Stereotactic arrhythmia radioablation: radiobiology, clinical evidence, and emerging applications

STereotactic Arrhythmia Radioablation (STAR) has emerged as a promising non-invasive treatment for patients with refractory cardiac arrhythmias who are unsuitable for or have failed conventional catheter ablation. Initially developed for ventricular tachycardia (VT), STAR has demonstrated encouraging efficacy in reducing arrhythmia burden while avoiding the risks associated with invasive procedures. More recently, limited and early clinical experience has explored the potential application of STAR in paroxysmal atrial fibrillation (AF), including the feasibility of non-invasive pulmonary vein isolation; however, clinical evidence in AF remains anecdotal and investigational. Despite these advances, the biological mechanisms underlying STAR remain incompletely understood. While early hypotheses attributed its therapeutic effects primarily to radiation-induced fibrosis, accumulating evidence suggests that rapid anti-arrhythmic effects are mediated by early electrophysiological reprogramming and conduction remodeling, whereas delayed vascular injury, inflammation, and fibrosis may contribute to durable substrate modification and long-term toxicity. This evolving paradigm has important implications for optimizing radiation dose, fractionation strategies, and minimizing cardiac toxicity. Advances in imaging, electroanatomical mapping, and treatment planning are further improving treatment precision. Ongoing prospective clinical trials and international collaborative initiatives are expected to provide robust evidence regarding efficacy, safety, and long-term outcomes. This review summarizes current knowledge on the radiobiological mechanisms, clinical applications, and future perspectives of STAR, highlighting the key challenges for its integration into contemporary cardiac electrophysiology, as well as describing our current clinical trial investigating the role of dose and fractionation for this technique.