Abstract 10714: Safety and Efficacy of GLP1 Agonists on Weight Loss and Symptoms in Hypertrophic Cardiomyopathy Evaluated as Part of a Prospective Registry

Abstract

Background: Obesity is highly prevalent in patients with hypertrophic cardiomyopathy (HCM) and associated with more severe phenotype, symptom burden and worse outcomes. While glucagon like peptide-1 (GLP-1) agonists improve symptoms and outcomes in patients with other forms of cardiac disease, their safety and efficacy in patients with obesity and HCM remains unknown. Objective: Determine the safety and efficacy of GLP-1 agonists in obese patients with HCM initiated on these medications for weight loss as part of a multi-disciplinary HCM center. Methods: Prospective registry of consecutive HCM patients with body mass index (BMI) of ≥30 initiated on a GLP-1 agonist from 2/2024 to 9/2025. Primary efficacy analysis was proportion of patients with weight reduction ≥5%, and improvement in symptom burden (measured by NYHA class and KCCQ-OS). Primary safety analysis was discontinuation of GLP-1 agonist for side effects deemed significant from perspective of patient or treating physician. Results: GLP-1 agonist was initiated in 56 patients at 55 ± 10 years of age, baseline BMI of 37.2 ± 5.7, and 19 (34%) with NYHA class I, 33 (59%) with class II, and 4 (7%) with class III symptoms; KCCQ-OS was 66 ± 25. Maximum LV wall thickness was 19 ± 5mm, ejection fraction of 65 ± 5%, and 18 (32%) with obstructive, 19 (34%) with nonobstructive HCM, and 19 (34%) with prior septal myectomy. In 30 patients GLP-1 agonist was primarily semaglutide and tirzepitide in 26. In 51 patients (91%) GLP-1 was continued over 9 ± 4 months of follow-up, while it was prematurely discontinued in 5 (9%) for side effects (n=2; dyspepsia in both) or cost (n=3). There were no serious adverse events related to GLP-1 agonists or deaths. 7 patients were concurrently treated with cardiac myosin inhibitors (CMI). In the 51 patients maintained on GLP-1, the mean percent change in body weight was -12 ± 6% (median decrease in BMI from 37 to 33, p<0.001), including 29% of patients with weight reduction of 5 to 9%, 31% with reduction of 10-14%, and 27% with reduction of ≥15% (Figure 1). Over follow-up, in 44 patients maintained on GLP-1 and not concurrently treated with a CMI, NYHA class improved by ≥ 1 in 17 patients (39%), including NYHA class improving in 59% of patients with NYHA class >1 at baseline (Figure 2). In contrast, NYHA class worsened in only 1 patient (2%). KCCQ-OS score improved by a median of 7 points (IQR of 0, 15; from 66 to 72, p=0.003). Conclusion: In a cohort of HCM patients with obesity, GLP-1 agonists were safe and effective in reducing body weight. Cardiac symptoms as measured by both NYHA class and KCCQ-OS improved during treatment. These data support future large prospective clinical trials of GLP-1 agonists in patients with obesity and HCM.