Obesity-Related Phenotype of Heart Failure With Preserved Ejection Fraction: A Comprehensive Review

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome with an obesity-related phenotype gaining prominence amid the global obesity epidemic. This review explores the distinct pathophysiological mechanisms, diagnostic challenges, and management strategies associated with obesity-induced HFpEF. Obesity contributes to HFpEF through several key mechanisms, including increased blood volume, myocardial hypertrophy and fibrosis, systemic inflammation, and metabolic dysregulation. These factors collectively exacerbate diastolic dysfunction and elevate left ventricular filling pressures, hallmark features of HFpEF. Diagnosing HFpEF in obese patients is particularly challenging due to overlapping comorbidities such as hypertension and diabetes, as well as the reduced reliability of traditional biomarkers such as N-terminal pro-B-type natriuretic peptide. Advanced imaging techniques are crucial in assessing diastolic dysfunction and myocardial remodeling. Managing obesity-related HFpEF requires a comprehensive approach. Lifestyle modifications, including weight loss and exercise, form the cornerstone of treatment, complemented by pharmacological therapies such as sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists. Optimizing comorbidity management is essential, while emerging therapies targeting inflammation, fibrosis, and metabolic dysfunction, alongside precision medicine approaches, offer promising future advancements. This review underscores the need for inclusive clinical trials and personalized treatment strategies to improve outcomes in obesity-related HFpEF. A deeper understanding of this phenotype is crucial for developing targeted interventions that enhance patient care and quality of life. Integrating these insights into clinical practice can help optimize diagnostic accuracy, refine therapeutic approaches, and guide risk stratification for better patient management.