While the presence of abnormal late gadolinium enhancement (LGE) in cardiac amyloidosis has been well established, its prognostic implication and utility to identify cardiac involvement in patients with systemic amyloidosis is unknown. We sought to assess the diagnostic and prognostic significance of cardiovascular magnetic resonance (CMR) imaging in patients with light chain (AL) amyloidosis but unknown cardiac involvement. CMR with LGE was performed in 28 patients with systemic amyloidosis. The presence of cardiac amyloidosis was determined by a separate clinical evaluation. The performance of LGE for the prediction of cardiac amyloidosis and prognostic implications of LGE were determined. LGE was observed in 19 (68%) patients. The sensitivity, specificity, positive predictive value and negative predictive value of LGE for the identification of clinical cardiac involvement was 86%, 86%, 95%, and 67% respectively. During a median follow-up of 29 months, there were 5 deaths (82% survival). LGE itself did not predict survival (p=0.62). LGE volume positively correlated to serum level of B-type natriuretic peptide (BNP) (R=0.64, p≤0.001) and in multivariable analysis, LGE volume proved the strongest independent predictor of BNP. BNP was correlated to New York Heart Association class (p=0.03). Reduced right ventricular end-diastolic volume (p < 0.01) and stroke volume (p = 0.02) were associated with mortality. In conclusion, in patients with systemic amyloidosis, LGE is highly sensitive and specific for the identification of cardiac involvement, but does not predict survival. LGE does correlate strongly to heart failure severity as assessed by BNP.
Amyloidosis; Cardiovascular magnetic resonance imaging; Cardiomyopathy; Congestive Heart Failure
Cardiac involvement is common in amyloidosis and associated with a variably adverse outcome. We have previously shown that cardiovascular magnetic resonance (CMR) can assess deposition of amyloid protein in the myocardial interstitium. In this study we assessed the prognostic value of late gadolinium enhancement (LGE) and gadolinium kinetics in cardiac amyloidosis in a prospective longitudinal study.
Materials and methods
The pre-defined study end point was all-cause mortality. We prospectively followed a cohort of 29 patients with proven cardiac amyloidosis. All patients underwent biopsy, 2D-echocardiography and Doppler studies, 123I-SAP scintigraphy, serum NT pro BNP assay, and CMR with a T1 mapping method and late gadolinium enhancement (LGE).
Patients with were followed for a median of 623 days (IQ range 221, 1436), during which 17 (58%) patients died. The presence of myocardial LGE by itself was not a significant predictor of mortality. However, death was predicted by gadolinium kinetics, with the 2 minute post-gadolinium intramyocardial T1 difference between subepicardium and subendocardium predicting mortality with 85% accuracy at a threshold value of 23 ms (the lower the difference the worse the prognosis). Intramyocardial T1 gradient was a better predictor of survival than FLC response to chemotherapy (Kaplan Meier analysis P = 0.049) or diastolic function (Kaplan-Meier analysis P = 0.205).
In cardiac amyloidosis, CMR provides unique information relating to risk of mortality based on gadolinium kinetics which reflects the severity of the cardiac amyloid burden.
In HCM, myocardial abnormalities are commonly heterogeneous. Two patterns of LGE have been reported: a bright “confluent” and an intermediate intensity abnormality termed “diffuse,” each representing different degrees of myocardial scarring. We used MRI to study the relation between intramural cardiac function and the extent of fibrosis in HCM. The aim of this study was to determine whether excess collagen or myocardial scarring, as determined by late gadolinium enhancement (LGE) MRI, are the primary mechanisms leading to heterogeneous regional contractile function in patients with hypertrophic cardiomyopathy (HCM).
Methods and Results
Intramural left ventricular (LV) strain, transmural LV function, and regions of myocardial fibrosis/scarring were imaged in 22 patients with HCM using displacement encoding with stimulated echoes (DENSE), cine MRI and LGE. DENSE systolic strain maps were qualitatively and quantitatively compared with LGE images. Intramural systolic strain by DENSE was significantly depressed within areas of confluent and diffuse LGE but also in the core of the most hypertrophic non-enhanced segment (all p<0.001 vs. non-hypertrophied segments). DENSE demonstrated an unexpected inner rim of largely preserved contractile function and a non-contracting outer wall within hypertrophic segments in 91% of patients.
LGE predicted some but not all of the heterogeneity of intramural contractile abnormalities. This indicates that myocardial scarring or excess interstitial collagen deposition does not fully explain the observed contractile heterogeneity in HCM. Thus, myofibril disarray or other non-fibrotic processes affect systolic function in a large number of patients with HCM.
hypertrophic cardiomyopathy; magnetic resonance imaging; DENSE; displacement encoding with stimulated echoes; myocardial function; strain; late gadolinium enhancement
Silent myocardial infarctions (MI) are prevalent among diabetic patients and inflict significant morbidity and mortality. While late gadolinium enhancement (LGE) imaging by cardiac MRI (CMR) can provide sensitive characterization of myocardial scar, its prognostic significance in diabetic patients without any clinical evidence of MI is unknown.
Method and Results
We performed clinically-indicated CMR in 187 diabetic patients who were grouped by an absence (STUDY group, n=109) or presence (CONTROL group, n=78) of clinical evidence of MI (clinical history of MI or Q waves on ECG). CMR imaging and follow-up were successful in 107 (98%) STUDY and 74 (95%) CONTROL patients. Cox regression analyses were performed to associate LGE with major adverse cardiovascular events (MACE) including death, acute MI, new congestive heart failure or unstable angina, stroke, and significant ventricular arrhythmias. LGE by CMR was present in 30/107 (28%) STUDY patients. At a median follow-up of 17 months, 38/107 patients (36%) experienced MACE including 18 deaths. Presence of LGE was associated with a >3-fold hazards increase for MACE and for death (HR: 3.71 and 3.61, P<0.001 and P=0.007, respectively). Adjusted to a model that combines patient age, gender, ST or T changes on ECG, and LV end-systolic volume index, LGE maintained a >4-fold hazards increase to MACE (adjusted HR: 4.13, 95% CI 1.74-9.79, P=0.001). In addition, LGE provided significant prognostic value with MACE and with death, adjusted to a diabetic-specific risk model for 5-year events. A presence of LGE was the strongest multivariable predictor of MACE and death by stepwise selection in the STUDY patients.
CMR can characterize occult myocardial scar consistent with MI in diabetics without clinical evidence of MI. This imaging finding demonstrates strong association with MACE and mortality hazards, incremental to clinical, ECG, and left ventricular function combined.
Diabetes Mellitus; Magnetic Resonance Imaging; Myocardial Infarction; Morbidity; Mortality
Clinical parameters are weak predictors of outcome in patients with idiopathic dilated cardiomyopathy (IDC). We assessed the prognostic value of cardiac magnetic resonance (CMR) parameters in addition to conventional clinical and electrocardiographic characteristics.
Methods and results
One hundred and forty-one IDC patients were studied. QRS and QTc intervals were measured in 12-lead surface electrocardiogram. Patients were followed for median 1339 days, including 483 patient-years. The primary endpoint—cardiac death or sudden death—occurred in 25 (18%) patients, including 16 patients with cardiac death, 3 patients with sudden cardiac death (SCD), and 6 patients with ICD shock. Late gadolinium enhancement (LGE) was detected in 36 patients (26%). Kaplan–Meier survival analysis displayed QRS >110 ms (P = 0.010), the presence of LGE (P = 0.037), and diabetes mellitus (P < 0.001) as significant parameters for a worse outcome. Multivariable analysis revealed cardiac index (P < 0.001), right ventricular end-diastolic volume index (RVEDVI) (P = 0.006) derived from CMR imaging, the presence of diabetes mellitus (P = 0.006), and QRS >110 ms (P = 0.045) as significant predictors for the primary endpoint.
Cardiac index and RVEDVI derived from CMR imaging in addition to QRS duration >110 ms from conventional surface ECG and diabetes mellitus provide prognostic impact for cardiac death and SCD in patients with IDC.
Idiopathic dilated cardiomyopathy; Magnetic resonance imaging; Late gadolinium enhancement; Prognosis
Our study aimed to investigate both the clinical implications of late gadolinium enhancement (LGE) by cardiovascular magnetic resonance (CMR) and the relation of LGE to clinical findings in patients with Takotsubo cardiomyopathy (TTC).
We evaluated 20 consecutive patients (2 men, 18 women; median age, 77 years; interquartile range [IQR] 67-82 years) who were admitted to our hospital with the diagnosis of TTC. CMR was performed within 1 week after admission, and follow-up studies were conducted 1.5 and 6 months later.
In 8 patients, CMR imaging during the sub-acute phase revealed LGE in the area matched with wall motion impairment. Cardiogenic shock was more frequently observed in patients with LGE than in those without LGE (38% vs 0%, p = 0.049). The patients with LGE needed a longer duration for ECG normalization and recovery of wall motion than did those without LGE (median 205 days, IQR [152-363] vs 68 days, [43-145], p = 0.005; 15 days, [10-185] vs 7 days, [4-13], p = 0.030, respectively). In 5 of these 8 patients, LGE disappeared within 45-180 days (170, IQR [56-180]) of onset. The patients with LGE remaining in the chronic phase had higher peak creatine kinase levels than did those without LGE (median 307 IU/L, IQR [264-460] vs 202 IU/L, [120-218], p = 0.017).
LGE by CMR in the sub-acute phase may be associated with the severity and prolonged recovery to normal of clinical findings in TTC.
Takotsubo cardiomyopathy; Cardiac magnetic resonance; Cardiac dysfunction
Cardiac magnetic resonance (CMR) is a noninvasive imaging method that can determine myocardial anatomy, function, perfusion, and viability in a relative short examination. In terms of viability assessment, CMR can determine viability in a non-contrast enhanced scan using dobutamine stress following protocols comparable to those developed for dobutamine echocardiography. CMR can also determine viability with late gadolinium enhancement (LGE) methods. The gadolinium-based contrast agents used for LGE differentiate viable myocardium from scar on the basis of differences in cell membrane integrity for acute myocardial infarction. In chronic myocardial infarction, the scarred tissue enhances much more than normal myocardium due to increases in extracellular volume. LGE is well validated in pre-clinical and clinical studies that now span from almost a cellular level in animals to human validations in a large international multicenter clinical trial. Beyond infarct size or infarct detection, LGE is a strong predictor of mortality and adverse cardiac events. CMR can also image microvascular obstruction and intracardiac thrombus. When combined with a measure of area at risk like T2-weighted images, CMR can determine infarct size, area at risk, and thus estimate myocardial salvage 1–7 days after acute myocardial infarction. Thus, CMR is a well validated technique that can assess viability by gadolinium-free dobutamine stress testing or late gadolinium enhancement.
We examined whether the presence and extent of late gadolinium enhancement (LGE) by CMR predict adverse outcomes in nonischemic cardiomyopathy (NICM) patients.
Morbidity and mortality is high in NICM patients. However, the clinical course of an individual patient is unpredictable and current risk stratification approaches are limited. Cardiovascular magnetic resonance (CMR) detects myocardial fibrosis, which appears as LGE after contrast administration and may convey prognostic importance.
In a prospective cohort study, 65 NICM patients with LVEF ≤35% underwent CMR before placement of an internal cardioverter defibrillator (ICD) for primary prevention of sudden cardiac death. CMRs were analyzed for the presence and extent of LGE, and for LV function, volumes, and mass. Patients were followed for an index composite endpoint of three cardiac events: hospitalization for heart failure, appropriate ICD firing, and cardiac death.
42% (n=27) of patients had CMR LGE, averaging 10±13% of LV mass. During a 17 month median follow-up, 44% (n=12) of patients with LGE had an index composite outcome event, versus only 8% (n=3) of those without LGE (p<0.001 for Kaplan-Meier survival curves). After adjustment for LV volume index and functional class, patients with LGE had an eight-fold higher risk of experiencing the primary outcome (hazard ratio 8.2, 95% CI 2.2–30.9, p=0.002).
CMR LGE in NICM patients strongly predicts adverse cardiac outcomes. CMR LGE may represent the end-organ consequences of sustained adrenergic activation and adverse LV remodeling, and its identification may significantly improve risk stratification strategies in this high risk population.
Predicting prognosis in nonischemic cardiomyopathy patients is challenging and current risk stratification approaches are limited. Cardiovascular magnetic resonance (CMR) detects myocardial fibrosis, which appears as late gadolinium enhancement (LGE). The presence of LGE predicts an eight-fold increased risk of an adverse cardiac outcome (HR 8.1, 95% CI 1.9–33.7, p=0.004), after controlling for baseline variables. CMR LGE may reflect the transition from compensated to decompensated state resulting from long-term stressors such as sustained adrenergic activation and/or the mechanical disadvantages caused by LV remodeling leading to increasing fibrosis. Identifying CMR LGE may significantly improve risk stratification strategies in this high risk population.
cardiomyopathy; prognosis; magnetic resonance imaging
Late gadolinium enhancement (LGE) occurs at the right ventricular (RV) insertion point (RVIP) in patients with pulmonary hypertension (PH) and has been shown to correlate with cardiovascular magnetic resonance (CMR) derived RV indices. However, the prognostic role of RVIP-LGE and other CMR-derived parameters of RV function are not well established. Our aim was to evaluate the predictive value of contrast-enhanced CMR in patients with PH.
RV size, ejection fraction (RVEF), and the presence of RVIP-LGE were determined in 58 patients with PH referred for CMR. All patients underwent right heart catheterization, exercise testing, and N-terminal pro-brain natriuretic peptide (NT-proBNP) evaluation; results of which were included in the final analysis if performed within 4 months of the CMR study. Patients were followed for the primary endpoint of time to clinical worsening (death, decompensated right ventricular heart failure, initiation of prostacyclin, or lung transplantation).
Overall, 40/58 (69%) of patients had RVIP-LGE. Patients with RVIP- LGE had larger right ventricular volume index, lower RVEF, and higher mean pulmonary artery pressure (mPAP), all p < 0.05. During the follow-up period of 10.2 ± 6.3 months, 19 patients reached the primary endpoint. In a univariate analysis, RVIP-LGE was a predictor for adverse outcomes (p = 0.026). In a multivariate analysis, CMR-derived RVEF was an independent predictor of clinical worsening (p = 0.036) along with well-established prognostic parameters such as exercise capacity (p = 0.010) and mPAP (p = 0.001).
The presence of RVIP-LGE in patients with PH is a marker for more advanced disease and poor prognosis. In addition, this study reveals for the first time that CMR-derived RVEF is an independent non-invasive imaging predictor of adverse outcomes in this patient population.
Objective: To examine the influence of genotype on late gadolinium enhancement (LGE) and the potential of cardiovascular magnetic resonance (CMR) to detect preclinical hypertrophic cardiomyopathy.
Design: Prospective, blinded cohort study of myocardial LGE in a genetically homogeneous population.
Patients: 30 patients with disease causing mutations in the recognised hypertrophic cardiomyopathy gene for cardiac troponin I (TNNI3): 15 with echocardiographically determined left ventricular hypertrophy (LVH+) and 15 without (LVH−).
Main outcome measures: CMR measures of regional left ventricular function, wall thickness, and mass, and the extent and distribution of LGE.
Results: LGE was found in 12 (80%) LVH+ patients but with variable extent (mean 15%, range 3–48%). LGE was also found in two (13%) LVH− patients but the extent was limited (3.6%) and both patients were found to have an abnormal ECG and regional hypertrophy by cine CMR. The extent of LGE was positively associated with clinical markers of sudden death risk (21% with ⩾ 2 risk factors v 7% with ⩽ 1 risk factor, p = 0.02) and left ventricular mass (r = 0.56, p < 0.001) and was inversely associated with ejection fraction (r = −0.58, p < 0.001). Segmental analysis showed that as regional wall thickness increased, LGE was more prevalent (p < 0.0001) and more extensive (r = 0.98, p = 0.001).
Conclusion: In patients with disease causing mutations in TNNI3, focal fibrosis was not detected by LGE CMR before LVH and ECG abnormalities were present. Once LVH is present, LGE is common and the extent correlates with adverse clinical parameters. This suggests that focal fibrosis is closely linked to disease development.
hypertrophic cardiomyopathy; magnetic resonance imaging; fibrosis; gadolinium
To quantify resting myocardial blood flow (MBF) in the left ventricular (LV) wall of HCM patients and to determine the relationship to important parameters of disease: LV wall thickness, late gadolinium enhancement (LGE), T2-signal abnormalities (dark and bright signal), LV outflow tract obstruction and age.
Materials and Methods
Seventy patients with proven HCM underwent cardiac MRI. Absolute and relative resting MBF were calculated from cardiac perfusion MRI by using the Fermi function model. The relationship between relative MBF and LV wall thickness, T2-signal abnormalities (T2 dark and T2 bright signal), LGE, age and LV outflow gradient as determined by echocardiography was determined using simple and multiple linear regression analysis. Categories of reduced and elevated perfusion in relation to non- or mildly affected reference segments were defined, and T2-signal characteristics and extent as well as pattern of LGE were examined. Statistical testing included linear and logistic regression analysis, unpaired t-test, odds ratios, and Fisher’s exact test.
804 segments in 70 patients were included in the analysis. In a simple linear regression model LV wall thickness (p<0.001), extent of LGE (p<0.001), presence of edema, defined as focal T2 bright signal (p<0.001), T2 dark signal (p<0.001) and age (p = 0.032) correlated inversely with relative resting MBF. The LV outflow gradient did not show any effect on resting perfusion (p = 0.901). Multiple linear regression analysis revealed that LGE (p<0.001), edema (p = 0.026) and T2 dark signal (p = 0.019) were independent predictors of relative resting MBF. Segments with reduced resting perfusion demonstrated different LGE patterns compared to segments with elevated resting perfusion.
In HCM resting MBF is significantly reduced depending on LV wall thickness, extent of LGE, focal T2 signal abnormalities and age. Furthermore, different patterns of perfusion in HCM patients have been defined, which may represent different stages of disease.
Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) enables state-of-the-art in vivo evaluations of myocardial fibrosis. Although LGE patterns have been well described in asymmetrical septal hypertrophy, conflicting results have been reported regarding the characteristics of LGE in apical hypertrophic cardiomyopathy (ApHCM). This study was undertaken to determine 1) the frequency and distribution of LGE and 2) its prognostic implication in ApHCM.
Forty patients with asymptomatic or minimally symptomatic pure ApHCM (age, 60.2 ± 10.4 years, 31 men) were prospectively enrolled. LGE images were acquired using the inversion recovery segmented spoiled-gradient echo and phase-sensitive inversion recovery sequence, and analyzed using a 17-segment model. Summing the planimetered LGE areas in all short axis slices yielded the total volume of late enhancement, which was subsequently presented as a proportion of total LV myocardium (% LGE).
Mean maximal apical wall thickness was 17.9±2.3mm, and mean left ventricular (LV) ejection fraction was 67.7 ± 8.0%. All but one patient presented with electrocardiographic negative T wave inversion in anterolateral leads, with a mean maximum negative T wave of 7.2 ± 4.7mm. Nine patients (22.5%) had giant negative T waves, defined as the amplitude of ≥10mm, in electrocardiogram. LGE was detected in 130 segments of 30 patients (75.0%), occupying 4.9 ± 5.5% of LV myocardium. LGE was mainly detected at the junction between left and right ventricles in 12 (30%) and at the apex in 28 (70%), although LGE-positive areas were widely distributed, and not limited to the apex. Focal LGE at the non-hypertrophic LV segments was found in some ApHCM patients, even without LGE of hypertrophied apical segments. Over the 2-year follow-up, there was no one achieving the study end-point, defined as all-cause death, sudden cardiac death and hospitalization for heart failure.
LGE was frequently observed not only in the thickened apex of the heart but also in other LV segments, irrespective of the presence or absence of hypertrophy. The simple presence of LGE on CMR was not representative of adverse prognosis in this population.
Apical hypertrophic cardiomyopathy; Cardiovascular magnetic resonance; Late gadolinium enhancement
While implications of myocardial fibrosis on left ventricular (LV) function at rest have been studied in hypertrophic cardiomyopathy (HCM), the pathophysiological consequences on dynamic LV outflow tract (LVOT) gradient have so far not been investigated in detail.
To evaluate the influence of myocardial fibrosis, detected by MRI as late-gadolinium enhancement (LGE), on LVOT gradient in HCM.
Retrospective database analysis.
A single Italian cardiomyopathies referral centre.
Seventy-six HCM patients with normal ejection fraction at rest.
Patients underwent cardiac MR and performed bicycle exercise echocardiogram within a month.
LGE was present in 54 patients (71%), ranging from 0.2% to 32.4% of LV mass. There was a weak correlation between the amount of fibrosis and LVOT gradient variation during exercise in the overall population (r=−0.243, p=0.034) and a stronger correlation in patients with obstructive HCM at rest (r=−0.524, p=0.021). Patients with an LVOT gradient increase ≥50 mm Hg during exercise had a significantly lesser extent of fibrosis than those with an increase <50 mm Hg (0.7% (IQR 0–2.4) vs 3.2% (IQR 0.2–7.4), p=0.006). The extent of fibrosis was significantly lower among the highest quartiles of LVOT gradient increase (p=0.009).
In patients with HCM and normal ejection fraction at rest, myocardial fibrosis was associated with a lower increase in LVOT gradient during exercise, probably due to a lesser degree of myocardial contractility recruitment. This negative association was more evident in patients with an obstructive form at rest.
Atrial fibrillation is a significant public health burden, with clinically, epidemiologically and economically significant repercussions. In the last decade, catheter ablation has provided an improvement in morbidity and quality of life, significantly reducing long-term healthcare costs and avoiding recurrences compared with drug therapy. Despite recent progress in techniques, current catheter ablation success rates fall short of expectations. Late gadolinium-enhancement cardiovascular MRI (LGE-MRI) is a well-established tool to image myocardium and most specifically the left atrium. Unique imaging protocols allow for left atrial structural remodeling and fibrosis assessment, which has been demonstrated to correlate with clinical outcomes after catheter ablation, assessment of the individual’s risks of thromboembolic events, and effective imaging of patients with left atrial appendage thrombus. LGE-MRI aids in the individualized treatment of atrial fibrillation, stratifying recurrence risk and guiding specific ablation strategies. Real-time MRI offers significant safety and effectiveness profiles that would optimize the invasive treatment of atrial fibrillation.
ablation; atrial; fibrillation; fibrosis; MRI; outcomes; stroke
The aim of the study was to assess cardiac involvement in patients with Wegener’s granulomatosis (WG), who failed to achieve remission following >6 months induction therapy for life or organ threatening disease.
Eleven WG patients (eight males, mean age 47 ± 13 years), who failed to achieve remission despite >6 months induction therapy, underwent transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR).
Cardiac involvement was present in 9 (82%) patients. Regional wall motion abnormalities were found in two individuals, but none had left ventricular (LV) ejection fraction <50%. Nine patients had late gadolinium enhancement (LGE) lesions involving LV myocardium and right ventricle free wall was involved in four patients. LGE lesions were found in subepicardial, midwall and subendocardial LV myocardial layers. CMR revealed myocarditis in six patients. Patients with myocarditis had a higher number of LV segments with LGE (5.2 ± 3.4 vs 1.0 ± 1.2, p = 0.03) and more frequent diastolic dysfunction by TTE (5 vs 0, p = 0.02) than those without. Pericardial effusion was observed in five patients, while localized pericardial thickening in six patients.
In WG resistant to >6 months induction therapy cardiac involvement is frequent and is characterized by foci of LGE lesions and signs of myocardial inflammatory process.
Wegener’s granulomatosis; Cardiac magnetic resonance; Echocardiography; Myocarditis; Remission
Some patients may have normal wall motion after myocardial infarction. The aim of this study was to determine the prevalence and prognosis of patients with myocardial scar in the absence of abnormal wall motion. We studied patients with suspected or known coronary artery disease (CAD) who were referred for cardiovascular magnetic resonance (CMR) for the assessment of global and regional cardiac function and late gadolinium enhancement (LGE) and had normal left ventricular wall motion. Prognostic value was determined by the occurrence of hard endpoints (cardiac death and nonfatal myocardial infarction) and major adverse cardiac events (MACE) which also included hospitalization due to unstable angina or heart failure or life threatening ventricular arrhythmia.
A total 1148 patients (70.3%) were studied. LGE was detected in 104 patients (9.1%). Prevalence of LGE increased in patients with increased left ventricular mass. Average follow-up time was 955 ± 542 days. LGE was the strongest predictor for hard endpoints and MACE.
LGE was detected in 9.1% of patients with suspected or known CAD and normal wall motion. LGE was the strongest predictor of significant cardiac events.
Progressive cardiomyopathy is a common cause of death in Duchenne muscular dystrophy (DMD), presumably secondary to fibrosis of the myocardium. The posterobasal and left lateral free wall of the left ventricle (LV) are initial sites of myocardial fibrosis pathologically. The purposes of this study were to assess whether cardiac magnetic resonance imaging (CMRI), utilizing late gadolinium enhancement (LGE), could identify fibrosis in selective areas of the myocardium, and to assess the relationship of the presence and extent of fibrosis to LV function.
The cardiology databases at Primary Children's Medical Center and Cincinnati Children's Hospital Medical Center were reviewed to identify patients with DMD who had undergone a CMRI within the last 2 years. Age, LV ejection fraction, LV mass, presence and location of LGE were documented. Volumes were measured using MASS (Medis, Inc.) to calculate ejection fraction and mass. LGE images were acquired and when positive, manual and customized computer assisted sizing of the areas of late gadolinium enhancement were performed on all slices. Normal function was defined as LV ejection fraction >54%.
A total of 74 patients with DMD had complete data sets (median age 13.7 years, range 7.7 − 26.4). Twenty-four patients (32%) had LGE involving the posterobasal region of the LV in a sub-epicardial distribution. Those patients with more involvement had spread to the inferior and left lateral free wall with progressive transmural fibrous replacement. There was relative sparing of the interventricular septum and right ventricle. Patients with LGE were significantly older than those without (mean age16.4 years vs 12.9 years, p<0.001). LGE was positively associated with BSA-adjusted LV mass, LV end-diastolic volume, LV end-systolic volume, and RV end-systolic volume but inversely correlated with ejection fraction of the LV (p<0.001) and RV (p = 0.004).
LGE by CMRI is able to detect fibrosis in selective regions of myocardium in patients with DMD. Unfavorable LV remodeling, with a corresponding decreased ejection fraction, is associated with the presence of LGE. Serial studies are warranted to determine if LGE precedes a decrease in function, and if early medical management is useful in preventing progression once LGE is documented.
Duchenne muscular dystrophy; Magnetic Resonance Imaging; cardiomyopathy
Myocardial infarction (MI) documented by late gadolinium enhancement (LGE) has clinical and prognostic importance, but its detection is sometimes compromised by poor contrast between blood and MI. MultiContrast Delayed Enhancement (MCODE) is a technique that helps discriminate subendocardial MI from blood pool by simultaneously providing a T2-weighted image with a PSIR (phase sensitive inversion recovery) LGE image. In this clinical validation study, our goal was to prospectively compare standard LGE imaging to MCODE in the detection of MI.
Imaging was performed on a 1.5 T scanner on patients referred for CMR including a LGE study. Prospective comparisons between MCODE and standard PSIR LGE imaging were done by targeted, repeat imaging of slice locations. Clinical data were used to determine MI status. Images at each of multiple time points were read on separate days and categorized as to whether or not MI was present and whether an infarction was transmural or subendocardial. The extent of infarction was scored on a sector-by-sector basis.
Seventy-three patients were imaged with the specified protocol. The majority were referred for vasodilator perfusion exams and viability assessment (37 ischemia assessment, 12 acute MI, 10 chronic MI, 12 other diagnoses). Forty-six patients had a final diagnosis of MI (30 subendocardial and 16 transmural). MCODE had similar specificity compared to LGE at all time points but demonstrated better sensitivity compared to LGE performed early and immediately before and after the MCODE (p = 0.008 and 0.02 respectively). Conventional LGE only missed cases of subendocardial MI. Both LGE and MCODE identified all transmural MI. Based on clinical determination of MI, MCODE had three false positive MI’s; LGE had two false positive MI’s including two of the three MCODE false positives. On a per sector basis, MCODE identified more infarcted sectors compared to LGE performed immediately prior to MCODE (p < 0.001).
While both PSIR LGE and MCODE were good in identifying MI, MCODE demonstrated more subendocardial MI’s than LGE and identified a larger number of infarcted sectors. The simultaneous acquisition of T1 and T2-weighted images improved differentiation of blood pool from enhanced subendocardial MI.
Late gadolinium enhancement; Myocardial infarction; MultiContrast Delayed Enhancement; Cardiovascular magnetic resonance
Owing to its variable course from asymptomatic cases to sudden death risk stratification is of paramount importance in newly diagnosed non-ischemic cardiomyopathy. We tested whether late gadolinium enhancement (LGE) assessed by cardiac magnetic resonance (CMR) imaging is a prognostic marker in consecutive patients with newly diagnosed non-ischemic cardiomyopathy.
We enrolled 185 patients who presented for evaluation of newly diagnosed non-ischemic cardiomyopathy. Coronary artery disease was excluded by coronary angiography. Following risk markers were additionally assessed: NYHA functional class (≥II), brain natriuretic peptide (>100 ng/l), troponin I (TnI, ≥0.03 µg/l), left ventricular ejection fraction (LVEF, ≤40%), left ventricular enddiastolic diameter (>55 mm) and QRS duration (>98 ms). Endpoint of the study was the composite of all-cause mortality, heart transplantation, aborted sudden death, sustained ventricular tachycardia or hospitalization due to decompensated heart failure within three years of follow-up.
During median follow-up of 21 months, 54 patients (29.2%) reached the composite endpoint. Ninety-four of the 185 patients (50.8%) were judged LGE-positive. Prognosis of LGE-positive patients was significantly worse than that of LGE-negative patients (cumulative 3-year event rates of 67.4% in LGE-positive and 27.2% in LGE-negative patients, respectively; p = 0.021). However, in multivariable analysis, presence of LGE was not an independent predictor of outcome. Only LVEF ≤40% and TnI ≥0.03 µg/l were independent risk predictors of the composite endpoint yielding relative risks of 3.9 (95% CI 1.9–8.1; p<0.0001) and 2.2 (95% CI 1.2–4.0; p = 0.014), respectively.
In consecutive patients presenting with newly diagnosed non-ischemic cardiomyopathy, LGE-positive patients had worse prognosis. However, only traditional risk parameters like left ventricular performance and cardiac biomarkers but not presence of LGE were independent risk predictors.
Myocardial infarction (MI) can be readily assessed using late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR). Inversion recovery (IR) sequences provide the highest contrast between enhanced infarct areas and healthy myocardium. Applying such methods to small animals is challenging due to rapid respiratory and cardiac rates relative to T1 relaxation.
Here we present a fast and robust protocol for assessing LGE in small animals using a multi-slice IR gradient echo sequence for efficient assessment of LGE. An additional Look-Locker sequence was used to assess the optimum inversion point on an individual basis and to determine most appropriate gating points for both rat and mouse. The technique was applied to two preclinical scenarios: i) an acute (2 hour) reperfused model of MI in rats and ii) mice 2 days following non-reperfused MI.
LGE images from all animals revealed clear areas of enhancement allowing for easy volume segmentation. Typical inversion times required to null healthy myocardium in rats were between 300-450 ms equivalent to 2-3 R-waves and ~330 ms in mice, typically 3 R-waves following inversion. Data from rats was also validated against triphenyltetrazolium chloride staining and revealed close agreement for infarct size.
The LGE protocol presented provides a reliable method for acquiring images of high contrast and quality without excessive scan times, enabling higher throughput in experimental studies requiring reliable assessment of MI.
Myocardial fibrosis is frequently identified in patients with hypertrophic cardiomyopathy (HCM). The aim of this study was to investigate the role of myocardial fibrosis detected by late gadolinium-enhancement (LGE) cardiovascular magnetic resonance (CMR) as a potential arrhythmogenic substrate in HCM. We hypothesized that the extent of LGE might be associated with the inducibility of ventricular tachyarrhythmias (VT) during programmed ventricular stimulation (PVS).
We evaluated retrospectively LGE CMR of 76 consecutive HCM patients, of which 43 presented with one or more risk factors for sudden cardiac death (SCD) and were therefore clinically classified as high-risk patients. Of these 43 patients, 38 additionally underwent an electrophysiological testing (EP). CMR indices and the extent of LGE, given as the % of LV mass with LGE were correlated with the presence of risk factors for SCD and the results of EP.
High-risk patients had a significant higher prevalence of LGE than low-risk patients (29/43 [67%] versus 14/33 [47%]; p = 0.03). Also the % of LV mass with LGE was significantly higher in high-risk patients than in low-risk patients (14% versus 3%, p = 0.001, respectively). Of the 38 high- risk patients, 12 had inducible VT during EP. LV function, volumes and mass were comparable in patients with and without inducible VT. However, the % of LV mass with LGE was significantly higher in patients with inducible VT compared to those without (22% versus 10%, p = 0.03). The prevalence of LGE was, however, comparable between HCM patients with and those without inducible VT (10/12 [83%] versus 15/26 [58%]; p = 0.12). In the univariate analysis the % of LV mass with LGE and the septal wall thickness were significantly associated with the high-risk group (p = 0.001 and 0.004, respectively). Multivariate analysis demonstrated that the extent of LGE was the only independent predictor of the risk group (p = 0.03).
The extent of LGE in HCM patients correlated with risk factors of SCD and the likelihood of inducible VT. Furthermore, LGE extent was the only independent predictor of the risk group. This supports the hypothesis that the extent of fibrosis may serve as potential arrhythmogenic substrate for the occurrence of VT, especially in patients with clinical risk factors for SCD.
To compare higher spatial resolution 3D late gadolinium enhancement (LGE) cardiovascular MR (Cardiac MR) with 2D LGE in patients with prior myocardial infarction.
Materials and Methods
Fourteen patients were studied using high spatial resolution 3D LGE (1.3×1.3× 5.0 mm3) and conventional 2D LGE (2×2×8mm3) scans. SNR and CNR were measured. Total infarct volume, peri-infarct volume measured in a limited slab, and papillary muscle scar volume were compared using Bland-Altman analysis. Image quality was graded.
3D LGE had higher scar SNR (p<0.001), higher myocardial SNR (p=0.001), higher papillary scar-blood CNR (p=0.01), and greater sharpness (p=0.01). The scar volumes agreed (14.5±8.2 for 2D, vs. 13.2±8.8 for 3D), with bias ±2 SDs of 0.5±6.8ml, p=0.59 R=0.91. The peri-infarct volumes correlated but less strongly than scar (p=0.40, R=0.77). For patients with more heterogeneous scar, larger peri-infarct volumes were measured by 3D (1.9±1.1ml for 2D vs. 2.4±1.6 ml for 3D, p=0.15, in the matched region). Papillary scar, present in 6/14 (42%) patients, was more confidently identified on 3D LGE.
Higher spatial resolution 3D LGE provides sharper images and higher SNR, but less myocardial nulling. Scar volumes agree well, with peri-infarct volumes correlating less well. 3D LGE may be superior in visualization of papillary muscle scar.
delayed enhancement; high spatial resolution; late gadolinium enhancement; papillary muscle scar; cardiac magnetic resonance; myocardial infarction
Myocardial scarring at the LV pacing site leads to incomplete resynchronization and a suboptimal symptomatic response to CRT. We sought to determine whether the use of late gadolinium cardiovascular magnetic resonance (LGE-CMR) to guide left ventricular (LV) lead deployment influences the long-term outcome of cardiac resynchronization therapy (CRT).
559 patients with heart failure (age 70.4 ± 10.7 yrs [mean ± SD]) due to ischemic or non-ischemic cardiomyopathy underwent CRT. Implantations were either guided (+CMR) or not guided (-CMR) by LGE-CMR prior to implantation. Fluoroscopy and LGE-CMR were used to localize the LV lead tip and and myocardial scarring retrospectively. Clinical events were assessed in three groups: +CMR and pacing scar (+CMR+S); CMR and not pacing scar (+CMR-S), and; LV pacing not guided by CMR (-CMR).
Over a maximum follow-up of 9.1 yrs, +CMR+S had the highest risk of cardiovascular death (HR: 6.34), cardiovascular death or hospitalizations for heart failure (HR: 5.57) and death from any cause or hospitalizations for major adverse cardiovascular events (HR: 4.74) (all P < 0.0001), compared with +CMR-S. An intermediate risk of meeting these endpoints was observed for -CMR, with HRs of 1.51 (P = 0.0726), 1.61 (P = 0.0169) and 1.87 (p = 0.0005), respectively. The +CMR+S group had the highest risk of death from pump failure (HR: 5.40, p < 0.0001) and sudden cardiac death (HR: 4.40, p = 0.0218), in relation to the +CMR-S group.
Compared with a conventional implantation approach, the use of LGE-CMR to guide LV lead deployment away from scarred myocardium results in a better clinical outcome after CRT. Pacing scarred myocardium was associated with the worst outcome, in terms of both pump failure and sudden cardiac death.
Viability assessment following acute myocardial infarction (MI) is important to guide revascularization. Two-dimensional strain echocardiography (2DSE) was shown to predict viability but the methodology assumed strain in each segment is independent of contiguous segments. We tested the hypotheses that segmental strain post-MI are spatially correlated and that using Bayesian approach improves prediction of non-viable myocardium. 21 subjects (58±12 years, 6 females) with ≥2 weeks MI underwent 2DSE and late gadolinium enhancement (LGE) cardiac magnetic resonance imaging within 48-hours of each other. The heart was divided into 16 segments and longitudinal, radial and circumferential strains were measured using software. Using similar segmentation, LGE was measured and segments with >50% LGE were considered nonviable. Spearman analyses assessed spatial correlation of strain and receiver operating characteristic curve analysis was used to determine prediction of non-viable myocardium without and with Bayesian logistic spatial conditionally autoregressive (CAR) model. There is significant spatial correlation in strain and LGE, especially in the apex. Longitudinal strain was the best predictor of non-viability and was impaired in non-viable myocardium (-12.1±0.6, -8.0±0.6 and -4.6±1% for 0, 1-50, >50% LGE, respectively, p<0.001). Use of CAR model improved the area under the curve for detection of non-viable myocardium (0.7 to 0.94). A CAR probabilistic score of 0.17 had 88% sensitivity and 86% specificity for detecting non-viable myocardium. In conclusion, longitudinal strain from 2DSE can predict myocardial viability following MI and exploiting spatial correlations in segmental strain using Bayesian CAR enhances the ability of 2D strain to predict non-viable myocardium.
myocardial infarction; strain echocardiography; viability; Bayesian analysis
Current cardiovascular magnetic resonance (CMR) methods, such as late gadolinium enhancement (LGE) and oedema imaging (T2W) used to depict myocardial ischemia, have limitations. Novel quantitative T1-mapping techniques have the potential to further characterize the components of ischemic injury. In patients with myocardial infarction (MI) we sought to investigate whether state-of the art pre-contrast T1-mapping (1) detects acute myocardial injury, (2) allows for quantification of the severity of damage when compared to standard techniques such as LGE and T2W, and (3) has the ability to predict long term functional recovery.
3T CMR including T2W, T1-mapping and LGE was performed in 41 patients [of these, 78% were ST elevation MI (STEMI)] with acute MI at 12-48 hour after chest pain onset and at 6 months (6M). Patients with STEMI underwent primary PCI prior to CMR. Assessment of acute regional wall motion abnormalities, acute segmental damaged fraction by T2W and LGE and mean segmental T1 values was performed on matching short axis slices. LGE and improvement in regional wall motion at 6M were also obtained.
We found that the variability of T1 measurements was significantly lower compared to T2W and that, while the diagnostic performance of acute T1-mapping for detecting myocardial injury was at least as good as that of T2W-CMR in STEMI patients, it was superior to T2W imaging in NSTEMI. There was a significant relationship between the segmental damaged fraction assessed by either by LGE or T2W, and mean segmental T1 values (P < 0.01). The index of salvaged myocardium derived by acute T1-mapping and 6M LGE was not different to the one derived from T2W (P = 0.88). Furthermore, the likelihood of improvement of segmental function at 6M decreased progressively as acute T1 values increased (P < 0.0004).
In acute MI, pre-contrast T1-mapping allows assessment of the extent of myocardial damage. T1-mapping might become an important complementary technique to LGE and T2W for identification of reversible myocardial injury and prediction of functional recovery in acute MI.