Zhang Feng, Lin Dawei, Jin Qi, Fan Jianing, Chen Dandan, Guan Lihua, Pan Wenzhi, Zhou Daxin
Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, National Clinical Research Center for Interventional Medicine, 200032 Shanghai, China.
Department of Cardiology, Jinshan Hospital, Fudan University, 201508 Shanghai, China.
Rev Cardiovasc Med. 2024 Jan 29;25(2):50. doi: 10.31083/j.rcm2502050. eCollection 2024 Feb.
Atrial septal defect (ASD) patients commonly experience severe pulmonary arterial hypertension (SPAH), which is frequently associated with a poor prognosis. While serum bilirubin levels, indicative of liver function, are known predictors of right heart failure (RHF), their potential to differentiate SPAH in ASD patients is yet to be ascertained. The purpose of this study was to discover the potential correlations between serum bilirubin levels and ASD patients with SPAH.
In this cross-sectional study, 102 ASD patients admitted from December 2019 to November 2020 were enrolled and divided into two cohorts: those with SPAH and those without. Blood tests were conducted to measure serum direct bilirubin (DBIL), total bilirubin (TBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), uric acid (UA) and N-terminal pro B-type natriuretic peptide (NT-proBNP). Additionally, all participants underwent transthoracic echocardiography, and invasive hemodynamic data were gathered through right heart catheterization.
ASD patients with SPAH exhibited significantly elevated serum DBIL (5.2 3.0 vs. 2.4 1.5 µmol/L, 0.001) and TBIL (24.6 20.7 vs. 10.1 4.8 µmol/L, 0.001) levels in comparison to those without SPAH. However, ALT and AST levels remained comparable between the cohorts. Additionally, the SPAH cohort displayed higher serum UA (403.5 131.6 vs. 317.8 67.9 µmol/L, 0.001) and NT-proBNP levels. Serum DBIL levels, when analyzed independently of other variables, correlated with an increased risk of mean pulmonary arterial pressure (mPAP) in ASD patients ( = 1.620, = 0.010). A DBIL concentration of 2.15 mg/dL effectively differentiated ASD patients with SPAH from those without, with a sensitivity of 92.9% and a specificity of 51.4% (area under the curve [AUC]: 0.794, 95% confidence interval [CI]: 0.701-0.886, 0.001). Notably, the combination of DBIL and UA had a higher sensitivity of 92.9% and specificity of 71.6% (AUC: 0.874, 95% CI: 0.799-0.949, 0.001).
Elevated serum DBIL and TBIL levels in ASD patients with SPAH were correlated with poor cardiac function and heightened pulmonary artery pressure. The combination of DBIL and UA has emerged as a strong noninvasive predictor for SPAH in ASD patients, presenting a potentially novel therapeutic biomarker.
房间隔缺损（ASD）患者常出现严重的肺动脉高压（SPAH），这通常与预后不良相关。虽然血清胆红素水平可反映肝功能，是已知的右心衰竭（RHF）预测指标，但其在区分ASD患者SPAH方面的潜力尚未确定。本研究的目的是发现血清胆红素水平与ASD合并SPAH患者之间的潜在相关性。
在这项横断面研究中，纳入了2019年12月至2020年11月收治的102例ASD患者，并将其分为两个队列：有SPAH的患者和无SPAH的患者。进行血液检测以测量血清直接胆红素（DBIL）、总胆红素（TBIL）、谷丙转氨酶（ALT）、谷草转氨酶（AST）、尿酸（UA）和N末端B型利钠肽原（NT-proBNP）。此外，所有参与者均接受经胸超声心动图检查，并通过右心导管插入术收集有创血流动力学数据。
与无SPAH的ASD患者相比，有SPAH的ASD患者血清DBIL（5.2±3.0 vs. 2.4±1.5 μmol/L, P<0.001）和TBIL（24.6±20.7 vs. 10.1±4.8 μmol/L, P<0.001）水平显著升高。然而，两个队列之间的ALT和AST水平相当。此外，SPAH队列的血清UA（403.5±131.6 vs. 317.8±67.9 μmol/L, P<0.001）和NT-proBNP水平更高。独立于其他变量分析时，血清DBIL水平与ASD患者平均肺动脉压（mPAP）升高风险相关（β = 1.620, P = 0.010）。DBIL浓度为2.15 mg/dL可有效区分有SPAH和无SPAH的ASD患者，敏感性为92.9%，特异性为51.4%（曲线下面积[AUC]：0.794, 95%置信区间[CI]：0.70,1-0.886, P<0.001）。值得注意的是,DBIL和UA联合检测具有更高敏感性（92.9%）和特异性（71.6%）（AUC：0.874, 95% CI：0.799-0.949, P<0.001）。
ASD合并SPAH患者血清DBIL和TBIL水平升高与心功能不良及肺动脉压升高相关.DBIL和UA联合检测已成为ASD患者SPAH的有力无创预测指标，是一种潜在新型治疗生物标志物。
