Novel Percutaneous Epicardial Autonomic Modulation in the Canine for Atrial Fibrillation: Results of an Efficacy and Safety Study.

BACKGROUND: Endocardial 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. METHODS: Phase 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. RESULTS: Phase 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. CONCLUSION: Percutaneous 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.

Compatibility of electroanatomical mapping systems with a concurrent percutaneous axial flow ventricular assist device.

BACKGROUND: Hemodynamic instability hinders activation and entrainment mapping during ventricular tachycardia ablation. The Impella 2.5 microaxial flow device (MFD; Abiomed Inc., Danvers, MA, USA) is used to prevent hemodynamic instability during electrophysiologic study. However, electromagnetic interference (EMI) generated by this device can preclude accurate electroanatomic mapping. METHODS: Impella was placed in the left ventricle of 7 canines for circulatory support. Electroanatomic mapping during sinus rhythm, ventricular pacing, and ventricular fibrillation (VF) was performed using magnet- (CARTO3, Biosense Webster Inc., Diamond Bar, CA, USA) and impedance- (EnSite Velocity System/EnSite NavX, St. Jude Medical Inc., St. Paul, MN, USA) based systems. Distance from device to points with severe EMI precluding acquisition was compared to points with mild/no EMI. Two methods were used to reduce EMI: (1) titration of MFD performance, and (2) impedance-only mapping combined with manual annotation of activation. RESULTS: Severe EMI did not occur during impedance-based mapping. Severe EMI was observed using CARTO3 at 9.4% of all points attempted at maximum performance level (P8) of device. Severe EMI occurred at points closer to device (40.1 ± 16.8 mm) versus (55.5 ± 20.0 mm) for mild/no EMI, P < 0.0001. Severe EMI using CARTO3 was resolved by either (1) reduction of performance from P8 to P6 or (2) impedance-only mapping with manual annotation. CONCLUSION: Concurrent use of MFD caused EMI to prevent acquisition of points with magnet-based mapping. Predictors for EMI were distance from device and performance level. Temporary reductions to P6 or impedance-only mapping are 2 methods to resolve EMI.

Transvenous stimulation of the renal sympathetic nerves increases systemic blood pressure: a potential new treatment option for neurocardiogenic syncope.

BACKGROUND: Neurocardiogenic syncope (NCS) is a common and sometimes debilitating disorder, with no consistently effective treatment. NCS is due to a combination of bradycardia and vasodilation leading to syncope. Although pacemaker devices have been tried in treating the bradycardic aspect of NCS, no device-based therapy exists to treat the coexistent vasodilation that occurs. The renal sympathetic innervation has been the target of denervation to treat hypertension. We hypothesized that stimulation of the renal sympathetic nerves can increase blood pressure and counteract vasodilation in NCS. METHODS AND RESULTS: High-frequency stimulation (800-900 pps, 10 V, 30-200 seconds) was performed using a quadripolar catheter in the renal vein of 7 dogs and 1 baboon. A significant increase in blood pressure (BP; mean [SD] systolic BP 117 [±28] vs. 128 [±33], diastolic BP 75 [±19] vs. 87 [±29] mmHg) was noted during the stimulation, which returned to baseline after cessation of stimulation. The mean increase in systolic and diastolic BP was 13.0 (±3.3) (P = 0.006) and 10.2 (±4.6) (P = 0.08), respectively. CONCLUSION: We report the first ever study of feasibility and safety of high-frequency electrical stimulation of the renal sympathetic innervation to increase BP in animal models. This has potential applications in the treatment of hypotensive states such as NCS.

Percutaneous epicardial left atrial appendage closure: intermediate-term results.

UNLABELLED: Chronic Percutaneous Epicardial Appendage Closure. OBJECTIVES: To assess the chronic safety and feasibility of percutaneous epicardial closure of the left atrial appendage (LAA) guided by electrical navigation. BACKGROUND: Atrial fibrillation (AF) is associated with stroke, and LAA occlusion may be a useful nonpharmacologic strategy for stroke prevention in AF. METHODS: Percutaneous epicardial access was obtained in 6 dogs under general anesthesia. The ligation system included a grabber that captures the LAA guided by local electrograms (EGMs) and a looped hollow suture preloaded with a central wire enabling control and visualization. After a satisfactory position is confirmed the loop is tightened remotely, and the suture cut. Transesophageal echocardiography (TEE) assessed LAA dimensions and flow. LAA EGMs were recorded pre- and postclosure, and neurohormonal markers measured. Pathologic examination was performed. RESULTS: LAA ligation was successful in all dogs. LAA flow was immediately abolished in 5 of 6 dogs. Disappearance of local LAA EGMs following ligation was observed in all animals. Follow-up TEE at mean 54 days (range 23-75 days) documented residual flow in only the first 2 dogs. Prior to necropsy the LAA was examined at thoracotomy in 3 animals. Following a minor design change, complete closure and fibrosis with a remnant atretic LAA was noted in all animals. No damage to adjacent structures was noted. Neurohormonal markers were unchanged. CONCLUSION: Percutaneous epicardial LAA ligation guided by electrical navigation is feasible with promising intermediate-term results in the canine model. The technique may be useful as an alternative to existing methods of LAA obliteration in humans.

Use of the aortoatrial continuity as means of providing left ventricular assist support without entering the ventricle: a feasibility study.

BACKGROUND: Left ventricular assist devices (LVADs) are increasingly used to treat patients with refractory heart failure. Current-generation LVADs have major limitations, including the need for open chest surgery, limiting their widespread use. We hypothesized that the aortoatrial continuity could be used as a unique anatomic vantage point for entirely percutaneous LVAD placement. METHODS AND RESULTS: Forty human autopsied hearts were examined to ascertain the presence and define the dimensions of the continuity between the posterior aortic wall and the left atrium. In all cases, a "septum" between the aorta and left atrium was identified. In 3 animal experiments, a custom mechanical shunt was deployed in the wall between the left atrium and noncoronary cusp. With continuous intracardiac ultrasound imaging, and at necropsy, there was no evidence of device dislodgement, pericardial effusion, or aortic or coronary artery trauma noted. CONCLUSIONS: It is feasible to use the wall between the aorta and left atrium as an access route for a potentially entirely percutaneous LVAD. Such a system obviates the need for accessing the left ventricle, minimizing complications. In the future, such devices may allow widespread treatment of heart failure, malignant cardiac arrhythmia, and severe aortic and mitral valvular disease.

Distortion of right superior pulmonary vein anatomy by balloon catheters as a contributor to phrenic nerve injury.

INTRODUCTION: Cryothermal, HIFU, and laser catheter-based balloon technologies have been developed to simplify ablation for AF. Initial enthusiasm for their widespread use has been dampened by phrenic nerve (PN) injury. The interaction between PN and pulmonary vein (PV) geometry contributing to PN injury is unclear. METHODS AND RESULTS: After right thoracotomy, the PN course along the epicardial right atrial surface was mapped directly in 10 dogs. The location of the PN and its relationship with the right superior (RS) PV, and potential RSPV surface distortions after balloon inflation were established by electroanatomic mapping. In 5 dogs, the PN was captured within the RSPV, but could not be stimulated in the remaining 5 dogs. The distance between the RSPV and the PN was significantly shorter in the captured group than in the noncaptured group (6.3 +/- 3.1 mm vs 10.2 +/- 3.2 mm, P < 0.001). Importantly, 96% of the captured sites within the RSPV were observed at a distance >5 mm into the PV. The inflated balloon surface anteriorly extended 5.6 +/- 3.7 mm outside the PV diameter, with distortion of anatomy narrowing the distance from the balloon surface to the PN to 4.8 +/- 2.3 mm. (Distance of the original RSPV-to-PN: 9.4 +/- 2.7 mm, P < 0.001.) CONCLUSION: PN injury with balloon technologies may stem from anatomic distortion of the PV orifice/PN relationship, through increasing contact or shortening the relative distance between the ablation site and the PN, even without displacement of the balloon into the PV. These data are important in the refinement of these technologies to improve procedural safety.

Percutaneous epicardial left atrial appendage closure: preliminary results of an electrogram guided approach.

BACKGROUND: Pharmacologic therapies to prevent stroke in atrial fibrillation (AF) have numerous limitations, prompting the development of device-based therapies. We investigated whether an electrogram-based approach using a novel hollow suture can safely capture and ligate the left atrial appendage (LAA). METHODS AND RESULTS: A novel system for closure of the LAA within the confines of the closed pericardium with a single sheath puncture was tested in 4 dogs. The tool used to grasp the appendage was fitted with electrodes and utilized electrical navigation to identify and confirm LAA capture. A hollow suture preloaded with a mechanical support wire to permit its manipulation and fluoroscopic visualization was advanced over the grasper, and the wire removed after the suture was positioned. The LAA was successfully closed in all dogs. In 2 dogs, after closure, a thoracotomy was performed and the LAA amputated without bleeding, confirming closure integrity. Necropsy confirmed closure in all animals. CONCLUSIONS: Using electrical navigation, percutaneous epicardial LAA ligation with a remotely tightened suture was performed successfully within the confines of the intact pericardial space. This technique may allow decreasing the risk of stroke in AF patients without the need for thoracotomy or an endocardially placed prosthetic device.

Synchronous ventricular pacing without crossing the tricuspid valve or entering the coronary sinus--preliminary results.

BACKGROUND: Right ventricular apical (RVA) pacing promotes tricuspid regurgitation (TR), electromechanical dyssynchrony, and ventricular dysfunction. We tested a novel intramyocardial bipolar lead to assess whether stimulation of the atrioventricular septum (AVS) produces synchronous ventricular activation without crossing the tricuspid valve (TV). METHODS: A lead with an active external helix and central pin was placed on the AVS and the RVA in three dogs. High-density electroanatomic (EA) mapping was performed of both ventricles endocardially and epicardially. Intracardiac echocardiography was used to access ventricular synchrony. RESULTS: The lead was successfully deployed into the AVS in all cases with consistent capture of the ventricular myocardium without atrial capture or sensing. The QRS duration was less with AVS compared with RVA pacing (89 +/- 4 ms vs. 100 +/- 11 ms [P < 0.0001, GEE P = 0.03]). There was decreased delay between color Doppler M-mode visualized peak contraction of the septum and the mid left ventricular free wall with AVS compared with RVA pacing (89 +/- 91 ms vs. 250 +/- 11 ms [P < 0.0001, GEE P = 0.006]). Activation time between the mid septum and mid free wall was shorter with AVS versus RVA pacing (20.4 +/- 7.7 vs. 30.8 +/- 11.6 [P = 0.01, GEE P = 0.07]). The interval between QRS onset to earliest free wall activation was shorter with AVS vs. RVA pacing (19.2 +/- 6.4 ms vs. 31.1 +/- 11.7 ms [P = 0.005, GEE P = 0.02]). CONCLUSION: The AVS was successfully paced in three dogs resulting in synchronous ventricular activation without crossing the TV.

Concurrent application of charge using a novel circuit prevents heat-related coagulum formation during radiofrequency ablation.

INTRODUCTION: Thromboembolism resulting from coagulum formation on the catheter and electrode surfaces is a serious complication with radiofrequency ablation procedures for heart rhythm disorders. Why coagulum occurs despite therapeutic heparinization is unclear. In this report, we demonstrate a novel approach to minimize coagulum formation based on the electromolecular characteristics of fibrinogen. METHODS AND RESULTS: Atomic force microscopy was used to establish that fibrinogen deposited on surfaces underwent conformational changes that resulted in spontaneous clot formation. We then immersed ablation catheters that were uncharged, negatively, or positively charged in heparinized blood for 30 minutes and noted the extent of clot formation. In separate experiments, ablation catheters were sutured to the ventricle of an excised porcine heart immersed in whole, heparinized blood and radiofrequency ablation performed for 5 minutes with and without charge delivered to the catheter tips. Electron microscopy of the catheter tips showed surface coverage of fibrin clot of the catheter to be 33.8% for negatively charged catheters, compared with 84.7% (P = 0.01) in noncharged catheters. There was no significant difference in surface coverage of fibrin clot between positively charged catheters (93.8%) and noncharged catheters (84.7%, P = ns). In contrast, the thickness of surface clot coverage for positively charged catheters was 87.5%, compared with 28.45% (P= 0.03) for noncharged catheters and 11.25% (P = 0.03) for negatively charged catheters, compared with noncharged catheters. CONCLUSIONS: We describe a novel method of placing negative charge on electrodes during ablation that reduced coagulum formation. This may decrease thromboembolism-related complications with radiofrequency ablation procedures.

A systematical analysis of in vivo contact forces on virtual catheter tip/tissue surface contact during cardiac mapping and intervention.

INTRODUCTION: While catheter tip/tissue contact has been shown to be an important determinant of ablative lesions in in vitro studies, the impact of contact on the outcomes of mapping and ablation in the intact heart has not been evaluated. METHODS AND RESULTS: Twelve dogs underwent atrial ablation guided by the Senesitrade mark robotic catheter remote control system. After intracardiac ultrasound (ICE) validation of contact force measured by an in-line mechanical sensor, the relationship between contact force and individual lesion formation was established during irrigated-tipped ablation (flow 17 mL/sec) at 15 watts for 30 seconds. Minimal contact by ICE correlated with force of 4.7 +/- 5.8 grams, consistent contact 9.9 +/- 8.6 grams and tissue tenting produced 25.0 +/- 14.0 grams. Conversely, catheter tip/tissue contact by ICE was predicted by contact force. A contact force of 10-20 and > or =20 grams generated full-thickness, larger volume ablative lesions than that created with <10 grams (98 +/- 69 and 89 +/- 70 mm(3) vs 40 +/- 42 mm(3), P < 0.05). Moderate (10 grams) and marked contact (15-20 grams) application produced 1.5 X greater electroanatomic map volumes that were seen with minimal contact (5 grams) (26 +/- 3 cm(3) vs 33 +/- 6, 39 +/- 3 cm(3), P < 0.05). The electroanatomic map/CT merge process was also more distorted when mapping was generated at moderate to marked contact force. CONCLUSION: This study shows that mapping and ablation using a robotic sheath guidance system are critically dependent on generated force. These findings suggest that ablative lesion size is optimized by the application of 10-20 grams of contact force, although mapping requires lower-force application to avoid image distortions.

Mechanism of tissue heating during high intensity focused ultrasound pulmonary vein isolation: implications for atrial fibrillation ablation efficacy and phrenic nerve protection.

INTRODUCTION: The purpose of this study was to examine tissue temperatures around pulmonary veins (PVs) during high intensity focused ultrasound (HIFU) balloon ablation for atrial fibrillation. The thermodynamics and extent of PV and phrenic nerve (PN) heating during HIFU ablation have not been established. METHODS AND RESULTS: Tissue temperatures were recorded from epicardial thermocouples at right superior (RS) PV orifice and PN in eight dogs undergoing 51 RSPV HIFU ablations (40 seconds, 40 W). Maximum tissue temperatures, reflected by 288 recording profiles, were negatively correlated with distance from balloon surface (r =-0.79, P < 0.001). Average maximum RSPV temperature was 56.8 +/- 16.8 degrees C (distance: 6.6 +/- 4.1 mm), resulting in full-thickness, circumferential PV isolation in 7 of 8 animals. Direct local mechanical heating restricted to the focused ultrasound zone showed temperature rise to > or =50 degrees C within 10 seconds to a maximum temperature of 82.6 +/- 8.9 degrees C (n = 31). Apparent conductive heating showed gradual heating patterns (<50 degrees C within 10 seconds) at greater distance. PN temperature at all recording sites was 45.0 +/- 11.3 degrees C (distance: 9.2 +/- 5.0 mm). Intentional PN injury (10 of 51 [19.6%] ablations), occurred at 63.7 +/- 16.0 degrees C with closest distance of 4.4 +/- 2.5 mm, which was closer than in PNs without injury (7.3 +/- 4.3 mm, P = 0.005). CONCLUSIONS: HIFU ablation is highly effective in generating temperatures needed for full-thickness, circumferential ablation through rapid direct mechanical heating. Gradual heating of surrounding tissue supports the presence of conductive heating. This study also discloses direct HIFU effects as the mechanism of PN injury occurring within 4-7 mm from balloon surface.

Successful radiofrequency ablation of the cerebral cortex in pigs using the venous system: possible implications for treating CNS disorders.

BACKGROUND: When pharmacotherapy for epilepsy fails, surgical options, although efficacious, are highly invasive. We explored whether ablation of the cerebral cortex can be performed utilizing the cerebral venous system. METHODS: Mapping and radiofrequency ablation was performed via the venous system in two pigs. RESULTS: Eight targeted sites were successfully accessed and four targeted sites successfully ablated via the central cerebral venous network. CONCLUSION: Electrophysiological mapping and radiofrequency ablation of the cerebral cortex can be performed via the cerebral veins.

New generation of electro-anatomic mapping: full intracardiac ultrasound image integration.

Surrogate electro-anatomic-derived geometries are used as the three-dimensional (3D) basis for mapping of cardiac arrhythmias. While merged computed tomography (CT) imaging may provide stellar pulmonary vein (PV) and left atrial (LA) anatomy, the applied scans must be obtained prior to ablation, and may not reflect physiologic conditions at the time of intervention. Patient-specific, ultrasound-derived 3D imaging has been developed as an alternative basis for new generation electro-anatomic mapping. An electro-anatomic sensor positioned at the tip of the phased-array intracardiac ultrasound catheter, provides the means to specify both location and orientation of each image as the 'context' for creating the 3D volumes for co-registration with electro-anatomic mapping. Specific anatomic details such as the pulmonary veins, membranous fossa, papillary muscles, or valve structures derived from real-time imaging can also be integrated into each segmented volume. This presentation reviews the basis and methods for this novel multi-modality image fusion for the creation of robust, nearly real-time anatomic images for guiding electro-anatomic mapping and ablation without requiring pre-acquired CT image sets, with accompanying limitations.

Impact of transforming growth factor-beta1 on atrioventricular node conduction modification by injected autologous fibroblasts in the canine heart.

BACKGROUND: Atrioventricular (AV) nodal ablation for management of atrial fibrillation (AF) is irreversible and requires permanent pacemaker implantation. We hypothesized that as an alternative, implantation of autologous fibroblasts in the perinodal region would focally modify AV nodal conduction and that this modulation would be enhanced by pretreatment with transforming growth factor-beta1 (TGF-beta1), a stimulant of fibroblasts. METHODS AND RESULTS: Skin biopsies were taken from 12 mongrel dogs, and derived fibroblasts were dissociated and grown in culture for 2 weeks. Multiple injections (0.25 mL) were made through an 8F NOGA catheter along the fast/slow AV nodal pathways as guided by an electroanatomic mapping system. Seven dogs received fibroblasts alone (1x10(6) cells/mL), 7 dogs received TGF-beta1 (5 microg), 4 dogs received fibroblasts and TGF-beta1 (1x10(6) cells/mL+5 microg), and 4 dogs received saline only. AV node function was assessed at baseline and after 4 weeks. Saline (80 mL) with assigned therapy (0.25 mL per injection) was injected into the peri-AV nodal region in each dog. At baseline, the AH interval (66+/-3 ms) and the average RR interval (331+/-17 ms) in pacing-induced AF were similar in each cohort. The increase in AH interval in normal sinus rhythm was longer after fibroblast (23+/-4 versus 5+/-5 ms; P=0.05) and fibroblast plus TGF-beta1 (50+/-5 versus 5+/-5 ms; P<0.001) injections than with saline alone, with similar findings during high right atrium and distal coronary sinus pacing. The AH interval was not significantly increased after TGF-beta1 injections. The AH interval was significantly longer after fibroblast plus TGF-beta1 injections than with either therapy (TGF-beta1 or fibroblasts) alone. The RR interval during AF was increased in dogs that received fibroblasts alone (110+/-36 versus -41+/-34 ms) and to a greater extent with the addition of TGF-beta1 (294+/-108 versus -41+/-34 ms). No AV block was seen in any cohort at 4 weeks. Labeled fibroblasts that expressed vimentin were identified in all dogs that received cell injections at 4 weeks. CONCLUSIONS: AV nodal modification can be achieved with injected fibroblasts without the creation of AV block. The effect on AV node conduction is substantially enhanced by pretreatment of fibroblasts with TGF-beta1. These data have therapeutic potential for the management of rapid ventricular rate during AF without pacemaker implantation.

External Arrhythmia Ablation Using Photon Beams: Ablation of the Atrioventricular Junction in an Intact Animal Model.

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.

Discrepancies between catheter tip and tissue temperature in cooled-tip ablation: relevance to guiding left atrial ablation.

BACKGROUND: It is not known whether catheter tip temperatures with a cooled-tip ablation can be reliably extrapolated to estimate actual tissue temperatures. The relationship between catheter tip temperatures, tissue temperatures, power, and microbubble formation is not known. METHODS AND RESULTS: Nine dogs underwent 111 radiofrequency energy deliveries at the pulmonary vein ostia with a cooled-tip catheter. Catheter tip and tissue temperatures were markedly discrepant. Catheter tip temperature plateaus at 36 degrees C to 39 degrees C with increasing power, whereas tissue temperature increases to a mean of 75+/-3 degrees C at 45 W (maximum temperature >100 degrees C). Seventy-two energy deliveries were performed, titrating power to microbubble formation guided by intracardiac echocardiography. Type I and II microbubble formation occurred in 45 (63%) and 19 (26%) ablations, respectively. Type I microbubble emergence occurred at lower powers (21+/-8 versus 26+/-4 W; P=0.05), catheter tip temperatures (38+/-5 degrees C versus 48+/-10 degrees C; P=0.02), and tissue temperatures (65+/-19 degrees C versus 81+/-9 degrees C; P<0.001) than type II microbubble formation. Maximum impedance decreases during ablation before microbubble formation were less with type I microbubble (20+/-9 versus 37+/-11 Omega; P<0.001) compared with type II microbubbles. One quarter of type I microbubbles abruptly transitioned to type II microbubbles with significant changes in power or catheter tip temperature. No microbubbles were seen in 19 ablations (26%) despite powers up to 26+/-9 W and tissue temperatures up to 81+/-17 degrees C. CONCLUSIONS: Catheter tip and tissue temperatures are markedly discrepant during cooled-tip ablation. Type I and II microbubble formation occurs at overlapping power and catheter tip and tissue temperature ranges. Neither the absence of microbubbles nor the presence of type I microbubble formation ensures against excessive tissue heating. The appearance of microbubbles may indicate possible tissue overheating and signal a need to decrease energy.

Prevention of Coagulum Formation With Simultaneous Charge Delivery in Radiofrequency Ablation: A Canine Model.

OBJECTIVES: This study reports on a novel method to prevent coagulum formation by continuously delivering a negative charge to the catheter tip to repel negatively charged fibrinogen molecules during RF ablation. BACKGROUND: Radiofrequency (RF) ablation for cardiac arrhythmias is associated with a 70% incidence of coagulum formation on the catheter tip during ablation and a 10% incidence of thromboembolic events. Catheter tip thrombus can impede RF energy to the tissue, reducing efficacy and increasing procedure times. METHODS: A novel circuit was built to deliver a negative, fixed-offset, direct current-based charge using a 9-V battery, placed in parallel with an RF delivery unit during RF ablation. In in vivo canine experiments, standard ablation catheters were advanced into atria and ventricles under fluoroscopic guidance. The presence of thrombus with and without RF delivery was identified with intracardiac echocardiography. RESULTS: Scanning electron microscopy of the catheter tips showed clot coverage of the catheter tip to be 90% for noncharged catheters compared to 0% (p < 0.01) in negatively charged catheters. Volume of clot formed on the catheter tip decreased with increased amount of charge (140 ± 5.3 arbitrary units with no charge vs. 0 arbitrary units with a 100-µA current delivering negative charge, p < 0.01). Application of a negative charge did not affect the quality of the intracardiac electrogram or induce malignant ventricular arrhythmias. CONCLUSIONS: Negative-charge delivery to ablation catheter tips and tissue during RF ablation is feasible and safe and can eliminate coagulum formation, potentially reducing thromboembolic complications.

Effect of Left Atrial Ablation Process and Strategy on Microemboli Formation During Irrigated Radiofrequency Catheter Ablation in an In Vivo Model.

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.

Novel Techniques in Epilepsy Management: Venous Pacing and Capture of Electrical Activity in the Primate Cortex.

OBJECTIVE: Pharmacotherapy for epilepsy is limited with 30% of patients refractory to this approach of suppressing seizures. Current surgical options are invasive and carry significant morbidities including infection, bleeding, and the potential for deleterious neurocognitive effects. As a result, there is a burgeoning need for innovation to develop safer and efficacious interventions. METHODS: Four distinct catheters (2 existing: Cardima catheter, Standard EPT Blazer catheter; 2 new prototypes: balloon catheter, basket catheters) were tested in 12 baboons (21-30 kg, 100% male). For each, we assessed whether or not the catheter was able to be maneuvered safely in various locations of the cerebral venous system, provide adequate cortical tissue contact to record signals, detect these signals as normal or abnormal, successfully stimulate the cortex, and capture the cortical tissue. Locations trialed included the petrosal sinus, straight sinus, vein of Galen, and occipital vein. Pacing cycle length and pacing thresholds varied among experiments. RESULTS: Successful mapping was conducted in all 12 baboons. The pacing cycle length varied from 75 ms to 650 ms depending on location of the cortex. Pacing threshold was recorded in 4/12 (33%) of the experiments; data is not available for the remaining 8/12 experiments. The threshold values ranged from 0.3 - 20 mAmps. Capture of cortical electrical activity was observed in 11/12 (91.7 %) experiments though the number of successful capture and stimulation attempts varied among experiments. The most reliable and consistent capture occurred with the use of our novel prototyped over-the-wire balloon catheter (9/12; 75%) and basket catheter (3/3; 100%). Necropsy and histology were performed post-experimentation, and only minimal complications were noted (Table 1). CONCLUSION: New electrode design can be maneuvered safely in the venous system, provide adequate cortical tissue contact to record signals, detect these signals as normal or abnormal, successfully stimulate the cortex, and capture cortical tissue. These novel devices merit further study in chronic baboons to establish long-term efficacy of continuous seizure recording.

Feasibility Study on Cardiac Arrhythmia Ablation Using High-Energy Heavy Ion Beams.

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.