Modulation of myocardial metabolism: an emerging therapeutic principle

• Published in: Current opinion in cardiology Vol. 25; no. 4; pp. 329 - 334
• Main Authors: Horowitz, John D, Chirkov, Yuliy Y, Kennedy, Jennifer A, Sverdlov, Aaron L
• Format: Journal Article
• Language: English
• Published: United States Lippincott Williams & Wilkins, Inc 01-07-2010
• Subjects: Acetanilides - therapeutic use; Amiodarone - therapeutic use; Cardiovascular Agents - therapeutic use; Heart Failure - metabolism; Heart Failure - pathology; Humans; Hypertrophy, Left Ventricular - metabolism; Hypertrophy, Left Ventricular - pathology; Myocardial Ischemia - metabolism; Myocardial Ischemia - pathology; Myocardial Perfusion Imaging; Myocardial Reperfusion; Myocardium - cytology; Myocardium - metabolism; Myocardium - pathology; Perhexiline - therapeutic use; Piperazines - therapeutic use; Ranolazine; Trimetazidine - therapeutic use; Vasodilator Agents - therapeutic use
• ISSN: 0268-4705; 1531-7080
• DOI: 10.1097/HCO.0b013e328339f191

PURPOSE OF REVIEWWe focus on the molecular and cellular basis of the improvement in myocardial energetics, which might represent an attractive therapeutic option in some forms of acute and chronic heart disease.
RECENT FINDINGSMyocardial dysfunction, whether related to left ventricular hypertrophy, heart failure or myocardial ischaemia, is frequently associated with impairment of myocardial energy balance. It is now apparent that this energetic impairment plays a pivotal role, not only in the evolution and outcomes of these disorders but also frequently in their pathogenesis. Despite the fact that energetic impairment may arise for many complex reasons, and the difficulty both in assessing the impairment in vivo and in determining its precise mechanism(s), a number of drugs have become available for treatment of ischaemia and heart failure, as well as potentially for limitation of pathological left ventricular hypertrophy, which act primarily by altering myocardial metabolism so as to improve energetic status. Recent studies with perhexiline and trimetazidine, agents which induce a ‘metabolic shift’ from long-chain fatty acid to glucose utilization, have demonstrated the utility of this therapeutic principle.
SUMMARYThere is ongoing need for more complete mechanistic understanding of the ‘metabolic agents’, as well as for the large-scale clinical trials of their impact on health outcomes.