Acute Modulation of Arrhythmogenic Ventricular Substrate Following Cardiac Stereotactic Body Radiation Therapy

Cardiac stereotactic body radiation therapy (cSBRT) is a noninvasive, investigational treatment for refractory ventricular tachycardia (VT). The antiarrhythmic effects and time course of action of cSBRT on abnormal ventricular substrate remain poorly understood.

This study aimed to investigate the electrophysiological, molecular, and structural changes following cSBRT in a porcine infarct model.

Anterior myocardial infarction was created in a porcine model of infarct-related re-entrant VT (n = 8). Swine were randomized to cSBRT (n = 4) or control infarct (n = 4) groups. Baseline electrophysiology study and high-resolution electroanatomic maps were performed 8 to 10 weeks postinfarction. The cSBRT group received 25 Gy single-fraction photon radiation guided by initial left ventricular substrate maps. Cardiac magnetic resonance imaging followed by repeat electrophysiology study and mapping studies were performed 6 weeks later.

cSBRT resulted in significant prolongation of the effective refractory period in remote, nontargeted myocardium (cSBRT: 216 ± 21-252 ± 11 ms, Δ +17% vs control: 234 ± 7-249 ± 1 ms, Δ +6.5%) and targeted scar tissue (cSBRT: 258 ± 10-291 ± 18 ms, Δ +13% vs control: 274 ± 13-284 ± 8 ms, Δ +3.7%; group × timepoint interaction P = 0.048). Sustained VT was inducible in all 8 subjects at the terminal timepoint. There was a trend toward more prolonged VT cycle length (cSBRT: 195 ± 19-295 ± 55 ms, Δ +53% vs control: 212 ± 15-261 ± 14 ms, Δ +23%; P = 0.22). Connexin-43 immunoreactive area density in the infarct region was lower in the cSBRT group (1.4% vs 2.7%, respectively; P < 0.01). There was no difference detected in late gadolinium enhancement volume (cSBRT: 29.3% ± 7.8% vs control: 27.2% ± 11.3%; P = 0.8) or histologic fibrosis (cSBRT: 54.9% ± 13.4% vs control: 54.6% ± 20.6%; P = 0.95).

Delivery of 25 Gy cSBRT produced early electrical remodeling with increased effective refractory period and decreased connexin-43 area density, without evidence of increased fibrosis.