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. 2025 Oct 1;46(37):3651-3662.
doi: 10.1093/eurheartj/ehaf450.

Artificial intelligence-enabled electrocardiography and echocardiography to track preclinical progression of transthyretin amyloid cardiomyopathy

Evangelos K Oikonomou  1   2 , Veer Sangha  1   2   3 , Sumukh Vasisht Shankar  1   2 , Andreas Coppi  2   4 , Harlan M Krumholz  1   4 , Khurram Nasir  5   6   7   8 , Edward J Miller  1 , Cesia Gallegos Kattan  1 , Mouaz H Al-Mallah  7 , Sadeer Al-Kindi  7   8 , Rohan Khera  1   2   4   9   10
Affiliations

Artificial intelligence-enabled electrocardiography and echocardiography to track preclinical progression of transthyretin amyloid cardiomyopathy

Evangelos K Oikonomou et al. Eur Heart J. .

Abstract

Background and aims: The diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM) requires advanced imaging, precluding large-scale preclinical testing. Artificial intelligence (AI)-enabled transthoracic echocardiography (TTE) and electrocardiography (ECG) may provide a scalable strategy for preclinical monitoring.

Methods: This was a retrospective analysis of individuals referred for nuclear cardiac amyloid testing at the Yale-New Haven Health System (YNHHS, internal cohort) and Houston Methodist Hospitals (HMH, external cohort). Deep learning models trained to discriminate ATTR-CM from age/sex-matched controls on TTE videos (AI-Echo) and ECG images (AI-ECG) were deployed to generate study-level ATTR-CM probabilities (0%-100%). Longitudinal trends in AI-derived probabilities were examined using age/sex-adjusted linear mixed models, and their discrimination of future disease was evaluated across preclinical stages.

Results: Among 984 participants at YNHHS (median age 74 years, 44.3% female) and 806 at HMH (median age 69 years, 34.5% female), 112 (11.4%) and 174 (21.6%) tested positive for ATTR-CM, respectively. Across cohorts and modalities, AI-derived ATTR-CM probabilities from 7352 TTEs and 32 205 ECGs diverged as early as 3 years before diagnosis in cases vs controls (ptime(x)group interaction ≤ .004). Among those with both AI-Echo and AI-ECG probabilities available 1 to 3 years before nuclear testing [n = 433 (YNHHS) sand 174 (HMH)], a double-negative screen at a 0.05 threshold [164 (37.9%) and 66 (37.9%), vs all else] had 90.9% and 85.7% sensitivity (specificity of 40.3% and 41.2%), whereas a double-positive screen [78 (18.0%) and 26 (14.9%), vs all else] had 85.5% and 88.9% specificity (sensitivity of 60.6% and 42.9%).

Conclusions: Artificial intelligence-enabled echocardiography and electrocardiography may enable scalable risk stratification of ATTR-CM during its preclinical course.

Keywords: Artificial intelligence; Cardiac amyloidosis; Echocardiography; Electrocardiography; Screening; Transthyretin.

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References

    1. Writing Committee; Kittleson MM, Ruberg FL, Ambardekar AV, Brannagan TH, Cheng RK, et al. 2023 ACC expert consensus decision pathway on comprehensive multidisciplinary care for the patient with cardiac amyloidosis: a report of the American College of Cardiology solution set oversight committee. J Am Coll Cardiol 2023;81:1076–126. 10.1016/j.jacc.2022.11.022 - DOI - PubMed
    1. Tanskanen M, Peuralinna T, Polvikoski T, Notkola I-L, Sulkava R, Hardy J, et al. Senile systemic amyloidosis affects 25% of the very aged and associates with genetic variation in alpha2-macroglobulin and tau: a population-based autopsy study. Ann Med 2008;40:232–9. 10.1080/07853890701842988 - DOI - PubMed
    1. Scully PR, Treibel TA, Fontana M, Lloyd G, Mullen M, Pugliese F, et al. Prevalence of cardiac amyloidosis in patients referred for transcatheter aortic valve replacement. J Am Coll Cardiol 2018;71:463–4. 10.1016/j.jacc.2017.11.037 - DOI - PMC - PubMed
    1. Castaño A, Narotsky DL, Hamid N, Khalique OK, Morgenstern R, DeLuca A, et al. Unveiling transthyretin cardiac amyloidosis and its predictors among elderly patients with severe aortic stenosis undergoing transcatheter aortic valve replacement. Eur Heart J 2017;38:2879–87. 10.1093/eurheartj/ehx350 - DOI - PMC - PubMed
    1. AbouEzzeddine OF, Davies DR, Scott CG, Fayyaz AU, Askew JW, McKie PM, et al. Prevalence of transthyretin amyloid cardiomyopathy in heart failure with preserved ejection fraction. JAMA Cardiol 2021;6:1267–74. 10.1001/jamacardio.2021.3070 - DOI - PMC - PubMed

Supplementary concepts