title: A new approach to inotropic therapy in the treatment of heart failure: cardiac myosin activators in treatment of HF.
abstract: Systolic heart failure remains a leading cause of death and disability, and available pharmacologic treatments for heart failure are limited in both safety and effectiveness. Existing drugs focus on diverse mechanisms related to the pathophysiology of heart failure, yet none directly target the central feature of systolic heart failure, decreased cardiac contractility. Cardiac myosin activators, specifically omecamtiv mecarbil (formerly CK-1827452), directly activate the enzymatic pathway within the cardiac myocyte leading to ventricular contraction. This unique inotropic agent has been shown in preclinical and clinical studies to be effective in improving cardiac contractility by increasing systolic ejection time without the unwanted effects of the currently available indirect inotropic drugs. Cardiac myosin activators show great promise and may prove to be a safer and more effective therapeutic approach for the treatment of systolic heart failure.
authors.affiliation: Department of Medicine, UCLA School of Medicine and Hospital, Los Angeles, CA, USA.
authors.forename: Vinisha
authors.initials: V
authors.lastname: Garg
authors.forename: William H
authors.initials: WH
authors.lastname: Frishman
mesh_terms: D000818:Animals; D024722:Cardiac Myosins / Q000187:drug effects*; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic; D004195:Disease Models, Animal; D004285:Dogs; D004341:Drug Evaluation; D054143:Heart Failure, Systolic / Q000188:drug therapy*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D051381:Rats; D017207:Rats, Sprague-Dawley; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D002316:Cardiotonic Agents; C547293:omecamtiv mecarbil; D014508:Urea; D024722:Cardiac Myosins