ArticlePloS one2016
A Small Molecule Inhibitor of Sarcomere Contractility Acutely Relieves Left Ventricular Outflow Tract Obstruction in Feline Hypertrophic Cardiomyopathy.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 3 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
64 citing papers in PubMed, 3 syntheses or guidelines pooled it, 127 citations in OpenAlex.
- Pooled it
- A systematic review and meta-analysis of the efficacy and safety of Mavacamten therapy in international cohort of 524 patients with hypertrophic cardiomyopathy.Heart failure reviews · 2024Pooled it
- The effect of mavacamten on echocardiographic parameters, cardiac function and biomarkers in hypertrophic cardiomyopathy patients, a systematic review and meta-analysis.Indian heart journalPooled it
- Mechanistic diversity within RLC-dependent myosin ATPase inhibitors differentiates EDG-7500, a diastolic-selective cardiac sarcomere modulator.JCI insight · 2026Article
- Mavacamten in Chinese Patients with Obstructive Hypertrophic Cardiomyopathy: Patient-Reported Health Status Analysis up to 78 Weeks in the EXPLORER-CN Study.Cardiology and therapy · 2026Article
- Unraveling the genetics of feline hypertrophic cardiomyopathy: a multiomics study of 138 cats.G3 (Bethesda, Md.) · 2025Article
- Novel Drug Targets in Diastolic Heart Disease.International journal of molecular sciences · 2025Review
- Establishing a robust genetic sequencing and gene expression data library in cardiovascularly healthy cats.Scientific reports · 2025Article
- Experimental Models of Hypertrophic Cardiomyopathy: A Systematic Review.JACC. Basic to translational science · 2025Review
- Single Cell Transcriptomic Profiling ofJournal of the American Heart Association · 2025Article
- Cardiac Myosin Inhibitors in Hypertrophic Cardiomyopathy: Clinical Advances and Therapeutic Prospects.Drug design, development and therapy · 2025Review
- Obstructive hypertrophic cardiomyopathy: from genetic insights to a multimodal therapeutic approach with mavacamten, aficamten, and beyond.The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology · 2024Review
- Efficacy and safety of mavacamten for the treatment of hypertrophic cardiomyopathy: an updated systematic review and meta-analysis of randomized controlled trials.Annals of medicine and surgery (2012) · 2024Review
- Novel Cardiac Myosin Inhibitor Therapy for Hypertrophic Cardiomyopathy in Adults: A Contemporary Review.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2024Review
- Danicamtiv affected isometric force and cross-bridge kinetics similarly in skinned myocardial strips from male and female rats.Journal of muscle research and cell motility · 2024Article
- Evolving Strategies for the Management of Obstructive Hypertrophic Cardiomyopathy.Journal of cardiac failure · 2024Review
- Efficacy and safety of Mavacamten for symptomatic Hypertrophic cardiomyopathy - an updated Meta-Analysis of randomized controlled trials.International journal of cardiology. Heart & vasculature · 2024Review
- Cardiac myosin inhibitor, CK-586, minimally reduces systolic function and ameliorates obstruction in feline hypertrophic cardiomyopathy.Scientific reports · 2024Article
- Human Genetics of Cardiomyopathies.Advances in experimental medicine and biology · 2024Article
- An overview of the treatments for hypertrophic cardiomyopathy.Frontiers in cardiovascular medicine · 2024Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Hypertrophic cardiomyopathy (HCM) is an inherited disease of the heart muscle characterized by otherwise unexplained thickening of the left ventricle. Left ventricular outflow tract (LVOT) obstruction is present in approximately two-thirds of patients and substantially increases the risk of disease complications. Invasive treatment with septal myectomy or alcohol septal ablation can improve symptoms and functional status, but currently available drugs for reducing obstruction have pleiotropic effects and variable therapeutic responses. New medical treatments with more targeted pharmacology are needed, but the lack of preclinical animal models for HCM with LVOT obstruction has limited their development. HCM is a common cause of heart failure in cats, and a subset exhibit systolic anterior motion of the mitral valve leading to LVOT obstruction. MYK-461 is a recently-described, mechanistically novel small molecule that acts at the sarcomere to specifically inhibit contractility that has been proposed as a treatment for HCM. Here, we use MYK-461 to test whether direct reduction in contractility is sufficient to relieve LVOT obstruction in feline HCM. We evaluated mixed-breed cats in a research colony derived from a Maine Coon/mixed-breed founder with naturally-occurring HCM. By echocardiography, we identified five cats that developed systolic anterior motion of the mitral valve and LVOT obstruction both at rest and under anesthesia when provoked with an adrenergic agonist. An IV MYK-461 infusion and echocardiography protocol was developed to serially assess contractility and LVOT gradient at multiple MYK-461 concentrations. Treatment with MYK-461 reduced contractility, eliminated systolic anterior motion of the mitral valve and relieved LVOT pressure gradients in an exposure-dependent manner. Our findings provide proof of principle that acute reduction in contractility with MYK-461 is sufficient to relieve LVOT obstruction. Further, these studies suggest that feline HCM will be a valuable translational model for the study of disease pathology, particularly LVOT obstruction.
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Registered trials
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.