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Piperanometozine (OPC-8212) is a new, orally effective inotropic agent. To evaluate the efficacy of this agent on systemic hemodynamics and clinical symptoms in patients with congestive heart failure, a multicenter study was performed. Thirty four patients with New York Heart Association (NYHA) functional classes II to IV and initially treated with digitalis were enrolled from ten centers. After a washout period of one or two weeks (placebo period), digitalis was replaced by piperanometozine (30 or 60 mg/day) for four weeks, while other drugs were continued. Clinical symptoms, routine physical findings, electrocardiogram, chest roentgenogram, echocardiogram, exercise tolerance time, and routine laboratory data were obtained in 34 patients. Four patients were withdrawn from the study before completion. After the withdrawal of digitalis, heart rate was increased and ejection fraction was decreased. Exercise tolerance time was increased while other parameters were unchanged. At the end of the treatment period with piperanometozine, ejection fraction significantly (p less than 0.05) increased with a decrease in LV end-systolic volume (p less than 0.05), whereas heart rate and blood pressure remained unchanged. Systolic blood pressure/LV end-systolic volume (P/V index) tended to decrease after the withdrawal of digitalis and increase during piperanometozine therapy. Exercise tolerance time was further increased (p less than 0.01) and NYHA functional class was improved in 11 patients, whereas it worsened in only one patient. No major adverse effects were observed. These results indicate that a short-term therapy of oral piperanometozine restored the depressed cardiac performance of the heart and improved clinical symptoms in patients with congestive heart failure. Thus, this promising agent deserves further clinical study in long-term trials.

The decline of the use of digitalis for the treatment of congestive heart failure was due to the introduction of oral diuretic therapy, the recognition of the frequency of digitalis induced arrhythmias and the uncontrolled observations that digitalis could frequently be withdrawn from patients with a history of heart failure without recurrence of heart failure. Subsequently, it has been well documented that digitalis has chronic beneficial hemodynamic effects in patients with chronic congestive heart failure. Moreover, digitalis has been shown to improve hemodynamics when added to other drugs including diuretics, ACE inhibitors and vasodilators. It is concluded that digitalis is a mild inotropic agent that is still a primary drug for the treatment of mild to moderate acute or chronic left ventricular failure.