Single-lead ECG biomarkers for cardiovascular and mortality risk prediction

Cardiovascular disease remains one of the leading causes of morbidity and mortality worldwide, highlighting the need for accurate risk prediction. Atrial fibrillation burden (AFB), premature ventricular contraction burden (PVCB), and T-wave alternans (TWA) have been individually associated with adverse outcomes. We hypothesized that these three digital ECG biomarkers provide complementary prognostic information for major cardiovascular endpoints and all-cause mortality, and developed a machine learning approach combining these biomarkers for risk prediction.

We analyzed 81,362 Holter recordings from 54,395 individuals across 20 primary care centers in Israel. A random forest model using AFB, PVCB, TWA, and age was trained to predict 5-year risk of heart failure (HF), ischemic stroke (IS), and all-cause mortality (ACM).

On the test set, best AUROCs were for HF 0.75 [95% CI: 0.74-0.77] (n_{pos}=622), for IS 0.69 [0.66-0.71] (n_{pos}=365), and for ACM 0.79 [0.77-0.80] (n_{pos}=1060). Combining the three ECG-derived biomarkers showed complementary predictive value and improved discrimination by up to 10% over age alone in individuals aged <75 years.

AFB, PVCB, and TWA contribute complementary prognostic information for risk stratification. When combined with age, these biomarkers improve predictive performance compared with age alone.