Acute and chronic effects of propionyl-L-carnitine on the hemodynamics,
exercise capacity, and hormones in patients with congestive heart failure.
Anand I; Chandrashekhan Y; De Giuli F; Pasini E; Mazzoletti A;
Confortini R; Ferrari R
Cardiovasc Drugs Ther 1998 Jul;12(3):291-9
Carnitine is an important cofactor in the intermediary metabolism of
the heart, and carnitine deficiency is associated with congestive heart
failure. We therefore studied the effects of acute (IV bolus, 30 mg/kg
body weight) and chronic administration (1.5 mg/d for 1 month) of propionyl-L-carnitine
on hemodynamics, hormone levels, ventricular function, exercise capacity,
and peak oxygen consumption in 30 patients with chronic congestive heart
failure (NYHA II-III, mean EF 29.5 +/- 7%) in a phase II, parallel, single-blind,
randomized, and placebo-controlled study. Acute administration of propionyl-L-carnitine
caused a significant 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 other hemodynamics changes. Hormone levels did not change
following acute administration of the drug. Chronic administration of
propionyl-L-carnitine 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 12% (P < 0.01). These changes were concomitant with a reduction
of pulmonary artery pressure. In the treated group, there was a slight,
but significant (P < 0.01), reduction in left ventricular dimensions.
Hemodynamics and hormones measured after 1 month of oral therapy remained
unchanged, except for a fall in pulmonary artery pressures, with a nonsignificant
trend towards a fall in filling pressures and plasma norepinephrine. The
chronic changes in the propionyl-L-carnitine group were seen at 15 days
of treatment, and no further changes in these parameters were seen at
1 month. We conclude that propionyl-L-carnitine increases exercise capacity
and reduces ventricular size in patients with congestive heart failure.
The drug has no significant effects on hemodynamics or neurohormone levels.
The use of a single-blind design reduces the impact of the positive finding
on exercise capacity.