Parker, Kay D.

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 < 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.

Background: Inability to eliminate intramural arrhythmogenic substrate may lead to recurrent ventricular tachycardia after catheter ablation. The aim of the present study was to evaluate intramural and full thickness lesion formation using a heated saline-enhanced radiofrequency (SERF) needle-tip catheter, compared with a conventional ablation catheter in normal and infarcted myocardium. Methods: Twenty-two adult mongrel dogs (30–40 kg, 15 normal and 7 myocardial infarct group) were studied. Lesions were created using the SERF catheter (40 W/50 °C) or a standard contact force (CF) catheter in both groups. Results: Comparing SERF to CF ablation, the SERF catheter produced larger lesion volumes than the standard CF catheter—even with >20 g of CF—in both normal (983.1±905.8 versus 461.9±178.3 mm 3 ; P =0.023) and infarcted left ventricular myocardium (1052.3±543.0 versus 340.3±160.5 mm 3 ; P =0.001). SERF catheter lesions were more often transmural than standard CF lesions with >20 g of CF in both groups (59.1% versus 7.7%; P <0.001 and 60.0% versus 12.5%; P =0.017, respectively). Using the SERF catheter, mean depth of ablated lesions reached 90% of the left ventricular wall in both normal and infarcted myocardium. Conclusions: The SERF catheter created more transmural and larger ablative lesions in both normal and infarcted canine myocardium. SERF ablation is a promising new approach for endocardial intramural and full thickness ablation of ventricular tachycardia substrate that is not accessible with current techniques.

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 electrophysiological 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 computed tomography scans were acquired at end-expiration breath hold. Structures (atrioventricular junction or left ventricular myocardium) and organs at risk were contoured. Doses of 30, 40, and 55 Gy were delivered during expiration to the atrioventricular junction (n=5) and left ventricular myocardium (n=20) of intact animals. Results: In this study, procedural success was tracked by pacemaker interrogation in the atrioventricular junction group, time-course magnetic resonance imaging in the left ventricular 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 55 Gy caused slowing and interruption of cardiac impulse propagation at the atrioventricular junction. In 40 left ventricular irradiated targets, all lesions were identified on magnetic resonance after 12 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.

Background: Noninvasive electrocardiographic imaging (ECGi) is used clinically to map arrhythmias before ablation. Despite its clinical use, validation data regarding the accuracy of the system for the identification of arrhythmia foci is limited. Methods: Nine pigs underwent closed-chest placement of endocardial fiducial markers, computed tomography, and pacing in all cardiac chambers with ECGi acquisition. Pacing location was reconstructed from biplane fluoroscopy and registered to the computed tomography using the fiducials. A blinded investigator predicted the pacing location from the ECGi data, and the distance to the true pacing catheter tip location was calculated. Results: A total of 109 endocardial and 9 epicardial locations were paced in 9 pigs. ECGi predicted the correct chamber of origin in 85% of atrial and 92% of ventricular sites. Lateral locations were predicted in the correct chamber more often than septal locations (97% versus 79%, P =0.01). Absolute distances in space between the true and predicted pacing locations were 20.7 (13.8–25.6) mm (median and [first–third] quartile). Distances were not significantly different across cardiac chambers. Conclusions: The ECGi system is able to correctly identify the chamber of origin for focal activation in the vast majority of cases. Determination of the true site of origin is possible with sufficient accuracy with consideration of these error estimates.

Background— This study sought to investigate external photon beam radiation for catheter-free ablation of the atrioventricular junction in intact pigs. Methods and Results— Ten pigs were randomized to either sham irradiation or irradiation of the atrioventricular junction (55, 50, 40, and 25 Gy). Animals underwent baseline electrophysiological evaluation, cardiac gated multi-row computed tomographic imaging for beam delivery planning, and intensity-modulated radiation therapy. Doses to the coronary arteries were optimized. Invasive follow-up was conducted ≤4 months after the irradiation. A mean volume of 2.5±0.5 mL was irradiated with target dose. The mean follow-up length after irradiation was 124.8±30.8 days. Out of 7 irradiated animals, complete atrioventricular block was achieved in 6 animals of all 4 dose groups (86%). Using the same targeting margins, ablation lesion size notably increased with the delivered dose because of volumetric effects of isodose lines around the target volume. The mean macroscopically calculated atrial lesion volume for all 4 dose groups was 3.8±1.1 mL, lesions extended anteriorly into the interventricular septum. No short-term side effects were observed. No damage was observed in the tissues of the esophagus, phrenic nerves, or trachea. However, histology revealed in-field beam effects outside of the target volume. Conclusions— 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.

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.

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— 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.