Changes in right ventricular (RV) morphology are associated with morbidity and mortality in heart and lung disease. We examined the association of abnormal RV structure and function with the risk of heart failure (HF) or cardiovascular death in a population-based multiethnic sample free of clinical cardiovascular disease at baseline.
Methods and Results
The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac magnetic resonance imaging (MRI) on 5098 participants between 2000–2002 with follow-up for incident heart failure and cardiovascular death (“death”) until January 2008. RV volumes and mass were available for 4204 participants. The study sample (N = 4,144) was 61.4 ± 10.1 years old and 47.6 % male. The presence of RV hypertrophy (increased RV mass) was associated with a more than twice the risk of heart failure or death after adjustment for demographics, body mass index, education, C-reactive protein level, hypertension, and smoking status (HR = 2.52, 95%CI 1.55–4.10, p < 0.001) and a doubling of risk (or more) with left ventricular mass at the mean value or lower (p for interaction = 0.05).
RV hypertrophy was associated with the risk of heart failure or death in a multi-ethnic population free of clinical cardiovascular disease at baseline.
right ventricle; pulmonary heart disease; magnetic resonance imaging; pulmonary hypertension; survival
Annually, ~80,000 Americans receive guideline-based primary prevention implantable cardioverter defibrillators (ICDs), but appropriate firing rates are low. Current selection criteria for ICDs rely on LVEF, which lacks sensitivity and specificity. Because scar-related, myocardial tissue heterogeneity is a substrate for life-threatening arrhythmias, we hypothesized that cardiac magnetic resonance (CMR) identification of myocardial heterogeneity improves risk stratification through: (1) its association with adverse cardiac events independent of clinical factors and biomarker levels; and (2) its ability to identify particularly high- and low-risk subgroups.
Methods and Results
In 235 ischemic and nonischemic patients with LVEF≤35%, undergoing clinically-indicated primary prevention ICD, gadolinium-enhanced CMR was prospectively performed to quantify the amount of heterogeneous myocardial tissue (gray zone-GZ) and dense core scar. Serum high sensitivity C-reactive protein (hsCRP) and other biomarkers were assayed. The primary endpoint was appropriate ICD shock for ventricular tachycardia/fibrillation or cardiac death, which occurred in 45 patients (19%) at 3.6 year median follow-up. On univariable analysis, only diuretics, hsCRP, GZ and core were associated with outcome. After multivariable adjustment, GZ and hsCRP remained independently associated with outcome (p<0.001). Patients in the lowest tertile for both GZ and hsCRP (n=42) were at particularly low risk (0.7%/year event rate) while those in the highest tertile for both GZ and hsCRP (n=32) had an event rate of 16.1%/year, p<0.001.
In a cohort of primary prevention ICD candidates, combining a myocardial heterogeneity index with an inflammatory biomarker identified a subgroup with a very low risk of adverse cardiac events, including ventricular arrhythmias. This novel approach warrants further investigation to confirm its value as a clinical risk stratification tool.
Clinical Trial Registration
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00181233.
implantable cardioverter-defibrillator; myocardial delayed enhancement; cardiovascular magnetic resonance imaging; cardiomyopathy; ventricular arrhythmia
The aim of this study was to use multi-detector computed tomography (MDCT) to assess therapeutic effects of myocardial regenerative cell therapies.
Cell transplantation is being widely investigated as a potential therapy in heart failure. Noninvasive imaging techniques are frequently used to investigate therapeutic effects of cell therapies in the preclinical and clinical setting. Previous studies have shown that cardiac MDCT can accurately quantify myocardial scar tissue and determine left ventricular (LV) volumes and ejection fraction (LVEF).
Twenty-two minipigs were randomized to intramyocardial injection of phosphate-buffered saline (placebo, n=9) or 200 million mesenchymal stem cells (MSCs, n=13), twelve weeks after myocardial infarction (MI). Cardiac MRI and MDCT acquisitions were performed prior to randomization 12 weeks after MI induction and at the study endpoint 24 week post-MI. None of the animals received medication to control the intrinsic heart rate during first-pass acquisitions for assessment of LV-volumes and LVEF. Delayed enhancement MDCT imaging was performed 10 min after contrast delivery. Two blinded observers analyzed MDCT acquisitions.
MDCT demonstrated that MSC therapy resulted in a reduction of infarct size from 14.3±1.2% to 10.3±1.5% of LV-mass (p=0.005) while infarct size increased in non-treated animals (from 13.8±1.3% to 16.5±1.5%; p=0.02) (Placebo vs MSC; p=0.003). Both observers had excellent agreement for infarct size (r=0.96; p<0.001). LVEF increased from 32.6±2.2% to 36.9±2.7% in MSC treated animals (p=0.03) and decreased in placebo animals (from 33.3±1.4 to 29.1±1.5%; p=0.01; at week 24: placebo vs MSC p=0.02). Infarct size, end-diastolic LV volume and LVEF assessed by MDCT compared favorably with MRI acquisitions (r=0.70; r=0.82; r=0.902; respectively, p<0.001).
This study demonstrates that cardiac MDCT can be used to evaluate infarct size, LV-volumes, and LVEF after intramyocardial delivered MSC therapy. These findings support the use of cardiac MDCT in preclinical and clinical studies for novel myocardial therapies. (word count 299)
MDCT; MRI; Delayed Contrast Enhancement; Göttingen Minipig; Mesenchymal Stem Cell; Myocardial Infarction; Heart failure
We examined whether MDCT improves the ability to define peri-infarct zone (PIZ) heterogeneity relative to MRI.
The PIZ as characterized by delayed enhanced (de) MRI identifies patients susceptible to ventricular arrhythmias and predicts outcome after myocardial infarction (MI).
Fifteen mini-pigs underwent coronary artery occlusion followed by reperfusion. MDCT and MRI were performed on the same day approximately 6 months after MI induction followed by animal sacrifice and ex-vivo MRI (n=5). Signal density threshold algorithms were applied to MRI and MDCT data sets reconstructed at various slice thicknesses (1–8mm) to define the PIZ and quantify partial volume effects.
De-MDCT reconstructed at 8mm slice thickness demonstrated excellent correlation of infarct size with post mortem pathology (r2=0.97; p<0.0001) and MRI (r2=0.92; p<0.0001). De-MDCT and de-MRI were able to detect a PIZ in all animals, which correlates to a mixture of viable and non-viable myocytes at the PIZ by histology. The ex-vivo de-MRI PIZ volume decreased with slice thickness from 0.9±0.2cc at 8mm to 0.2±0.1cc at 1mm (p=0.01). PIZ volume/mass by de-MDCT increased with decreasing slice thickness due to declining partial volume averaging in the PIZ, but was susceptible to increased image noise.
De-MDCT provides a more detailed assessment of the PIZ in chronic MI and is less susceptible to partial volume effects than MRI. This increased resolution best reflects the extent of tissue mixture by histopathology and has the potential to further enhance the ability to define the substrate of malignant arrhythmia in ischemic heart disease non-invasively.
MDCT; delayed enhancement; peri-infarct zone; MRI
Right ventricular (RV) morphology is an important predictor of outcomes in heart and lung disease, however determinants of RV anatomy have not been well-studied. We examined the demographic factors associated with RV morphology and function in a population-based multiethnic sample free of clinical cardiovascular disease.
Methods and Results
The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac magnetic resonance imaging (MRI) on 5098 participants. RV volumes and mass were available for 4204 participants. Normative equations for RV parameters were derived using an allometric approach. The study sample (N = 4123) was 61.5 ± 10.1 years old and 47.5% male. Older age was associated with lower RV mass (~5% lower mass per decade) with larger age-related decrements in men than in women (p for interaction < 0.05). Older age was also associated with higher RV ejection fraction (RVEF), an association which differed between races/ethnicities (p for interaction ≤ 0.01). Overall, men had greater RV mass (~8%) and larger RV volumes than women, but had lower RVEF (4% in absolute terms) (p < 0.001). African Americans had lower RV mass than Caucasians (p ≤ 0.002), whereas Hispanics had higher RV mass (p ≤ 0.02). Using the derived normative equations, 7.3% (95%CI, 6.5–8.1%) met criteria for RV hypertrophy and 5.9% (95%CI, 5.2–6.6%) had RV dysfunction.
In conclusion, age, sex, and race are associated with significant differences in RV mass, RV volumes and RVEF, potentially explaining distinct responses of the RV to cardiopulmonary disease.
right ventricle; pulmonary heart disease; magnetic resonance imaging; pulmonary hypertension
Coronary artery calcium (CAC), carotid intima-media thickness, and left ventricular (LV) mass and geometry offer the potential to characterize incident cardiovascular disease (CVD) risk in clinically asymptomatic individuals. The objective of the study was to compare these cardiovascular imaging measures for their overall and sex-specific ability to predict CVD.
Methods and Results
The study sample consisted of 4965 Multi-Ethnic Study of Atherosclerosis participants (48% men; mean age, 62±10 years). They were free of CVD at baseline and were followed for a median of 5.8 years. There were 297 CVD events, including 187 coronary heart disease (CHD) events, 65 strokes, and 91 heart failure (HF) events. CAC was most strongly associated with CHD (hazard ratio [HR], 2.3 per 1 SD; 95% CI, 1.9 to 2.8) and all CVD events (HR, 1.7; 95% CI, 1.5 to 1.9). Most strongly associated with stroke were LV mass (HR, 1.3; 95% CI, 1.1 to 1.7) and LV mass/volume ratio (HR, 1.3; 95% CI, 1.1 to 1.6). LV mass showed the strongest association with HF (HR, 1.8; 95% CI, 1.6 to 2.1). There were no significant interactions for imaging measures with sex and ethnicity for any CVD outcome. Compared with traditional risk factors alone, overall risk prediction (C statistic) for future CHD, HF, and all CVD was significantly improved by adding CAC, LV mass, and CAC, respectively (all P<0.05).
There was no evidence that imaging measures differed in association with incident CVD by sex. CAC was most strongly associated with CHD and CVD; LV mass and LV concentric remodeling best predicted stroke; and LV mass best predicted HF.
imaging; cardiovascular diseases; sex
Left ventricular (LV) mass is a strong predictor of cardiovascular disease (CVD), and magnetic resonance imaging (MRI) of the heart is a standard of reference for LV mass measurement. Ethnicity is believed to affect ECG performance. We evaluated the diagnostic and prognostic performance of ECG for left ventricular hypertrophy (LVH) as defined by MRI in relationship to ethnicity.
Methods and Results
Data were analyzed from 4967 participants (48% males, mean age 62 ± 10 years; 39% Caucasian, 13% Chinese, 26% African American, 22% Hispanic) enrolled in the Multi-Ethic Study of Atherosclerosis (MESA) who were followed for a median of 4.8 yearsfor incident CVD. Thirteen traditional ECG-LVH criteria were assessed and showed overall and ethnicity-specific low sensitivity (10–26%) and high specificity (88–99%) in diagnosing MRI-defined LVH. 10 out of 13 ECG-LVH criteria showed superior sensitivity and diagnostic performance in African Americans as compared to Caucasians (p=0.02–0.001). The sum of amplitudes of S wave in V1, S wave in V2 and R wave in V5 (a MESA specific ECG-LVH criterion) offered higher sensitivity (40.4%) compared to prior ECG-LVH criteria while maintaining good specificity (90%) and diagnostic performance (ROC area=0.65). In fully adjusted models, only the MESA-specific ECG-LVH criterion, Romhilt-Estes score, Framingham score, Cornell voltage, Cornell duration product and Framingham-adjusted Cornell voltage predicted increased CVD risk (p<0.05).
ECG has low sensitivity but high specificity for detecting MRI-defined LVH. The performance of ECG for LVH detection varies by ethnicity, with African Americans showing higher sensitivity and overall performance compared to other ethnic groups.
Coronary artery wall magnetic resonance imaging (MRI) has been developed to assess coronary lumen diameter and wall thickness. The purpose of this study was to evaluate the physiological parameters that affect the measures of coronary wall thickness using black-blood MRI pulse sequences.
Eighty-seven participants (38 men and 49 women) of the Multi-Ethnic Study of Atherosclerosis were enrolled in the coronary artery wall MRI study. Cine 4-chamber imaging was used to determine the coronary artery rest period. Free-breathing whole-heart magnetic resonance angiography with motion adaptor navigator was performed to localize the coronary arteries in 64 participants. Cross-sectional free-breathing black-blood images were acquired using electrocardiogram-gated, turbo spin echo sequence. Imaging parameters were as follows: repetition time = 2 R-R intervals, time to echo = 33 milliseconds, echo train length = 13, bandwidth = 305 Hz/pixel, matrix = 416 × 416, field of view = 420 × 420 mm, and slice thickness = 4 to 5 mm.
Imaging was completed in 215 (92%) of 234 coronary segments; 9 participants had incomplete scans. Mean age was 62.6 ± 8.4 years (range, 45–81 years). Mean body mass index was 29.2 ± 5.9 kg/m2. A higher proportion of images with quality of “good” was seen in the right coronary artery (40.5%) compared to the left main and left anterior descending coronary arteries (31.9% and 26.4%, respectively). There was a very good agreement between observers in the image quality scores (κ = 0.79, P < 0.001). Lower heart rate, male sex, and longer coronary rest period were associated with higher image quality score (P < 0.05). Signal-to-noise ratio was higher in participants with Agatston calcium score of more than 10 in the right coronary and left main arteries (48.5 vs 69.7, P = 0.001; and 53.4 vs 61.6, P = 0.032, respectively).
Improved depiction of the coronary artery wall with MRI is related to coronary rest period and atherosclerotic plaque burden as measured by calcium score and inversely related to heart rate. Because longer coronary artery rest periods are associated with improved image quality both for angiography with MRI and coronary artery wall imaging, heart rate–lowering methods in association with these techniques appear to be a logical application.
coronary; magnetic resonance imaging; image quality; MRI; cardiac
Multidetector computed tomography coronary angiography (CTA) is a robust method for the noninvasive diagnosis of coronary artery disease. However, in its current form, CTA is limited in its prediction of myocardial ischemia. The purpose of this study was to test whether adenosine stress computed tomography myocardial perfusion imaging (CTP), when added to CTA, can predict perfusion abnormalities caused by obstructive atherosclerosis.
Methods and Results
Forty patients with a history of abnormal single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) underwent adenosine stress 64-row (n=24) or 256-row (n=16) detector CTP and CTA. A subset of 27 patients had invasive angiography available for quantitative coronary angiography. CTA and quantitative coronary angiography were evaluated for stenoses ≥50%, and SPECT-MPI was evaluated for fixed and reversible perfusion deficits using a 17-segment model. CTP images were analyzed for the transmural differences in perfusion using the transmural perfusion ratio (subendocardial attenuation density/subepicardial attenuation density). The sensitivity, specificity, positive predictive value, and negative predictive value for the combination of CTA and CTP to detect obstructive atherosclerosis causing perfusion abnormalities using the combination of quantitative coronary angiography and SPECT as the gold standard was 86%, 92%, 92%, and 85% in the per-patient analysis and 79%, 91%, 75%, and 92% in the per vessel/territory analysis, respectively.
The combination of CTA and CTP can detect atherosclerosis causing perfusion abnormalities when compared with the combination of quantitative coronary angiography and SPECT.
imaging; atherosclerosis; ischemia; perfusion; myocardium
Very severe chronic obstructive pulmonary disease causes cor pulmonale with elevated pulmonary vascular resistance and secondary reductions in left ventricular filling, stroke volume, and cardiac output. We hypothesized that emphysema, as detected on computed tomography (CT), and airflow obstruction are inversely related to left ventricular end-diastolic volume, stroke volume, and cardiac output among persons without very severe lung disease.
We measured left ventricular structure and function with the use of magnetic resonance imaging in 2816 persons who were 45 to 84 years of age. The extent of emphysema (expressed as percent emphysema) was defined as the percentage of voxels below −910 Hounsfield units in the lung windows on cardiac computed tomographic scans. Spirometry was performed according to American Thoracic Society guidelines. Generalized additive models were used to test for threshold effects.
Of the study participants, 13% were current smokers, 38% were former smokers, and 49% had never smoked. A 10-point increase in percent emphysema was linearly related to reductions in left ventricular end-diastolic volume (−4.1 ml; 95% confidence interval [CI], −3.3 to −4.9; P<0.001), stroke volume (−2.7 ml; 95% CI, −2.2 to −3.3; P<0.001), and cardiac output (−0.19 liters per minute; 95% CI, −0.14 to −0.23; P<0.001). These associations were of greater magnitude among current smokers than among former smokers and those who had never smoked. The extent of airflow obstruction was similarly associated with left ventricular structure and function, and smoking status had similar modifying effects on these associations. Percent emphysema and airflow obstruction were not associated with the left ventricular ejection fraction.
In a population-based study, a greater extent of emphysema on CT scanning and more severe airflow obstruction were linearly related to impaired left ventricular filling, reduced stroke volume, and lower cardiac output without changes in the ejection fraction.
The purpose of this study was to assess coronary arterial remodeling as a marker of subclinical atherosclerosis using coronary wall MRI in an asymptomatic population-based cohort.
In early atherosclerosis, compensatory enlargement of both the outer wall of the vessel as well as the lumen, termed compensatory enlargement or positive remodeling, occurs before luminal narrowing.
179 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) were evaluated using black-blood coronary wall MRI. Coronary cross-sectional area (vessel size), lumen area, and mean wall thickness of the proximal coronary arteries were measured.
Men had a greater vessel size, lumen area, and mean wall thickness than women (38.3±11.3 versus 32.6±9.4 mm2, 6.7±3.2 versus 5.3±2.4 mm2, and 2.0±0.3 versus 1.9±0.3 mm, respectively, p<0.05). No significant coronary artery narrowing was present by magnetic resonance angiography. Overall, coronary vessel size increased 25.9 mm2 per millimeter increase in coronary wall thickness, while lumen area increased only slightly at 3.1 mm2 for every millimeter increase in wall thickness (difference in slopes, p<0.0001). Adjusting for age and gender, participants with Agatston score greater than zero were more likely to have wall thickness greater than 2.0 mm (odds ratio 2.0, 95% CI 1.01–3.84).
Coronary wall MRI detected positive arterial remodeling, in asymptomatic men and women with subclinical atherosclerosis.
subclinical atherosclerosis; magnetic resonance imaging; coronary artery disease; plaque
Age-related alterations of left ventricular (LV) structure and function that may predispose to cardiovascular events are not well understood.
Methods and Results
We used cardiac magnetic resonance imaging (MRI) to examine age-related differences in LV structure and function in 5004 participants without overt cardiovascular disease when enrolled in the Multi-Ethnic Study of Atherosclerosis; 1099 participants received additional strain analyses by MRI tagging. We also assessed the relation of age-associated remodeling with cardiovascular outcomes using Cox proportional hazard models adjusting for cardiovascular risk factors. Although LV mass decreased with age (−0.3 g per year), the mass-to-volume ratio markedly increased (+5 mg/mL per year, p<0.0001), driven by a substantial reduction in end-diastolic volume (−0.8 mL per year, p<0.0001). Age was also associated with a significant fall in stroke volume (−0.4 mL per year, p<0.0001) along with strain patterns reflecting systolic (p<0.0001) as well as diastolic (p<0.01) myocardial dysfunction – despite a modestly enhanced ejection fraction (+0.1% per year, p<0.0001). Increased mass-to-volume ratio conferred a significant risk for total cardiovascular events; this trend was strongest among younger (<65 years, HR 3.69 [CI 1.34–10.10]) versus older (≥65 years, HR 1.68 [CI 0.77–3.68]) individuals with the highest compared to lowest mass-to-volume ratio quintile (Pinteraction=0.013).
Age is associated with a phenotype of LV remodeling marked by increased mass-to-volume ratio and accompanied by systolic, as well as diastolic, myocardial dysfunction that is not reflected by preserved ejection fraction. This pattern of ventricular remodeling confers significant cardiovascular risk, particularly when present earlier in life.
aging; magnetic resonance imaging; myocardium; remodeling
The purpose of this study was to evaluate the relationship of left ventricular mass and geometry measured with cardiac MRI to incident cardiovascular events in the Multi-Ethnic Study of Atherosclerosis (MESA) study.
MRI is highly accurate for evaluation of heart size and structure and has not previously been used in a large epidemiologic study to predict cardiovascular events.
5098 participants in the MESA study underwent cardiac MRI at the baseline examination and were followed for a median of 4 years. Cox proportional hazard models were constructed to predict the endpoints of coronary heart disease (CHD), stroke and heart failure (HF) after adjustment for cardiovascular risk factors.
216 incident events were observed during the follow-up period. In adjusted models, the endpoints of incident CHD and stroke were positively associated with increased left ventricular mass to volume ratio (coronary heart disease, hazard ratio 2.1 per g/ml, p = 0.02; stroke, hazard ratio 4.2 per g/ml, p =0.005). In contrast, left ventricular mass showed the strongest association with incident HF events (hazard ratio 1.4 per 10% increment, p < 0.0001). HF events occurred primarily in participants with left ventricular hypertrophy, i.e.,≥ 95th percentile of left ventricular mass (hazard ratio 8.6, confidence interval, 3.7 – 19.9, reference group <50th percentile of LV mass).
Left ventricular size was related to incident HF, stroke and CHD in this multi-ethnic cohort. While body-size adjusted left ventricular mass alone predicted incident HF, concentric ventricular remodeling predicted incident stroke and CHD.
Heart failure; stroke; coronary heart disease; epidemiology; magnetic resonance imaging; left ventricular hypertrophy
Myocardial scarring from infarction (MI) or nonischemic fibrosis forms an arrhythmogenic substrate. The Selvester QRS-score has been extensively validated for estimating MI scar size in the absence of ECG confounders, but has not been tested to quantify scar in patients with hypertrophy, bundle branch/fascicular blocks or nonischemic cardiomyopathy. We assessed the hypotheses that (1) QRS-scores (modified for each ECG confounder) correctly identify and quantify scar in ischemic and nonischemic patients as compared to the reference standard of Cardiac Magnetic Resonance-Late Gadolinium Enhancement (CMR-LGE) and (2) QRS-estimated scar size predicts inducible sustained monomorphic ventricular tachycardia (MVT) during electrophysiologic (EP) testing.
Methods and Results
162 patients with left ventricular ejection fraction ≤35% (95 ischemic, 67 nonischemic) received 12-lead ECG and CMR-LGE before defibrillator (ICD) implantation for primary prevention of sudden cardiac death. QRS-scores correctly diagnosed CMR-scar presence with receiver operating characteristics area under the curve (AUC)=0.91 and correlation for scar quantification of r=0.74, p<0.0001, for all patients. Performance within hypertrophy, conduction defect and nonischemic subgroups ranged from AUC 0.81-0.94, r=0.60-0.80, p<0.001 for all. Among the 137 patients undergoing EP or device testing, each 3 point QRS-score increase (9% LV scarring) was associated with an odds ratio for inducing MVT of 2.2 [95% CI: 1.5-3.2, p<0.001] for all patients, 1.7 [1.0-2.7, p=0.04] for ischemics and 2.2 [1.0-5.0, p=0.05] for nonischemics.
QRS-scores identify and quantify scar in ischemic and nonischemic cardiomyopathy patients despite ECG confounders. Higher QRS-estimated scar size is associated with increased arrhythmogenesis and warrants further study as a risk-stratifying tool.
electrocardiography; imaging; infarction; arrhythmia
To determine the relationship between aortic wall thickness (WT) and distensibility with traditional cardiovascular risk factors in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort; 1053 participants of the MESA study with cardiac MRI were consecutively selected for measurement of aortic wall thickness and distensibility. Double inversion recovery fast spin echo images of the thoracic aorta were obtained to measure average and maximum WT. Aortic distensibility (AD) was measured at the same level using a gradient echo cine sequence. Both average and maximum WT were positively correlated with increasing age, and AD was inversely related to age (p<0.01). Compared to normotensive participants, those with hypertension had significantly greater mean average WT (2.45 mm vs. 2.23 mm, p<0.01), maximum WT (3.61 mm vs. 3.41 mm, p<0.01) and lower AD (0.15 vs. 0.2 mm Hg−1, p<0.01), respectively. In multiple regression analysis, older age and hypertension were significantly associated with higher mean average WT, while older age, male gender, and higher blood pressure were associated with higher mean maximum WT. AD was inversely related to older age, hypertension, current smoker status, African-American ethnicity and lower HDL-cholesterol (HDL-c) levels. In conclusion, in the MESA cohort, older age and higher blood pressure were associated with higher aortic wall thickness and lower aortic distensibilility. Decreased aortic distensibility was further associated with current smoking, African American ethnicity and higher HDL-c levels.
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
To determine the correlation function between the steady-state free precession (SSFP) and fast gradient echo (FGRE) cine MRI pulse sequences for measuring the myocardial mass and volumes.
Materials and Methods
Cardiac cine MRI examinations were acquired in 50 individuals (female: 35, male: 15, mean age 64.1 ± 9.1 years, range 48–83) using SSFP and FGRE cardiac pulse sequences.
The mean (standard deviation [SD]) left ventricular end diastolic volume measured by SSFP was significantly larger (4.5%) than by FGRE (p < 0.001); this was also the case for end systolic volume (15.0%, p < 0.001). The relationship between SSFP and FGRE measures were linear and highly correlated (p < 0.001) for both left ventricular end diastolic and end systolic volumes (r2 = 0.90 vs. 0.91, respectively). We determined linear regression models to estimate the SSFP values based on the FGRE measures. Slope (intercept) for ejection fraction, stroke volume, and cardiac output were 0.99 (−2.79), 0.77 (17.5), and 0.76 (1.29), respectively.
Linear relationships exist for key LV function parameters when comparing SSFP and FGRE cine MRI. These results indicate that existing databases and normal values for FGRE LV function may be converted to corresponding LV function values for SSFP MRI.
magnetic resonance imaging; normal cardiac function; steady state free precession; fast gradient echo
Left Ventricular Hypertrophy (LVH) is associated with end-stage renal disease and chronic kidney disease, but the association of LVH with mild impairment in kidney function is not known. We hypothesized that mild and moderate reductions in kidney function, reflected in higher serum cystatin C concentrations, would be linearly associated with a higher prevalence of LVH.
Cross-sectional observational study.
Settings and Participants:
4,971 participants participating in baseline examinations in the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based study with several sites in the U.S.
Cystatin C-based estimated glomerular filtration rate (eGFRcysC)
LVH and left ventricular (LV) mass index.
Serum cystatin C and creatinine, LV mass obtained by magnetic resonance imaging (MRI). LVH cutoffs for males and females were defined by the upper 95th percentile of LV mass index of all MESA participants without hypertension.
LVH was distinctly more prevalent (>12%) only in the lowest two deciles of eGFRcysC (<75 ml/min/1.73 m2). When participants with stage III or higher chronic kidney disease (creatinine eGFR <60 ml/min/1.73 m2) were excluded, the odds for LVH increased for each lower category of eGFRcysC below 75 ml/min/1.73 m2: 1.6 the odds for LVH with an eGFRcysC between 60-75 ml/min/1.73 m2 (95% confidence interval 1.20-2.07, P = 0.001), and 2.0 the odds for an eGFRcysC <60 ml/min/1.73 m2 (1.03-3.75, P = 0.04), after adjustment for demographic factors, study site, diabetes, and smoking. The association of the a lower eGFRcysC with LVH was attenuated after further adjustment for hypertension.
Cross-sectional, rather than longitudinal design, lack of participants with more advanced kidney disease, lack of a direct measurement of glomerular filtration rate.
Among subjects without CKD, eGFRcysC ≤ 75 ml/min/1.73 m2 was associated with a higher odds of LVH.
kidney disease; cystatin C; glomerular filtration rate; left ventricular hypertrophy; left ventricular mass; magnetic resonance imaging (MRI)
The extent of the peri-infarct zone by magnetic resonance imaging (MRI) has been related to all-cause mortality in patients with coronary artery disease. This relationship may result from arrhythmogenesis in the infarct border. However, the relationship between tissue heterogeneity in the infarct periphery and arrhythmic substrate has not been investigated. In the present study, we quantify myocardial infarct heterogeneity by contrast-enhanced MRI and relate it to an electrophysiological marker of arrhythmic substrate in patients with left ventricular (LV) systolic dysfunction undergoing prophylactic implantable cardioverter defibrillator placement.
Methods and Results
Before implantable cardioverter defibrillator implantation for primary prevention of sudden cardiac death, 47 patients underwent cine and contrast-enhanced MRI to measure LV function, volumes, mass, and infarct size. A method for quantifying the heterogeneous infarct periphery and the denser infarct core is described. MRI indices were related to inducibility of sustained monomorphic ventricular tachycardia during electrophysiological or device testing. For the noninducible versus inducible patients, LV ejection fraction (30±10% versus 29±7%, P=0.79), LV end-diastolic volume (220±70 versus 228±57 mL, P=0.68), and infarct size by standard contrast-enhanced MRI definitions (P=NS) were similar. Quantification of tissue heterogeneity at the infarct periphery was strongly associated with inducibility for monomorphic ventricular tachycardia (noninducible versus inducible: 13±9 versus 19±8 g, P=0.015) and was the single significant factor in a stepwise logistic regression.
Tissue heterogeneity is present and quantifiable within human infarcts. More extensive tissue heterogeneity correlates with increased ventricular irritability by programmed electrical stimulation. These findings support the hypothesis that anatomic tissue heterogeneity increases susceptibility to ventricular arrhythmias in patients with prior myocardial infarction and LV dysfunction.
myocardial infarction; arrhythmia; cardiomyopathy; diagnosis; imaging; magnetic resonance imaging
Patients with DM are at risk for atrioventricular block and left ventricular (LV) dysfunction. Non-invasive detection of diffuse myocardial fibrosis may improve disease management in this population.
Our aim was to define functional and post-contrast myocardial T1 time cardiac magnetic resonance (CMR) characteristics in myotonic muscular dystrophy (DM) patients.
Thirty-three DM patients (24 with type 1 and 9 with type 2) and 13 healthy volunteers underwent CMR for assessment of LV indices and evaluation of diffuse myocardial fibrosis by T1 mapping. The association of myocardial T1 time to ECG abnormalities and LV indices were examined among DM patients.
DM patients had lower end-diastolic volume index (68.9 vs. 60.3 ml/m2, p=0.045), cardiac index (2.7 vs. 2.33 L/min/m2, p=0.005) and shorter myocardial T1time (394.5 vs. 441.4 ms, p<0.0001), compared to control subjects. Among DM patients, there was a positive association between higher T1 time and LV mass index (2.2 ms longer per gm/m2, p=0.006), LV end-diastolic volume index (1.3 ms longer per ml/m2, p=0.026), filtered QRS duration (1.2 ms longer per unit, p=0.005) and low-amplitude (<40mcV) late-potential duration (0.9 ms longer per unit, p=0.01). Using multivariate random effects regression, each 10 ms increase in myocardial T1 time of type 1 DM patients was independently associated with 1.3 ms increase in longitudinal PR and QRS intervals during follow-up.
DM is associated with structural alterations on CMR. Post-contrast myocardial T1 time was shorter in DM patients than controls likely reflecting the presence of diffuse myocardial fibrosis.
Myotonic muscular dystrophy; MRI; T1 mapping; ventricular function
All cardiac magnetic resonance (CMR) techniques aim to create still depictions of a dynamic and ever-adapting organ. Most CMR methods rely on cardiac gating to capture information during fleeting periods of relative cardiac quiescence, at end diastole or end systole, or to acquire partial images throughout the cardiac cycle and average these signals over several heart beats. Since the inception of clinical CMR in the early 1980s, priority has been given to improving methods for image gating. The aim of this work is to provide a basic understanding of the ECG acquisition, demonstrate common ECG-related artifacts and to provide practical methods for overcoming these issues. Meticulous ECG preparation is essential for optimal CMR acquisition and these techniques must be adaptable to the individual patient.
Magnetic resonance imaging; ECG; Trigger
Increased left ventricular myocardial thickness (LVMT) is a feature of several cardiac diseases. The purpose of this study was to establish standard reference values of normal LVMT with cardiac MR (CMR) and to assess variation with image acquisition plane, demographics and LV function.
Methods and Results
End-diastolic LVMT was measured on CMR steady-state free precession cine long and short axis images in 300 consecutive participants free of cardiac disease (169 women; 65.6±8.5 years) of the Multi-Ethnic Study of Atherosclerosis cohort. Mean LVMT on short axis images at the mid-cavity level was 5.3±0.9mm and 6.3±1.1mm for women and men, respectively. The average of the maximum LVMT at the mid-cavity for women/men were 7mm/9mm (long axis) and 7mm/8mm (short axis). Mean LVMT was positively associated with weight (0.02mm/kg, p=0.01) and body-surface-area (1.1mm/m2, p<0.001). No relationship was found between mean LVMT and age or height. Greater mean LVMT was associated with lower LV end-diastolic volume (0.01mm/ml, p<0.01), a lower LV end-systolic volume (−0.01mm/ml, p=0.01) and lower LV stroke volume (−0.01mm/ml, p<0.05). LVMT measured on long axis images at the basal and mid-cavity level were slightly greater (by 6% and 10%, respectively) than measurements obtained on short axis images; apical LVMT values on long axis images were 20% less than those on short axis images.
Normal values for wall thickness are provided for middle-aged and older subjects. Normal LVMT is lower for women than men. Observed values vary depending on the imaging plane for measurement.
magnetic resonance imaging; myocardial thickness; normal values
A high degree of non-compacted (trabeculated) myocardium in relationship to compact myocardium (T/M ratio >2.3) has been associated with a diagnosis of left ventricular non-compaction (LVNC). The purpose of this study was to determine the normal range of the T/M ratio in a large population-based study and to examine the relationship to demographic and clinical parameters.
Methods and Results
The thickness of trabeculation and the compact myocardium were measured in eight LV regions on long axis cardiac magnetic resonance (CMR) steady-state free precession cine images in 1000 participants (551 women; 68.1±8.9 years) of the Multi-Ethnic Study of Atherosclerosis cohort. Of 323 participants without cardiac disease or hypertension and with all regions evaluable 140 (43%) had a T/M ratio >2.3 in at least one region; in 20/323 (6%), T/M>2.3 was present in more than two regions. Multivariable linear regression model revealed no association of age, gender, ethnicity, height and weight with maximum T/M ratio in participants without cardiac disease or hypertension (p>0.05). In the entire cohort (n=1000) LVEF (β=−0.02/%; p=0.015), LVEDV (β=0.01/ml; p=<0.0001) and LVESV (β=0.01/ml; p<0.001) were associated with maximum T/M ratio in adjusted models while there was no association with hypertension or myocardial infarction (p>0.05). At the apical level T/M ratios were significantly lower when obtained on short- compared to long-axis images (p=0.017).
A ratio of trabeculated to compact myocardium of more than 2.3 is common in a large population based cohort. These results suggest reevaluation of the current CMR criteria for LVNC may be necessary.
cardiovascular magnetic resonance imaging; cardiomyopathy; non-compaction; trabeculation
The association of right ventricular (RV) structure and function with symptoms in individuals without cardiopulmonary disease is unknown. We hypothesized that greater RV mass and RV end-diastolic volume (RVEDV), smaller RV stroke volume (RVSV), and lower RV ejection fraction (RVEF) measured by cardiac magnetic resonance imaging (MRI) in participants free of clinical cardiovascular disease at baseline would be associated with a greater risk of self-reported dyspnea.
The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac MRIs on participants without clinical cardiovascular disease between 2000 and 2002. We excluded subjects who reported “prevalent” dyspnea at the first assessment (24 months). The presence of dyspnea was assessed at 24 months, 42 months, and 60 months from baseline. Cox proportional hazards models were used to examine the relationship between RV measures and incident dyspnea.
In the final study sample (N = 2763), there were significant interactions between RV measures and sex in terms of the risk of dyspnea (p<0.05). Among men (N = 1453), lower RV mass (p = 0.003), smaller RVEDV (p<0.001), smaller RV end-systolic volume (RVESV) (p = 0.03) and decreased RVSV (p<0.001) were associated with an increased risk of developing dyspnea after adjusting for covariates. Associations remained after adjusting for left ventricular function and lung function. However, there were no significant associations between RV measures and the risk of dyspnea in women.
Lower RV mass and smaller RV volumes were associated with an increased risk of dyspnea in men, but not in women.