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
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