Bio‐Adrenomedullin Predicts Death and Major Adverse Cardiovascular Events in Cardiac Amyloidosis: A Cross‐Continental Multicenter Study

Background Bio‐ADM (bioactive adrenomedullin) is a vasoactive peptide hormone that predicts clinical outcomes in heart failure—the main driver of adverse outcomes in cardiac amyloidosis (CA). This prospective observational study sought to assess the prognostic role of bio‐ADM in CA. Methods Patients with CA were enrolled from amyloid centers in Germany (observation cohort), Japan, and the United States (combined validation cohort). Bio‐ADM was quantified using the sphingotest bio‐ADM assay. Associations of bio‐ADM with all‐cause death and major adverse cardiovascular events over 2 years were assessed using Kaplan–Meier and Cox regression analyses. Likelihood ratio chi‐square tests for nested models evaluated whether adding bio‐ADM improves validated prognostic staging systems. Results In both the German observation cohort (n=86) and the combined validation cohort from Japan and the United States (n=124), elevated bio‐ADM (>29 pg/mL) was associated with more frequent all‐cause death and major adverse cardiovascular events. Bio‐ADM remained independently associated with impaired overall ( P 29 pg/mL) significantly improved the prognostic accuracy of the National Amyloidosis Centre (C‐index 0.674 to 0.787; P =0.002) and MayoATTR (C‐index 0.662 to 0.757; P <0.001) staging systems for cardiac transthyretin amyloidosis. Adding bio‐ADM to staging systems for cardiac immunoglobulin light chain amyloidosis yielded no significant changes. Conclusions Bio‐ADM is a promising prognostic biomarker, especially in cardiac transthyretin amyloidosis, where it improved risk stratification when added to established staging systems. Further research is needed to clarify its role as part of staging systems for cardiac immunoglobulin light chain amyloidosis.