Exercise-based rehabilitation programmes for pulmonary hypertension

Abstract

Background: Individuals with pulmonary hypertension (PH) have reduced exercise capacity and quality of life. Despite initial concerns that exercise training may worsen symptoms in this group, several studies have reported improvements in functional capacity and well-being following exercise-based rehabilitation.

Objectives: To evaluate the benefits and harms of exercise-based rehabilitation for people with PH compared with usual care or no exercise-based rehabilitation.

Search methods: We used standard, extensive Cochrane search methods. The latest search date was 28 June 2022.

Selection criteria: We included randomised controlled trials (RCTs) in people with PH comparing supervised exercise-based rehabilitation programmes with usual care or no exercise-based rehabilitation.

Data collection and analysis: We used standard Cochrane methods. Our primary outcomes were 1. exercise capacity, 2. serious adverse events during the intervention period and 3. health-related quality of life (HRQoL). Our secondary outcomes were 4. cardiopulmonary haemodynamics, 5. Functional Class, 6. clinical worsening during follow-up, 7. mortality and 8. changes in B-type natriuretic peptide. We used GRADE to assess certainty of evidence.

Main results: We included eight new studies in the current review, which now includes 14 RCTs. We extracted data from 11 studies. The studies had low- to moderate-certainty evidence with evidence downgraded due to inconsistencies in the data and performance bias. The total number of participants in meta-analyses comparing exercise-based rehabilitation to control groups was 462. The mean age of the participants in the 14 RCTs ranged from 35 to 68 years. Most participants were women and classified as Group I pulmonary arterial hypertension (PAH). Study durations ranged from 3 to 25 weeks. Exercise-based programmes included both inpatient- and outpatient-based rehabilitation that incorporated both upper and lower limb exercise. The mean six-minute walk distance following exercise-based rehabilitation was 48.52 metres higher than control (95% confidence interval (CI) 33.42 to 63.62; I² = 72%; 11 studies, 418 participants; low-certainty evidence), the mean peak oxygen uptake was 2.07 mL/kg/min higher than control (95% CI 1.57 to 2.57; I² = 67%; 7 studies, 314 participants; low-certainty evidence) and the mean peak power was 9.69 W higher than control (95% CI 5.52 to 13.85; I² = 71%; 5 studies, 226 participants; low-certainty evidence). Three studies reported five serious adverse events; however, exercise-based rehabilitation was not associated with an increased risk of serious adverse event (risk difference 0, 95% CI -0.03 to 0.03; I² = 0%; 11 studies, 439 participants; moderate-certainty evidence). The mean change in HRQoL for the 36-item Short Form (SF-36) Physical Component Score was 3.98 points higher (95% CI 1.89 to 6.07; I² = 38%; 5 studies, 187 participants; moderate-certainty evidence) and for the SF-36 Mental Component Score was 3.60 points higher (95% CI 1.21 to 5.98 points; I² = 0%; 5 RCTs, 186 participants; moderate-certainty evidence). There were similar effects in the subgroup analyses for participants with Group 1 PH versus studies of groups with mixed PH. Two studies reported mean reduction in mean pulmonary arterial pressure following exercise-based rehabilitation (mean reduction: 9.29 mmHg, 95% CI -12.96 to -5.61; I² = 0%; 2 studies, 133 participants; low-certainty evidence).

Authors' conclusions: In people with PH, supervised exercise-based rehabilitation may result in a large increase in exercise capacity. Changes in exercise capacity remain heterogeneous and cannot be explained by subgroup analysis. It is likely that exercise-based rehabilitation increases HRQoL and is probably not associated with an increased risk of a serious adverse events. Exercise training may result in a large reduction in mean pulmonary arterial pressure. Overall, we assessed the certainty of the evidence to be low for exercise capacity and mean pulmonary arterial pressure, and moderate for HRQoL and adverse events. Future RCTs are needed to inform the application of exercise-based rehabilitation across the spectrum of people with PH, including those with chronic thromboembolic PH, PH with left-sided heart disease and those with more severe disease.

Trial registration: ClinicalTrials.gov clinicaltrials.gov/ct2/show/NCT04254289 clinicaltrials.gov/ct2/show/NCT04559516 clinicaltrials.gov/ct2/show/NCT04683822 clinicaltrials.gov/ct2/show/NCT02371733.