Cardiac Calcitropes, Myotropes, and Mitotropes: JACC Review Topic of the Week

• Published in: Journal of the American College of Cardiology Vol. 73; no. 18; p. 2345
• Main Authors: Psotka, Mitchell A, Gottlieb, Stephen S, Francis, Gary S, Allen, Larry A, Teerlink, John R, Adams, Jr, Kirkwood F, Rosano, Giuseppe M C, Lancellotti, Patrizio
• Format: Journal Article Web Resource
• Language: English
• Published: United States Elsevier Limited 14.05.2019; Elsevier USA
• Subjects: Adenosine triphosphatase; Adenosine triphosphate; Calcium (intracellular); Calcium - metabolism; Calcium signalling; Cardiac function; Cardiology; Cardiotonic Agents - pharmacology; Cardiovascular & respiratory systems; Clinical outcomes; Communication; Heart; Heart failure; Heart Failure - drug therapy; Heart Failure - metabolism; Heart Failure - physiopathology; Human health sciences; Humans; Long-term effects; Metabolism; Mortality; Myocardial Contraction - drug effects; Myocardial Contraction - physiology; Myocardium; Pharmaceuticals; Sciences de la santé humaine; Stroke; Systèmes cardiovasculaire & respiratoire; heart failure; systolic function; cardiac contractility; inotrope
• ISSN: 0735-1097; 1558-3597; 1558-3597
• DOI: 10.1016/j.jacc.2019.02.051

The term "inotrope" is familiar and intimately connected with pharmaceuticals clinically used for treatment of low cardiac output with cardiogenic shock. Traditional inotropic agents exert their effect by modulating calcium signaling in the myocardium. Their use is associated with poor long-term outcomes. Newer molecules in development intend to break from calcium mediation and the associated detrimental long-term effects by targeting distinct mechanisms of action to improve cardiac performance. Thus, "inotropy" does not sufficiently describe the range of potential novel pharmaceutical products. To enhance communication around and evaluation of current, emerging, and potential therapies, this review proposes a novel nuanced and holistic framework to categorize pharmacological agents that improve myocardial performance based on 3 myocardial mechanisms: calcitropes, which alter intracellular calcium concentrations; myotropes, which affect the molecular motor and scaffolding; and mitotropes, which influence energetics. Novel chemical entities can easily be incorporated into this structure, distinguishing themselves based on their mechanisms and clinical outcomes.