3 Key Takeaways
Plain English Summary- 01Core Finding
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.
- 02Study Evidence
Tested in a randomized controlled trial (49 participants) at the randomized clinical trial stage.
- 03Practical Meaning
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.
What This Means for You
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.
The Discovery
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 (inactive comparison treatment), 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).
How It Works, Simply
This pharmacology research focuses on receptor targeting. Researchers evaluated it using a randomized controlled trial (49 participants) at the randomized clinical trial stage of medical research.
3 Key Takeaways
Clinical Takeaways- 01Core Finding
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.
- 02Study Evidence
Tested in a randomized controlled trial (49 participants) at the randomized clinical trial stage.
- 03Practical Meaning
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.
Biological Mechanism & Study Design
Study Design & Cohort
Randomized controlled trial
Randomized controlled trial (49 participants) · Randomized Clinical Trial
Biological Pathway & Modality
Receptor targeting
Intervention: Effects of semaglutide on cardiac structure and function in heart failure with
Experimental Findings & Endpoints
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).
Clinical Translation & Practice Context
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.
The Bottom Line · Clinical Pearl
“ClinicalTrials.gov number: NCT05371496.”
Published in Nature Medicine · Current Stage: Randomized Clinical Trial