Acute effect of acetazolamide on exercise haemodynamics in patients with pulmonary arterial and chronic thromboembolic pulmonary hypertension: a randomised controlled trial

Abstract

Background: The aim of this study was to investigate the acute effect of acetazolamide on pulmonary haemodynamics during exercise in patients with pulmonary vascular disease (PVD).

Methods: Patients with PVD diagnosed as pulmonary arterial (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) underwent right-heart catheterisation with haemodynamic measurements at rest and during stepwise incremental cycling exercise 60 min after receiving intravenous acetazolamide (500 mg) or saline placebo in accordance with a double-blind, randomised-controlled, crossover design. The main outcomes were the difference between pulmonary vascular resistance (PVR) and its components mean pulmonary artery pressure (mPAP), cardiac output (CO) and pulmonary arterial wedge pressure (PAWP), during exercise, assessed by a mixed linear regression analysis.

Results: A total of 24 patients (n=7 PAH, n=17 CTEPH; n=17 male) were included (mean±sd age 59±14 years). Treatment with acetazolamide compared with saline placebo showed the following average marginal effects during exercise: unchanged end-exercise power (mean difference -0.8 W, 95% CI -5.7-4.1 W; p=0.740), reduced mPAP (mean difference -1.7 mmHg, 95% CI -2.9- -0.5 mmHg; p=0.007), tendency to reduced CO (mean difference -0.3 L·min^-1, 95% CI -0.7-0.1 L·min^-1; p=0.097), unchanged PVR (mean difference -0.1 Wood units (WU), 95% CI -0.3-0.2 WU; p=0.694), unchanged PAWP (mean difference 0.0 mmHg, 95% CI -0.2-0.3 mmHg; p=0.783) and unchanged mPAP/CO slope (mean difference 0.1 WU, 95% CI -1.0-1.3 WU; p=0.839).

Conclusion: Intravenous acetazolamide was well tolerated and resulted in a significant but small decrease in mPAP, while CO, PVR and the pressure-flow slope during exercise were unchanged.

FIGURE 1

Patient flow. RHC: right-heart catheterisation; PH: pulmonary hypertension.

FIGURE 2

a–e) Haemodynamic variables as data points depending on exercise power until end-exercise; f) Pressure–flow curve (the difference in mean pulmonary arterial pressure (mPAP) between end-exercise and rest divided by the difference in cardiac output (CO) between end-exercise and rest). The data points are colour-coded for treatment (red indicating saline placebo, turquoise indicating acetazolamide). A linear trend line colour-coded for each treatment has been laid over the corresponding data. The corresponding grey areas of each trend line indicate the range uncertainty depending on data density and distribution. p-values from the respective mixed model regression are displayed for each panel. a) Pulmonary vascular resistance (PVR). b) mPAP. c) CO. d) Pulmonary arterial wedge pressure (PAWP). e) Total pulmonary resistance (TPR).

FIGURE 3

Pulmonary vascular resistance (PVR) is shown as data points depending on a) the arterial oxygen tension (P_aO2) and b) the arterial carbon dioxide tensions (P_aCO2), colour-coded for treatment (red indicating saline placebo, turquoise indicating acetazolamide), with the left panel showing data at rest and the right panel showing data at end-exercise. A linear trend line colour-coded for each treatment has been laid over the corresponding data. The corresponding grey areas of each trend line indicate the range uncertainty depending on data density and distribution. WU: Wood unit.