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

Abstract

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 (P_ETO₂) 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.

Keywords:

• sex difference
• chronic thromboembolic pulmonary hypertension
• cardiopulmonary exercise testing
• severity

Acknowledgments

We thank Prof Rui Zhang, Jing He, and all the other study investigators, fellows, nurses, and research coordinators who participated in this study. This work was supported by the National Health and Family Planning Commission of the People’s Republic of China (W2015RNA09B and 2015BAI12B10), the Program of Shanghai Natural Science Foundation (16ZR1429000), the Program of National Natural Science Foundation of China (81500040 and 81600032) and the YangFan Program of Shanghai Science and Technology Committee (15YF1409700). All the work in this study was completed in the Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of China.

Author contributions

Tian-Xiang Chen, Jin-Ming Liu, and Ping Yuan designed the study; Tian-Xiang Chen, Bigyan Pudasaini, and Ping Yuan contributed to data acquisition; Tian-Xiang Chen, Jian Guo, Rong Jiang, and Ping Yuan contributed to statistical analysis; Jin-Ming Liu contributed to study supervision; Wen-Hui Wu, Ping Yuan, and Jin-Ming Liu contributed to the acquisition of funding. All authors contributed toward data analysis, drafting and critically revising the paper, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.