SUPPRESSING SYMPATHETIC ACTIVATION IN CONGESTIVE-HEART-FAILURE - A NEW THERAPEUTIC STRATEGY

Neurohormonal activation with increased plasma renin activity and nore pinephrine and vasopressin levels is characteristic of congestive hear t failure and contributes to further decompensation and poor prognosis . We treated 20 such patients with the centrally acting sympathoinhibi tory 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 we re taken again after 1 week of therapy. The initial dose produced sign ificant decreases of 8% in mean arterial pressure, 23% in right atrial pressure, 21% in pulmonary capillary wedge pressure, 19% in mean pulm onary artery pressure; and 12% in heart rate; a 17% increase in stroke volume; and no significant changes in cardiac output and systemic vas cular 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 essenti ally unchanged. Plasma vasopressin tended to increase, its levels bein g 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 t o show more improvement with clonidine, although their data remained s ignificantly worse than patients whose baseline norepinephrine was wit hin the normal range. Sympathetic suppression with clonidine in conges tive heart failure reduces preload, heart rate, and arterial pressure, all indexes of myocardial energy demand; the lack of significant redu ction in systemic vascular resistance and increase in cardiac output m ight be attributable in part to enhanced release of vasopressin. The d ata suggest that suppression of activated presser neurohormones is a r ational approach to treatment of congestive heart failure.