Heart failure with preserved ejection fraction (HFpEF) is a growing global health burden, accounting for more than half of all heart failure cases. Obesity has emerged as a major independent risk factor for HFpEF, contributing to systemic inflammation, neurohormonal activation, myocardial fibrosis (stiffening of the heart muscle, thus limiting its ability to pump blood) and impaired ventricular relaxation. Increasing evidence suggests that obesity-related HFpEF represents a distinct clinical phenotype with unique pathophysiological characteristics and poorer prognosis.1
Visceral and epicardial adipose (fat) tissue promote inflammation, extracellular matrix remodeling, and cardiac stiffening, leading to adverse atrial and ventricular remodeling in HFpEF. Recent evidence shows that severe obesity further impairs the function and organization of the contractile protein of the cardiomyocyte (heart muscle cell), contributing to myocardial dysfunction in obesity-related HFpEF.1,2
A recent study found that patients with severe obesity-related HFpEF exhibit markedly impaired cardiomyocyte contractile reserve i.e., decreased ability to contract due to alterations in the contractile protein structure, leading to reduced force generation during cardiac muscle contraction. The study also suggested that weight reduction may improve cardiac function in obese patients with HFpEF.2,3
(Sources: 1. Rodrigues MM, Falcão LM. Pathophysiology of heart failure with preserved ejection fraction in overweight and obesity – Clinical and treatment implications. Int J Cardiol. 2025 Jul 1;430:133182. Doi: 10.1016/j.ijcard.2025.133182; 2. Jani VP, Rhodehamel M, Fenwick AJ, et al. Severe obesity in human HFpEF alters contractile protein function and organization. Science. Published online April 24, 2026. Doi:10.1126/science.adz7118; 3. Obesity increases heart failure risk but weight loss can reverse it, study finds, [internet]. Cited 2026, May 8. Available from: https://www.medicalnewstoday.com/articles/severe-obesity-may-weaken-heart-health-but-weight-loss-may-help-reverse-this.)