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Updated: May 20, 2025

Author Spotlight: Exploring the Relationship Between Lipotoxicity and HFpEF
Published on: March 29, 2024
Insights Into the Role of Obesity in Heart Failure With Preserved Ejection Fraction: Pathophysiology and Management
Brandon Hathorn1, Mark J Haykowsky2, Jaime Almandoz3
1Applied Physiology and Advanced Imaging Laboratory, University of Texas at Arlington, Arlington, Texas, USA.
Abstract:
Heart failure (HF) is a significant global health issue, categorized by left ventricular ejection fraction, being either reduced (HFrEF < 0.40) or preserved (HFpEF > 0.50), or in the middle of this range. Although the overall incidence of HF remains stable, HFpEF cases are increasing, representing about 50% of all HF cases. Outcomes for HFpEF are similar to those for HFrEF, leading to substantial health-care resource use. Despite extensive research over the past 2 decades, the prognosis and mortality rates for HFpEF remain high. A key feature of HFpEF is exercise intolerance, characterized by severe exertional dyspnea and fatigue, which significantly impacts quality of life. The underlying mechanisms of exercise intolerance are not fully understood due to the complex pathophysiology and multisystem involvement. Obesity is a common comorbidity in HFpEF, especially in North America, leading to worsening symptoms, hemodynamics, and mortality rates. Increased adiposity leads to inflammation, hypertension, dyslipidemia, and insulin resistance, and impairing cardiac, vascular, pulmonary, and skeletal muscle function. Therefore, managing obesity is crucial in treating HFpEF. In this review we explore the pathophysiologic mechanisms of HFpEF, emphasizing obesity's role, and we discuss current management strategies while identifying areas needing further research.
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