Impact of Beta-blockers on Cardiopulmonary Exercise Testing in Patients With Advanced Liver Disease

M. P. Wallen; A. Hall; K. A. Dias; J. S. Ramos; S. E. Keating; A. J. Woodward; T. L. Skinner; G. A. Macdonald; R. Arena; J. S. Coombes


Aliment Pharmacol Ther. 2017;46(8):741-747. 

In This Article

Abstract and Introduction


Background Patients with advanced liver disease may develop portal hypertension that can result in variceal haemorrhage. Beta-blockers reduce portal pressure and minimise haemorrhage risk. These medications may attenuate measures of cardiopulmonary performance, such as the ventilatory threshold and peak oxygen uptake measured via cardiopulmonary exercise testing.

Aim To determine the effect of beta-blockers on cardiopulmonary exercise testing variables in patients with advanced liver disease.

Methods This was a cross-sectional analysis of 72 participants who completed a cardiopulmonary exercise test before liver transplantation. All participants remained on their usual beta-blocker dose and timing prior to the test. Variables measured during cardiopulmonary exercise testing included the ventilatory threshold, peak oxygen uptake, heart rate, oxygen pulse, the oxygen uptake efficiency slope and the ventilatory equivalents for carbon dioxide slope.

Results Participants taking beta-blockers (n = 28) had a lower ventilatory threshold (P <.01) and peak oxygen uptake (P = .02), compared to participants not taking beta-blockers. After adjusting for age, the model of end-stage liver-disease score, liver-disease aetiology, presence of refractory ascites and ventilatory threshold remained significantly lower in the beta-blocker group (P = .04). The oxygen uptake efficiency slope was not impacted by beta-blocker use.

Conclusions Ventilatory threshold is reduced in patients with advanced liver disease taking beta-blockers compared to those not taking the medication. This may incorrectly risk stratify patients on beta-blockers and has implications for patient management before and after liver transplantation. The oxygen uptake efficiency slope was not influenced by beta-blockers and may therefore be a better measure of cardiopulmonary performance in this patient population.


One-third of cirrhotic patients with gastroesophageal varices suffer acute haemorrhage, which increases rates of morbidity and mortality.[1] Nonselective beta-blockers decrease portal blood flow and pressure[2] and are therefore the first-line therapy to reduce the incidence of small and large variceal haemorrhaging.[3] Beta-blockers have been found to effectively reduce the incidence of variceal haemorrhaging and related mortality.[4] Moreover, they also reduce heart rate and cardiac output which are variables central to cardiopulmonary performance.[5]

Several studies have demonstrated the prognostic utility of cardiopulmonary performance, as determined by the ventilatory threshold (VT) and peak oxygen uptake ( ) during cardiopulmonary exercise testing(CPET), to peri- and post-operatively risk stratify liver transplant patients.[6–8] The oxygen uptake efficiency slope(OUES), representing a linear depiction of ventilatory efficiency for a given , has also been shown to be a valid, effort independent, measure of cardiopulmonary performance and may offer utility in quantifying physiological reserve in this population.[9] It is unclear whether beta-blockers impact CPET-derived variables used in the risk stratification of patients for the development of peri- and post-operative complications. This may potentially affect clinical decision-making related to liver transplantation.

The aim of this investigation was to determine the effects of beta-blocker therapy on CPET-derived variables in patients with advanced liver disease prior to liver transplantation. We hypothesised that patients taking beta-blockers would have a lower VT and peak
compared to those patients not taking the medication. It was also hypothesised that there would be no significant difference in the OUES between the groups.