Hemodynamic and clinical effects of a new inotropic agent TA-064 in patients with refractory heart failure due to cardiomyopathy with special reference to dose-response effects.

Abstract

A new hydroxybenzyl alcohol derivative TA-064 exerts a positive inotropic action in experimental preparations. To assess the acute effects in man, we made a cardiac catheterization study of the hemodynamic responses to TA-064 (20 mg and/or 40 mg given orally) in eleven patients with refractory heart failure due to cardiomyopathy (nine patients with dilated cardiomyopathy and one with amyloidosis). All patients were already receiving full digitalis and diuretics therapy. The following statistically significant (P less than 0.05-0.01) effects were noted: Upon administration of 20 mg of the drug, the cardiac index (CI) increased from a mean +/- 1 SD of 1.6 +/- 0.4 to 2.1 +/- 0.6 l/min/m2; pulmonary capillary wedge pressure (PCW) fell from 25 +/- 5 to 21 +/- 5 mm Hg; right atrial pressure (RA) fell from 12 +/- 3 to 10 +/- 4 mm Hg. In contrast, when 40 mg TA-064 were administered orally, the CI increased from 1.7 +/- 0.4 to 2.4 +/- 0.9 l/min/m2; PCW fell from 25 +/- 8 to 20 +/- 6 mm Hg; pulmonary arterial mean pressure fell from 35 +/- 11 to 29 +/- 9 mm Hg. Neither systemic arterial mean pressure nor heart rate increased. No toxicity was observed. The plasma concentration of TA-064 increased dose-dependently and reached a peak value 0.5-1.5 h after oral administration. Plasma catecholamine levels revealed no significant changes before and after use of the drug; therefore, the mechanism of action may not have been mediated by catecholamine.