Prognostic Relevance of Cardiopulmonary Exercise Testing for Patients with Chronic Thromboembolic Pulmonary Hypertension

Background: Following acute pulmonary embolism (PE), a relevant number of patients experience decreased exercise capacity which can be associated with disturbed pulmonary perfusion. Cardiopulmonary exercise testing (CPET) shows several patterns typical for disturbed pulmonary perfusion. Research question: We aimed to examine whether CPET can also provide prognostic information in chronic thromboembolic pulmonary hypertension (CTEPH). Study Design and Methods: We performed a multicenter retrospective chart review in Germany between 2002 and 2020. Patients with CTEPH were included if they had >= 6 months of follow-up and complete CPET and hemodynamic data. Symptom-limited CPET was performed using a cycle ergometer (ramp or Jones protocol). The association of anthropometric data, comorbidities, symptoms, lung function, and echocardiographic, hemodynamic, and CPET parameters with survival was examined. Mortality prediction models were calculated by Cox regression with backward selection. Results: 345 patients (1532 person-years) were included; 138 underwent surgical treatment (pulmonary endarterectomy or balloon pulmonary angioplasty) and 207 received only non-surgical treatment. During follow-up (median 3.5 years), 78 patients died. The death rate per 1000 person-years was 24.9 and 74.2 in the surgical and non-surgical groups, respectively (p < 0.001). In age- and sex-adjusted Cox regression analyses, CPET parameters including peak oxygen uptake (VO(2)peak, reflecting cardiopulmonary exercise capacity) were prognostic in the non-surgical group but not in the surgical group. In mortality prediction models, age, sex, VO(2)peak (% predicted), and carbon monoxide transfer coefficient (% predicted) showed significant prognostic relevance in both the overall cohort and the non-surgical group. In the non-surgical group, Kaplan-Meier analysis showed that patients with VO(2)peak below 53.4% predicted (threshold identified by receiver operating characteristic analysis) had increased mortality (p = 0.007). Interpretation: The additional measurement of cardiopulmonary exercise capacity by CPET allows a more precise prognostic evaluation in patients with CTEPH. CPET might therefore be helpful for risk-adapted treatment of CTEPH.