Background:Existing models for prediction of major adverse cardiovascular events (MACE) after repair of tetralogy of Fallot have been limited by modest predictive capacity and limited applicability to routine clinical practice. We hypothesized that an artificial intelligence model using an array of parameters would enhance 5-year MACE prediction in adults with repaired tetralogy of Fallot.Methods:A machine learning algorithm was applied to 2 nonoverlapping, institutional databases of adults with repaired tetralogy of Fallot: (1) for model development, a prospectively constructed clinical and cardiovascular magnetic resonance registry; (2) for model validation, a retrospective database comprised of variables extracted from the electronic health record. The MACE composite outcome included mortality, resuscitated sudden death, sustained ventricular tachycardia and heart failure. Analysis was restricted to individuals with MACE or followed ≥5 years. A random forest model was trained using machine learning (n=57 variables). Repeated random sub-sampling validation was sequentially applied to the development dataset followed by application to the validation dataset.Results:We identified 804 individuals (n=312 for development and n=492 for validation). Model prediction (area under the curve [95% CI]) for MACE in the validation dataset was strong (0.82 [0.74–0.89]) with superior performance to a conventional Cox multivariable model (0.63 [0.51–0.75];P=0.003). Model performance did not change significantly with input restricted to the 10 strongest features (decreasing order of strength: right ventricular end-systolic volume indexed, right ventricular ejection fraction, age at cardiovascular magnetic resonance imaging, age at repair, absolute ventilatory anaerobic threshold, right ventricular end-diastolic volume indexed, ventilatory anaerobic threshold % predicted, peak aerobic capacity, left ventricular ejection fraction, and pulmonary regurgitation fraction; 0.81 [0.72–0.89];P=0.232). Removing exercise parameters resulted in inferior model performance (0.75 [0.65–0.84];P=0.002).Conclusions:In this single-center study, a machine learning-based prediction model comprised of readily available clinical and cardiovascular magnetic resonance imaging variables performed well in an independent validation cohort. Further study will determine the value of this model for risk stratification in adults with repared tetralogy of Fallot.