Imamura, Kimitake

Background: Cardiac proton beam ablation therapy has emerged as a promising tool for catheter-free arrhythmia ablation. The time course of the lesion change was demonstrated in MRI 8 weeks following the ablation; however, the pericardial effusion after the ablation has not been fully analyzed. Objective: The purpose of this study was to evaluate the pericardial effusion after pencil-beam scanned proton therapy on normal myocardium in swine in MRI. Methods: 32 domestic swine were irradiated with pencil-beam scanned proton therapy using irradiation doses of 30/40Gy to the left ventricle (LV) anterior wall, posterior wall, and apex. Each swine was subjected to monthly contrast-enhanced cardiac MRI to evaluate the post-irradiation effects. Results: Moderate to significant pericardial effusion (PE) was observed in 10 swine (31%), starting at 4 weeks, and increasing from 8-16 weeks until 24 weeks. With the exception of one case,, improvement was observed in all animals within a month from when the PE first became moderate or significant. . In the case where the significant PE did not improve, the PE was non-septic and transudate. Clinically, the PE did not cause cardiac tamponade and did not correlate to sudden death. Also, there was no correlation between animals with larger tissue volumes receiving higher dose (more than 20Gy) and the grade of PE . Conclusion: Proton beam radiation caused various grades of pericardial effusion, but in 90% of the animals, it resolved without intervention within a month with no major adverse events.

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.

Abstract Aims With the implementation of saline-enhanced radiofrequency (SERF) needle-tip ablation, real-time validation of lesion formation is needed for the controllable creation of transmural lesions. The aim of the study was to analyse the ability of two-dimensional intracardiac echocardiography (2D-ICE) to guide and validate SERF ablation in real-time. Methods and results Fifty-six SERF energy deliveries at left ventricular sites of 11 dogs guided by 2D-ICE were analysed (power: 15–50 W; time: 25–120 s; irrigation saline: 60°C with 10 mL/min flow rate). Catheter tip/tissue orientation and lesion formation could be well detected by 2D-ICE in 49 (87.5%) energy deliveries. Gross pathology analysis confirmed excellent 2D-ICE lesion localization, the ability to detect transmural lesions (70% sensitivity, 47% specificity) and positive correlation between 2D-ICE and the corresponding gross pathology measurements of ‘maximal lesion depth’; (repeated measures correlation: rrm = 0.43, P = 0.012) and ‘depth at maximal lesion width’ (D@MW; rrm = 0.51, P = 0.003). The median angle between SERF catheter tip and endocardium was 76° [interquartile range (IQR) 58–83°]. The more perpendicular the catheter tip/tissue orientation was the deeper D@MW (rrm = 0.32, P = 0.045). Grade 3 microbubbles on 2D-ICE during ablation, indicating inadequate catheter tip/tissue contact, was associated with smaller lesion volumes than with Grade 1 microbubbles (284.8 mm3 [IQR 151.3–343.1] vs. 2114.1 mm3 [IQR 1437.0–3026.3], P &lt; 0.001). Conclusion With excellent lesion localization and a 70% detection rate of transmural lesions, 2D-ICE is well suited to validate SERF ablation lesion formation in real-time. The catheter tip/tissue angle impacts the lesion formation and through perpendicular catheter positioning, deeper intramural areas of the myocardium can be reached.