In patients with chronic heart failure (CHF), the addition of coenzyme Q10 to conventional therapy reduces the hospitalization rate for worsening of heart failure and the incidence of serious cardiovascular complications. The present study was planned to assess the hemodynamic mechanisms underlying this phenomenon. Cardiac hemodynamics was evaluated continuously using an ambulatory radionuclide detector (VEST) which allows a noninvasive monitoring of left ventricular function. Six patients wit CHF (mean ejection fraction (EF): 29%) clinically documented were studied. This study was organized as a randomized double-blind, placebo controlled, cross-over trial. The enrolled patients, after a washout period, underwent the first hemodynamic evaluation with VEST. Subsequently they were randomized to receive placebo or coenzyme Q10 for 4 weeks. At the end of this period they underwent the second VEST study. The third VEST study was performed after a further 4-week period with inverted treatment. Cardiac hemodynamics were evaluated during bicycle exercise. The EF in control conditions (CC) changed from 27 +/- 11%, at rest, to 24 +/- 8%, at peak exercise. During coenzyme Q10 treatment EF showed a significant increase both at rest (33 +/- 13%, P < 0.05 vs CC) and at peak exercise (30 +/- 12%, P < 0.05 vs CC). The same trends were recorded for the stroke volume and the cardiac output. Our results demonstrate that coenzyme Q10 improves cardiac hemodynamic response to exercise in patients with CHF and suggest that noninvasive monitoring of left ventricular function allows a more reliable assessment of therapy efficacy.