Cardiac radiotherapy induces electrical conduction reprogramming in absence of transmural fibrosis

Cardiac radiotherapy may be effective in treating heart failure patients with refractory ventricular tachycardia.

• The previously proposed mechanism of radiation-induced fibrosis does not explain the rapidity and magnitude with which ventricular tachycardia reduction occurs clinically.

• Here, scientists demonstrate in hearts from cardiac radiotherapy patients that radiation does not achieve transmural fibrosis within the timeframe of ventricular tachycardia reduction.

• Electrophysiologic assessment of irradiated murine hearts reveals a persistent supraphysiologic electrical phenotype, mediated by increases in NaV1.5 and Cx43.

• By sequencing and transgenic approaches, they identify Notch signaling as a mechanistic contributor to NaV1.5 upregulation after cardiac radiotherapy.

• Clinically, cardiac radiotherapy was associated with increased NaV1.5 expression in 1 of 1 explanted heart.

• On electrocardiogram, post-cardiac radiotherapy QRS durations were shortened in 13 of 19 patients and lengthened in 5 patients.

Collectively, this study provides evidence for radiation-induced reprogramming of cardiac conduction as a potential treatment strategy for arrhythmia management in ventricular tachycardia patients.

Published: 24 September 2021

source:

https://www.nature.com/articles/s41467-021-25730-0

https://doi.org/10.1038/s41467-021-25730-0