STAR Locally Prolongs Effective Refractory Period and Increases Ventricular Tachycardia Cycle Length Without Short-Term Scar Formation or Functional Decline: Insights From a Translational Porcine Model Study.

Background: Stereotactic arrhythmia radiotherapy (STAR) has emerged as a potential therapy for treatment-refractory ventricular tachycardia (VT). However, the mechanisms underlying STAR efficacy, such as scar or other electromechanical changes, are still unclear. The goal of this study was to develop a translational porcine model of ischemic monomorphic VT treated with STAR to examine the physiological changes after a typical clinical STAR treatment.

Methods: We treated a previously validated porcine model of monomorphic VT after myocardial infarction with a clinically derived STAR protocol. A dose of 25 Gy was prescribed to the planning target volume and 35 Gy to the clinical target volume (regions of scar), while controls underwent a sham STAR treatment. All investigators in the study were blinded except the treating investigator. The primary study outcome was VT inducibility at 6 weeks post-STAR. Animals underwent pre- and post-STAR cardiac magnetic resonance imaging to quantify myocardial scar and function, as well as body surface mapping. Six weeks post-STAR, animals underwent a VT induction study, and tissue was harvested for optical mapping and histological analysis.

Results: Six animals completed the study, which ended before finishing enrollment because all animals had inducible VT. We found a significantly longer local effective refractory period in the left ventricular apex and longer VT cycle lengths in STAR-treated animals compared with controls (P<0.05). We found no difference in myocardial scar burden, mechanical function, or body surface recordings when comparing pre- and post-STAR.

Conclusions: Our data suggest a novel therapeutic mechanism of STAR driven by increasing the effective refractory period in locally treated areas, corresponding to increased tissue wavelength. Our results corroborate clinical case reports and anecdotal evidence that STAR increases VT cycle length. Importantly, these effects were not mediated by an increase in myocardial scar burden. However, our studies do not examine the long-term effects of STAR.