RESUMO
Background: Pulmonary hypertension (PH) is a debilitating condition characterized by elevated pulmonary arterial pressure and progressive vascular remodelling, leading to exercise intolerance. The progression of PAH is regulated at a cellular and molecular level which influences various physiological processes. Exercise plays an important role in improving function in PH. Although the signalling pathways that regulate cardio-protection through exercise have not been fully understood, the positive impact of exercise on the various physiological systems is well established. Summary: Exercise has emerged as a potential adjunctive therapy for PH, with growing evidence supporting its beneficial effects on various aspects of the disease pathophysiology. This review highlights the contributions of cellular and molecular pathways and physiological processes to exercise intolerance. Preclinical studies have provided insight into the mechanisms underlying exercise-induced improvements in PH which are modulated through improvements in endothelial function, inflammation, oxidative stress, and mitochondrial function. Along with preclinical studies, various clinical studies have demonstrated that exercise training can lead to significant improvements in exercise capacity, haemodynamics, quality of life, and functional status. Moreover, exercise interventions have been shown to improve skeletal muscle function and enhance pulmonary vascular remodelling, contributing to overall disease management. Further research efforts aimed at better understanding the role of exercise in PH pathophysiology, and refining exercise interventions are warranted to realize its full potential in the management of this complex disease. Key Messages: Despite the promising benefits of exercise in PH, several challenges remain, including the optimal intensity, duration, and type of exercise training, as well as patient selection criteria and long-term adherence. Additionally, the mechanisms underlying the observed improvements require further elucidation to optimize exercise protocols and personalize treatment strategies. Nonetheless, exercise represents a promising therapeutic approach that can complement existing pharmacological therapies and improve outcomes in PH patients.
RESUMO
PURPOSE: Given that previous reviews on exercise training in pulmonary hypertension (PH) were largely based on a small number of randomized controlled trials (RCT), their conclusions are subject to bias. This review sought to identify the impact of exercise training on functional capacity and health-related quality of life (HRQoL) in PH using advanced statistical approaches such as meta-analysis by stratification according to study design. REVIEW METHODS: Five databases were searched from January 2015 to April 2020 to update a previous review. Included articles had data extracted, risk of bias (ROB) assessed, and quality rating performed. Data were analyzed using meta-analysis with a random-effects model for 6-min walk test (6MWT) distance and HRQoL. Heterogeneity was explored using stratified meta-analysis, within patient correlation and meta-regression. RESULTS: A total of 28 studies (11 RCT, 12 pre-/post-studies, 2 two-group non-RCT, and three case series) consisting of 1264 patients were included. Meta-analysis of six RCT demonstrated an improved 6MWT distance by 49.5 m (95% CI, 27.2-71.8: I2 = 73%; 254 participants; low-moderate ROB) with a low correlation coefficient of 0.34, while the 12 pre-/post-non-RCT showed an improvement of 68.69 m (95% CI, 50.50-86.69: I2 = 36%; 784 participants; high ROB) along with improvements in VË o2peak (weighted mean difference [WMD] = 3.03 mL/kg/min, 95% CI, 2.17-3.90: I2 = 0%, P = .82), and HRQoL (WMD = 2.74: 95% CI, -0.82 to 6.30). Metaregression showed that the benefit of exercise on 6MWT distance did not significantly vary across the trial study characteristics. CONCLUSION: This updated review identified an additional body of evidence supporting the efficacy of exercise training on 6MWT distance and HRQoL in stable PH patients. These benefits appeared to be consistent across models of delivery.
