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

In brief

Cardiac radiation lengthened refractory periods by 13% to 17% in pigs

In a porcine heart attack model, four pigs given cardiac radiation had refractory periods lengthen by 13% in scar tissue and 17% in untreated heart muscle, compared with smaller increases in four controls. Sustained ventricular tachycardia remained inducible in every pig, and there was no increase in fibrosis; whether these electrical changes reduce arrhythmias in patients remains unknown.

Journal
JACC. Clinical electrophysiology (Q1)
Published
12 September 2026
Study design
Unclassified
Evidence level
Level 5, Expert Opinion (CEBM 5)
Authors
Negar Raissi-Dehkordi, Nastaran Raissi-Dehkordi, Jonathan A Salas, Weihow Hsue, Julia Wilson, Myles S Miller, et al.
PMID
42782228
DOI
10.1016/j.jacep.2026.08.009

Why clinicians should know about it

  • Picked for Radiation Oncology (paper of the day, 27 September 2026): Acute modulation after cardiac SBRT, already captured above

Abstract

BACKGROUND: 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. OBJECTIVES: This study aimed to investigate the electrophysiological, molecular, and structural changes following cSBRT in a porcine infarct model. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Abstract as published, via PubMed.

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For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.