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

Eur J Prev Cardiol. 2012 Jun;19(3):444-51. doi: 10.1177/1741826711402736. Epub 2011 Mar 7.

Abstract

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 (.VO2 ) and heart rate (HR) on-kinetics at constant workload were assessed calculating the time constant (τ) with a monoexponential equation. .VO2 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 .VO2 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 beta-blockade. The higher τ of .VO2 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% .VO2 increase without trouble at the beginning of exercise when treated with carvedilol.

Trial registration: ClinicalTrials.gov NCT00517725.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic Antagonists / therapeutic use*
  • Aged
  • Altitude*
  • Carbazoles / therapeutic use*
  • Carvedilol
  • Chronic Disease
  • Exercise Test
  • Female
  • Heart Failure / diagnosis
  • Heart Failure / drug therapy*
  • Heart Failure / metabolism
  • Heart Failure / physiopathology
  • Heart Rate / drug effects*
  • Humans
  • Hypoxia / metabolism
  • Hypoxia / physiopathology*
  • Kinetics
  • Male
  • Middle Aged
  • Myocardium / metabolism*
  • Oxygen Consumption / drug effects*
  • Propanolamines / therapeutic use*
  • Treatment Outcome

Substances

  • Adrenergic Antagonists
  • Carbazoles
  • Propanolamines
  • Carvedilol

Associated data

  • ClinicalTrials.gov/NCT00517725