Cardio Amyloid-AI: Advanced Multimodal Screening for Transthyretin Cardiac Amyloidosis in Severe Aortic Stenosis Patients

Abstract Background and Aims Early detection is important given the availability of new disease-modifying therapies and the high prevalence of transthyretin amyloid cardiomyopathy (ATTR-CM) among patients with aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). We developed a multimodal artificial intelligence (AI) model for early detection of ATTR-CM using chest computed tomography (CT), echocardiography, and electrocardiography. This approach may provide a scalable strategy for preclinical monitoring. Methods This retrospective study included patients who underwent technetium-99m–pyrophosphate scintigraphy (PYP) at two academic medical centers: Columbia University Irving Medical Center and Weill Cornell Medicine. ATTR-CM status was determined using a composite reference standard incorporating PYP scan interpretation, laboratory tests, and endomyocardial biopsy results when available. The diagnostic performance of the model was measured by the area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, and predictive values at various thresholds. Results Among 816 patients (median age 79.0 years, 61.2% male), 127 (15.6%) had confirmed ATTR-CM. Patients with ATTR-CM were older, more often male, and had characteristic echocardiographic features, including increased wall thickness and reduced ejection fraction. In the independent TAVR test cohort, the multimodal AI model achieved an AUROC of 0.85 (95% CI: 0.74-0.93), significantly outperforming single-modality approaches in our data. At the optimal threshold, the model demonstrated 73.3% sensitivity, 82.9% specificity, and 96% negative predictive value. Conclusion and Relevance A multimodal AI approach using routinely acquired chest computed tomography, echocardiography, and electrocardiography data can enable screening for ATTR-CM in TAVR patients, potentially facilitating earlier diagnosis and treatment initiation.