Carvedilol reduces the inappropriate increase of ventilation during exercise in heart failure patients

Study objective: To evaluate the effects of β-blockers on ventilation in heart failure patients. Indeed, β-blockers ameliorate the clinical condition and cardiac function of heart failure patients, but not exercise capacity. Because ventilation is inappropriately elevated in heart failure patients due to overactive reflexes from ergoreceptors and chemoreceptors, we hypothesized that β-blockers can elicit their positive clinical effects through a reduction of ventilation. Design: This was a double-blind, randomized, placebo-controlled study. Setting: University hospital heart failure unit. Patients and interventions: While receiving placebo (2 months) and a full dosage of carvedilol (4 months), 15 chronic heart failure patients were evaluated by quality-of-life questionnaire, pulmonary function tests, cardiopulmonary exercise tests with constant workload, and a ramp protocol. Results: Therapy with carvedilol did not affect resting pulmonary function and exercise capacity. However, carvedilol improved the results of the quality-of-life questionnaire, reduced the mean (± SD) slope of the minute ventilation (VE)/carbon dioxide output (VCO2) ratio (from 36.4 ± 8.9 to 31.7 ± 3.8; p < 0.01) and reduced ventilation at the following times: at peak exercise (from 60 ± 14 to 48 ± 15 L/min; p < 0.05); during the intermediate phases of a ramp-protocol exercise; and during the steady-state phase of a constant-workload exercise (from 42 ± 14 to 34 ± 13 L/min; p < 0.05, at third min). The end-expiratory pressure for carbon dioxide increased as ventilation decreased. The reduction in the VE/VCO2 ratio was correlated with improvement in quality of life (r = 0.603; p < 0.02). Conclusions: Improvement in the clinical conditions of heart failure patients treated with carvedilol is associated with reductions in the inappropriately elevated ventilation levels observed during exercise.