Long-term therapy with a new cardiotonic agent, WIN 47203: Drug-dependent improvement in cardiac performance and progression of the underlying disease

Abstract

Seven patients with severe chronic congestive heart failure were treated with a new cardiotonic agent, WIN 47203 (an analog of amrinone), for an average of 7.4 weeks (range 2 to 15). At the initiation of therapy, hemodynamic improvement occurred in all patients as the cardiac index increased from 1.79 +/- 0.39 to 2.30 +/- 0.44 liters/min per m2 (probability [p] less than 0.05) and pulmonary capillary wedge pressure decreased from 24.1 +/- 6.7 to 16.1 +/- 7.8 mm Hg (p less than 0.05). Long-term therapy produced a substantial symptomatic improvement in five of the seven patients. This improvement was fully sustained in two patients and the remaining three experienced a partial return of their symptoms even though the initial hemodynamic improvements at rest remained evident in all seven patients. Withdrawal of WIN 47203 precipitated hemodynamic deterioration in all patients. The cardiac index decreased from 2.25 +/- 0.40 to 1.64 +/- 0.46 liters/min per m2 (p less than 0.05) while the pulmonary capillary wedge pressure increased from 17.1 +/- 7.8 to 23.2 +/- 12.0 mm Hg (p less than 0.05). Stroke volume index after withdrawal was lower than the control level before therapy (17.0 +/- 6.6 versus 20.3 +/- 4.7 ml/m2; p less than 0.05) and pulmonary capillary wedge pressure was similar. During long-term therapy, no undesirable side effects or hematologic changes were observed. Thus, drug-dependent hemodynamic benefits and apparent progression of the underlying cardiac disease were demonstrated during long-term therapy with WIN 47203.