Validation of Sudden Cardiac Arrest Risk Factors in Patients With CAD

Sudden cardiac arrest (SCA) and sudden cardiac death (SCD) are most commonly caused by malignant ventricular arrhythmias in patients with underlying coronary artery disease (CAD). Current risk stratification strategies, largely based on left ventricular ejection fraction, identify only a minority of patients who will experience SCA/SCD. Traditional cardiovascular risk factors lack sufficient specificity for arrhythmic death and are frequently associated with competing non-arrhythmic mortality. Improved, biologically informed risk prediction tools are therefore needed.

This prospective, multicenter observational study is designed to validate and refine multimodal risk prediction models for SCA/SCD in patients with imaging-confirmed CAD. Recruitment is planned between 2024 and 2026 across centers in Finland, Israel, Romania, and Moldova, with long-term follow-up extending up to 10-15 years. The anticipated total sample size is approximately 1,500-2,000 participants.

Baseline data collection includes comprehensive clinical information, imaging findings, electrocardiographic parameters, circulating biomarkers, lifestyle factors, and genetic samples. Imaging and biosignal data are stored in standardized digital formats to enable advanced analyses. Biological samples are stored for future genomic (including full genome sequencing and RNA expression data) and molecular analyses. All participants receive guideline-directed care; no experimental interventions are introduced.

The primary objective is to evaluate the performance of an AI-based risk assessment framework in identifying CAD patients at elevated risk of SCA/SCD, particularly during the first year after coronary angiography, and to assess its long-term predictive performance. Additional objectives include validation of previously reported arrhythmic risk markers, development of updated multivariable risk models, and evaluation of postoperative atrial fibrillation risk in patients undergoing coronary artery bypass grafting.

Primary endpoints include incident SCA, SCD, or equivalent malignant ventricular arrhythmic events. Secondary endpoints include major cardiovascular events, device therapies, heart failure hospitalization, new-onset atrial fibrillation, and all-cause mortality. Endpoints are adjudicated locally by blinded physician panels based on registry data and clinical documentation, with competing causes of death taken into account in the analyses.

Data analysis focuses on evaluating associations between predefined exposure variables and clinical outcomes, validating predictive models across participating centers, and applying federated analytical approaches when appropriate to enable cross-population validation without sharing individual-level data.

The study is observational and does not alter patient management. All procedures comply with applicable regulatory and ethical requirements. Genetic and exploratory biomarker analyses are conducted for research purposes only and are not returned to participants.

Inclusion criteria

• Age ≥ 18 years old
• Ability to give informed consent
• Imaging confirmed diagnosis within the past 12 months (coronary artery angiography or contrast enhanced coronary computed tomography)

•>50% of stenosis and/or fractional flow-reserve <0.8 verified by selective coronary angiography or by contrast enhanced coronary computed tomography (CT) or type I MI with atherosclerotic origin (despite stenosis percentage)

• Patients may be recruited during index event visit (out-patient clinic visit, invasive procedure, hospitalization) (or if logistically possible recall patients previously diagnosed within 12 months)

Exclusion criteria

• Age > 75 years of age
• Clinically significant previously treated valvular heart disease or requiring operative (surgical or endovascular) treatment within following three months
• Diagnosed severe neurodegenerative disease (ALS, myositis, multiple sclerosis, or Parkinson's disease) or known impaired cognitive function (MMSE <23)
• Known developmental disability impairing legal ability to give written consent
• Serious/active malignancy with possibly reduced life expectancy of <1 year (estimated by a physician)
• Inability to give written consent for some other reason
• Other significant cardiac condition severely linked to the risk of fatal ventricular arrhythmia (for example ARVCD, non-ischemic DCM, HCM or genetic long or short QT syndrome)
• Other cardiac disease with <1 years of life expectancy
• Do-Not-Resuscitate (DNR) order made due to any reason
• Previously done or planned cardiac, renal, or liver transplant
• Participation in another clinical trial where the active treatment