Association of tirzepatide with reverse cardiac remodeling and improved diastolic function in obesity-related HFpEF: A prospective real-world cohort study

Background Obesity-related heart failure with preserved ejection fraction (HFpEF) is characterized by concentric remodeling, diastolic dysfunction, and systemic inflammation. Tirzepatide, a dual GIP/GLP-1 receptor agonist, produces substantial weight loss, but real-world echocardiographic evidence of cardiac reverse remodeling remains limited, particularly in prospective cohorts. Methods We conducted a prospective, single-center, longitudinal observational cohort study of 50 adults with obesity-related HFpEF (LVEF ≥50%, BMI ≥30 kg/m 2 ) initiating tirzepatide in routine care. Co-primary endpoints were changes in left ventricular (LV) mass and the E/e' ratio from baseline to ≈6 months. Multiplicity was controlled via hierarchical gate-keeping with Benjamini–Hochberg false discovery rate (FDR) correction. Results Over a median follow-up of 5.8 months, mean LV mass decreased by −12.4 g (95% CI −15.4 to −9.4; q < 0.001; SRM −1.16) and E/e' improved by −1.45 (95% CI −1.85 to −1.11; q < 0.001; SRM −1.08). KCCQ score increased by +13.1 points (q < 0.001), 6-min walk distance by +43 m (q < 0.001), and BMI decreased by −5.8 kg/m 2 (q < 0.001). NT-proBNP, hs-CRP, and hs-TnT all declined significantly (all q < 0.01). NYHA class improved in 30 patients (60%) with none worsening ( p < 0.001). Conclusions In real-world practice, tirzepatide use was associated with reverse cardiac remodeling, improved diastolic function, and better health status in obesity-related HFpEF. These findings complement randomized trial evidence and support further evaluation of incretin-based therapy in obesity-related HFpEF.