Key result
Mavacamten cuts peak force up to ~85% in engineered heart tissues while reducing diastolic stiffness.
Why the study?
To comprehensively characterize the length and load-dependent behaviors of engineered human cardiac muscle treated with the cardiac beta-myosin inhibitor mavacamten.
Does mavacamten alter length-dependent contractility and diastolic function in human engineered heart tissue?
Does mavacamten alter length-dependent contractility and diastolic function in human engineered heart tissue?
p-value: p=0.0009
Mavacamten decreases inotropy and improves lusitropy (diastolic function) in human engineered heart tissue while preserving length-dependent contractility, providing mechanistic support for its clinical use in hypertrophic cardiomyopathy.
May support lusitropic effects in engineered tissue; leaves open clinical translation in hypertrophic cardiomyopathy.
We applied innovative methods to comprehensively characterize the length and load-dependent behaviors of engineered human cardiac muscle when treated with the cardiac β-myosin specific inhibitor mavacamten, a drug on the verge of clinical implementation for hypertrophic cardiomyopathy. We find mechanistic support for the role of mavacamten in improving diastolic function of cardiac tissue and note novel effects on work and power.
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Sewanan et al. (2021) studied Hypertrophic cardiomyopathy (in vitro model). Mavacamten vs. Baseline (paired measurements) was evaluated on Peak force (p=0.0009). Mavacamten reduced peak force by 40% at 0.33 µM and by 85% at 0.5 µM in human engineered heart tissues, while improving diastolic function by reducing diastolic stiffness.
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