Weight loss as the optimal cardiometabolic management strategy for preventing and treating heart failure

To synthesize current evidence supporting intentional weight reduction as a cardiometabolic strategy for treating and preventing heart failure (HF) across the ejection-fraction spectrum, examine the influence of baseline obesity on treatment effects of established HF therapies, and highlight key knowledge gaps and future research directions.

Visceral adipose tissue, central obesity, and dysfunctional adipose mass are linked to the development and progression of HF with preserved ejection fraction (HFpEF). Recent trials show that incretin-based therapies (semaglutide, tirzepatide) improve exercise capacity, symptoms, and quality of life in HFpEF, and potentially reduce HF events. Patients with higher degrees of obesity may derive greater benefit from incretin-based therapies and other guideline-directed therapies, including mineralocorticoid receptor antagonists (MRA), sodium-glucose transport 2 (SGLT2) inhibitors, and angiotensin receptor-neprilysin inhibitor (ARNI). While observational studies suggest intentional weight loss may lower HF risk, randomized trials of antiobesity medications have yet to further clarify this potential benefit.

Weight loss is currently recommended as an optimal strategy for individuals with obesity and HFpEF, given consistent benefits for exercise capacity, functional status, and quality of life, with a potential for reducing clinical events. Intentional weight loss impact in HFrEF and its role in primary HF prevention remains uncertain. Large, well designed cardiovascular outcome trials of intentional weight-loss interventions in populations with obesity and HF, or obesity and elevated HF risk, are needed to establish clinical efficacy and better define individuals who benefit from those interventions across the spectrum of ejection fraction.