Supplementary Material for: Role of adrenomedullin as a prognostic biomarker in acute heart failure patients: a systematic review and meta-analysis

Introduction: Residual congestion is associated with a high rehospitalization rate in acute heart failure (HF) patients. This study aims to evaluate the role of adrenomedullin (MR-pro ADM and bio-ADM) as a prognostic marker of tissue congestion with clinical outcomes in acute heart failure patients. Methods: Three databases were systematically searched until November 2024 to include both observational and post hoc clinical trial studies that suit the research question. Outcomes assessed are clinical outcomes of in-hospital mortality, composite outcome of all-cause mortality and major adverse cardiovascular events (MACEs), and heart failure rehospitalization. Statistical analyses conducted are pooled hazard ratio, correlation coefficient, and area under the curve (AUC) with a random effect model. Results: Twenty-one studies of 18,110 patients with low to medium risk of bias are included of which 20 of them are prospective cohort studies. Both MR-pro ADM and bio-ADM measured at admission or discharge are associated with a statistically significant increasing risk of composite outcome, MACE outcome, and all-cause mortality (HR 1.17 – 2.72,). MR-pro ADM is also associated with a statistically significant increasing risk of in-hospital mortality and HF rehospitalization (HR 1.72 – 2.20). Bio-ADM measured at discharge is found to have a better prognostic value for all-cause mortality outcome than bio-ADM measured at admission (HR 1.90 and 1.17, respectively, p 0.007). MR-pro ADM showed a strong and moderate linear correlation with bio-ADM and NT-pro BNP (R 0.784, 0.461, respectively). Conclusion: MR-pro ADM and bio-ADM are both reliable prognostic markers in acute heart failure patients.