Radiation-Induced Changes in Ventricular Myocardium After Stereotactic Body Radiotherapy for Recurrent Ventricular Tachycardia

Kautzner, Josef; Jedlickova, Kristina; Šramko, Marek; Peichl, Petr; Cvek, Jakub; Ing, Lukas Knybel; Neuwirth, Radek; Jiravský, Otakar; Voska, Luděk; Kucera, Tomas

doi:10.1016/j.jacep.2021.07.012

Cited by 21 publications

(45 citation statements)

References 9 publications

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“…Most of the experimental studies suggested that electrophysiological effects are rather delayed and that the development of fibrosis is important for clinical effect ( 25 , 26 ). Our recent report analyzing 3 post-mortem hearts after SBRT is in line with the above experimental data on early apoptosis and delayed fibrosis ( 27 ). Furthermore, the clinical effect of SBRT was delayed and a similar pattern was observed also in the current series ( 28 , 29 ).…”

Section: Discussionsupporting

confidence: 87%

Case Report: Repeated Stereotactic Radiotherapy of Recurrent Ventricular Tachycardia: Reasons, Feasibility, and Safety

Haskova

Peichl

Šramko

et al. 2022

Front. Cardiovasc. Med.

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Stereotactic body radiotherapy (SBRT) has been reported as an attractive option for cases of failed catheter ablation of ventricular tachycardia (VT) in structural heart disease. However, even this strategy can fail for various reasons. For the first time, this case series describes three re-do cases of SBRT which were indicated for three different reasons. The purpose in the first case was the inaccuracy of the determination of the treatment volume by indirect comparison of the electroanatomical map and CT scan. A newly developed strategy of co-registration of both images allowed precise targeting of the substrate. In this case, the second treatment volume overlapped by 60% with the first one. The second reason for the re-do of SBRT was an unusual character of the substrate–large cardiac fibroma associated with different morphologies of VT from two locations around the tumor. The planned treatment volumes did not overlap. The third reason for repeated SBRT was the large intramural substrate in the setting of advanced heart failure. The first treatment volume targeted arrhythmias originating in the basal inferoseptal region, while the second SBRT was focused on adjacent basal septum without significant overlapping. Our observations suggested that SBRT for VT could be safely repeated in case of later arrhythmia recurrences (i.e., after at least 6 weeks). No acute toxicity was observed and in two cases, no side effects were observed during 32 and 22 months, respectively. To avoid re-do SBRT due to inaccurate targeting, the precise and reproducible strategy of substrate identification and co-registration with CT image should be used.

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Section: Discussionsupporting

confidence: 87%

Case Report: Repeated Stereotactic Radiotherapy of Recurrent Ventricular Tachycardia: Reasons, Feasibility, and Safety

Haskova

Peichl

Šramko

et al. 2022

Front. Cardiovasc. Med.

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“…The patient described in our study was not considered for epicardial ablation due to anatomical constraints, nor received a left ventricle assist device, both of which can lead to significant scarring, hemorrhage, and edema ( 16 , 17 ) reported by previous authors ( 6 , 7 ). The lack of visible necrosis could also be associated with the modality of heart rhythm cessation.…”

Section: Discussionmentioning

confidence: 99%

“…The patient underwent cardioplegia with isotonic and osmotic solution, which lowers the metabolism and prevents degenerative changes and cell death in cardiomyocytes. Cardiopulmonary resuscitation and postmortem period in hearts explanted from deceased patients can induce previously described necrosis and cardiomyocyte vacuolization ( 6 , 7 ).…”

Section: Discussionmentioning

confidence: 99%

“…Kiani et al were the first to report on human heart pathology changes after STAR and found that even with relatively long follow-up, despite signs of cell death and injury, there is limited fibrosis (6). In a later study by Kautzner et al, the authors supported the pre-clinical theorem of myocardial apoptosis (up to three months post-STAR) followed by a creation of fibrotic lesion (six to nine months post-STAR) in the irradiated region (7). Zhang et al suggested that the visible fibrosis is likely a consequence of primary heart disease, previously received treatments and that the intensity of fibrosis is not significantly different from what would be observed pre-treatment (5).…”

Section: Introductionmentioning

confidence: 95%

“…Significant differences in the description of post-STAR organ pathology ( 5 – 7 ), but most important clinically relevant differences in efficacy described by the authors ( 1 ) could be associated with individual radiosensitivity. The irradiated regions of the myocardium are initially subjected to cardiomyopathies of ischemic and non-ischemic origin and invasive treatment methods (i.e., RFA, ventricular assist device).…”

Section: Introductionmentioning

confidence: 97%

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Histopathological Examination of an Explanted Heart in a Long-Term Responder to Cardiac Stereotactic Body Radiotherapy (STereotactic Arrhythmia Radioablation)

Miszczyk

Sajdok

Nożyński

et al. 2022

Front. Cardiovasc. Med.

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Cardiac stereotactic body radiotherapy is an emerging treatment method for recurrent ventricular tachycardia refractory to invasive treatment methods. The single-fraction delivery of 25 Gy was assumed to produce fibrosis, similar to a post-radiofrequency ablation scar. However, the dynamics of clinical response and recent preclinical findings suggest a possible different mechanism. The data on histopathological presentation of post-radiotherapy hearts is scarce, and the authors provide significantly different conclusions. In this article, we present unique data on histopathological examination of a heart explanted from a patient who had a persistent anti-arrhythmic response that lasted almost a year, until a heart failure exacerbation caused a necessity of a heart transplant. Despite a complete treatment response, there was no homogenous transmural fibrosis in the irradiated region, and the overall presentation of the heart was similar to other transplanted hearts of patients with advanced heart failure. In conclusion, our findings support the theorem of functional changes as a source of the anti-arrhythmic mechanism of radiotherapy and show that durable treatment response can be achieved in absence of transmural fibrosis of the irradiated myocardium.

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Radiosurgery for ventricular tachycardia (RAVENTA): interim analysis of a multicenter multiplatform feasibility trial

et al. 2023

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Background Single-session cardiac stereotactic radiation therapy (SBRT) has demonstrated promising results for patients with refractory ventricular tachycardia (VT). However, the full safety profile of this novel treatment remains unknown and very limited data from prospective clinical multicenter trials are available. Methods The prospective multicenter multiplatform RAVENTA (radiosurgery for ventricular tachycardia) study assesses high-precision image-guided cardiac SBRT with 25 Gy delivered to the VT substrate determined by high-definition endocardial and/or epicardial electrophysiological mapping in patients with refractory VT ineligible for catheter ablation and an implanted cardioverter defibrillator (ICD). Primary endpoint is the feasibility of full-dose application and procedural safety (defined as an incidence of serious [grade ≥ 3] treatment-related complications ≤ 5% within 30 days after therapy). Secondary endpoints comprise VT burden, ICD interventions, treatment-related toxicity, and quality of life. We present the results of a protocol-defined interim analysis. Results Between 10/2019 and 12/2021, a total of five patients were included at three university medical centers. In all cases, the treatment was carried out without complications. There were no serious potentially treatment-related adverse events and no deterioration of left ventricular ejection fraction upon echocardiography. Three patients had a decrease in VT episodes during follow-up. One patient underwent subsequent catheter ablation for a new VT with different morphology. One patient with local VT recurrence died 6 weeks after treatment in cardiogenic shock. Conclusion The interim analysis of the RAVENTA trial demonstrates early initial feasibility of this new treatment without serious complications within 30 days after treatment in five patients. Recruitment will continue as planned and the study has been expanded to further university medical centers. Trial registration number NCT03867747 (clinicaltrials.gov). Registered March 8, 2019. Study start: October 1, 2019.

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Radiation-Induced Changes in Ventricular Myocardium After Stereotactic Body Radiotherapy for Recurrent Ventricular Tachycardia

Cited by 21 publications

References 9 publications

Case Report: Repeated Stereotactic Radiotherapy of Recurrent Ventricular Tachycardia: Reasons, Feasibility, and Safety

Case Report: Repeated Stereotactic Radiotherapy of Recurrent Ventricular Tachycardia: Reasons, Feasibility, and Safety

Histopathological Examination of an Explanted Heart in a Long-Term Responder to Cardiac Stereotactic Body Radiotherapy (STereotactic Arrhythmia Radioablation)

Radiosurgery for ventricular tachycardia (RAVENTA): interim analysis of a multicenter multiplatform feasibility trial

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