Pathophysiology of heart failure with preserved ejection fraction in overweight and obesity - Clinical and treatment implications

Abstract

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome with vast prevalence worldwide. Despite recent advances in understanding its pathophysiology, HFpEF remains under-diagnosed in clinical practice. Obesity-related HFpEF is a distinct and frequent phenotype with an additionally challenging diagnosis. We address the importance of overweight and obesity in HFpEF, focusing on the influence of adipose tissue in inflammation and neurohormonal activity. We also discuss atrial and ventricular remodelling in obesity-related HFpEF and potential clinical implications.

Obesity is an independent risk factor for HFpEF. Adipose tissue synthesizes aldosterone, causing lower levels of natriuretic peptide. Adipocytes dysfunction promotes a pro-inflammatory state and leads to extracellular matrix remodelling and consequently stiffening of the heart and vessels. Thus, the quantity, distribution and quality of the excess fat influences cardiovascular risk. Visceral and epicardial adipose tissue are often associated with an increased likelihood of developing HFpEF. Obesity-related HFpEF presents higher risk of left ventricular concentric remodelling and inadequate accommodation of the expanded volume due to the obesity, resulting in higher left ventricular filling pressure. Nevertheless, microvascular endothelium inflammation modifies cardiomyocyte elasticity and increases collagen deposition, which enhances myocardial fibrosis and results in HFpEF. Furthermore, neurohormonal activation may also contribute to cardiac remodelling by inducing plasma volume expansion. In turn, leptin also stimulates aldosterone synthesis and enhances renin–angiotensin–aldosterone system.

Obesity-related HFpEF presents worse overall prognosis, with increased risk of heart failure hospitalization and all-cause mortality. Intentional weight loss through caloric restriction, physical activity, pharmacological intervention and/or bariatric surgery are promising strategies.