Screening for patients at risk for cardiac amyloidosis via electronic health records: A multicenter machine learning development and validation study
Journal:
medRxiv
Published Date:
Apr 28, 2026
Abstract
Background Timely detection is crucial to improve outcomes in patients with cardiac amyloidosis (CA) by initiation of life-saving treatments. Although confirmatory bone scintigraphy is highly accurate for CA detection, identifying at-risk patients for referral remains challenging. Objectives This study aimed to develop and validate a machine learning model, Amylo-Detect, using structured multimodal electronic health record (EHR) data to guide referrals for confirmatory scintigraphy and monoclonal protein testing. Methods Consecutive all-comer patients (n=11,616) referred for bone scintigraphy at the Vienna General Hospital (2010-2023) were retrospectively included. Patients referred before August 2020 formed the development cohort. The remaining patients comprised the internal validation cohort. External validation was performed at the University Hospital Essen (n=1,521). Amylo-Detect was trained using 50 routinely available parameters to predict CA-suggestive uptake (Perugini grade >=2) and compared with an existing score and clinical routine. Results High-grade uptake was present in 388 patients (3.0%). Amylo-Detect demonstrated excellent performance in development (AUC 0.93), independent internal validation (AUC 0.91), and external validation cohort (AUC 0.91), outperforming existing scoring systems and clinical routine. Results were consistent across subgroups, even when crucial predictors were missing. Of the 42/388 (10.8%) patients missed in clinical routine, 12/42 (29%) were additionally detected by Amylo-Detect. The model further conveyed significant prognostic value for mortality and heart failure hospitalization. Conclusions We present Amylo-Detect, a validated EHR-based tool for CA risk prediction, available as a web app, allowing application and further evaluation. By improving timely detection and referral, Amylo-Detect promises to address diagnostic delays and improve outcomes.
