Yau-Huei Lai

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.

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.

Independent Effects of Body Fat and Inflammatory Markers on Ventricular Geometry, Midwall Function, and Atrial Remodeling

The effect of body fat distribution on left ventricular (LV) mass and geometry has been recently recognized. However, data regarding circulating inflammatory markers in relation to regional visceral fat deposits, which are metabolically active tissues that can impact cardiac structural remodeling, remain sparse.

The relationship among atrium electromechanical interval, insulin resistance, and metabolic syndrome.

BACKGROUND Metabolic syndrome (MS) is an important risk factor of atrial fibrillation. However, an understanding of the adverse effects of MS on left atrial (LA) functional assessment in terms of electromechanical interval, a convenient parameter that can reflect the process of LA remodelling, has been lacking. The goal of this study was to investigate the association between electromechanical interval and MS. METHODS In all, 337 patients (91 with MS) with mean age of 51.9 ± 9.0 years were enrolled. Metabolic syndrome was defined by National Cholesterol Education Program-Adult Treatment Panel III score. Insulin resistance was assessed by the homeostasis model assessment-insulin resistance method. The electromechanical interval, defined as the time from initiation of P wave deflection to peak of mitral inflow Doppler A wave (PA-PDI), was measured. RESULTS Patients with MS had significantly longer PA-PDI intervals compared with those of patients without MS (131.0 ± 12.4 milliseconds vs. 123.2 ± 14.0 milliseconds, P < 0.001). Longer PA-PDI intervals were observed in subjects with higher metabolic scores (P < 0.05). In patients with small LA size, PA-PDI intervals, but not LA dimensions, were significantly different between groups with and without MS (P < 0.05). Additionally, PA-PDI interval was positively correlated with insulin resistance (r = 0.267, P < 0.001). CONCLUSIONS PA-PDI intervals were longer in patients with MS compared with those of patients without MS and tracked with insulin resistance. PA-PDI may be a useful clinical parameter to represent the degree of atrial remodelling in subjects with metabolic derangements.

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.

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.

Cardiac mechanics and ventricular twist by three-dimensional strain analysis in relation to B-type natriuretic peptide as a clinical prognosticator for heart failure patients.

Background Three dimensional (3D) echocardiography-derived measurements of myocardial deformation and twist have recently advanced as novel clinical tools. However, with the exception of left ventricular ejection fraction and mass quantifications in hypertension and heart failure populations, the prognostic value of such imaging techniques remains largely unexplored. Methods We studied 200 subjects (mean age: 60.2±16 years, 54% female, female n = 107) with known hypertension (n = 51), diastolic heart failure (n = 61), or systolic heart failure (n = 30), recruited from heart failure outpatient clinics. Fifty-eight healthy volunteers were used as a control group. All participants underwent 3D-based myocardial deformation and twist analysis (Artida, Toshiba Medical Systems, Tokyo, Japan). We further investigated associations between these measures and brain natriuretic peptide levels and clinical outcomes. Results The global 3D strain measurements of the healthy, hypertension, diastolic heart failure, and systolic heart failure groups were 28.03%, 24.43%, 19.70%, and 11.95%, respectively (all p<0.001). Global twist measurements were estimated to be 9.49°, 9.77°, 8.32°, and 4.56°, respectively. We observed significant differences regarding 3D-derived longitudinal, radial, and global 3D strains between the different disease categories (p<0.05), even when age, gender, BMI and heart rate were matched. In addition, 3D-derived longitudinal, circumferential, and 3D strains were all highly correlated with brain natriuretic peptide levels (p<0.001). At a mean 567.7 days follow-up (25th–75th IQR: 197–909 days), poorer 3D-derived longitudinal, radial, and global 3D strain measurements remained independently associated with a higher risk of cardiovascular related death or hospitalization due to heart failure, after adjusting for age, gender, and left ventricular ejection fraction (all p<0.05). Conclusions 3D-based strain analysis may be a feasible and useful diagnostic tool for discriminating the extent of myocardial dysfunction. Furthermore, it is able to provide a prognostic value beyond traditional echocardiographic parameters in terms of ejection fraction.

Cardiac Structural Remodeling, Longitudinal Systolic Strain, and Torsional Mechanics in Lean and Nonlean Dysglycemic Chinese Adults

Background: Diabetes mellitus and pre–diabetes mellitus are associated with lower body mass indices and increased risk of cardiovascular events (including heart failure) at lower glucose thresholds in Chinese compared with Western cohorts. However, the extent of cardiac remodeling and regulation on cardiac mechanics in lean and nonlean dysglycemic Chinese adults is understudied. Methods and Results: We studied 3950 asymptomatic Chinese (aged 49.7±10.7 years; 65% male; body mass index: 24.3±3.5 kg/m2) with comprehensive echocardiography including speckle tracking for left ventricular global longitudinal strain/torsion, with plasma sugar, glycosylated hemoglobin (HbA1c), and insulin resistance (homeostasis model assessment of insulin resistance) obtained. Participants were classified as (1) nondiabetic (fasting glucose <100 mg/mL; HbA1c <5.7%; n=1416), prediabetic (fasting glucose 100–126 mg/dL; HbA1c 5.7%–6.4%; n=2029), or diabetic (n=505) and (2) lean (body mass index <23 kg/m2; n=1445) or nonlean (n=2505). Higher sugar, HbA1c, and homeostasis model assessment of insulin resistance were independently associated with higher left ventricular mass, greater mass-to-volume ratio, more impaired diastolic indices, and worse global longitudinal strain even after adjusting for clinical covariates (adjusted coefficient value: 0.28/0.12 for global longitudinal strain per 1 U HbA1c/homeostasis model assessment of insulin resistance increment; both P<0.001), with a consistent trend toward greater torsion (all trend P<0.001). The optimal cutoffs in identifying subclinical systolic dysfunction (global longitudinal strain more impaired than −18%) for lean versus nonlean individuals were 97 versus 106 mg/dL for fasting sugar, 130 versus 135 mg/mL for postprandial sugar, 5.62% versus 6.28% for HbA1c, and 1.81 versus 2.40 for homeostasis model assessment of insulin resistance, respectively. Conclusions: These data demonstrate the presence of preclinical cardiac remodeling and systolic dysfunction in prediabetic and diabetic Chinese adults, occurring at lower thresholds of glycemic indices than defined by international standards, particularly in lean individuals.

Age, Sex, and Blood Pressure-Related Influences on Reference Values of Left Atrial Deformation and Mechanics From a Large-Scale Asian PopulationCLINICAL PERSPECTIVE

Background— Left atrial (LA) function is tightly linked to several cardiovascular diseases and confers key prognostic information. Speckle tracking-based deformation as a feasible and sensitive LA mechanical assessment has proven its clinical significance beyond volume measures; however, the reference values remain largely unknown. Methods and Results— We studied 4042 participants undergoing annual cardiovascular survey. Among them, 2812 healthy participants (65% men; mean age, 47.4±9.9 years) were eligible for speckle tracking analysis. Peak atrial longitudinal systolic strain and strain rate (SR) at systolic (SRs), early diastolic (SRe), and late diastolic atrial contraction phases (SRa) were analyzed by dedicated software (EchoPAC, GE) and compared in terms of age, sex, and blood pressure. Overall, women demonstrated higher peak atrial longitudinal systolic strain (39.34±7.99% versus 37.95±7.96%; P<0.001) and showed age-dependent more pronounced peak atrial longitudinal systolic strain functional decay than those of men (P value for interaction, <0.05), with men showing higher SRs and SRa, although lower SRe (all P<0.001). Both increasing age and higher blood pressure were independently associated with deteriorated peak atrial longitudinal systolic strain, SRs, and SRe, although augmented LA SRa, even after accounting for baseline clinical covariates in multivariable models that incorporated LA volume, NT-proBNP (N-terminal pro-B-type natriuretic peptide), or left ventricular E/e′ (all P<0.001). Conclusions— Our findings suggest LA mechanical functional decays in association with increasing age and higher blood pressure, which seem to be compensated for by augmentation of atrial pump function. We have also provided age- and sex-stratified reference values for strain and SR based on a large-scale Asian population.

Excessive interatrial adiposity is associated with left atrial remodeling, augmented contractile performance in asymptomatic population

Abstract Purpose Pericardial adipose tissue had been shown to exert local effects on adjacent cardiac structures. Data regarding the mechanistic link between such measures and left atrial (LA) structural/functional remodeling, a clinical hallmark of early stage heart failure (HF) and atrial fibrillation (AF) incidence, in asymptomatic population remain largely unexplored. Methods This retrospective analysis includes 356 subjects free from significant valvular disorders, atrial fibrillation, or clinical HF. Regional adipose tissue including pericardial and periaortic fat volumes, interatrial septal (IAS), and left atrioventricular groove (AVG) fat thickness were all measured by multidetector computed tomography (MDCT) (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA). We measured LA volumes, booster performance, reservoir capacity as well as conduit function, and analyzed their association with adiposity measures. Results All four adiposity measures were positively associated with greater LA volumes (all P < 0.05), while IAS and AVG fat were also related to larger LA kinetic energy and worse reservoir capacity (both P < 0.01). In multivariate models, IAS fat thickness remained independently associated with larger LA volumes, increased LA kinetic energy and ejection force (β-coef: 0.17 & 0.15, both P < 0.05), and impaired LA reservoir and conduit function (β-coef: −0.20 & −0.12, both P < 0.05) after adjusting for clinical variables. Conclusion Accumulated visceral adiposity, especially interatrial fat depots, was associated with certain LA structural/functional remodeling characterized by impaired LA reservoir and conduit function though augmented kinetic energy and ejection performance. Our data suggested that interatrial fat burden may be associated with certain detrimental LA functions with compensatory LA adaptation in an asymptomatic population.