Faculty Bibliography

Background: Cardiomyocytes are dependent on inward sodium currents for rapid phase 0 depolarization to initiate normal excitation-contraction coupling. In cardiovascular diseases where inward sodium currents are decreased, such as Brugada syndrome, calcium currents are thought to safeguard against conduction failure. Consequently, it has been suggested that combined sodium and calcium channel blockade may be more effective in unmasking Brugada syndrome. Fibroblast growth factor homologous factor 2 (FHF2) binds to sodium channels and modulates their function. Loss of FHF2 reduces inward sodium currents secondary to accelerated rates of both closed-state and open-state sodium channel inactivation. As a result, FHF2 KO mice are susceptible to conduction disturbances at elevated temperatures, with electrocardiogram tracings appearing similar to those seen in Brugada syndrome.

Background: Left atrial posterior wall (LAPW) isolation is associated with favorable outcomes for catheter ablation of persistent atrial fibrillation (AF) in several studies. Reported techniques for LAPW isolation include ablation at the periphery without ablation within the LAPW, and high density ablation of all sites of electrical activity within the LAPW. The proportion of LA isolated by the lesion set in various reports also varies greatly. The optimal technique to achieve LAPW isolation is not clear.
Objective(s): To assess impact of ablation lesion density within the LAPW and dimensions of LAPW isolation region on arrhythmia recurrence in catheter ablation of persistent AF.
Method(s): LAPW lesion density, and LAPW isolation surface area relative to total LA surface area were calculated using electroanatomic maps of 110 consecutive patients undergoing LAPW isolation for persistent AF (CARTO 3, Biosense Webster, Inc.) LAPW isolation lesion sets were created at the discretion of 5 experienced operators after LA voltage mapping. LAPW and PV entrance block and exit block were confirmed. Arrhythmia recurrence at one year was assessed by the Kaplan-Meier method.
Result(s): LAPW lesion density ranged from 0% - 99%. Proportion of LA surface area isolated ranged from 35% - 75%. There was no significant difference in arrhythmia-free survival by quartile of LAPW ablation density (81% vs. 68% vs. 85% vs. 78%, p=0.8), or by quartile of LA surface area proportion isolated (85% vs. 75% vs. 79% vs. 74%, p=0.3). Voltage map guided LAPW isolation resulted in no significant difference in incidence of recurrent arrhythmia by quartile of total LA surface area (81% vs. 78% vs. 78% vs. 74%, p=0.5).
Conclusion(s): Neither the density of ablation within the LAPW nor the dimensions of the isolated region predicted arrhythmia-free survival LAPW isolation for catheter ablation of persistent AF. Voltage map guided LAPW isolation resulted in similar ablation efficacy regardless of LA size.
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Background: Implantable loop recorder (ILR) based monitoring of patients with LQTS allows enhanced arrhythmia surveillance and can help distinguish life-threatening from benign arrhythmias.
Objective(s): We present a case of a child with LQTS and wide complex tachycardia detected by ILR.
Result(s): An asymptomatic 12 year old with LQT2 syndrome, positive for a G648S hERG mutation, with baseline QTc of 510-550ms despite maximally tolerated Nadolol (Figure 1A) was followed in our inherited arrhythmia center. His affected mother has had multiple syncopal events related to polymorphic ventricular tachycardia (VT) and appropriate ICD shocks. We elected to implant him with ILR to allow longitudinal monitoring and early detection of arrhythmia. He presented 6 months later with 2 alerts for asymptomatic polymorphic, wide complex tachycardia at ~200 bpm during sleeping (Figure 1B). Electrophysiology study (EPS) was performed to determine etiology of the arrhythmia. Dual AV node physiology was present. Sinus tachycardia at 200 bpm with left bundle branch block (LBBB) morphology was induced with Isoproterenol and atrio-fascicular pathway was excluded. Respiratory changes resulted in the tachycardia appearing as polymorphic on the ILR during the EPS.
Conclusion(s): This is the first reported case of sinus tachycardia with LBBB aberrancy in a child with LQTS. Pseudopolymorphic wide complex tachycardia was the result of aberrancy and respiratory artifact. Combined ILR monitoring and EP study provided a correct diagnosis, thus avoiding further interventions. [Figure presented]
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Background: Deficits in myocardial conduction velocity (CV) are associated with ventricular arrhythmias and conduction block. Abnormal organization and expression of cardiac sodium channel NaV1.5 and gap junction protein Cx43, key determinants of myocardial CV, are known features of arrhythmogenic heart disease. We previously identified fibroblast growth factor homologous factor 2 (FHF2) as a modulator of CV through its effects on NaV1.5. The aim of this study was to investigate whether modulating junctional conductance synergizes with loss of FHF2 to create conduction reserve deficits and susceptibility for arrhythmias. Method(s): ECGs were acquired to characterize conduction intervals of 2-3 month old wildtype (WT), cardiomyocyte-specific Cx43 heterozygous (Cx43 cHet), FHF2 KO, and FHF2 KO/Cx43 cHet mice. ECGs were then acquired with increasing doses of a gap junction channel blocker, carbenoxolone (CBX). Result(s): WT, Cx43 cHet, and FHF2 KO mice had normal conduction while FHF2 KO/Cx43 cHet mice showed ventricular conduction slowing at baseline. FHF2 KO and FHF2 KO/Cx43 cHet mice showed ventricular conduction slowing with CBX in a dose dependent fashion. Lethal conduction slowing was observed in FHF2 KO/Cx43 cHet mice given 120mg/kg CBX. Conclusion(s): These results identify a key role for FHF2 in maintaining myocardial conduction reserve which protects against stressors that depress junctional conductance (aging, pharmacologic blockade, genetic deficiency) and subsequent arrhythmias. [Figure presented]2019 American College of Cardiology Foundation. All rights reserved

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