- This SUMMIT imaging substudy tested whether tirzepatide changes the right ventricle and both atria in obesity-related heart failure with preserved ejection fraction, areas an earlier imaging analysis did not cover.
- At 52 weeks, tirzepatide lowered right ventricular mass by 5 g and right ventricular end-diastolic volume by 10 mL compared with placebo, with no change in right ventricular ejection fraction.
- Maximal left and right atrial volumes also fell, and patients with larger drops in atrial volume reported larger improvements in heart failure symptoms and physical limitations.
Obesity drives heart failure with preserved ejection fraction (HFpEF) in several ways. It promotes sodium retention, expands plasma volume, and changes visceral fat in ways that inflame and thicken the heart muscle. In the SUMMIT trial, published in the New England Journal of Medicine in 2025, 731 patients with heart failure, an ejection fraction of at least 50%, and a body mass index of at least 30 kg/m2 were randomized to receive tirzepatide (up to 15 mg subcutaneously once per week) or placebo for at least 52 weeks. Tirzepatide lowered the hazard of cardiovascular death or worsening heart failure by 38% compared to placebo(HR 0.62; 95% CI 0.41–0.95; P=0.026). How the drug changes the heart itself is less clear.
An earlier cardiac magnetic resonance (CMR) substudy, published in the Journal of the American College of Cardiology in 2025, found that left ventricular (LV) mass fell from 120 g to 110 g with tirzepatide and stayed flat with placebo (P=0.004), while paracardiac fat fell from 221 mL to 182 mL (P<0.001). That analysis measured left atrial (LA) volume in 2D and did not look at the right ventricle.
At the 2026 American Heart Association Scientific Sessions, Dr. Christopher M. Kramer of University of Virginia Health presented a follow-up CMR analysis on behalf of the SUMMIT investigators (NCT04847557). Of the 175 patients recruited to the imaging substudy, 94 had complete CMR scans at baseline and at 52 weeks: 42 on tirzepatide and 52 on placebo. Their mean age was 65 years, and 56% were women. This time, the investigators measured right ventricular (RV) mass and volumes and measured the volumes of both atria in 3D.
Compared with placebo, tirzepatide reduced RV mass by 5 g (95% CI –10 to –1; P<0.02) and RV end-diastolic volume by 10 mL (95% CI –19 to –2; P<0.02). RV end-systolic volume and stroke volume each fell by 7 mL. RV ejection fraction and cardiac output did not change (P=0.80 and P=0.69, respectively). Relative to placebo, maximal LA volume fell by about 8 mL and maximal right atrial (RA) volume by about 10 mL (both P<0.03).
The atrial changes tracked with how patients felt. Larger drops in LA volume correlated with larger gains on the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) (r=–0.40; 95% CI –0.63 to –0.11; P<0.01). RA volume showed a similar relationship (r=–0.37; 95% CI –0.61 to –0.07; P<0.02).
The substudy was small. Only 94 of the 175 patients recruited had complete paired scans, and a single analyst read all images. The link between atrial volume and KCCQ-CSS is a correlation, so it does not show that the structural changes caused the improvement in symptoms.
Together with the earlier LV findings, the results suggest that tirzepatide remodels all four chambers of the heart in obesity-related HFpEF. Kramer and colleagues concluded that “these physiologic changes may reflect a mechanism of improved clinical outcomes in the main SUMMIT trial.”