A New Approach to Inotropic Therapy in the Treatment of Heart Failure Cardiac Myosin Activators in Treatment of HF

被引:11
作者
Garg, Vinisha [1 ]
Frishman, William H. [2 ]
机构
[1] UCLA Sch Med & Hosp, Dept Med, Los Angeles, CA USA
[2] New York Med Coll, Dept Med, Westchester Med Ctr, Valhalla, NY 10595 USA
关键词
cardiac myosin activator; omecamtiv mecarbil; CK-1827452; systolic ejection time; heart failure; inotrope; OMECAMTIV MECARBIL; CONSCIOUS DOGS; MILRINONE; AGENTS;
D O I
10.1097/CRD.0b013e318275889c
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:155 / 159
页数:5
相关论文
共 24 条
[1]   Lack of desensitization and enhanced efficiency of calcium channel promoter in conscious dogs with heart failure [J].
Asai, K ;
Uechi, M ;
Sato, N ;
Shen, WQ ;
Meguro, T ;
Mathier, MA ;
Shannon, RP ;
Vatner, SF .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 1998, 275 (06) :H2219-H2226
[2]   Comparative effects of levosimendan, OR-1896, OR-1855, dobutamine, and milrinone on vascular resistance, indexes of cardiac function, and O2 consumption in dogs [J].
Banfor, Patricia N. ;
Preusser, Lee C. ;
Campbell, Thomas J. ;
Marsh, Kennan C. ;
Polakowski, James S. ;
Reinhart, Glenn A. ;
Cox, Bryan F. ;
Fryer, Ryan M. .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2008, 294 (01) :H238-H248
[3]   Heart Failure [J].
Braunwald, Eugene .
JACC-HEART FAILURE, 2013, 1 (01) :1-20
[4]   DECREASED CATECHOLAMINE SENSITIVITY AND BETA-ADRENERGIC-RECEPTOR DENSITY IN FAILING HUMAN HEARTS [J].
BRISTOW, MR ;
GINSBURG, R ;
MINOBE, W ;
CUBICCIOTTI, RS ;
SAGEMAN, WS ;
LURIE, K ;
BILLINGHAM, ME ;
HARRISON, DC ;
STINSON, EB .
NEW ENGLAND JOURNAL OF MEDICINE, 1982, 307 (04) :205-211
[5]   The effects of the cardiac myosin activator, omecamtiv mecarbil, on cardiac function in systolic heart failure: a double-blind, placebo-controlled, crossover, dose-ranging phase 2 trial [J].
Cleland, John G. F. ;
Teerlink, John R. ;
Senior, Roxy ;
Nifontov, Evgeny M. ;
Mc Murray, John J. V. ;
Lang, Chim C. ;
Tsyrlin, Vitaly A. ;
Greenberg, Barry H. ;
Mayet, Jamil ;
Francis, Darrel P. ;
Shaburishvili, Tamaz ;
Monaghan, Mark ;
Saltzberg, Mitchell ;
Neyses, Ludwig ;
Wasserman, Scott M. ;
Lee, Jacqueline H. ;
Saikali, Khalil G. ;
Clarke, Cyril P. ;
Goldman, Jonathan H. ;
Wolff, Andrew A. ;
Malik, Fady I. .
LANCET, 2011, 378 (9792) :676-683
[6]   A dose-dependent increase in mortality with vesnarinone among patients with severe heart failure [J].
Cohn, JN ;
Goldstein, SO ;
Greenberg, BH ;
Lorell, BH ;
Bourge, RC ;
Jaski, BE ;
Gottlieb, SO ;
McGrew, F ;
DeMets, DL ;
White, BG .
NEW ENGLAND JOURNAL OF MEDICINE, 1998, 339 (25) :1810-1816
[7]   Short-term intravenous milrinone for acute exacerbation of chronic heart failure - A randomized controlled trial [J].
Cuffe, MS ;
Califf, RM ;
Adams, KF ;
Benza, R ;
Bourge, R ;
Colucci, WS ;
Massie, BM ;
O'Connor, CM ;
Pina, I ;
Quigg, R ;
Silver, MA ;
Georghiade, M .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2002, 287 (12) :1541-1547
[8]   Digoxin remains useful in the management of chronic heart failure [J].
Dec, GW .
MEDICAL CLINICS OF NORTH AMERICA, 2003, 87 (02) :317-+
[9]   Heart failure etiology and response to milrinone in decompensated heart failure - Results from the OPTIME-CHF study [J].
Felker, GM ;
Benza, RL ;
Chandler, AB ;
Leimberger, JD ;
Cuffe, MS ;
Califf, RM ;
Gheorghiade, M ;
O'Connor, CM .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2003, 41 (06) :997-1003
[10]   Phase II Safety Study Evaluating the Novel Cardiac Myosin Activator, CK-1827452, in Patients with Ischemic Cardiomyopathy and Angina [J].
Greenberg, Barry H. ;
Chou, Will ;
Escandon, Rafael ;
Lee, Jacqueline H. ;
Saikali, Khalil G. ;
Malik, Fady ;
Wolff, Andrew A. ;
Shaburishvili, Tamaz .
JOURNAL OF CARDIAC FAILURE, 2009, 15 (06) :S67-S67