Sai Kumar Samala, Khashayar Hematpour, Ramesh Hariharan, Danai Kitkungvan, Sriram Nathan, Biswajit Kar, Jagat Narula, Prapannajeet Biswal, Khashayar Fattah, Xander H T Wehrens, Sotirios Nedios, Felix Hohendanner, Joanne Alfieri, Martin L Bernier, Kenneth W Merrell, Konstantinos C Siontis, Alejandro Vidal Margenat, Sunil Krishnan
Stereotactic arrhythmia radioablation (STAR) is a novel and emerging treatment approach for managing treatment-refractory ventricular arrhythmias (VAs), particularly in patients deemed ineligible for or failing antiarrhythmic medications and catheter ablation. Preclinical studies suggest that STAR generates reactive oxygen species and causes rapid ultrastructural changes in cardiomyocytes, with ion channel modulation and gap junction remodeling that result in electrophysiological reprogramming. Several clinical studies have demonstrated the safety and efficacy of STAR, showing a significant reduction in arrhythmia burden with a low risk of severe treatment-related complications. Despite these promising results, the recurrence rate reported is still high, especially in patients with advanced heart failure. The convergence of advancements and refinements in procedural workflows, such as noninvasive electrocardiographic imaging, respiratory and cardiac motion management strategies, and the seamless integration of multiple radiographic imaging modalities for radiation treatment planning, promises to enhance treatment delivery accuracy and precision. However, questions remain regarding the optimal dose regimens, patient selection criteria, and potential long-term toxicities. Ongoing clinical trials and preclinical studies will provide further insights that can help improve the current practice. STAR is currently considered investigational pending randomized controlled trials comparing it with standard therapies. This review critically appraises STAR's readiness for broader clinical adoption, examining molecular mechanisms, treatment planning and delivery strategies, clinical outcomes and their heterogeneity, safety concerns, emerging beam technologies, and practical considerations for multidisciplinary teams establishing new STAR programs.