Cardiovascular MRI has effectively become a reference standard for quantifying ventricular volumes and function and for measuring the myocardial scar burden after myocardial infarction. Imaging of late gadolinium enhancement and microvascular obstruction carries strong prognostic information for identifying patients who would benefit from anti-remodeling therapy. The combination of gadolinium enhancement, perfusion, and cine imaging should make MRI the modality of choice in the assessment of left ventricular dysfunction and remodeling. The use of MRI in clinical trials of heart failure could help reduce sample size requirements because of its accuracy and reproducibility. This review describes the use of MRI in assessing ventricular remodeling and viability and summarizes the few studies that have relied on MRI for image-based markers of ventricular remodeling.
Purpose of review
This review is meant as a balanced summary of the current state of cardiac magnetic resonance (CMR) perfusion imaging in assessing alterations in myocardial blood flow due to coronary artery disease (CAD). We aim to provide first an accessible technical overview of first-pass CMR perfusion imaging and contrast it with other conventional perfusion imaging modalities, and then address the potential advantages of CMR for a qualitative assessment of perfusion defects, as well as quantitative blood flow measurements. Most recent results from clinical trials on the utility of CMR perfusion and novel directions will be explored.
Recent results of the first multicenter multivendor CMR perfusion study demonstrated superior diagnostic utility in detecting CAD by CMR compared with conventional nuclear single-photon emission computed tomography. Several large clinical trials provide additional evidence indicating the strong prognostic implications when CMR perfusion was performed in a clinical setting in patients with an intermediate clinical likelihood of CAD. A negative adenosine stress CMR perfusion study conferred a favorable 3-year prognosis towards nonfatal myocardial infarction or cardiac death.
CMR perfusion imaging during the first pass of gadolinium-based contrast agents has undergone many technical improvements and levels of clinical validation. Rapidly increasing clinical use worldwide over the last years in diagnosing chest pain syndromes supports the role of CMR in a comprehensive and efficient noninvasive assessment of altered myocardial physiology in CAD.
first-pass myocardial perfusion; gadolinium; ischemia; mortality; myocardial blood flow; myocardial infarction
Editorials; imaging; diagnostic; magnetic resonance imaging; ventricular remodeling
Assessment of myocardial ischemia in symptomatic patients remains a common and challenging clinical situation faced by physicians. Risk stratification by presence of ischemia provides important utility for both prognostic assessment and management. Unfortunately, current noninvasive modalities possess numerous limitations and have limited prognostic capacity. More recently, ischemia assessment by cardiovascular magnetic resonance (CMR) has been shown to be a safe, available, and potentially cost-effective alternative with both high diagnostic and prognostic accuracy. Cardiovascular magnetic resonance has numerous advantages over other noninvasive methods, including high temporal and spatial resolution, relatively few contraindications, and absence of ionizing radiation. Furthermore, studies assessing the clinical utility and cost effectiveness of CMR in the short-term setting for patients without evidence of an acute myocardial infarction have also demonstrated favorable results. This review will cover techniques of ischemia assessment with CMR by both stress-induced wall motion abnormalities as well as myocardial perfusion imaging. The diagnostic and prognostic performance studies will also be reviewed, and the use of CMR for ischemia assessment will be compared with other commonly used noninvasive modalities.
Acute coronary syndrome; Adenosine; Cardiac magnetic resonance imaging (CMR); Chest pain; Coronary artery disease; Dobutamine; Echocardiography; Ischemia; Myocardial infarction; Perfusion; Persantine; Regadenoson; Positron emission tomography; Single-photon emission computed tomography; Vasodilators
The aim of this study was to perform direct quantification of myocardial extracellular volume fraction (ECF) with T1-weighted cardiac magnetic resonance (CMR) imaging in patients suspected to have infiltrative heart disease.
Infiltrative heart disease refers to accumulation of abnormal substances within the myocardium. Qualitative assessment of late gadolinium enhancement (LGE) remains the most commonly used method for CMR evaluation of patients suspected with myocardial infiltration. This technique is widely available and can be performed in a reproducible and standardized manner. However, the degree of extracellular matrix expansion due to myocardial infiltration in the intercellular space has, to date, not been amenable to noninvasive quantification with LGE.
We performed 3-T CMR in 38 patients (mean age 68 ± 15 years) who were referred for assessment of infiltrative heart disease and also in 9 healthy volunteers as control subjects. The T1 quantification by Look-Locker gradient-echo before and after contrast determined segmental myocardial partition coefficients. The ECF was obtained by referencing the tissue partition coefficient for gadolinium to the plasma volume fraction in blood, derived from serum hematocrit. Cine CMR and LGE imaging in matching locations were also performed.
Seventeen patients (45%) had cardiac amyloidosis (CA) (biopsy-confirmed or clinically highly probable), 20 (53%) had a non-amyloid cardiomyopathy, and 1 had lysosomal storage disease. Median global ECF was substantially higher in CA patients (0.49) compared with non-amyloid cardiomyopathy patients (0.33, p < 0.0001) and volunteers (0.24, p < 0.0001). The ECF strongly correlated with visually assessed segmental LGE (r = 0.80, p < 0.0001) and LV mass index (r = 0.69, p < 0.0001), reflecting severity of myocardial infiltration. In patients with CA, ECF was highest in segments with LGE, although it remained elevated in segments without qualitative LGE.
The CMR ECF quantification identified substantial expansion of the interstitial space in patients with CA compared with volunteers. Further studies using this technique for diagnosis and assessment of the severity of myocardial infiltration are warranted.
amyloid; infiltrative cardiomyopathy; left ventricular mass; myocardial delayed enhancement; T1 mapping
The major aim of this study is to test the hypothesis that stress cardiac magnetic resonance (CMR) imaging can provide robust prognostic value in women presenting with suspected ischemia, to the same extent as in men.
Compelling evidence indicates that women with coronary artery disease (CAD) experience worse outcomes than men owing to a lack of early diagnosis and management. Numerous clinical studies have shown that stress CMR detects evidence of myocardial ischemia and infarction at high accuracy. Compared to nuclear scintigraphy, CMR is free of ionizing radiation, has high spatial resolution for imaging small hearts, and overcomes breast attenuation artifacts, which are substantial advantages when imaging women for CAD.
We performed stress CMR in 405 patients (168 women, mean age 58 ± 14 years) referred for ischemia assessment. CMR techniques included cine cardiac function, perfusion imaging during vasodilating stress, and late gadolinium enhancement imaging. All patients were followed for major adverse cardiac events (MACE).
At a median follow-up of 30 months, MACE occurred in 36 patients (9%) including 21 cardiac deaths and 15 acute myocardial infarctions. In women, CMR evidence of ischemia (ISCHEMIA) demonstrated strong association with MACE (unadjusted hazard ratio: 49.9, p < 0.0001). While women with ISCHEMIA(+) had an annual MACE rate of 15%, women with ISCHEMIA(−) had very low annual MACE rate (0.3%), which was not statistically different from the low annual MACE rate in men with ISCHEMIA(−) (1.1%). CMR myocardial ischemia score was the strongest multivariable predictor of MACE in this cohort, for both women and men, indicating robust cardiac prognostication regardless of sex.
In addition to avoiding exposure to ionizing radiation, stress CMR myocardial perfusion imaging is an effective and robust risk-stratifying tool for patients of either sex presenting with possible ischemia.
cardiac magnetic resonance; infarction; major cardiac adverse events; mortality; myocardial ischemia; women
This study sought to determine whether the extent of late gadolinium enhancement (LGE) can provide additive prognostic information in patients with a nonischemic dilated cardiomyopathy (NIDC) with an indication for implantable cardioverter-defibrillator (ICD) therapy for the primary prevention of sudden cardiac death (SCD).
Data suggest that the presence of LGE is a strong discriminator of events in patients with NIDC. Limited data exist on the role of LGE quantification.
The extent of LGE and clinical follow-up were assessed in 162 patients with NIDC prior to ICD insertion for primary prevention of SCD. LGE extent was quantified using both the standard deviation–based (2-SD) method and the full-width half-maximum (FWHM) method.
We studied 162 patients with NIDC (65% male; mean age: 55 years; left ventricular ejection fraction [LVEF]: 26 ± 8%) and followed up for major adverse cardiac events (MACE), including cardiovascular death and appropriate ICD therapy, for a mean of 29 ± 18 months. Annual MACE rates were substantially higher in patients with LGE (24%) than in those without LGE (2%). By univariate association, the presence and the extent of LGE demonstrated the strongest associations with MACE (LGE presence, hazard ratio [HR]: 14.5 [95% confidence interval (CI): 6.1 to 32.6; p < 0.001]; LGE extent, HR: 1.15 per 1% increase in volume of LGE [95% CI: 1.12 to 1.18; p < 0.0001]). Multivariate analyses showed that LGE extent was the strongest predictor in the best overall model for MACE, and a 7-fold hazard was observed per 10% LGE extent after adjustments for patient age, sex, and LVEF (adjusted HR: 7.61; p < 0.0001). LGE quantitation by 2-SD and FWHM both demonstrated robust prognostic association, with the highest MACE rate observed in patients with LGE involving >6.1% of LV myocardium.
LGE extent may provide further risk stratification in patients with NIDC with a current indication for ICD implantation for the primary prevention of SCD. Strategic guidance on ICD therapy by cardiac magnetic resonance in patients with NIDC warrants further study.
cardiac magnetic resonance; implantable cardioverter-defibrillators; late gadolinium enhancement; nonischemic cardiomyopathy
We aimed to determine whether the myocardial extracellular volume (ECV), measured using T1 measurements obtained during cardiac magnetic resonance (CMR) imaging were increased in patients treated with anthracyclines. We performed CMR imaging, an echocardiogram, and measured the ECV in 42 patients with treated with anthracyclines. Data from the CMR study were compared to healthy volunteers. The anthracycline-treated cohort consisted of 21 males and 21 females with a mean age of 55±17 years, presenting a median of 84 months after chemotherapy with a cumulative anthracycline exposure of 282±65 mg/m2, and a mean left ventricular ejection fraction of 52±12%. The ECV was elevated in anthracycline-treated patients in comparison to age and gender-matched controls (0.36±0.03 vs. 0.28±0.02, p < 0.001). There was a positive association between the ECV and left atrial volume (LAV) (ECV vs. indexed LAV, r=0.65, p < 0.001) and negative association between the ECV and diastolic function (E′ lateral, r=−.64, p < 0.001). In conclusion, the myocardial extracellular volume is elevated in patients with prior anthracycline treatment and is associated with diastolic function and increased atrial volumes.
Anthracyclines; Cardiac Magnetic Resonance; T1 Measurements; Extracellular Volume Fraction; Myocardial Fibrosis
The myocardial extracellular volume fraction (MECVF) has been used to detect diffuse fibrosis. Estimation of MECVF relies quantification of the T1 relaxation time after contrast enhancement, which can be sensitive to equilibrium transcytolemmal water exchange. We hypothesized that MECVF, quantified with a parsimonious 2-space water-exchange model, correlates positively with the connective tissue volume fraction (CTVF) in a rodent model of hypertensive heart disease, while the widely used analysis based on assuming fast transcytolemmal water exchange could result in a significant underestimate of MECVF.
Methods and Results
Nω–nitro-L-arginine-metyl-ester (L-NAME) or placebo was administered to 22 and 15 wild-type mice, respectively. MECVF was measured at baseline and 7-week follow-up by pre- and post-contrast T1 CMR imaging at 4.7 T, using a 2-space water-exchange model. CTVF was quantified, using Masson’s trichrome stain. L-NAME induced hypertrophy (weight-indexed LV mass 2.2±0.3 vs. 4.1±0.4 µg/g, p<0.001), and increased CTVF (8.6%±1.5 vs. 2.58%±0.6, p<0.001), compared to controls. MECVF was higher in L-NAME-treated animals (0.43±0.09 vs, 0.26±0.03, p<0.001), and correlated with CTVF and weight-indexed LV mass (r=0.842 and r=0.737 respectively, both P<0.0001). Neglecting transcytolemmal water-exchange caused a significant underestimate of MECVF changes. Ten patients with history of hypertension had significantly higher MECVF (0.446±0.063) compared to healthy controls 0.307±0.030, p<0.001).
CMR allowed detection of myocardial extracellular matrix expansion in a mouse model, and in patients with a history of hypertension. Accounting for the effects of transcytolemmal water exchange can result in a substantial difference of MECVF, compared to assuming fast transcytolemmal water exchange.
cardiac magnetic resonance; gadolinium-DTPA; myocardial fibrosis; extracellular volume fraction; transcytolemmal; water-exchange; Nω–nitro-L-arginine-metyl-ester; mice
Aortic stenosis (AS) is the commonest valve disorder in the developed world requiring surgery. Surgery in patients with severe asymptomatic AS remains controversial. Exercise testing can identify asymptomatic patients at increased risk of death and symptom development, but with limited specificity, especially in older adults. Cardiac MRI (CMR), including myocardial perfusion reserve (MPR) may be a novel imaging biomarker in AS.
(1) To improve risk stratification in asymptomatic patients with AS and (2) to determine whether MPR is a better predictor of outcome than exercise testing and brain natriuretic peptide (BNP).
Multicentre, prospective observational study in the UK, comparing MPR with exercise testing and BNP (with blinded CMR analysis) for predicting outcome.
170 asymptomatic patients with moderate-to-severe AS, who would be considered for aortic valve replacement (AVR).
Composite of: typical symptoms necessitating referral for AVR and major adverse cardiovascular events. Follow-up: 12–30 months (minimum 12 months).
MPR will be a better predictor of outcome than exercise testing and BNP.
The study has full ethical approval and is actively recruiting patients. Data collection will be completed in November 2014 and the study results will be submitted for publication within 6 months of completion.
We aimed to describe the cardiac magnetic resonance (CMR) findings and to determine prognostic variables in patients with a cardiomyopathy after treatment with anthracyclines. CMR imaging was performed in 91 patients (58% male, mean age of 43 ± 18 years and anthracycline dose of 276 ± 82 mg/m2) with reduced ejection fraction (EF) after anthracycline-based chemotherapy. Major adverse cardiovascular events (MACE) were defined as cardiovascular death, appropriate implantable cardioverter defibrillator therapy, and admission for decompensated heart failure. Patients presented a median of 88 months (IQR 37 to 138) after chemotherapy and were followed for 27 months (IQR 22 to 38). Late gadolinium enhancement was an uncommon finding (5 patients, 6%) despite a reduced EF (36 ± 8%). There was an inverse association between anthracycline dose and the indexed left ventricular (LV) mass by CMR (r = −0.67, p < 0.001). There were 52 adverse cardiac events (event rate of 22% per year). When patients were grouped according to the presence or absence of a MACE, indexed LV mass and glomerular filtration rate were lower and anthracycline dose was higher among patients that experienced an adverse event. In a multivariable model, indexed LV mass demonstrated the strongest association with MACE (HR = 0.89, chi-squared = 26, p < 0.001). In conclusion, scar by LGE-CMR imaging is infrequent in patients with an anthracycline-induced cardiomyopathy despite a reduced EF, the event rate in patients with an established anthracycline-induced cardiomyopathy is high, and indexed LV-mass by CMR is a predictor of adverse cardiovascular events.
Anthracyclines; Doxorubicin; Cardiac Magnetic Resonance; Heart Failure
Sleep apnea (SA) is associated with an increased risk of atrial fibrillation (AF). We sought to determine the effect of SA on cardiac structure in patients with AF, whether therapy for SA was associated with beneficial cardiac structural remodelling, and whether beneficial cardiac structural remodelling translated into a reduced risk of recurrence of AF after pulmonary venous isolation (PVI).
Methods and Results
A consecutive group of 720 patients underwent a cardiac magnetic resonance study before PVI. Patients with SA (n=142, 20%) were more likely to be male, diabetic, and hypertensive and have an increased pulmonary artery pressure, right ventricular volume, atrial dimensions, and left ventricular mass. Treated SA was defined as duration of continuous positive airway pressure therapy of >4 hours per night. Treated SA patients (n=71, 50%) were more likely to have paroxysmal AF, a lower blood pressure, lower ventricular mass, and smaller left atrium. During a follow‐up of 42 months, AF recurred in 245 patients. The cumulative incidence of AF recurrence was 51% in patients with SA, 30% in patients without SA, 68% in patients with untreated SA, and 35% in patients with treated SA. In a multivariable model, the presence of SA (hazard ratio 2.79, CI 1.97 to 3.94, P<0.0001) and untreated SA (hazard ratio 1.61, CI 1.35 to 1.92, P<0.0001) were highly associated with AF recurrence.
Patients with SA have an increased blood pressure, pulmonary artery pressure, right ventricular volume, left atrial size, and left ventricular mass. Therapy with continuous positive airway pressure is associated with lower blood pressure, atrial size, and ventricular mass, and a lower risk of AF recurrence after PVI.
atrial fibrillation; cardiac magnetic resonance; sleep apnea
Childhood obesity is a significant risk factor for cardiovascular disease in adulthood. Although ventricular remodeling has been reported in obese youth, early tissue‐level markers within the myocardium that precede organ‐level alterations have not been described.
Methods and Results
We studied 21 obese adolescents (mean age, 17.7±2.6 years; mean body mass index [BMI], 41.9±9.5 kg/m2, including 11 patients with type 2 diabetes [T2D]) and 12 healthy volunteers (age, 15.1±4.5 years; BMI, 20.1±3.5 kg/m2) using biomarkers of cardiometabolic risk and cardiac magnetic resonance imaging (CMR) to phenotype cardiac structure, function, and interstitial matrix remodeling by standard techniques. Although left ventricular ejection fraction and left atrial volumes were similar in healthy volunteers and obese patients (and within normal body size‐adjusted limits), interstitial matrix expansion by CMR extracellular volume fraction (ECV) was significantly different between healthy volunteers (median, 0.264; interquartile range [IQR], 0.253 to 0.271), obese adolescents without T2D (median, 0.328; IQR, 0.278 to 0.345), and obese adolescents with T2D (median, 0.376; IQR, 0.336 to 0.407; P=0.0001). ECV was associated with BMI for the entire population (r=0.58, P<0.001) and with high‐sensitivity C‐reactive protein (r=0.47, P<0.05), serum triglycerides (r=0.51, P<0.05), and hemoglobin A1c (r=0.76, P<0.0001) in the obese stratum.
Obese adolescents (particularly those with T2D) have subclinical alterations in myocardial tissue architecture associated with inflammation and insulin resistance. These alterations precede significant left ventricular hypertrophy or decreased cardiac function.
CT or MRI; obesity; type 2 diabetes
This study sought to assess myocardial perfusion and tissue oxygenation during vasodilator stress in patients with overt hypertrophic cardiomyopathy (HCM), as well as in HCM mutation carriers without left ventricular (LV) hypertrophy, and to compare findings to those in athletes with comparable hypertrophy and normal controls.
Myocardial perfusion under vasodilator stress is impaired in patients with HCM. Whether this is associated with impaired myocardial oxygenation and tissue ischemia is unknown. Furthermore, it is not known whether perfusion and oxygenation are impaired in HCM mutation carriers without left ventricular hypertrophy (LVH).
A total of 27 patients with overt HCM, 10 HCM mutation carriers without LVH, 11 athletes, and 20 healthy controls underwent cardiovascular magnetic resonance (CMR) scanning at 3-T. Myocardial function, perfusion (perfusion reserve index [MPRI]), and oxygenation (blood-oxygen level dependent signal intensity [SI] change) under adenosine stress were assessed.
MPRI was significantly reduced in HCM (1.3 ± 0.1) compared to controls (1.8 ± 0.1, p < 0.001) and athletes (2.0 ± 0.1, p < 0.001), but remained normal in HCM mutation carriers without LVH (1.7 ± 0.1; p = 0.61 vs. controls, p = 0.02 vs. overt HCM). Oxygenation response was attenuated in overt HCM (SI change 6.9 ± 1.4%) compared to controls (18.9 ± 1.4%, p < 0.0001) and athletes (18.7 ± 2.0%, p < 0.001). Interestingly, HCM mutation carriers without LVH also showed an impaired oxygenation response to adenosine (10.4 ± 2.0%; p = 0.001 vs. controls, p = 0.16 vs. overt HCM, p = 0.003 vs. athletes).
In overt HCM, both perfusion and oxygenation are impaired during vasodilator stress. However, in HCM mutation carriers without LVH, only oxygenation is impaired. In athletes, stress perfusion and oxygenation are normal. CMR assessment of myocardial oxygenation has the potential to become a novel risk factor in HCM.
athletes; cardiac magnetic resonance imaging; hypertrophy; ischemia; perfusion; BOLD, blood-oxygen level-dependent; CMR, cardiovascular magnetic resonance; ECG, electrocardiogram; HCM, hypertrophic cardiomyopathy; LGE, late gadolinium enhancement; LVH, left ventricular hypertrophy; MPRI, myocardial perfusion reserve index; PET, positron emission tomography; SI, signal intensity
Smoking causes endothelial dysfunction and systemic microvascular disease with resultant end-organ damage in the kidneys, eyes and heart. Little is known about microvascular changes in smoking-related lung disease. We tested if microvascular changes in the retina, kidneys and heart were associated with obstructive spirometry and low lung density on computed tomography. The Multi-Ethnic Study of Atherosclerosis recruited participants age 45–84 years without clinical cardiovascular disease. Measures of microvascular function included retinal arteriolar and venular caliber, urine albumin-to-creatinine ratio and, in a subset, myocardial blood flow on magnetic resonance imaging. Spirometry was measured following ATS/ERS guidelines. Low attenuation areas (LAA) were measured on lung fields of cardiac computed tomograms. Regression models adjusted for pulmonary and cardiac risk factors, medications and body size. Among 3,397 participants, retinal venular caliber was inversely associated with forced expiratory volume in one second (FEV1) (P<0.001) and FEV1/forced vital capacity (FVC) ratio (P = 0.04). Albumin-to-creatinine ratio was inversely associated with FEV1 (P = 0.002) but not FEV1/FVC. Myocardial blood flow (n = 126) was associated with lower FEV1 (P = 0.02), lower FEV1/FVC (P = 0.001) and greater percentage LAA (P = 0.04). Associations were of greater magnitude among smokers. Low lung function was associated with microvascular changes in the retina, kidneys and heart, and low lung density was associated with impaired myocardial microvascular perfusion. These cross-sectional results suggest that microvascular damage with end-organ dysfunction in all circulations may pertain to the lung, that lung dysfunction may contribute to systemic microvascular disease, or that there may be a shared predisposition.
Aortic enlargement and impaired bioelasticity are of interest in several cardiac and non-cardiac diseases as they can lead to cardiovascular complications. Cardiovascular magnetic resonance (CMR) is increasingly accepted as a noninvasive tool in cardiovascular evaluation. Assessment of aortic anatomy and bioelasticity, namely aortic distensibility and pulse wave velocity (PWV), by CMR is accurate and reproducible and could help to identify anatomical and bioelastic abnormalities of the aorta. However, normal CMR values for healthy children and young adults are lacking.
Seventy-one heart-healthy subjects (age 16.4 ± 7.6 years, range 2.3 - 28.3 years) were examined using a 3.0 Tesla CMR scanner. Aortic cross-sectional areas and aortic distensibility were measured at four positions of the ascending and descending thoracic aorta. PWV was assessed from aortic blood flow velocity measurements in a aortic segment between the ascending aorta and the proximal descending aorta. The Lambda-Mu-Sigma (LMS) method was used to obtain percentile curves for aortic cross-sectional areas, aortic distensibility and PWV according to age.
Aortic areas, PWV and aortic distensibility (aortic cross-sectional areas: r = 0.8 to 0.9, p < 0.001; PWV: r = 0.25 to 0.32, p = 0.047 to 0.009; aortic distensibility r = -0.43 to -0.62, p < 0.001) correlated with height, weight, body surface area, and age. There were no significant sex differences.
This study provides percentile curves for cross-sectional areas, distensibility and pulse wave velocity of the thoracic aorta in children and young adolescents between their 3rd and 29th year of life. These data may serve as a reference for the detection of pathological changes of the aorta in cardiovascular disease.