Basic/Translational Science -> Intact Heart Electrophysiology (includes Pharmacology and Optical Mapping) D-MP01 - Insights into novel genes, biomarkers and radioablation in arrhythmias (ID 31) Moderated ePoster

D-MP01-05 - Electrical Substrate Remodeling Underlies The Anti-Arrhythmic Effects Of Cardiac Radioablation (ID 1486)

Abstract

Background: Noninvasive cardiac radioablation has been used for treatment refractory VT. Though the presumed effect is via cardiac fibrosis, VT suppression occurs acutely (days to weeks), inconsistent with the timing of radiation-induced fibrosis (months).
Objective: To better understand the relevant tissue effects, we tested whether radioablation 1) creates fibrosis, and/or 2) alters electrical conduction.
Methods: Explanted hearts from 4 patients who previously received radioablation (25 Gy, single fraction) were examined. Trichrome staining was analyzed in the following regions: a) catheter ablation, b) radioablation, and c) no ablation. In mice (n=6), hearts were radiated with 25 Gy. Optical mapping was performed after 6 weeks. Conduction-related gene expression and protein levels were quantified with qPCR and immunoblotting.
Results: In patient hearts, catheter ablation caused substantial superficial fibrosis. In contrast, there was no difference in fibrosis between the radioablation target and no ablation regions within the same hearts (A), despite cessation of VT in all 4 patients. In murine hearts, conduction velocity was increased 6 weeks following treatment (B), without fibrosis or heart block. Radiation increased levels of cardiac conduction proteins and activated electrical reprogramming pathways.
Conclusion: Fibrosis alone cannot account for the clinical effects of radioablation. Alternatively, radioablation effects may occur via electrical substrate remodeling to prevent reentry. A deeper understanding of the mechanisms whereby radioablation reduces VT burden is expected to lead to improvements in therapy and wider adoption.

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