Abstract

Background: An electrocardiogram (ECG)-based artificial intelligence (AI) algorithm has shown good performance in detecting hypertrophic cardiomyopathy (HCM AI-score). However, its clinical application may be challenging due to the low disease prevalence and potentially high false-positive rate when screening unenriched cohorts. Aims: To identify clinical characteristics associated with false-positive HCM AI-score results to improve screening tool application. Methods: From a cohort of 20,677 patients with a digital 12-lead ECG in routine clinical practice in 2021, we performed a detailed chart review of the 200 patients with highest HCM AI-score to determine their HCM status and collect clinical data. Stepwise forward logistic regression was used to create a clinical variable-based “candidacy for HCM screening” score (CHS score), differentiating true- and likely true-positive from likely false-positive HCM AI-score results. We then validated the CHS score in 200 patients with the highest HCM AI-scores from an independent cohort of 15,147 patients with an ECG in 2022. Results: Among the 200 patients in 2021 (median age 71 years, 48% female), 96 (48%) were likely false-positive HCM AI-score results, 71 (36%) definite or likely true-positive results, and 33 (16%) indeterminate. The CHS score included a history of surgical septal myectomy, coronary artery bypass graft surgery, cardiac valve replacement, and pacemaker, and had an AUC of 0.88 (95% CI 0.83-0.92) for the differentiation of true- versus false-positive AI results. In the 2022 cohort, the CHS score had an AUC of 0.82 (95% CI 0.76 - 0.88). After limiting the cohort to HCM candidates identified by the CHS score, the false-positive results rate was reduced to 27/114 (24%). Conclusions: By applying the CHS score to patients with positive HCM AI-screening results, the false-positive rate decreased from 49% to 24%. Utilizing a clinical model used in tandem with an AI model improved diagnostic yield.

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