Catheter-Free Arrhythmia Ablation Using Scanned Proton Beams

Abstract

Background - Proton beam therapy offers radiophysical properties that are appealing for noninvasive arrhythmia elimination. This study was conducted to use scanned proton beams for ablation of cardiac tissue, investigate electrophysiologic outcomes, and characterize the process of lesion formation in a porcine model using particle therapy. Methods - Twenty-five animals received scanned proton beam irradiation. ECG-gated CT scans were acquired at end-expiration breath hold. Structures (atrioventricular junction [AVJ] or left ventricular myocardium [LV]) and organs at risk were contoured. Doses of 30, 40, and 55Gy were delivered during expiration to the AVJ (AVJ; n=5) and LV myocardium (LV; n=20) of intact animals. Results - In this study, procedural success was tracked by pacemaker interrogation in the AVJ group, time-course magnetic resonance imaging (MR) in the LV group, and correlation of lesion outcomes displayed in gross and microscopic pathology. Protein extraction (active caspase-3) was performed to investigate tissue apoptosis. Doses of 40 and 55Gy caused slowing and interruption of cardiac impulse propagation at the AVJ. In 40 LV irradiated targets, all lesions were identified on MR after twelve weeks, being consistent with outcomes from gross pathology. In the majority of cases, lesion size plateaued between 12 and 16 weeks. Active caspase-3 was seen in lesions 12 and 16 weeks after irradiation, but not after 20 weeks. Conclusions - Scanned proton beams can be used as a tool for catheter-free ablation, and time-course of tissue apoptosis was consistent with lesion maturation.

Successful ventricular tachycardia radioablation in a patient with previous chemical pleurodesis: A case report

“…Anticipated STAR effects may be explained by a preclinical study by Zhang et al ( 16) that showed how radiotherapy also induces myocardial electrical conduction reprogramming through increased expression of sodium channels (Nav1.5), upregulation of Connexin 43 (involved in gap junction coupling) and Notch signaling activation. Their findings also elucidate a possible reason behind STAR's effectiveness on transmural scars despite the fact that the standard 25 Gy radiation dose doesn't create transmural myocardial lesions in animal models (17).…”

Feasibility study on stereotactic radiotherapy for total pulmonary vein isolation in a canine model

“…In the previous largest animal study of RSPV isolation using SABR, mild functional echocardiographic abnormalities were reported in some animals during echocardiographic evaluations at 3–6 months, despite no structural abnormalities at the histopathological examination performed immediately after 14 . Additionally, six cases of sudden death after 40 Gy proton-therapy in multiple left ventricular sites among eight pigs associated with a significant left ventricular ejection fraction depression were reported by Hohman et al 25 . The issue of the safety of surrounding organs, including untargeted cardiac tissue, should be considered before applying this technique for human AF treatments.…”

“…The overall reduction of LV function without apparent pathological structural changes was also reported by Zei et al 14 . The study by Hohman et al 25 reported cases of sudden death and a clear dose response relationship with the LV dose. In the in vivo study by Bode et al, collateral damage to the AV node that resulted in an AV block after 40 Gy irradiation to RSPV was observed 26 .…”

Leveraging Radiobiology for Arrhythmia Management: A New Treatment Paradigm?

“…Preclinical studies that created structural ablative lesions in the heart utilised doses in the range of 30e55 Gy to create moderate to severe, but not necessarily fullthickness, fibrosis in the atrioventricular node [37,68e70], pulmonary veins [35e37,40] and ventricles [37,70,71] over a 6e24-month period. Independent of location, doses in excess of 40 Gy were effective at producing fibrotic, nonconducting lesions after 6 months [35e37, 70,71]. Of note, these reported dose ranges are higher than the 25 Gy dose described clinically (Figure 2) and the timing of this fibrosis [60] occurs later than the observed clinical benefit [19,20,23e26].…”

“…Excessive ROS production after radiation therapy can alter mitochondrial membrane stability, create local redox imbalances and cause substantial mitochondrial dysfunction or genomic instability. Although long-term mitochondrial dysfunction may lead to cytochrome c release and induction of apoptosis [85,93,94], as evidenced by the detection of caspase-3 in porcine ventricles treated with >30 Gy after 12e16 weeks [70], short-term dysfunction may cause an acute conduction block in highly metabolic cardiomyocytes. These potential mechanisms may be consistent with several of the phenotypic changes described to date, and the progression from these subacute observations to collagen deposition and scar formation is still under investigation [70].…”