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2.  Regional Left Ventricular Myocardial Dysfunction as a Predictor of Incident Cardiovascular Events 
We sought to examine the prognostic value of subclinical left ventricular (LV) regional myocardial dysfunction (RMD) measured by magnetic resonance imaging (MRI) among asymptomatic individuals.
LV RMD, defined as segmental impairment in systolic wall thickening, predicts adverse events in patients with established cardiovascular disease. MRI is highly accurate for detecting subtle RMD, of which the prognostic significance in a large multiethnic asymptomatic population is not known.
We used MRI to evaluate baseline regional LV myocardial function and prospectively followed a multiethnic (African American, Caucasian, Chinese, and Hispanic) population-based sample of 4,510 men and women without cardiovascular disease for a mean of 4.6 years. Regional myocardial dysfunction was defined as the presence of impaired systolic wall thickening (<10th percentile of segment-specific population distribution) in ≥2 contiguous LV segments within any given coronary artery territory.
Baseline prevalence of RMD was 25.6%. Heart failure developed in 34 (1.0%) and 30 (2.6%) participants without and with RMD, respectively (p < 0.001). After adjustment for demographics and traditional risk factors, RMD remained independently associated with incident heart failure (hazard ratio [HR]: 2.62; 95% confidence interval [CI]: 1.56 to 4.39; p < 0.001). The relationship persisted after further adjustment for biomarkers of reported association with cardiovascular disease and indexes of global LV systolic dysfunction and hypertrophy (HR: 1.80; 95% CI: 1.02 to 3.20; p = 0.044). Similarly, RMD independently conferred an increased risk for hard coronary events (myocardial infarction or death from coronary heart disease; HR: 1.75; 95% CI: 1.06 to 2.89; p = 0.029), the composite of hard coronary events and stroke (HR: 1.72; 95% CI: 1.16 to 2.56; p = 0.005), and all atherosclerotic cardiovascular events (HR: 1.50; 95% CI: 1.09 to 2.07; p = 0.012).
Among an asymptomatic multiethnic American cohort, RMD is an independent predictor beyond traditional risk factors and global LV assessment for incident heart failure and atherosclerotic cardiovascular events. The clinical utility of early recognition of this subclinical phenotype deserves further investigation.
PMCID: PMC4124734  PMID: 21511109
epidemiology; heart failure; magnetic resonance imaging; myocardial dysfunction; prognosis
3.  Prognostic Implications of Left Ventricular Dyssynchrony for Major Adverse Cardiovascular Events in Asymptomatic Women and Men: The Multi‐Ethnic Study of Atherosclerosis 
Left ventricular (LV) dyssynchrony is related to adverse outcomes in systolic heart failure, but its prognostic importance in asymptomatic population is not known. Our objective was to assess the prognostic implications of LV mechanical dyssynchrony in a large multiethnic population before the occurrence of global LV dysfunction.
Methods and Results
A total of 1392 participants in the Multi‐Ethnic Study of Atherosclerosis (MESA; mean age: 64.7 years; 46% were women) with cardiac magnetic resonance imaging at baseline were followed for a median duration of 8.3 years. Harmonic phase imaging analysis was used to derive systolic circumferential strain. Greater standard deviation of time to peak systolic strain (SD‐TPS) indicates greater dyssynchrony. With SD‐TPS as a continuous variable, Cox proportional hazards analysis was used to assess hazards ratio after adjusting for demographics, cardiovascular risk factors, LV mass‐to‐volume ratio, and ejection fraction. Using the 75th percentile of SD‐TPS as a cutoff, Kaplan–Meier analysis was performed between 2 categorical groups for each gender. Higher values of dyssynchrony in women predicted major adverse cardiovascular events, defined as myocardial infarction, heart failure, stroke, and death (hazard ratio: 1.01 per 1‐ms increment in SD‐TPS, P=0.015), hard coronary events (hazard ratio: 1.05 per 1‐ms increment in SD‐TPS, P=0.026), and cerebrovascular events (hazard ratio: 1.03 per 1‐ms increment in SD‐TPS, P=0.013). In contrast, dyssynchrony in men was not predictive of events. Kaplan–Meier analyses in women revealed increased event occurrence in the higher dyssynchrony group, but this was not the case in men.
In an asymptomatic cohort, greater LV dyssynchrony determined by cardiac magnetic resonance imaging predicts adverse cardiovascular outcome in women but not in men.
Clinical Trial Registration
URL: Unique identifier: NCT00005487.
PMCID: PMC4310386  PMID: 25092789
cardiac magnetic resonance imaging; cardiovascular events; left ventricular dyssynchrony; prognosis
4.  Evaluation of Age-Related Interstitial Myocardial Fibrosis With Cardiac Magnetic Resonance Contrast-Enhanced T1 Mapping in the Multi-Ethnic Study of Atherosclerosis (MESA) 
Journal of the American College of Cardiology  2013;62(14):10.1016/j.jacc.2013.05.078.
This study sought to determine the relationship of cardiovascular magnetic resonance (CMR) measures of tissue composition to age in the Multi-Ethnic Study of Atherosclerosis (MESA).
Animal and human studies have demonstrated increased collagen deposition in senescent hearts. New CMR indices of tissue composition by using T1 mapping are sensitive to the presence of myocardial fibrosis.
A total of 1,231 study participants (51% women; age range 54 to 93 years) of the MESA cohort were evaluated with T1 mapping by using 1.5-T CMR scanners. None of the participants had focal scar on delayed enhancement CMR. Single-slice T1 mapping was performed at the midventricular level before and at 12- and 25-min delay after administration of gadolinium contrast by using a modified Look-Locker inversion recovery sequence. The partition coefficient was determined by the slope of the linear relationship of (1/T1myo vs. 1/T1blood). The extracellular volume fraction (ECV) was derived accounting for the hematocrit level. Multivariable regression analyses were performed, adjusting for traditional risk factors and left ventricular structure.
Women had significantly greater partition coefficient, ECV, and precontrast T1 than men, as well as lower post-contrast T1 values (all p < 0.05). In general, linear regression analyses demonstrated that greater partition coefficient, pre-contrast T1 values, and ECV were associated with older age in men (multivariate regression coefficients = 0.01; 5.9 ms; and 1.04% per 10 years’ change; all p < 0.05). ECV was also significantly associated with age in women after multivariable adjustments.
CMR parameters that have been associated with myocardial fibrosis were related to older age in the MESA study. Women had higher ECV than men but less ECV change over time.
PMCID: PMC3807823  PMID: 23871886
aging; magnetic resonance imaging; myocardial fibrosis; T1 mapping
5.  Relation of Left Ventricular Mass at Age 23 to 35 years to Global Left Ventricular Systolic Function 20 Years Later (From the Coronary Artery Risk Development in Young Adults Study) 
The American journal of cardiology  2013;113(2):377-383.
Left ventricular (LV) mass and LV ejection fraction (EF) are major independent predictors of future cardiovascular disease. The association of LV mass with future LVEF in younger populations has not been studied. We investigated the relation of LV mass index (LVMI) at age 23 to 35 years to LV function after 20 years of follow-up in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. CARDIA is a longitudinal study that enrolled young adults in 1985–1986. We included participants with echocardiographic examinations at both years-5 and -25. LVMI and LVEF were assessed using M-mode echocardiography at year-5 and using both M-mode and 2-dimensional images at year-25. Statistical analytic models assessed the correlation between LVMI and LV functional parameters both cross-sectionally and longitudinally. A total of 2,339 participants were included. The mean LVEF at year-25 was 62%. Although there was no cross-sectional correlation between LVMI and LVEF at year-5, there was a small, but statistically significant negative correlation between LVMI at year-5 and LVEF 20 years later (r = −0.10, p < 0.0001); this inverse association persisted for LVMI in the multivariable model. High LVMI was an independent predictor of systolic dysfunction (LVEF < 50%) 20 years later (odds ratio 1.46, p = 0.0018). In conclusion, we have shown that LVMI in young adulthood in association with chronic risk exposure impacts systolic function in middle age; the antecedents of heart failure may occur at younger ages than previously thought.
PMCID: PMC3901209  PMID: 24176073
left ventricular mass; left ventricular ejection fraction; echocardiography; left ventricular remodeling
6.  Left ventricular mass and hypertrophy by echocardiography and cardiac magnetic resonance: The Multi-Ethnic Study of Atherosclerosis 
Echocardiography (Mount Kisco, N.Y.)  2013;31(1):10.1111/echo.12303.
Left ventricular mass (LVM) and hypertrophy (LVH) are important parameters, but their use is surrounded by controversies. We compare LVM by echocardiography and cardiac magnetic resonance (CMR), investigating reproducibility aspects and the effect of echocardiography image quality. We also compare indexing methods within and between imaging modalities for classification of LVH and cardiovascular risk.
MESA enrolled 880 participants in Baltimore City; 146 had echocardiograms and CMR on the same day. LVM was then assessed using standard techniques. Echocardiography image quality was rated (good/limited) according to the parasternal view. LVH was defined after indexing LVM to body surface area, height1.7, height2.7, or by the predicted LVM from a reference group. Participants were classified for cardiovascular risk according to Framingham score. Pearson’s correlation, Bland-Altman plots, percent agreement, and kappa coefficient assessed agreement within and between modalities.
LVM by echocardiography (140 ± 40 g) and by CMR were correlated (r = 0.8, p < 0.001) regardless of the echocardiography image quality. The reproducibility profile had strong correlations and agreement for both modalities. Image quality groups had similar characteristics; those with good images compared to CMR slightly superiorly. The prevalence of LVH tended to be higher with higher cardiovascular risk. The agreement for LVH between imaging modalities ranged from 77% to 98% and the kappa coefficient from 0.10 to 0.76.
Echocardiography has a reliable performance for LVM assessment and classification of LVH, with limited influence of image quality. Echocardiography and CMR differ in the assessment of LVH, and additional differences rise from the indexing methods.
PMCID: PMC3830716  PMID: 23930739
Left ventricular mass; left ventricular hypertrophy; echocardiography; image quality
7.  The Association Between Physical Activity and Both Incident Coronary Artery Calcification and Ankle Brachial Index Progression: The Multi-Ethnic Study of Atherosclerosis 
Atherosclerosis  2013;230(2):278-283.
Both coronary artery calcification (CAC) and the ankle brachial index (ABI) are measures of subclinical atherosclerotic disease. The influence of physical activity on the longitudinal change in these measures remains unclear. To assess this we examined the association between these measures and self-reported physical activity in the Multi-Ethnic Study of Atherosclerosis (MESA).
At baseline, the MESA participants were free of clinically evident cardiovascular disease. We included all participants with an ABI between 0.90 and 1.40 (n=5656). Predictor variables were based on self-reported measures with physical activity being assessed using the Typical Week Physical Activity Survey from which metabolic equivalent-minutes/week of activity were calculated. We focused on physical activity intensity, intentional exercise, sedentary behavior, and conditioning. Incident peripheral artery disease (PAD) was defined as the progression of ABI to values below 0.90 (given the baseline range of 0.90 to 1.40). Incident CAC was defined as a CAC score >0 Agatston units upon follow up with a baseline score of 0 Agatston units.
Mean age was 61 years, 53% were female, and mean body mass index was 28 kg/m2. After adjusting for traditional cardiovascular risk factors and socioeconomic factors, intentional exercise was protective for incident peripheral artery disease (Relative Risk (RR)= 0.85, 95% Confidence Interval (CI): 0.74 to 0.98). After adjusting for traditional cardiovascular risk factors and socioeconomic factors, there was a significant association between vigorous PA and incident CAC (RR=0.97, 95% CI: 0.94 to 1.00). There was also a significant association between sedentary behavior and increased amount of CAC among participants with CAC at baseline (Δlog(Agatston Units +25)=0.027, 95% CI 0.002, 0.052).
These data suggest that there is an association between physical activity/sedentary behavior and the progression of two different measures of subclinical atherosclerotic disease.
PMCID: PMC4085097  PMID: 24075757
Ankle Brachial Index; Coronary Artery Calcification; Physical Activity; Epidemiology; Prospective Cohort Study
8.  Differences in the Incidence of Congestive Heart Failure by Ethnicity 
Archives of internal medicine  2008;168(19):2138-2145.
The relationship between incident congestive heart failure (CHF) and ethnicity as well as racial/ethnic differences in the mechanisms leading to CHF have not been demonstrated in a multiracial, population-based study. Our objective was to evaluate the relationship between race/ethnicity and incident CHF.
The Multi-Ethnic Study of Atherosclerosis (MESA) is a cohort study of 6814 participants of 4 ethnicities: white (38.5%), African American (27.8%), Hispanic (21.9%), and Chinese American (11.8%). Participants with a history of cardiovascular disease at baseline were excluded. Cox proportional hazards models were used for data analysis.
During a median follow-up of 4.0 years, 79 participants developed CHF (incidence rate: 3.1 per 1000 person-years). African Americans had the highest incidence rate of CHF, followed by Hispanic, white, and Chinese American participants (incidence rates: 4.6, 3.5, 2.4, and 1.0 per 1000 person-years, respectively). Although risk of developing CHF was higher among African American compared with white participants (hazard ratio, 1.8; 95% confidence interval, 1.1-3.1), adding hypertension and/or diabetes mellitus to models including ethnicity eliminated statistical ethnic differences in incident CHF. Moreover, African Americans had the highest proportion of incident CHF not preceded by clinical myocardial infarction (75%) compared with other ethnic groups (P = .06).
The higher risk of incident CHF among African Americans was related to differences in the prevalence of hypertension and diabetes mellitus as well as socioeconomic status. The mechanisms of CHF also differed by ethnicity; interim myocardial infarction had the least influence among African Americans, and left ventricular mass increase had the greatest effect among Hispanic and white participants.
PMCID: PMC3038918  PMID: 18955644
9.  Metabolic Syndrome, Strain, and Reduced Myocardial Function: Multi-Ethnic Study of Atherosclerosis 
Arquivos Brasileiros de Cardiologia  2014;102(4):327-335.
Subclinical cardiovascular disease is prevalent in patients with Metabolic Syndrome (MetSyn). Left ventricular (LV) circumferential strain (εCC) and longitudinal strain (εLL), assessed by Speckle Tracking Echocardiography (STE), are indices of systolic function: shortening is indicated by negative strain, and thus, the more negative the strain, the better the LV systolic function. They have been used to demonstrate subclinical ventricular dysfunction in several clinical disorders.
We hypothesized that MetSyn is associated with impaired myocardial function, as assessed by STE.
We analyzed Multi-Ethnic Study of Atherosclerosis (MESA) participants who underwent STE and were evaluated for all MetSyn components.
Among the 133 participants included [women: 63%; age: 65 ± 9 years (mean ± SD)], the prevalence of MetSyn was 31% (41/133). Individuals with MetSyn had lower εCC and lower εLL than those without MetSyn (-16.3% ± 3.5% vs. -18.4% ± 3.7%, p < 0.01; and -12.1% ± 2.5% vs. -13.9% ± 2.3%, p < 0.01, respectively). The LV ejection fraction (LVEF) was similar in both groups (p = 0.09). In multivariate analysis, MetSyn was associated with less circumferential myocardial shortening as indicated by less negative εCC (B = 2.1%, 95%CI:0.6 3.5, p < 0.01) even after adjusting for age, ethnicity, LV mass, and LVEF). Likewise, presence of MetSyn (B = 1.3%, 95%CI:0.3 2.2, p < 0.01) and LV mass (B = 0.02%, 95% CI: 0.01-0.03, p = 0.02) were significantly associated with less longitudinal myocardial shortening as indicated by less negative εLL after adjustment for ethnicity, LVEF, and creatinine.
Left ventricular εCC and εLL, markers of subclinical cardiovascular disease, are impaired in asymptomatic individuals with MetSyn and no history of myocardial infarction, heart failure, and/or LVEF < 50%.
PMCID: PMC4028951  PMID: 24844874
Atherosclerosis; Metabolic X Syndrome; Diabetes Mellitus / mortality; Ventricular Dysfunction / physiopathology; Ethnic Group
10.  Assessment of Cardiac Involvement in Myotonic Muscular Dystrophy by T1 Mapping on 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.
PMCID: PMC3459147  PMID: 22710483
Myotonic muscular dystrophy; MRI; T1 mapping; ventricular function
12.  Cardiac magnetic resonance imaging and its electrocardiographs (ECG): tips and tricks 
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.
PMCID: PMC3476721  PMID: 22033762
Magnetic resonance imaging; ECG; Trigger
13.  Pulmonary Artery Pressure, Gender, Menopause, and Pregnancy in Schistosomiasis-Associated Pulmonary Hypertension 
Arquivos brasileiros de cardiologia  2013;101(2):154-159.
Schistosomiasis-associated pulmonary arterial hypertension (SPAH) is a major concern worldwide. However, the role of gender specific contributing factors in SPAH is unknown.
We investigated how systolic pulmonary artery pressure (SPAP) values and the presence of severe SPAP relate to gender, menopausal status, and pregnancy history in SPAH patients.
Seventy-nine patients diagnosed with SPAH from 2000 to 2009 were assessed and 66 were enrolled in the study. Information about age, menopausal status, pregnancy, echocardiography-derived SPAP, and invasive mean pulmonary artery pressure (mPAP) was collected from medical records. The relation between values of SPAP and mPAP and their agreement for severe disease were assessed. Regression models assessed the association of gender, menopausal status, and pregnancy history with SPAP values and the presence of severe SPAP.
Moderate correlation and good agreement for severe disease were found between mPAP and SPAP. Mean SPAP values were similar for men and women. A trend toward higher values of SPAP was found for non-menopausal women compared to men. Higher SPAP values were found for menopausal compared to non-menopausal women; the values were non-significant after adjustment for age. Pregnancy history had no association with SPAP. Menopause and positive pregnancy had no association with severe SPAP.
In SPAH patients, neither gender, nor menopausal status, nor pregnancy history showed independent correlation with SPAP values assessed by echocardiography.
PMCID: PMC3998155  PMID: 23821406
Hypertension, Pulmonary; Schistosomiasis; Pregnancy; Menopause; Echocardiography, Doppler
14.  Normal left ventricular myocardial thickness for middle aged and older subjects with SSFP cardiac MR: The Multi-Ethnic Study of Atherosclerosis 
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.
PMCID: PMC3412148  PMID: 22705587
magnetic resonance imaging; myocardial thickness; normal values
15.  Trabeculated (Non-Compacted) and Compact Myocardium in Adults: The Multi-Ethnic Study of Atherosclerosis 
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.
PMCID: PMC3399115  PMID: 22499849
cardiovascular magnetic resonance imaging; cardiomyopathy; non-compaction; trabeculation
16.  Right Ventricular Morphology and the Onset of Dyspnea: The MESA-Right Ventricle Study 
PLoS ONE  2013;8(2):e56826.
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.
PMCID: PMC3574101  PMID: 23457622
17.  Myocardial T1 Mapping with MRI: comparison of Look-Locker and MOLLI sequences 
To evaluate the relationship between “Look-Locker” (LL) and modified Look-Locker Inversion recovery (MOLLI) approaches for T1 mapping of the myocardium.
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.
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.
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.
PMCID: PMC3221792  PMID: 21954119
Magnetic resonance imaging; diffuse myocardium fibrosis; T1 mapping
18.  T1 Mapping of the Gadolinium-Enhanced Myocardium: Adjustment for Factors Affecting Interpatient Comparison 
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.
PMCID: PMC3092826  PMID: 21500267
T1 mapping; myocardial fibrosis; patient T1 comparison; GFR; delayed enhancement
19.  The Absence of Coronary Calcification Does Not Exclude Obstructive Coronary Artery Disease or the Need for Revascularization in Patients Referred for Conventional Coronary Angiography 
This study was designed to evaluate whether the absence of coronary calcium could rule out ≥50% coronary stenosis or the need for revascularization.
The latest American Heart Association guidelines suggest that a calcium score (CS) of zero might exclude the need for coronary angiography among symptomatic patients.
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.
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.
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.
PMCID: PMC3294287  PMID: 20170786
coronary artery disease; calcium score; computed tomography; coronary angiography; coronary stenosis
20.  Racial and ethnic differences in subclinical myocardial function: the Multi-Ethnic Study of Atherosclerosis 
Heart (British Cardiac Society)  2011;97(5):405-410.
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.
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.
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.
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.
PMCID: PMC3034784  PMID: 21258000
21.  Coronary CT angiography using 64 detector rows: methods and design of the multi-centre trial CORE-64 
European Radiology  2008;19(4):816-828.
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.
PMCID: PMC3289939  PMID: 18998142
Computed tomography; Coronary vessels; Multi-centre study; Methods; Design
22.  Physical Activity and Right Ventricular Structure and Function 
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.
PMCID: PMC3056232  PMID: 20813888
exercise; pulmonary heart disease; pulmonary hypertension; magnetic resonance imaging
23.  The Impact of Obesity on the Left Ventricle 
JACC. Cardiovascular imaging  2010;3(3):266-274.
The purpose of this study was to evaluate the relationship of left ventricular (LV) remodeling assessed by cardiac magnetic resonance to various measures of obesity in a large population-based study.
Obesity is a well-known risk factor for cardiovascular disease, yet its relationship with LV size and function is poorly understood.
A total of 5,098 participants (age 45 to 84 years; 48% men) in the Multi-Ethnic Study of Atherosclerosis who were free of clinically apparent cardiovascular disease underwent cardiac magnetic resonance to assess LV size and function as well as measures of obesity, including body mass index, waist-to-hip ratio and waist circumference, and cardiovascular risk factors. Fat mass (FM) was estimated based on height-weight models derived from bioelectrical impedance studies. The associations of obesity measures with LV size and function were evaluated using linear spline regression models for body mass index and multivariable regression models for other measures of obesity; they were displayed graphically using generalized additive models.
LV mass and end-diastolic volume were positively associated with measures of obesity in both sexes after adjustment for risk factors (e.g., 5.7-g and 6.9-g increase in LV mass per 10-kg increase in FM in women and men, respectively [p < 0.001]). LV mass-to-volume ratio was positively associated with increased body mass index, waist-to-hip ratio, waist circumference, and estimated FM (e.g., 0.02-g/ml and 0.06-g/ml increase in mass-to-volume ratio per 10-kg increase in FM in women and men, respectively [p < 0.001]). The increased mass-to-volume ratio was due to a greater increase in LV mass relative to LV end-diastolic volume. All associations were stronger for men than for women. Ejection fraction showed no significant association with measures of obesity.
Obesity was associated with concentric LV remodeling without change in ejection fraction in a large, multiethnic cohort study.
PMCID: PMC3037096  PMID: 20223423
cardiac magnetic resonance; cardiac morphology; epidemiology; left ventricular function; obesity
24.  Adenosine Stress 64- and 256-Row Detector Computed Tomography Angiography and Perfusion Imaging A Pilot Study Evaluating the Transmural Extent of Perfusion Abnormalities to Predict Atherosclerosis Causing Myocardial Ischemia 
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.
PMCID: PMC3035629  PMID: 19808590
imaging; atherosclerosis; ischemia; perfusion; myocardium
25.  Age-Related Left Ventricular Remodeling and Associated Risk for Cardiovascular Outcomes: The Multi-Ethnic Study of Atherosclerosis 
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.
PMCID: PMC2744970  PMID: 19808592
aging; magnetic resonance imaging; myocardium; remodeling

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