TIRZEPATIDE significantly reduces left ventricular (LV) mass and paracardiac adipose tissue in patients with obesity-related heart failure with preserved ejection fraction (HFpEF), according to findings from the cardiac magnetic resonance (CMR) substudy of the SUMMIT trial.
Obesity-related HFpEF is a distinct phenotype characterised by increased LV mass and epicardial adipose tissue, both of which contribute to adverse cardiovascular outcomes. The SUMMIT trial previously demonstrated that tirzepatide, a dual GLP-1 and GIP receptor agonist, led to substantial weight loss and a 38% reduction in heart failure events in this patient population. The CMR substudy was designed to assess whether tirzepatide-induced weight loss translates into structural cardiac improvements, particularly reductions in LV mass and paracardiac adipose tissue.
A total of 175 participants with obesity-related HFpEF underwent baseline CMR imaging, with 106 completing follow-up scans at 52 weeks. Compared to placebo, tirzepatide treatment resulted in a significant reduction in LV mass by 11 g (95% CI: −19 to −4 g, P = 0.004) and a decrease in paracardiac adipose tissue volume by 45 mL (95% CI: −69 to −22 mL, P < 0.001). These changes correlated with reductions in body weight (P < 0.02) and showed a trend towards associations with waist circumference and blood pressure (P = 0.06 for both). Additionally, reductions in LV mass were linked to improvements in LV end-diastolic volume and left atrial volume parameters (P < 0.03 for all).
The findings suggest that tirzepatide’s cardiovascular benefits in obesity-related HFpEF extend beyond weight loss alone, with direct structural cardiac improvements that may underlie the observed reduction in heart failure events. Given the superiority of CMR in detecting changes in LV mass compared to echocardiography, this study provides robust evidence supporting tirzepatide’s role in modifying cardiac morphology in HFpEF. Future research should explore whether GIP agonism contributes uniquely to these effects and further assess the implications for long-term cardiovascular outcomes. Clinicians managing obesity-related HFpEF may consider tirzepatide as a therapeutic option to not only promote weight loss but also improve cardiac structure and potentially reduce heart failure progression.
Katrina Thornber, EMJ
Reference
Kramer CM et al. Tirzepatide reduces LV Mass and paracardiac adipose tissue in obesity-related heart failure: SUMMIT CMR substudy. JACC. 2025;85(7):699-706.
