High-energy ion beams are successfully used in cancer therapy and precisely deliver high doses of ionizing radiation to small deep-seated target volumes. A similar noninvasive treatment modality for cardiac arrhythmias was tested here. This study used high-energy carbon ions for ablation of cardiac tissue in pigs. Doses of 25, 40, and 55 Gy were applied in forced-breath-hold to the atrioventricular junction, left atrial pulmonary vein junction, and freewall left ventricle of intact animals. Procedural success was tracked by (1.) in-beam positron-emission tomography (PET) imaging; (2.) intracardiac voltage mapping with visible lesion on ultrasound; (3.) lesion outcomes in pathohistolgy. High doses (40–55 Gy) caused slowing and interruption of cardiac impulse propagation. Target fibrosis was the main mediator of the ablation effect. In irradiated tissue, apoptosis was present after 3, but not 6 months. Our study shows feasibility to use high-energy ion beams for creation of cardiac lesions that chronically interrupt cardiac conduction.

Background-Formation of microemboli during catheter ablation has been suggested as a cause for asymptomatic cerebral emboli. However, it is unknown which part of the process and ablation setting/strategy is most strongly related to this occurrence. Methods and Results-A total of 27 pigs were used. Catheter/sheath manipulations in left atrium were performed in 25 of 27 pigs outfitted with microemboli monitoring systems. Ablations using open-irrigated radiofrequency catheters were performed in 18 of 25 pigs. Two of 27 pigs did not undergo left atrial procedures and were injected with microembolic materials in the carotid artery to serve as positive controls. In total, 334 sheath/catheter manipulations (transseptal puncture, sheath flushing, catheter insertion, pulmonary vein venography, and sheath exchange) and 333 radiofrequency applications (power setting, 30/50 W; point-by-point/drag ablations) were analyzed. High microbubble volume in the extracorporeal circulation loop and a high number of microembolic signals in carotid artery were observed during sheath/ catheter manipulations especially in saline/contrast injections at fast speed and ablations with steam pop. Fast sheath flushing produced significantly higher microbubble volume than slow sheath flushing (median, 12 200 versus 121 nL; P<0.0001). A total of 44 of 126 (35%) blood filters in the circulation loop showed microparticles (thrombus/coagulum and tissue). Most of them were seen after radiofrequency application especially in 50-W ablations, drag ablations, and steam pop. Brain magnetic resonance imaging showed positive-embolic lesions in control pigs. Conclusions-Formation of microbubbles was the greatest during fast saline/contrast injections and steam pops, whereas high-power radiofrequency applications, drag ablations, and steam pops produced most of the microparticles.(Circ Arrhythm Electrophysiol. 2016;9:e003226.

Treatment planning of 12C with delivery of physical ionizing radiation doses that have been described to induce complete block is feasible for AF ablation, considering human anatomy, dose constraints, and encasing underlying motion patterns from respiration and cardiac contraction at the LA-PV junction into treatment planning.

Single-fraction doses as low as 25 Gy caused a lesion with interruption of cardiac impulse propagation using this respective target volume. With doses of ≤55 Gy, maximal point-doses to coronary arteries could be kept <7Gy, but target conformity of lesions was not fully achieved using this approach.

Variance in tissue thermodynamics during cryothermal ablation depends on the distance from balloon and peri-balloon blood flow leaks. This information may be useful for successful PVI without severe complications.

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.

BackgroundRecently, pulmonary vein isolation (PVI) using the second generation cryoballoon, introduced as a therapy for patients with drug-refractory atrial fibrillation, has shown better outcomes than with the first generation cryoballoon. [1][2][3][4][5] However, some questions about the second generation cryoballoon remain. Several studies in cryobiology have shown that prolongation of freeze duration produces a greater destructive effect in noncardiac tissue. 6,7 However, ablation duration to achieve acute and long-term PVI is still debatable. It is also unclear how different sized balloons (23 and 28 mm) should be used, as the impact of the balloon size on tissue and balloon temperature profiles and ablative lesion size have not been studied. Information on the effects of ablation duration and balloon size is required to achieve high PVI success rates without severe complications using the second generation cryoballoon.The purpose of this study was to investigate the impact of ablation duration and balloon size on tissue and balloon thermodynamics, acute and chronic PVI success rates, complications, and chronic histological changes of the PV and left atrium (LA). Methods GeneralThis study was designed to compare the ablation effect and safety of different ablation durations (3 versus 4 minutes) and different balloon sizes (23 versus 28 mm) in an in vivo model. Twenty-six dogs underwent PVI using second generation cryoballoon. Animal PreparationThe protocol was approved by Mayo Foundation Institutional Animal Care and Use Committee. Dogs (30.3±2.5 kg) were anesthetized with intravenous ketamine and diazepam, intubated, and maintained on 1% to 3% isoflurane. The surface ECG, body temperature, and blood pressure were monitored. Tissue Temperature MonitoringTissue temperatures were monitored by implanted thermocouples, as reported previously. 8,9 All dogs underwent left/right thoracotomy for access to the superior/inferior PVs. The pericardium was opened to © 2015 American Heart Association, Inc. Original Article Circ Arrhythm ElectrophysiolBackground-The differences in ablation characteristics of freezing time and balloon size using second generation cryoballoon are still unknown. Methods and Results-Twenty-six dogs underwent pulmonary vein (PV) isolation. Balloon and tissue temperatures (left atrial-PV junction, phrenic nerve, and internal esophagus) were monitored. The ablation duration was randomized to either 3 or 4 minutes, which did not show significant differences in temperature profiles, PV isolation success rate, complications, or histological changes. Twenty dogs underwent cryoablation using 28-mm cryoballoon, 6 dogs were done using the 23-mm cryoballoon. Positioning of the 23-mm cryoballoon was more distal in the PV, which resulted in better PV occlusion. Temperature profiles showed lower temperatures in the 23-mm cryoballoon than in the 28-mm cryoballoon

Noninvasive X-ray stereotactic treatment is considered a promising alternative to catheter ablation in patients affected by severe heart arrhythmia. High-energy heavy ions can deliver high radiation doses in small targets with reduced damage to the normal tissue compared to conventional X-rays. For this reason, charged particle therapy, widely used in oncology, can be a powerful tool for radiosurgery in cardiac diseases. We have recently performed a feasibility study in a swine model using high doses of high-energy C-ions to target specific cardiac structures. Interruption of cardiac conduction was observed in some animals. Here we report the biological effects measured in the pig heart tissue of the same animals six months after the treatment. Immunohistological analysis of the target tissue showed (1.) long-lasting vascular damage, i.e. persistent hemorrhage, loss of microvessels, and occurrence of siderophages, (2.) fibrosis and (3.) loss of polarity of targeted cardiomyocytes and wavy fibers with vacuolization. We conclude that the observed physiological changes in heart function are produced by radiation-induced fibrosis and cardiomyocyte functional inactivation. No effects were observed in the normal tissue traversed by the particle beam, suggesting that charged particles have the potential to produce ablation of specific heart targets with minimal side effects.