Mechanistic insights and knowledge gaps in the effects of radiation therapy on cardiac arrhythmias

Stereotactic body radiation therapy (SBRT) is an innovative modality for treatment of refractory ventricular arrhythmias (VA). Phase I/II clinical trials have demonstrated the remarkable efficacy of SBRT at reducing VA burden(by>85%) in patients with good short-term safety. SBRT as an option for VA treatment delivered in an ambulatory, non-sedated patient in a single fraction, during an outpatient session of 15–30 minutes, without added risks of anesthetic or surgery is clinically relevant. However, the underlying mechanism remains unclear. Currently used clinical dosing of SBRT has been derived from preclinical studies aimed to induce transmural fibrosis in the atria. The propitious clinical effects of SBRT appear earlier than the time-course for fibrosis. This review addresses the plausible mechanisms by which radiation alters the electrophysiological properties of myocytes and myocardial conduction to impart an anti-arrhythmic effect to elucidate clinical observations and point the direction for further research in this promising area.