Cancer Radiation Therapy May Be Associated With Atrial Fibrillation

Apte, Nachiket; Dherange, Parinita; Mustafa, Usman; Ya’qoub, Lina; Dawson, Desiree; Higginbotham, Kathleen; Boerma, Marjan; Morin, Daniel P.; Gupta, Dhiraj; McLarty, Jerry; Mansour, Richard; Dominic, Paari

doi:10.3389/fcvm.2021.610915

Cited by 21 publications

(15 citation statements)

References 35 publications

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“…Together, these indicate that 15 Gy irradiation caused marked alterations in electrical conduction in our mouse model, consistent with that observed in large clinical cohort studies 14 .…”

Section: A/j Mice Develop Cardiac Toxicity Following Whole Heart Irra...supporting

confidence: 91%

Radiation-induced persistent DNA damage response and late toxicity in cardiac tissue

Shigemori

Jiang

Martin

et al. 2023

Preprint

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Background: Radiotherapy treatment is a mainstay of cancer treatments including for thoracic malignancies such as lung or breast cancer. Cardiac toxicity is a recognised long-term complication of thoracic radiotherapy which persists despite improvements in therapeutic modalities. The mechanisms and potential therapeutic targets that could provide cardiac protection in the context of radiation therapy remain incompletely understood. Here we investigated early and late cardiac toxicity following irradiation using the A/J mouse model to identify potential molecular drivers. Methods: Single doses of irradiation of either 13 or 15 Gy were delivered to female A/J mice aged 6 to 8 weeks using a SmART PLAN system. ECG traces and analysis were performed on anaesthetised mice. Cardiac tissue was harvested up to 32 weeks following irradiation for histological analysis and second-harmonic imaging microscopy. Results: Cardiac RT resulted in cardiac conductivity abnormalities including prolonged QTc interval. Additionally, an increase in pericardial and perivascular fibrosis was noted with a marked increase in pericardial fibrosis at 15 Gy compared to 13 Gy. Persistent DNA damage response was identified in cardiomyocytes at 7 days post irradiation and polarisation of cardiac-infiltrating macrophages towards a CD206+ M2-like phenotype at the same timepoint. Conclusions: Our data introduce the A/J mouse as a novel model for the study of physiologically relevant early and late cardiac toxicities following irradiation. Early events that could contribute to long term toxicities include persistent DNA damage response and repolarisation of macrophages, further investigation of which could identify potential future cardioprotective therapeutic strategies.

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“…Together, these indicate that 15 Gy irradiation caused marked alterations in electrical conduction in our mouse model, consistent with that observed in large clinical cohort studies 14 .…”

Section: A/j Mice Develop Cardiac Toxicity Following Whole Heart Irra...supporting

confidence: 91%

Radiation-induced persistent DNA damage response and late toxicity in cardiac tissue

Shigemori

Jiang

Martin

et al. 2023

Preprint

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“…It is not uncommon for the practicing electrophysiologist to encounter large regions of abnormally reduced left atrial voltage (consistent with fibrotic scar) in the course of catheter ablation for AF in relatively young patients with a history of mantle irradiation for the treatment of Hodgkin lymphoma. Recently, a large retrospective single-center study of 14 600 patients concluded that a history of radiation therapy was an independent risk factor for developing AF . A separate, smaller case-control study found mediastinal irradiation to be an independent predictor of AF recurrence following catheter ablation in women with a history of breast cancer …”

supporting

confidence: 83%

“…Recently, a large retrospective single-center study of 14 600 patients concluded that a history of radiation therapy was an independent risk factor for developing AF. 6 A separate, smaller case-control study found mediastinal irradiation to be an independent predictor of AF recurrence following catheter ablation in women with a history of breast cancer. 7 The present study by Kim et al 2 extends and adds granularity to these findings.…”

mentioning

confidence: 95%

Keeping the Heartbeat Off-Target in Cancer Therapy

Starobin

Kwaku

2022

JAMA Oncol

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“…Those risk factors that were no longer significant were then dropped from the base model, thus arriving among those receiving radiation therapy (doses were not reported). 18 For a low to moderate range of radiation (not exceeding 4 Gy), we have examined radiation-associated risks of Brugada-type ECG, 19 early repolarization, 20 and complete right bundle branch block 21 among atomic bomb survivors, but found no evidence of altered risk.…”

Section: Discussionmentioning

confidence: 99%

Relationship Between Radiation Exposure and Incident Atrial Fibrillation Among Atomic Bomb Survivors

et al. 2021

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peutic purposes has increased worldwide. Recently, several studies reported that moderate to high doses (0.5-20 Gy) of radiation exposure were associated with an increased risk of cardiovascular diseases, such as ischemic heart disease, congestive heart disease, rheumatic valvular disease, and hypertensive heart disease. [13][14][15] With regard to radiation-associated conducting system abnormalities and arrhythmias, there are case reports of advanced sick sinus syndrome, atrioventricular block, and bundle branch block long after radiotherapy with high doses >30 Gy. 16 Of 48 Hodgkin disease survivors who received mediastinal irradiation (27-52 Gy), 74.5% had conduction abnormalities or arrhythmia on resting electrocardiograms (ECGs) 6-27 years after irradiation. 17 A recent report found that among cancer patients, the prevalence of AF was higher A trial fibrillation (AF) is the most common arrhythmia in clinical practice. The prevalence and incidence of AF increase with age. 1-3 AF is associated with an increased risk of ischemic stroke, congestive heart failure, reduced quality of life, and mortality. 4-6 AF is a multifactorial disease affected by both environmental and genetic factors. 7 Past studies have established various risk factors for AF, such as aging, male sex, hypertension, obesity, diabetes, hyperthyroidism, alcohol consumption, smoking tobacco, hyperuricemia, and organic heart diseases. 7-9 As possible underlying pathways, there is emerging evidence linking inflammation and oxidative stress to the pathogenesis of AF through atrial fibrosis and electrical and structural remodeling. [10][11][12] The use of ionizing radiation for diagnostic and thera-

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Cancer Radiation Therapy May Be Associated With Atrial Fibrillation

Cited by 21 publications

References 35 publications

Radiation-induced persistent DNA damage response and late toxicity in cardiac tissue

Radiation-induced persistent DNA damage response and late toxicity in cardiac tissue

Keeping the Heartbeat Off-Target in Cancer Therapy

Relationship Between Radiation Exposure and Incident Atrial Fibrillation Among Atomic Bomb Survivors

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