In vivo porcine characterization of atrial lesion safety and efficacy utilizing a circular pulsed-field ablation catheter including assessment of collateral damage to adjacent tissue in supratherapeutic ablation applications.

INTRODUCTION: Pulsed-field ablation (PFA), an ablative method that causes cell death by irreversible electroporation, has potential safety advantages over radiofrequency ablation and cryoablation. Pulmonary vein (PV) isolation was performed in a porcine model to characterize safety and performance of a novel, fully-integrated biphasic PFA system comprising a multi-channel generator, variable loop circular catheter, and integrated PFA mapping software module. METHODS: Eight healthy porcine subjects were included. To evaluate safety, multiple ablations were performed, including sites not generally targeted for therapeutic ablation, such as the right inferior PV lumen, right superior PV ostium, and adjacent to the esophagus and phrenic nerve. To evaluate the efficacy, animals were recovered, followed for 30(±3) days, then re-mapped. Gross pathological and histopathological examinations assessed procedural injuries, chronic thrombosis, tissue ablation, penetration depth, healing, and inflammatory response. RESULTS: All eight animals survived follow-up. PV narrowing was not observed acutely nor at follow-up, even when ablation was performed deep to the PV ostium. No injury was seen grossly or histologically in adjacent structures. All PVs were durably isolated, confirmed by bidirectional block at re-map procedure. Histological examination showed complete, transmural necrosis around the circumference of the ablated section of right PVs. CONCLUSION: This preclinical evaluation of a fully-integrated PFA system demonstrated effective and durable ablation of cardiac tissue and PV isolation without collateral damage to adjacent structures, even when ablation was performed in more extreme settings than those used therapeutically. Histological staining confirmed complete transmural cell necrosis around the circumference of the PV ostium at 30 days.

Percutaneous Implantation of an Entirely Intracardiac Leadless Pacemaker.

BACKGROUND: Cardiac pacemakers are limited by device-related complications, notably infection and problems related to pacemaker leads. We studied a miniaturized, fully self-contained leadless pacemaker that is nonsurgically implanted in the right ventricle with the use of a catheter. METHODS: In this multicenter study, we implanted an active-fixation leadless cardiac pacemaker in patients who required permanent single-chamber ventricular pacing. The primary efficacy end point was both an acceptable pacing threshold (≤2.0 V at 0.4 msec) and an acceptable sensing amplitude (R wave ≥5.0 mV, or a value equal to or greater than the value at implantation) through 6 months. The primary safety end point was freedom from device-related serious adverse events through 6 months. In this ongoing study, the prespecified analysis of the primary end points was performed on data from the first 300 patients who completed 6 months of follow-up (primary cohort). The rates of the efficacy end point and safety end point were compared with performance goals (based on historical data) of 85% and 86%, respectively. Additional outcomes were assessed in all 526 patients who were enrolled as of June 2015 (the total cohort). RESULTS: The leadless pacemaker was successfully implanted in 504 of the 526 patients in the total cohort (95.8%). The intention-to-treat primary efficacy end point was met in 270 of the 300 patients in the primary cohort (90.0%; 95% confidence interval [CI], 86.0 to 93.2, P=0.007), and the primary safety end point was met in 280 of the 300 patients (93.3%; 95% CI, 89.9 to 95.9; P<0.001). At 6 months, device-related serious adverse events were observed in 6.7% of the patients; events included device dislodgement with percutaneous retrieval (in 1.7%), cardiac perforation (in 1.3%), and pacing-threshold elevation requiring percutaneous retrieval and device replacement (in 1.3%). CONCLUSIONS: The leadless cardiac pacemaker met prespecified pacing and sensing requirements in the large majority of patients. Device-related serious adverse events occurred in approximately 1 in 15 patients. (Funded by St. Jude Medical; LEADLESS II ClinicalTrials.gov number, NCT02030418.).

Acute and Long-Term Outcomes of Catheter Ablation of Atrial Fibrillation Using the Second-Generation Cryoballoon versus Open-Irrigated Radiofrequency: A Multicenter Experience.

INTRODUCTION: There are limited comparative data on catheter ablation of atrial fibrillation (CAAF) using the second-generation cryoballoon (CB-2) versus point-by-point radiofrequency (RF). This study examines the acute/long-term CAAF outcomes using these 2 strategies. METHODS AND RESULTS: In this multicenter, retrospective, nonrandomized analysis, procedural and clinical outcomes of 1,196 patients (76% with paroxysmal AF) undergoing CAAF using CB-2 (n = 773) and open-irrigated, non-force sensing RF (n = 423) were evaluated. Pulmonary vein isolation was achieved in 98% with CB-2 and 99% with RF (P = 0.168). CB-2 was associated with shorter ablation time (40 ± 14 min vs. 66 ± 26 min; P < 0.001) and procedure time (145 ± 49 minutes vs. 188 ± 42 minutes; P < 0.001), but greater fluoroscopic utilization (29 ± 13 minutes vs. 23 ± 14 minutes; P < 0.001). While transient (7.6% vs. 0%; P < 0.001) and persistent (1.2% vs. 0%; P = 0.026) phrenic nerve palsy occurred exclusively with CB-2, other adverse event rates were similar between CB-2 (1.6%) and RF (2.6%); P = 0.207. However, freedom from AF/atrial flutter/tachycardia at 12 months following a single procedure without antiarrhythmic therapy was greater with CB-2 (76.6%) versus RF (60.4%); P < 0.001. While this difference was evident in patients with paroxysmal AF (P < 0.001), it did not reach significance in those with persistent AF (P = 0.089). Additionally, CB-2 was associated with reduced long-term need for antiarrhythmic therapy (16.7% vs. 22.0%; P = 0.024) and repeat ablations (14.6% vs. 24.1%; P < 0.001). CONCLUSION: In this multicenter, retrospective, nonrandomized study, CAAF using CB-2 coupled with RF as occasionally required was associated with greater freedom from atrial arrhythmias at 12 months following a single procedure without antiarrhythmic therapy when compared to open-irrigated, non-force sensing RF, alone.

Pulsed Field Ablation Index-Guided Ablation for Lesion Formation: Impact of Contact Force and Number of Applications in the Ventricular Model.

BACKGROUND: The effect of contact force (CF) on lesion formation is not clear during pulsed field ablation (PFA). The aim of this study was to evaluate the impact of CF, PFA, and their interplay through the PFA index (PF index) formula on the ventricular lesion size in swine. METHODS: PFA was delivered through the CF-sensing OMNYPULSE catheter. Predefined PFA applications (×3, ×6, ×9, and ×12) were delivered maintaining low (5-25 g), high (26-50 g), and very high (51-80 g) CFs. First, PFA lesions were evaluated on necropsy in 11 swine to investigate the impact of CF/PFA-and their integration in the PF index equation-on lesion size (study characterization). Then, 3 different PF index thresholds-300, 450, and 600-were tested in 6 swine to appraise the PF index accuracy to predict the ventricular lesion depth (study validation). RESULTS: In the study characterization data set, 111 PFA lesions were analyzed. CF was 32±17 g. The average lesion depth and width were 3.5±1.2 and 12.0±3.5 mm, respectively. More than CF and PFA dose alone, it was their combined effect to impact lesion depth through an asymptotically increasing relationship. Likewise, not only was the PF index related to lesion depth in the study validation data set (r2=0.66; P<0.001) but it also provided a prediction accuracy of the observed depth of ±2 mm in 69/73 lesions (95%). CONCLUSIONS: CF and PFA applications play a key role in lesion formation during PFA. Further studies are required to evaluate the best PFA ablation settings to achieve transmural lesions.

Dual-chamber leadless pacing: Atrioventricular synchrony in preclinical models of normal or blocked atrioventricular conduction.

BACKGROUND: Dual-chamber leadless pacemakers (LPs) require robust communication between distinct right atrial (RA) and right ventricular (RV) LPs to achieve atrioventricular (AV) synchrony. OBJECTIVE: The purpose of this preclinical study was to evaluate a novel, continuous implant-to-implant (i2i™) communication methodology for maintaining AV-synchronous, dual-chamber DDD(R) pacing by the 2 LPs. METHODS: RA and RV LPs were implanted and paired in 7 ovine subjects (4 with induced complete heart block). AV synchrony (% AV intervals <300 ms) and i2i communication success (% successful i2i transmissions between LPs) were evaluated acutely and chronically. During acute testing, 12-lead electrocardiographic and LP diagnostic data were collected from 5-minute recordings, in 4 postures and 2 rhythms (AP-VP and AS-VP, or AP-VS and AS-VS) per subject. Chronic i2i performance was evaluated through 23 weeks postimplant (final i2i evaluation period: week 16-23). RESULTS: Acute AV synchrony and i2i communication success across multiple postures and rhythms were median [interquartile range] 100.0% [100.0%-100.0%] and 99.9% [99.9%-99.9%], respectively. AV synchrony and i2i success rates did not differ across postures (P = .59, P = .11) or rhythms (P = 1, P = .82). During the final i2i evaluation period, the overall i2i success was 98.9% [98.1%-99.0%]. CONCLUSION: Successful AV-synchronous, dual-chamber DDD(R) leadless pacing using a novel, continuous, wireless communication modality was demonstrated across variations in posture and rhythm in a preclinical model.

Retrieval of Chronically Implanted Dual-chamber Leadless Pacemakers in an Ovine Model.

BACKGROUND: The clinical utilization of leadless pacemakers (LPs) as an alternative to traditional transvenous pacemakers is likely to increase with the advent of dual-chamber LP systems. Since device retrieval to allow LP upgrade or replacement will become an important capability, the first such dual-chamber, helix-fixation LP system (Aveir DR; Abbott, Abbott Park, IL) was specifically designed to allow catheter-based retrieval. In this study, the preclinical performance and safety of retrieving chronically implanted dual-chamber LPs was evaluated. METHODS: Atrial and ventricular LPs were implanted in the right atrial appendage and right ventricular apex of 9 healthy ovine subjects. After ≈2 years, the LPs were retrieved using a dedicated transvenous retrieval catheter (Aveir Retrieval Catheter; Abbott) by snaring, docking, and unscrewing from the myocardium. Comprehensive necropsy/histopathology studies were conducted to evaluate device- and procedure-related outcomes. RESULTS: At a median of 1.9 years postimplant (range, 1.8-2.6), all 18 of 18 (100%) LPs were retrieved from 9 ovine subjects without complications. The median retrieval procedure duration for both LPs, from first-catheter-in to last-catheter-out, was 13.3 minutes (range, 2.5-36.4). Postretrieval, all right atrial, and right ventricular implant sites demonstrated minimal tissue disruption, with intact fibrous tissue limited to the distal device body. No significant device-related trauma, perforation, pericardial effusion, right heart or tricuspid valve injury, or chronic pulmonary thromboembolism were observed at necropsy. CONCLUSIONS: This preclinical study demonstrated the safe and effective retrieval of chronically implanted, helix-fixation, dual-chamber LP systems, paving the way for clinical studies of LP retrieval.

Wireless Communication Between Paired Leadless Pacemakers for Dual-Chamber Synchrony.

BACKGROUND: Leadless pacemakers (LPs) can mitigate conventional pacemaker complications related to the transvenous leads and subcutaneous pocket surrounding the pulse generator. Although single-chamber leadless pacing has been established, multichamber pacing requires wireless bidirectional communication across multiple LPs to maintain synchrony. This preclinical study demonstrates the chronic performance of implant-to-implant (i2i) communication that achieves synchronous, dual-chamber pacing with 2 LPs. METHODS: The i2i communication modality employs subthreshold electrical signals conducted between implanted LPs through the blood and myocardial tissue on a beat-by-beat basis. Right atrial and right ventricular LPs were implanted in 9 ovine subjects. The i2i transmission performance was evaluated 13 weeks after implant. RESULTS: Right atrial and right ventricular LPs were implanted successfully and without complication in 9 ovine subjects. A total of 8715±457 right atrial-to-right ventricular and right ventricular-to-right atrial transmissions were sent per hour, with a success rate of 99.2±0.9%. Of periods with i2i communication failure when DDD pacing was not possible, 97.3±1.8% were resolved within 6 s. CONCLUSIONS: For the first time, synchronized, dual-chamber pacing has been demonstrated in a chronic preclinical feasibility study by 2 leadless pacemakers using beat-to-beat, wireless communication, achieving a success rate of 99.2%.

Preclinical safety and electrical performance of novel atrial leadless pacemaker with dual-helix fixation.

BACKGROUND: Complications associated with transvenous pacemakers, specifically those involving the lead or subcutaneous pocket, may be avoided with leadless pacemakers (LPs). The safety and efficacy of single-chamber right ventricular LPs have been demonstrated, but their right atrium (RA) use poses new design constraints. OBJECTIVES: The purpose of this study was to evaluate the implant success, electrical performance, and safety of a novel RA LP design in benchtop and preclinical studies. METHODS: A new LP was designed with a dual-helix fixation mechanism specific to the RA anatomy. A 12-week preclinical ovine study was conducted to evaluate implant success, electrical performance, mechanical stability, and safety in vivo, with supporting benchtop measurements to quantify the mechanical forces needed for device retrieval and dislodgment. RESULTS: LPs were successfully implanted in all 10 ovine subjects with no complications. The pacing capture threshold improved significantly over time from implant to week 12 (1.1 ± 0.7 V vs 0.4 ± 0.2 V, P = .008). Sensing amplitudes and pacing impedances were stable from implant to week 12 (4.8 ± 1.8 mV vs 6.0 ± 1.9 mV, P = .160; and 393 ± 77 Ω vs 398 ± 65 Ω, P = .922, respectively). Gross pathology and microscopic histology revealed no adverse interactions and no evidence of device dislodgment or clinically significant myocardial perforation. Benchtop ex vivo porcine atrial tissue measurements revealed greater pull forces required to dislodge the LP vs transvenous active fixation lead (0.42 ± 0.18 lbf vs 0.29 ± 0.08 lbf, P = .020), and greater rotational forces required for deliberate extraction (0.28 ± 0.04 lbf vs 0.14 ± 0.07 lbf, P <.001). CONCLUSION: The novel atrial LP demonstrated successful implantation, with acceptable electrical performance, mechanical stability, and safety in a 12-week preclinical study.

The learning curve associated with the implantation of the Nanostim leadless pacemaker.

PURPOSE: Use of novel medical technologies, such as leadless pacemaker (LP) therapy, may be subjected to a learning curve effect. The objective of the current study was to assess the impact of operators' experience on the occurrence of serious adverse device effects (SADE) and procedural efficiency. METHODS: Patients implanted with a Nanostim LP (Abbott, USA) within two prospective studies (i.e., LEADLESS ll IDE and Leadless Observational Study) were assessed. Patients were categorized into quartiles based on operator experience. Learning curve analysis included the comparison of SADE rates at 30 days post-implant per quartile and between patients in quartile 4 (> 10 implants) and patients in quartiles 1 through 3 (1-10 implants). Procedural efficiency was assessed based on procedure duration and repositioning attempts. RESULTS: Nanostim LP implant was performed in 1439 patients by 171 implanters at 60 centers in 10 countries. A total of 91 (6.4%) patients experienced a SADE in the first 30 days. SADE rates dropped from 7.4 to 4.5% (p = 0.038) after more than 10 implants per operator. Total procedure duration decreased from 30.9 ± 19.1 min in quartile 1 to 21.6 ± 13.2 min (p < 0.001) in quartile 4. The need for multiple repositionings during the LP procedure reduced in quartile 4 (14.8%), compared to quartiles 1 (26.8%; p < 0.001), 2 (26.6%; p < 0.001), and 3 (20.4%; p = 0.03). CONCLUSIONS: Learning curves exist for Nanostim LP implantation. Procedure efficiency improved with increased operator experience, according to a decrease in the incidence of SADE, procedure duration, and repositioning attempts.

Comparative study of acute and mid-term complications with leadless and transvenous cardiac pacemakers.

BACKGROUND: Leadless cardiac pacemakers (LCPs) aim to mitigate lead- and pocket-related complications seen with transvenous pacemakers (TVPs). OBJECTIVE: The purpose of this study was to compare complications between the LCP cohort from the LEADLESS Pacemaker IDE Study (Leadless II) trial and a propensity score-matched real-world TVP cohort. METHODS: The multicenter LEADLESS II trial evaluated the safety and efficacy of the Nanostim LCP (Abbott, Abbott Park, IL) using structured follow-up, with serious adverse device effects independently adjudicated. TVP data were obtained from Truven Health MarketScan claims databases for patients implanted with single-chamber TVPs between April 1, 2010 and March 31, 2014 and more than 1 year of preimplant enrollment data. Comorbidities and complications were identified via International Classification of Diseases, Ninth Revision and Current Procedural Terminology codes. Short-term (≤1 months) and mid-term (>1-18 months) complications were compared between the LCP cohort and a propensity score-matched subset of the TVP cohort. RESULTS: Among 718 patients with LCPs (mean age 75.6 ± 11.9 years; 62% men) and 1436 patients with TVPs (mean age 76.1 ± 12.3 years; 63% men), patients with LCPs experienced fewer complications (hazard ratio 0.44; 95% confidence interval 0.32-0.60; P < .001), including short-term (5.8% vs 9.4%; P = .01) and mid-term (0.56% vs 4.9%; P < .001) events. In the short-term time frame, patients with LCPs had more pericardial effusions (1.53% vs 0.35%; P = .005); similar rates of vascular events (1.11% vs 0.42%; P = .085), dislodgments (0.97% vs 1.39%; P = .54), and generator complications (0.70% vs 0.28%; P = .17); and no thoracic trauma compared to patients with TVPs (rate of thoracic trauma 3.27%). In short- and mid-term time frames, TVP events absent from the LCP group included lead-related, pocket-related, and infectious complications. CONCLUSION: Patients with LCPs experienced fewer overall short- and mid-term complications, including infectious and lead- and pocket-related events, but more pericardial effusions, which were uncommon but serious.