Effects of acute and chronic minoxidil administration on rest and exercise hemodynamics and clinical status in patients with severe, chronic heart failure

Abstract

The effects of acute and chronic oral administration of the vasodilator minoxidil on hemodynamics, oxygen consumption, exercise performance, and clinical status were investigated in 10 patients with severe, chronic heart failure refractory to digitalis and diuretic therapy. The cardiac index was 1.99 +/- 0.38 liters/min/m2 at rest and 2.88 +/- 0.79 at symptom-limited maximal exercise on conventional therapy, compared with 2.64 +/- 0.33 liters/min/m2 at rest and 3.55 +/- 0.84 at maximal exercise after short-term minoxidil administration (p less than 0.02, control versus minoxidil at both rest and exercise). Stroke volume was increased after minoxidil treatment, without significant effect on heart rate. Systemic vascular resistance was decreased by minoxidil from 2,050 +/- 722 to 1,325 +/- 374 dynes . s/cm-5 at rest and from 1,500 +/- 830 to 1,206 +/- 589 dynes . s/cm-5 at maximal exercise (p = 0.01, control versus minoxidil). No significant effect was observed on left ventricular filling, right atrial, or mean pulmonary arterial pressure, but pulmonary vascular resistance decreased both at rest and on exercise (p less than 0.05). Maximal exercise oxygen consumption increased from 8.9 +/- 3.2 ml/kg/min on conventional therapy to 10.5 +/- 2.4 on minoxidil therapy (p less than 0.03), median maximal exercise work load increased from 25 to 50 W and medium exercise duration increased from 6.0 to 9.0 minutes. On chronic minoxidil administration all 5 patients who completed a scheduled 6 week follow-up showed symptomatic improvement. However, worsening edema developed in all patients, requiring increased diuretic dosage and close supervision. Symptoms of ischemic heart disease worsened in 2 of 10 patients. We tentatively conclude that minoxidil may be a useful vasoactive agent in the pharmacologic therapy of severe chronic heart failure.