Clinical and hemodynamic improvement of congestive heart failure by long-term vasodilator therapy with postjunctional alpha 1-adrenoceptor blockade

Abstract

Eleven of 12 patients with severe congestive heart failure who were pretreated with diuretics and digitalis benefited from long-term therapy with prazosin which was titrated to the individual's maximally tolerated dose. Nine of the 11 patients improved their functional state by one (n = 4) or two (n = 5) New York Heart Association (NYHA) classes. Within 4 weeks the stroke volume index increased from 23 +/- 10 to 29 +/- 9 SD (ml/beat/m2) while pulmonary capillary pressure decreased from 29 +/- 8 +/- 9 mm Hg (p less than 0.05 for both) and peripheral vascular resistance fell from 2,245 +/- 792 to 1,603 +/- 355 dyn/s cm-5 (p less than 0.01). Hemodynamics results were similar on the same regimen in eight patients assessed for 6 months. Death of three patients (week 5 and week 17) was unrelated to prazosin therapy. Prazosin resulted in improved cardiac performance during leg-up-tilt or supine ergometry. Increase in stroke volume index was related to the fall in peripheral vascular resistance (r = -0.79, p less than 0.01). Plasma adrenaline (301 +/- 480 pg/Ml), noradrenaline (1,312 +/- 1,382 pg/ml), and renin activity (22 +/- 30 ng/ml/h) were in the range observed with pheochromocytoma; variables did not change on prazosin. This reflects an important role of alpha-adrenoceptor-mediated vascular regulation in patients with heart failure in whom long-term treatment with prazosin produces a sustained and well-tolerated vasodilator effect without further rise in catecholamines and renin.