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1.  The association between cardiovascular risk and cardiovascular magnetic resonance measures of fibrosis: the Multi-Ethnic Study of Atherosclerosis (MESA) 
Risk scores for cardiovascular disease (CVD) are in common use to integrate multiple cardiovascular risk factors in order to identify individuals at greatest risk for disease. The purpose of this study was to determine if individuals at greater cardiovascular risk have T1 mapping indices by cardiovascular magnetic resonance (CMR) indicative of greater myocardial fibrosis.
CVD risk scores for 1208 subjects (men, 50.8%) ages 55–94 years old were evaluated in the Multiethnic Study of Atherosclerosis (MESA) at six centers. T1 times were determined at 1.5Tesla before and after gadolinium administration (0.15 mmol/kg) using a modified Look-Locker pulse sequence. The relationship between CMR measures (native T1, 12 and 25 minute post-gadolinium T1, partition coefficient and extracellular volume fraction) and 14 established different cardiovascular risk scores were determined using regression analysis. Bootstrapping analysis with analysis of variance was used to compare different CMR measures. CVD risk scores were significantly different for men and women (p < 0.001).
25 minute post gadolinium T1 time showed more statistically significant associations with risk scores (10/14 scores, 71%) compared to other CMR indices (e.g. native T1 (7/14 scores, 50%) and partition coefficient (7/14, 50%) in men. Risk scores, particularly the new 2013 AHA/ASCVD risk score, did not correlate with any CMR fibrosis index.
Men with greater CVD risk had greater CMR indices of myocardial fibrosis. T1 times at greater delay time (25 minutes) showed better agreement with commonly used risk score indices compared to ECV and native T1 time.
Clinical trial registration, NCT00005487.
PMCID: PMC4326517
Myocardium; Cardiovascular magnetic resonance; Risk factors
7.  Axial Black Blood Turbo Spin Echo Imaging of the Right Ventricle 
Black blood turbo spin echo (TSE) imaging of the right ventricle (RV) free wall is highly sensitive to cardiac motion, frequently resulting in non-diagnostic images. Temporal and spatial parameters of a black blood TSE pulse sequence were evaluated for visualization of the RV free wall. 74 patient studies were retrospectively evaluated for the effects of acquisition timing on image quality. Axial black blood TSE images were acquired on 10 healthy volunteers to assess the role of spatial misregistration on right ventricle visualization; increasing the double inversion recovery (DIR) slice thickness beyond 300% had no effect on image quality (p=0.2). 35 patient studies were prospectively evaluated with inversion times (TIs) corresponding to the mid-diastolic rest period and end-systole based on visual analysis of a four chamber cine. When TIs were chosen to be within the patients’ RV rest period, mean image quality score was significantly improved (2.3 vs. 1.86, p<0.001) and the number of clinically diagnostic images increased from 32% to 46%. Black blood TSE imaging of the RV free wall is highly sensitive to cardiac motion. Image quality can be improved by choosing TIs concordant with the rest period of the patient’s RV that may occur at mid-diastole or end-systole.
PMCID: PMC4301616  PMID: 19165884
cardiac MRI; black blood; turbo spin echo; right ventricle
8.  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
9.  Relation of Thoracic Aortic Distensibility to Left Ventricular Area (From the Multi-ethnic Study of Atherosclerosis [MESA]) 
The American journal of cardiology  2013;113(1):178-182.
Decreased arterial compliance is an early manifestation of adverse structural and functional changes within the vessel wall. Its correlation with left ventricular (LV) area on computed tomography (CT), a marker of LV remodeling, has not been well demonstrated. We tested the hypothesis that decreasing aortic compliance and increasing arterial stiffness is independently associated with increased LV area. The study population consisted of 3,540 (61±10 years, 46% men) from the MESA study who underwent aortic distensibility (AD) assessment on magnetic resonance imaging (MRI) and LV area measurement on CT (adjusted to body surface area). Multivariable logistic regression was performed to assess the association between body surface area (BSA) normalized LV area >75th percentile and AD after adjusting for baseline clinical, historical and imaging covariates. The mean LV area /BSA was 2,153 cm2 and mean AD was 1.84 mm Hg−1 x103. Subjects in the lowest AD quartile were older with higher prevalence of hypertension, diabetes, and hypercholesterolemia (p<0.05 for all comparisons). Using multivariate linear regression adjusting for demographics, traditional risk factors, coronary artery calcium and C-reactive protein, each standard deviation decrease was associated with 18 cm2 increase in the LV area. In addition, decreasing AD quartiles were independently associated with increased BSA LV area defined as >75th percentile. In this multi-ethnic cohort, reduced AD was associated with increased LV area. Longitudinal studies are needed to determine if decreased distensibility precedes and directly influences increased LV area.
PMCID: PMC3912190  PMID: 24210674
Arterial compliance; Left ventricular area; Computed tomography; Aortic Distensibility
10.  Impact of Nonischemic Scar Features on Local Ventricular Electrograms and Scar-Related Ventricular Tachycardia Circuits in Patients with Nonischemic Cardiomyopathy 
Circulation. Arrhythmia and electrophysiology  2013;6(6):10.1161/CIRCEP.113.000159.
The association of local electrogram features with scar morphology and distribution in nonischemic cardiomyopathy (NICM) has not been investigated. We aimed to quantify the association of scar on late-gadolinium enhanced cardiac magnetic resonance (LGE-CMR) with local electrograms and ventricular tachycardia (VT) circuit sites in patients with NICM.
Methods and Results
Fifteen patients with NICM underwent LGE-CMR before VT ablation. The transmural extent and intramural types (endocardial, mid-wall, epicardial, patchy, transmural) of scar were measured in LGE-CMR short axis planes. Electro-anatomic map (EAM) points were registered to LGE-CMR images. Myocardial wall thickness, scar transmurality, and intramural scar types were independently associated with electrogram amplitude, duration, and deflections in linear mixed effects multivariable models, clustered by patient. Fractionated and isolated potentials were more likely to be observed in regions with higher scar transmurality (P<0.0001 by ANOVA) and in regions with patchy scar (versus endocardial, mid wall, epicardial scar, P<0.05 by ANOVA). Most VT circuit sites were located in scar with >25% scar transmurality.
Electrogram features are associated with scar morphology and distribution in patients with NICM. Prior knowledge of electrogram image associations may optimize procedural strategies including the decision to obtain epicardial access.
PMCID: PMC3884514  PMID: 24235267
ventricular tachycardia; nonischemic cardiomiopathy; cardiac magnetic resonance imaging; electrophysiology mapping
11.  Mutation Positive Arrhyhmogenic Right Ventricular Dysplasia/Cardiomyopathy: The Triangle of Dysplasia Displaced 
The traditional description of the Triangle of Dysplasia in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C) predates genetic testing and excludes biventricular phenotypes.
Methods and Results
We analyzed Cardiac Magnetic Resonance (CMR) studies of 74 mutation-positive ARVD/C patients for regional abnormalities on a 5-segment RV and 17-segment LV model. The location of electroanatomic endo- and epicardial scar and site of successful VT ablation was recorded in 11 ARVD/C subjects. Among 54/74 (73%) subjects with abnormal CMR, the RV was abnormal in almost all (96%), and 52% had biventricular involvement. Isolated LV abnormalities were uncommon (4%). Dyskinetic basal inferior wall (94%) was the most prevalent RV abnormality, followed by basal anterior wall (87%) dyskinesis. Subepicardial fat infiltration in the posterolateral LV (80%) was the most frequent LV abnormality. Similar to CMR data, voltage maps revealed scar (<0.5 mV) in the RV basal inferior wall (100%), followed by the RV basal anterior wall (64%) and LV posterolateral wall (45%). All 16 RV VTs originated from the basal inferior wall (50%) or basal anterior wall (50%). Of 3 LV VTs, 2 localized to the posterolateral wall. In both modalities, RV apical involvement never occurred in isolation.
Mutation-positive ARVD/C exhibits a previously unrecognized characteristic pattern of disease involving the basal inferior and anterior RV, and the posterolateral LV. The RV apex is only involved in advanced ARVD/C, typically as a part of global RV involvement. These results displace the RV apex from the Triangle of Dysplasia, and provide insights into the pathophysiology of ARVD/C.
PMCID: PMC3971054  PMID: 23889974
Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy; magnetic resonance imaging; electroanatomic mapping; ventricular tachcardia; phenotype; genetics; implantable cardioverter defibrillator
12.  Thoracic Aortic Distensibility and Thoracic Aortic Calcium (From the Multi-ethnic Study of Atherosclerosis [MESA]) 
The American journal of cardiology  2010;106(4):575-580.
Decreased arterial distensibility is an early manifestation of adverse structural and functional changes within the vessel wall. Its correlation with thoracic aortic calcium (TAC), a marker of atherosclerosis, has not been well demonstrated. We tested the hypothesis that decreasing aortic compliance and increasing arterial stiffness is independently associated with increased TAC. We included 3,540 (61±10 years, 46% males) subjects from the Multi-ethnic Study of Atherosclerosis (MESA) study who underwent aortic distensibility (AD) assessment on MRI. TAC was calculated using modified Agatston algorithm on non-contrast cardiac CT. Multivariate regression models were calculated for the presence of TAC. Overall, 861 (24%) individuals had detectable TAC. A lower AD was observed among those with vs. without TAC (2.02±1.34 vs. 1.28±0.74, p<0.0001). The prevalence of TAC increased significantly across decreasing quartiles of AD (7%, 17%, 31%, and 42%, p<0.0001). Using multivariate analysis, TAC was independently associated with AD after adjusting for age, gender, ethnicity and other covariates. In conclusion, our analysis demonstrates that increased arterial stiffness is associated with increased TAC independent of ethnicity and other atherosclerotic risk factors.
PMCID: PMC4228943  PMID: 20691319
13.  Incremental Value of Cardiac Magnetic Resonance Imaging in Arrhythmic Risk Stratification of Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy Associated Desmosomal Mutation Carriers 
To identify the incremental value and optimal role of Cardiac Magnetic Resonance (CMR) imaging in arrhythmic risk stratification of Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C) associated desmosomal mutation carriers without a prior history of sustained ventricular arrhythmia.
Risk stratification of ARVD/C mutation carriers is challenging.
We included 69 patients (age 27.0 ± 15.3 years, 42% male) harboring ARVD/C associated pathogenic mutations (83% PKP-2) without prior sustained ventricular arrhythmias. Electrocardiography (ECG) and 24-hours Holter monitoring closest to presentation were analyzed for electrical abnormalities as per revised Task Force Criteria. CMR studies were done to identify abnormal cardiac structure and function according to the revised Task Force Criteria.
Overall, 42 (61%) patients presented with electrical abnormalities based on their ECG and Holter monitor, of whom 20 (48%) had an abnormal CMR. Only 1 (4%) of 27 patients without electrical abnormalities at initial evaluation had an abnormal CMR. Over a mean follow-up of 5.8 ± 4.4 years, 11 (16%) patients experienced a sustained ventricular arrhythmia, exclusively in patients with both electrical abnormalities (ECG and/or Holter) and abnormal CMR.
Our results suggest that electrical abnormalities on ECG and Holter monitoring precede detectable structural abnormalities in ARVD/C mutation carriers. Therefore, evaluation of cardiac structure and function using CMR is probably not necessary in the absence of baseline electrical abnormalities. Among ARVD/C mutation carriers, the presence of both electrical and CMR abnormalities identifies patients at high risk of events and thus patients who might benefit from prophylactic implantable cardioverter-defibrillator implantation.
PMCID: PMC3971056  PMID: 23810894
cardiomyopathy; electrocardiography; magnetic resonance imaging; risk stratification; tachyarrhythmias
14.  Atlas-Based Quantification of Cardiac Remodeling Due to Myocardial Infarction 
PLoS ONE  2014;9(10):e110243.
Myocardial infarction leads to changes in the geometry (remodeling) of the left ventricle (LV) of the heart. The degree and type of remodeling provides important diagnostic information for the therapeutic management of ischemic heart disease. In this paper, we present a novel analysis framework for characterizing remodeling after myocardial infarction, using LV shape descriptors derived from atlas-based shape models. Cardiac magnetic resonance images from 300 patients with myocardial infarction and 1991 asymptomatic volunteers were obtained from the Cardiac Atlas Project. Finite element models were customized to the spatio-temporal shape and function of each case using guide-point modeling. Principal component analysis was applied to the shape models to derive modes of shape variation across all cases. A logistic regression analysis was performed to determine the modes of shape variation most associated with myocardial infarction. Goodness of fit results obtained from end-diastolic and end-systolic shapes were compared against the traditional clinical indices of remodeling: end-diastolic volume, end-systolic volume and LV mass. The combination of end-diastolic and end-systolic shape parameter analysis achieved the lowest deviance, Akaike information criterion and Bayesian information criterion, and the highest area under the receiver operating characteristic curve. Therefore, our framework quantitatively characterized remodeling features associated with myocardial infarction, better than current measures. These features enable quantification of the amount of remodeling, the progression of disease over time, and the effect of treatments designed to reverse remodeling effects.
PMCID: PMC4215861  PMID: 25360520
15.  Relationship of CRP, IL-6, and Fibrinogen with Right Ventricular Structure and Function: The MESA-Right Ventricle Study 
International journal of cardiology  2013;168(4):3818-3824.
Inflammation contributes to the pathogenesis of disease associated with the left ventricle (LV); yet, our understanding of the effect of inflammation on the right ventricle (RV) is quite limited.
Methods and results
The relationships of C-reactive protein (CRP), interleukin-6 (IL-6) and fibrinogen with RV morphology and function (from cardiac MRI) were examined in participants free of clinical cardiovascular disease (n=4,009) from the Multi-Ethnic Study of Atherosclerosis (MESA)-RV study. Multivariable regressions (linear, quantile [25th and 75th] and generalized additive models [GAM]) were used to examine the independent association of CRP, IL-6 and fibrinogen with RV mass, RV end-diastolic volume (RVEDV), RV end-systolic volume (RVESV), RV stroke volume (RVSV) and RV ejection fraction (RVEF). Unadjusted and adjusted analyses revealed strong inverse associations between both CRP and IL-6 with RV mass, RVEDV, RVESV and RVSV (all p<0.01); there were no associations with RVEF. These relationships remained significant after adjustment for the respective LV parameters and lung function. However, GAM models suggested that extreme values of CRP and IL-6 might have positive associations with RV parameters. Fibrinogen showed significant associations in unadjusted models, but no associations after adjustment or in sensitivity analyses.
Levels of CRP and IL-6 are independently associated with RV morphology even after adjustment for the respective LV measure in this multi-ethnic population free of cardiovascular disease. Systemic inflammation may contribute to RV structural changes independent of effects on the LV.
PMCID: PMC3805818  PMID: 23932860
Systemic inflammation; right ventricle; heart failure; Multi-Ethnic Study of Atherosclerosis
16.  Effects of Prior Intensive Versus Conventional Therapy and History of Glycemia on Cardiac Function in Type 1 Diabetes in the DCCT/EDIC 
Diabetes  2013;62(10):3561-3569.
Intensive diabetes therapy reduces the prevalence of coronary calcification and progression of atherosclerosis and the risk of cardiovascular disease (CVD) events in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study. The effects of intensive therapy on measures of cardiac function and structure and their association with glycemia have not been explored in type 1 diabetes (T1DM). We assess whether intensive treatment compared with conventional treatment during the DCCT led to differences in these parameters during EDIC. After 6.5 years of intensive versus conventional therapy in the DCCT, and 15 years of additional follow-up in EDIC, left ventricular (LV) indices were measured by cardiac magnetic resonance (CMR) imaging in 1,017 of the 1,371 members of the DCCT cohort. There were no differences between the DCCT intensive versus conventional treatment in end diastolic volume (EDV), end systolic volume, stroke volume (SV), cardiac output (CO), LV mass, ejection fraction, LV mass/EDV, or aortic distensibility (AD). Mean DCCT/EDIC HbA1c over time was associated with EDV, SV, CO, LV mass, LV mass/EDV, and AD. These associations persisted after adjustment for CVD risk factors. Cardiac function and remodeling in T1DM assessed by CMR in the EDIC cohort was associated with prior glycemic exposure, but there was no effect of intensive versus conventional treatment during the DCCT on cardiac parameters.
PMCID: PMC3781466  PMID: 23520132
17.  The prospective association of Chlamydia pneumoniae and four other pathogens with development of coronary artery calcium: the Multi-Ethnic Study of Atherosclerosis (MESA) 
Atherosclerosis  2013;230(2):10.1016/j.atherosclerosis.2013.07.053.
Previous basic and cross-sectional studies obtained conflicting results regarding the association of pathogens with coronary artery calcium (CAC). The aim of this study is to prospectively evaluate this association in a population-based cohort.
We examined 5,744 individuals aged 45-84 years at baseline (2000-02) who underwent repeated CAC assessment on average 2.4 years later (a half at visit 2 [2002-04] and the other half at visit 3 [2004-05]). CAC incidence was defined as newly detectable CAC at follow-up (475 cases of 2,942 participants). CAC progression was defined as annualized change in CAC Agatston score ≥10 units/year if baseline CAC score >0 to <100 or ≥10%/year if baseline score ≥100 (1,537 cases of 2,802 participants). Seropositivity was assessed in the entire cohort for Chlamydia pneumonia and in a random sample (n=873) for Helicobacter pylori, cytomegalovirus, herpes simplex virus, and hepatitis A virus.
Seropositivity to Chlamydia pneumoniae was not significantly associated with CAC incidence (odds ratio [OR] 1.11 [95% CI, 0.88-1.39], P=0.371) or progression (1.14 [0.96-1.36], P=0.135) even in unadjusted models. When CAC incidence and progression were combined, we observed significant association with Chlamydia pneumoniae seropositivity before adjustment (OR 1.17 [1.03-1.33], P=0.016) but not in a model adjusting for traditional risk factors (1.04 [0.90-1.19], P=0.611). The results were consistent across subgroups according to age, sex, and race/ethnicity. None of five pathogens or their accrual was associated with CAC incidence and progression in the subsample.
Our prospective study does not support the pathophysiological involvement of these pathogens in CAC development.
PMCID: PMC3815605  PMID: 24075755
Coronary Calcium; Atherosclerosis; Pathogens; Infection
18.  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
19.  A Cross-Platform and Distributive Database System for Cumulative Tumor Measurement 
This paper discusses the development of a cross-platform, web accessible, vendor-independent database system capable of storing and comparing longitudinal tumor measurements for multiple tumors. This innovative system can create a comprehensive cumulative report that summarizes clinical findings and links to the original image studies, which will clinically enhance the workflow of oncologists. A case study on a pancreatic tumor data set with 524 tumor measurements and 134 patients is demonstrated.
PMCID: PMC4161952  PMID: 23366129
20.  Point-Guided Modeling and Segmentation of Myocardium for Low Dose Cardiac CT Images 
Cardiac CT is emerging as a preferable modality to detect myocardial stress/rest perfusion; however the insufficient contrast of myocardium on CT image makes its segmentation difficult. In this paper, we present a point-guided modeling and deformable model-based segmentation method. This method first builds a triangular surface model of myocardium through Bézier contour fitting based on a few points selected by clinicians. Then, a deformable model-based segmentation method is developed to refine the segmentation result. The experiments on 8 cases show the accuracy of the segmentation in terms of true positive volume fraction, false positive volume fractions, and average surface distance can reach 91.0%, 0.3%, and 0.6mm, respectively. The comparison between the proposed method and a graph cut-based method is performed. The results demonstrate that this method is effective in improving the accuracy further.
PMCID: PMC4159764  PMID: 23367132
21.  Relation of Leptin to Left Ventricular Hypertrophy (From the Multi-Ethnic Study of Atherosclerosis) 
The American journal of cardiology  2013;112(5):726-730.
Increasing adiposity increases the risk for left ventricular hypertrophy. Adipokines are hormone-like substances from adipose tissue that influence several metabolic pathways relevant to LV hypertrophy. Data was from participants enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA) who underwent magnetic resonance imaging of the heart and who also had fasting venous blood assayed for 4 distinct adipokines (adiponectin, leptin, tumor necrosis factor – alpha and resistin). 1,464 MESA participants had complete data. The mean age was 61.5 years, the mean body mass index was 27.6 kg/m2 and 49% were female. With adjustment for age, sex, race, height and weight, multivariable linear regression modeling revealed that a 1-SD increment in leptin was significantly associated with smaller LV mass (ß: −4.66 % predicted, p-value: < 0.01), LV volume (−5.87 % predicted, < 0.01), stroke volume (−3.23 ml, p < 0.01) and cardiac output (−120 mL/min, p = 0.01) as well as a lower odds ratio for the presence of LV hypertrophy (OR: 0.65, p < 0.01), but a higher ejection fraction (0.44%, p = 0.05). Additional adjustment for the traditional cardiovascular disease (CVD) risk factors, insulin resistance, physical activity, education, income, inflammatory biomarkers, other selected adipokines and pericardial fat did not materially change the magnitude or significance of the associations. The associations between the other adipokines and LV structure and function were inconsistent and largely non-significant. In conclusion, the results indicate that higher levels of leptin are associated with more favorable values of several measures of LV structure and function.
PMCID: PMC3745795  PMID: 23711806
leptin; left ventricle; hypertrophy; mass
22.  Cardiac magnetic resonance T1 mapping of left atrial myocardium 
Cardiac magnetic resonance (CMR) T1 mapping is an emerging tool for objective quantification of myocardial fibrosis.
To (a) establish the feasibility of left atrial (LA) T1 measurements, (b) determine the range of LA T1 values in patients with atrial fibrillation (AF) vs healthy volunteers, and (c) validate T1 mapping vs LA intracardiac electrogram voltage amplitude measures.
CMR imaging at 1.5 T was performed in 51 consecutive patients before AF ablation and in 16 healthy volunteers. T1 measurements were obtained from the posterior LA myocardium by using the modified Look-Locker inversion-recovery sequence. Given the established association of reduced electrogram amplitude with fibrosis, intracardiac point-by-point bipolar LA voltage measures were recorded for the validation of T1 measurements.
The median LA T1 relaxation time was shorter in patients with AF (387 [interquartile range 364–428] ms) compared to healthy volunteers (459 [interquartile range 418–532] ms; P < .001) and was shorter in patients with AF with prior ablation compared to patients without prior ablation (P = .035). In a generalized estimating equations model, adjusting for data clusters per participant, age, rhythm during CMR, prior ablation, AF type, hypertension, and diabetes, each 100-ms increase in T1 relaxation time was associated with 0.1 mV increase in intracardiac bipolar LA voltage (P = .025).
Measurement of the LA myocardium T1 relaxation time is feasible and strongly associated with invasive voltage measures. This methodology may improve the quantification of fibrotic changes in thin-walled myocardial tissues.
PMCID: PMC3757110  PMID: 23643513
Atrial fibrillation; Cardiac magnetic resonance; T1 mapping; Left atrial fibrosis; Late gadolinium enhancement
23.  Association of resting heart rate with carotid and aortic arterial stiffness: Multi-Ethnic Study of Atherosclerosis (MESA) 
Hypertension  2013;62(3):10.1161/HYPERTENSIONAHA.113.01605.
Resting heart rate is an easily measured, non-invasive vital sign that is associated with cardiovascular disease events. The pathophysiology of this association is not known. We investigated the relationship between resting heart rate and stiffness of the carotid (a peripheral artery) and the aorta (a central artery) in an asymptomatic multi-ethnic population. Resting heart rate was recorded at baseline in the Multi-Ethnic Study of Atherosclerosis (MESA). Distensibility was used as a measure of arterial elasticity, with a lower distensibility indicating an increase in arterial stiffness. Carotid distensibility was measured in 6,484 participants (98% of participants) using B-mode ultrasound and aortic distensibility was measured in 3,512 participants (53% of participants) using cardiac MRI. Heart rate was divided into quintiles and we used progressively adjusted models that included terms for physical activity and AV-nodal blocking agents. Mean resting heart rate of participants (mean age 62 years, 47% male) was 63 beats per minute (SD 9.6 beats per minute). In unadjusted and fully adjusted models, carotid distensibility and aortic distensibility decreased monotonically with increasing resting heart rate (p for trend <0.001 and 0.009 respectively). The relationship was stronger for carotid versus aortic distensibility. Similar results were seen using the resting heart rate taken at the time of MRI scanning. Our results suggest that a higher resting heart rate is associated with an increased arterial stiffness independent of AV-nodal blocker use and physical activity level, with a stronger association for a peripheral (carotid) compared to a central (aorta) artery.
PMCID: PMC3838105  PMID: 23836802
heart rate; cardiovascular disease; stiffness; ultrasound; cardiac magnetic resonance imaging
24.  Prevalence and Pathophysiologic Attributes of Ventricular Dyssynchrony in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy 
To study the prevalence and mechanisms underlying right ventricular (RV) dyssynchrony in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C) using tissue Doppler echocardiography (TDE).
ARVD/C is characterized by fibrofatty replacement of RV myocardium and RV dilatation. These pathologic changes may result in electromechanical dyssynchrony.
Electrocardiography, conventional and TDE was performed in 52 ARVD/C patients fulfilling Task Force criteria and 25 controls. RV end-diastolic and end-systolic areas, RV fractional area change (RVFAC), and left ventricular (LV) volumes and function were assessed. Mechanical synchrony was assessed by measuring differences in time-to-peak systolic velocity (TSV) between the RV free wall, ventricular septum and LV lateral wall. RV dyssynchrony was defined as the difference in TSV between the RV free wall and the ventricular septum, >2 SD above the mean value for controls.
Mean difference in RV TSV was higher in ARVD/C compared to controls (55 ± 34 ms vs. 26 ± 15 ms, p<0.001). Significant RV dyssynchrony was not noted in any of the controls. Based on a cut-off value of 56 ms, significant RV dyssynchrony was present in 26 ARVD/C patients (50%). Patients with RV dyssynchrony had larger RV end-diastolic area (22 ± 5 vs. 19 ± 4 cm2, p=0.02), and lower RVFAC (29 ± 8 vs. 34 ± 8%, p=0.03) compared to ARVD/C patients without RV dyssynchrony. No differences in QRS duration, LV volumes and function were present between the two groups.
RV dyssynchrony may occur in up to 50% of ARVD/C patients, and is associated with RV remodeling. This finding may have therapeutic and prognostic implications in ARVD/C.
PMCID: PMC4138506  PMID: 19628120
Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy; Echocardiography; Ventricular dyssynchrony
25.  Myocardial fibrosis detected by cardiac CT predicts ventricular fibrillation/ventricular tachycardia events in patients with hypertrophic cardiomyopathy 
Myocardial fibrosis (MF) occurs in up to 80% of subjects with asymptomatic or mildly symptomatic hypertrophic cardiomyopathy (HCM) and can constitute an arrhythmogenic substrate for re-entrant, life-threatening ventricular arrhythmias in predisposed persons.
The aim was to investigate whether MF detected by delayed enhancement cardiac CT is predictive of ventricular tachycardia (VT) and fibrillation (VF) that require appropriate therapy by an implantable cardioverter defibrillator (ICD) in patients with HCM.
Twenty-six patients with HCM with previously (for at least 1 year) implanted ICD underwent MF evaluation by cardiac CT. MF was quantified by myocardial delayed enhanced cardiac CT. Data on ICD firing were recorded every 3 months after ICD implantation. Risk factors for sudden cardiac death in patients with HCM were evaluated in all patients.
MF was present in 25 of 26 patients (96%) with mean fibrosis mass of 20.5 ± 15.8 g. Patients with appropriate ICD shocks for VF/VT had significantly greater MF mass than patients without (29.10 ± 19.13 g vs 13.57 ± 8.31 g; P = .01). For a MF mass of at least 18 g, sensitivity and specificity for appropriate ICD firing were 73% (95% CI, 49%–88%) and 71% (95% CI, 56%–81%), respectively. Kaplan–Meier curves indicated a significantly greater VF/ VT event rate in patients with MF mass ≥18 g than in patients with MF <18 g (P = .02). In the Cox regression analysis, the amount of MF was independently associated with VF/VT in ICD-stored electrograms.
The mass of MF detected by cardiac CT in patients with HCM at high risk of sudden death was associated with appropriate ICD firings.
PMCID: PMC4128834  PMID: 23849490
Hypertrophic cardiomyopathy; Myocardial fibrosis; Ventricular arrhythmias; Delayed enhancement cardiac computed tomography; Implantable cardiac defibrillator

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