ArticleAmerican journal of physiology. Heart and circulatory physiology2021
Mavacamten preserves length-dependent contractility and improves diastolic function in human engineered heart tissue.
Article in American journal of physiology. Heart and circulatory physiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
- Myofilament-level effects of aficamten increase diastolic chamber volumes and maintain cardiac output through preserved length-dependent force generation in healthy rat and canine myocardium.Basic research in cardiology · 2026Article
- Mechanistic diversity within RLC-dependent myosin ATPase inhibitors differentiates EDG-7500, a diastolic-selective cardiac sarcomere modulator.JCI insight · 2026Article
- Mavacamten's Dose-Time Dynamics and Predictive Factors in Hypertrophic Obstructive Cardiomyopathy Cardiac Remodeling.Echocardiography (Mount Kisco, N.Y.) · 2026Article
- Mavacamten in the Treatment of Obstructive Hypertrophic Cardiomyopathy: from Pathophysiology To Real World Data.Current cardiology reports · 2025Review
- Classification, Diagnosis, and Prognosis of Cardiomyopathy: A Comprehensive Narrative Review.Reviews in cardiovascular medicine · 2025Review
- Myosin binding protein-C modulates loaded sarcomere shortening in rodent permeabilized cardiac myocytes.The Journal of general physiology · 2025Article
- Mechanisms of a novel regulatory light chain-dependent cardiac myosin inhibitor.The Journal of general physiology · 2024Article
- Novel Cardiac Myosin Inhibitor Therapy for Hypertrophic Cardiomyopathy in Adults: A Contemporary Review.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2024Review
- Circular RNA circZFPM2 regulates cardiomyocyte hypertrophy and survival.Basic research in cardiology · 2024Article
- Physiological stress improves stem cell modeling of dystrophic cardiomyopathy.Disease models & mechanisms · 2024Article
- Engineered heart tissue: Design considerations and the state of the art.Biophysics reviews · 2024Review
- Myosin in autoinhibitedProceedings of the National Academy of Sciences of the United States of America · 2024Article
- From amoeboid myosin to unique targeted medicines for a genetic cardiac disease.Frontiers in physiology · 2024Review
- One-year real-world experience with mavacamten and its physiologic effects on obstructive hypertrophic cardiomyopathy.Frontiers in cardiovascular medicine · 2024Article
- Evaluation of Porcine Psoas Major as a Scaffold Material for Engineered Heart Tissues.Tissue engineering. Part C, Methods · 2023Article
- Mavacamten, a precision medicine for hypertrophic cardiomyopathy: From a motor protein to patients.Science advances · 2023Review
- Muscle Mechanics and Thick Filament Activation: An Emerging Two-Way Interaction for the Vertebrate Striated Muscle Fine Regulation.International journal of molecular sciences · 2023Review
- Increased length-dependent activation of human engineered heart tissue after chronic αAmerican journal of physiology. Heart and circulatory physiology · 2023Article
- Reproducibility of drug-induced effects on the contractility of an engineered heart tissue derived from human pluripotent stem cells.Frontiers in pharmacology · 2023Article
- Dystrophic cardiomyopathy: role of the cardiac myofilaments.Frontiers in physiology · 2023Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Comprehensive functional characterization of cardiac tissue includes investigation of length and load dependence. Such measurements have been slow to develop in engineered heart tissues (EHTs), whose mechanical characterizations have been limited primarily to isometric and near-isometric behaviors. A more realistic assessment of myocardial function would include force-velocity curves to characterize power output and force-length loops mimicking the cardiac cycle to characterize work output. We developed a system that produces force-velocity curves and work loops in human EHTs using an adaptive iterative control scheme. We used human EHTs in this system to perform a detailed characterization of the cardiac β-myosin specific inhibitor, mavacamten. Consistent with the clinically proposed application of this drug to treat hypertrophic cardiomyopathy, our data support the premise that mavacamten improves diastolic function through reduction of diastolic stiffness and isometric relaxation time. Meanwhile, the effects of mavacamten on length- and load-dependent muscle performance were mixed. The drug attenuated the length-dependent response at small stretch values but showed normal length dependency at longer lengths. Peak power output of mavacamten-treated EHTs showed reduced power output as expected but also shifted peak power output to a lower load. Here, we demonstrate a robust method for the generation of isotonic contraction series and work loops in engineered heart tissues using an adaptive-iterative method. This approach reveals new features of mavacamten pharmacology, including previously unappreciated effects on intrinsic myosin dynamics and preservation of Frank-Starling behavior at longer muscle lengths.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.