Characteristics of the CTEPH subjects
55 patients with CTEPH were involved in the test set. They were divided into “Mild”, “Moderate” and “Severe” groups according to PAP (mm Hg). Mild: 35>PAP (mm Hg)≥25; Moderate: 45>PAP (mm Hg) ≥35; Severe: PAP (mm Hg)≥45.
The characteristics of all groups were summarized in Table 1 and Figure 1. The “Severe” group had the highest NT-proBNP (pg/mL) value when compared with the “Mild” and “Moderate” groups (143.0(63.8, 286.7) vs. 648.5(266.3,2049) vs. 1082(642.0,2674) pg/mL; P=0.001). The PAP (mm Hg) value of the “Mild”, “Moderate” and “Severe” groups were significantly different (28.60±3.27 vs. 39.50±3.87 vs. 56.40±8.03 mm Hg; P<0.0001). Additionally, significant differences in PVR and RAP values among the three groups were noted. PVR (wood u) value for the “Mild”, “Moderate” and “Severe” groups (3.7±1.3 vs. 7.6±2.4 vs. 10.9±3.8 wood u; P<0.0001), and for RAP (mm Hg) value of the “Mild”, “Moderate” and “Severe” groups (0.5(0,4.5) vs. 1.0(0,1.3) vs. 4.0(2.0,7.0) mm Hg; P=0.001).
CPET and PFT performance differences in subjects with CTEPH
During PFT, we noted FEV1/FVC (%) as the only parameter differing among the “Severe”, “Mild” and “Moderate” groups (78.8±9.3 vs. 81.7±8.0 vs. 73.4±8.0 %; P=0.013). Details are listed in Table 1 and Figure 1.
During CPET, several parameters were found to be different among the “Mild”, “Moderate” and “Severe” groups. They are listed as followed: Load @ Peak (W), VO2 @ Peak (mL/Kg/min), VE @ AT (L/min), BR @ Rest (%), BR @ AT (%), VE/VCO2 @ AT, VE/VCO2 @ Peak, VO2/VE @ AT, PETCO2 @ Rest, PETCO2 @ AT, PETCO2 @ Peak, PETO2 @ Rest, PETO2 @ AT, PETO2 @ Peak, VE/VCO2 slope and LOWEST VE/VCO2. Details are listed in Table 2, Table 3 and Figure 1.
Predictive value of the CPET and PFT parameters for the severe CTEPH
Furthermore, 55 patients with CTEPH in the test set were re-grouped into “Mild-Moderate” and “Severe” group to analyze predictors for severe CTEPH. All the parameters measured were analyzed with the univariate analysis for the severe CTEPH, and 21 parameters were found to have a P<0.05. They are listed as followed: VE @ AT (L/min), VO2/VE @ AT, BR @ AT (%), LOWEST VE/VCO2, VE/VCO2 @ AT, PETO2 @ AT, PETCO2 @ Peak, FEV1/FVC (%), PETCO2 @ Rest, Load @ Peak (W), VE/VCO2 @ Peak, BR @ Rest (%),VO2 @ Peak (mL/Kg/min), VCO2 @ Peak, VE/VCO2 slope, FEV1 (% Pred), VE/VCO2 @ Rest, BMI (kg/m2), NT-proBNP (pg/mL), VO2/VE @ Peak and RER @ Peak. Considering the sample size, 11 parameters with the minimum P value were fitted into the multivariate analysis, including VE @ AT (L/min) (OR: 1.169, P=0.004), VO2/VE @ AT (OR: 0.762, P=0.004), BR @ AT (%) (OR: 0.936, P=0.006), LOWEST VE/VCO2 (OR: 1.129, P=0.006), VE/VCO2 @ AT (OR: 1.100, P=0.008), PETO2 @ AT (OR: 1.184, P=0.009), PETCO2 @ Peak (OR: 0.859, P=0.009), FEV1/FVC (%) (OR: 0.900, P=0.010), PETCO2 @ Rest (OR: 0.769, P=0.011), Load @ Peak (W) (OR: 0.961, P=0.011) and VE/VCO2 @ Peak (OR: 1.068, P=0.014). By using multivariate logistic regression analysis, VE @ AT (L/min) (OR: 1.400, P=0.048), FEV1/FVC (%) (OR: 0.756, P=0.007) and Load @ Peak (W) (OR: 0.881, P=0.021) were significant independent predictors for the severe CTEPH. Details are listed in Table 4 and Figure 2.
Combining these three parameters, we got the prediction equation for the severe CTEPH which was Logit(P)=7.397+0.205*[email protected]*FEV1/FVC-0.059* Load @ Peak. To evaluate the ability of the VE @ AT (L/min), FEV1/FVC (%), Load @ Peak (W) and the prediction equation to differentiate severe from mild-moderate CTEPH, ROC curves and calibration curves were performed. Details are listed in Table 5 and Figure 3. It must be noted that the AUC of the prediction equation was better than that for each parameter, indicating that the equation based on three parameters yielded the highest AUC value and could significantly improve the prediction performance for severe CTEPH.
Additionally, we analyzed the prediction equation in the validation datasets to validate the results. Only 4 of 31 patients with CTEPH of the validation set were ambiguous, and the accuracy was 87.10%. Details are listed in Table 6.