Prognostic value of composite hemodynamic indices in congenital heart disease-associated pulmonary hypertension: insights from a national multicenter prospective registry study
Q Yu, Y Wu, J HeAbstract
Background
In congenital heart disease-associated pulmonary arterial hypertension (CHD-PAH), right heart catheterisation is essential, but conventional haemodynamic indices from the ESC simplified four-strata model have limited prognostic value. Whether composite indices—PVRI, effective arterial elastance (Ea), pulmonary arterial compliance (PAC), and cardiac power output (CPO)—confer incremental value remains unknown.
Purpose
To evaluate the independent prognostic value and incremental discriminative ability of four composite RHC-derived indices over the ESC simplified four-strata risk model in a large prospective CHD-PAH cohort, and to characterise mechanistic pathways linking these indices to mortality.
Methods
From a national 30-centre prospective registry (2009–2019), 625 CHD-PAH patients with complete RHC data were included. Multivariable Cox models with progressive adjustment were applied. Incremental performance was quantified by C-statistic, NRI, and IDI at 1, 3, and 5 years. Causal mediation analysis explored body weight as a mechanistic intermediary.
Results
In fully adjusted models, all four composite indices independently predicted all-cause mortality per 1-SD increase: PVRI (HR 1.28, 95% CI 1.06–1.55; P=0.010), Ea (HR 1.34, 95% CI 1.11–1.62; P=0.002), PAC (HR 0.68, 95% CI 0.49–0.93; P=0.018), and CPO (HR 0.76, 95% CI 0.58–0.99; P=0.039). Conventional indices CI and SVI were non-significant across all adjustment models. Adding all four novel indices to the ESC simplified four-strata risk score improved the C-statistic from 0.553 to 0.612 (P=0.023), with NRI 0.18 (95% CI 0.06–0.30; P=0.004) and IDI 0.017 (P=0.040) at 3 years. The composite model incorporating mean right atrial pressure alongside Ea, PAC, and CPO achieved the greatest incremental benefit: NRI 0.22 (95% CI 0.07–0.36; P=0.003) and IDI 0.025 (95% CI 0.008–0.050; P=0.021) at 3 years, with time-dependent AUC increasing from 0.596 to 0.633 at 3 years and from 0.573 to 0.727 at 1 year. Causal mediation analysis identified a haemodynamic–nutritional coupling pathway: body weight significantly mediated 29.8%, 18.6%, and 28.7% of the total mortality effects of Ea, PAC, and CPO, respectively, whereas PVRI exerted its prognostic influence entirely independent of body weight (indirect effect P=0.753). Significant interactions were observed for WHO functional class (PVRI P-interaction=0.003) and sex (PAC P-interaction=0.041).
Conclusions
Composite RHC-derived haemodynamic indices (PVRI, Ea, PAC, and CPO) independently predict all-cause mortality and meaningfully improve risk reclassification beyond the ESC simplified four-strata risk model in CHD-PAH, whereas conventional indices provide limited incremental value. The identification of a haemodynamic–nutritional coupling axis opens a mechanistically informed avenue for integrated haemodynamic and nutritional intervention strategies in CHD-PAH.Novel vs Traditional Hemodynamic IndicesFor image description, please refer to the figure legend and surrounding text.Incremental Value Over ESC Risk ModelFor image description, please refer to the figure legend and surrounding text.