Wearable Single-Lead ECG Detects Fine-Grained Structural Heart Disease Through Echo-Report Supervision

Abstract Structural heart disease (SHD) is a primary driver of heart failure and cardiovascular mortality, yet early detection remains constrained by the limited accessibility of echocardiography. While single-lead electrocardiogram (ECG) is ubiquitous through wearables, existing AI screening models often depend on 12-lead inputs, generalize poorly across institutions, or require massive, condition-specific labeled datasets. Recent work has demonstrated the feasibility of contrastive pre-training between single-lead ECGs and echocardiography reports within a single health system. Here, we present AnyECG-Echo, a framework that advance this paradigm toward clinical translation through three key developments: (1) evaluation in a geographically independent external cohort (n = 16,621); (2) diagnostic coverage of 13 fine-grained SHD subtypes spanning myocardial, chamber, valvular, and great-vessel pathologies; and (3) dual-axis mechanistic interpretability combining electrophysiology-grounded Shapley attribution with emergent correlations to quantitative measurements. Across validation cohorts totaling n = 25,222, the model demonstrated high AUROC for high-impact subtypes, including reduced left ventricular systolic functon(AUROC 0.866–0.924), global heart enlargement (0.877–0.931), and mitral stenosis (0.836–0.906). Furthermore, we successfully validated the alignment of model outputs with established medical physiological traits, thereby enhancing interpretability. Notably, we discovered that AnyECG-Echo’s outputs function as physiologically grounded digital biomarkers that accurately track objective metrics such as LVEF and myocardial wall thickness. These findings prove that wearable single-lead ECGs can effectively detect fine-grained structural heart disease, offering a practical solution for population-scale screening.