Novel cardiac myosin activators for acute heart failure

Abstract

Heart failure remains a leading cause of hospitalisation and death. Treatment of acute heart failure has not improved as rapidly as treatment for chronic heart failure. There are three classes of inotropic agents that are in use at present: the catecholamines, phosphodiesterase inhibitors and calcium sensitisers. Cardiac-specific myosin ATPase activators are a novel class of agents designed to improve myocardial contractility by accelerating the productive phosphate-release step of the crossbridge cycle. This article reviews the mechanism of action of myosin ATPase activators, the results of preclinical and Phase I studies and their potential role in the management of heart failure.

Keywords::

• crossbridge cycle
• heart failure
• inotropes
• myosin activators

Conflict of interest

JG Cleland was the principal investigator of a study on the three agents for Cytokinetics and Amgen. The authors' department is one of the participating centres in the Phase II trial of myosin activator.

Notes