Epicardial Adiposity in Relation to Metabolic Abnormality, Circulating Adipocyte FABP, and Preserved Ejection Fraction Heart Failure

Epicardial adipose tissue (EAT) as a source of pro-inflammatory cytokines tightly linked to metabolic abnormalities. Data regarding the associations of EAT with adipocyte fatty acid-binding protein (A-FABP), a cytokine implicated in the cardiometabolic syndrome, might play an important part in mediating the association between EAT and cardiac structure/function in preserved ejection fraction heart failure (HFpEF). We conducted a prospective cohort study comprising 252 prospectively enrolled study participants classified as healthy (n = 40), high-risk (n = 161), or HFpEF (n = 51). EAT was assessed using echocardiography and compared between the three groups and related to A-FABP, cardiac structural/functional assessment utilizing myocardial deformations (strain/strain rates) and HF outcomes. EAT thickness was highest in participants with HFpEF (9.7 ± 1.7 mm) and those at high-risk (8.2 ± 1.5 mm) and lowest in healthy controls (6.4 ± 1.9 mm, p \u3c 0.001). Higher EAT correlated with the presence of cardiometabolic syndrome, diabetes and renal insufficiency independent of BMI and waist circumference (pinteraction for all \u3e 0.1), and was associated with reduced LV global longitudinal strain (GLS) and LV mass-independent systolic/diastolic strain rates (SRs/SRe) (all p \u3c 0.05). Higher A-FABP levels were associated with greater EAT thickness (pinteraction \u3e 0.1). Importantly, in the combined control cohort, A-FABP levels mediated the association between EAT and new onset HF. Excessive EAT is independently associated with the metabolic syndrome, renal insufficiency, and higher A-FABP levels. The association between EAT and new onset HF is mediated by A-FABP, suggesting a metabolic link between EAT and HF. Keywords: adipocyte fatty acid-binding protein (A-FABP); epicardial adipose tissue (EAT); heart failure (HF); metabolic syndrome; preserved ejection fraction heart failure (HFpEF); pro-inflammatory cytokines; strain; strain rate

Incremental prognostic value of coronary computed tomography angiography over coronary calcium scoring for major adverse cardiac events in elderly asymptomatic individuals

Aims: Coronary computed tomography angiography (CCTA) and coronary artery calcium score (CACS) have prognostic value for coronary artery disease (CAD) events beyond traditional risk assessment. Age is a risk factor with very high weight and little is known regarding the incremental value of CCTA over CAC for predicting cardiac events in older adults. Methods and results: Of 27 125 individuals undergoing CCTA, a total of 3145 asymptomatic adults were identified. This study sample was categorized according to tertiles of age (cut-off points: 52 and 62 years). CAD severity was classified as 0, 1-49, and ≥50% maximal stenosis in CCTA, and further categorized according to number of vessels ≥50% stenosis. The Framingham 10-year risk score (FRS) and CACS were employed as major covariates. Major adverse cardiovascular events (MACE) were defined as a composite of all-cause death or non-fatal MI. During a median follow-up of 26 months (interquartile range: 18-41 months), 59 (1.9%) MACE occurred. For patients in the top age tertile, CCTA improved discrimination beyond a model included FRS and CACS (C-statistic: 0.75 vs. 0.70, P-value = 0.015). Likewise, the addition of CCTA improved category-free net reclassification (cNRI) of MACE in patients within the highest age tertile (e.g. cNRI = 0.75; proportion of events/non-events reclassified were 50 and 25%, respectively; P-value \u3c0.05, all). CCTA displayed no incremental benefit beyond FRS and CACS for prediction of MACE in the lower age tertiles. Conclusion: CCTA provides added prognostic value beyond cardiac risk factors and CACS for the prediction of MACE in asymptomatic older adults

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

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 \u3c 0.05), while IAS and AVG fat were also related to larger LA kinetic energy and worse reservoir capacity (both P \u3c 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 \u3c 0.05), and impaired LA reservoir and conduit function (β-coef: -0.20 & -0.12, both P \u3c 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

Associations between CT-determined visceral fat burden, hepatic steatosis, circulating white blood cell counts and neutrophil-to-lymphocyte ratio

Visceral adiposity is associated with cardiovascular disease, an association that may be mediated in part by inflammation. We hypothesized that regional measures of visceral adiposity would associate with commonly obtained clinical measures of immune status. We consecutively studied 3,291 subjects (mean age, 49.8±9.8 years) who underwent an annual cardiovascular risk survey. Peri-cardial (PCF) and thoracic peri-aortic adipose tissue (TAT) volumes were determined by dedicated computed tomography (CT) software (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA). Hepatic steatosis was assessed by abdominal ultrasonography. We explored cross-sectional associations between visceral fat measures and high-sensitivity C-reactive protein (hs-CRP), leukocyte counts, and the neutrophil-to-lymphocyte ration (NLR). Among 3,291 study participants, we observed positive linear associations between PCF and TAT, higher degree of hepatic steatosis and hs-CRP, various leukocyte counts, either total and its differential counts, and NLR (all trend p\u3c0.001). Multi-variate linear and logistic regression models showed independent associations between PCF/TAT (ß-Coef: 0.14/0.16, both p\u3c0.05) and total WBC counts, with only TAT further demonstrated significant relations with neutrophil counts and NLR (both p\u3c0.05) and independently identified abnormally high WBC and NLR (Odds ratio: 1.18 & 1.21, both p\u3c0.05). C-statistics showed significant incremental model prediction for abnormally high WBC and NLR (both ΔAUROC\u3c0.05) when TAT was superimposed on traditional cardiovascular risks and biochemical information. Greater visceral adiposity burden and hepatic steatosis may be associated with higher circulating leukocyte counts and markers for atherosclerosis, with more pronounced influences for peri-aortic adiposity. Our data suggested the differential biological impacts for region-specific visceral adiposity

Coronary revascularization vs. medical therapy following coronary-computed tomographic angiography in patients with low-, intermediate- and high-risk coronary artery disease: results from the CONFIRM long-term registry

Aims: To identify the effect of early revascularization on 5-year survival in patients with CAD diagnosed by coronary-computed tomographic angiography (CCTA). Methods and results: We examined 5544 stable patients with suspected CAD undergoing CCTA who were followed a median of 5.5 years in a large international registry. Patients were categorized as having low-, intermediate-, or high-risk CAD based on CCTA findings. Two treatment groups were defined: early revascularization within 90 days of CCTA (n = 1171) and medical therapy (n = 4373). To account for the non-randomized referral to revascularization, we developed a propensity score by logistic regression. This score was incorporated into Cox proportional hazard models to calculate the effect of revascularization on all-cause mortality. Death occurred in 363 (6.6%) patients and was more frequent in medical therapy. In multivariable models, when compared with medical therapy, the mortality benefit of revascularization varied significantly over time and by CAD risk (P for interaction 0.04). In high-risk CAD, revascularization was significantly associated with lower mortality at 1 year (hazard ratio [HR] 0.22, 95% confidence interval [CI] 0.11-0.47) and 5 years (HR 0.31, 95% CI 0.18-0.54). For intermediate-risk CAD, revascularization was associated with reduced mortality at 1 year (HR 0.45, 95% CI 0.22-0.93) but not 5 years (HR 0.63, 95% CI 0.33-1.20). For low-risk CAD, there was no survival benefit at either time point. Conclusions: Early revascularization was associated with reduced 1-year mortality in intermediate- and high-risk CAD detected by CCTA, but this association only persisted for 5-year mortality in high-risk CAD. KEYWORDS: CAD; coronary-computed tomographic angiography; revascularizatio

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

Excessive 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 \u3c 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 \u3c 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 \u3c 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

Qualitative and semi-quantitative evaluation of myocardium perfusion with 3 T stress cardiac MRI

Background3 T MRI has been adopted by some centers as the primary choice for assessment of myocardial perfusion over conventional 1.5 T MRI. However, there is no data published on the potential additional value of incorporating semi-quantitative data from 3 T MRI. This study sought to determine the performance of qualitative 3 T stress magnetic resonance myocardial perfusion imaging (3 T-MRMPI) and the potential incremental benefit of using a semi-quantitative perfusion technique in patients with suspected coronary artery disease (CAD).MethodsFifty eight patients (41 men; mean age: 59 years) referred for elective diagnostic angiography underwent stress 3 T MRMPI with a 32-channel cardiac receiver coil. The MR protocol included gadolinium-enhanced stress first-pass perfusion (0.56 mg/kg, dipyridamole), rest perfusion, and delayed enhancement (DE). Visual analysis was performed in two steps. Ischemia was defined as a territory with perfusion defect at stress study but no DE or a territory with DE but additional peri-infarcted perfusion defect at stress study. Semi-quantitative analysis was calculated by using the upslope of the signal intensity-time curve during the first pass of contrast medium during dipyridamole stress and at rest. ROC analysis was used to determine the MPRI threshold that maximized sensitivity. Quantitative coronary angiography served as the reference standard with significant stenosis defined as \u3e70 % diameter stenosis. Diagnostic performance was determined on a per-patient and per-vessel basis.ResultsQualitative assessment had an overall sensitivity and specificity for detecting significant stenoses of 77 % and 80 %, respectively. By adding MPRI analysis, in cases with negative qualitative assessment, the overall sensitivity increased to 83 %. The impact of MPRI differed depending on the territory; with the sensitivity for detection of left circumflex (LCx) stenosis improving the most after semi-quantification analysis, (66 % versus 83 %).ConclusionsPure qualitative assessment of 3 T MRI had acceptable performance in detecting severe CAD. There is no overall benefit of incorporating semi-quantitative data; however a higher sensitivity can be obtained by adding MPRI, especially in the detection of LCx lesions