Evaluating the Performance and Potential Bias of Predictive Models for Detection of Transthyretin Cardiac Amyloidosis

Delays in the diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM) contribute to the significant morbidity of the condition, especially in the era of disease-modifying therapies. Screening for ATTR-CM with artificial intelligence and other algorithms may improve timely diagnosis, but these algorithms have not been directly compared.

The aim of this study was to compare the performance of 4 algorithms for ATTR-CM detection in a heart failure population and assess the risk for harms due to model bias.

We identified patients in an integrated health system from 2010 to 2022 with ATTR-CM and age- and sex-matched them to controls with heart failure to target 5% prevalence. We compared the performance of a claims-based random forest model (Huda et al model), a regression-based score (Mayo ATTR-CM), and 2 deep learning echo models (EchoNet-LVH and EchoGo Amyloidosis). We evaluated for bias using standard fairness metrics.

The analytical cohort included 176 confirmed cases of ATTR-CM and 3,192 control patients with 79.2% self-identified as White and 9.0% as Black. The Huda et al model performed poorly (AUC: 0.49). Both deep learning echo models had a higher AUC when compared to the Mayo ATTR-CM Score (EchoNet-LVH 0.88; EchoGo Amyloidosis 0.92; Mayo ATTR-CM Score 0.79; DeLong P < 0.001 for both). Bias auditing met fairness criteria for equal opportunity among patients who identified as Black.

Deep learning, echo-based models to detect ATTR-CM demonstrated best overall discrimination when compared to 2 other models in external validation with low risk of harms due to racial bias.