What question did this study set out to answer?

This study aims to assess whether the small molecule MYK-461 can reduce left ventricular outflow tract obstruction in feline hypertrophic cardiomyopathy.

December 14, 2016PLoS ONEOpen Access

A Small Molecule Inhibitor of Sarcomere Contractility Acutely Relieves Left Ventricular Outflow Tract Obstruction in Feline Hypertrophic Cardiomyopathy

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Why the study?

Does IV MYK-461 infusion reduce contractility and relieve LVOT obstruction in a feline model of hypertrophic cardiomyopathy?

Population

n=5 mixed-breed cats with naturally-occurring hypertrophic cardiomyopathy exhibiting systolic anterior…

Design

Preclinical

Authors

JSJoshua A. SternNorth Carolina State University SMSvetlana MarkovaVoronezh State Medical Academy named after N.N. Burdenko YUYu UedaNorth Carolina State University

Discussion

Member takes

Implication

Supports myosin inhibition for HCM obstruction; leaves open translation from feline models to patients.

Key Points

This study aims to assess whether the small molecule MYK-461 can reduce left ventricular outflow tract obstruction in feline hypertrophic cardiomyopathy.
Evaluated mixed-breed cats with naturally-occurring hypertrophic cardiomyopathy from a research colony.
Used echocardiography to observe systolic anterior motion of the mitral valve and LVOT obstruction under anesthesia.
Administered IV MYK-461 infusion to gauge its effect on contractility and LVOT gradient at various concentrations.
Treatment with MYK-461 effectively reduced contractility in the evaluated cats.
Systolic anterior motion of the mitral valve was eliminated, alleviating LVOT pressure gradients.
The degree of relief in LVOT obstruction was dose-dependent based on MYK-461 concentrations.

Structured PICO

Does IV MYK-461 infusion reduce contractility and relieve LVOT obstruction in a feline model of hypertrophic cardiomyopathy?

Population

n=5 mixed-breed cats with naturally-occurring hypertrophic cardiomyopathy (HCM) exhibiting systolic anterior motion of the mitral valve and left ventricular outflow tract (LVOT) obstruction at rest and under anesthesia when provoked with an adrenergic agonist.

Intervention

IV MYK-461 infusion at multiple concentrations

Outcome

Contractility and LVOT pressure gradient assessed serially by echocardiographysurrogate

Acute reduction in contractility with the small molecule MYK-461 is sufficient to relieve LVOT obstruction in a feline model of HCM, providing proof of principle for targeted pharmacological therapy.

Cite This Study

Stern et al. (2016) studied this question.

synapsesocial.com/papers/6a08db1e3589fa5d64d5ff61 https://doi.org/10.1371/journal.pone.0168407

Topics

Hypertrophic cardiomyopathy

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A Small Molecule Inhibitor of Sarcomere Contractility Acutely Relieves Left Ventricular Outflow Tract Obstruction in Feline Hypertrophic Cardiomyopathy

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Topics

A Small Molecule Inhibitor of Sarcomere Contractility Acutely Relieves Left Ventricular Outflow Tract Obstruction in Feline Hypertrophic Cardiomyopathy

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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