Elsevier

Heart Rhythm

Volume 17, Issue 8, August 2020, Pages 1381-1392
Heart Rhythm

Contemporary Review
Cardiac radioablation—A systematic review

https://doi.org/10.1016/j.hrthm.2020.03.013Get rights and content

Failure of drugs and catheter ablation procedures for the treatment of ventricular arrhythmias is still extremely relevant. Recently, stereotactic body radiotherapy has been introduced to treat therapy refractory patients. In this systematic review (International Prospective Register of Systematic Reviews, CRD42019133212), we aimed to summarize electrophysiological and histopathological effects of radioablation in animals, patients, and extracted and perfused hearts. A systematic search was performed in OVID MEDLINE, OVID Embase, the Cochrane Central Register of Controlled Trials, Web of Science, Google Scholar, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) from inception to September 2019. Identified records were independently screened for eligibility by 2 reviewers. Risk of bias and methodological quality were assessed using the SYRCLE, ROBINS-I, or Murad tool and tailored to the different study designs. We included 13 preclinical and 10 clinical publications. Large heterogeneity in study designs prompted a narrative synthesis approach. Baseline, (pre-)procedural details, outcome, target tissue analyses, and safety data were extracted and summarized. In animal studies evaluating electrophysiological parameters, radioablation induced a reduction in voltage/potential amplitude or bidirectional block in target areas in 93.2% of animals. Atrioventricular block (first to third degree) was induced in 78.3% of animals, and in studies evaluating ventricular arrhythmia inducibility, 75% reduction was achieved. In patients, predominantly ventricular tachycardias were targeted with >85% reduction in arrhythmia episodes during follow-up with an encouraging short-term safety profile. Preclinical and clinical evidence on the efficacy and safety of radioablation is limited in both quantity and quality. The results of radioablation for therapy refractory patients with ventricular tachycardia are promising, but further research is needed.

Introduction

Patients with ventricular arrhythmias are treated with antiarrhythmic drugs and invasive catheter ablation procedures in order to reduce the risk of recurrences. Unfortunately, failure of drugs and/or catheter ablation to prevent ventricular tachycardia (VT) and ventricular fibrillation (VF) is common and recurrence remains an import concern. Conventional VT ablation can be limited by incomplete or difficult target accessibility with subsequent arrhythmia persistence or recurrence after ablation.1 Stereotactic body radiotherapy, also known as stereotactic ablative radiotherapy, stereotactic arrhythmia radiotherapy, or radioablation, has the potential to overcome several limitations of conventional VT catheter ablation procedures.2, 3, 4

The effect of radioablation has been explored in several animal species with varying radiotherapy doses and outcomes. Experience in patients is limited but steadily growing since the first reported cases in 2014 and 2015.5,6

In this systematic review, we aim to summarize all the available evidence on radioablation in animals, patients, and extracted and perfused hearts in order to improve our understanding of the electrophysiological and histopathological effects of this novel treatment modality.

Section snippets

Methods

This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.7,8 The review is registered in the International Prospective Register of Systematic Reviews, CRD42019133212.

C.1. Search results and risk of bias

Of 473 unique records, 23 publications were included comprising 13 publications on animal data and 10 clinical publications. Only 1 prospective trial is currently available.3 Figure 1 shows a flowchart of the included publications. Risk of bias tools determined that most preclinical publications had a high risk of bias. Methodological quality tools indicated that clinical publications were mostly of low methodological quality. Online Supplemental Tables 1 and 2 present the results of the

Discussion

We performed a systematic review of the current knowledge base of cardiac radioablation in animals, extracted and perfused hearts, and patients. Although the current quality of evidence is not high enough to draw robust conclusions, the data presented in this review suggest that in animals, (1) radioablation is able to induce a change in electrophysiological parameters (ie, a decrease in voltage or conduction delay) within target areas, (2) radioablation is able to decrease ventricular

Conclusion

Preclinical and clinical evidence on the efficacy and safety of radioablation is limited in both quantity and quality. The results of the only clinical prospective trial show that radioablation is a promising treatment modality for patients with therapy refractory VT. Further research regarding the mechanism of action, optimum doses, and long-term efficacy and safety is crucial to making this novel therapy a success.

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    Dr Blanck reports to have been an employee of CyberHeart from 2008 to 2010, though he reports no financial ties or obligations or conflict of interest to or with the company or its legal predecessor Varian. Dr de Groot is supported by a personal grant from Nederlandse Organisatie voor Wetenschappelijk Onderzoek Zorgonderzoek en Medische Wetenschappen (NWO ZonMW) 016.146.310 and reports research grants to his institution from AtriCure, Boston Scientific, Medtronic, and Abbot and consultancy/speaker fees from AtriCure, Bayer, Daiichi Sankyo, Novartis Medtronic, and Servier. Dr Robinson reports research grants from Elekta, Merck, and Varian Medical Systems and consulting and speaking honoraria from AstraZeneca, EMD Serono, and Varian Medical. Dr Slotman reports research grants and speaker fees from Varian Medical Systems and ViewRay. Dr Zei reports research support from CyberHeart and Biosense Webster, advisory board work for Varian, and consultancy fees from Abbott and Boehringer Ingelheim. The rest of the authors report no conflicts of interest.

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