Prevalence of arrhythmias and cardiac risks in adults with familial ST depression syndrome
P Tawde, D Savage-Lobeck, K Vijayaraghavan, M CastroAbstract
Introduction
Familial ST depression syndrome is an inherited cardiac condition characterized by persistent, nonischemic ST-segment depression on electrocardiogram (ECG) and heightened arrhythmia susceptibility. First described in 2018, this emerging clinical entity is associated with ion channel gene mutations (e.g., KCNQ1) and carries significant risks of sudden cardiac death (SCD), heart failure, and thromboembolic events. Despite growing recognition, comprehensive data on arrhythmia prevalence and associated cardiac risks remain fragmented across individual cohort studies.
Purpose
To synthesize evidence from peer-reviewed studies quantifying the prevalence of arrhythmias and the spectrum of cardiac risks in adults diagnosed with familial ST depression syndrome and to identify key predictors of adverse outcomes.
Methods
A systematic data synthesis was conducted across 50 peer-reviewed studies examining arrhythmia prevalence, cardiac outcomes, and risk factors in familial ST depression syndrome. Studies employed ECG screening, ambulatory Holter monitoring, and genetic testing for arrhythmia detection. Outcomes included atrial fibrillation (AF), ventricular tachycardia (VT), ventricular fibrillation (VF), heart failure, left ventricular (LV) dysfunction, and SCD. Prevalence rates were stratified by diagnostic approach, gender, age, genetic status, and comorbidities.
Results
Arrhythmia prevalence ranged from 13% to 60% depending on population and diagnostic methodology. In a Danish cohort (mean follow-up 9.3 years), 13% developed sustained ventricular arrhythmias or aborted SCD, 25% developed AF, and 25% developed LV ejection fraction ≤50%. Family-based genetic screening studies reported arrhythmia prevalence up to 60%, with higher rates in males. Routine ECG screening yielded a 15–30% prevalence. Serious ventricular arrhythmias (Lown 4–5) occurred in 29.4% of men with ST depression. AF was the most common supraventricular arrhythmia, associated with increased stroke and hospitalization risk. Arrhythmias conferred a 2.0–2.5-fold increased risk of heart failure. SCD risk was 5–10% over 10 years. Key predictors included male gender, older age, pathogenic ion channel variants, family history of sudden death, and comorbidities (hypertension, diabetes, and obesity).
Conclusion
Adults with familial ST depression syndrome exhibit substantially elevated arrhythmia prevalence (13–60%) compared to the general population, with AF and VT being most clinically significant. These arrhythmias are associated with a two- to 2.5-fold increased heart failure risk and a 5–10% decade-long SCD risk. Male gender, genetic mutations, and cardiovascular comorbidities are major risk determinants. These findings support systematic ECG surveillance, genetic testing in familial cases, and aggressive cardiovascular risk factor management in this population.