Inflammation and fibrosis characterize different stages of myocardial remodeling in patients after stereotactic body radiotherapy of ventricular myocardium for recurrent ventricular tachycardia

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

doi:10.1016/j.carpath.2022.107488

Cited by 6 publications

(5 citation statements)

References 24 publications

(47 reference statements)

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“…Moreover, other studies reported: i) clear histological evidence of STAR effect on the target area, found by the loss of myocyte architecture and increased fibrin, vacuoles and calcification (12), and ii) fibrosis in the same area, detected by loss of the smooth cellular organization usually seen in normal AV nodes, extensive fibrin deposition and marked elastosis, but not in the surrounding tissues (21,24,26,30). Finally, a study on human explanted hearts showed subendocardial necrosis characterized by degenerative changes in myocytes with irregular and convoluted intercalated disc regions, loss of contractile elements and edematous mitochondria with loss of cisternae, and the myocardium surrounded by a border of fibrosis (23,30) (Figure 1). Dose effect.…”

Section: Resultsmentioning

confidence: 99%

Stereotactic Arrhythmia Radioablation (STAR): A Multidisciplinary Narrative Minireview of Preclinical Studies

Galietta¹,

Strolin²,

Bisello³

et al. 2023

In Vivo

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The aim of this narrative review of the literature was to collect and analyze the results of the published preclinical studies on stereotactic arrhythmia radioablation (STAR) in the treatment of refractory cardiac arrhythmias. A literature search was conducted on PubMed using the following terms: ("stereotactic" OR "SBRT" OR "SABR" OR "radioablation" OR "radiosurgery") AND ("arrhythmia" OR "tachycardia"). Preclinical and pathological reports published in English without time limit, comprising studies of STAR in animal models and histological analyzes of explanted animal and human hearts were included. The analyzed studies confirm that doses lower than 25 Gy seem to produce sub-optimal therapeutic results whereas doses >35 Gy are less safe in terms of radiation-induced toxicity. However, long-term results (>1 year) are still missing and reporting outcomes based on low dose irradiation (≤15 Gy). Finally, STAR proved to be an effective therapy in the analyzed studies despite the irradiation of rather different cardiac targets. Therefore, additional studies are needed to: 1) compare the outcomes of STAR at doses of 25 Gy versus 30 Gy; 2) evaluate the long-term results (>1 year) in animal models irradiated at doses similar to those used in the clinic; 3) define the optimal target. Stereotactic arrhythmia radioablation (STAR) has been suggested as a promising therapeutic alternative in cases of failed catheter ablation for recurrent ventricular tachycardia (VTs) and other cardiac arrhythmias in patients with structural heart disease (1-4). In fact, some clinical studies demonstrated the efficacy and safety of STAR in this setting, at least in the short term, particularly in reducing VT episodes (5-9).Furthermore, some preclinical studies have been conducted in order to study the mechanisms of action and the biological-pathological effects of STAR (10-30). However, while some literature revisions of clinical studies are available (31-36), reviews specifically addressed to preclinical studies only are currently lacking.For these reasons we considered as potentially useful a summary of available evidence in this field (10-30), in order 963

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Section: Resultsmentioning

confidence: 99%

Stereotactic Arrhythmia Radioablation (STAR): A Multidisciplinary Narrative Minireview of Preclinical Studies

Galietta¹,

Strolin²,

Bisello³

et al. 2023

In Vivo

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“…3,5 Several studies have also reported on electrophysiological effects of photon irradiation ablation. 8,10,12 The bipolar voltage amplitude changes showed both active and passive effects on electrical conduction. In our study, electrophysiological changes were detected earlier than structural changes.…”

Section: Discussionmentioning

confidence: 99%

“…Our changes in CV and other electrophysiological changes have been described by others. Inflammation and fibrosis characterizing different stages of myocardial remodeling have also been seen in patients after stereotactic radiotherapy of ventricular myocardium for recurrent VT. 12 This report also examined other biomarkers derived from 3 patients who died between 3-9 months. after radiotherapy.…”

Section: Time Frame For the Effect Of Proton Irradiationmentioning

confidence: 99%

“…A possible solution is emerging through the development of ionizing radiation technology as a method of noninvasive, catheter-free ablation. [3][4][5][6][7][8][9][10][11] Both photons 8,12,13 and charged particle therapy are used in the capacity of radiation therapy, [3][4][5][6] as guided by cardiac magnetic resonance (CMR) imaging and electrophysiological mapping.…”

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confidence: 99%

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Early Impact of Proton Beam Therapy on Electrophysiological Characteristics in a Porcine Model

Imamura¹,

Deisher

Dickow³

et al. 2023

Circ: Arrhythmia and Electrophysiology

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Background: Particle therapy is a noninvasive, catheter-free modality for cardiac ablation. We previously demonstrated the efficacy for creating ablation lesions in the porcine heart. Despite several earlier studies, the exact mechanism of early biophysical effects of proton and photon beam delivery on the myocardium remain incompletely resolved. Methods: Ten normal and 9 infarcted in situ porcine hearts received proton beam irradiation (40 Gy) delivered to the left ventricular myocardium with follow-up for 8 weeks. High-resolution electroanatomical mapping of the left ventricular was performed at baseline and follow-up. Bipolar voltage amplitude, conduction velocity, and connexin-43 were determined within the irradiated and nonirradiated areas. Results: The irradiated area in normal hearts showed a significant reduction of bipolar voltage amplitude (10.1±4.9 mV versus 5.7±3.2, P <0.0001) and conduction velocity (85±26 versus 55±13 cm/s, P =0.03) beginning at 4 weeks after irradiation. In infarcted myocardium after irradiation, bipolar voltage amplitude of the infarct scar (2.0±2.9 versus 0.8±0.7 mV, P =0.008) was significantly reduced as well as the conduction velocity in the infarcted heart (43.7±15.7 versus 26.3±11.4 cm/s, P =0.02). There were no significant changes in bipolar voltage amplitude and conduction velocity in nonirradiated myocardium. Myocytolysis, capillary hyperplasia, and dilation were seen in the irradiated myocardium 8 weeks after irradiation. Active caspase-3 and reduction of connexin-43 expression began in irradiated myocardium 1 week after irradiation and decreased over 8 weeks. Conclusions: Irradiation of the myocardium with proton beams reduce connexin-43 expression, conduction velocity, and bipolar conducted electrogram amplitude in a large porcine model. The changes in biomarkers preceded electrophysiological changes after proton beam therapy.

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“…(1) vacuolization, fibrosis and necrosis after doses exceeding 30 Gy [23,24], and (2) protein changes due to notch activation resulting in increased conduction velocity [25,26]. Clinically, patients may respond to STAR within a few days showing no fibrosis in the treated area [25,27,28] or up to weeks and months later with small pathological lesions [29,30]. Further understanding of these complex interactions and variable treatment effects may eventually lead to different concepts and requirements for target definition, treatment planning and treatment precision.…”

Section: Editorial Precision Requirements In Stereotactic Arrhythmia ...mentioning

confidence: 99%

Precision requirements in stereotactic arrhythmia radioablation for ventricular tachycardia

Fast,

Lydiard,

Boda-Heggemann

et al. 2023

Physics and Imaging in Radiation Oncology

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Inflammation and fibrosis characterize different stages of myocardial remodeling in patients after stereotactic body radiotherapy of ventricular myocardium for recurrent ventricular tachycardia

Cited by 6 publications

References 24 publications

Stereotactic Arrhythmia Radioablation (STAR): A Multidisciplinary Narrative Minireview of Preclinical Studies

Stereotactic Arrhythmia Radioablation (STAR): A Multidisciplinary Narrative Minireview of Preclinical Studies

Early Impact of Proton Beam Therapy on Electrophysiological Characteristics in a Porcine Model

Precision requirements in stereotactic arrhythmia radioablation for ventricular tachycardia

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