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

Abstract

BackgroundSex 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.MethodsData 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.ResultsNumerous 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.ConclusionEven 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.

Sex Differences in Right Ventricular Dysfunction: Insights From the Bench to Bedside

“…However, it is uncertain whether this survival difference is due to differences in comorbidity burden (Barco et al, 2020 ). Studies of a Chinese CTEPH cohort (Chen et al, 2018 ) and the Spanish Registry of Pulmonary Arterial Hypertension, which includes CTEPH patients (Escribano-Subias et al, 2012 ) also show improved survival in females (male HR 1.38, 95% CI: 1.03–1.83 ; p = 0.03) (Escribano-Subias et al, 2012 ). In a Japanese cohort of CTEPH patients, females have significantly higher cardiac index (2.7 ± 0.6 vs. 2.4 ± 0.7 L·min −1 ·m −2 ; p = 0.01) and lower right atrial pressure (4 ± 4 vs. 7 ± 6 mmHg; p = 0.0002) compared to males despite no difference in pulmonary vascular resistance (Shigeta et al, 2008 ).…”

Cardiac remodelling in a swine model of chronic thromboembolic pulmonary hypertension: comparison of right vs. left ventricle

“…Also in humans, endothelial dysfunction is often present both in patients with acute pulmonary embolism, as well as with CTEPH, and correlates with disease severity (Reesink et al 2006;In et al 2016;Chibana et al 2017). In humans, CTEPH prevalence is higher in females (Kirson et al 2011), although male patients typically have a worse prognosis (Chen et al 2018). In the present study, male and female swine were used because we have previously shown that there are subtle differences in regulation of pulmonary vascular tone (de Beer et al 2010;de Wijs-Meijler et al 2017) and hence it is possible that sex also affects development of CTEPH and subsequent RV remodelling in our animals.…”

Sex Differences in Pulmonary Hypertension

“…In an observational study aimed to estimate the incidence of risk factors of CTEPH in a cohort with first venous thromboembolism (N 23,329 patients), female sex was significantly associated with the development of the disease (Martinez et al, 2018). However, studies carried out in Spanish and Chinese cohorts have showed a better survival in women as compared with their male counterparts (Escribano-Subias et al, 2012;Chen et al, 2018). This improved survival could be related to better cardiac performance, with lower atrial pressure and higher cardiac index to similar PVR compared to men (Shigeta et al, 2008).…”