Noninvasive Monitoring of Severe Pulmonary Artery Hypertension in Atrial Septal Defect Patients: Role of Serum Bilirubin Combined with Uric Acid

¹ Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, National Clinical Research Center for Interventional Medicine, 200032 Shanghai, China

² Department of Cardiology, Jinshan Hospital, Fudan University, 201508 Shanghai, China

^*Correspondence: peden@sina.com (Wenzhi Pan); 1194180219@qq.com (Daxin Zhou)
^†These authors contributed equally.

Rev. Cardiovasc. Med. 2024, 25(2), 50; https://doi.org/10.31083/j.rcm2502050

Submitted: 19 April 2023 | Revised: 28 August 2023 | Accepted: 27 September 2023 | Published: 29 January 2024

This is an open access article under the CC BY 4.0 license.

Abstract

Background: 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. Methods: 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. Results: ASD patients with SPAH exhibited significantly elevated serum DBIL (5.2 $\pm{}$ 3.0 vs. 2.4 $\pm{}$ 1.5 µmol/L, p $<$ 0.001) and TBIL (24.6 $\pm{}$ 20.7 vs. 10.1 $\pm{}$ 4.8 µmol/L, p $<$ 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 $\pm{}$ 131.6 vs. 317.8 $\pm{}$ 67.9 µmol/L, p $<$ 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 ( $\beta{}$ = 1.620, p = 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, p $<$ 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, p $<$ 0.001). Conclusions: 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.

Keywords

severe pulmonary artery hypertension

atrial septal defect

bilirubin

uric acid

Funding

19MC1910300/Shanghai Clinical Research Center Project for Interventional Medicine

JYQN-JC-202010/Youth research project of Jinshan Hospital, Fudan University

Figures

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Fig. 1.

Serum biomarkers levels in ASD patients with or without SPAH. (A–F) demonstrated the serum DBIL, TBIL, NT-proBNP, UA, ALT, and AST level in ASD patients with and without SPAH groups respectively (*** means p $<$ 0.001, ns means p $>$ 0.5). Abbreviation: ASD, atrial septal defect; SPAH, severe pulmonary artery hypertension; DBIL, direct bilirubin; TBIL, total bilirubin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; UA, uric acid; NT-proBNP, N-terminal pro B-type natriuretic peptide.

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Rev. Cardiovasc. Med. Print ISSN 1530-6550 Electronic ISSN 2153-8174