The Impact of Maladaptive Adipose Tissue on Measures of Heart Failure Severity in Older, Obese Adults With and Without Heart Failure and Preserved Ejection Fraction

Abstract

Introduction:Obesity is a leading risk factor for heart failure with preserved ejection fraction (HFpEF), prevalent in more than 70% of patients. Compared to non-obese patients with HFpEF, obese patients with HFpEF demonstrate more profound abnormalities in cardiovascular (CV) structure and function and worse exercise capacity. Visceral adipose tissue (VAT) and epicardial adipose tissue (EAT) are associated with systemic inflammation and impaired nitric oxide availability. These abnormalities are implicated in CV remodeling and functional abnormalities, and may contribute to the development and severity of HFpEF. Despite this evidence, no prior study has directly examined visceral and ectopic adipose tissue depots and their relation to the severity or pathophysiology of HFpEF. Hypothesis:We hypothesized that compared to healthy controls, patients with HFpEF would have more VAT and that greater VAT would be indirectly associated with chronic physical activity (PA), measures of submaximal and peak exercise capacity (VO2), and symptom burden (dyspnea and fatigue). Additionally, we hypothesized that among obese patients with HFpEF, excess EAT would be associated with more severe hemodynamic derangements, increased pericardial restraint, and poorer aerobic capacity. Methods:Body Composition, Submaximal and Peak Exercise Capacity and Chronic Physical Activity Participants with HFpEF (n=78) and healthy control participants (n=50) were prospectively enrolled and underwent cardiopulmonary exercise testing with echocardiography to measure exercise capacity and CV structure and function. To measure the amount (area, cm2) of visceral (VAT), subcutaneous (SAT) and inter/intramuscular (IMAT) adipose tissue, images of the abdomen and thigh were obtained by magnetic resonance imaging (MRI). Chronic PA was measured via accelerometry over a two-week duration. Epicardial Adipose Tissue, Cardiac Structure and Function and Aerobic Capacity Patients referred for invasive cardiopulmonary exercise testing at the Mayo Clinic Cardiac Catheterization Laboratory between 2000 and 2014 were identified retrospectively. Patients with HFpEF and obesity (BMI ≥30 kg/m2) with recent echocardiography (≤1 month of cath) were included in the final analysis (n=169). Invasive exercise hemodynamics and VO2 were obtained during a right heart catheterization with expired gas analysis. Cardiac structure and function and EAT thickness were measured via two-dimensional Doppler and tissue Doppler echocardiography. Conclusions :Our data demonstrate a significantly greater amount of VAT in patients with HFpEF compared to non-HFpEF controls, which was related to greater submaximal symptom severity, poorer peak exercise capacity (peak VO2) and lower levels of chronic PA. Furthermore, our data revealed more abnormal cardiac hemodynamics in obese HFpEF patients with greater EAT than patients with minimal EAT. Future longitudinal studies are needed to examine mechanisms of visceral and other ectopic adipose tissue depots as they relate to the development and severity of HFpEF.