Milrinone for long-term therapy of severe heart failure: clinical experience with special reference to maximal exercise tolerance.
Thirty-seven patients with severe chronic heart failure were entered into an open-ended trial with milrinone at an initial daily dose ranging form 20 to 30 mg. Mean duration of treatment was 48 weeks and ranged from 1 to 134 weeks. Twenty-five patients (67%) reported a substantial improvement in well-being with less dyspnea or fatigue, but this was not associated with a significant increase in maximal oxygen uptake: 10.2 +/- 2.9 vs 10.7 +/- 2.4 ml/kg/min (NS). At intervals ranging from 6 to 54 weeks, they experienced a recurrence of symptoms that was partially reversed by increasing the dose of milrinone to a maximum of 50 mg/day. In 15 patients whose symptoms could not be controlled by milrinone alone, captopril was added. The combination of captopril and milrinone was well tolerated and produced a symptomatic improvement in 10 of the 15 patients (67%). Maximal oxygen uptake, however, was not significantly increased by addition of captopril to milrinone: 10.6 +/- 2.7 vs 11.6 +/- 3.3 ml/kg/min. Twenty-four patients died: 12 of sudden death and 12 of gradual worsening of heart failure. During prolonged administration of milrinone, no patient experienced overt clinical adverse reactions directly attributable to the drug. Left ventricular end-diastolic dimension increased from 3.6 +/- 0.7 to 4.1 +/- 0.9 cm/m2 (p less than .05) after a mean duration of 50 weeks of milrinone therapy. Accordingly, long-term therapy with milrinone appears to improve functional status without eliciting overt clinical adverse reactions. However, the possibility that milrinone might have contributed to the high mortality noted during this therapeutic trial cannot be excluded.(ABSTRACT TRUNCATED AT 250 WORDS)