Johnson, Susan B.

Introduction: Highly precise irradiation using carbon-12 (12C) ions is a new means for catheter-free ablation. Besides energy deposition leading to the dose distribution, nuclear interactions lead to by-product β+-activity that can be measured using positron-emission-tomography (PET). Hypothesis: In-beam PET scanning during focused myocardial irradiation using 12C can adequately depict 12C dose deposition. Methods: Pigs were irradiated with 25, 40, and 55 Gy for AV node (AVN), LA-PV junction, and local LV freewall ablations. PET measurement was performed by means of a double head camera system installed at irradiation site. Coincidences were captured in end-expiration during beam extraction pauses of the accelerator. Results: Evaluation of PET images was qualitatively performed using the coronal plane of the activity distribution superimposed on the contrast-CT in the center of the target contour. Strong β+-activities were measured in AVN and LV ablations. In AVN ablations, activity was localized to the target location, without target activity spreading to the level of the aortic root or coronary sinus (Figure A). Local LV irradiations revealed strong activity in the target location, slightly extending into left lung and chest wall (Figure B). In 55 Gy animals, the cardiac entry channel showed increased activity, decreasing in 40 Gy and more so in 25 Gy animals. Conclusion: This is the first study applying in-beam PET to track 12C dose-deposition into the target location for catheter-free ablation in intact animals. Correlation of β+-activity to electrophysiological outcome, lesion induction, and potential side-effects may be critically important in dosing therapy and predicting outcomes.

Background: Current mapping systems use simultaneous displays of overlapping 3D maps and pre-acquired CT images of the LA to “pseudo-register” data sets rather than specifically “register” each point of one mapping data set to the other. The appropriateness of the 2 data set match has not been validated. Since significant surface to surface mismatch errors may occur, this study was undertaken to quanititatively validate NavX map to CT registration and determine its suitability for guiding AF ablation. Methods: Sixty-four slice, multidetector CT scans were acquired in 8 dogs and segmented to establish subject-specific LA/PV volumes for importation into the EnSite mapping system. A detailed multi-surface geometry (NavX map) was collected by navigating a mapping catheter in target LA and PVs. Using a novel developmental registration algorithm the map was registered to LA/PV CT volume. Validation was performed using the registered 3D CT model for the guidance of ablation at the location of multiple implanted radio-opaque markers. Results: A total of 39 radio-opaque markers were implanted before CT including 9 LSPV, 8 RSPV, 7 RIPV, 9 LIPV, 3 roof, and 3 LAA locations. Subsequent registration of individual NavX maps to acquired 3D CT volume was successfully completed in all animals. RF ablations were performed at the predicted 3D registered model locations of the radio-opaque markers using 5 mm tip RF ablation catheter. Resulting mean lesion size was 5.3 x 6.5 mm. The lesions enveloped the point of marker attachment to the myocardium in 31/36 (86%) ablations. The average distance from the center of the RF lesion to the targeted site was 2.5 ± 1.5mm. 47 points were successfully navigated under fluorscopic and ICE guidance. All points were accurately portrayed on the 3D registered model. 3 points in the region of the RSPV floor did have minor offsets on the model due to technically difficult segmentation of the RSPV from the right pulmonary artery. Conclusion: These data demonstrate the feasibility of registering NavX derived geometries to CT data sets accommodating sources of cardiac, respiratory, and translational cycle dependent error. Catheter navigation precisely conducted using the registered model demonstrates accuracy within the range required for RF ablation.

Background: Current technologies to fully “register” surrogate maps onto 3D CT (CartoMerge, NavxMerge) or 3D ICE images (CartoSound) have emerged to guide ablation. The feasibility of navigation with the Hansen Robotic Catheter Sheath System (HRCS) has also been reported. Integrated 3D Image and contact force sensor with this robotic system may allow for feasibility and safety for guiding complex anatomic-based ablation. Methods: Circumferential pulmonary vein (PV) ablation with the robotic system guided by integrated 3D images (CartoMerge, NavxMerge or CartoSound) (n=3), were done and compared to manual manipulation guided by the integrated 3D images (CartoSound) (n=8). Each ablation was performed using contact force ranges of 10 –20 grams (20W, 17 ml/min flow, 30 seconds). Accuracy of PV ablation was assessed by comparing distance from the PV ostia (specific 4 sites) to the ablative points on the 3D image structures, and the corresponding distances of the actual ablative lesions at pathologic exam. Results: Using three integrated 3D image systems, circumferential PV ablation was successfully guided in 6 PVs (3 RSPVs and 3 LSPVs) with the robotic system. During all ablations with contact forces of 10 –20 grams, no impedance rises, pops or type 2 microbubbles were seen. Accuracy of the PV ablation was 0.22±0.84 mm (range 0 –2). The PV rings were 100% circumferential by electroanatomic mapping, yielding an 86±7% (range 80 –98%) uninterrupted circumferential ablative ring around each PV with 1.1 ± 0.4 gaps (3.0 ± 0.9 mm). These resulting parameters were equal to those in the integrated 3D image-based manual navigation (Accuracy: 0.5±0.9 (range 0 –2.5) mm, Gaps:1.3 ± 0.9 ( 2.6 ± 0.9 mm), circumferential lesions 88 ± 10% (range 70 –100). Conclusions: This feasibility study demonstrated successful integrated 3D image and contact force-guided robotic ablation. Contact sensor guided 3D volume construction and real time 3D images accurately replicated atrial and venous anatomy, resulting in successful circumferential ablation.

Introduction: Unstable scar related ventricular tachycardia (VT) is a common problem after myocardial infarction. Aggressive ablation may be limited, however, by incomplete scar penetration with available RF energy delivery technologies. The purpose of this study was to test the feasibility of full thickness linear ablation of infarcted ventricular substrate with a high penetration virtual electrode needle based electrode system. Methods: Chronic infarcted (> 2months) mongrel dogs (35–40 kg) underwent percutaneous catheter ablation of the LV with a saline-injection needle catheter employing an 8 mm 20-GA tip. Constant power at 40W was delivered for 90 sec via the virtual electrode needle during infusion of saline 10 ml/h at 50°C. The lines were created under electroanatomic map guidance and intracardiac ultrasound (ICE). The ejection fraction was monitored immediately before and after the ablation. One week after ablation, the dogs where restudied using CARTO epicardial and endocardial voltage mapping and hemodynamic testing. Results: The ablation lines created by a virtual electrode energy delivery made in the antero-lateral wall showed mean length of 4.4±1.4 cm. The mean area of ablation per lesion in the endocardium, mid myocardium and epicardium was 1.1±1.0, 2.6±1.3 and 1.9±1.3 cm 2 (p<0.05) respectively, with a mean ablation depth of 1.5±0.5 cm. Sixty-four percent of the length of lesions were transmural and in non-transmural areas had an average depth of 90±16% of wall thickness. The mean number of gaps/line was 0.5±0.7 with a length of 0.6 cm. Ejection fraction was 50±14, 52±17 and 52±13% before, after and 1 week post ablation respectively. At one week the epicardial and endocardial areas of low bipolar voltage < 1.5mV and dense scar < 0.5mV in the Carto map were 11.4±1.2 and 7.9±6.1cm 2 respectively which measurements were confirmed at necropsy by macroscopic scar in the epicardium and endocardium of 11.8±4.3 and 6.6±4.1 cm 2 respectively. Conclusion: This new novel saline-injection needle catheter effectively creates continuous long transmural lines in the infarcted LV. These data also confirm that the macroscopic ablation lesions can be consistently and accurately monitored by 3D electroanatomical mapping in both endocardium and epicardium.

Radiofrequency (RF) ablation for cardiac arrythmias is an established curative therapy. However, catheter-tip coagulum formation leading to thromboembolic stroke is a persistent problem despite heparinization. Recent studies demonstrated an up to 70% incidence of thrombus formation on the catheter tip during ablation and a 10 % incidence of thromboembolic events. Catheter tip thrombus can impede the delivery of RF energy to the tissue, resulting in reduced efficacy and longer procedure times. Here we report on a novel method to prevent coagulum formation on ablation catheters by delivering a negative charge to the catheter tip to repel negatively charged fibrinogen molecules during RF ablation. A novel circuit was built with a charge delivery unit using a 9 voltage battery to deliver a fixed offset direct current charge, placed in parallel to the RF delivery unit for negative charge placement during RF delivery. In in-vivo canine experiments (n=50) standard 6/4, 8/5 ablation catheters and catheters with abraded tips were advanced from right femoral veins into atria and ventricles under intra-cardiac echo (ICE) and biplane fluoroscopic guidance. The dogs received 1 of 2 therapies: no RF energy delivered with and without negative charge delivery, RF energy delivery with and without negative charge delivery. The presence of thrombus was identified with ICE. The catheter tips were examined also macroscopically with visual inspection and also with field emission scanning electron microscopy (FESEM). FESEM of the catheter tips showed surface coverage of fibrin clot of the catheter tip to be 90 % for non-charged catheters compared to 0 % (p< 0.01) in negatively-charged catheters. There was no significant difference in surface coverage of fibrin clot between negatively-charged catheters with the abraded tips (98.8%) and non-charged catheters with smooth tips (90.7 %, p=ns). Clot volume formed on the catheter tip decreased with increased amount of charge. Application of a negative charge did not affect the quality of the intracardiac electrograms or induce malignant ventricular arrhythmias. Negative charge delivery during RF ablation is feasible and safe and can eliminate coagulum formation, potentially reducing thromboembolic complications.

Background: Although pulmonary vein (PV) isolation has been used to treat AF, complications create important limitations. New energy sources, including cryothermal, have been developed to minimize these complications. The purpose of this study was to evaluate the effect of PV cryoablation on esophageal (ESO) temperatures acutely and correlate them with chronic effects on the esophageal wall. Methods: A 23 mm cryoballoon was placed in the LA of 10 dogs through a 12 Fr deflectable sheath. PV and ESO temperatures (TEMP) were recorded using 7–9 thermocouples (TC) outside the PVs and on the external and internal ESO surfaces during 2 cryoablations of 4 min duration. Results : Cryoablation of 15 PV (10 RIPV and 5 LIPV) during 1.7±0.6 ablations yielded a total of 168 TC time-TEMP profiles (6.4±2.4/PV). Minimum tissue TEMP was inversely dependent on the distance of the TC from the balloon surface (Table 1 ). All PVs were isolated acutely and 14/15 (93%) chronically. Minimum TEMP achieved at the PV surface and external ESO were similar (−32±8 and −37±9 at targets within 2.5 mm from the balloon respectively [P=NS]). A TEMP decrease at the internal ESO was seen during 15 of 25 (60%) ablations, but was significantly less pronounced than the external TEMP (17.9°C±13.3 and 6.1°C±24.8 [p<0.05]) resulting in a minimum recorded internal TEMP of −6.2°C. The ESO histological examination in 5 dogs showed very limited external lesions in these dogs (depth= 2.2±1.1, width3 18.6±7.4 and length= 12±5.7 mm), but no transmural or internal ulceration, fibrosis or scarring seen. Conclusion: Although PV cryoablation decreases external ESO temperature and produces minor lesions, significant chronic disruptive tissue damage was not seen. Esophageal injury is an unlikely, but potential complication of cryoablation, with internal temperature proving unhelpful in predict negative outcome.

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.

BackgroundEndocardial ablation of atrial ganglionated plexi (GP) has been described for treatment of atrial fibrillation (AF). Our objective in this study was to develop percutaneous epicardial GP ablation in a canine model using novel energy sources and catheters.MethodsPhase 1: The efficacy of several modalities to ablate the GP was tested in an open chest canine model (n = 10). Phase 2: Percutaneous epicardial ablation of GP was done in six dogs using the most efficacious modality identified in phase 1 using two novel catheters.ResultsPhase 1: Direct current (DC) in varying doses (blocking [7–12 μA], electroporation [300–500 μA], ablation [3,000–7,500 μA]), radiofrequency ablation (25–50 W), ultrasound (1.5 MHz), and alcohol (2–5 mL) injection were successful at 0/8, 4/12, 5/7, 3/8, 1/5, and 5/7 GP sites. DC (500–5,000 μA) along with alcohol irrigation was tested in phase 2. Phase 2: Percutaneous epicardial ablation of the right atrium, oblique sinus, vein of Marshall, and transverse sinus GP was successful in 5/6 dogs. One dog died of ventricular fibrillation during DC ablation at 5,000 μA. Programmed stimulation induced AF in six dogs, preablation and no atrial arrhythmia in three, flutter in one, and AF in one postablation. Heart rate, blood pressure, effective atrial refractory period, and local atrial electrogram amplitude did not change significantly postablation. Microscopic examination showed elimination of GP, and minimal injury to atrial myocardium.ConclusionPercutaneous epicardial ablation of GP using DC and novel catheters is safe and feasible and may be used as an adjunct to pulmonary vein isolation in the treatment of AF in order to minimize additional atrial myocardial ablation.

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.