Lehmann, H. Immo

Noninvasive AF Ablation With Carbon IonsIntroductionCatheter ablation with isolation of the pulmonary veins is a common treatment option for atrial fibrillation but still has insufficient success rates and carries several interventional risks. These treatment planning studies assessed if high‐dose single fraction treatment with scanned carbon ions (12C) can be reliably delivered for AF ablation, while sparing risk structures and considering respiratory and contractile target motion.Methods and ResultsTime resolved CT scans of complete respiratory and cardiac cycles of 9 and 5 patients, respectively, were obtained. Ablation lesions and organs at risk for beam delivery were contoured. Single fraction intensity‐modulated particle therapy with target doses of 25 and 40 Gy were studied and motion influences on these deliveries mitigated. Respiration had a large influence on lesion displacement (≤ 2 cm). End expiration could be exploited as a stable gating window. Smaller, but less predictable, heartbeat displacements (< 6 mm) remained to be mitigated because cardiac contraction resulted in insufficient dose coverage (V95 < 90 %) if uncompensated. Repeated irradiation (12C beam rescanning) during breath hold was used to accommodate contractile motion, resulting in good dose coverage. Dose depositions to all organs at risk were carefully examined and did not exceed values for X‐ray cancer treatment.ConclusionTreatment 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.

Background— 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 (inner balloon, median [range]: −51.5 [−66.0 to −31.0] versus −43.0 [−64.0 to −26.0]°C, P <0.001; balloon surface: −43.0 [−60.0 to −15.8] versus −6.5 [−46.2 to 28.9]°C, P <0.001; left atrial–PV junction: −6.7 [−20.0 to 21.4] versus 15.8 [−14.4 to 35.1]°C, P <0.001), and trended toward a higher PV isolation success rate in the 23-mm cryoballoon. Histologically, deeper extensions of ablative lesions into the PV were seen with 23-mm cryoballoon, and larger ablative lesions were seen in the left atrial antrum using 28-mm cryoballoon. Conclusions— The efficacy of 3-minute ablation was not significantly different from 4-minute ablation in dogs. The 23-mm cryoballoon had a greater cooling effect than the 28-mm cryoballoon for small PVs, but showed narrower ablative lesions in the left atrial antrum.

Background— Particle therapy, with heavy ions such as carbon-12 ( 12 C), delivered to arrhythmogenic locations of the heart could be a promising new means for catheter-free ablation. As a first investigation, we tested the feasibility of in vivo atrioventricular node ablation, in Langendorff-perfused porcine hearts, using a scanned 12C beam. Methods and Results— Intact hearts were explanted from 4 (30–40 kg) pigs and were perfused in a Langendorff organ bath. Computed tomgraphic scans (1 mm voxel and slice spacing) were acquired and 12 C ion beam treatment planning (optimal accelerator energies, beam positions, and particle numbers) for atrioventricular node ablation was conducted. Orthogonal x-rays with matching of 4 implanted clips were used for positioning. Ten Gray treatment plans were repeatedly administered, using pencil beam scanning. After delivery, positron emission tomography-computed tomgraphic scans for detection of β + ( 11 C) activity were obtained. A 12 C beam with a full width at half maximum of 10 mm was delivered to the atrioventricular node. Delivery of 130 Gy caused disturbance of atrioventricular conduction with transition into complete heart block after 160 Gy. Positron emission computed tomgraphy demonstrated dose delivery into the intended area. Application did not induce arrhythmias. Macroscopic inspection did not reveal damage to myocardium. Immunostaining revealed strong γH2AX signals in the target region, whereas no γH2AX signals were detected in the unirradiated control heart. Conclusions— This is the first report of the application of a 12 C beam for ablation of cardiac tissue to treat arrhythmias. Catheter-free ablation using 12C beams is feasible and merits exploration in intact animal studies as an energy source for arrhythmia elimination.

Background— Thermodynamics in the left atrium–pulmonary vein (PV) junction, phrenic nerve, and esophagus during PV isolation (PVI) using the second-generation cryoballoon are not known. Methods and Results— Twenty dogs underwent PVI using second-generation cryoballoon. Ablations were performed for ≤2 deliveries based on PVI without a bonus freeze. Inner balloon, balloon surface, and tissue temperatures were monitored during cryoablation. The tissue thermocouples were placed on the epicardial surface of the left atrium–PV junction, as well as on the phrenic nerve and within the esophagus. A total of 259 cryoballoon and 229 tissue tissue thermocouples profiles during 53 cryoablations of 40 PVs were analyzed. Acutely, PVI was achieved in 36 of 40 PVs (90%). Conductive tissue cooling spread radially from the balloon–left atrium–PV contact point. The lowest tissue temperatures were dependent on the distance of the tissue thermocouples to the balloon surface ( r =0.85; P <0.001). In addition, blood flow leaks around the balloon had a warming effect on the balloon and tissue temperature profiles. Chronic isolation (mean, 48±16 days) was achieved in 27 of 36 PVs (75%). In 8 of 9 acutely isolated but with chronic reconnection PVs, the blood flow leak location was concordant with chronic reconnection gap. Although only 1 esophageal ulcerated lesion was observed, neither phrenic nerve palsy nor severe PV stenosis was seen in any dogs. Conclusions— 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.