Hey #EPeeps and #RadOnc communities... we have some new data to share today about how **radiation can actually reprogram heart cells to make them act younger**. This is my first attempt at a Twitter thread 🧵 Please be kind...
(1) To develop a better/safer/faster way to fix abnormal heart rhythms, we helped create *noninvasive cardiac radioablation* - a 7-minute precision-focused radiation treatment to arrhythmia circuit(s) in the heart. bit.ly/NEJM2017
(2) The goal with noninvasive cardiac radioablation is to deliver full-thickness ablation (read: destruction) to the semi-scarred heart tissue causing problems. It solves many shortcomings of ablating heart scar with catheters.
(3) Led by @SBRT_CR, our team @WUDeptMedicine @WashURadOnc completed a proper prospective clinical trial which confirmed a dramatic reduction in arrhythmia episodes after focused cardiac radioablation. The results weren't perfect for everyone, but it helped nearly everyone.
(4) Here’s where the story gets really cool… along the way, we noticed that heart rhythms generally got better in days. This was MUCH faster than expected for radiation-induced fibrosis (typically months).
(5) We also expected that radiation would cause substantial destruction & delay in the electrical signal through the heart. However, in many patients, we noticed that the ECG changes showed that the heart was beating more synchronously.
(6) When we compared MRI images from before v. after cardiac radioablation, there was very little evidence of new fibrosis from the radiation. So, although arrhythmias were disappearing, we were not causing more obvious cardiac tissue destruction.
(7) Our paper, released today in @Nature Comm, completes the story. Led by Stacey @RentschlerLab and @JulieSchwarz14, we show that lower doses of radiation to the heart induces **durable electrical changes to heart muscle** bit.ly/NATCOMM2021
(8) The electrical reprogramming from cardiac radiation upregulates Nav1.5 & Connexin-43. These changes (observed in mice and humans) result in **increased conduction velocities** and happen in both normal heart and scar border-zone. Scarred hearts depolarize faster.
(9) Cardiac radiation triggers a cellular reprogramming process (at least in part) through Notch signalling (which I still don’t understand, but @RentschlerLab is an expert). In simple terms, it gives Teen Spirit to older, scarred-up heart cells (watch)
(10) As my #EPeeps know, electrical re-entry happens because of unidirectional block, slow conduction through a channel, then activation of recovered tissue.
(11) So, #EPeeps, what would happen if we increased conduction velocity through the entire scar? We would homogenize the conduction of the scar and eliminate the differences between fast and slow conduction. This means no re-entry and no arrhythmia.
(12) One more thing… radioablation achieves the cellular reprogramming & VT cessation **without any rise in serum troponin**. No acute cardiac cell death. That data will be shared soon...
(13) Conclusion: with 25 Gray (the dose of radiation) in a single fraction (treatment) to the heart, we are not destroying heart tissue.
And in a way, we might be “healing” it.
Come to our website to learn more: cardiacradioablation.wustl.edu
(14) Acknowledgements to the talented team @WUSTL #CNCR who made this discovery happen: (lead author David Zhang) @RentschlerLab @JulieSchwarz14 @carmenbergom @SBRT_CR @gdhugo @samsonpp @cooper_dh @DrRachitaEP Kaitlin Moore & others below. #RadiateVT @HRSonline @ASTRO_org
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