(Circulation. 2002;105:140.)
© 2002 American Heart Association, Inc.
Editorials |
Metabolic Modulation
A Means to Mend a Broken Heart
From the Cardiovascular Research Group (G.D.L., I.M.R.), University of Alberta, Edmonton, Alberta, Canada; and McDonald Research Laboratories/The iCAPTURE Centre (M.F.A.), Department of Pathology and Laboratory Medicine, University of British Columbia-St. Paul’s Hospital, Vancouver, British Columbia, Canada.
Correspondence to Dr G.D. Lopaschuk, 423 Heritage Medical Research Bldg, University of Alberta, Edmonton, Alberta, Canada T6G 2S2. E-mail gary.lopaschuk@ualberta.ca
Key Words: Editorials • fatty acids • ischemia • metabolism • heart failure
Heart failure is a clinical syndrome characterized by progressive deterioration of heart pump function that is very common in our society.1 It is a highly lethal disease with an annual mortality rate ranging from 5% to 10% in those with mild symptoms to 30% to 40% in those with severe symptoms.1 The morbidity associated with heart failure is also substantial such that heart failure is currently the leading cause of hospitalization in the United States, with direct costs related to treatment amounting to $20 000 million annually.1,2 As a result, the socioeconomic impact of heart failure is great. The need to prevent and, when necessary, effectively treat heart failure is, therefore, of utmost importance.
See p 194
Angiotensin-converting enzyme inhibitors, ß-adrenergic receptor antagonists, and diuretics, with or without aldosterone antagonists and digoxin, are mainstays of long-term pharmacological treatment of heart failure.1 Use of inotropic therapy to increase contractility in heart failure is not routinely used due to the fact that currently used inotropic agents simultaneously increase myocardial oxygen demand, a clinically undesirable effect.3 Development of agents that increase performance of the dysfunctional heart in the absence of significant alterations in oxygen demand would have great clinical utility. An experimental study by Hasenfuss et al4 featured in this issue of Circulation presents data showing that pyruvate, which dose-dependently improved performance in myocardium from failing human hearts, may be one such agent.
A number of abnormalities in both energy metabolism and contractile function have been identified in failing cardiac muscle. Metabolic changes
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