ACUTE AND CHRONIC EFFECTS OF PROPINOYL-L-CARNITINE ON THE HEMODYNAMICS, EXERCISE CAPACITY, AND HORMONES IN PATIENTS WITH CONGESTIVE-HEART-FAILURE

Carnitine is an important cofactor in the intermediary metabolism of t he heart, and carnitine deficiency is associated with congestive heart failure. We therefore studied the effects of acute (IV bolus, 30 mg/k g body weight) and chronic administration (1.5 mg/d for 1 month) of pr opionyl-L-carnitine on hemodynamics, hormone levels, ventricular funct ion, exercise capacity, and peak oxygen consumption in 30 patients wit h chronic congestive heart failure (NYHA II-III, mean EF 29.5 +/- 7%) in a phase II, parallel, single-blind, randomized, and placebo-control led study. Acute administration of propionyl-L-carnitine caused a sign ificant reduction in pulmonary artery and pulmonary wedge pressures at both day 1 (P < 0.001) and day 30 (P < 0.05) of the study but no othe r hemodynamics changes. Hormone levels did not change following acute administration of the drug. Chronic administration of propionyl-L-carn itine increased peak oxygen consumption by 45% (from 16.0 +/- 3 to 23. 5 +/- 2 mL/kg/min, P +/- 0.001), exercise time by 21% (from 8.1 +/- 0. 5 to 9.8 +/- 0.4 minutes, P < 0.01), and peak exercise heart rate by 1 2% (P < 0.01). These changes were concomitant with a reduction of pulm onary artery pressure. In the treated group, there was a slight, but s ignificant (P < 0.01), reduction in left ventricular dimensions. Hemod ynamics and hormones measured after 1 month of oral therapy remained u nchanged, except for a fall in pulmonary artery pressures, with a nons ignificant trend towards a fall in filling pressures and plasma norepi nephrine. The chronic changes in the propionyl-L-carnitine group were seen at 15 days of treatment, and no further changes in these paramete rs were seen at 1 month. We conclude that propionyl-L-carnitine increa ses exercise capacity and reduces ventricular size in patients with co ngestive heart failure. The drug has no significant effects on hemodyn amics or neurohormone levels. The use of a single-blind design reduces the impact of the positive finding on exercise capacity.