Background: Sudden cardiac death (SCD) due to ventricular tachycardia/ventricular fibrillation (VT/VF) remains a leading cause of mortality after myocardial infarction (MI). Existing management strategies fail to capture the dynamic, multifactorial lifelong evolution of arrhythmic risks.
Methods: We developed a discrete-time, state-transition microsimulation model to simulate lifetime trajectories of post-MI VT/VF. The model comprised 5 health states, including healthy, MI with SCD, MI without SCD, VT/VF, and death, with age- and sex-dependent transition probabilities calculated at daily resolution. Additionally, post-MI remodeling was modeled dynamically through phenomenological representations of left ventricular ejection fraction (LVEF) changes and progressive arrhythmogenic substrate accumulation, which was dependent on individual clinical history and fed back into VT/VF risks. Model calibration was performed in virtual cohorts of 10,000 individuals by matching simulated all-cause mortality, MI incidence, and temporal patterns of post-MI VT/VF incidence to real-world data.
Results: At the individual level, the model generated detailed longitudinal event histories for virtual patients. At the population level, the model reproduced key epidemiological trend, including age- and sex-dependent increases in MI incidence and mortality, with higher risks in males and older individuals. Importantly, it captured the clinically observed temporal pattern of post-MI VT/VF incidence, with an early peak within 48 hours, a secondary peak at 1–2 weeks, and a subsequent plateau phase.
Conclusion: This study presents a novel, mechanistically-informed microsimulation framework linking dynamic post-MI ventricular remodeling to long-term population-level outcomes. By bridging mechanistic and epidemiological scales, the model has the potential to explore personalized risks and provides a platform for virtual randomized clinical trials to optimize post-MI VT/VF management strategies, such as the implantation of cardioverter-defibrillators.