This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Packer, M. Articles by Yushak, M. Search for Related Content PubMed PubMed Citation Articles by Packer, M. Articles by Yushak, M.

Circulation, Vol 70, 1038-1047, Copyright © 1984 by American Heart Association

ARTICLES

Hemodynamic and clinical limitations of long-term inotropic therapy with amrinone in patients with severe chronic heart failure

M Packer, N Medina and M Yushak

To determine the hemodynamic and clinical effects of long-term positive inotropic stimulation on the myocardium, we treated 31 patients with severe chronic heart failure with oral amrinone (600 mg daily) and performed invasive hemodynamic studies during short- and long-term treatment with the drug. Stroke volume and stroke work indexes increased markedly during the first 48 hr of therapy (p less than .01) but returned to pretreatment values after 2 to 10 weeks; upon drug withdrawal, both variables deteriorated rapidly to values significantly lower than those observed before treatment with amrinone (p less than .01), despite similar values for left ventricular filling pressure, mean arterial pressure, and systemic vascular resistance. This pattern of response indicated that progression of the underlying heart disease had occurred during treatment with amrinone and contributed importantly to its failure to produce long-term benefits. Progression of left ventricular dysfunction was associated with a progressive increase in heart rate and plasma renin activity and a decline in serum sodium concentration. Clinically, amrinone therapy was complicated by sustained symptomatic ventricular tachycardia in four patients, worsening myocardial ischemia in four patients, and worsening congestive heart failure in eight patients, all of whom had been stable before entry into the study; only three of the 31 patients improved clinically. Ten patients died during the first 2 weeks of treatment, and 16 (52%) were dead within 3 months, a mortality rate twice as great as that seen during comparable trials with vasodilating drugs. Although noncardiac adverse effects were frequent, they were not the primary reason for drug failure. In conclusion, long-term therapy with amrinone may accelerate progression of left ventricular dysfunction, exacerbate myocardial ischemia, and provoke life-threatening ventricular tachyarrhythmias, thereby shortening survival in patients with severe chronic heart failure. Prolonged administration of inotropic drugs may achieve short-term gains at the expense of long-term detrimental effects on the myocardium.

This article has been cited by other articles:

				F. Triposkiadis, G. Karayannis, G. Giamouzis, J. Skoularigis, G. Louridas, and J. Butler The sympathetic nervous system in heart failure physiology, pathophysiology, and clinical implications. J. Am. Coll. Cardiol., November 3, 2009; 54(19): 1747 - 1762. [Abstract] [Full Text] [PDF]

				B. Greenberg, C. Borghi, and S. Perrone Pharmacotherapeutic approaches for decompensated heart failure: a role for the calcium sensitiser, levosimendan? Eur J Heart Fail, January 1, 2003; 5(1): 13 - 21. [Abstract] [Full Text] [PDF]

				B. D. Lowes, M. Higginbotham, L. Petrovich, M. A. DeWood, M. A. Greenberg, P. S. Rahko, G. W. Dec, T. H. LeJemtel, R. L. Roden, M. M. Schleman, et al. Low-dose enoximone improves exercise capacity in chronic heart failure J. Am. Coll. Cardiol., August 1, 2000; 36(2): 501 - 508. [Abstract] [Full Text] [PDF]

				A. Tsunoo and M. Kamijo Non-Cyclic AMP-Dependent, Positive Inotropic Cyclodepsipeptides with Negative Chronotropy J. Pharmacol. Exp. Ther., September 1, 1999; 290(3): 1006 - 1012. [Abstract] [Full Text]

				Y. J. Chiu, S.-H. Hu, and I. A. Reid Inhibition of Phosphodiesterase III with Milrinone Increases Renin Secretion in Human Subjects J. Pharmacol. Exp. Ther., July 1, 1999; 290(1): 16 - 19. [Abstract] [Full Text]

				L. W. Stevenson Inotropic Therapy for Heart Failure N. Engl. J. Med., December 17, 1998; 339(25): 1848 - 1850. [Full Text]

				B. E. Sobel and C. D. Furberg Surrogates, Semantics, and Sensible Public Policy Circulation, March 18, 1997; 95(6): 1661 - 1663. [Full Text]

				E. J. Eichhorn and M. R. Bristow Medical Therapy Can Improve the Biological Properties of the Chronically Failing Heart: A New Era in the Treatment of Heart Failure Circulation, November 1, 1996; 94(9): 2285 - 2296. [Abstract] [Full Text]

				A. M. Feldman Can We Alter Survival in Patients With Congestive Heart Failure? JAMA, April 8, 1992; 267(14): 1956 - 1961. [Abstract] [PDF]

				K. P. ANDERSON, R. A. FREEDMAN, and J. W. MASON Sudden Death in Idiopathic Dilated Cardiomyopathy Ann Intern Med, July 1, 1987; 107(1): 104 - 106. [Abstract] [PDF]