<p>Pulmonary arterial hypertension (PAH) is a life-threatening disorder marked by progressive elevation of pulmonary vascular resistance and ultimate right heart failure. Its diagnosis and risk stratification largely depend on invasive right heart catheterization (RHC). This study aimed to integrate routine laboratory and echocardiographic data to develop a novel multi-organ prognostic indicator and construct non-invasive hemodynamic estimation prediction models. This was a multi-center retrospective study enrolling a total of 44 routine laboratory and echocardiographic indices of pre-capillary pulmonary hypertension. Key prognostic variables were screened using Least absolute shrinkage and selection operator-Cox (LASSO-Cox) regression and random survival forest (RSF) analysis. The novel composite index was constructed based on correlation analysis with hemodynamic parameters. Prognostic performance was evaluated using Cox regression, Time-Dependent Receiver Operating Characteristic (time-dependent ROC) curve analysis, stratified analysis, and decision curve analysis (DCA). Linear prediction models for invasive hemodynamic parameters were established using variable selection and internal validation. A total of 179 patients with pre-capillary pulmonary hypertension were included. Using LASSO-Cox and random survival forest, 13 core prognostic variables were identified, including total bilirubin (TB) and B-type natriuretic peptide (BNP). The novel hepatic-cardiac index--TBI (log [total bilirubin × BNP]) was constructed and validated as an independent prognostic factor (HR=1.64, 95%CI: 1.287–2.09, P=0.0001). Predictive efficacy at 36 months was significantly higher for TBI (area under the curve, AUC = 0.777) than for BNP (AUC = 0.723, <i>P</i> = 0.021 with false discovery rate [FDR] adjustment). Stratified analysis confirmed that TBI remained prognostic in patients with BNP levels between 200 and 800 pg/mL (χ<sup>2</sup>=7.075, P = 0.008). Additionally, non-invasive linear prediction models for mean pulmonary arterial pressure(mPAP), pulmonary vascular resistance (PVR), and PVR×CO (cardiac output) were established with moderate accuracy (R<sup>2</sup>=0.575, 0.507, 0.523, respectively) Integration of laboratory and echocardiographic parameters enables improved non-invasive evaluation in pulmonary hypertension. The novel hepatic-cardiac index (TBI, log[TB×BNP]) serves as a robust and independent prognostic biomarker. Routine non-invasive indices can reliably estimate key hemodynamic parameters in clinical practice.</p>

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Development and validation of novel prognostic hepatic-cardiac index and hemodynamic prediction models in pre-capillary pulmonary hypertension patients

  • Jun Tong,
  • An Wang,
  • Chuanxue Wan,
  • Mengqi Chen,
  • Qi Zhuang,
  • Binqian Ruan,
  • Jinyao Jiang,
  • Menghui Yang,
  • Jieyan Shen

摘要

Pulmonary arterial hypertension (PAH) is a life-threatening disorder marked by progressive elevation of pulmonary vascular resistance and ultimate right heart failure. Its diagnosis and risk stratification largely depend on invasive right heart catheterization (RHC). This study aimed to integrate routine laboratory and echocardiographic data to develop a novel multi-organ prognostic indicator and construct non-invasive hemodynamic estimation prediction models. This was a multi-center retrospective study enrolling a total of 44 routine laboratory and echocardiographic indices of pre-capillary pulmonary hypertension. Key prognostic variables were screened using Least absolute shrinkage and selection operator-Cox (LASSO-Cox) regression and random survival forest (RSF) analysis. The novel composite index was constructed based on correlation analysis with hemodynamic parameters. Prognostic performance was evaluated using Cox regression, Time-Dependent Receiver Operating Characteristic (time-dependent ROC) curve analysis, stratified analysis, and decision curve analysis (DCA). Linear prediction models for invasive hemodynamic parameters were established using variable selection and internal validation. A total of 179 patients with pre-capillary pulmonary hypertension were included. Using LASSO-Cox and random survival forest, 13 core prognostic variables were identified, including total bilirubin (TB) and B-type natriuretic peptide (BNP). The novel hepatic-cardiac index--TBI (log [total bilirubin × BNP]) was constructed and validated as an independent prognostic factor (HR=1.64, 95%CI: 1.287–2.09, P=0.0001). Predictive efficacy at 36 months was significantly higher for TBI (area under the curve, AUC = 0.777) than for BNP (AUC = 0.723, P = 0.021 with false discovery rate [FDR] adjustment). Stratified analysis confirmed that TBI remained prognostic in patients with BNP levels between 200 and 800 pg/mL (χ2=7.075, P = 0.008). Additionally, non-invasive linear prediction models for mean pulmonary arterial pressure(mPAP), pulmonary vascular resistance (PVR), and PVR×CO (cardiac output) were established with moderate accuracy (R2=0.575, 0.507, 0.523, respectively) Integration of laboratory and echocardiographic parameters enables improved non-invasive evaluation in pulmonary hypertension. The novel hepatic-cardiac index (TBI, log[TB×BNP]) serves as a robust and independent prognostic biomarker. Routine non-invasive indices can reliably estimate key hemodynamic parameters in clinical practice.