Evrim B. Turkbey

The Impact of Obesity on the Left Ventricle: The Multi-Ethnic Study of Atherosclerosis (MESA)

OBJECTIVES 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. BACKGROUND Obesity is a well-known risk factor for cardiovascular disease, yet its relationship with LV size and function is poorly understood. METHODS 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. RESULTS 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. CONCLUSIONS Obesity was associated with concentric LV remodeling without change in ejection fraction in a large, multiethnic cohort study.

T1 Mapping in Cardiomyopathy at Cardiac MR: Comparison with Endomyocardial Biopsy

PURPOSE To determine the utility of cardiac magnetic resonance (MR) T1 mapping for quantification of diffuse myocardial fibrosis compared with the standard of endomyocardial biopsy. MATERIALS AND METHODS This HIPAA-compliant study was approved by the institutional review board. Cardiomyopathy patients were retrospectively identified who had undergone endomyocardial biopsy and cardiac MR at one institution during a 5-year period. Forty-seven patients (53% male; mean age, 46.8 years) had undergone diagnostic cardiac MR and endomyocardial biopsy. Thirteen healthy volunteers (54% male; mean age, 38.1 years) underwent cardiac MR as a reference. Myocardial T1 mapping was performed 10.7 minutes ± 2.7 (standard deviation) after bolus injection of 0.2 mmol/kg gadolinium chelate by using an inversion-recovery Look-Locker sequence on a 1.5-T MR imager. Late gadolinium enhancement was assessed by using gradient-echo inversion-recovery sequences. Cardiac MR results were the consensus of two radiologists who were blinded to histopathologic findings. Endomyocardial biopsy fibrosis was quantitatively measured by using automated image analysis software with digital images of specimens stained with Masson trichrome. Histopathologic findings were reported by two pathologists blinded to cardiac MR findings. Statistical analyses included Mann-Whitney U test, analysis of variance, and linear regression. RESULTS Median myocardial fibrosis was 8.5% (interquartile range, 5.7-14.4). T1 times were greater in control subjects than in patients without and in patients with evident late gadolinium enhancement (466 msec ± 14, 406 msec ± 59, and 303 msec ± 53, respectively; P < .001). T1 time and histologic fibrosis were inversely correlated (r = -0.57; 95% confidence interval: -0.74, -0.34; P < .0001). The area under the curve for myocardial T1 time to detect fibrosis of greater than 5% was 0.84 at a cutoff of 383 msec. CONCLUSION Cardiac MR with T1 mapping can provide noninvasive evidence of diffuse myocardial fibrosis in patients referred for evaluation of cardiomyopathy.

Normal values for cardiovascular magnetic resonance in adults and children

Morphological and functional parameters such as chamber size and function, aortic diameters and distensibility, flow and T1 and T2* relaxation time can be assessed and quantified by cardiovascular magnetic resonance (CMR). Knowledge of normal values for quantitative CMR is crucial to interpretation of results and to distinguish normal from disease. In this review, we present normal reference values for morphological and functional CMR parameters of the cardiovascular system based on the peer-reviewed literature and current CMR techniques and sequences.

A New 2.5D Representation for Lymph Node Detection Using Random Sets of Deep Convolutional Neural Network Observations

Automated Lymph Node (LN) detection is an important clinical diagnostic task but very challenging due to the low contrast of surrounding structures in Computed Tomography (CT) and to their varying sizes, poses, shapes and sparsely distributed locations. State-of-the-art studies show the performance range of 52.9% sensitivity at 3.1 false-positives per volume (FP/vol.), or 60.9% at 6.1 FP/vol. for mediastinal LN, by one-shot boosting on 3D HAAR features. In this paper, we first operate a preliminary candidate generation stage, towards -100% sensitivity at the cost of high FP levels (-40 per patient), to harvest volumes of interest (VOI). Our 2.5D approach consequently decomposes any 3D VOI by resampling 2D reformatted orthogonal views N times, via scale, random translations, and rotations with respect to the VOI centroid coordinates. These random views are then used to train a deep Convolutional Neural Network (CNN) classifier. In testing, the CNN is employed to assign LN probabilities for all N random views that can be simply averaged (as a set) to compute the final classification probability per VOI. We validate the approach on two datasets: 90 CT volumes with 388 mediastinal LNs and 86 patients with 595 abdominal LNs. We achieve sensitivities of 70%/83% at 3 FP/vol. and 84%/90% at 6 FP/vol. in mediastinum and abdomen respectively, which drastically improves over the previous state-of-the-art work.

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. Magn Reson Med, 2011.

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.

Obesity and Right Ventricular Structure and Function: The MESA-Right Ventricle Study

BACKGROUND The relationship between obesity and right ventricular (RV) morphology is not well studied. We aimed to determine the association between obesity and RV structure and function in a large multiethnic population-based cohort. METHODS The MESA-Right Ventricle Study measured RV mass and volumes by cardiac MRI in participants aged 45 to 84 years without clinical cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis (MESA). Participants were divided into three categories based on BMI: lean ( ≤ 24.9 kg/m(2)), overweight (25-29.9 kg/m(2)), and obese ( ≥ 30 kg/m(2)). RESULTS The study sample included 4,127 participants. After adjustment for demographics, height, education, and cardiovascular risk factors, overweight and obese participants had greater RV mass (6% and 9% greater, respectively), larger RV end-diastolic volume (8% and 18% greater, respectively), larger RV stroke volume (7% and 16% greater, respectively), and lower RV ejection fraction ( ≥ 1% lower) than lean participants (all P < .001). These findings persisted after adjusting for the respective left ventricular (LV) parameters. CONCLUSIONS Overweight and obesity were independently associated with differences in RV morphology even after adjustment for the respective LV measure. This association could be explained by increased RV afterload, increased blood volume, hormonal effects, or direct obesity-related myocardial effects.

Original ResearchPulmonary Vascular DiseaseObesity and Right Ventricular Structure and Function: The MESA-Right Ventricle Study

BACKGROUND The relationship between obesity and right ventricular (RV) morphology is not well studied. We aimed to determine the association between obesity and RV structure and function in a large multiethnic population-based cohort. METHODS The MESA-Right Ventricle Study measured RV mass and volumes by cardiac MRI in participants aged 45 to 84 years without clinical cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis (MESA). Participants were divided into three categories based on BMI: lean ( ≤ 24.9 kg/m(2)), overweight (25-29.9 kg/m(2)), and obese ( ≥ 30 kg/m(2)). RESULTS The study sample included 4,127 participants. After adjustment for demographics, height, education, and cardiovascular risk factors, overweight and obese participants had greater RV mass (6% and 9% greater, respectively), larger RV end-diastolic volume (8% and 18% greater, respectively), larger RV stroke volume (7% and 16% greater, respectively), and lower RV ejection fraction ( ≥ 1% lower) than lean participants (all P < .001). These findings persisted after adjusting for the respective left ventricular (LV) parameters. CONCLUSIONS Overweight and obesity were independently associated with differences in RV morphology even after adjustment for the respective LV measure. This association could be explained by increased RV afterload, increased blood volume, hormonal effects, or direct obesity-related myocardial effects.

Sex Differences in Diabetes and Risk of Incident Coronary Artery Disease in Healthy Young and Middle-Aged Adults

OBJECTIVE Controversy exists about the coronary artery disease (CAD) risk conveyed by diabetes in young and middle-aged women. We investigated sex differences in CAD by diabetes status among healthy individuals with different underlying risks of heart disease. RESEARCH DESIGN AND METHODS We examined subjects aged <60 years without CAD at enrollment in the high-risk GeneSTAR Study (n = 1,448; follow-up ∼12 years), Multi-Ethnic Study of Atherosclerosis (MESA; n = 3,072; follow-up ∼7 years), and National Health and Nutrition Examination Survey III (NHANES III) Mortality Follow-up Study (n = 6,997; follow-up ∼15 years). Diabetes was defined by report, hypoglycemic use, and/or fasting glucose ≥126 mg/dL. The outcome was any CAD event during follow-up (fatal CAD in NHANES). RESULTS In the absence of diabetes, CAD rates were lower among women in GeneSTAR, MESA, and NHANES (4.27, 1.66, and 0.40/1,000 person-years, respectively) versus men (11.22, 5.64, and 0.88/1,000 person-years); log-rank P < 0.001 (GeneSTAR/MESA) and P = 0.07 (NHANES). In the presence of diabetes, CAD event rates were similar among women (17.65, 7.34, and 2.37/1,000 person-years) versus men (12.86, 9.71, and 1.83/1,000 person-years); all log-rank P values > 0.05. Adjusting for demographics, diabetes was associated with a significant four- to fivefold higher CAD rate among women in each cohort, without differences in men. In meta-analyses of three cohorts, additionally adjusted for BMI, smoking, hypertension, HDL, and non-HDL cholesterol, antihypertensive and cholesterol-lowering medication use, the hazard ratio of CAD in men versus women among nondiabetes was 2.43 (1.76–3.35) and diabetes was 0.89 (0.43–1.83); P = 0.013 interaction by diabetes status. CONCLUSIONS Though young and middle-aged women are less likely to develop CAD in the absence of diabetes, the presence of diabetes equalizes the risk by sex. Our findings support aggressive CAD prevention strategies in women with diabetes and at similar levels to those that exist in men.

Myocardial Structure, Function, and Scar in Patients With Type 1 Diabetes Mellitus

Background— We report relationships between cardiovascular disease risk factors and myocardial structure, function, and scar in patients with type 1 diabetes mellitus in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. Methods and Results— Cardiac magnetic resonance was obtained in 1017 patients with type 1 diabetes mellitus. Gadolinium cardiac magnetic resonance was also obtained in 741 patients. The mean age was 49±7 years; 52% were men; and mean duration of diabetes mellitus was 28±5 years. Associations of cardiovascular disease risk factors with cardiac magnetic resonance parameters were examined with linear and logistic regression models. History of macroalbuminuria was positively associated with left ventricular mass (by 14.8 g), leading to a significantly higher ratio of left ventricular mass to end-diastolic volume (by 8%). Mean hemoglobin A1c levels over the preceding 22 years were inversely associated with end-diastolic volume (−3.0 mL per unit mean hemoglobin A1c percent) and stroke volume (−2.3 mL per unit mean hemoglobin A1c percent) and positively related to the ratio of elevated left ventricular mass to end-diastolic volume (0.02 g/mL per unit). The overall prevalence of myocardial scar was 4.3% by cardiac magnetic resonance and 1.4% by clinical adjudication of myocardial infarction. Both mean hemoglobin A1c (odds ratio, 1.5 [95% confidence interval, 1.0–2.2] per unit) and macroalbuminuria (odds ratio, 3.5 [95% confidence interval, 1.2–9.9]) were significantly associated with myocardial scar and traditional cardiovascular disease risk factors. Conclusions— In addition to traditional cardiovascular disease risk factors, elevated mean hemoglobin A1c and macroalbuminuria were significantly associated with alterations in left ventricular structure and function. The prevalence of myocardial scar was 4.3% in this subcohort of DCCT/EDIC participants with relatively preserved renal function. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00360893 and NCT00360815.