THERAPY AND PREVENTION CONGESTIVE HEART FAILURE Sustained-improvement of cardiac function in patients with congestive heart failure after short- term infusion of dobutamine

Fifteen patients with congestive cardiomyopathy (six idiopathic and nine alcoholic) manifested by heart failure (New York Heart Association class III or IV) were randomly assigned to a protocol in which dobutamine (n = 8) or 5% dextrose in water (n = 7) was infused continuously for 72 hr. The dose of dobutamine was titrated to increase cardiac output to twice the baseline values. The patients were evaluated before infusion, shortly after infusion, and 1, 2, and 4 weeks thereafter. Functional class improved in six of eight dobutamine-treated patients but in only two of seven control patients during the 4 week observation period. Maximal exercise time and left ventricular ejection fraction increased significantly above baseline only in the dobutamine group. However, neither dobutamine nor placebo infusion produced significant changes shortly after infusion in heart rate, cardiac index, or total peripheral vascular resistance at rest or during exercise at similar workloads. The group receiving dobutamine did show a reduction in systemic systolic and pulmonary arterial mean and diastolic pressure at rest (123 + 5 to 108 + 6, 32 ± 5, to 24 ± 3, and 26 + 4 to 20 ± 2 mm Hg, respectively). In addition, total body oxygen consumption during similar workloads was lower after dobutamine infusion than before. These changes occurred without alteration in plasma catecholamine or arterial blood lactate concentrations. The improvement in resting hemodynamics, exercise tolerance, and symptoms observed for at least several weeks after dobutamine infusion suggests that there is a sustained effect on cardiac function after short-term inotropic stimulation. This may represent an innovative form of long-term therapy for debilitating cardiac failure. Circulation 69, No. 1, 113-119, 1984. DOBUTAMINE, a synthetic sympathomimetic amine with predominant 1,3-adrenergic activity, is a potent inotropic agent that is less arrhythmogenic and chronotropic than naturally occurring catecholamines. 1.2 Continuous short-term infusion of dobutamine in man caused a sustained improvement in systolic function, left ventricular ejection fraction, and cardiac index in the failing heart 30 min after termination of the infusion.3 These improved parameters of left ventricular performance as well as functional class have also been shown to be sustained over several months.4 The From the Departments of Medicine and Pharmacology and the Cardiovascular Institute, Boston University School of Medicine, the Departments of Cardiology and Nuclear Medicine and the Thorndike Memorial Laboratory, Boston City Hospital, Boston, and the University of Rochester Medical Center, Rochester, NY. Supported in part by USPHS grants HL-17403, HL-24214, HL14646, and HL-18318. Address for correspondence: Chang-seng Liang. M.D.. University of Rochester Medical Center, Cardiology Research Laboratories, Box 679, 601 Elmwood Ave., Rochester, NY 14642. Received Feb. 15, 1983; revision accepted Sept. 22, 1983. Presented in part at the 55th Annual Meeting of the American Heart Association, Dallas, November 1982. Vol. 69, No. 1, January 1984 mechanism for the sustained effects of dobutamine in the failing heart are not known. Limited data have been reported pertaining to parameters of metabolism or function that may be altered by continuous dobutamine infusion in patients with severe congestive heart failure. The purpose of this double-blind controlled study was to determine whether 72 hr of continuous dobutamine infusion in patients with symptomatic congestive cardiomyopathy is associated with any hemodynamic or metabolic alterations of cardiovascular function to account for the sustained improvement in left ventricular performance.