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Pseudopolymorphic Wide Complex Tachycardia in a Child With Long QT Syndrome [Case Report]

Cerrone, Marina; Magnani, Silvia; Borneman, Linda; Cecchin, Frank; Tan, Reina; Fowler, Steven J; Chinitz, Larry; Jankelson, Lior
Implantable loop recorders (ILRs) can be a valuable tool in monitoring patients with inherited arrhythmia. This paper reports on a family with long QT syndrome (type 2 [LQT2]) in which a pseudopolymorphic wide complex tachycardia detected by ILR was ultimately diagnosed as a supraventricular aberrant rhythm, facilitated by noncompliance with beta-blocker therapy. (Level of Difficulty: Intermediate.).
PMCID:8298547
PMID: 34317300
ISSN: 2666-0849
CID: 4949452

Multimodality Imaging of Danon Disease in a Patient with a Novel LAMP2 Mutation [Case Report]

McLeod, Jennifer M; Fowler, Steven J; Cerrone, Marina; Aizer, Anthony; Chinitz, Larry A; Raad, Roy; Saric, Muhamed
PMCID:6833129
PMID: 31709377
ISSN: 2468-6441
CID: 4184922

Impact of RNA testing on cardiac variant interpretation and patient management [Case Report]

Jankelson, Lior; Zimmermann, Heather; Fowler, Steven; Borneman, Linda; Conner, Blair; Wu, Sitao; Karam, Rachid; Chinitz, Larry; Cerrone, Marina
PMCID:6700669
PMID: 31453089
ISSN: 2214-0271
CID: 4054342

Implantable Loop Recorder in Inherited Arrhythmia Diseases: A Critical Tool for Symptom Diagnosis and Advanced Risk Stratification [Letter]

Dwivedi, Aeshita; Joza, Jacqueline; Malkani, Kabir; Mendelson, Todd B; Priori, Silvia G; Chinitz, Larry A; Fowler, Steven J; Cerrone, Marina
PMID: 30336885
ISSN: 2405-5018
CID: 3368792

Two procedure outcomes for non-paroxysmal atrial fibrillation using a contact-force sensing radiofrequency ablation catheter: Left atrial posterior wall isolation versus stepwise linear ablation [Meeting Abstract]

Knotts, R; Barbhaiya, C R; Soria, C; Bernstein, S A; Park, D S; Fowler, S J; Holmes, D; Aizer, A; Chinitz, L A
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
EMBASE:622470830
ISSN: 1556-3871
CID: 3151272

Catheter spatial instability predicts arrhythmia recurrence following atrial fibrillation ablation [Meeting Abstract]

Yankelson, L; Dai, M; Bernstein, S A; Fowler, S J; Park, D S; Holmes, D; Aizer, A; Chinitz, L A; Barbhaiya, C R
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
EMBASE:622470104
ISSN: 1556-3871
CID: 3151302

Quantitative analytics of spatio-temporal catheter stability and lesion sequence in atrial fibrillation ablation [Meeting Abstract]

Yankelson, L; Dai, M; Bernstein, S; Fowler, S; Park, D; Holmes, D; Aizer, A; Chinitz, L A; Barbhaiya, C
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
EMBASE:622469477
ISSN: 1556-3871
CID: 3151342

Pacing Mediated Heart Rate Acceleration Improves Catheter Stability and Enhances Markers for Lesion Delivery in Human Atria During Atrial Fibrillation Ablation

Aizer, Anthony; Cheng, Austin V; Wu, Patrick B; Qiu, Jessica K; Barbhaiya, Chirag R; Fowler, Steven J; Bernstein, Scott A; Park, David S; Holmes, Douglas S; Chinitz, Larry A
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).
PMID: 30067488
ISSN: 2405-5018
CID: 3217102

Plakophilin-2 is required for transcription of genes that control calcium cycling and cardiac rhythm

Cerrone, Marina; Montnach, Jerome; Lin, Xianming; Zhao, Yan-Ting; Zhang, Mingliang; Agullo-Pascual, Esperanza; Leo-Macias, Alejandra; Alvarado, Francisco J; Dolgalev, Igor; Karathanos, Thomas V; Malkani, Kabir; Van Opbergen, Chantal J M; van Bavel, Joanne J A; Yang, Hua-Qian; Vasquez, Carolina; Tester, David; Fowler, Steven; Liang, Fengxia; Rothenberg, Eli; Heguy, Adriana; Morley, Gregory E; Coetzee, William A; Trayanova, Natalia A; Ackerman, Michael J; van Veen, Toon A B; Valdivia, Hector H; Delmar, Mario
Plakophilin-2 (PKP2) is a component of the desmosome and known for its role in cell-cell adhesion. Mutations in human PKP2 associate with a life-threatening arrhythmogenic cardiomyopathy, often of right ventricular predominance. Here, we use a range of state-of-the-art methods and a cardiomyocyte-specific, tamoxifen-activated, PKP2 knockout mouse to demonstrate that in addition to its role in cell adhesion, PKP2 is necessary to maintain transcription of genes that control intracellular calcium cycling. Lack of PKP2 reduces expression of Ryr2 (coding for Ryanodine Receptor 2), Ank2 (coding for Ankyrin-B), Cacna1c (coding for CaV1.2) and Trdn (coding for triadin), and protein levels of calsequestrin-2 (Casq2). These factors combined lead to disruption of intracellular calcium homeostasis and isoproterenol-induced arrhythmias that are prevented by flecainide treatment. We propose a previously unrecognized arrhythmogenic mechanism related to PKP2 expression and suggest that mutations in PKP2 in humans may cause life-threatening arrhythmias even in the absence of structural disease.It is believed that mutations in desmosomal adhesion complex protein plakophilin 2 (PKP2) cause arrhythmia due to loss of cell-cell communication. Here the authors show that PKP2 controls the expression of proteins involved in calcium cycling in adult mouse hearts, and that lack of PKP2 can cause arrhythmia in a structurally normal heart.
PMCID:5524637
PMID: 28740174
ISSN: 2041-1723
CID: 2653852

Utilization of a radiation safety time out significantly reduces radiation exposure during electrophysiology procedures [Meeting Abstract]

Aizer, A; Cheng, A V; Wu, P; Holmes, D; Fowler, S J; Bernstein, S A; Park, D S; Wagner, S R; Barbhaiya, C R; Chinitz, L A
Background: Pre-procedure time outs are integral to medicine to improve quality and safety. We hypothesized that a radiation safety time out for EP procedures would reduce radiation exposure levels for patients and staff. Objective: To design, implement and assess the effect of a radiation safety time out on radiation exposure in the EP lab. Methods: Baseline data on all adult EP procedures were collected for 6 months prior to implementation of the radiation safety time out. Upon implementation of the time out, data were collected prospectively with analyses to be performed every 3 months for up to 12 months. The primary endpoint was mean dose area product (DAP). Secondary endpoints were reference dose, fluoroscopy time, use of additional shielding, and use of alternative imaging. Results: The study was halted after three months. In total, 592 cases prior to the time out and 448 cases during implementation of the time out were included. Use of the time out resulted in a 22% reduction in the DAP (p = 0.013). The mean reference dose was also reduced by 26%. The use of additional radiation shields and ultrasound imaging for venous access increased significantly during the time out period. These differences remained significant when adjusted for BMI, proceduralist, and procedure type. There was no increase in procedure time or complications with the time out (Table). Conclusion: Implementation of a radiation safety time out significantly reduces radiation exposure during EP procedures. EP laboratories, as well as other areas of medicine that use fluoroscopy, should strongly consider the use of radiation safety time outs to reduce radiation exposures and improve safety. (Table presented)
EMBASE:617042238
ISSN: 1556-3871
CID: 2620902