Environmental Exposures and Epigenetic Remodeling in Supraventricular Tachycardias: What Atrial Fibrillation Can and Cannot Tell Us

Supraventricular tachycardias (SVTs), including atrial fibrillation (AF), atrioventricular nodal re-entrant tachycardia (AVNRT), atrioventricular re-entrant tachycardia (AVRT), and focal atrial tachycardias, can possibly arise from the interaction of genetic predisposition and environmental exposures. While genome-wide association studies (GWASs) have identified 525 loci for atrial fibrillation and a small number of loci for AVNRT and accessory pathway-mediated tachycardia, the contribution of air pollution, lifestyle factors and psychosocial stress to epigenetic remodeling of atrial tissue remains insufficiently integrated into current mechanistic models of arrhythmogenesis. This review aims to synthesize evidence on how environmental exposures, including PM2.5, NO2, ozone, tobacco smoke, obesity, alcohol use, and physical inactivity, modulate epigenetic pathways relevant to SVT susceptibility, and to evaluate whether AF-derived epigenetic insights can be extrapolated to other SVTs. Thus, a narrative synthesis was conducted across studies examining environmental determinants, epigenetic mechanisms (DNA methylation, histone modifications, non-coding RNAs), and genetic susceptibility in SVTs. Literature from cardiac tissue studies, circulating epigenetic biomarker analyses, and mechanistic AF models was integrated to construct a unified gene–environment–epigenome framework. In atrial fibrillation, environmental exposures are consistently associated with epigenetic alterations affecting atrial electrophysiology, inflammation, oxidative stress and structural remodeling, and air pollutants and lifestyle factors modulate methylation signatures, histone-modifying enzymes and microRNA networks implicated in atrial conduction and re-entry. For AVNRT, AVRT and focal atrial tachycardia the evidential position is different. Large prospective cohort and case-crossover analyses now link air pollution to incident and acute supraventricular tachycardia, and genome-wide association studies have identified susceptibility loci for AVNRT and for accessory-pathway-mediated tachycardia, including one gene encoding a cardiac chromatin-remodeling protein; but no epigenomic profiling of nodal or accessory-pathway tissue has been reported, and no study has measured an environmental exposure, an atrial epigenetic mark and a non-AF SVT endpoint in the same participants. Twin data indicate that approximately 35% of SVT risk is attributable to genetic and 65% to unique environmental factors, which motivates a gene–environment–epigenome framework without validating its mechanistic detail outside AF. Mapping GWAS-identified loci onto environmentally responsive regulatory pathways identifies candidate convergence points between inherited risk and exposure-driven remodeling; for non-AF SVT, these are designated working hypotheses rather than established mechanisms. Air pollution and lifestyle factors are associated with supraventricular arrhythmia across the spectrum, and in atrial fibrillation there is direct evidence that they act, in part, through epigenetic reprogramming of atrial tissue. No epigenetic panel has been prospectively validated for the prediction of any supraventricular arrhythmia, and precision risk stratification therefore remains a research objective rather than a near-term clinical horizon. Integrating environmental exposure data with genetic and epigenomic profiling is nonetheless the most plausible route toward it. Future priorities include exposure-stratified, cell-resolved epigenomic profiling of atrial and nodal tissue, prospective validation of candidate circulating markers against incident arrhythmia, and replication in non-European populations and in both sexes.