Exercise testing in chronic thromboembolic pulmonary hypertension and chronic thromboembolic pulmonary disease without pulmonary hypertension: a comprehensive systematic review and meta-analysis

Background and aim The role of exercise testing in the follow up of patients with persistent dyspnea after pulmonary embolism (PE) is currently limited, with cardiopulmonary exercise test (CPET) mainly recommended in patients with a low probability of pulmonary hypertension (PH) at rest. Methods We conducted a comprehensive systematic review of studies retrieved from EMBASE and MEDLINE. When appropriate, meta-analysis was conducted. Results Twenty-eight studies were included. At CPET, pooled VE/VCO₂ slope was lower in CTEPD without PH compared to chronic thromboembolic pulmonary hypertension (CTEPH) (mean difference = 12.34, 95% CI =17.19 to 7.48, I² =76%). CPET parameters indicated more severe cardiopulmonary impairment in CTEPH than in pulmonary arterial hypertension (PAH), with a lower pooled Peak VO₂ (mean difference=–0.57 mL·kg⁻¹·min⁻¹, 95% CI=–0.94 to –0.20, I²=0%), higher VE/VCO₂ slope (mean difference=8.44, 95% CI=3.31 to 13.57, I²=19%), lower peak PETCO₂ (mean difference=–3.55 mmHg, 95% CI=–4.75 to –2.34 mmHg, I²=0%), and lower PETCO₂ at anaerobic threshold (mean difference=–3.55 mmHg, 95% CI=–4.75 to –2.34 mmHg, I²=0%). In CTEPH, peak VO2 correlated with mPAP and survival: in two studies, different VO2 thresholds were associated with survival differences of 30% and 35%, respectively. The prevalence of exercise-induced PH, assessed by exercise right heart catheterization (exRHC), was reported as 50% and 45% in two studies. Discussion CTEPH is associated with worse CPET profile compared with both CTEPD without PH and PAH. Peak VO₂ and ventilatory efficiency may have prognostic value in CTEPH, while evidence in CTEPD without PH remains largely exploratory and hypothesis-generating