Deep Learning-Based Risk Assessment and Prediction of Cardiac Outcomes Using Single-Lead 24-Hour Holter-ECG in Patients with Heart Failure or Myocardial Infarction

<b>Background:</b> Deep learning (DL) models using Holter-ECG may enhance risk stratification after heart failure (HF) or myocardial infarction (MI). <b>Objective:</b> To evaluate the prognostic performance of a Holter-based DL model for predicting major adverse cardiac events (MACE), compared with conventional noninvasive markers. <b>Methods:</b> In the K-REDEFINE study, 1108 patients with acute MI or HF underwent 24 h Holter monitoring. A DL model was trained using raw Holter-ECG data and tested for predicting a composite of cardiac death and ventricular arrhythmias. Its performance was compared with heart rate turbulence (HRT), T-wave alternans (TWA), and ejection fraction (EF). <b>Results:</b> During follow-up, 56 adjudicated cardiac deaths (1.18%/yr) and 21 ventricular arrhythmias (0.44%/yr) occurred. The DL model showed an area under the receiver operating characteristic curve (AUROC) of 0.74 (95% CI, 0.70-0.77) for the composite outcome, improving to 0.77 (0.74-0.81) when combined with EF. In comparison, HRT and TWA showed lower AUROCs of 0.62 and 0.55, respectively. For cardiac death alone, the AUROC reached 0.79, further improving to 0.82 with EF. Model-derived risk stratification revealed a seven-fold increase in cardiac death risk in the high-risk group compared to the low-risk group (HR 7.47, 95% CI 2.24-24.96, <i>p</i> < 0.001). This stratification remained particularly effective in patients with EF > 40%. <b>Conclusions:</b> A DL algorithm trained on single-lead Holter-ECG data effectively predicted cardiac death and ventricular arrhythmia. Its performance surpassed conventional markers and was further enhanced when integrated with EF, supporting its potential for noninvasive, scalable risk stratification.