BACKGROUND: Patients with chronic thromboembolic pulmonary hypertension (CTEPH) still have impaired exercise training and quality of life (QoL) despite pulmonary arterial hypertension (PAH)-targeted drugs. Exercise training is considered to improve exercise capacity and QoL in patients with pulmonary hypertension (PH), but this has not been fully studied in CTEPH patients. We conducted the meta-analysis and systematic review to evaluate the effectiveness and safety of exercise training in patients with CTEPH. METHODS: The relevant literature was retrieved for the meta-analysis using the PubMed, Embase, and Cochrane Library databases published before December 2020. The primary outcome was a change in six-minute walk distance (6MWD). We also assessed the effect of exercise training on peak oxygen uptake per kilogram (peak VO2/kg), mean pulmonary artery pressure (mPAP) assessed by right heart catheterization (RHC), N-terminal pro-brain-type natriuretic peptide (NT-proBNP), and QoL. RESULTS: A total of 6 studies with 234 exercise training patients were included. In the pooled analysis, 6MWD significantly improved by 70.14 m (WMD 58.33 to 81.95, I2 = 0%) after 3-week exercise training. After 12 or 15-week exercise training, 6MWD and peak VO2/kg significantly improved (WMD 106.22 m, 95% CI 65.90 to 146.55, I2 = 87.4%, p < 0.0001; 1.84 mL/min/kg, 95% CI 0.72 to 2.96, p = 0.001, respectively). Furthermore, the mPAP decreased by 12.17 mmHg after 12-week exercise training (95% CI -14.53 to -9.82, p < 0.001, I2 = 99%). The subscales of QoL such as physical function, general health perception, and mental health improved in varying degrees. NT-proBNP did not improve significantly in the pooled analysis. In addition, exercise training was well tolerated without major adverse events occurred during training, and the dropout rate was low. DISCUSSION: Exercise training may improve exercise capacity, mPAP, and QoL, and was well tolerated among patients with CTEPH. However, more large-scale multicenter studies are needed to confirm the effectiveness and safety of exercise training in patients with CTEPH.

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