Causative predictors of sudden cardiac death after myocardial infarction

Sudden cardiac death (SCD) is a natural death due to cardiac causes within one hour of acute symptoms onset. It’s preventable by implantable cardioverter-defibrillators (ICDs), recommended only for post-infarction patients with left ventricular ejection fraction (LVEF) < 35%. However, LVEF is an insensitive and non-specific SCD predictor with many false negatives, and no other marker has proven clinically useful. This project explores the predictive value of phenotypic and genetic variables to enhance SCD risk models in post-MI patients, using Mendelian randomization on two cohorts. Dataset 1 derives from the IGSEMI case-control study on early-onset MI genetics, while Dataset 2 involves 1000 prospectively recruited post-MI patients from 25 Italian centres. Preliminary data on patients at risk of SCD presented a worse clinical profile, including higher rates of hypertension, diabetes, prior thromboembolic events, severe coronary atherosclerosis (higher SYNTAX scores), and lower post-event LVEF. Multivariable analysis confirmed diabetes, hypertension, thromboembolism history, increased atherosclerotic burden, and reduced LVEF as independent SCD predictors during follow-up. No monogenic variants with significant discriminatory power for SCD/VAs were identified, but analysis is ongoing, including patients with clinical VAs and/or appropriate ICD activations to increase statistical power. This study shows that young MI survivors face a significant long-term risk of sudden cardiac death driven by progressive coronary disease, with predictors including classic risk factors, reduced LVEF, and high coronary atherosclerosis burden. Clinically, it stresses aggressive risk-factor management, use of angiographic markers like SYNTAX score for better stratification, periodic LVEF imaging, and sustained secondary prevention for this understudied group.