of the right ventricle with persistence of late-enhanced pericardium with gadolinium. The patient is now 12 months post-diagnosis and clinically stable with improved peripheral edema and dyspnea.

Conclusions: This is a case of heart failure as a manifestation of cardiac involvement in a multisystemic disease. Cardiac MRI is an important tool for a correct assessment of ECD. This technique allows a precise definition of localization and extension of the fibrotic involvement. An accurate evaluation of the cardiovascular system is mandatory because if affected by ECD, the prognosis will worsen. Cardiac MRI represents also the best imaging exam for the evaluation of the response to the treatment.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.33

Predictive value of cardiac magnetic resonance for future adverse cardiac events in patients with ST-segment elevation myocardial infarction


Purpose: The aim of the study was to determine prognostic value of infarct size (IS), microvascular obstruction (MVO) and left ventricular ejection fraction (EF) evaluated by cardiac magnetic resonance imaging (CMR), markers of necrosis, electrocardiographic and echocardiographic parameters in patients with ST-elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (pPCI).

Material and Methods: 85 STEMI patients treated by pPCI within 12 hours after symptom onset had an evaluation of CMR within three days. Markers of necrosis were measured every 8 hours from the admission to the hospital.

Electrocardiography (Selvester and Aldrich score) were assessed at the admission, after pPCI and before CMR and echocardiography (WMSI) within the first day after pPCI. CMR was performed on the 1.5T system within 96 hours after pPCI. Morphology and function of LV was estimated by steady-state free precession (SSFP). To evaluate the infarct size and MVO, late gadolinium enhancement (LGE) sequence was (10-15 min after administration of gadobutrol). Infarct size was defined as area above 50% of the maximal signal intensity within LGE (FWMH–full-width half maximum). MVO was described as the area of absence or hyperenhancement of myocardium surrounded by LGE. IS and MVO were determined by planimetry and summation of discs method. All patients were observed 24 months to evaluate major adverse cardiovascular events (MACE). The primary endpoint was defined as a composite of death, myocardial reinfarction, coronary reintervention and congestive heart failure.

Results: Multiple regression analysis showed that that left ventricular ejection fraction, IS and MVO were the strongest independent predictors of MACE (p = 0.0001, p = 0.00001 and p = 0.028 respectively). IS larger than 20% of left ventricular mass predicts MACE with a sensitivity of 85% and specificity of 86%. The presence of MVO also predicts MACE within 2-year follow-up with a sensitivity and specificity of 80%. WMSI, troponin I serum concentration, ECG derived parameters do not provide accurate information of cardiovascular events.

Conclusions: CMR has predictive value for future cardiovascular events. Infarct size, MVO and left ventricular ejection fraction evaluated by CMR are independent predictors of outcome after STEMI.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.34

Time-to-treatment but not thrombectomy influence infarct size and microvascular obstruction in patients with acute ST-segment elevation myocardial infarction treated with primary coronary intervention


Background: Infarct size and microvascular obstruction evaluated by cardiac magnetic resonance (CMR) have a prognostic value in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). Time to treatment and successful reperfusion are essential in those patients. Some trials have shown that thrombectomy improves surrogate and clinical outcome. Lastly thrombectomy is questioned to be effective in patients with STEMI.

The aim of the study: The aim of the study was to evaluate the influence of time-to-treatment and manual thrombectomy on infarct size (IS) and microvascular obstruction (MVO) in patients with STEMI.

Material and methods: We examined 85 patients (mean age 59 ± 11 years; 59 males and 26 females) with first STEMI treated with pPCI within 12 hours from symptoms onset. Infarct related artery TIMI flow and MBG were evaluated after pPCI. CMR was performed on the 1.5T system within 96 hours after pPCI. Morphology and function of myocardium was estimated by steady-state free precession (SSFP) sequence. To evaluate the infarct size and MVO, a late gadolinium enhancement (LGE) sequence was performed (10-15 min after administration of gadobutrol). Infarct size was defined as area above 50% of the maximal signal intensity within LGE (FWMH–full-width half maximum), MVO was described as the area of absence or hyperenhancement of myocardium surrounded by LGE. IS and MVO were determined by planimetry and summation of discs method.

Results: The mean size of infarct size in study group was 16.52 ± 10.54% of LV myocardial mass. The presence of MVO was observed in 28 patients (32.94%) with a mean size of 8 ± 6% of infarct size. Patients treated in 90 minutes from the symptoms onset had lower infarct size than patients treated after 360 minutes from the beginning of chest pain (p = 0.048). Manual thrombectomy during pPCI was performed in 37 patients (43.53%) and these patients had mean ejection fraction 54.36 ± 8.8% with IS estimated on CMR 16.96 ± 9.8% of myocardial mass and MVO 3.85% of infarct size. The patients treated by pPCI alone, without thrombectomy, had similar EF (54.8 ± 10.7%; p = ns) and CMR findings: IS = 16.25 ± 10.05% of LV myocardial mass (p = ns) and MVO = 4.84% of infarct size (p = ns).

Conclusion: Rapid treatment of patients with STEMI results in smaller infarct size evaluated by CMR. Manual thrombectomy during pPCI does not improve CMR outcomes in STEMI patients.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.35

Primary PCI versus Early Routine Post Fibrinolysis PCI for ST Elevation Myocardial Infarction


Background: The rationale for Pharmaco-invasive strategy is that many patients have a persistent reduction in flow in the infarct-related artery. The aim of the present study is to assess safety and efficacy of pharmaco-invasive strategy compared to primary PCI and ischemia driven PCI on degree of myocardial salvage and outcomes.

Methods and Results: Sixty patients with 1st attack of acute STEMI within 12h were randomized to 4 groups (15 patients each): primary PCI for patients presented to PPCI-capable centers (group I), transfer to PCI if presented to non-PCI capable center (group II), pharmaco-invasive strategy (group III) and fibrinolytic (streptokinase) and ischemia driven PCI (group VI). The primary endpoint is the infarct size measured by cardiac MRI 3-5 days post MI. Pharmaco-invasive strategy led to significant reduction in infarction size and major adverse cardiac and cerebrovascular event (MACCE) compared to group IV and decrease -but not significant- in infarction size and MACCE compared to group I and II. Minor bleeding was significantly higher in pharmaco-invasive group compared to other groups.

Conclusions: Pharmaco-invasive strategy resulted in effective reperfusion and smaller infarction size in patients with early STEMI who could not undergo primary PCI within 2 hours after the first medical contact. This can provides a wide time window for PCI when the application of primary PCI within the optimal time limit is not possible. However, pharmaco-invasive strategy was associated with a slightly increased risk of minor bleeding.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.36

Evaluation of ventricular function in Fontan patients undergoing feature tracking magnetic resonance strain


Introduction: Feature tracking strain (FTS) is a new technique to assess cardiac function from cardiac magnetic resonance (CMR). We compared FTS with conventional function parameters in single ventricle subjects with Fontan physiology undergoing CMR.

Methods: 18 Fontan subjects (mean age 17.6 + /-9.2 years, post Fontan period 14.2 + /-8.2 years, 13/18 morphologic right ventricle, 5/18 morphologic left ventricle) underwent a CMR study. Ventricular volumes and cardiac output were calculated offline (Medis QMass advanced edition, the Netherlands). Offline strain and strain rate (SR) analyses were performed (TomTec Image Arena, Germany) on the 4-chamber and short-axis views at the basal, mid, and apical levels of the ventricle.

Results: Basal endocardial circumferential strain/SR (-11 + /-9 % and -0.8 + /-0.5 1/s) were lower than it at the mid (-17 + /-6 % and -1.1 + /-0.5 1/s; p = 0.02 and 0.02) and apical (-26 + /-9 % and -1.9 + /-1.0 1 /s; p = 0.001 and 0.003) levels. There was correlation between average endocardial longitudinal strain/SR and ventricular end-diastolic volume (r = 0.73 and 0.68). At the mid and apical levels, there was correlation between average endocardial circumferential strain/SR and ventricular end-systolic volume, and ejection fraction (r = 0.53 to 0.85). There was also correlation between average endocardial radial strain/SR and ventricular stroke volume at the mid level (r = 0.69 and 0.77).

Conclusions: There is correlation between strain/SR and measures of ventricular volume, ejection fraction and cardiac output in single ventricle subjects with Fontan physiology. FTS is independent of inadequate acoustic windows unlike echocardiography and could have clinical relevance. Analysis of regional strain may helpful in understanding myocardial mechanics in the single ventricle in further studies.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.37

Impacts of atrialized right ventricle and left ventricular displacement in Ebstein's anomaly on left ventricular function assessed by cardiovascular MRI


Background: Left ventricular (LV) failure is common in Ebstein's anomaly, though remains poorly understood. The objective of this study was to investigate whether atrialized right ventricle (ARV) and LV displacement impact LV function in Ebstein's anomaly by cardiovascular MRI (CMR).

Methods: We analyzed CMR studies in patients with Ebstein's anomaly for measures of severity, including ARV, functional (FRV) and total right ventricular (TRV) volumes, LV volumes, LV and RV ejection fraction (EF). And, we analyzed LV longitudinal, radial and circumferential strain/strain rate in accordance with the 16-segment model proposed by the American Society of Echocardiography. We also measured ARV global longitudinal strain. We related those CMR values to LV failure in Ebstein's anomaly. The MRI imaging was obtained using the 1.5-Tesla system (Siemens MAGNETOM Sonata). The analyses were performed using a workstation (Medis QMass advanced edition and Tomtec Image Arena).

Results: Twelve unrepaired patients (mean age 17 + /-7 years, 75 % female) were included. LV end-diastolic volume was normal (87 + /-24 ml/m2) and LVEF (59 + /-6 %) was preserved. TRV end-diastolic volume (188 + /-127 ml/m2) was dilated and FRVEF (37 + /-16 %) was reduced. At basal and middle cavity of LV, anterior radial strain were higher than it of the septal segments (p = 0.01 and 0.02). At middle and apical cavity of LV, septal circumferential strain were higher than it of the anterior segments (p = 0.001 and <0.05) on the contrary. ARV, FRV and TRV were negatively correlated with LVEF (r = -0.58 to -0.88). However, ARV, FRV and TRV were positively correlated with LV global circumferential strain at middle cavity (r = 0.62 to 0.87), and ARV global longitudinal strain was with LVEF (r = 0.77).

Conclusions: The apparent basal and middle septal radial hypokinesis with middle and apical septal circumferential hyperkinesis observed in most patients is likely attributable to anterior cardiac displacement rather than true paradoxical motion. LVEF was negatively affected by RV volumes; however, right and left ventricular interaction was indeed proved in Ebstein's anomaly.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.38

Final diagnosis for patients presenting with chest pain, electrocardiographic changes or troponin rise and normal coronary arteries: insights from Cardiovascular MRI in our population


Literature states that about 75% of patients with chest pain, electrocardiographic (EKG) alteration at admission or troponin (Tn) rise and normal coronary arteries (NCA: normal or stenosis <50%) are diagnosed of myocarditis in CMR.

The purpose of this review was to know the real final diagnosis of patients suffering from this condition in our centre.

Methods: All patients referred to CMR from January 2012 to October 2015 with these criteria were included. Studies were performed within the first week of admission on a 1.5 T or 3T scanners. SSFP cines, T2-weighted black-blood fat-sat images and DE-segmented GE IR images 10-20 minutes after iv gadolinium-DTPA administration (0.15mmol/kg) were performed in 3 long-axis and 11-15 parallel short-axis views. All images were reviewed and analyzed off-line with specialized post-processing software (Philips IntelliSpace Portal®, Philips).

Results: 84 patients met the inclusion criteria. Medium age was 43yo. Males 71%. Main EKG alterations were ST segment elevation (STE) (57%) and T wave inversion (25%). Mean peak TnI levels (12h of admission) was 9.4ng/ml. Mean LVEF was 57% (range 20-84%). Regional wall motion abnormalities were present in 56 cases (63%). High signal in T2w images was detected in 65% of cases and LGE in 60 cases (71%). Final CMR diagnosis resulted in myocarditis (48%), myocardial infarct (MI) (18%), Takotsubo (13%), dilated cardiomyopathy (DCM) (3.6%) and cardiac sarcoid and pericarditis in 1.2%. 8 cases were normal (9.6%). CMR was not conclusive in 1.

Myocarditis patients had the highest peak TnI levels (15.5 vs 4.1; p = 0.02). STE was more frequent in Takotsubo and pericarditis (100%) than myocarditis (54.3%) or MI (35.7%) [p = 0.032]. Interestingly, only 11.4% of patient with STE at admission had final diagnosis of MI. Edema was more frequent in myocarditis (80%) and Takotsubo (81%) as compared to the rest [p < 0.01], being its extention more important in Takotsubo, myocarditis and MI (mean segments affected: 5.7, 3.2 and 1.53 respectively; p = 0.02). Patients with myocarditis and pericarditis were significantly younger (33yo vs 48yo; p < 0.01). DCM patients had larger ventricles (iLVEDV 154ml vs 80ml) and poorer LVEF (26% vs 61%) [p < 0.01].

Conclusions: Less than half of patients of our cohort had final diagnosis for myocarditis. A not insignificant proportion of patients had myocardial infarcts despite NCA (18%). More interestingly, only 11.4% of of patients that presented with STE at admission had MI.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.39

Early Predictive Factors of LV Remodeling after STEMI; Assessment by Coronary Angiogram and Cadiovascular Magnetic Resonance


Despite advances in acute myocardial infarction (MI) care, left ventricular remodeling (LVR) after revascularization is one of the major determining factor for heart failure development and cardiovascular events. The aims of our National multicentre Regsitry PREGICA-MRI was to explore angiographic and cardiovascular magnetic resonance (CMR) parameters that were predictive factors of LVR. LVR was defined as a >20% increase in 6-month end-diastolic volume (EDV) from baseline values.

CMR has been recently recognized as one of the best imaging technique for left ventricular (LV) function assessment, myocardial viability and infarct size (IS) or microvascular obstruction (MVO) measurement. It therefore be an optimal imaging modality to predict LVR, assessing IS and MVO.

Material and Methods: Forty six patients (mean age 56,7 ± 10 years) presenting with first episode of acute MI and treated by primary PCI <12h of chest pain onset were studied

CMR was performed within the first week (day 4 ± 2) of ST elevation MI and repeated at a mean time of 6.0 ± 1.4 months. Steady state free precession cines, T2 STIR, first pass perfusion (FP), delayed hyper-enhancement (DHE) images were obtained on a 1.5-T MR system.

Ventricular volumes, ejection fraction (EF), LV mass, and FP perfusion defects were recorded. IS and MVO was measured on DHE images. MVO was defined as areas of hypo-enhancement within hypersignal of necrosed myocardium in DHE images.

Revascularization of culprit lesion was performed by primary PCI within 12 hours of chest pain onset. Myocardial blush index (MBI) and TIMI score was recorded and Index of Microcirculatory Resistance (IMR) was measured using a pressure guide wire.

Results: LVR 6 months after myocardial infarction was found in 16 patients (35%) of the cohort PREGICA-MRI.

IMR level was significantly higher in patients associated with LVR (73,95 versus 27,23 p < 0,03).

A significant risk of LVR was found in patients with IMR > 40 (OR 15 (1,030-218,4), p = 0,03).

LVR was associated with patients having a large transmural infarct on DHE images (OR 25,46 (1,397 - 463,8), p = 0,002), higher number of akinetc segments (6,26 versus 4, p = 0,001), and higher number of segments with MVO (4,43 versus 2,26, p = 0,03).

Conclusions: High level of IMR, number of segments with MVO and transmural DHE can be considered as predictive factors of LVR 6 months after acute MI and early revascularization.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.40

The Pathobiologic Mechanisms and the Prognostic Meaning of t wave Inversion in Acute Myocarditis. a Study Performed by Cardiac Magnetic Resonance


Background: The pathobiologic mechanisms as the prognostic meaning of electrocardiographic (ECG) T-wave inversion (TWI) occurring in a subgroup of patients with acute myocarditis remain to be elucidated. Contrast-enhanced cardiac magnetic resonance (CMR) offers the potential to identify myocardial tissue changes such as edema and/or fibrosis. A pathophysiologic link between dynamic TWI and transient myocardial edema in other cardiac disease such asTako-tsubo cardiomyopathy was already described.

Aims: The aims are understand the myocardial substrates that underlie TWI in myocarditis and investigate the prognostic value during follow up.

Methods: We enrolled consecutive patients with acute myocarditis according European Society of Cardiology position statement. All patients to be enrolled had to using a comprehensive CMR protocol which included T2 weighted sequences for myocardial edema and post constrast sequences for necrosis. A 12-lead ECG was collected at the same day. After six months patients underwent clinical follow up consisting of echocardiogram, ECG and -in case of reduced ejection fraction- a second CMR.

Results: We studied 76 consecutive patients (median age 34 years). At the time of CMR, TWI was observed in 21 (27%) patients. There was a statistically significant association of TWI with the median number of left ventricular (LV) segments showing either any pattern of myocardial edema (transmural and non-trasmural) [3(2-4) vs 5(3-7);p = 0.015] or myocardial late-gadolinium-enhancement [3(2-4) vs 4(3-7); p = 0.002]. Transmural myocardial edema involving ≥2 LV segments was found in 17/21 (81%) patients with TWI versus 13/55 (24%) patients without TWI (p < 0.001) and remained the only independent predictor of TWI at multivariable analysis (OR = 9.96; 95%CI = 2.71-36.6; p = 0.001). Overall, topographic concordance between the location of TWI across the ECG leads and the regional distribution of transmural myocardial edema was 88%. There was no association between acute TWI and reduced LV ejection fraction (<55%) at 6-months of follow-up.

Conclusion: LV transmural myocardial edema as evidenced by CMR was demonstrated to be the anatomical substrate associated with the occurence of TWI in patiens with acute myocarditis, As an expression of reversible myocardial edema, the development of TWI during the acute disease phase doesn't represent an adverse marker since doesn't predict systolic LV dysfunction at 6 months follow-up.

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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.43

The Influence of Left Atrial Function on Exercise Tolerance in Patients with Heart Failure and Preserved Ejection Fraction: A Cardiac Magnetic Resonance Feature Tracking Study


Background: Heart failure with preserved ejection fraction (HFpEF) is a syndrome which accounts for impaired exercise capacity in a growing number of patients. Intrinsic ventricular stiffness constant Beta is a known factor resulting in impaired exercise capacity. Cardiovascular magnetic resonance myocardial feature tracking (CMR-FT) is a novel tool measuring atrial strain and phasic performance from routine cine CMR images using standard steady-state free precession sequences (SSFP). The interplay between left atrial (LA) function and exercise capacity in HFpEF patients remains to be elucidated.

Methods: We performed CMR-FT in 20 patients with HFpEF and 10 patients without heart failure symptoms. LA function can be analyzed using 2- and 4-chamber views for assessment of LA reservoir function (total strain [εs], peak positive strain rate [SRs]), LA conduit function (passive strain [εe], peak early negative strain rate [SRe]) and LA booster pump function (active strain [εa], late peak negative strain rate [SRa]). Invasive pressure-volume-loops were obtained with a conductance catheter during basal conditions, transient preload reduction and handgrip exercise. Diastolic stiffness constant Beta was extrapolated during transient preload reduction. During exercise testing on an upright cycle ergometer functional capacity (max Watts) and maximum oxygen uptake (VO2max ml/kg*min) was measured.

Results: Patients with HFpEF showed greater left atrial volumes (LAV max 48 ± 11 vs. 36 ± 13 ml/m2, p < 0.05) and lower exercise capacity (92 ± 29 vs. 168 ± 41 Watts, p < 0.001) and oxygen uptake (17 ± 6 vs. 33 ± 15 ml/kg*min, p < 0.001). LA reservoir and conduit function were significantly lower in HFpEF patients (εs 23 ± 6 vs. 28 ± 6%, p < 0.05; εe 9 ± 5 vs. 15 ± 5%, p < 0.01). HFpEF patients had a higher intrinsic stiffness constant Beta (0.036 ± 0.006 vs. 0.021 ± 0.008, p < 0.001). Beta showed a weak correlation with VO2max (r = -0.37, p < 0.05). Strain measurement for LA conduit function showed the best correlation with VO2max (r = 0.824, p < 0.001). Multivariate regression analysis including Beta, isovolumetric relaxation constant Tau and LA conduit function (εe) was performed. In this model, εe remained the only predictor of VO2max (R= 0.81, R2 = 0.67, p < 0.001).

Conclusion: LA dysfunction, especially impaired conduit function, significantly contributes to impaired functional capacity in HFpEF patients. These results propose LA dysfunction as another important contributor to HFpEF, independent of LV stiffness.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.44

Microvascular Obstruction in Patients with Anterior ST-Elevation Myocardial Infarction who Underwent Primary Percutaneous Coronary Intervention: Predictors and Impact on the Left Ventricular Function


Introduction: Microvascular obstruction (MVO) is an independent predictor of left ventricular remodelling and mortality following ST-segment Elevation Myocardial Infarction (STEMI). Cardiac Magnetic Resonance (CMR) is a method for quantitative evaluation of Myocardial Blood Flow (MBF) that might provide superior predictive data in the assessment of MVO.

Hypothesis: We sought to compare angiographic and CMR-derived assessment of MVO to determine the optimal methodology that best correlates with left ventricular function post-STEMI, as well as predictors of MVO.

Methods: Thirty patients presented with anterior STEMI were successfully reperfused with final TIMI 3 flow in the infarct-related artery (IRA). Following primary Percutaneous Coronary Intervention (PCI), angiographic assessment of microvascular perfusion was performed with Myocardial Blush Grade (MBG). Assessment of CMR-derived MVO was performed from day 2 - 4 after primary PCI. MVO volume was evaluated with late gadolinium enhancement CMR sequences. Infarction size was also measured. Echocardiography was done within 48 hours after Primary PCI and repeated after 3 months for assessment of the Left Ventricular ejection fraction (LVEF). Patients were followed up clinically for Major Adverse Cardiac Events (MACE) during hospital stay and up to 3 months. 46 %. MBG showed no correlation to CMR-derived MVO. There was a strong positive correlation between infarction size and MVO volume (p = 0.001) in CMR. There was more delayed peaking of Creatine Kinase (CK) total and (CK)-MB in patients with CMR-derived MVO compared to patients with no CMR-derived MVO (p = 0.016). On multivariate analysis, of all angiographic and CMR variables, CMR-derived MVO was the strongest predictor of LVEF at 90 days (p = 0.004). CMR-derived MVO had a positive association with occurrence of MACE (p = 0.02). The only procedural predictor of CMR-derived MVO was pre-stenting balloon angioplasty (p < 0.05).

Conclusions: CMR-derived MVO in late gadolinium enhancement sequences strongly predicts left ventricular function following Anterior STEMI at 90 days. CMR-derived MVO is associated with a lower LVEF, increased infarct size, and a greater risk of MACE. Pre-stenting balloon angioplasty strongly affects CMR-derived MVO after Primary PCI.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.45

Histological Validation of ECV Quantification by Cardiac Magnetic Resonance T1 Mapping in Cardiac Amyloidosis


Background: Cardiac amyloidosis (CA) is caused by accumulation of amyloid fibrils in the myocardium, which leads to an increase in extracellular volume (ECV). Cardiac magnetic resonance (CMR) T1 mapping allows accurate non-invasive ECV measurement. However, it has not been investigated weather CMR-ECV accurately quantifies ECV in CA.

Materials and Methods: Between July 2011 and November 2015 21 CA patients were enrolled. The study population consisted of 7 (33.3%) wild-type transthyretin (TW-TTR) and 14 (66.6%) light chain (AL) CA patients. All patients underwent myocardial biopsy (EMB) and CMR. EMB specimens were stained with Modified Trichrome and ECV was quantified via ImageJ software using a color-threshold macro. CMR-ECV was quantified with T1 mapping using the Modified Look-Locker Inversion recovery (MOLLI) sequence. Spearman's correlation and Bland-Altman plots were used for correlation analysis and assessment of agreement between histological ECV (H-ECV) and CMR-ECV.

Results: All CA patients (N = 21) had a CMR-ECV median of 48.5% (23.6%-71.0%), an H-ECV median of 50.2% (10.7%-80.6%), a combined (CMR-ECV + H-ECV) median of 48.3% (18.8%-75.5%), a median difference between CMR-ECV and H-ECV of -0.376 (-40.7-18.1) and a correlation coefficient of R = 0.752; p= <0.001. For WT-TTR-CA patients (N = 7) results were as follows. Median CMR-ECV of 48.6% (40.8%-70.5%), median H-ECV of 54.2% (32.1%-80.6%), combined ECV median of 54.4% (36.5%-75.5%), a median difference between CMR-ECV and H-ECV of 10.132 (-9.8-18.1) and a correlation coefficient of R = 0.714; p = 0.071. AL-CA patients (N = 14) showed a median CMR-ECV of 47.8% (23.6%-71.0%), a median of H-ECV of 46.8% (10.7%-69.7%), a combined median of 45.9% (18.8%-69.0%), a median difference between CMR-ECV and H-ECV of -0.746 (-40.7-8.4) and a correlation coefficient of R= 0.807; p= <0.001.

Conclusions: We are the first to histologically validate CMR-ECV in cardiac amyloidosis patients. Our results show excellent correlation and good agreement of CMR-ECV with H-ECV in the whole study population as well as in subgroup analysis for AL-CA and WT-TTR-CA. CMR-ECV quantification by T1 mapping accurately reflects ECV in cardiac amyloidosis patients. As many current phase II and phase III trials for treatment of CA are under way, ECV measurement via CMR may provide important information on weather CA therapies can indeed reduce ECV in CA. Therefore, CMR-ECV quantification might be an appealing method in evaluating success.

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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.46

Comparative Evaluation of Flow Quantification Across the Atrioventricular Valve in Patients with Functional Univentricular Heart After Fontan's Surgery and Healthy Controls: Measurement by 4D Flow Magnetic Resonance Imaging and Streamline Visualization


Purpose: To evaluate the inflow pattern and flow quantification in patients with functional univentricular heart after Fontan's operation using 4D flow magnetic resonance imaging (MRI) with streamline visualization when compared with the conventional 2D flow approach.

Method: Seven patients with functional univentricular heart after Fontan's operation and twenty-three healthy controls underwent 4D flow MRI. In two orthogonal two-chamber planes, streamline visualization was applied, and inflow angles with peak inflow velocity (PIV) were measured. Trans-atrioventricular flow quantification was assessed using conventional 2D multiplanar reformation (MPR) and 4D MPR tracking the annulus and perpendicular to the streamline inflow at PIV, and they were validated with net forward aortic flow.

Results: Inflow angles at PIV in the patient group demonstrated wide variation of angles and directions when compared with the control group (p < 0.01). The use of 4D flow MRI with streamlines visualization in quantification of the trans-atrioventricular flow had smaller limits of agreement (2.2 ± 4.1mL; 95% limit of agreement -5.9-10.3mL) when compared with the static plane assessment from 2DFlow MRI (-2.2 ± 18.5mL; 95% limit of agreement agreement -38.5-34.1mL). Stronger correlation was present in the 4D flow between the aortic and trans-atrioventricular flow (R2 correlation in 4D flow: 0.893; in 2D flow: 0.786).

Conclusions: Streamline visualization in 4D flow MRI confirmed variable atrioventricular inflow directions in patients with functional univentricular heart with previous Fontan's procedure. 4D flow aided generation of measurement planes according to the blood flood dynamics and has proven to be more accurate than the fixed plane 2D flow measurements when calculating flow quantifications.

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Figure 1. MRI 4D flow with streamline visualization (a,b) Healthy volunteer four-chamber view with streamline visualization by velocity encoding (c,d) A patient with functional univentricular heart, two-chamber view with streamline visualization at diastole and systole demonstrating regurgitant jet

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Figure 2. Agreement between atrioventricular valve forward flow and aorta. Bland–Altman graphs between aortic flow and effective forward flow in healthy patients with (a) 2D flow (b) 4D flow and patients with functional univentricular heart with (c) 2D flow and (d) 4D flow.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.47

Does arterial switch for d-transposition of the great arteries alter myocardial deformation of the ventricles?


Introduction: The arterial switch operation (ASO) is currently the surgical technique of choice for repair of d-transposition of the great arteries. The main pulmonary artery is moved forward (Lecompte maneuver) and its branches are stretched on either side of the ascending aorta. The coronary arteries are removed from and reinserted into the aorta. We sought to assess myocardial deformation changes in the right (RV) and left ventricles (LV) as signs of subclinical myocardial functional impairment after ASO and re-positioning of the coronary arteries.

Methods: Patients after ASO and normal controls underwent cardiac magnetic resonance (CMR) imaging including 2D SSFP for ventricular function. 2D SSFP cine images were post-processed with a feature tracking software (TomTec 2D CPA). Global circumferential strain was measured on short axis mid-ventricular slices and global longitudinal strain on horizontal long-axis images, separately for each ventricle. Patients with pulmonary arteries stenoses or history, symptoms, or CMR findings suspicious for coronary compromise were excluded.

Results: Eighteen patients after ASO (age 16.8± 6.7y) were compared to 18 normal controls (age 22.2± 11.4y; p = 0.098). RVs of ASO patients showed lower longitudinal strains (-14.1± 6.4% vs. -18.3± 3.8%; p < 0.05) but higher circumferential strains (-16.6± 3.2% vs. -13.1± 4.3%; p < 0.01) compared to normal RVs. LV longitudinal strain (-15.4± 5.1% vs. -17.5± 4.6%; n.s.) and LV circumferential strain (26± 5.6% vs. -23± 13.1%; n.s.) were not significantly different in patients vs. controls. There were no differences between ASO patients and controls regarding ejection fractions of the RV (54± 6% vs. 52%± 5%; n.s.) and LV (58± 8% vs. 60%± 5%; n.s.) or regarding end-diastolic volumes of the RV (91± 21ml/m2 vs. 94± 12ml/m2; n.s.) and LV (87± 26ml/m2 vs. 80± 11ml/m2; n.s.) indexed to body surface area, respectively.

Conclusions: LV deformation is preserved after the ASO operation, despite coronary artery surgery. In contrast, even in the absence of significant pulmonary artery stenosis, RV deformation is altered with decreased global longitudinal strain and increased circumferential strain, while preserving RV volume and ejection fraction. This may be the result of abnormal ventriculo-arterial coupling after the Lecompte maneuver and its changes in the outflow tract geometry.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.48

Accuracy of T1 Mapping by multi-professional CMR operators to predict myocardial infarct


Background: Native T1 mapping is increasingly used in clinical and research applications to distinguish between normal myocardium and fibrosis or scar. Online reconstruction of T1 maps on the scanner console is now widely available and can delineate areas of myocardial infarction prior to late gadolinium enhancement (LGE) imaging. Such advance knowledge may help in optimising timings and obtaining targeted views during LGE. The aim of the study was to establish the feasibility and accuracy of detecting myocardial infarction from T1 maps obtained during live scanning and to compare the performance of clinicians and non-clinicians.

Methods: Native T1-maps were generated on a Philips scanner (1.5T Ingenia CV, Philips Healthcare) during live scanning. The colour scales for the maps were set between 200msec and 1600msec. 8 CMR professionals of varying scanning ability (4 Cardiologists, 3 Radiographers, 1 Medical Physicist) received basic T1 mapping reading instructions to identify abnormal myocardium with infarct. Each individual then assessed 40 segments (in total 320 segments by 8 assessors) of short-axis native T1 maps and were asked blindly to identify normal, area(s) of infarct and affected coronary territories. Sensitivity and specificity to detect infarction on subsequent LGE images was determined.

Results: In total 320 segments involving 10 cases were assessed by eight readers. There were no significant differences in detecting myocardial infarction between the three groups readers (cardiologists: sensitivity of 87%, 95% CI 66-98 and specificity of 67%, 95% CI 46-76; radiographers: sensitivity of 83%, 95% CI 69-92 and specificity of 75%, 95% CI 54-89; physicist: sensitivity of 83% and specificity of 75%). The accuracy of all observers to identify infarction on LGE and to identify the correct coronary artery territory are listed in Table 1. The highest sensitivity and specificity were demonstrated for inferior infarction while sensitivity to detect septal infarction was low.

Conclusions: T1 Mapping is an additional tool that may be used by the CMR operator to predict infarct size and location prior to LGE. Information obtained pre-LGE is beneficial where patients have a limited tolerance to breath-hold commands and the targeting of infarct areas over normal myocardium is a priority during a limited window of opportunity for LGE. In this pilot study all clinicians and non-clinicians perform similarly.

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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.49

Detecting hypertensive heart disease: the additive value of cardiovascular magnetic resonance imaging

Mr Max Charalambos,1 Dr Jonathan Rodrigues, BSc(Hons), MBChB(Hons), MRCP, FRCR,2,3 Dr Amy Burchell, MA, BM BCh, MRCP,4 Dr Amardeep Ghosh Dastidar, MBBS, MRCP,2 Dr Laura Ratcliffe BSc(Hons), MBBS, MRCP,4 Dr Emma Hart, BSc, PhD,4 Dr Mark Hamilton, MBChB, MRCP, FRCR,2 Professor Julian Paton, BSc(Hons), PhD,3,4 Dr Angus Nightingale, MA, MB BChir, FRCP, MD,4 and Dr Nathan Manghat, MBChB, MRCP, FRCR, MD2


Introduction: Arterial hypertension is common. Hypertensive heart disease (HHD) is associated with significant morbidity and mortality. European Society of Hypertension/Cardiology guidelines advise screening for HHD in hypertensive subjects, to aid risk stratification which may impact clinical management. Cardiac magnetic resonance (CMR) is current non–invasive gold standard for assessing ventricular structure and function. We aimed to determine the additive value of CMR in hypertensives who had already undergone echocardiography.

Methods: 85 subjects from the tertiary hypertension clinic with preceding echo underwent 1.5T CMR. Left ventricular mass and volumes were estimated from short–axis steady–state free precession cines. LVH was defined on the basis of echo and CMR normal reference ranges. LV wall thickness in the mid–cavity interventricular septum (IVS) and the mid–cavity posterolateral wall (PLW) were compared between modalities. Gadolinium was administered to all subjects undergoing CMR. The presence and pattern of myocardial late gadolinium enhancement (LGE) was documented.

Results: 85 subjects were included (60% men, office systolic BP: 165 ± 28mmHg, office diastolic BP: 94 ± 14mmHg). Overall, there was no difference in prevalence of LVH by echo compared to CMR (68% vs 66%, P = 0.746). However, there was a discrepancy between echo and CMR in 28%. Relative to CMR gold– standard, echo over–diagnosed LVH in 15% and missed LVH in 13%. The diagnostic performance of echo at detecting LVH was as follows: specificity 55%, sensitivity 80%, positive predictive value 78%, negative predictive value 59% and overall accuracy 72%. The echo measurement of PLW was >2mm than the corresponding CMR measurement in 45%. Ischaemic LGE was present in 7% of subjects (Figure 1A) and non–ischaemic LGE was present in 9% (Figure 1B).

Conclusion: Although there was no significant difference in overall prevalence of hypertensive LVH between echocardiography and CMR, echocardiography over–diagnosed and under–diagnosed LVH in an important minority of patients. Echocardiographic measurement of PLW was particularly prone to error relative to CMR. LGE tissue characterization is unique to CMR and identified ischaemic and non–ischaemic myocardial fibrosis is an important minority of hypertensive patients. Our findings support an extended role of CMR in hypertension where documenting in the presence/absence of HHD may have clinical management implications.

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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.50

Diagnostic Performance of Cardiac Magnetic Resonance Strain Parameters in Assesment of Myocardial Ischemia


Recently new tools for analysis of myocardial strain by cardiac magnetic resonance (CMR) have been developed and must be analyzed to establish their clinical utility. We aim to study usefulness and diagnostic performance of CMR strain parameters in patients with early ischemia.

Methods: patients with chest pain and CMR dipyridamole stress test conducted prior catheterization were included. All of them had positive stress test and coronary artery stenosis ≥70% confirmed by coronary angiogram. CMR stress protocol included functional study with steady state free precession sequences in cardiac long and short axis at rest and after administration of 0,84mg/kg of intravenous dipyridamole and also 4-6 slices of spoiled fast gradient echo sequences acquired post- stress every two beats during al least two minutes at the same time of administration of 0,15mmol/kg of God-BOPTA to study myocardial perfusion.

Inducible wall motion abnormalities (IWMAs) and also global and segmental circumferential (C) and radial strain and their time to peak (TTP) were measured with dedicated software. Changes of these parameters after stress were also analyzed. Segmental ischemia analysis was performed using as standard reference the presence of inducible perfusion deficit along with stenosis ≥70% in the responsible coronary artery. Assessment of strain, inducible wall motion abnormalities (IWMAs) and perfusion were performed blindly by three independent observers using AHA standard myocardial segmentation.

Results: 203 basal and medium myocardial segments were studied. CMR strain parameters with significant association, AUROC, cut- off points and diagnostic value are shown in the table. Assessment of IWMAs in this setting showed low sensitivity, 30%, and positive predictive value 56% but high specificity and negative predictive value 90% and 76% respectively (P > 0.05).

Conclusions: 1.CTTP after stress and its change were the parameters with best diagnostic performance for diagnosis of early ischemia by CMR strain. 2. Despite their modest specificity computational assessment of strain had better diagnostic performance than visual assessment of IWMAs.

ParametersAUROCpLimits of confidenceCut-offSe/Sp
Stress CTTP0.630.0160.52-0.6535190/30
CTTP change0,330.0020.23-0.43-16393/15
CTTP: circumferential time to peak.
CTTP change: changes in CTTP stress vs rest.
Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.51

Relationships between left ventricular filling pressures and longitudinal dysfunction with myocardial fibrosis in uncomplicated hypertensive patients


Objective: We explored relationships between left ventricular filling pressures (LVFP) and longitudinal dysfunction with myocardial fibrosis in hypertensive patients without left ventricular (LV) hypertrophy.

Methods: Thirty-five hypertensive patients without echocardiographically determined LV hypertrophy underwent a complete echo-Doppler exam including Speckle Tracking and cardiac magnetic resonance with late gadolinium enhancement (LGE).

Results: LGE was identified in 13 patients (37%): mainly non-subendocardial and involving always the ventricular septum. Regardless the type of diastolic pattern, E/e' was higher (p < 0.0001) in patients with LGE than in those without LGE. All patients with LGE had E/e' > 8. Elevated LVFP (E/e' ≥ 13 or E/e'> 8 with left atrial volume index ≥34 ml/m2) were found in 39% of LGE patients (all showing LGE at the right ventricular attachment to ventricular septum) and only in 5% of patients without LGE (p = 0.01). Tissue Doppler s' velocity (p = 0.0003) and global longitudinal strain (GLS) (p = 0.0005) were lower in presence of LGE. LGE volume varied substantially with the type of quantification used (Figure), but no difference of manual with 6 standard deviations (SD), 5SD and full width at half maximum (FWHM) was found. Manual quantification showed high intra-observer and inter-observer reproducibility (mean difference and 95% CI = - 0.42± 0.82%, ICC = 0.94, p = 0.004 and -0.37± 0.81%, ICC = 0.94, p = 0.005; respectively). 6SD and FWHM were the semi-automated techniques with the highest intra- and inter-observer reproducibility (both p < 0.0001). E/e' correlated with mean LGE volume quantified manually (r = 0.75, p = 0.003), FWHM (r = 0.81, p = 0.0007) and 6SD (r = 0.74, p = 0.004). GLS correlated with LGE quantified manually (r = 0.66, p = 0.01), FWHM (r = 0.66, p = 0.01) and 6SD (r = 0.66, p = 0.01). s' correlated with LGE quantified manually (r = 0.64, p = 0.01), FWHM (r = 0.68, p = 0.01) and 6SD (r = 0.66, p = 0.01). By adjusting for age and relative wall thickness in separate multilinear regression analyses, LGE presence was independently associated with E/e' (β = 0.74; p <0.0001) and GLS (β = 0.61; p = 0.003) or s' (β = -0.59; p < 0.005).

Conclusion: Even in absence of LV hypertrophy, in hypertensive patients LVFP and GLS are independently associated with evidence and magnitude of LGE. LVFP increase and longitudinal dysfunction should be considered as indicators of the extent of myocardial fibrosis induced by pressure overload.

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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.52

Predictive Clinical Factors of Tissue Damage Severity in Reperfused Acute Myocardial Infarction as Visualized by Cardiac Magnetic Resonance


Primary percutaneus coronary intervention (PCI) has been shown to decreased mortality in patients with ST -segment elevation myocardial infarction (STEMI) reperfused by primary PCI, nevertheless its usefulness to preserve myocardial tissue is influenced by some clinical and technical factors. We aim to study which factors are associated with size and severity of myocardial damage as visualized by cardiac magnetic resonance (CMR) in patients with STEMI reperfused by primary PCI.

Methods: Consecutive patients with STEMI were studied by CMR in a first week post -STEMI and clinical and imaging data were collected. CMR protocol included short and long axis b-SSFP cine sequences, STIR sequences in identical slices to cine sequences to quantify myocardial mass at risk (RA) and also early (i.e. 1-2 minutes) and late (i.e. 5-8 minutes) post contrast LGE- FGE sequences to asses mass of microvascular obstruction and necrosis as shown in fig1. Quantification of necrosis and OMV mass was performed with dedicated software.

Necrosis ratio was derived as percentage of risk area (NR) and microvascular damage was analyzed as percentage of necrosis mass (MVOR). Demographic data, cardiovascular risk factors, TIMI flow prior PCI, successful trombectomy, severity of associated coronary artery disease and delay of revascularization (i.e. total ischemic time (IT), door to device time, pain to drug time and transfer delay) were also analyzed. Linear regression multivariate analysis was employed to find the best predictive model for cellular and vascular myocardial damage as visualized by CMR.

Results: Seventy one patients, 55 (76%) males, mean age 65± 13 years were included. All but one of patients had TIMI 3 flow in culprit artery after PCI. Necrosis ratio was significantly associated with pain to drug time (PTD) as shown by the algorithm: NR = 0.3PTD-173. (R = 0.3, P = 0.04). Nevertheless total ischemic time (IT) was the only independent predictor of microvascular damage as shown by the algorithm: OMVR= IT 0.5 (R = 0.52, p < 0.001)

Conclusions: 1. Necrosis ratio is significantly associated to time to drug in multivariate analysis. 2. OMV ratio is significantly predicted by total ischemic time.

OMV ratio: (OMV mass in early LGE sequences/Necrosis mass in late LGE) sequences)x100.

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Figure 1. left panel: LGE-FGE late enhancement sequences: right panel LGE-FGE early enhancement sequences.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.53

Which CMR derived parameter predicts better the need of invasive treatment in aortic coarctation?


Severity of aortic coarctation (AC) is actually evaluated using clinical and imaging parameters in a comprehensive manner. We aim to analyze which cardiac magnetic resonance (CMR) derived parameters predicts better the need of surgical or percutaneous treatment of aortic coarctation.

Methods: Consecutive patients with AC referred for CMR were selected. Patients without focal stenosis or loss of follow up were excluded. Clinical data were obtained reviewing medical records with a range of follow up (1-70 months). CMR protocol includes: 1.Angiographic evaluation with multiplanar reconstructions to estimate the minimum diameter and area at proximal aorta indexed by body surface area and relative stenosis (RE) referred to the maximum diameter of distal descending aorta; 2. Physiological evaluation with phase-contrast sequences quantifying maximum velocity post-coarctation, derived gradient and flow pattern in thoracic aorta expressed as flow increase rate (FIR= distal thoracic aorta flow–proximal thoracic aorta flow)/proximal thoracic aorta flow %.)

Results: 105 patients 21 (78%) male, mean age (25+ 15 years), 12 excluded, 5 due to suceptibility artefacts, 2 due to absence of focal stenosis and five for losing follow up. Ninety seven patients, 50 of them with native AC were finally studied. Twenty seven (28%) required treatment during follow up and in 9 of them (9.3%) was percutaneous. Area under receiver operator characteristics curves (AUROC), statistical significance, cut-off points and confidence limits are shown in the table. Associated variables were entered into a multivariate model in order to find the best model to predict the need for intervention within a year after CMR. The best diagnostic model included both RE and FIR and entering FIR in the evaluation accounts for 11.5 % more patients correctly predicted over only anatomic evaluation. In addition if Cox model is used for evaluation FIR is the only independent predictor with HR de 1.1 for every 1% increase in FIR.

Conclusions: 1. Flow pattern in thoracic descending aorta expressed as flow increase rate is the CMR parameter that predicts better the need of invasive treatment of aortic coarctation with HR of 1.1 every 1% increase in FIR. 2.Entering FIR in the evaluation accounts for 11.5 % more patients correctly predicted over anatomic evaluation using ER within the first year after CMR.

VariablesAUROCPConfidenceCut-offS/E %
Minimum diameter(i)0.72<0,050.14 -0.425mm/m292/53
Peak gradient0.600,30.43 -0.7720mmHg77/50
Flow increase rate%0.90<0,0010.82-0.9815%88/99
Maximum velocity0.600,30.43 -0.772.2m/seg.77/50
Relative stenosis0.85<0,0010.75 -0.9548%82/79
Minimum area (i)0.84<0.0010.72-0.9533mm289/73
Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.54

Contrast-enhanced magnetic resonance tomography in patients with supraventricular tachyarrhythmias


The aim of this study was quantitative assessment of the relationship of signs of damage to the atrial myocardium revealed with using contrast-enhanced MRI (CE MRI), with the risk of development of supraventricular tachyarrhythmias.

Methods: The study included 34 patients (29 men, 5 women, aged 54 ± 9). Patients were assembled into two clinical groups: 1 - with single supraventricular and ventricular extrasystoles or with episodes of atrial fibrillation (14); 2 - with frequent episodes of paroxysmal supraventricular tachyarrhythmias (20) and the control group, without signs of clinically significant atherosclerosis (9 persons).

All patients underwent CE MRI of the heart (contrast agent (CA) was injected at a dose of 0.1 mmol/1 kg body weight). According to the MRI the volume of the left atrium (LA), cm3; index of enhancement (IE) T1-WI of the largest area in the LA; the volume of accumulation of CA in the area of its greatest accumulation cm3; total volume of the accumulation of CA in the LA, cm3 were determined.

Results: In Group 2 the accumulation of CA was of multifocal character in 17 of 20 patients (p <0,05, criterion χ2), whereas in Group 1 multifocal character was seen only in 1 patient. In Group 2 the volume of LA was significantly higher compared to Group 1 (94.3 ± 10.2 cm3 и 55.3 ± 9.5 cm3, respectively). Patients in whom the volume of the LA was more than 80 cm3 tended to develop persons atrial tachyarrhythmia (probability 90%). A statistically significant difference was determined by the IE between the groups (1.43 ± 0.07 vs. 1.15 ± 0.04): the IE > 1.27, meant belonging to Group 2. The volume of CA accumulation in area of the greatest accumulation (0.516 ± 0.111 and 0.279 ± 0.085 cm3, p < 0.05) and total amount of accumulation of the LA (0.769 ± 0,212 and 0.325 ± 0.103 cm3, p<0.05) were significantly higher in Group 2. The combination of signs: atrium expansion >80 cm3, the IE > 1.27, the multiple character of the accumulation of CA - points to the inevitability of the development of supraventricular tachyarrhythmias.

Conclusion: CE MRI of atrial myocardium is an important additional method of investigation and prediction of development of supraventricular arrhythmias.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.55

Prognostic Value of CMR Imaging Biomarkers on Outcome in Peripheral Arterial Disease: a 6-year Follow-up Pilot Study


Objectives: To explore whether cardiovascular magnetic resonance (CMR) imaging biomarkers show prognostic value of outcome after six year follow-up in patients with symptomatic peripheral arterial disease (PAD).

Methods: Forty-two consecutive patients (mean age 64 ± 10 years), referred for contrast-enhanced MR angiography (CE-MRA) evaluation in the work-up for PAD, were included. In all patients, a comprehensive CMR examination was performed consisting of multi-station CE-MRA of the infra-renal aorta and run-off vessels, carotid vessel wall imaging from dual-inversion black blood imaging, cardiac cine imaging using steady-state free-precession, and assessment of the proximal and distal aortic pulse wave velocity (PWV) from two high-temporal through-plane velocity-encoded MRI acquisitions placed perpendicular to the aorta. After a follow-up period of 72 ± 5 months patients were categorized for outcome: all-cause mortality, cardiac event (coronary artery disease, heart failure, myocardial infarction) or cerebral event (stroke, transient ischemic attack).

Results: At baseline, mean MRA stenosis class (i.e., the average stenosis severity visually scored over 27 standardized segments on a 5-point scale) over all patients was 1.6 ± 0.5. Mean proximal aorta PWV was 9.8 ± 6.3m/s and descending aorta PWV 9.1 ± 3.8m/s. Mean left ventricular ejection fraction (LVEF) from short-axis planimetry was 58 ± 10% and mean carotid normalized wall index 0.46 ± 0.07. During follow-up, six patients had died, six patients experienced a cardiac event and three patients a cerebral event. Binomial logistic regression analysis showed mean stenosis class as a significant independent predictor for all-cause mortality (beta 3.0 ± 1.3, p = 0.02). Descending aorta PWV and age were interrelated with PAD stenosis severity and associated with all-cause mortality, but were not significant independent predictors. For occurrence of a cardiac event, LVEF was a significant independent predictor (beta -0.20 ± 0.08, p = 0.008). None of the CMR imaging biomarkers was a significant independent predictor for cerebral event.

Conclusion: Mean MRA stenosis class was a significant independent predictor for all-cause mortality in patients with symptomatic PAD after a follow-up period of six years. LVEF was a significant independent predictor for cardiac morbidity in this patient population. Further studies with larger patient groups and a longer follow up period have to confirm these results of the present pilot study.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.56

Dobutamine-Stress-CMR in Young Adults after Arterial Switch Operation as Neonates


Introduction: Neonatal arterial switch operation (ASO) is the standard of care in patients with simple transposition of the great arteries (TGA). Follow up can be complicated by stenosis or kinking of the reinserted coronary arteries causing myocardial ischemia, and, after Lecompte maneuver, stenosis or kinking of the central pulmonary arteries (PA) resulting in abnormal left/right pulmonary blood flow distribution (PBFD).

The aim of this study is to evaluate the rate and extend of stress induced myocardial ischemia and of abnormal differential PBFD at rest and under dobutamine stress.

Methods: 23 patients (age 18-28; 16 male) underwent CMR (1,5 Tesla) at rest (coronary scan, cine, phase contrast flow) and under dobutamine/atropine stress (cine, phase contrast flow pulmonary perfusion), followed by angiography and late gadolinium enhancement (LGE).

Results: Coronary arteries: 1x known prox. LAD occlusion (collateralized via RCA; coronary type AB1), 1x proximal LCA-occlusion, LIMA-bypass). No other stenosis or kinking of the proximal coronary arteries. Coronary classification (Sauer/Gittenberger-de Groot): 14x A1 (normal type), 5x AB1 (RCX originates from RCA), 4x B1 (right single ostium, LCA retroaortal). 3 patients were reclassified compared to the operation report.

Dobutamine-stress: 21/23 reached target heart rate; 1x abort at 120/min (20 µ dobu) due to complex ventricular extrasystoles, 1x abort at 160/min due to problems with ECG-triggering. 1 patient with known LAD occlusion showed strong chest pain and hypokinesia in 1 segment under maximum stress.

Pulmonary perfusion at rest: 2 patients showed relevant stenosis of the mean PA. 2 patients had abnormal PBFD (>2:1). 3 patients had prior intervention for RVOT/PA-stenosis. (PBFD > 2:1). -> cumulative rate of relevant RVOT/PA stenosis 7/23 (30%).

Pulmonary perfusion under dobutamine stress: there was no relevant difference of PBFD under dobutamine stress compared to rest-PBFD (Friedman test: p= 0,75; see table). On individual patient level, no worsening of abnormal PBFD was found.

Conclusion: CMR found no new proximal coronary stenosis or kinking. Coronary type was reclassified in 3 patients. 2/23 DSMR were pathologic. 4 patients had relevant RVOT/PA stenosis, 2 patients had abnormal pulmonary blood flow distribution at rest (PBFD >2:1). PBFD did not worsen under dobutamine stress.

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LGE: no myocardial scarring. 1 patient had intramyocardial fibrosis.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.57

Impact of posteromedial papillary muscle infarction on mitral regurgitation after ST-segment elevation myocardial infarction


Introduction: Recently there is a growing interest in the role of papillary muscle infarction (PMI) as a cause of mitral regurgitation and unfavorable outcome after ST-segment elevation myocardial infarction (STEMI). We hypothesized that PMI of the posteromedial papillary muscle might be associated with a higher incidence of mitral regurgitation (MR) after STEMI.

Methods: We included 242 patients with first STEMI who underwent a late-enhancement cardiac magnetic resonance scan within a median of 2 (IQR: 2-4) days and echocardiography within 3 (IQR: 2-5) days after primary angioplasty for the index event. PMI was scored based on the extent of LE in at least 2 consecutive short axis slices (AL-PMI: anterolateral PMI, PM-PMI: posteromedial PMI). MR was reviewed and graded by at least one experienced observer based on the recommendations of the European Association of Echocardiography.

Results: PMI occurred in (40%) of the study population. 23% had isolated PM-PMI, 7% AL-PMI and 11% had infarction of both PM. We observed a higher incidence of PM-PMI (28% versus 13%) and a lower incidence in AL-PMI (4% versus 13%) in patients with MR. Patients with isolated PM-PMI had higher odds for the occurrence of MR than patients with no-PMI, AL-PMI or both-PMI (OR: 2.62, CI: 1.27–5.40, p < 0.01), whereas isolated AL-PMI resulted in a decreased odds-ratios for MR (OR: 0.267, CI: 0.1–0.751, p < 0.01). Furthermore age above the median of 56 years resulted in an increase in the odds for MR (OR: 2.400, CI: 1.391–4.140, p < 0.01). In patients with non-anterior STEMI patients with PM-PMI had increased odds for the occurrence of MR (OR: 3.19, CI: 1.21–8.40, p < 0.02).

Conclusion: Isolated PM-PMI increases, and isolated AL-PMI decreases, the odds for MR after STEMI independent of infarct location.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.58

Role of cardiac magnetic resonance imaging in assessment of left ventricular hypertrophy

aSara E. Fawal, MD and aMamdouh Zidan, MD, FRCR


Background: Determination of the etiology of left ventricular hypertrophy (LVH) is a common clinical problem that can be challenging, because pathological forms of LVH present with overlapping phenotypes in various diseases of the myocardium.

Left ventricular hypertrophy is frequently encountered in the setting of uncontrolled systemic hypertension and aortic stenosis. While aortic stenosis is a straightforward differential diagnosis, other conditions can be difficult.

In some cases, the differentiation between hypertensive heart disease and other cardiomyopathies causing ventricular hypertrophy may be difficult.

A number of other conditions can mimic LVH such as infiltrative diseases, hypertrophic cardiomyopathy (HCM), Fabry's disease, cardiac sarcoidosis, aortic stenosis, and exercise-induced ventricular hypertrophy or athlete's heart.

The unique capacity of CMR to non-invasively characterize myocardial tissue represents an important advantage over other non-invasive imaging modalities.

Echocardiography is still the first-line imaging modality for assessment of myocardial disease, but it has its limitations, including restricted echo windows and poor tissue characterization ability. With technical advances in the field of cardiovascular magnetic resonance imaging, it has been shown to be helpful in reaching a more precise diagnosis in most of the cases.

Patients and Methods: This study was conducted on 54 patients who showed various patterns of left ventricular hypertrophy by echocardiography. All patients were examined by cardiac magnetic resonance imaging (Philips Achieva 1.5T). Sequences included ECG-gated SSFP, black-blood imaging, phase contrast flow imaging, and late gadolinium enhancement.

Results: MRI confirmed the diagnosis of HCM in 18 patients, assessing the various phenotypes and patterns of left ventricular hypertrophy. It showed left ventricular outflow tract obstruction in 9 of those 18 patients, and midcavitary obstruction in 6 patients. Myocardial fibrosis was detected in 9 of the 18 patients by late gadolinium enhancement.

Eleven patients were diagnoses by MRI as having cardiac amyloidosis, another 9 patients as having other types of restrictive cardiomyopathies further assessed by laboratory and pathologic testing.

In 3 patients, left ventricular hypertrophy was attributed to aortic stenosis, and the remaining 9 patients the cause of LVH was attributed to systemic hypertension.

Conclusion: Cardiac MRI is a valuable tool in assessment of left ventricular hypertrophy, for assessment of ventricular size, function, global and regional mass, presence of outflow tract and cavitary obstruction, as well as myocardial fibrosis. The overall acquired data can help guide the diagnosis and management of the underlying cause of left ventricular hypertrophy.

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42-year-old male patient with hypertension and palpitations. 4C and SA images captured from SSFP sequences, showing LVH, mild pericardial effusion, and a mitral regurgitation jet with bi-atrial dilatation. Ventricular volumes were normal with low-normal systolic function, with diastolic dysfunction.

LGE image in SA plane acquired after challenging TI scout, showing dark blood-pool with global subendocardial LV and RV wall enhancement. Features were suggestive of amyloidosis.

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50-year-old female patient suffering from hypertension and rheumatoid arthritis. LGE images in SA and 4C plane, showing diffuse ring of subendocardial LV wall enhancement. Suggested diagnosis was amyloidosis versus Loeffler endocarditis, biopsy and laboratory investigations were requested.

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19 year old female patient suffering from palpitation and effort intolerance. 4C and SA images captured from SSFP sequences. 4C image in systole, showing LVH mainly midcavitary and apical, with obliteration of LV cavity in systole. SA image at the apical region in diastole also showing LVH. LGE image in SA plane, showing no evidence of myocardial fibrosis. Features were suggestive of apical HCM.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.59

Using intrinsic Cardiac Shear Waves to measure Myocardial Stiffness: Preliminary results from Patients with Heart failure with preserved Ejection Fraction


Background: Heart Failure with preserved Ejection Fraction (HFpEF) is common and challenging to diagnose. Transient Magnetic Resonance Elastography (tMRE) has been shown to detect stiffness in many organs and so we have applied this concept in vivo to measure myocardial stiffness.

Methods: Aortic valve closure results in a shear wave that propagates through the myocardium. The speed of this wave can be measured if the sequence is timed to the exact valve closure time. Individual sequences are ECG and navigator gated and take approximately 90 seconds, the complete scan including planning takes approximately 40 minutes. Increased myocardial stiffness results in increased speed of shear wave propagation.

Our study has three parts: sequence development and implementation on a clinical 3T MR scanner (Philips Medical Systems), a volunteer study (n = 5) to assess cardiac and respiratory motion compensation strategies and the sensitivity of the motion encoding gradients; and a patient study (n = 8) comparing with traditional echocardiographic measures of diastolic dysfunction and serum NT proBNP.

Results: The tMRE sequence was successfully developed and implemented. Motion-encoded images (motion sensitized gradient at 165Hz) demonstrated myocardial wall shear waves associated with the aortic valve closure at 329ms (range 280-375ms) after the R wave. tMRE successfully showed a difference in speed of propagation between volunteers and patients (speed volunteers 12.6m/s ± 2.0m/s, speed patients 21.4m/s ±4.9m/s, p < 0.05, Figure 1). One patient who had invasive pressure volume loop studies was found to have increased left ventricular end diastolic pressure (LVEDP) and prolonged tau (represents the exponential decay of the ventricular pressure during isovolumic relaxation)–this patient had a faster speed of sheer wave propagation in tMRE. There was no clear correlation shown between the speed of propagation in patients and the degree of diastolic dysfunction (measured by degree of LVH, LA dilatation and E/E') but the Pearson coefficient with plasma NT-proBNP was 0.63 in patients presenting with acute heart failure.

Conclusions: We have successfully developed and applied a new technique to quantify myocardial stiffness in vivo from shear waves generated by aortic valve closure.

tMRE is patient friendly and does not require a transducer. We have shown that tMRE has potential to be an important diagnostic tool for the early detection of myocardial stiffness.

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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.60

Relationship of cerebrovascular reactivity and MRI pattern of carotid atherosclerotic plaque


Objectives: The ultrastructure of carotid and coronary atherosclerotic plaques is now discussed among factors determining risk of future ishaemic events. The aim of our study was to compare in patients with carotid atherosclerosis the structure of atherosclerotic plaques imaged using MRI with cerebral vascular reactivity quantified by echo.

Methods: The patients population comprised 21 persons (as old as 64 ± 13) with hemodynamically significant carotid artery stenosis > 70 % of lumen, quantified with high-resolution MR imaging of arterial wall. To assess the cerebrovascular reactivity transcranial ultrasound of middle cerebral artery was carried out with quantification of blood flow parameters at rest and during the stress tests: first with breath holding and then with hyperventilation, with calculation of reactivity index.

From visual evaluation of MRI of carotid stenoses four types of plaques were assembled: mixed plaque with severe fibrosis and lipid core, plaque with lipid component, with intraplaque hemorrhage and calcified plaque.

To assess the patterns of autoregulative reaction to the stress test the following conventional patterns were used: positive reaction (reactivity index 1.1-1.4), negative reaction (reactivity index 0.9-1.1) and paradoxical reaction (reactivity index of less than 0.9).

Results: It was found that at breath holding hypercapnic test there is a statistically significant association between MRI plaque structure and type of the reaction (p = 0.081), whereas at the test with hyperventilation no significant differences were found. At breath hold test in 56 % of patients with MR images of plaque hypointense on T1-weighted scans and hyperintense on T2-weighted ones unidirectional positive response was observed; pathologic unidirectional negative response or multidirectional response were observed in patients with MR evidence of hemorrhagic plaques hyperintense on T1-weighted scans and hypointense on T2-weighted ones.

Conclusion: Atherosclerotic lesions of the internal carotid artery with intra-plaque hemorrhage are accompanied with critical deterioration of cerebrovascular reactivity. Probably any hemorrhage to carotid plaque could be assumed as critical risk factor and requires removal of the plaque by carotid endarterectomy. High-resolution MRI of carotid arterii may be suggested as screening test in all patients of risk groups of atherosclerosis.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.61

Feasibility study of an MR conditional pedal ergometer for cardiac stress MRI–preliminary results in healthy volunteers and patients with suspected coronary artery disease


Background: Stress cardiac magnetic resonance imaging (CMR) is increasingly being used to assess chest pain in patients with known or suspected coronary artery disease and is most often performed by use of pharmacological agents such as adenosine and dobutamine. However, exercise stress testing provides a physiological challenge to the myocard and is generally regarded as superior to pharmacological stress testing. The purpose of this study was to evaluate the use of an MR conditional pedal ergometer for cardiac stress CMR in healthy volunteers as well as patients with suspected coronary artery disease.

Methods: All participants (10 healthy volunteers (45 ± 15, 10% women) and 11 patients (60 ± 8, 27% women) with known or suspected coronary heart disease) underwent exercise stress MRI at a whole-body 3 Tesla MR system. CMR protocol included first-pass perfusion (FPP) and real-time CINE imaging before and after exercise stress with a MR conditional pedal ergometer and late enhancement (LE) PSIR sequences after stress as well. Patients were examined in short term prior to elective coronary angiography (CAG). Image-quality regarding artifacts as well as visual analysis of left ventricular wall motion abnormalities (LVWMA) and FPP stress defects were rated by two experienced radiologists, functional parameters were determined from short-axis cine MR sequences before and after exercise stress.

Results: 88% of real-time Cine studies (90% of Rest-Cine images, 85% of Stress Cine images) were regarded with good to slightly impaired image-quality, whereas there was no significant difference of Cine image quality between patients and healthy volunteers (p > 0.05). Left ventricular ejection fraction (LV EF) improved from resting to stress conditions in both groups, healthy volunteers (LV EF 62 ± 6 to 65 ± 7 p =0.04) as well as patients (LV EF 55 ± 6 to 60 ± 7, p = 0.003), whereas EDV and ESV did not show significant alterations. 5/11 patients showed regional LVWMA on stress images. Out of these patients two patients get coronary stenting of corresponding vessels whereas one patient showed an instent restenosis at CAG with subsequent balloon-PTCA and another patient was conducted to bypass grafting. However, stress FFP sequences revealed only in two of the patients with LVWMA a subendocardial stress defect. LE sequences showed a subendocardial scar from silent myocardial infarction in one patient.

Conclusion: Cardiac stress CMR by the use of a MR conditional pedal ergometer is feasible with the ability to acquire images with good to slightly impaired quality. Exercise stress CMR provides physiological dynamic conditions to evaluate contractile reserve as well as detection of LVWMA. However, stress defects at FPP seem to fail a reliable presentation in this setting. Further improvements are necessary and confirmations in larger trials are needed.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.62

Pulmonary valve replacement for severe pulmonary stenosis has a positive effect on left ventricular remodeling


Background: Right ventricular (RV) volumes and function play a key role in the decision-making on pulmonary valve replacement (PVR) in patients with pulmonary valve stenosis (PS) or regurgitation (PR). Although left ventricular (LV) function has been described to be equally important as RV function in these patient's symptomatology and prognosis, little is known about LV response to PVR. Therefore, we aim to evaluate LV remodeling after PVR in PS or PR patients.

Methods: We performed cardiovascular magnetic resonance imaging (CMR) before and after PVR in 18 consecutive patients; nine with severe PR (mean age at intervention 27 ± 16), and ten with severe PS (mean age at intervention 27 ± 8). Outcome parameters were change in LV end-diastolic (ΔLVEDV), LV end-systolic (ΔLVESV) volumes, and ejection fraction (ΔLVEF), before and after PVR.

Results: Most patients had congenital aortic stenosis, with previous Ross procedures (6 patients) or Tetralogy of Fallot (5 patients). Fifteen patients had undergone previous PVR (6 in the PR group; 9 in the PS group). After PVR, patients with severe PR showed only minor change in LVEDV, in LVESV and in LVEF (ΔLVEDV 1.5 ml/m2, p = ; ΔLVESV 0.1 ml/m2; ΔLVEF 1.2%; p = 0.7). However, there was an important trend in positive remodeling of the LV in patients who underwent PVR with severe PS (ΔLVEDV 8.5 ml/m2; ΔLVESV -1.1 ml/m2; ΔLVEF 5.1%; p = 0.08).

Conclusion: Patients who undergo PVR for PS seem to benefit more from biventricular remodeling compared to those who undergo PVR for PR. This superior LV remodeling could be due to superior remodeling of the pressure overloaded RV, with subseqent disburden of the LV, or to intrinsic characteristics of the LV, which was pre-operatively protected from overload by the PS.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.63

The RV after cardiac surgery, more resilient than thought: multiparametric quantification shows altered rather than reduced function


Background: Right ventricular (RV) function declines after cardiac surgery, particularly long axis function. Three principal speculated causes are suggested: (a) loss of constraint when opening pericardium; (b) intra-operative ischemia (c) post-operative tethering. The impact of relative contributors of RV function (AV plane descent, apical movement) is obscure. The complexity of cardiac operation is also thought to contribute to RV impairment. We sought to untangle these factors by comparing pre- and post-surgery RV function changes in a cohort of patients with aortic valve replacement (AVR) and 1/3 had in addition grafting (CBAG).

Method: 81 patients were scanned prior to, and 1 year following AVR (n = 59) or combined AVR and CABG (n = 22). RV volume and function were calculated with standard techniques. RV longitudinal function was assessed as follows, Figure 1a.

• A - Tricuspid annular displacement: TAD, distance measured between tricuspid annulus in diastole and systole

• B - TAPSEout, distance between tricuspid annulus and a fixed point on chest wall in diastole and systole

• C - RV apical motion, distance between the RV apex and a fixed point on the anterior chest wall in systole and diastole.

• D- TAPSEin, distance between tricuspid annulus and RV apex in diastole and systole (includes apical motion)

Results: RV volumes and ejection fraction were in normal limits, pre and post, Table 1.

RV longitudinal function however assessed using tricuspid annular displacement and TAPSEout declined after surgery by 41% (p < 0.0001) and 43% (p < 0.0001) respectively. Apical motion increased post operatively by 52% (p < 0.0001), meaning that overall TAPSEin only fell by 21% (p < 0.0001), Figure 1b.

RVEF had weak correlation with each of the markers of RV longitudinal function, (r = 0.30 for TAD, p < 0.01) and considering a value of TAD <16mm alone, 84% of patients were classified as RV dysfunction post-operatively, despite preserved RVEF. There were no significant differences between the AVR + CABG and AVR alone groups in any of the measures of RV function (RVEF: 65% ± 9% versus 64% ± 9%, p = 0.88) respectively.

Conclusion: The effect of cardiac surgery on RV function is overstated, tricuspid annular displacement falls, but apical basal contraction increased in compensation. Doing additional grafts has no incremental detrimental effect on RV function. Ischaemia is not the cause of changes - tethering and/or loss of pericardial constraint appear to be the principal mechanisms of RV change.

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Figure 1. Right Ventricle after Cardiac Surgery: Methods and change in function.

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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.64

Usefulness of cardiovascular magnetic resonance to differentate coronary artery disease from non ischemic cardiomyoptathy in patients with heart failure


Introduction: We evaluated the capacity of cardiovascular magnetic resonance (CMR) to distinguish between underlying coronary artery disease (CAD) from non ischemic cardiomyoptathy in patients (pts) with left ventricular (LV) dysfunction.

Methods: We prospectively studied 140 consecutive patients with heart failure and an ejection fraction (EF) ≤40% assessed by echocardiogrpahy referred for stress CMR (1.5 Tesla). Standard protocol consisted of: 1) assessment of myocardial function at rest; 2) pharmacological stress induced either by dobutamine or by adenosine; 3) assessment of late gadolinium enhancement (LGE) sequences.

Results: All tests were performed in 140 patients, 114 males (81%), mean age 64.42 ± 12.6 years. Stress was induced using adenosine in 98 patients (70 %) and with dobutamine in 42 patients (30%). Mean duration with adenosine was 46 ± 8 minutes and with dobutamine 58 ± 8 minutes. LVEF was 30.8 ± 8.6%. Myocardial ischemia was present in 20 pts (14%). Subendocardial or transmural LGE was found in 90 (64%) pts, corresponding to a previous myocardial infarction (MI). Intramoycardial LGE was only seen in 5 pts (4%), in 3 with dilated cardiomyopathy (DCM) and in 2 with myopericarditis. No LGE was observed in 35 pts (25%) with DCM.

Conclusion: With the use of CMR we could clearly distinguish pts with CAD from those with non ischemic cardiomyopathy. Of note, a high percentage of pts with DCM had no LGE, suggeting a potential recuperation of the LV function.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.65

What does CMR add to the ESC Risk Prediction Model to Assess the Occurrence of Sudden Cardiac Death in Patients with HCM?


Objective: Hypertrophic cardiomyopathy (HCM) is a complex genetic heart disease. Although the overall risk for sudden cardiac death is relatively low some patients with HCM die suddenly from fatal arrhythmic events. The recently published ESC clinical risk prediction model uses clinical parameters to estimate the probability of sudden cardiac death (SCD) at 5 years. Since this risk prediction model does not take into account CMR parameters, the aim of our study was to compare patients with low, intermediate and high ESC risk scores of SCD according to CMR characteristics.

Methods: In 149 HCM patients the ESC risk score was retrospectively calculated according to the following formulas: Prognostic index = [0.15939858 x maximal wall thickness(mm)] - [0.00294271 x maximal wall thickness2 (mm2)] +[0.0259082 x left atrial diameter (mm)] + [0.00446131 x maximal(rest/Valsalva) left ventricular outflow tract gradient (mm Hg)] +[0.4583082 x family history SCD] + [0.82639195 x NSVT] +[0.71650361 x unexplained syncope] - [0.01799934 x age at clinical evaluation (years)] and probability of SCD at 5 years =1–0.998exp (Prognostic index). CMR characteristics were compared among patients with low (risk of SCD < 4%), intermediate (risk of SCD 4- < 6%) and high risk (risk of SCD ≥ 6%).

Results: Of 149 patients with HCM 121 (81%) belonged to the low, 18 (12%) to the intermediate and 10 (7%) to the high risk group. The probability of SCD at 5 years was 2 ± 1% in the low risk, 5 ± 1% in the intermediate and 12 ± 8% in the high risk group. Comparing CMR characteristics, left and right ventricular EF as well as left and right ventricular volumes were comparable among the different risk groups. However, patients with a high ESC risk score revealed a significantly higher extent of fibrosis defined as extent of LGE 29 ± 22 compared to patients with an intermediate risk score and an exent LGE % of 12 ± 12 (p = 0.02) and patients with a low risk score and an extent LGE % of 10 ± 11% (p < 0.001).

Conclusion: Patients with a high clinical risk of SCD according to the ESC clinical risk prediction model reveal a higher extent of LGE compared to patients with HCM and lower risk scores. Therefore, the extent of LGE seems to be an additional risk marker in these patients.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.66

Detecting Progression of Diffuse Interstitial Fibrosis in Alstrom Syndrome


Introduction: Alstrom Syndrome (ALMS) is a rare inherited disorder caused by mutation in ALMS1 gene. The syndrome is a multi-system disorder with exaggerated features of metabolic syndrome and although rare, provides a monogenic model for end-organ fibrosis and as a paradigm for the effects of severe metabolic syndrome. Adults with ALMS have a high risk of death from heart failure in their twenties due to a cardiomyopathy which (in small post-mortem series) is characterised by coarse fibrosis on histology. Our previous work has identified expansion of the extracellular space (ECV) consistent with diffuse interstitial fibrosis in over half of asymptomatic ALMS patients compared to controls. The aim of this study was to investigate the longitudinal change in ECV and assess the impact on ventricular structure and function.

Methods: A prospective longitudinal cohort study of patients attending the national service for ALMS at the Centre for Rare Disease in Birmingham from 2012. At referral and on annual follow up, all subjects underwent comprehensive LV and RV assessment with cardiac MRI (CMR 1.5T Siemens Avanto). The presence of diffuse interstitial myocardial fibrosis was assessed using native myocardial T1 relaxation mapping and extracellular volume (ECV) in the LV septum (MOLLI) using cvi42® (Circle Cardiovascular Imaging). Coarse replacement fibrosis was assessed using standard late gadolinium enhancement imaging.

Results: In total 14 patients (male gender 71%, age 28 ± 8years) had baseline and follow up data (median 1.7 [1.1-2.8] years). CMR data is presented in Table 1. The native LV myocardial T1 values and ECV were increased in the septum at basal and mid levels at follow up. Left ventricular mass increased (54 ± 9g/m2 vs. 62 ± 12g/m2) but with a reduction in septal myocardial intracellular volume (ICV 0.74 ± 0.06 vs. 0.68 ± 0.04, p < 0.05) suggesting ECV expansion rather than myocyte hypertrophy was the driver. There were no differences in LV or RV volumes or RVEF. Four patients had LGE; two patients had focal at RV insertion points LGE and two patients had mid-wall LGE in the basal infero-lateral segments.

Conclusion: ALMS is associated with increases in ECV and progressive change in T1 values over time that reflects progression of diffuse interstitial fibrosis in asymptomatic adults. Cross-sectional studies have identified ECV as a biomarker of cardiovascular “vulnerability” but longitudinal tracking has the potential to highlight those at greatest risk.

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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.67

Diffuse fibrosis in the ventricles of patients with transposition of great arteries late after atrial switch


Objectives: In adult patients with transposition of great arteries late after atrial switch (Mustard or Senning), the subaortic morphologic right ventricle (RV) is hypertrophic, while the subpulmonary morphologic left ventricle (LV), is usually hypotrophic.

The extent of diffuse fibrosis in the RV and LV in these patients remains unclear. Therefore, the aim of this study was to determine myocardial extracellullar volume (ECV) in both ventricles in these patients.

Methods: We determined ECV by cardiac magnetic resonance (CMR) in 10 patients (36.8 ± 5.3 years old), without relevant pulmonary stenosis, late after atrial switch by acquiring T1-maps of the myocardium before and 10 minutes after injection of Gadolinium-based contrast agent.

Results: ECV of the LV was significantly increased compared to the RV (LV 36 ± 4% vs. RV 27 ± 3%, p = 0.05).

Conclusions: In patients late after atrial switch, ECV of the hypotrophic, subpulmonary morphologic LV is significantly increased compared to ECV of the hypertrophic, subaortic morphologic RV. ECV of the RV is in the upper normal range. Increased ECV in the LV may be due to diffuse fibrosis, induced by long time reduced activity of LV, or simply due to relatively higher ECV surrounding hypotrophic myocardial cells of the LV.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.68

Utility of Cardiac Magnetic Resonance in the diagnosis and stratification of arrhythmic risk in patients with confirmed or suspected ventricular arrhythmias


Purpose: The etiological diagnosis of cardiac arrhythmias is often difficult. Cardiac Magnetic Resonance (CMR) as gold standard in anatomical and functional cardiac evaluation can be used as a fundamental technique in the diagnostic evaluation of patients (P) with cardiac arrhythmias. The purpose of the study is to determine the impact of CMR in the diagnosis and stratification of arrhythmic risk in P with confirmed or suspected ventricular arrhythmias.

Methods: Prospective study during 3 years where we evaluate all P who underwent CMR for etiological clarification of aborted sudden cardiac death, ventricular arrhythmias, suspected structural heart disease with high arrhythmic potential or unexplained recurrent syncope. We excluded all P who already had etiological diagnosis by other diagnostic methods. Acquisitions were performed in all P to evaluate anatomically and functionally the right and left ventricles and to look for the presence of late enhancement.

Results: A total of 54 P were evaluated, of which 32 were male. The mean age was 45,8 ± 16,58 years. The indications for the CMR were: aborted sudden cardiac death due to ventricular fibrillation - 4 P; sustained Ventricular Tachycardia (VT) - 8 P; non-sustained VT - 3 P; very frequent ventricular extrasystoles - 25 P; suspected structural heart disease with high potential arrhythmic–5 P and unexplained syncope - 9 P.

In only one patient it was not possible complete the CMR due to gating artifacts conditioned by the presence of cardiac arrhythmias and respiratory synchrony. In 7 P, we verified the presence of gating artifacts conditioned by the presence of cardiac arrhythmias which precluded the accurate measurement of ventricular volumes, but did not affect the diagnostic accuracy. Overall, CMR was normal in 39 P, in 5 P we found nonspecific changes deserving a future control and in 10 P it was possible to establish a definitive diagnosis which was unknown before the realization of the CMR. The diagnoses established were: arrhythmogenic right ventricular dysplasia - 2 P, left ventricular non compaction - 3 P, silent myocardial infarction sequel–2 P; acute myocarditis–1 patient; hypertrophic cardiomyopathy–1 patient; and amyloidosis–1 patient.

Conclusions: CMR is a technique with high spatial resolution, feasible and safe which allowed the diagnosis and risk stratification in 17% of our study population of patients with high arrhythmic potential when the first-line tests are normal.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.69

Size matters: pulmonary veins geometry by cardiac magnetic resonance imaging in atrial fibrillation patients


Background: The study of pulmonary vein (PV) anatomy is a crucial step prior to successful ablation therapy for atrial fibrillation (AF).

PV anatomy is variable in the number of independent veins draining to the LA, in their ostial shape and course, and this can be visualised with Cardiovascular Magnetic Resonance (CMR). PV anatomy was investigated in a small series of consecutive patients referred for a clinical CMR exam before ablation therapy for AF.

Methods: 10 consecutive patients aged 56 ± 11.6 years old were referred for a pre-­procedural clinical CMR from Oct 2015 to Jan 2016.

Imaging was performed using a 3 Tesla scanner (Siemens Avanto, Siemens, Erlangen, Germany). Magnetic resonance angiograms (MRAs) were obtained with a breath-­hold 3D fast spoiled gradient-­echo imaging sequence in the coronal plane, after the administration of gadolinium contrast agent. All images were analyzed by a single investigator. The ostial cross-­sectional diameters, area and perimeter were measured for each PV: left upper (LUPV), left lower (LLPV), right upper (RUPV) and right lower (RLPV). Eccentricity index (a measure of the cross-­sectional shape of the vein) was calculated as a ratio maximum over minimum ostial diameter, and defined as follows: round (≤ 1.2);; oval (>1.2 and ≤1.4);; flat (>1.4).

Results: PVs measurements are presented in Table 1. Left PVs were more often flat (40% LUPV, 70% LLPV) or oval (40% LUPV, 30% LLPV), with a minimum diameter in the antero-­posterior direction. Inversely, right PVs were rounder (80% RLPV;; 50% RUPV) or oval shaped (20% RLPV;; 30% RUPV). LLPV was significantly different from RLPV in all the measurements (p < 0.05), and from RUPV in all the measurements except for the maximum diameter. No significant differences were found between LLPV and LUPV.

Conclusions: The cross-­sectional appearance of the left lower pulmonary vein differs significantly from that of the other veins. It often appears elliptically deformed which appears to be related to an interposition between the descending aorta and the left atrium. As both anatomical structures are under pressure in arterial hypertension, the relationship between atrial fibrillation and arterial hypertension may in part be related to this deformation. The prognosis of atrial fibrillation may also be related to this anomaly. Thus, further studies comparing AF population with a control group of healthy subjects are needed to better investigate a possible pathogenetic implication of our finding.

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Figure 1. Example of LLPV course.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.70

How do the differences in Left Ventricular wall measurements from Echocardiography and CMR in patients with Hypertrophic Cardiomyopathy affect current Sudden Cardiac Death Risk Scores?

Jessica Webb, BM BCh, MA MRCP FHEA,1,2 Adriana Villa, MD,2 Imane Bekri,1 Joy Shome, MD,2 Tom Teall,1 Gabriella Di Giovine,2 Eva Sammut,2 Gerald Carr-White, MD PhD,1 Khaled Al-Fakih, MD,3 and Amedeo Chiribiri, MD PhD FHEA2


Background: Hypertrophic Cardiomyopathy (HCM) is defined by the presence of increased Left ventricular (LV) wall thickness not solely explained by abnormal loading conditions. All studies investigating the prognostic value of LV hypertrophy (LVH) in HCM and the recent ESC Sudden Cardiac Death (SCD) risk stratification have used echocardiography. Studies have suggested improved accuracy measuring LV wall thickness using cardiac magnetic resonance (CMR) due to improved spatial resolution. In our institution patients diagnosed with HCM are referred for both echocardiography and CMR. Their annual risk stratification usually involves echocardiography.

Objectives: Objectives of the study were to assess the presence of any systematic difference with echocardiography and CMR in patients with HCM and to assess these results on patients' SCD risk scores.

Methods: Maximal LV wall thickness measurements were recorded by four operators on 50 consecutive patients referred for echocardiography and CMR. Maximal LV wall measurements were taken at 12 points in each patient.

Results: There were 600 CMR LV wall thicknesses, compared to only 421 that could be measured on echocardiography and for direct comparison only matched data was used. There was excellent agreement on the location of maximal LV wall thickness and the 50 measures of myocardial maximal LV wall thickness were higher on echo that CMR (echo mean 1.9cm, SD 0.5; CMR 1.6, SD 0.3 (p < 0.01)). The Bland Altman plots confirmed improved inter-observer reliability with CMR than echo (Figure 1A and B).

The SCD risk score was calculated for all 50 patients and using the different maximal wall thicknesses from echo and CMR, there was a mean difference in 5-year risk SCD of 0.49%, SD 0.45 (p = 0.37) (Figure 2).

Conclusion: Echocardiography systematically over reports maximal LV wall thickness in patients with HCM, when compared to CMR. Despite this, when LV maximal wall thickness results are entered into established SCD risk models, there is no statistically significant difference. Clinicians need to be aware of this disparity between imaging modalities.

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Figure 1. A: Bland Altman Plot for LV wall thickness measurements measured by echocardiography. B: Bland Altman Plot for LV wall thickness measurements measured by CMR.

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Figure 2. Bland Altman Plot for the difference between ESC SCD risk score for patient using echocardiography and CMR

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.71

Noninvasive assessment of intracardiac viscous energy loss in Fontan patients from 4D Flow CMR


Introduction: In the normal heart, ventricular viscous energy loss (EL) is the kinetic energy that is lost due to frictional forces between blood and surrounding structures in the ventricle and induced by blood viscosity.[1] Patients with a Fontan circulation have abnormal morphology of the atrioventricular (AV) valves and ventricles, which may promote inefficient flow-structure interaction that can increase viscous energy loss. The purpose of this study was to noninvasively assess intracardiac EL in Fontan patients with various underlying pathologies 4D flow CMR compared to the left ventricle in healthy volunteers.

Methods: 11 patients with a Fontan circulation (age 15.0 ± 5.1 years) and 11 volunteers (15.4 ± 5.7 years) underwent whole-heart 4D Flow CMR at 3T (VENC =150 cm/s, spatial resolution 3 × 2.6 × 3 mm3, 30 retrospectively reconstructed phased over one cardiac cycle). The systematic ventricle in patients and left ventricle (LV) in volunteers were segmented and EL was computed over diastole (EL_diastole), systole (EL_systole) and total cardiac cycle (EL_total), all in Joule, using the Navier-Stokes energy equations [1]. Measured EL was then normalized by stroke volume (m3). Normal range of LV viscous energy loss was derived from volunteers as the 95%CI (confidence interval). Patients' ventricular EL parameters were classified as: below, within or above 95%CI. An independent samples T-test was used to compare EL_total between both patients and controls.

Results: Patients showed significantly higher EL_total than controls (mean ± SD, 8.8 ± 3.4 vs. 4.5 vs. 0.84, P-value 0.001). Detailed results are shown in Figure 1. In three patients, EL_total was in the normal range (95% CI 3.34-6.04): two patients with hypoplastic left heart syndrome (HLHS) and one patient with tricuspid atresia (TA) with concordant VA connection. EL_diastole was in the normal range in four patients (95% CI 2.05-3.68): three HLHS patients and one patient with transposition of the great arteries (TGA). One patient with TA with concordant VA connection was below the normal range. In two patients, EL_systole was in the normal range (95% CI 0.98-2.57): one HLHS patient and one TA patient with concordant VA connection. Highest values of different EL parameters were consistently found in a TA patient with discordant VA connection.

Conclusion: Patients with a Fontan circulation show elevated ventricular viscous energy loss compared to healthy LV.


1. Elbaz et al. MRM 2016 (in press)

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Figure 1. Viscous energy loss in patients with a Fontan circulation.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.72

Behcet and Myocardial Infarction: A Rare Combination


Introduction: Myocardial infarction during Behçet disease is rare. And may be the first manifestation.

Case Report: A 45-years-old man with a history of angio-behcet since 2009 and ischemic heart disease treated by interventricular artery stenting in 2008, was admitted with signs of congestive heart failure. The electrocardiogram showed an inverted T waves in lateral leads. Echocardiography demonstrated left ventricular dilatation with akinetic movement of the septum and the anterior wall. It also revealed a severe left ventricular dysfunction. A cardiac MRI was realized to differentiate beteween specific inflammatory myocardial damage and myocardial damage resulting from a coronary artery involvement, this technique showed a transmural late enhancement in the territory of the interventricular artery and part of a territory of the circumflex artery. These data was confirm by the coronary angiography that demonstrated a intra stent occlusion with a good down stream bed. Considering the patient history of Behcet a medical treatment was required including colchicine and heart failure traitement.

Discussion: Coronary involvement is exceptional and predominantly affects males with an average age of 40.The lesion is frequently proximal, located on one coronary artery and it primarily affects the interventricular artery.

The diagnosis of coronary vasculitis should be considered in a yong patient without traditional risk factor of atherosclerosis.

About 20 cases of myocardial infarction were reported in the litterature but the etiopathogeny, the causal relationsheep and the treatment are yet unknown.

Conclusion: Our patient highlight the importance of MRI in the distinguishing between specific inflammatory myocardial damage and myocardial infarction thereby providing a better medical decisions.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.73

Impact of New Cerebral Ischemic Lesions On the Occurrence of Delirium after Transcatheter Aortic Valve Implantation


Aims: To investigate the impact of new cerebral ischemic injury evaluated by diffusion weighted magnetic resonance imaging (DWI) on the occurrence of postoperative delirium (POD) after transcatheter aortic valve implantation (TAVI).

Methods: All TAVI patients participating in prospective studies that involved postprocedural cerebral DWI were identified. Periprocedural, clinical and imaging data had been prospectively collected. Cerebral DWI was performed within 5 days after TAVI. Quantification of cerebral injury was performed by measurement of the number and volume of lesions. The occurrence of POD was assessed using the Diagnostic and Statistical Manual of Mental Disorder 4rd Edition criteria.

Results: Post-procedural cerebral DWI was performed in 103 patients. A total of 673 new DWI-lesions (IQR: 5[2-8]) were detected in 94 (91%) patients after TAVI. POD occurred in 15 (14.5%) patients, and 47% (n = 7) of these cases were associated with at least one peri-procedural complications, including permanent pacemaker implantation (n = 2), atrial fibrillation (n = 5), acute kidney injury stage II/III (n = 1), major vascular or major/ life-threatening bleeding (n = 3). POD was associated with higher number of DWI-lesions regardless of complications (in uncomplicated TAVI: 9[7-24] vs.4[2-7], p = 0.008; and in complicated TAVI: 7[2-9] vs.5[1-7], p = 0.611) and longer hospital-stay (6[5-8] vs. 5[4-6], p = 0.038). Factors independently associated with POD were higher number of DWI-lesions (Odds Radio [OR] 1.09; 95% confidence interval [CI] 1.02-1.17), pre-existing cerebral global atrophy (OR 4.72; 95% CI 1.06-21.11) and logistic EuroSCORE (OR 1.09; 95% CI 1.01-1.18).

Conclusions: Higher number of cerebral ischemic lesion detected with DWI is associated with the occurrence of postoperative delirium after transcatheter aortic implantation. Patients with postoperative delirium showed longer hospital stay.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.74

Heart T2* assessment to measure iron overload using different software tools in patients with Thalassemia Major


Aims and Objectives: To evaluate the correlation and the interchangeability between a generic mapping T2* and specific protocols T2* in the myocardium with iron overload (IO) in patients with Thalassemia Major (TM).

Methods and Materials: Within Myocardial Iron Overload in Thalassemia (MIOT) project database we extract 60 TM patients with global heart T2* values covering entire clinical range: 20 without IO, 20 with moderate IO, 20 with severe IO. Midpapillary short axis GRE multi-echo images of the left ventricle acquired by a GE 1.5T scanner were processed by a general purpose T2* mapping tool (SEGMENTS T2* module 1.9, Medviso, Lund, SE) and by a dedicated tool validated in IO measurements in TM (HIPPO MIOT, FTGM, Pisa, IT). T2* value in the midventricular septum was evaluated by manually tracing a ROI in the T2* map in SEGMENT and by averaging the T2* values in segments 8 and 9 in HIPPO MIOT. Manual truncation of later echoes was used in HIPPO MIOT in patients with severe IO if needed.

Results: Table shows the paired-t-test analysis results for measurement in the midventricular septum. A significant difference between the two programs was detected in patients with severe IO, leading to a significant difference in the whole population. The Bland-Altman plot confirmed statistical analysis findings.

Conclusions: The two software tools are not interchangeable in measurement of low T2* values: different image analysis algorithms are exploited in the two tools, ROI-based mono-exponential fitting with manual truncation in HIPPO MIOT and pixel-wise hybrid fitting method in SEGMENT.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.75

Hypertrabeculated Left Ventricle at Cardiac Magnetic Resonance Imaging: β-Thalassemia Major vs. Left Ventricular Non -Compaction Disease


Background: Cardiac magnetic resonance (CMR) is used to differentiate left ventricle noncompaction (LVNC) from other pathological and physiological conditions characterized by prominent LV trabeculae. The hypertrabeculated LV reported in β-thalassemia major (β-TM) patients has not been considered so far as a potential differential diagnosis. We tested the diagnostic accuracy of CMR imaging in differentiating the hypertrabeculated left ventricle (LV) in patients with β-TM from LVNC disease.

Methods: CMR cine images were analyzed in 10 patients previously diagnosed with LVNC and in 38 patients with β-TM. Two CMR diagnostic criteria were applied at end-diastole: a ratio of noncompacted to compacted myocardium (NC/C ratio) >2.5 at a segmental level and a percentage of trabeculated LV mass >20% of global LV mass.

Results: In β-TM patients at least 1 positive NC/C segment was found in 51% of cases. Compared with LVNC patients, in β-TM patients the non-compaction areas were less frequent (7% vs. 37% of overall myocardial segments, p < 0.0001), with a similar distribution within the LV (predominant at the apex and postero-lateral wall, uncommon at the septum) precluding differential diagnosis. To distinguish LVNC from β-TM patients, a NC/C ratio of >2.5 showed low specificity (58%) whereas a trabeculated LV mass >20% was more accurate (sensitivity 100%, specificity 87%). Best specificity (92%) was obtained with a trabeculated LV mass percentage of >26%.

Conclusions: Differentiation of LVNC from hypertrabeculated LV in β-TM patients may depend on the selected CMR criterion. In our patient population, trabeculated LV mass percentage showed to be better than NC/C ratio.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.76

Aortic Regurgitation following Transcatheter Aortic Valve Implantation (TAVI): a CMR Study of two prosthesis designs


Background: Aortic regurgitation following TAVI is an independent predictor of mortality in the postoperative period and has prompted development of novel bioprostheses designed to facilitate precise deployment and minimise paravalvular regurgitation. CMR offers full volumetric quantitation independent of the number or eccentricity of regurgitant jets.

Aim: To compare the degree of early post-procedure aortic regurgitation following implantation of the Medtronic CoreValve and Boston Scientific Lotus Valve systems in patients treated for severe symptomatic aortic stenosis.

Methods: All patients underwent an identical 1.5T CMR scan (Intera, Phillips Healthcare, Best, Netherlands) post-procedure prior to discharge. Through-plane phase contrast velocity encoded imaging was performed perpendicular to the aortic valve jet at a level above the aortic prosthesis. Aortic flow was subsequently quantified offline (QFlow version 7.2, Medis Medical Imaging Systems, Leiden, The Netherlands) and regurgitant fraction (%) derived. AR was defined as regurgitant fraction of none/trivial ≤5%, mild 6-15%, moderate 16-25%, moderate-severe 26-48%, and severe >48% The invasive AR index derived at the time of TAVI was also recorded ([(Diastolic BP-LVEDP)/Systolic BP] x100).

Results: 18 Medtronic CoreValve patients (age 79.6 ± 6.3years, 67% male, EuroSCORE II 4.59 ± 3.59%) and 24 Boston Lotus TAVI patients (age 78.6 ± 8.7years, 54% male, EuroSCORE II 4.07 ± 3.37%) were studied at a median interval of 6 days following implantation. The residual peak aortic pressure gradient observed following Boston Lotus implantation was higher than that following Medtronic CoreValve (25.8 ± 12.1 vs.15.0 ± 5.5mmHg, p = 0.001). The absolute regurgitant fraction was significantly lower following Boston Lotus implantation than following Medtronic CoreValve (Lotus: 4.0 ± 3.5% vs. CoreValve: 11.7 ± 7.2%, p = 0.001). There was a negative correlation between invasive AR index and regurgitant fraction from CMR imaging (Spearman's coefficient -0.4, p = 0.016).

Conclusions: CMR directly quantifies AR following TAVI and there is agreement with invasive AR measurements. Significantly less aortic regurgitation but a higher residual peak pressure gradient was observed following the Boston Lotus valve compared with the Medtronic CoreValve. Further work is required to assess whether this translates into a mortality benefit.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.77

Incremental value of semi-quantitative evaluation of myocardium perfusion with 3T stress cardiac MRI


Background: 3T MRI has been adopted by some centers as the primary choice for assessment of myocardial perfusion over conventional 1.5T MRI. However, there is no data published on the potential additional value of incorporating semi-quantitative data from 3T MRI. This study sought to determine the performance of qualitative 3T stress magnetic resonance myocardial perfusion imaging (3T-MRMPI) and the potential incremental benefit of using a semi-quantitative perfusion technique in patients with suspected coronary artery disease (CAD).

Methods: Fifty eight patients (41 men; mean age: 59 years) referred for elective diagnostic angiography underwent stress 3T MRMPI with a 32-channel cardiac receiver coil. The MR protocol included gadolinium-enhanced stress first-pass perfusion (0.56mg/kg, dipyridamole), rest perfusion, and delayed enhancement (DE). Visual analysis was performed in two steps. Ischemia was defined as a territory with perfusion defect at stress study but no DE or a territory with DE but additional peri-infarcted perfusion defect at stress study. Semi-quantitative analysis was calculated by using the upslope of the signal intensity-time curve during the first pass of contrast medium during dipyridamole stress and at rest. ROC analysis was used to determine the MPRI threshold that maximized sensitivity. Quantitative coronary angiography served as the reference standard with significant stenosis defined as >70% diameter stenosis. Diagnostic performance was determined on a per-patient and per-vessel basis.

Results: Qualitative assessment had an overall sensitivity and specificity for detecting significant stenoses of 77% and 80%, respectively. By adding MPRI analysis, in cases with negative qualitative assessment, the overall sensitivity increased to 83%. The impact of MPRI differed depending on the territory; with the sensitivity for detection of left circumflex (LCx) stenoses improving the most after semi-quantification analysis, (66% versus 83%).

Conclusions: Pure qualitative assessment of 3T MRI had acceptable performance in detecting severe CAD. There is no overall benefit of incorporating semi-quantitative data; however a higher sensitivity can be obtained by adding MPRI, especially in the detection of LCx lesions.

Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.78

Left ventricular morphological quantification with single shot and free-breathing SSFP cine imaging compared with standard breath-hold SSFP cine imaging


Introduction: Multiple breath hold cine balanced steady state free procession (SSFP) imaging is the reference standard technique for the cardiovascular magnetic resonance (CMR) assessment of left ventricular mass (LVM), volumes and ejection fraction (LVEF). Single shot (SS) cine imaging is an alternative for left ventricular (LV) volumetric assessment in a shorter acquisition time, but still requires several breath-holds. Modern SSFP imaging allows excellent image quality, even when free breathing (fbSSFP). We evaluated the feasibility and accuracy of fbSSFP with signal averaging and SS imaging for LV quantitation in comparison with the reference technique of multiple breath-hold SSFP.

Methods: We prospectively recruited 26 consecutive patients (male n = 18(69%),age 49 ± 21yrs) attending for evaluation of various cardiac conditions using a 1.5T Philips Ingenia scanner. Multi-slice, multi-phase cine imaging using standard SSFP with retrospective gating was used to cover the LV in short axis (typically: 12 slices, 8mm thick, 2mm gap, 30 phases, TR/TE 4.4/2.2ms, flip angle 60°, temporal resolution 27ms, 1.1x1.1mm in-plane resolution). The identical pulse sequence was repeated with 4 signal averages during free-breathing (fbSSFP) followed by a SS-acquisition (15 phases, temporal resolution 118ms, 1.5x1.5mm in-plane resolution,1-2 breath-holds; all phases acquired in 1 heartbeat). LV end diastolic volume (LVEDV), LVM & LVEF were quantified by manually contouring endo and epicardial borders using dedicated computer software(cmr42 ). Bland-Altman analysis was used to assess the agreement of SS and fbSSFP with SSFP. Percent agreement of SS and fbSSFP with SSFP was calculated by dividing the SD of the difference between measurements by the mean. Mean differences were compared using Student's t test.

Results: All 78 LV stack acquisitions were of suitable image quality (Fig 1). Results can be seen in Table 1 and Fig 1. Agreement for fbSSFP vs SSFP was 94.5%, 93.6% and 93.8% for LVEDV, LVM and LVEF respectively. Agreement for SS vs. SSFP was 92.3%, 90.5% and 93.2% for LVEDV, LVM and LVEF respectively. Differences in quantitation led to a change in LVEF category (by one grade) in 2 patients for the fbSSFP acquisition and 3 patients in the SS acquisition group.

Conclusion: Both SS and fbSSFP imaging allow diagnostic quality imaging with good reproducibility and agreement with the reference standard SSFP. These two techniques may be helpful in patients unable to breath-hold.

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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.79

Changes of cardiac iron and function during pregnancy in transfusion-dependent thalassemia patients


Objectives: Our aim was to assess the changes in cardiac and hepatic iron overload and in morpho-functional cardiac parameters by Magnetic Resonance Imaging (MRI) in transfusion-dependent (TD) thalassemia patients who got pregnant and interrupted their chelation treatment.

Methods: We considered 17 women (14 with thalassemia major and 3 with thalassemia intermedia) enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) project who had a pregnancy with successful delivery and who performed a MRI scan before and after the pregnancy. The T2* technique was used for iron overload assessment. For the heart, a multislice multiecho approach was used. Liver T2* was converted into liver iron concentration (LIC). Atrial areas and biventricular function were quantified in a standard way by cine images.

Results: The pre-pregnancy MRI was performed 15.02 ± 5.31 months before the delivery and the post-partum MRI 5.73 ± 4.45 months later. For 16 new-mothers the post-partum MRI was performed after the restart of the chelation therapy (3.95 ± 4.10 months later). One new-mother performed the post-partum MRI 3 months before restarting the chelation therapy. The table shows the MRI parameters at the two MRIs. The pre-pregnancy and the post-partum global heart T2* values and number of pathological segments were comparable. Two patients with a normal global heart T2* value (>20 ms) before pregnancy showed a pathological post-partum value. After pregnancy there was a significant increase of MRI liver iron concentration (LIC) values. At the pre-partum MRI six (35.3%) patients had a MRI LIC < 3 mg/g/dw while at the post-partum MRI all patients had a pathological MRI LIC.Among the biventricular function parameters, there was a significant increase of right ventricular (RV) end-systolic volume index and a significant reduction of RV ejection fraction.

Conclusion: In TD patients cessation of chelation therapy can cause rapid iron overload. Pregnant women with thalassemia should be monitored carefully for iron loading and cardiac status before they embark upon a pregnancy and afterwards and consideration should be given to offering desferrioxamine immediately after delivery. In women showing severe iron overload before pregnancy desferrioxamine should be started after the middle of the second trimester. The negative impact on the RV parameters could reflect the effect of the high cardiac output state independent of the physiological changes during pregnancy.

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Eur Heart J Cardiovasc Imaging. 2016 May; 17(Suppl 1): i1–i80.
Published online 2016 May 13. doi:  10.1093/ehjci/jew093.80

Significant improvement of survival by T2* MRI in thalassemia major


Introduction: In 2004 seven Italian centers reported survival data for patients with thalassemia major (TM) and showed that heart disease due to iron overload was the most common cause of death. In the same years the accurate and noninvasive assessment of cardiac siderosis was made possible in Italy by the introduction of the T2* cardiovascular magnetic resonance (CMR). We aimed to evaluate if the deployment of T2* CMR had an impact on the mortality rate.

Methods: Four centers contributed to the present study, updating the data of the enrolled patients until August 31, 2010. For the patients who died, the date of the death represented the end of the study. 577 patients (264 females and 313 males) were included. All patients were born on or after January 1, 1960 and mean age at the follow-up was 28.04 ± 10.88 years.

Results: One-hundred and fifty-nine (27.6%) patients died, 124 of whom (77.9%) died before the year 2000.

Dead patients were significantly younger and they were more frequently males. Dead patients started chelation therapy significantly later. Dead patients showed an higher frequency of HIV, arrhythmias and heart failure. According to the Cox model, the following variables were identified as significant univariate prognosticators for the death: male sex (HR = 1.87, 95%CI = 1.34-2.60, P < 0.0001), HIV (HR = 2.55, 95%CI = 1.25-5.20, P = 0.010) and heart failure (HR = 8.86, 95%CI = 6.37-12.31, P < 0.0001).

MRI was not performed in 406 patients (70.4%) and no patient had been scanned before his/her death. Am