Analysis of the efficacy of the new cardiotonic agent TA-064

TA-064 is a new cardiotonic agent which is also effective orally, according to investigations conducted in Japan. We analyzed computer-assisted alterations of pressure-volume relationships serially and of indirect myocardial oxygen consumption (MVO2) estimations on line during TA-064 influence in 16 patients with congestive cardiomyopathy: left ventricular function was moderately decreased in seven patients (group A) and drastically decreased in nine (group B). Results showed that TA-064, 8 micrograms/kg/min intravenously, exerted positive inotropic effects in both groups and induced mean maximal delta percentage changes at about 5 minutes of infusion as follows: left ventricular stroke work index +65% and +47%; dP/dtmax +61% and 59%; left ventricular efficiency +62% and 53%; MVO2 +31% and +11% (p less than 0.05). TA-064, 20 mg by mouth induced serum levels (group A = 23.8 +/- 12ng/ml and group B = 26.4 +/- 20 ng/ml) corresponding to the effects with dosages of 1 to 2 ng/kg/min intravenously (p greater than 0.05), thus implying that significant changes in left ventricular function require higher oral dosages. We conclude that TA-064 improves left ventricular function, primarily via a contractility increase, also in group B patients without toxic side effects. On-line indirect MVO2 assessment and analysis of serial pressure-volume relationships helped to provide a more complex definition of the mechanism and efficiency of the cardiotonic agent under study.