Focal Pulsed Field Ablation for Pulmonary Vein Isolation and Linear Atrial Lesions: A Preclinical Assessment of Safety and Durability.

BACKGROUND: A novel ablation and mapping system can toggle between delivering biphasic pulsed field (PF) and radiofrequency energy from a 9-mm lattice-tip catheter. We assessed the preclinical feasibility and safety of (1) focal PF-based thoracic vein isolation and linear ablation, (2) combined PF and radiofrequency focal ablation, and (3) PF delivered directly atop the esophagus. METHODS: Two cohorts of 6 swine were treated with pulsed fields at low dose (PFLD) and high dose (PFHD) and followed for 4 and 2 weeks, respectively, to isolate 25 thoracic veins and create 5 right atrial (PFLD), 6 mitral (PFHD), and 6 roof lines (radiofrequency+PFHD). Baseline and follow-up voltage mapping, venous potentials, ostial diameters, and phrenic nerve viability were assessed. PFHD and radiofrequency lesions were delivered in 4 and 1 swine from the inferior vena cava onto a forcefully deviated esophagus. All tissues were submitted for histopathology. RESULTS: Hundred percent of thoracic veins (25 of 25) were successfully isolated with 12.4±3.6 applications/vein with mean PF times of <90 seconds/vein. Durable isolation improved from 61.5% PFLD to 100% with PFHD (P=0.04), and all linear lesions were successfully completed without incurring venous stenoses or phrenic injury. PFHD sections had higher transmurality rates than PFLD (98.3% versus 88.1%; P=0.03) despite greater mean thickness (2.5 versus 1.3 mm; P<0.001). PF lesions demonstrated homogenous fibrosis without epicardial fat, nerve, or vessel involvement. In comparison, radiofrequency+PFHD sections revealed similar transmurality but expectedly more necrosis, inflammation, and epicardial fat, nerve, and vessel involvement. Significant ablation-related esophageal necrosis, inflammation, and fibrosis were seen in all radiofrequency sections, as compared with no PF sections. CONCLUSIONS: The lattice-tip catheter can deliver focal PF to durably isolate veins and create linear lesions with excellent transmurality and without complications. The PF lesions did not damage the phrenic nerve, vessels, and the esophagus.

Termination of persistent atrial fibrillation during pulmonary vein isolation: insight from the MAGIC-AF trial.

AIMS: Controversy on the optimal ablation strategy for persistent atrial fibrillation (AF) exists with limited work evaluating a strategy of pulmonary vein isolation (PVI) alone when AF terminates during PVI. Thirty-five patients had AF termination during PVI in the Modified Ablation Guided by Ibutilide Use in Chronic Atrial Fibrillation (MAGIC-AF; ClinicalTrials.gov number: NCT01014741) study. The objective of the current study is to report the 1-year outcome after PVI alone in this unique patient group. METHODS AND RESULTS: The 1-year single procedure freedom from atrial arrhythmia off anti-arrhythmic drugs was reported for the 35 patients in the MAGIC-AF study with persistent AF termination during or upon completion of PVI. Freedom from recurrent atrial arrhythmia was achieved in 60% of patients where AF terminated during PVI. Cavotricuspid isthmus flutter was common when AF terminated to a macro re-entrant flutter during PVI, and responsible for 92% of all flutter circuits with AF termination. CONCLUSIONS: Persistent AF termination during PVI may identify a subgroup of patients who experience a similar long-term clinical outcome with PVI ablation alone when compared with other more extensive persistent AF ablation strategies. Pulmonary vein isolation alone may be an appropriate tactic in this subgroup of persistent AF patients.

The modified stepwise ablation guided by low-dose ibutilide in chronic atrial fibrillation trial (The MAGIC-AF Study).

AIMS: Complex fractionated atrial electrograms (CFAE) are targeted during persistent atrial fibrillation (AF) ablation. However, many CFAE sites are non-specific resulting in extensive ablation. Ibutilide has been shown to reduce left atrial surface area exhibiting CFAE. We hypothesized that ibutilide administration prior to CFAE ablation would identify sites critical for persistent AF maintenance allowing for improved procedural efficacy and long-term freedom from atrial arrhythmias. METHODS AND RESULTS: Two hundred patients undergoing a first-ever persistent AF catheter ablation procedure were randomly assigned to receive either 0.25 mg of intravenous ibutilide or saline placebo upon completion of pulmonary vein isolation. Complex fractionated atrial electrogram sites were then targeted with ablation. The primary efficacy endpoint was the 1-year single procedure freedom from atrial arrhythmia off anti-arrhythmic drugs. Similar procedural characteristics (procedure, fluoroscopy, and ablation times) were observed with both strategies despite a greater reduction in left atrial surface area with CFAE sites (8 vs. 1%, P < 0.0001) and AF termination during CFAE ablation with ibutilide compared with placebo (75 vs. 57%, P = 0.007). The primary efficacy endpoint was achieved in 56% of patients receiving ibutilide and 49% receiving placebo (P = 0.35). No significant differences in peri-procedural complications were observed in both groups. CONCLUSION: Despite a reduction in CFAE area and greater AF termination during CFAE ablation, procedural characteristics and clinical outcomes were unchanged when CFAE ablation was guided by ibutilide administration. CLINICAL TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov number: NCT01014741.

Characteristics of ventricular tachycardia ablation in patients with continuous flow left ventricular assist devices.

BACKGROUND: Left ventricular assist devices (LVADs) are increasingly used as a bridge to cardiac transplantation or as destination therapy. Patients with LVADs are at high risk for ventricular arrhythmias. This study describes ventricular arrhythmia characteristics and ablation in patients implanted with a Heart Mate II device. METHODS AND RESULTS: All patients with a Heart Mate II device who underwent ventricular arrhythmia catheter ablation at 9 tertiary centers were included. Thirty-four patients (30 male, age 58±10 years) underwent 39 ablation procedures. The underlying cardiomyopathy pathogenesis was ischemic in 21 and nonischemic in 13 patients with a mean left ventricular ejection fraction of 17%±5% before LVAD implantation. One hundred and ten ventricular tachycardias (VTs; cycle lengths, 230-740 ms, arrhythmic storm n=28) and 2 ventricular fibrillation triggers were targeted (25 transseptal, 14 retrograde aortic approaches). Nine patients required VT ablation <1 month after LVAD implantation because of intractable VT. Only 10/110 (9%) of the targeted VTs were related to the Heart Mate II cannula. During follow-up, 7 patients were transplanted and 10 died. Of the remaining 17 patients, 13 were arrhythmia-free at 25±15 months. In 1 patient with VT recurrence, change of turbine speed from 9400 to 9000 rpm extinguished VT. CONCLUSIONS: Catheter ablation of VT among LVAD recipients is feasible and reasonably safe even soon after LVAD implantation. Intrinsic myocardial scar, rather than the apical cannula, seems to be the dominant substrate.

Areas with complex fractionated atrial electrograms recorded after pulmonary vein isolation represent normal voltage and conduction velocity in sinus rhythm.

AIMS: Although complex fractionated atrial electrograms (CFAEs) are purported to represent critical sites for atrial fibrillation (AF) perpetuation, the mechanism and the significance of CFAE in the genesis of AF remain poorly understood. This study evaluated the relationship between CFAE and areas of abnormal atrial tissue defined by low-voltage electrograms (LVE) and signal average of the P-wave (SAPW). METHODS AND RESULTS: Complex fractionated atrial electrogram maps were obtained after pulmonary vein isolation in 15 patients with persistent AF. Patients were then cardioverted and voltage/activation maps were acquired in normal sinus rhythm (NSR). Total left atrium (LA), CFAE and LVE areas were measured as % of total LA area (mean ± SD). Conduction velocities of normal, LVE and CFAE areas were also measured during NSR. Patients underwent signal averaged ECG of the P-wave in NSR within 24 h of the procedure. Complex fractionated atrial electrograms areas accounted for 33 ± 24% of total LA. In NSR, only 12 ± 10% of LA area had LVE. There was no anatomic correlation between CFAE sites and LVE; the area of overlap between CFAE and LVE was only 1.6 ± 1.5%. Conduction velocity was faster in CFAE areas (2.3 ± 1.4 m/s) than in normal voltage areas (1.3 ± 0.3 m/s), and LVE areas (1.1 ± 0.7 m/s, P = 0.06). A positive correlation was only found between LVE areas and SAPW duration (r = 0.7, P = 0.04). CONCLUSION: Areas of CFAEs correspond to areas of normal atrial voltage and normal conduction velocity during NSR. Complex fractionated atrial electrogram probably represents the response of normal healthy atrial tissue to rapid pulmonary vein activation.

Percutaneous hemodynamic support with Impella 2.5 during scar-related ventricular tachycardia ablation (PERMIT 1).

BACKGROUND: Percutaneous left ventricular assist devices (pLVADs) are increasingly being used to facilitate ablation of unstable ventricular tachycardia (VT), but the safety profile and hemodynamic benefits of these devices have not been described in a systematic, prospective manner. METHODS AND RESULTS: Twenty patients with scar VT underwent ablation with a pLVAD. Neuromonitoring using cerebral oximetry was performed to evaluate a cerebral desaturation threshold to guide the duration of activation/entrainment mapping. The efficacy of pLVAD support was tested in a controlled manner with simulated VT. Complete procedural success was achieved in 50% (n=8) of patients, who were initially inducible for sustained VT, and partial procedural success in 37% (n=6). Using a cerebral desaturation level of 55% as a lower safety limit to guide the duration of sustained VT, 3 patients (15%) developed mild acute kidney injury (all resolved), and 1 (5%) patient developed mild cognitive dysfunction. During fast simulated VT (300 ms), cerebral desaturation to ≤55% occurred in more than half (53%) of patients tested without pLVAD support, compared with only 5% with full pLVAD support (P=0.003). CONCLUSIONS: In a consecutive series of patients with severe left ventricular dysfunction, pLVAD-supported scar VT ablation was safe and feasible. During fast simulated VT, a miniaturized axial flow pump imparted a more favorable hemodynamic profile compared with pharmacological agents alone. Cerebral oximetry is a complimentary monitoring modality during scar VT ablation, and avoidance of cerebral desaturations below a threshold of 55% may safely guide the duration of mapping during unstable VT.

Acute electrical isolation is a necessary but insufficient endpoint for achieving durable PV isolation: the importance of closing the visual gap.

AIMS: Temporary, ablation-mediated effects such as oedema may cause reversible pulmonary vein (PV) isolation. To investigate this, point-by-point circumferential ablation was performed to achieve acute electrical PV isolation with an incomplete circumferential ablation line. Then, the impact of this intentional 'visual gap' (ViG) on the conduction properties of the ablation lesion set was assessed with adenosine and pacing manoeuvres. METHODS AND RESULTS: Twenty-eight patients undergoing ablation for paroxysmal (n= 20) or persistent atrial fibrillation (n= 8) were included. Pulmonary vein (PV) ablation was performed around ipsilateral vein pairs. Once acute isolation was achieved, ablation was halted and the presence and size of the ViG were calculated. The ViG electrophysiological properties were tested with pace capture along the ViG at 10 mA/2 ms, and assessment for dormant PV conduction with adenosine. Despite electrical isolation, a ViG was present in 75% (n= 42/56) of vein pairs (21 of 28 left PVs and 21 of 28 right PVs). There was no difference in the ViG size between the left and right PVs (22.1 ± 14.2 and 17.3 ± 11.3 mm, P > 0.05). Dormant PV connections were revealed by adenosine in more than a quarter (n= 12/42) of acutely isolated PV pairs, of which the majority were dependent on conduction through the ViG. CONCLUSIONS: Electrical PV isolation can usually be achieved without complete circumferential ablation. However, more than a quarter of these 'isolated' PVs exhibit dormant conduction-predominantly via the un-ablated 'ViGs' in the ablation lesion set. These findings support the hypothesis that reversible tissue injury contributes to PV isolation that may be acute but not necessarily durable.

The durability of pulmonary vein isolation using the visually guided laser balloon catheter: multicenter results of pulmonary vein remapping studies.

BACKGROUND: The visually guided laser ablation (VGLA) catheter is a compliant, variable-diameter balloon that delivers laser energy around the pulmonary vein (PV) ostium under real-time endoscopic visualization. While acute PV isolation has been shown to be feasible, limited data exist regarding the durability of isolation. OBJECTIVE: We sought to determine the durability of PV isolation following ablation using the balloon-based VGLA catheter. METHODS: The VGLA catheter was evaluated in patients with paroxysmal atrial fibrillation (3 sites, 10 operators). Following transseptal puncture, the VGLA catheter was advanced through a 12-F deflectable sheath and inflated at the target PV ostium. Under endoscopic guidance, the 30° aiming arc was maneuvered around the PV and laser energy was delivered to ablate tissue in a contiguous/overlapping manner. At ∼3 months, all patients returned for a PV remapping procedure. RESULTS: In 56 patients, 202 of 206 PVs (98%) were acutely isolated. At 105 ± 44 (mean ± SD) days, 52 patients returned for PV remapping at which time 162 of 189 PVs (86%) remained isolated and 32 of 52 patients (62%) had all PVs still isolated. On comparing the operators performing <10 vs ≥ 10 procedures, the durable PV isolation rate and the percentage of patients with all PVs isolated were found to be 73% vs 89% (P = .011) and 57% vs 66% (P = .746), respectively. After 2 procedures and 12.0 ± 1.9 months of follow-up, the drug-free rate of freedom from atrial fibrillation was 71.2%. CONCLUSIONS: In this multicenter, multioperator experience, VGLA resulted in a very high rate of durable PV isolation with a clinical efficacy similar to that of radiofrequency ablation.

The Modified Ablation Guided by Ibutilide Use in Chronic Atrial Fibrillation (MAGIC-AF) Study: clinical background and study design.

BACKGROUND: Beyond pulmonary vein isolation (PVI), adjuvant ablation at the sites of complex fractionated atrial electrograms (CFAE) has been shown to improve the long-term success of catheter ablation of persistent atrial fibrillation (AF). However, this approach often requires extensive ablation due to the widespread distribution of CFAE within the left atrium. An optimal strategy would identify areas of CFAE which, when selectively targeted with ablation, result in AF termination with an acceptable long-term freedom from AF. It is possible that the intraprocedural administration of an antiarrhythmic drug may help accomplish this. OBJECTIVE: The Modified Ablation Guided by Ibutilide Use in Chronic AF (MAGIC-AF) Study is an international multicenter prospective randomized double-blinded clinical trial assessing the utility of the intraprocedural administration of 0.25 mg of intravenous ibutilide before performing CFAE ablation. The primary efficacy endpoint of this study will be the freedom from AF at 1 year after a single procedure off antiarrhythmic agents. Safety endpoints will include procedural and radiofrequency ablation time as well as overall procedural complication rate. METHODS: Patients undergoing a first ever catheter ablation procedure for persistent AF will be included. Individuals with hypertrophic cardiomyopathy, complex congenital heart disease including atrial septal defects, and ejection fraction <35% will be excluded from the study. All patients will first undergo PVI. Those patients who remain in AF will then be randomized in a 1:1 fashion to receive either 0.25 mg intravenous ibutilide or saline placebo followed by a CFAE based ablation strategy. Two hundred randomized patients will be enrolled in this study-100 in each study arm. CONCLUSION: The MAGIC-AF study will assess the utility of a combined pharmaco-ablative strategy in patients with persistent AF undergoing a CFAE based ablation strategy.

Unusual complications of percutaneous epicardial access and epicardial mapping and ablation of cardiac arrhythmias.

BACKGROUND: Percutaneous epicardial access and mapping/ablation of cardiac arrhythmias are being increasingly performed. Although complications such as pericardial effusion are relatively common, other unusual complications may occur due to the complex anatomic architecture of the heart and surrounding tissues. In this report, we report a series of rare and unusual complications related to percutaneous epicardial procedures. METHODS AND RESULTS: Between 2006 and 2011, 334 patients underwent attempts at percutaneous, subxiphoid access for epicardial mapping/ablation at 5 experienced centers. Seven selected complications are highlighted in this case series. Patient 1 had a 1-cm right ventricular pseudoaneurysm after several unsuccessful attempts at epicardial access. This was successfully managed conservatively. Patient 2 had intra-abdominal bleeding related to puncture of the left lobe of the liver during access that required surgical repair. Patient 3 had a subcapsular hepatic hematoma that was probably related to percutaneous access and was successfully managed conservatively. Patient 4 had severe pericardial bleeding followed by ventricular fibrillation, immediately after obtaining percutaneous epicardial access. A lacerated middle cardiac vein was repaired surgically. However, the patient ultimately died of complications. Patient 5 had a history of cardiothoracic surgery and developed a right ventricle-abdominal fistula after multiple attempts at percutaneous access. This was surgically repaired without major sequelae. Patient 6 had cardiac tamponade caused by a lacerated coronary sinus branch during epicardial catheter ablation and required surgical repair. Patient 7 had severe left coronary vasospasm and ventricular fibrillation during catheter manipulation in the pericardium. This complication was successfully managed with intracoronary nitrates. CONCLUSIONS: Though generally safe, percutaneous epicardial access and mapping/ablation can result in uncommon complications. Awareness of these rare complications may facilitate early detection and successful management.

Long-term outcomes of combined epicardial and endocardial ablation of monomorphic ventricular tachycardia related to hypertrophic cardiomyopathy.

BACKGROUND: Monomorphic ventricular tachycardia (MMVT) is rare in patients with hypertrophic cardiomyopathy (HCM). There are limited data on the utility of catheter ablation for the treatment of MMVT in this population. This study details a series of case reports from multiple centers where combined epicardial-endocardial ablation was performed in a highly selected group of patients with HCM-related MMVT. METHODS AND RESULTS: The cohort consisted of 10 patients with HCM-related MMVT. Pericardial access was achieved using the percutaneous subxyphoid approach. Epicardial and endocardial ventricular 3D bipolar voltage maps were generated. Ablation sites were identified using a combination of entrainment, activation, late/fractionated potential, and pace mapping. Electrophysiological-identified epicardial scar was present in 8 (80%) patients, endocardial scar in 6 (60%), and no scar in 1 (10%). In the 5 patients with inducible, stable MMVT, 3 cases were successfully terminated with ablation from the epicardium and 1 from the endocardium. The case that failed catheter ablation required surgical cryoablation to abolish the incessant VT. In the remaining 5 patients, 4 underwent epicardial and endocardial ablation of sites with good pace maps and late/fractionated potentials. No ablation was performed in the remaining patient because of noninducibility and lack of identifiable scar. After 37±17 months (limits, 2 to 62 months; median, 37 months), the freedom from recurrent implantable cardioverter-defibrillator shocks was 78% (7/9 patients) in those who underwent ablation. CONCLUSIONS: In highly selected patients with HCM, combined epicardial and endocardial mapping and ablation is a feasible and reasonably efficacious option for MMVT if refractory to aggressive trials of antiarrhythmic drugs and antitachycardia pacing.

Visual balloon-guided point-by-point ablation: reliable, reproducible, and persistent pulmonary vein isolation.

BACKGROUND: While conceptually straightforward, placing point-to-point contiguous radiofrequency lesions to achieve pulmonary vein isolation (PVI) is technically challenging in patients with paroxysmal atrial fibrillation. Furthermore, chronic efficacy is limited by late PV reconnections. A novel compliant balloon ablation catheter able to deliver visually guided short arcs/spots of laser energy was tested in initial preclinical and clinical cases to determine if visual guidance could predict reliable and persistent PVI. METHODS AND RESULTS: This study consisted of (1) an experimental porcine phase with both acute (n=15 pigs) and 4-week chronic (n=10) data and (2) a single-center clinical feasibility phase (n=27 patients with paroxysmal atrial fibrillation), again with acute and 3-month chronic data. Under endoscopic guidance, point-by-point perivenous ablation was performed in a contiguous and overlapping manner. Each porcine PV was longitudinally sectioned for detailed histological analysis. At 3 months after ablation, patients underwent a prespecified remapping procedure regardless of symptomotology. In the acute and chronic animals, 29 of 30 (97%) PVs were electrically isolated after placing the initial circumferential lesion set. For the 4-week chronic animals, 80% of PVs remained isolated; lesions were histologically circumferential in 120 of 120 (100%) PV sections and transmural in 116 of 120 (96.7%) PV sections (average transmurality=99.0+/-5.5%). In patients, 100% of the PVs were isolated after 1.3 attempts per PV-84% of them (85 of 101) isolated after the initial visually guided lesion set. At 3 months, 61 of 68 (90%) PVs continued to be electrically isolated. CONCLUSIONS: Using a visually guided, compliant balloon ablation catheter with point-by-point ablative capability, PV isolation can be achieved in a reliable, reproducible, and persistent manner.

Electroanatomic mapping of the left ventricle in a porcine model of chronic myocardial infarction with magnetic resonance-based catheter tracking.

BACKGROUND: X-ray fluoroscopy constitutes the fundamental imaging modality for catheter visualization during interventional electrophysiology procedures. The minimal tissue discriminative capability of fluoroscopy is mitigated in part by the use of electroanatomic mapping systems and enhanced by the integration of preacquired 3-dimensional imaging of the heart with computed tomographic or magnetic resonance (MR) imaging. A more ideal paradigm might be to use intraprocedural MR imaging to directly image and guide catheter mapping procedures. METHODS AND RESULTS: An MR imaging-based electroanatomic mapping system was designed to assess the feasibility of navigating catheters to the left ventricle in vivo using MR tracking of microcoils incorporated into the catheters, measuring intracardiac ventricular electrograms, and integrating this information with 3-dimensional MR angiography and myocardial delayed enhancement images to allow ventricular substrate mapping. In all animals (4 normal, and 10 chronically infarcted swine), after transseptal puncture under fluoroscopic guidance, catheters were successfully navigated to the left ventricle with MR tracking (13 to 15 frames per second) by both transseptal and retrograde aortic approaches. Electrogram artifacts related to the MR imaging gradient pulses were successfully removed with analog and digital signal processing. In all animals, it was possible to map the entire left ventricle and to project electrogram voltage amplitude maps to identify the scarred myocardium. CONCLUSIONS: It is possible to use MR tracking to navigate catheters to the left ventricle, to measure electrogram activity, and to render accurate 3-dimensional voltage maps in a porcine model of chronic myocardial infarction, completely in the MR imaging environment. Myocardial delayed enhancement guidance provided dense sampling of the proximity of the infarct and accurate localization of complex infarcts.