Artificial Intelligence-Enhanced Risk Stratification of Cancer Therapeutics-Related Cardiac Dysfunction Using Electrocardiographic Images.

Background: Risk stratification strategies for cancer therapeutics-related cardiac dysfunction (CTRCD) rely on serial monitoring by specialized imaging, limiting their scalability. We aimed to examine an application of artificial intelligence (AI) to electrocardiographic (ECG) images as a surrogate for imaging risk biomarkers, and its association with early CTRCD. Methods: Across a U.S.-based health system (2013-2023), we identified 1,550 patients (age 60 [IQR:51-69] years, 1223 [78.9%] women) without cardiomyopathy who received anthracyclines and/or trastuzumab for breast cancer or non-Hodgkin lymphoma and had ECG performed ≤12 months before treatment. We deployed a validated AI model of left ventricular systolic dysfunction (LVSD) to baseline ECG images and defined low, intermediate, and high-risk groups based on AI-ECG LVSD probabilities of <0.01, 0.01 to 0.1, and ≥0.1 (positive screen), respectively. We explored the association with early CTRCD (new cardiomyopathy, heart failure, or left ventricular ejection fraction [LVEF]<50%), or LVEF<40%, up to 12 months post-treatment. In a mechanistic analysis, we assessed the association between global longitudinal strain (GLS) and AI-ECG LVSD probabilities in studies performed within 15 days of each other. Results: Among 1,550 patients without known cardiomyopathy (median follow-up: 14.1 [IQR:13.4-17.1] months), 83 (5.4%), 562 (36.3%) and 905 (58.4%) were classified as high, intermediate, and low risk by baseline AI-ECG. A high- vs low-risk AI-ECG screen (≥0.1 vs <0.01) was associated with a 3.4-fold and 13.5-fold higher incidence of CTRCD (adj.HR 3.35 [95%CI:2.25-4.99]) and LVEF<40% (adj.HR 13.52 [95%CI:5.06-36.10]), respectively. Post-hoc analyses supported longitudinal increases in AI-ECG probabilities within 6-to-12 months of a CTRCD event. Among 1,428 temporally-linked echocardiograms and ECGs, AI-ECG LVSD probabilities were associated with worse GLS (GLS -19% [IQR:-21 to -17%] for probabilities <0.1, to -15% [IQR:-15 to -9%] for ≥0.5 [p<0.001]). Conclusions: AI applied to baseline ECG images can stratify the risk of early CTRCD associated with anthracycline or trastuzumab exposure in the setting of breast cancer or non-Hodgkin lymphoma therapy.