Background

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.

Conclusions

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.

Objective

The aim of this study was to use multi-detector computed tomography (MDCT) to assess therapeutic effects of myocardial regenerative cell therapies.

Background

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).

Methods

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.

Results

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).

Conclusions

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)

Objectives

We examined whether MDCT improves the ability to define peri-infarct zone (PIZ) heterogeneity relative to MRI.

Background

The PIZ as characterized by delayed enhanced (de) MRI identifies patients susceptible to ventricular arrhythmias and predicts outcome after myocardial infarction (MI).

Methods

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.

Results

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.

Conclusion

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.

Background

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.

Conclusions

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.

Background

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).

Conclusions

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.

Background

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).

Conclusions

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.

Objective

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.

Methods

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.

Results

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).

Conclusion

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.

Background

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.

Conclusions

The combination of CTA and CTP can detect atherosclerosis causing perfusion abnormalities when compared with the combination of quantitative coronary angiography and SPECT.

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

OBJECTIVES

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.

BACKGROUND

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.

METHODS

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.

RESULTS

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).

CONCLUSIONS

Coronary wall MRI detected positive arterial remodeling, in asymptomatic men and women with subclinical atherosclerosis.

Background

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).

Conclusion

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.

Objective

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.

Background

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.

Methods

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.

Results

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).

Conclusions

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.

Background

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.

Conclusions

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.

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.

Structured Abstract

Objectives

We examined whether the presence and extent of late gadolinium enhancement (LGE) by CMR predict adverse outcomes in nonischemic cardiomyopathy (NICM) patients.

Background

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.

Methods

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.

Results

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).

Conclusions

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.

Condensed Abstract

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.

Purpose

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.

Results

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.

Conclusion

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.

Background:

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.

Study Design:

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.

Predictor:

Cystatin C-based estimated glomerular filtration rate (eGFRcysC)

Outcomes:

LVH and left ventricular (LV) mass index.

Measurements:

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.

Results:

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.

Limitations:

Cross-sectional, rather than longitudinal design, lack of participants with more advanced kidney disease, lack of a direct measurement of glomerular filtration rate.

Conclusions:

Among subjects without CKD, eGFRcysC ≤ 75 ml/min/1.73 m2 was associated with a higher odds of LVH.

Background

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.

Conclusions

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.

Background

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.

Methods

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.

Results

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.

Conclusions

Lower RV mass and smaller RV volumes were associated with an increased risk of dyspnea in men, but not in women.

PURPOSE

To evaluate the relationship between “Look-Locker” (LL) and modified Look-Locker Inversion recovery (MOLLI) approaches for T1 mapping of the myocardium.

MATERIALS AND METHODS

168 myocardial T1 maps using MOLLI and 165 maps using LL were obtained in human subjects at 1.5 Tesla. The T1 values of the myocardium were calculated before and at five time points after gadolinium administration. All time and heart rate normalizations were done. The T1 values obtained were compared to determine the absolute and bias agreement.

RESULTS

The pre-contrast global T1 values were similar when measured by the LL and by MOLLI technique (mean 1004.9 ms +/- 120.3 vs. 1034.1 ms +/- 53.1, respectively, p = 0.26). Post-contrast myocardial T1 time from LL was significantly longer than MOLLI from 5 to 25 minutes (mean difference, LL - MOLLI was +61.8 +/- 46.4 ms, p < 0.001). No significant differences in T1 values were noted between long and short axis measurements for either MOLLI or LL.

CONCLUSION

Post-contrast LL and MOLLI showed very good agreement, although LL vaules are higher than MOLLI. Pre-contrast T1 values showed good agreement, however LL has greater limits of agreement. Short and long axis planes can reliably assess T1 values.

Quantitative T1 mapping of delayed gadolinium-enhanced cardiac magnetic resonance imaging has shown promise in identifying diffuse myocardial fibrosis. Despite careful control of magnetic resonance imaging parameters, comparison of T1 times between different patients may be problematic because of patient specific factors such as gadolinium dose, differing glomerular filtration rates, and patient specific delay times. In this work, a model driven approach to account for variations between patients to allow for comparison of T1 data is provided. Kinetic model parameter values were derived from healthy volunteer time-contrast curves. Correction values for the factors described above were used to normalize T1 values to a matched state. Examples of pre- and postcorrected values for a pool of normal subjects and in a patient cohort of type 1 diabetic patients shows tighter clustering and improved discrimination of disease state.

Objectives

This study was designed to evaluate whether the absence of coronary calcium could rule out ≥50% coronary stenosis or the need for revascularization.

Background

The latest American Heart Association guidelines suggest that a calcium score (CS) of zero might exclude the need for coronary angiography among symptomatic patients.

Methods

A substudy was made of the CORE64 (Coronary Evaluation Using Multi-Detector Spiral Computed Tomography Angiography Using 64 Detectors) multicenter trial comparing the diagnostic performance of 64-detector computed tomography to conventional angiography. Patients clinically referred for conventional angiography were asked to undergo a CS scan up to 30 days before.

Resutls

In all, 291 patients were included, of whom 214 (73%) were male, and the mean age was 59.3 ± 10.0 years. A total of 14 (5%) patients had low, 218 (75%) had intermediate, and 59 (20%) had high pre-test probability of obstructive coronary artery disease. The overall prevalence of ≥50% stenosis was 56%. A total of 72 patients had CS = 0, among whom 14 (19%) had at least 1 ≥50% stenosis. The overall sensitivity for CS = 0 to predict the absence of ≥50% stenosis was 45%, specificity was 91%, negative predictive value was 68%, and positive predictive value was 81%. Additionally, revascularization was performed in 9 (12.5%) CS = 0 patients within 30 days of the CS. From a total of 383 vessels without any coronary calcification, 47 (12%) presented with ≥50% stenosis; and from a total of 64 totally occluded vessels, 13 (20%) had no calcium.

Conclusions

The absence of coronary calcification does not exclude obstructive stenosis or the need for revascularization among patients with high enough suspicion of coronary artery disease to be referred for coronary angiography, in contrast with the published recommendations. Total coronary occlusion frequently occurs in the absence of any detectable calcification.

Background

Racial/ethnic differences in the incidence and severity of heart failure (HF) are not well understood, but may be related to pre-existing variations in myocardial function.

Objective

To examine racial/ethnic differences in regional myocardial function among asymptomatic individuals free of known cardiovascular disease.

Design, setting and patients

The Multi-Ethnic Study of Atherosclerosis is a prospective, observational study of individuals without baseline cardiovascular disease, representing four major racial/ethnic groups. A total of 1099 study participants underwent cardiac MRI with tissue tagging; for each study, peak systolic strain (Ecc) and strain rate (SRs) were determined in four left ventricular (LV) regions.

Main outcome measures

Multiple linear regression was used to analyse the relationship between race/ethnicity and regional strain (Ecc and SRs) while adjusting for cardiovascular risk factors.

Results

Compared with other racial/ethnic groups, Chinese-Americans had the greatest magnitude of Ecc in a majority of LV regions (–19.60±3.78, p<0.05); Chinese-Americans also had the greatest absolute values for SRs in all regions, reflecting higher rate of systolic contraction (–2.01±0.76, p<0.05). Conversely, African-Americans had the lowest Ecc values (–17.50±4.00, p<0.05) in the majority of wall regions while Hispanics demonstrated the lowest rate of contractility in all wall regions (–1.44±0.50, p≤0.001) in comparison with the other racial/ethnic groups. These race-based differences remained significant in the majority of LV wall regions after adjusting for multiple variables, including hypertension and LV mass.

Conclusions

Important race-based differences in regional LV systolic function in a large cohort of asymptomatic individuals have been demonstrated. Further research is needed to investigate the possible mechanisms related to the race/ethnicity-based variations found in this study.

Multislice computed tomography (MSCT) for the noninvasive detection of coronary artery stenoses is a promising candidate for widespread clinical application because of its noninvasive nature and high sensitivity and negative predictive value as found in several previous studies using 16 to 64 simultaneous detector rows. A multi-centre study of CT coronary angiography using 16 simultaneous detector rows has shown that 16-slice CT is limited by a high number of nondiagnostic cases and a high false-positive rate. A recent meta-analysis indicated a significant interaction between the size of the study sample and the diagnostic odds ratios suggestive of small study bias, highlighting the importance of evaluating MSCT using 64 simultaneous detector rows in a multi-centre approach with a larger sample size. In this manuscript we detail the objectives and methods of the prospective “CORE-64” trial (“Coronary Evaluation Using Multidetector Spiral Computed Tomography Angiography using 64 Detectors”). This multi-centre trialwas unique in that it assessed the diagnostic performance of 64-slice CT coronary angiography in nine centres worldwide in comparison to conventional coronary angiography. In conclusion, the multi-centre, multi-institutional and multi-continental trial CORE-64 has great potential to ultimately assess the per-patient diagnostic performance of coronary CT angiography using 64 simultaneous detector rows.

Rationale: Intense exercise in elite athletes is associated with increased left ventricular (LV) and right ventricular (RV) mass and volumes. However, the effect of physical activity on the RV in an older community-based population is unknown.

Objectives: We studied the association between levels of physical activity in adults and RV mass and volumes.

Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac magnetic resonance imaging on community-based participants without clinical cardiovascular disease. RV volumes were determined from manually contoured endocardial margins. RV mass was determined from the difference between epicardial and endocardial volumes multiplied by the specific gravity of myocardium. Metabolic equivalent–minutes/day were calculated from the self-reported frequency, duration, and intensity of physical activity.

Measurements and Main Results: The study sample (n = 1,867) was aged 61.8 ± 10 years, 48% male, 44% white, 27% African American, 20% Hispanic, and 9% Chinese. Higher levels of moderate and vigorous physical activity were linearly associated with higher RV mass (P = 0.02) after adjusting for demographics, anthropometrics, smoking, cholesterol, diabetes mellitus, hypertension, and LV mass. Higher levels of intentional exercise (physical activity done for the sole purpose of conditioning or fitness) were nonlinearly associated with RV mass independent of LV mass (P = 0.03). There were similar associations between higher levels of physical activity and larger RV volumes.

Conclusions: Higher levels of physical activity in adults were associated with greater RV mass independent of the associations with LV mass; similar results were found for RV volumes. Exercise-associated RV remodeling may have important clinical implications.