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Obesity and Heart Failure With Preserved Ejection Fraction: A Clinical Nexus for Exercise Intolerance
Abhishek Pandit1,2, Mahima Gupta3, Daniel A Arabie1
1Vascular Metabolism Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
Obesity (Silver Spring, Md.)
|March 27, 2026
Summary
Obesity significantly worsens heart failure with preserved ejection fraction (HFpEF) by impairing exercise capacity through cardiac, vascular, and skeletal muscle dysfunction. Addressing obesity is key to improving HFpEF outcomes.
Area of Science:
- Cardiology
- Metabolic Diseases
- Exercise Physiology
Background:
- Heart failure with preserved ejection fraction (HFpEF) is the predominant type of heart failure in the US.
- Obesity affects approximately 80% of HFpEF patients, exacerbating the condition.
Purpose of the Study:
- To review the central role of obesity in HFpEF pathophysiology and clinical presentation.
- To highlight obesity's impact on exercise intolerance, a key HFpEF symptom.
Main Methods:
- Review of evidence linking obesity to cardiac remodeling, diastolic dysfunction, and atrial enlargement.
- Analysis of cardiopulmonary exercise testing (CPET) findings in obese HFpEF patients.
- Examination of peripheral factors including vascular, skeletal muscle, and inflammatory pathways.
Main Results:
- Obesity promotes concentric remodeling, diastolic dysfunction, and reduces natriuretic peptide utility.
- CPET reveals obesity-related impairments in peak oxygen uptake, chronotropic response, and pulmonary pressures.
- Obesity amplifies peripheral drivers of exercise intolerance and is linked to chronic inflammation, fibrosis, and atrophy.
Conclusions:
- Obesity is a central, modifiable determinant of HFpEF.
- Targeting skeletal muscle, vascular, and inflammatory pathways is crucial for future HFpEF research and treatment.
Keywords:
cardiopulmonary exercise testing (CPET)exercise intoleranceglucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs)heart failure with preserved ejection fraction (HFpEF)inflammationobesityskeletal muscle dysfunctionvascular dysfunctionMore Related Videos
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