Sex-specific cardiopulmonary exercise testing indices to estimate the severity of inoperable chronic thromboembolic pulmonary hypertension

Background: Sex differences in chronic thromboembolic pulmonary hypertension (CTEPH) have been revealed in few studies. Although right heart catheterization (RHC) is the gold standard for clinical diagnosis and assessment of prognosis in pulmonary hypertension (PH), cardiopulmonary exercise testing (CPET) has been a more widely used assessment of functional capacity, disease severity, prognosis, and treatment response in PH. We hypothesized that the "sex-specific" CPET indices could estimate the severity of inoperable CTEPH. Methods: Data were retrieved for 33 male (age, mean ± standard deviation [SD] =62.5±13.4 years) and 40 female (age, mean ± SD =56.3±11.8 years) patients with stable CTEPH who underwent both RHC and CPET at Shanghai Pulmonary Hospital from February 2010 to February 2016. Univariate and forward/backward multiple stepwise regression analysis was performed to assess the predictive value of CPET indices to hemodynamic parameters. Event-free survival was estimated using the Kaplan-Meier method and analyzed with the log-rank test. Cox proportional hazards models were performed to determine the independent event-free survival predictors. Results: Numerous CPET parameters were different between male and female patients with CTEPH and the control group. There were no significant differences in both clinical variables and RHC parameters between male and female patients with CTEPH. O2 pulse, workload, minute ventilation (VE), and end-tidal partial pressure of O2 (PETO2) at anaerobic threshold, as well as peak O2 pulse, workload, VE, and nadir VE/CO2 were significantly higher in male patients than in female patients (P<0.05). Only oxygen uptake efficiency plateau (OUEP) showed a significantly higher difference in female than male patients (P<0.05). In addition, several CPET indices correlated with hemodynamic parameters, especially pulmonary vascular resistance (PVR), which was distinctly different between the sexes. Nadir VE/CO2 was an independent predictor of PVR in male patients with CTEPH, whereas OUEP was an independent predictor of PVR in female patients with CTEPH. Conclusion: Even after confounding for age and body mass index, different CPET measurements of gas exchange efficiency correlated with PVR differently between male and female patients. This potentially could be used to estimate the severity of CTEPH.