Effects of carvedilol on oxygen uptake and heart rate kinetics in patients with chronic heart failure at simulated altitude

Background: The response to moderate exercise at altitude in heart failure (HF) is unknown.Methods and results: We evaluated 30 HF patients, (NYHA I-III, 25 M/5 F; 59 ± 10 years; LVEF = 39.6 ± 7.1%), in stable clinical conditions, treated with carvedilol at the maximal tolerated dose. We performed a maximal cardiopulmonary exercise test (CPET) with ramp protocol at sea level to evaluate patients' performance and two moderate intensity constant workload CPETs (50% of peak workload) at sea level (normoxia) and simulated altitude (hypoxia). Oxygen uptake (V•O2) and heart rate (HR) on-kinetics at constant workload were assessed calculating the time constant (τ) with a monoexponential equation. V•O2 and HR were higher in hypoxia (0.944 ± 0.233 vs 1.031 ± 0.264 l/min; 100 ± 23 vs 108 ± 22 bpm; p < 0.001). On-kinetics showed a different behavior of τ being V•O2 faster in hypoxia (67.1 ± 23.0 vs. 56.3 ± 19.7 s; p = 0.026) and HR faster in normoxia (49.3 ± 19.4 vs. 62.2 ± 22.5 s; p = 0.018). Ten patients, who lowered oxygen kinetics in hypoxia, had greater HR increase during maximal CPET suggesting lower functional betablockade. The higher τ of V•O2 in hypoxia is likely to be due to a peripheral effect of carvedilol mediated either by β- or α-receptor.Conclusion: HF patients performing moderate exercise at 2000 m simulated altitude have 20% V•O2 increase without trouble at the beginning of exercise when treated with carvedilol. © The European Society of Cardiology 2011 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.