Clinical impact of circulating biomarkers in prediction of adverse cardiac events in patients with congenital heart disease: A systematic review

Introduction: Patients with congenital heart disease (ConHD) are at increased risk for adverse cardiac events. Predicting long-term outcomes and guidance of patient management might benefit from a range of (new) biomarkers. This is a rapidly evolving field with potentially large consequences for clinical decision making. With a systematic review of available biomarkers in ConHD we identified the clinical role of these markers, knowledge gaps and future research directions. Methods: We systematically reviewed the literature on associations between blood biomarkers and outcome measures (mortality or composite adverse outcomes in patients with ConHD. Results: The inclusion criteria were met by 102 articles. Biomarkers assessed in more than 3 studies are discussed in the main text, those studied in 3 or less studies are summarized in the supplement. Thus, we discuss 15 biomarkers from 92 studies. These biomarkers were studied in 32,399 / 10,735 patients for the association with mortality and composite adverse outcomes, respectively. Biomarkers that were studied most and had statistically significant associations with mortality or composite adverse outcomes were (NT-pro)BNP, MELD-XI score, Hs-CRP, creatinine, albumin and sodium. Most of these biomarkers are involved in intracardiac processes associated with inflammation or are markers of renal function. Conclusion: For (NT-pro)BNP, clinical value for prediction of mortality and composite adverse outcomes in adult and paediatric ConHD has been shown. For MELD-XI, hs-CRP, albumin, creatinine, sodium, RDW, and GDF-15, correlations with mortality and composite adverse outcomes have been demonstrated in patient groups with mixed types of ConHD, but clinical utility needs additional exploration.