Myocardial energetics and clinical response to the cardiotonic agent MDL 17043 in advanced heart failure

Cardiotonic agents may prove useful in the long-term treatment of chronic heart failure provided myocardial efficiency is enhanced and clinical status is improved. Accordingly, the short-term hemodynamic and clinical response to the phosphodiesterase inhibitor, MDL 17043, was evaluated. Intravenous increments of 0.05 mg/kg (maximal total 3 mg/kg) were given to a peak cardiac output response in 13 patients with New York Heart Association functional class IV heart failure secondary to ischemic or myopathic disease. Significant (p less than 0.05) responses at peak effect (1.7 mg/kg) included an increase in cardiac output (3.5 to 4.6 liters/min) and heart rate (86 to 90 beats/min) and a decrease in pulmonary capillary wedge (25 to 17 mm Hg), mean arterial (85 to 78 mm Hg) and right atrial (10 to 7 mm Hg) pressures. Coronary sinus flow (measured in nine patients) increased (122 to 144 ml/min, p less than 0.01) as did myocardial oxygen uptake (14.1 to 15.1 ml/min, p less than 0.01), whereas myocardial extraction of oxygen (78 to 72%, p less than 0.01) and lactate (24 to 9%, p less than 0.01) decreased with three patients producing lactate at the time of their peak cardiac output response. Nine of the 12 patients given long-term oral therapy improved at least one functional class at 2 weeks. This improvement was sustained at 20 weeks in five patients. Thus, MDL 17043 acutely improves the function of the failing heart. However, the decrease in oxygen extraction occurring with increased myocardial oxygen uptake suggests that intracoronary shunting may occur along with an increase in oxygen demand and contribute to myocardial anaerobiosis in some patients.(ABSTRACT TRUNCATED AT 250 WORDS)