Between April 2012 and March 2016, 840 consecutive treatment-naïve patients with suspected PH were identified who underwent MRI and RHC, of whom 491 patients underwent CT pulmonary angiography within 90 days. Patients underwent CT imaging at 68 different institutions and 78% of CT pulmonary angiograms were performed at the Sheffield Pulmonary Vascular Disease Unit. Patient demographics, RHC and CT metrics for patients with PH (n = 420), with mPAP < 25 mmHg (n = 71) and with mPAP ≤ 20 mmHg are shown in Table 1. Patients with PH were older (p < 0.001) and more likely to be female (p < 0.013) and have a higher WHO functional class (p < 0.001) and lower walking distance (p < 0.001), than patients without PH. Correlation of CT metrics with mPAP and PVR is presented in Supplementary Table 1 and key correlations are in Fig. 2. Table 2 presents the sensitivity, specificity and positive and negative predictive value of pulmonary artery diameter, right ventricular outflow tract thickness, interventricular septal angle and RV/LV diameter ratio.
Table 1 Demographics of patients with and without PH for the full cohort Table 2 Diagnostic accuracy of predictive thresholds for PA diameter, RVOT thickness, septal angle and RV diameter/LV diameter ratio in the validation cohort Derivation cohort
Random patient selection identified a derivation cohort of 247 and a validation cohort of 244 patients. There were no significant differences in age, proportion of patients with PH, WHO functional class or right heart catheterisation metrics between the two cohorts (p > 0.05). However, there was a higher proportion of females in the derivation cohort as compared with the validation cohort (Supplementary Table 2).
CT diagnostic model A
In the derivation cohort, a regression model was identified. The model incorporated main pulmonary artery diameter, right ventricle outflow tract thickness, left ventricular area and interventricular septal angle as follows: model A score = − 14.299 + (0.192 × main pulmonary artery diameter, mm) + (0.518 × right ventricle outflow tract thickness, mm) − (0.001 × left ventricular area, mm2) + (0.068 × interventricular septal angle, degrees). The area under the curve (AUC) in the derivation cohort was 0.92 (see Fig. 3). The AUC in the derivation cohort with adjustment for body surface area was 0.86. The following thresholds were identified in the derivation cohort: high sensitivity (model A score 0), high specificity (model A score 2.5) and a compromise threshold (model A score 1.25). The diagnostic model performed better than individual CT metrics. Of the individual CT metrics, the AUC for pulmonary artery diameter was 0.79, right ventricular outflow tract thickness 0.79, left ventricular area 0.64 and interventricular septal angle 0.84.
For the prediction of mPAP > 20 mmHg, a model of − 13.843 + (0.94 × right ventricle outflow tract thickness, mm) + (0.094 × interventricular septal angle, degrees) was identified. The diagnostic accuracy of this model was AUC 0.88 for detecting mPAP > 20 mmHg; this was of lower accuracy in comparison with model A that had a diagnostic accuracy of 0.90 for detecting mPAP > 20 mmHg.
CT diagnostic model B
In the derivation cohort, a second model was developed; the model incorporated main pulmonary artery diameter, right ventricle outflow tract thickness and RV/LV diameter ratio, as follows: model B score = − 9.181 + (0.174 × main pulmonary artery diameter, mm) + (0.480 × right ventricle outflow tract thickness, mm) + (2.539 × RV/LV diameter, ratio). This model had an AUC of 0.89 in the derivation cohort. The following thresholds were identified in the derivation cohort: high sensitivity (model B score 0.5), compromise threshold (model B score 1.0) and a high specificity threshold (model B score 1.5) (see Table 4). CT diagnostic prediction model to detect mPAP > 20 mmHg was also derived: − 4.553 + (0.661 × right ventricle outflow tract thickness, mm) + (3.027 × RV/LV diameter, ratio). This model had lower accuracy for prediction of mPAP > 20 mmHg at ROC analysis: AUC 0.86 compared with 0.89 for model B.
Validation cohort
Identification of patients with mPAP greater than or equal to 25 mmHg
CT diagnostic model A
In the validation cohort, the CT diagnostic model A showed high diagnostic accuracy for the detection of PH (AUC at 0.94; Fig. 3). The CT diagnostic model A adjusted for BSA did not improve the diagnostic performance of the model (AUC 0.92). Sensitivity, specificity and positive and negative predictive values are presented for high sensitivity, specificity and compromise thresholds in Table 3.
Table 3 Regression CT diagnostic models A and B thresholds and their accuracy for predicting the presence of PH in the validation cohort
CT diagnostic model B
Model B was derived excluding the single parameter that required reconstruction (interventricular septal angle). In the validation cohort, diagnostic CT model B had an accuracy of 0.92. Table 3 details the sensitivity, specificity and positive and negative predictive values for high sensitivity, specificity and compromise thresholds.
Identification of patients with mPAP greater than 20 mmHg
CT diagnostic model A
In the validation cohort, the CT diagnostic model A showed high diagnostic accuracy for the detection of PH (AUC at 0.91). The CT diagnostic model A adjusted for BSA marginally improved the diagnostic performance of the model (AUC 0.93).
CT diagnostic model B
Model B was derived excluding the single parameter that required reconstruction (interventricular septal angle). In the validation cohort, diagnostic CT model B was marginally weaker than model A with an accuracy of 0.87.
Table 4 details the sensitivity, specificity and positive and negative predictive values for high sensitivity, specificity and compromise thresholds for identification of patients with mPAP greater than or equal to 20 mmHg.
Table 4 Regression CT diagnostic models A and B thresholds and their accuracy for predicting the presence of patients with mPAP greater than 20 mmHg in the validation cohort
Prognostic significance of CT and right heart catheterisation thresholds
CT diagnostic model A
In the validation cohort, 93 patients died; mean follow-up was 42 months. The CT diagnostic model A sensitive (0), compromise (1.25) and (2.5) specific thresholds for mPAP ≥ 25 mmHg were strongly predictive of mortality log rank 11.13 (p = 0.0009 and 9.70; p = 0.002 and 9.49; p = 0.002 respectively). The CT diagnostic model A sensitive (0), compromise (1.0) and (2.25) specific thresholds for mPAP > 20 mmHg were also strongly predictive of mortality log rank 11.13 (p = 0.0009 and 6.25; p = 0.010 and 10.57; p = 0.001).
CT diagnostic model B
The CT diagnostic model B sensitive (0.5), compromise (1.0) and (1.5) specific thresholds for mPAP ≥ 25 mmHg were as follows (mortality log rank 6.92): p = 0.009 and 3.25; p = 0.071 and 6.28; p = 0.012 respectively. The CT diagnostic model B sensitive (0.5), compromise (0.8) and (1.4) specific thresholds for mPAP > 20 mmHg were also strongly predictive of mortality log rank 6.92 (p = 0.009 and 6.56; p = 0.010 and 535; p = 0.021).
At Cox regression analysis, CT diagnostic models A and B were prognostic; z score hazard ratios were 1.56 and 1.42, both p < 0.0001.
Right heart catheter diagnostic thresholds
RHC diagnostic thresholds ≥ 25 mmHg and > 20 mmHg were not prognostic in this cohort (log rank 2.86, p = 0.09 and log rank 1.77, p = 0.18 respectively; see Fig. 4).
Correlations and diagnostic value of individual CT metrics with pulmonary haemodynamics and MRI metrics in the full cohort
Correlations between CT vascular and cardiac measures are shown in Supplementary Table 1. Figure 2 shows the correlation of CT metrics and mean pulmonary artery pressure. A detailed description of the MRI findings is found in Supplementary Results.
Reproducibility
High reproducibility of interventricular septal angle (ICC 0.921), pulmonary artery diameter (ICC 0.954) and left ventricular area (ICC 0.953) was demonstrated. In comparison, good reproducibility was recorded for the variables RV/LV diameter ratio (ICC 0.810) and right ventricular outflow tract thickness (ICC 0.76) (see Table 5).
Table 5 Reproducibility tests of the variables selected in model