Echocardiography-led multimodal assessment for pulmonary hypertension in a right heart catheterization-referred cohort: incremental value of ECG and natriuretic peptides

BACKGROUND: Right heart catheterization (RHC) is the reference standard for diagnosing pulmonary hypertension (PH), whereas echocardiography is the primary noninvasive tool for identifying patients who require further evaluation. Whether electrocardiography (ECG) and natriuretic peptides provide incremental diagnostic information beyond echocardiographic assessment in patients referred for RHC remains uncertain. METHODS: This single-center retrospective study included 130 hospitalized patients with suspected PH who underwent echocardiography, 12-lead ECG, B-type natriuretic peptide (BNP) or N-terminal pro-B-type natriuretic peptide (NT-proBNP) testing, and RHC during the same admission. PH was defined as mean pulmonary arterial pressure > 20 mmHg on RHC. A temporal validation cohort of 42 consecutive eligible patients was used to evaluate the final model without refitting. To reduce collinearity, the final multimodal model included pulmonary artery systolic pressure estimated by echocardiography (PASP ECHO), ECG positivity, and BNP/NT-proBNP positivity. Model discrimination was assessed using receiver operating characteristic analysis, areas under the curve (AUCs) were compared using DeLong's test, calibration was assessed using calibration plots and calibration metrics, and internal validation was performed using bootstrap resampling. RESULTS: Among 130 patients in the derivation cohort, 111 had PH and 19 did not. The final multimodal model showed higher discrimination than PASP ECHO alone in the derivation cohort (AUC 0.825, 95% CI 0.722-0.928 vs. 0.730, 95% CI 0.620-0.841; DeLong P = 0.008). At the Youden threshold, the final model showed high specificity but limited sensitivity, whereas a sensitivity-oriented threshold increased sensitivity at the expense of specificity. Bootstrap internal validation yielded an optimism-corrected AUC of 0.811. In the temporal validation cohort, the final model showed an AUC of 0.792, compared with 0.749 for PASP ECHO alone; this difference was not statistically significant. Bland-Altman analysis showed wide limits of agreement between PASP ECHO and invasive systolic pressure estimates, indicating that echocardiographic and invasive pressure estimates are associated but not interchangeable. CONCLUSIONS: In this RHC-referred suspected PH cohort, ECG and natriuretic peptide positivity provided complementary information beyond PASP ECHO. However, because of the small sample size, marked class imbalance, and limited subtype characterization, the proposed multimodal approach should be considered exploratory. Larger prospective studies with subtype stratification and external validation are required before clinical implementation.