Effect of betaxolol on the hemodynamic, gas exchange, and cardiac output response to exercise in chronic atrial fibrillation

Background: β-blockade controls the ventricular response to exercise in chronic atrial fibrillation (AF), but the effects of β-blockers on exercise capacity in AF have been debated. Methods: Twelve men with AF (65 ± 8 years) participated in a randomized, double-blind, placebo-controlled study of betaxolol (20 mg daily). Patients underwent maximal exercise testing with ventilatory gas exchange analysis, and a separate, submaximal test (50% of maximum) during which cardiac output was measured by a CO₂ rebreathing technique. Results: After betaxolol therapy, heart rate was reduced both at rest (92 ± 27 vs 62 ± 12 beats/min; p < 0.001) and at peak exercise (173 ± 22 vs 116 ± 24 beats/min; p < 0.001). Maximal oxygen uptake (VO₂) was reduced by 19% after betaxolol (21.8 ± 5.3 with placebo vs 17.6 ± 5.1 mL/kg/min with betaxolol; p < 0.05), with similar reductions observed for maximal exercise time, minute ventilation, and CO₂ production. VO₂ was reduced by a similar extent (19%) at the ventilatory threshold. Submaximal cardiac output was reduced by 15% during betaxolol therapy (12.9 ± 2.3 vs 10.9 ± 1.3 L/min; p < 0.05), and stroke volume was higher (88.0 ± 21 vs 105.6 ± 19 mL/beat; p < 0.05). Conclusion: Betaxolol therapy in patients with AF effectively controlled the ventricular rate at rest and during exercise, but also caused considerable reductions in maximal VO₂ and cardiac output during exercise. The observed increase in stroke volume could not adequately compensate for reduced heart rate to maintain VO₂ during exercise.