Severe obesity in human HFpEF alters contractile protein function and organization
Summary
Heart failure with preserved ejection fraction (HFpEF) causes substantial morbidity and mortality and has few effective therapies. Its phenotype has changed over time, with morbid obesity and metabolic defects supplanting hypertension and cardiac hypertrophy. We reveal that cardiomyocytes from patients with severe obesity and HFpEF have very depressed contractile reserve, including reduced calcium- and length-stimulated tension, power, and myosin activation compared to less-obese HFpEF and
Content
# Severe obesity in human HFpEF alters contractile protein function and organization
*Published: 2026 Apr 23*
Heart failure with preserved ejection fraction (HFpEF) causes substantial
morbidity and mortality and has few effective therapies. Its phenotype has
changed over time, with morbid obesity and metabolic defects supplanting
hypertension and cardiac hypertrophy. We reveal that cardiomyocytes from
patients with severe obesity and HFpEF have very depressed contractile reserve,
including reduced calcium- and length-stimulated tension, power, and myosin
activation compared to less-obese HFpEF and non-failing (NF) controls ±obesity,
but similar to advanced HF with reduced EF. Myocyte defects correlate with body
mass index and exercise hemodynamics in patients with HFpEF but not NF and
appear reversible upon weight loss. Increased troponin-I phosphorylation at
Thr181 occurs only in HF+obesity contributing to sarcomere dysfunction. Weight
reduction and sarcomere enhancers may offer benefits in HFpEF with obesity.
DOI: 10.1126/science.adz7118