Effects of semaglutide on cardiac structure and function in heart failure with preserved ejection fraction and obesity: a pre-specified cardiac magnetic resonance substudy of the CAMEO-SEMA trial

Glucagon-like peptide-1 receptor agonists improve symptoms in patients with obesity and heart failure with preserved ejection fraction (HFpEF). We recently demonstrated that semaglutide reduces exertional pulmonary artery wedge pressure (PAWP) in obesity-related HFpEF, but potential effects of semaglutide on cardiac structure and function that may underlie these hemodynamic improvements remain unclear. In this prespecified cardiovascular magnetic resonance (CMR) substudy of the randomized CAMEO-SEMA trial, 49 participants (33 semaglutide, 16 placebo, 28 female) underwent CMR at baseline and 52 weeks, within 1 day of invasive exercise hemodynamic assessment. The prespecified primary CMR endpoint was change in left atrial (LA) reservoir strain; other prespecified CMR endpoints included LV filling dynamics, which were assessed by early filling rate indexed to end-diastolic volume (eFR/EDV). Compared with placebo, semaglutide improved LA reservoir strain (+5.7% [95% CI, +0.3 to +9.7]; P=0.037) and eFR/EDV (+0.64 s −1 [95% CI, +0.42 to +1.00]; P<0.0001). Improvements in LA reservoir strain and LV filling dynamics were associated with reductions in exercise PAWP (r=−0.46, P<0.001 and r=−0.65, P<0.0001, respectively). With respect to other prespecified CMR endpoints, semaglutide reduced LV mass, restored more physiologic LV geometry, and improved right ventricular function and biventricular myocardial mechanics. The results of this CMR substudy indicate that in patients with obesity-related HFpEF, semaglutide improves LA function and LV diastolic filling dynamics, identifying improvements in myocardial function that may contribute to semaglutide’s improvement of hemodynamics. ClinicalTrials.gov number: NCT05371496 .