Faculty Bibliography

PURPOSE/OBJECTIVE:Elimination of pace-capture along pulmonary vein isolation (PVI) lesion sets reduces atrial fibrillation (AF) recurrence in catheter ablation of paroxysmal AF. Pacing from the RF ablation electrode during RF application is prevented within the CARTO electroanatomic mapping system (Biosense Webster, Inc.) due to theoretical safety considerations. We evaluated a method of pacing the distal ablation electrode during RF application in the CARTO system, thus avoiding repeated activation and inactivation of the pacing channel and facilitating immediate recognition of pace-capture loss. We investigated the safety, feasibility, and utility of simultaneous pace-ablate (SPA) during AF ablation with the CARTO-3 system and a contact-force sensing RF ablation catheter. METHODS:Safety of feasibility of SPA was evaluated in 250 patients undergoing first-time AF ablation. Frequency and regional distribution of pace-capture following PVI was evaluated in a cohort of 50 consecutive patients undergoing catheter ablation of paroxysmal AF. RESULTS:SPA was successfully performed in all 250 patients without adverse event. At least one pace-capture site was noted in 22 of 50 PAF patients (44%), and pace-capture following PVI was most common at anterior and superior left atrial sites. There were 2.0 ± 3.3 RF applications during pacing via the distal ablation electrode per patient, and all lesions sets were successfully rendered unexcitable. CONCLUSIONS:Pace-capture along the completed PVI lesion set remains common despite utilization of contact-force sensing RF ablation catheters and automated lesion annotation. Simultaneous pace-ablate in AF ablation using the CARTO system may be safely used to render atrial lesion sets unexcitable.

Rapid impulse propagation is a defining attribute of the pectinated atrial myocardium and His-Purkinje system (HPS) that safeguards against atrial and ventricular arrhythmias, conduction block, and myocardial dyssynchrony. The complex transcriptional circuitry that dictates rapid conduction remains incompletely understood. Here, we demonstrate that ETV1 (ER81)-dependent gene networks dictate the unique electrophysiological characteristics of atrial and His-Purkinje myocytes. Cardiomyocyte-specific deletion of ETV1 results in cardiac conduction abnormalities, decreased expression of rapid conduction genes (Nkx2-5, Gja5, and Scn5a), HPS hypoplasia, and ventricularization of the unique sodium channel properties that define Purkinje and atrial myocytes in the adult heart. Forced expression of ETV1 in postnatal ventricular myocytes (VMs) reveals that ETV1 promotes a HPS gene signature while diminishing ventricular and nodal gene networks. Remarkably, ETV1 induction in human induced pluripotent stem cell-derived cardiomyocytes increases rapid conduction gene expression and inward sodium currents, converting them towards a HPS phenotype. Our data identify a cardiomyocyte-autonomous, ETV1-dependent pathway that is responsible for specification of rapid conduction zones in the heart and demonstrate that ETV1 is sufficient to promote a HPS transcriptional and functional program upon VMs.

Background: Biophysical markers of effective lesion formation during radiofrequency (RF) ablation include impedance decline, stable catheter-tissue contact and local unipolar electrogram change suggesting lesion transmurality The interactions between these factors as well as the implications of lesion sequence are not well understood. Objective: To analyze the impact of catheter stability and lesion sequence on markers of lesion formation during atrial fbrillation (AF) ablation. Methods: Sequential or time-spaced paired RF lesions with goal force-time integral (FTI) 400 gs were placed in prespecifed locations in 20 patients undergoing frst time RF ablation for paroxysmal AF. Custom developed software (MATLAB, Mathworks, USA) was used to extract and analyze lesion data, and 3D catheter position sampled at 60Hz from the CARTO3 mapping system (Biosense Webster, Inc.). All cases were performed using jet ventilation and irrigated force-sensing catheters. Results: 282 ablation lesions were studied, with mean FTI 410.8+/-18.2 gs. Mean impedance decline was greater for the frst lesion in a given pair, 13.6+/-7.9OMEGA vs. 10.7+/-4.6OMEGA, (p < 0.01). Compared to time-spaced lesions, sequential lesions resulted in signifcantly smaller impedance decline (9.8+/-3.8OMEGA vs. 11.8+/-5.2OMEGA, p<0.01), but increased probability of achieving transmurality, as evident by unipolar signal change (68% vs 42% p=0.01). Mean catheter excursion for a single lesion was 0.67+/-0.54mm and maximal catheter excursion was 1.64+/-1.3mm. Ablation catheter spatial stability was found to be inversely related to both amplitude (rho=0.51, p<0.0001) and maximal rate (dI/dT) of impedance decline (rho=0.32, p<0.0001). Conclusion: Lesion sequence and catheter spatial stability were major modifers of impedance change and unipolar electrographic evidence of lesion transmurality during RF ablation. Sequential ablation resulted in transmural lesions more frequently, despite lesser impedance decline. In contrast to previously reported positive association between contact-force and impedance decline, increased ablation catheter spatial stability was associated with lesser impedance decline

Background: Optimal contact-force during atrial fbrillation (AF) radiofrequency (RF) ablation is associated with improved procedural outcomes The extent to which ablation catheter spatial stability varies between patients and predicts procedural success is unknown. Objective: To examine the prognostic signifcance of intra-procedure ablation catheter spatial stability on one year arrhythmia recurrence following ablation of paroxysmal atrial fbrillation. Methods: 100 consecutive patients undergoing frst time RF ablation for paroxysmal AF under general anesthesia were analyzed. Spatial localization of the ablation catheter sampled at 60 Hz during RF application was extracted from the CARTO3 system (Biosense Webster, Inc.) and analyzed using custom software (MATLAB, Mathworks, USA) to determine mean and maximum catheter excursion relative to mean catheter location during point-by-point RF ablation. All lesions for a given patient were then averaged to form composite measures of catheter stability The primary end point was freedom from documented recurrence of atrial arrhythmia lasting longer than 30 seconds after a single ablation procedure. Results: At one year, 86% of patients were free from recurrent AF. There was no signifcant difference in clinical and echocardiographic baseline characteristics between patients with and without recurrent arrhythmia There was no signifcant difference in lesion number, average contact-force, average impedance decrease, or RF time between patients who did recur and those who did not. For all patients, maximum catheter excursion was 2.84 +/- 0.40mm and mean catheter excursion was 0.99 +/- 0.16mm. Patients with arrhythmia recurrence had signifcantly greater maximum (3.07 +/- 0.38mm vs 2.80 +/- 0.40mm, p = 0.03) and mean (1.08 +/- 0.13mm vs 0.98 +/- 0.17mm, p = 0.01) catheter excursion compared to those without recurrence. Univariate regression demonstrated that maximal catheter excursion was a signifcant predictor of arrhythmia recurrence (OR 5.1 per 1mm excursion increase, 95% CI 1.2-21.9, p=0.03). Conclusion: Quantitative measures of ablation catheter spatial stability may be novel and potentially modifable predictors of procedural success during RF ablation of AF

Background: Unfavorable outcomes for stepwise linear ablation of non-paroxysmal atrial fbrillation (NPAF) in clinical trials may be attributable to pro-arrhythmic effects of incomplete ablation lines. It is unknown if recurrent arrhythmia following stepwise linear ablation is more likely to be successfully ablated compared to recurrent arrhythmia following a more limited initial procedure The optimal ablation strategy for catheter ablation of NPAF using a contact-force sensing (CFS) radiofrequency ablation (RFA) catheter remains unclear. Objective: To compare 2-procedure outcomes of stepwise linear RFA to left atrial posterior wall isolation in patients undergoing NPAF ablation using a CFS RFA catheter. Methods: We compared clinical outcomes of two cohorts of 100 consecutive NPAF patients undergoing frst-time RFA using a CFS RFA catheter. Group 1: stepwise linear ablation (July 2014-July 2015); Group 2: left atrial posterior wall isolation (October 2015-June 2016). Arrhythmia recurrence was assessed using 2-week event monitors at 3-month intervals following ablation procedures. Results: Baseline characteristics of the two groups were similar. Mean follow-up time was 656 +/- 361 days for Group 1 and 436 +/- 228 days for Group 2. At 24-month follow up, Kaplan-Meier estimated single procedure arrhythmia free survival was signifcantly greater in Group 2 compared to Group 1 (76% vs 59%, respectively; p = 0.01), primarily driven by a higher rate of recurrence of atrial tachycardia (12% vs 35%, respectively; p < 0.001). Among patients with recurrent arrhythmia after a single procedure, Group 2 patients were less likely to require repeat ablation compared to Group 1 (6/24 vs 34/41, respectively; p < 0.001) and less likely to recur after repeat ablation (1/6 vs 13/34, respectively; p = 0.001). Conclusion: Compared to stepwise linear ablation, LA posterior wall isolation for catheter ablation of NPAF resulted in a lower incidence of recurrent arrhythmia at 2 years, a lower likelihood of requiring repeat ablation amongst patients with recurrence, and a lower likelihood of recurrence following a second ablation

OBJECTIVES/OBJECTIVE:This study sought to investigate the effect of pacing mediated heart rate modulation on catheter-tissue contact and impedance reduction during radiofrequency ablation in human atria during atrial fibrillation (AF) ablation. BACKGROUND:In AF ablation, improved catheter-tissue contact enhances lesion quality and acute pulmonary vein isolation rates. Previous studies demonstrate that catheter-tissue contact varies with ventricular contraction. The authors investigated the impact of modulating heart rate on the consistency of catheter-tissue contact and its effect on lesion quality. METHODS:Twenty patients undergoing paroxysmal AF ablation received ablation lesions at 15 pre-specified locations (12 left atria, 3 right atria). Patients were assigned randomly to undergo rapid atrial pacing for either the first half or the second half of each lesion. Contact force and ablation data with and without pacing were compared for each of the 300 ablation lesions. RESULTS:Compared with lesion delivery without pacing, pacing resulted in reduced contact force variability, as measured by contact force SD, range, maximum, minimum, and time within the pre-specified goal contact force range (p < 0.05). There was no difference in the mean contact force or force-time integral. Reduced contact force variability was associated with a 30% greater decrease in tissue impedance during ablation (p < 0.001). CONCLUSIONS:Pacing induced heart rate acceleration reduces catheter-tissue contact variability, increases the probability of achieving pre-specified catheter-tissue contact endpoints, and enhances impedance reduction during ablation. Modulating heart rate to improve catheter-tissue contact offers a new approach to optimize lesion quality in AF ablation. (The Physiological Effects of Pacing on Catheter Ablation Procedures to Treat Atrial Fibrillation [PEP AF]; NCT02766712).

Heart failure (HF) has been referred to as the cardiovascular epidemic of our time. Understanding the molecular determinants of HF disease progression and mortality risk is of utmost importance. In this issue of the JCI, Zhang et al. uncover an important link between clinical HF mortality risk and a common variant that regulates SCN5A expression through microRNA-dependent (miR-dependent)mechanisms. They also demonstrate that haploinsufficiency of SCN5A is associated with increased accumulation of reactive oxygen species (ROS) in a genetically engineered murine model. Their data suggest that even modest depression of SCN5A expression may promote pathologic cardiac remodeling and progression of HF.