Title: Visceral Adipose Tissue and Exercise Capacity in Heart Failure with preserved Ejection Fraction (HFpEF) Background: People with Heart Failure and preserved Ejection Fraction (HFpEF) experience poor quality of life (QOL) due to symptoms of dyspnea, fatigue, and exercise intolerance. Compared to healthy peers, people with HFpEF experience marked exercise intolerance manifested by decreased peak aerobic capacity and workload. Obesity is a major risk factor for the development of HFpEF and is related to poor exercise tolerance. Prior studies in non-HFpEF cohorts have shown that excess visceral adipose tissue (VAT) is associated with cardiovascular disease and chronic systemic inflammation. While, there are no proven effective therapies to reduce mortality in HFpEF, the relationship between VAT and HFpEF severity may be one area for improved understanding of the pathophysiology of HFpEF. No prior study has directly evaluated the relationships between VAT and the pathophysiology of HFpEF.
Specific Aims : We will determine if people with HFpEF have greater amounts of VAT compared to healthy, matched controls using magnetic resonance imaging (Aim #1) and evaluate if greater VAT is related to reduced exercise capacity (Aim#2), biomarkers of inflammation, chronic activity, and QOL (Aim #3). Methods and Objectives: This study will be conducted utilizing HFpEF patients (n=25) enrolled in an ongoing NIH sponsored clinical trial, Inorganic Nitrate to Amplify the Benefits and tolerability of Exercise training in HFpEF (Inorganic Nitrate to Amplify the Benefits and toLerability of Exercise in HFpEF, INABLE, RO1 HL128526-1) and healthy age, sex, and BMI matched controls (n=25) enrolled through this proposed study. All participants will undergo Magnetic Resonance Imaging and Dual X-ray Absorptiometry to quantify VAT (Aim #1) and cardiopulmonary exercise testing with expired gas analysis to quantify aerobic capacity (peak VO2), hemodynamics (cardiac output, heart rate, and blood pressure) (Aim#2). Chronic activity will be measured using external accelerometer devices, QOL will be assessed by the Kansas City Cardiomyopathy questionnaire, and biomarkers of inflammation will be assessed using blood laboratory specimens.
(Aim #3). Expected Outcomes: Upon completion of this research we expect to observe a difference in the amount of VAT in HFpEF compared to controls. Across all people we expect an inverse relationship between the amount of VAT and exercise capacity, chronic activity levels, and QOL. Interaction analysis will be performed to determine whether the associations between VAT and disease severity are amplified in subjects with HFpEF.
Visceral adipose tissue (VAT) has been shown in laboratory and preclinical studies to be associated with vascular stiffening, inflammation, and poor exercise capacity; processes that are known to be directly related to the development of heart failure with preserved ejection fraction (HFpEF). The proposed project will seek to translate these basic observations to the human disease model by direct measurement in the clinical HFpEF population. If a relationship between VAT and exercise capacity (surrogate measure of morbidity and mortality) is observed in HFpEF, we will have identified an underlying contributory mechanism for which future research can be developed to work towards novel interventions and therapeutic strategies to target visceral adipose tissue and improve outcomes in a clinically meaningful way.
