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

Evangelos K. Oikonomou, Veer Sangha, Sumukh Vasisht Shankar, Andreas Coppi, Harlan M. Krumholz, Khurram Nasir, Edward J. Miller, Cesia Gallegos Kattan, Mouaz H. Al-Mallah, Sadeer Al-Kindi, Rohan Khera

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)3651-3662
Number of pages12
JournalEuropean heart journal
Volume46
Issue number37
DOIs
StatePublished - Oct 1 2025

Keywords

  • Artificial intelligence
  • Cardiac amyloidosis
  • Echocardiography
  • Electrocardiography
  • Screening
  • Transthyretin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Fingerprint

Dive into the research topics of 'Artificial intelligence-enabled electrocardiography and echocardiography to track preclinical progression of transthyretin amyloid cardiomyopathy'. Together they form a unique fingerprint.

Cite this