Chun-Ho Yun

Pericardial and thoracic peri-aortic adipose tissues contribute to systemic inflammation and calcified coronary atherosclerosis independent of body fat composition, anthropometric measures and traditional cardiovascular risks

BACKGROUND Coronary atherosclerosis has traditionally been proposed to be associated with several cardiovascular risk factors and anthropometric measures. However, clinical data regarding the independent value of visceral adipose tissue in addition to such traditional predictors remains obscure. MATERIALS AND METHODS We subsequently studied 719 subjects (age: 48.1±8.3 years, 25% females) who underwent multidetector computed tomography (MDCT) for coronary calcium score (CCS) quantification. Baseline demographic data and anthropometric measures were taken with simultaneous body fat composition estimated. Visceral adipose tissue of pericardial and thoracic peri-aortic fat was quantified by MDCT using TeraRecon Aquarius workstation (San Mateo, CA). Traditional cardiovascular risk stratification was calculated by metabolic (NCEP ATP III) and Framingham (FRS) scores and high-sensitivity CRP (Hs-CRP) was taken to represent systemic inflammation. The independent value of visceral adipose tissue to systemic inflammation and CCS was assessed by utilizing multivariable regression analysis. RESULTS Of all subjects enrolled in this study, the mean values for pericardial and peri-aortic adipose tissue were 74.23±27.51 and 7.23±3.69ml, respectively. Higher visceral fat quartile groups were associated with graded increase of risks for cardiovascular diseases. Both adipose burdens strongly correlated with anthropometric measures including waist circumference, body weight and body mass index (all p<0.001). In addition, both visceral amount correlates well with ATP and FRS scores, all lipid profiles and systemic inflammation marker in terms of Hs-CRP (all p<0.001). After adjustment for baseline variables, both visceral fat were independently related to Hs-CRP levels (all p<0.05), but only pericardial fat exerted independent role in coronary calcium deposit. CONCLUSION Both visceral adipose tissues strongly correlated with systemic inflammation beyond traditional cardiovascular risks and anthropometric measures, though only pericardial fat exerted independent role in coronary calcium deposit. Our data suggested that visceral adipose tissue may thus contribute to systemic inflammation and play an independent role in the pathogenesis of atherosclerosis.

Epicardial adipose tissue relating to anthropometrics, metabolic derangements and fatty liver disease independently contributes to serum high-sensitivity C-reactive protein beyond body fat composition: a study validated with computed tomography.

BACKGROUND Epicardial adipose tissue (EAT) measured by echocardiography has been proposed to be associated with metabolic syndrome and increased cardiovascular risks. However, its independent association with fatty liver disease and systemic inflammation beyond clinical variables and body fat remains less well known. METHODS The relationships between EAT and various factors of metabolic derangement were retrospectively examined in consecutive 359 asymptomatic subjects (mean age, 51.6 years; 31% women) who participated in a cardiovascular health survey. Echocardiography-derived regional EAT thickness from parasternal long-axis and short-axis views was quantified. A subset of data from 178 randomly chosen participants were validated using 16-slice multidetector computed tomography. Body fat composition was evaluated using bioelectrical impedance from foot-to-foot measurements. RESULTS Increased EAT was associated with increased waist circumference, body weight, and body mass index (all P values for trend = .005). Graded increases in serum fasting glucose, insulin resistance, and alanine transaminase levels were observed across higher EAT tertiles as well as a graded decrease of high-density lipoprotein (all P values for trend <.05). The areas under the receiver operating characteristic curves for identifying metabolic syndrome and fatty liver disease were 0.8 and 0.77, with odds ratio estimated at 3.65 and 2.63, respectively. In a multivariate model, EAT remained independently associated with higher high-sensitivity C-reactive protein and fatty liver disease. CONCLUSIONS These data suggested that echocardiography-based epicardial fat measurement can be clinically feasible and was related to several metabolic abnormalities and independently associated fatty liver disease. In addition, EAT amount may contribute to systemic inflammation beyond traditional cardiovascular risks and body fat composition.

Association between diabetes and different components of coronary atherosclerotic plaque burden as measured by coronary multidetector computed tomography

OBJECTIVE The aim of the study was to assess differences in the presence, extent, and composition of coronary atherosclerotic plaque burden as detected by coronary multidetector computed tomography (MDCT) between patients with and without diabetes mellitus. METHODS We compared coronary atherosclerotic plaques (any plaque, calcified [CAP], non-calcified [NCAP, and mixed plaque [MCAP]]) between 144 symptomatic diabetic and non-diabetic patients (36 diabetics, mean age: 54.4+/-12, 64% females) who underwent coronary 64-slice MDCT (Siemens Medical Solutions, Forchheim, Germany) for the evaluation of acute chest pain but proven absence of myocardial ischemia. RESULTS Patients with diabetes had a higher prevalence of any plaque, CAP, MCAP, and NCAP (p=0.08, 0.07, 0.05, and 0.05, respectively) and a significantly higher extent of any plaque, CAP, MCAP, and NCAP (3.8+/-4.2 vs. 2.0+/-3.2, p=0.01; 3.3+/-4.0 vs. 1.7+/-3.0, p=0.03; 1.4+/-2.6 vs. 0.6+/-1.5, p=0.03; and 1.9+/-3.0 vs. 1.0+/-1.9, p=0.03, respectively) as compared to controls. In addition, patients with diabetes had a significant higher prevalence of significant coronary artery stenosis (42% vs. 14%, p=0.0004) and an approximately 3.5-fold higher risk of significant coronary stenosis independent of the presence of hypertension and BMI (OR: 3.46, 95% CI: 1.37-8.74, p=0.009). CONCLUSION Patients with diabetes have an approximately 3.5-fold higher risk of coronary stenosis independent of other cardiovascular risk factors and an overall increased coronary atherosclerotic plaque burden.

Relation of Carotid Artery Diameter With Cardiac Geometry and Mechanics in Heart Failure With Preserved Ejection Fraction

Background Central artery dilation and remodeling are associated with higher heart failure and cardiovascular risks. However, data regarding carotid artery diameter from hypertension to heart failure have remained elusive. We sought to investigate this issue by examining the association between carotid artery diameter and surrogates of ventricular dysfunction. Methods and Results Two hundred thirteen consecutive patients including 49 with heart failure and preserved ejection fraction (HFpEF), 116 with hypertension, and an additional 48 healthy participants underwent comprehensive echocardiography and tissue Doppler imaging. Ultrasonography of the common carotid arteries was performed for measurement of intima‐media thickness and diameter (CCAD). Cardiac mechanics, including LV twist, were assessed by novel speckle‐tracking software. A substantial graded enlargement of CCAD was observed across all 3 groups (6.8±0.6, 7.7±0.73, and 8.7±0.95 mm for normal, hypertension, and HFpEF groups, respectively; ANOVA P<0.001) and correlated with serum brain natriuretic peptide level (R2=0.31, P<0.001). Multivariable models showed that CCAD was associated with increased LV mass, LV mass‐to‐volume ratio (β‐coefficient=10.9 and 0.11, both P<0.001), reduced LV longitudinal and radial strain (β‐coeffficient=0.81 and −3.1, both P<0.05), and twist (β‐coefficient=−0.84, P<0.05). CCAD set at 8.07 mm as a cut‐off had a 77.6% sensitivity, 82.3% specificity, and area under the receiver operating characteristic curves (AUROC) of 0.86 (95% CI 0.80 to 0.92) in discriminating HFpEF. In addition, CCAD superimposed on myocardial deformation significantly expanded AUROC (for longitudinal strain, from 0.84 to 0.90, P of ΔAUROC=0.02) in heart failure discrimination models. Conclusions Increased carotid artery diameter is associated with worse LV geometry, higher brain natriuretic peptide level, and reduced contractile mechanics in individuals with HFpEF.

The normal limits, subclinical significance, related metabolic derangements and distinct biological effects of body site-specific adiposity in relatively healthy population.

Background The accumulation of visceral adipose tissue that occurs with normal aging is associated with increased cardiovascular risks. However, the clinical significance, biological effects, and related cardiometabolic derangements of body-site specific adiposity in a relatively healthy population have not been well characterized. Materials and Methods In this cross-sectional study, we consecutively enrolled 608 asymptomatic subjects (mean age: 47.3 years, 27% female) from 2050 subjects undergoing an annual health survey in Taiwan. We measured pericardial (PCF) and thoracic peri-aortic (TAT) adipose tissue volumes by 16-slice multi-detector computed tomography (MDCT) (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA) and related these to clinical characteristics, body fat composition (Tanita 305 Corporation, Tokyo, Japan), coronary calcium score (CCS), serum insulin, high-sensitivity C-reactive protein (Hs-CRP) level and circulating leukocytes count. Metabolic risk was scored by Adult Treatment Panel III guidelines. Results TAT, PCF, and total body fat composition all increased with aging and higher metabolic scores (all p<0.05). Only TAT, however, was associated with higher circulating leukocyte counts (ß-coef.:0.24, p<0.05), serum insulin (ß-coef.:0.17, p<0.05) and high sensitivity C-reactive protein (ß-coef.:0.24, p<0.05). These relationships persisted after adjustment in multivariable models (all p<0.05). A TAT volume of 8.29 ml yielded the largest area under the receiver operating characteristic curve (AUROC: 0.79, 95%CI: 0.74–0.83) to identify metabolic syndrome. TAT but not PCF correlated with higher coronary calcium score after adjustment for clinical variables (all p<0.05). Conclusion In our study, we observe that age-related body-site specific accumulation of adipose tissue may have distinct biological effects. Compared to other adiposity measures, peri-aortic adiposity is more tightly associated with cardiometabolic risk profiles and subclinical atherosclerosis in a relatively healthy population.

High pericardial and peri-aortic adipose tissue burden in pre-diabetic and diabetic subjects

BackgroundCentral obesity in relation to insulin resistance is strongly linked to the development of type 2 diabetes. However, data regarding the association between pericardial and peri-aortic adiposity, a potential estimate of visceral adipose tissue burden, and pre-diabetes status remains unclear.The aim of this study was to examine whether the degree of pericardial and thoracic peri-aortic adipose tissue, when quantified by multi-detector computed tomography (MDCT), differs significantly in a normal, pre-diabetic, and overtly diabetic population.MethodsWe studied 562 consecutive subjects including 357 healthy, 155 pre-diabetic, and 50 diabetic patients selected from participants who underwent annual health surveys in Taiwan. Pre-diabetes status was defined by impaired fasting glucose or impaired glucose intolerance according to American Diabetes Association guidelines. Pericardial (PCF) and thoracic peri-aortic (TAT) adipose tissue burden was assessed using a non-contrast 16-slice multi-detector computed tomography (MDCT) dataset with off-line measurement (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA). Body fat composition, serum high-sensitivity C-reactive protein (hs-CRP) level and insulin resistance (HOMA-IR) were also assessed.ResultsPatients with diabetes and pre-diabetes had greater volume of PCF (89 ± 24.6, 85.3 ± 28.7 & 67.6 ± 26.7 ml, p < 0.001) as well as larger TAT (9.6 ± 3.1 ml vs 8.8 ± 4.2 & 6.6 ± 3.5 ml, respectively, p < 0.001) when compared to the normal group, although there were no significant differences in adiposity between the diabetic and pre-diabetic groups. For those without established diabetes in our study, increasing TAT burden, but not PCF, appear to correlate with insulin resistance (HOMA-IR) and hs-CRP in the multivariable models.ConclusionsPre-diabetic and diabetic subjects, compared to normoglycemia, were associated with significantly higher pericardial and peri-aortic adipose tissue burden. In addition, visceral fat accumulation adjacent to the thoracic aorta seemed to exert a significant impact on insulin resistance and systemic inflammation.

Solitary accessory and papillary muscle hypertrophy manifested as dynamic mid-wall obstruction and symptomatic heart failure: diagnostic feasibility by multi-modality imaging

BackgroundSolitary papillary muscle (PM) hypertrophy is an unique type of hypertrophic cardiomyopathy (HCM), which is characterized by predominant papillary muscle hypertrophy sparing the rest of other left ventricular segments. It has recently drawn our attention about the mechanism of left ventricular mid-cavity obstruction and the influence of pressure gradient in the left ventricular outflow tract (LVOT), thus carries clinical importance.Case presentationWe reported a symptomatic, 83-year-old woman who presented with dynamic, high resting left ventricle (LV) mid-wall gradient without obvious septal hypertrophy or systolic anterior motion (SAM). Subsequent real-time (RT) three-dimensional echocardiography (3DE) and cardiac magnetic resonance imaging (MRI) demonstrated large, hypertrophic accessory papillary muscles squeezing mid-cavity of left ventricle producing dynamic pressure gradient during systole in the absence of left ventricular wall anomalies.ConclusionWe proposed that combined use of echocardiography particularly RT-3DE and cardiac magnetic resonance imaging (MRI) can accurately identify this specific type of hypertrophic cardiomyopathy without remarkable traditional features.

An observational study of the association among interatrial adiposity by computed tomography measure, insulin resistance, and left atrial electromechanical disturbances in heart failure.

AbstractExcessive visceral adiposity, hypothesized to be a key mediator in metabolic derangements, has recently been shown to exert toxic effects on cardiac structure and function. Data regarding the mechanistic link between regional adiposity, left atrial (LA) electromechanical remodeling, and heart failure with preserved ejection fraction (HFpEF) have been lacking.Various visceral adiposity measures, including pericardial fat (PCF), thoracic periaortic (TAT) fat, regional inter-atrial fat (IAF), and atrioventricular groove fat (AV Groove Fat), were assessed by multidetector computed tomography in 2 study cohorts (an annual health survey cohort and an outpatient cohort). We related such measures to cardiometabolic profiles in health survey cohort and LA electromechanical indices in our outpatient cohort, with Cox proportional hazards performed to examine the temporal trends of heart failure (HF).In our annual health survey cohort (n = 362), all 4 adiposity measures were positively related to unfavorable anthropometrics and systemic inflammation (high-sensitivity C-reactive protein) (all P < 0.05). In addition, both greater IAF and AV Groove Fat were positively associated with higher fasting glucose, HbA1c levels, and insulin resistance (all P < 0.05). In the outpatient cohort, the HFpEF group demonstrated the greatest adiposity measures, with greater IAF (≥8.2 mm, hazard ratio: 4.11, 95% confidence interval: 1.50–11.32) associated with reduced LA strain (ß-coef: –0.28), higher LA stiffness (ß-coef: 0.23), and longer P wave duration (ß-coef: 0.23) in multivariate models (all P < 0.05), and further related to higher HF hospitalization during follow-up.We therefore propose a possible pathophysiologic link among greater visceral adiposity, systemic inflammation, cardiometabolic risks, and HFpEF. Regional adiposity, especially IAF, was tightly linked to altered LA electromechanical properties and likely plays a key role in HF prognosis.

Characteristic Features on Morphologic and Topographic Findings of Pulmonary Vein Orifices in Transition From Diastolic Dysfunction to Heart Failure: A Computerized Tomography Study

BACKGROUND Diastolic dysfunction (DD), a precursor to clinical heart failure (HF), has traditionally been evaluated by means of echocardiography. Data regarding morphologic descriptions of pulmonary vein (PV) orifices in transition from DD to HF have been lacking. METHODS AND RESULTS We retrospectively studied 124 subjects with computerized tomography (CT)-derived PV parameters and echocardiography-derived diastolic indices. We categorized our subjects as 1) non-DD, 2) DD, or 3) heart failure with preserved ejection fraction (HFpEF) and observed a graded enlargement for 4 PV orifice areas across these groups. Positive linear relationship between the 4 PV orifice areas, echocardiography-derived mean pulmonary capillary wedge pressure (PCWP), and velocity of propagation (VP) were observed. Finally, maximum areas of left superior pulmonary vein (LSPV) and left inferior pulmonary vein (LIPV) significantly increased clinical diagnosis of HFpEF (likelihood-ratio χ(2): from 42.92 to 50.75 and 54.67 for LSPV and LIPV, respectively) when superimposed on left ventricular mass index, PCWP, and left atrial volume. CONCLUSIONS PV size measurements with the use of CT are feasible and further aid in diseases discrimination between preclinical DD and those progressed into HF, even with preserved global pumping. Our data suggest that CT-based PV measures may help to identify subjects at risk for HF.

The association between atrium electromechanical interval and pericardial fat.

Objectives Pericardial fat (PCF) may induce local inflammation and subsequent structural remodeling of the left atrium (LA). However, the adverse effects of PCF on LA are difficult to be evaluated and quantified. The atrial electromechanical interval determined by transthoracic echocardiogram was shown to be a convenient parameter which can reflect the process of LA remodeling. The goal of the present study was to investigate the association between the electromechanical interval and PCF. Methods and Results A total of 337 patients with mean age of 51.9±9.0 years were enrolled. The electromechanical interval (PA-PDI) defined as the time interval from the initiation of the P wave deflection to the peak of the mitral inflow A wave on the pulse wave Doppler imaging was measured for every patient. The amount of PCF was determined by multi-detector computed tomography. The PA-PDI interval was significantly correlated with the amount of PCF (r = 0.641, p value <0.001). Graded prolongation of PA-PDI interval was observed across 3 groups of patients divided according to the tertile values of PCF. The AUC for the PA-PDI interval in predicting an increased amount of PCF (third tertile) was 0.796. At a cutoff value of 130 ms identified by the ROC curve, the sensitivity and specificity of PA-PDI interval in identifying patients with a highest tertile of PCF were 63.4% and 85.3%, respectively. Conclusions The PA-PDI intervals were longer in patients with an increased amount of PCF. It may be a useful parameter to represent the degree of PCF-related atrial remodeling.