Suppressing Sympathetic Activation in Congestive Heart Failure

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Abstract
Abstract Neurohormonal activation with increased plasma renin activity and norepinephrine and vasopressin levels is characteristic of congestive heart failure and contributes to further decompensation and poor prognosis. We treated 20 such patients with the centrally acting sympathoinhibitory drug clonidine 0.15 mg BID and obtained hemodynamic measurements by cardiac catheterization and plasma neurohormone levels before and 2 to 3 hours after the first dose; in 7 patients, these measurements were taken again after 1 week of therapy. The initial dose produced significant decreases of 8% in mean arterial pressure, 23% in right atrial pressure, 21% in pulmonary capillary wedge pressure, 19% in mean pulmonary artery pressure, and 12% in heart rate; a 17% increase in stroke volume; and no significant changes in cardiac output and systemic vascular resistance. All changes remained virtually constant after 1 week. Plasma norepinephrine decreased by 28% after the initial dose and 62% after 1 week ( P <.01), whereas plasma renin activity remained essentially unchanged. Plasma vasopressin tended to increase, its levels being inversely correlated with those of posttreatment norepinephrine ( r =−.48, P <.03). Patients with baseline norepinephrine levels >0.400 ng/mL had significantly poorer baseline hemodynamic parameters and tended to show more improvement with clonidine, although their data remained significantly worse than patients whose baseline norepinephrine was within the normal range. Sympathetic suppression with clonidine in congestive heart failure reduces preload, heart rate, and arterial pressure, all indexes of myocardial energy demand; the lack of significant reduction in systemic vascular resistance and increase in cardiac output might be attributable in part to enhanced release of vasopressin. The data suggest that suppression of activated pressor neurohormones is a rational approach to treatment of congestive heart failure.