Effects of carvedilol on oxidative stress and chronotropic response to exercise in patients with chronic heart failure

Background: Our previous studies suggest that the increase in heart rate from rest to peak exercise is reduced in patients with chronic heart failure (CHF) and this is associated with increased oxidative stress, as determined by malondialdehyde (MDA) plasma levels. Aim: To investigate the effects of carvedilol on the heart rate response to exercise and oxidative stress in patients with CHF. Methods and results: Thirty stable NYHA classes II-III CHF patients received carvedilol therapy for 6 months, at a mean maintenance dose of 25 mg (range 6.25-50 mg/day). After treatment, the patients showed a significant improvement in their functional NYHA class (p=0.013), increased left ventricular ejection fraction (LVEF) (24±1.4% to 31±2.3%, p=0.003) and 6-min walk distance (499±18 to 534±18 m, p=0.03), without changes in the peak VO₂. At baseline, norepinephrine (NE) plasma levels increased with exercise (510±51 to 2513±230 pg/mL, p<0.001), and these levels were not affected by carvedilol. Chronotropic responsiveness index (increase in heart rate divided by the increase in NE from rest to peak exercise) was not changed by carvedilol (0.049±0.001 to 0.042±0.001, p=0.6). MDA levels of CHF patients decreased after treatment with carvedilol (2.4±0.2 to 1.1±0.2 μM, p<0.001), without changes in antioxidant enzyme activities. Conclusions: Carvedilol treatment in patients with CHF results in reduced oxidative stress without restoration of the chronotropic responsiveness index.