Cardiomyocytes from patients with severe obesity and HFpEF have depressed contractile reserve and increased troponin-I phosphorylation at Thr181 compared to less-obese HFpEF and controls.
Observational
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.
Jani et al. (2026) conducted an observational in Heart failure with preserved ejection fraction (HFpEF) and severe obesity. Cardiomyocytes from patients with severe obesity and HFpEF have depressed contractile reserve and increased troponin-I phosphorylation at Thr181 compared to less-obese HFpEF and controls.