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Introduction: Accessory pathway (AP) ablation is a straightforward approach with high success rates, but the fluoroscopy time (FT) is significantly longer in conventional technique. Electroanatomical mapping systems (EMS), reduce the FT, but anatomical and activation mapping may prolong the procedure time (PT). The fluoroscopy integration module (FIM) uses prerecorded fluoroscopy images and allows ablation similar to conventional technique without creating an anatomical map. In this study, we investigated the effects of combining the FIM with traditional technique on PT, success, and radiation exposure. Methods: A total of 131 patients who had undergone AP ablation were included in our study. In 37 patients, right and left anterior oblique (RAO‐LAO) images were acquired after catheter placement and integrated with the FIM. The ablation procedure was then similar to the conventional technique, but without the use of fluoroscopy. For the purpose of acceleration, anatomical and activation maps have not been created. Contact‐force catheters were not used. 94 patients underwent conventional ablation using fluoroscopy only. Results: FIM into AP ablation procedures led to a significant reduction in radiation exposure, lowering FT from 7.4 to 2.8 min (p <.001) and dose‐area product from 12.47 to 5.8 μGym² (p <.001). While the FIM group experienced a reasonable longer PT (69 vs. 50 min p <.001). FIM reduces FT regardless of operator experience and location of APs Conclusion: Combining FIM integration with conventional AP ablation offers reduced radiation exposure without compromising success rates and complication. [ABSTRACT FROM AUTHOR]

Aim: Data on ablation for atypical recurrent atrioventricular nodal reentry tachycardia (AVNRT) and long‐term follow‐up are generally sparse. Furthermore, the rate of recurrence and safety of cryoablation for atypical AVNRT has not been established. We compared patients cryoablated for atypical AVNRT and typical AVNRT during long‐term follow‐up. Methods: All patients (n = 2612) who underwent catheter ablation for AVNRT at the Karolinska University Hospital between January 2009 and August 2019 were analyzed. A total of 91 patients undergoing first‐time cryoablation for atypical AVNRT were included. A control group with first‐time cryoablation for typical AVNRT was matched in a 1:1 ratio. Patients were followed‐up for recurrences for a median of 5.0 years (interquartile range: 3.1–7.5 years). Results: After 5 years, AVNRT recurrence occurred in 10 patients (11.0%) in the atypical AVNRT group and in 8 patients (8.8%) in the typical AVNRT group (hazard ratio: 1.31 [95% confidence interval: 0.52–3.32]; p = 0.568). The duration of the index procedure was significantly longer for atypical compared to typical AVNRT ablation (132.1 ± 49.2 min vs. 110.1 ± 38.8 min; p = 0.001). Transient AV blocks occurred in a similar fashion in the atypical compared to typical group (11 [12.1%] vs. 4 [4.9%]; p = 0.103). However, no ablation induced persistent AV block developed in either group. Conclusion: Cryoablation for atypical AVNRT showed similar rate of recurrences and safety compared to typical AVNRT during long‐term follow‐up. [ABSTRACT FROM AUTHOR]

Introduction: The need for transparency in financial relationships in the healthcare system, has culminated in Open Payments database, managed by the Center for Medicare and Medicaid Services (CMS). Since its inception in 2013, the trend in such payments to physicians practicing cardiac electrophysiology was not examined. Methods and Results: Payment information reported to CMS from January 2013 to December 2018 was obtained from the publicly available Open Payments data set using the online query tool. The data were analyzed by an individual provider and by state. An in‐depth analysis of payments in the year 2018 payments was performed. From 2014 to 2018, there was an 18% increase in the total number of payments reported from 88 877 payments in 2014 to 105 000 in 2018. Despite the increase in the total number of payments reported, the average payment steadily decreased over time, resulting in an overall reduction in the total amount of payments from 2014 to 2018 ($34.9 million to $28.2 million). Payments to the top 5% of individual recipients have also decreased over this time. In 2018, 2888 unique providers received reportable payments, a total of 105 000 payments, with a median payment amount of $1378 (interquartile range: $165–$5781). The majority of these payments were for food and beverage (82%) and travel/lodging (10%). The top five payers include Boston Scientific, Medtronic Vascular, Abbott Laboratories, Janssen Pharmaceuticals, and Biotronik. Conclusion: Among cardiac electrophysiologists, there is increased reporting of payments in the Open Payments program over time, with a notable decrease in the payment amount. [ABSTRACT FROM AUTHOR]

The article provides a priority plan for invasive cardiac electrophysiology procedures during the COVID-19 pandemic. Topics discussed include recommendations issued by the Heart Rhythm Society (HRS) COVID-19 Task Force, the American College of Cardiology and the American Hearth Association, challenges for cardiac electrophysiology, and safety and resource utilization.

Accessing the pericardial space safely and efficiently is an important skill for interventional cardiac electrophysiologist. With the increased recognition of the complexity of the 3-dimensional arrhythmogenic substrate due to advances in imaging and mapping technologies there has been an expansion of epicardial procedures in recent years. Equally, minimally invasive implantation of epicardial pacing, cardiac resynchronization, or defibrillation leads is expanding in specific patients where transvenous systems are contraindicated or their long term sequelae should be ideally avoided. Selective delivery of intrapericardial pharmacological antiarrhythmic therapy is yet another potential indication, albeit still investigational. The expanding indications for percutaneous epicardial procedures is contrasted by the still substantial risk and challenges associated with accessing the pericardial space. Myocardial perforation, coronary artery laceration, and damage to the surrounding organs are all recognized and feared complications. A number of innovative epicardial access techniques have been proposed to overcome the difficulties and risks of traditional dry subxiphoid punctures and may allow for more widespread use of epicardial access in the future. We review 10 different established and novel subxiphoidal epicardial access techniques describing procedural success rates, safety profile and overall experience. The technical aspects as well as access times and costs for extra equipment will be reviewed. Finally, an outlook of reported preclinical techniques awaiting in-human feasibility studies is provided., (©2023 The Authors. Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

The care of patients with heart rhythm disorders is often dependent on technologies developed to address their unique clinical needs. Although much innovation occurs in the United States, recent decades have seen a significant proportion of early clinical studies performed outside the United States, driven largely by costly and time-inefficient processes seemingly inherent to the United States research ecosystem. As a result, the goals of early patient access to novel devices to address unmet needs and efficient technology development in the United States remain incompletely realized. This review will introduce key aspects of this discussion, organized by the Medical Device Innovation Consortium, in an effort to broaden awareness and encourage engagement by stakeholders in an effort to address central issues and therefore further a growing effort to shift Early Feasibility Studies to the United States for the benefit of all involved., (© 2023 Wiley Periodicals LLC.)

Background: The electrophysiological responses of the left atrial appendage (LAA) during pulsed-field electrical isolation have not been established., Objective: This study aims to investigate the electrical responses of the LAA during pulsed-field electrical isolation using a novel device and their relations to acute isolation success., Methods: Six canines were enrolled. The E-SeaLA™ device, which is able to perform LAA occlusion and ablation simultaneously, was deployed into the LAA ostium. LAA potentials (LAAp) were mapped via a mapping catheter, and the LAAp recovery time (LAAp RT, the time between the last pulsed spike and the first recovered LAAp) was measured after pulsed-train delivery. The initial pulse index (PI, corelated to pulsed-field intensity) was adjusted during the ablation procedure until LAAEI was achieved. Acute LAA electrical isolation (LAAEI) success was defined as LAAp disappearance or exit and entrance conduction block, confirmed through a drug test and a 60-minute waiting period., Result: All canines achieved successful LAA occlusion without peri-device leaks. Acute LAA electrical isolation (LAAEI) was achieved in five out of six canines (5/6, 83.3%). Very late LAAp recurrence (LAAp RT > 600 s) was observed during PFA. Early recurrence (LAAp RT < 30 s) was observed in two canines (2/6, 33.3%) post-PFA. Intermediate recurrence (LAAp RT ~ 120 s) was observed in three canines (3/6, 50%) post-PFA. The two canines with intermediate recurrence achieved LAAEI with higher PI ablations. The one canine with early LAAp recurrence had a peri-device leak and achieved LAAEI by the same PI after replacing with a larger size device and eliminating the peri-device leak. Another canine with early recurrence (1/6, 16.7%) failed to achieve LAAEI due to epicardial connection with persistent left superior vena cava. No coronary spasm, stenosis or other complications were observed., Conclusion: These results suggest that with proper device-tissue contact and pulse intensity, LAAEI can be achieved using this novel device without serious complications. The LAAp RT patterns observed in this study could inform and guide the adjustment of the ablation strategy., (© 2023 Wiley Periodicals LLC.)

Introduction: A quantifiable, automated standard of analyzing heart rhythm has long eluded cardiologists due, in part, to the limitations in technology and the ability to analyze large electrogram datasets. In this proof-of-concept study, we propose new measures to quantify plane activity in atrial fibrillation (AF) using our Representation of Electrical Tracking of Origin (RETRO)-Mapping software., Methods: We recorded 30 s segments of electrograms at the lower posterior wall of the left atrium using a 20-pole double loop catheter (AFocusII). The data were analyzed with the custom RETRO-Mapping algorithm in MATLAB. Thirty second segments were analyzed for number of activation edges, conduction velocity (CV), cycle length (CL), activation edge direction, and wavefront direction. These features were compared across 34 613 plane edges in three types of AF: persistent AF treated with amiodarone (11 906 wavefronts), persistent AF without amiodarone (14 959 wavefronts), and paroxysmal AF (7748 wavefronts). Change in activation edge direction between subsequent frames and change in overall wavefront direction between subsequent wavefronts were analyzed., Results: All activation edge directions were represented across the lower posterior wall. The median change in activation edge direction followed a linear pattern for all three types of AF with R 2  = 0.932 for persistent AF treated without amiodarone, R 2  = 0.942 for paroxysmal AF, and R 2  = 0.958 for persistent AF treated with amiodarone. All medians and the standard deviation error bars remained below 45° (suggesting all activation edges were traveling within a 90° sector, a criterion for plane activity). The directions of approximately half of all wavefronts (56.1% for persistent without amiodarone, 51.8% for paroxysmal, 48.8% for persistent with amiodarone) were predictive of the directions of the subsequent wavefront., Conclusion: RETRO-Mapping can measure electrophysiological features of activation activity and this proof-of-concept study suggests that this can be extended to the detection of plane activity in three types of AF. Wavefront direction may have a role in future work for predicting plane activity. For this study, we focused more on the ability of the algorithm to detect plane activity and less the differences between the types of AF. Future work should be in validating these results with a larger data set and comparing with other types of activation such as rotational, collision, and focal. Ultimately, this work can be implemented in real-time for prediction of wavefronts during ablation procedures., (© 2023 The Authors. Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

CT Imaging for Phrenic Nerve Anatomy Introduction Phrenic nerve injury and diaphragmatic stimulation are common complications following arrhythmia ablation and pacing therapies. Preoperative comprehension of phrenic nerve anatomy via non-invasive CT imaging may help to minimize the electrophysiological procedure-related complications. Methods Coronary CT angiography data of 121 consecutive patients were collected. Imaging of left and right pericardiophrenic bundles was performed with volume rendering and multi-planar reformation techniques. The shortest spatial distances between phrenic nerves and key electrophysiology-related structures were determined. The frequencies of the shortest distances ≤5 mm, >5 mm and direct contact between phrenic nerves and adjacent structures were calculated. Results Left and right pericardiophrenic bundles were identified in 86.8% and 51.2% of the patients, respectively. The right phrenic nerve was <5 mm from right superior and inferior pulmonary veins in 92.0% and 3.2% of the patients, respectively. The percentage of right phrenic nerve, <5 mm from right atrium, superior caval vein, and superior caval vein-right atrium junction was 87.1%, 100%, and 62.9%, respectively. Left phrenic nerve was <5 mm from left atrial appendage, great cardiac vein, anterior and posterior interventricular veins, and left ventricular posterior veins in 81.9%, 1.0%, 39.1%, 28.6%, and 91.4% of the patients, respectively. Merely 0.06% left phrenic nerve had a distance <5 mm with left superior pulmonary vein, and none left phrenic nerve showed a distance <5 mm with left inferior pulmonary vein. Conclusion One-stop enhanced CT scanning enabled detection of phrenic nerve anatomy, which might facilitate avoidance of the phrenic nerve-related complications in interventional electrophysiology. [ABSTRACT FROM AUTHOR]

The article presents case study of A 62-year-old woman with a history of a paroxysmal supraventricular tachycardia (SVT) underwent catheter ablation. A dual antegrade atrioventricular nodal (AVN) physiology was observed during programmed atrial stimulation. During right ventricular entrainment pacing, tachycardia resetting occurred. A single premature atrial contractions with different coupling intervals were delivered via the coronary sinus electrode until the tachycardia was terminated.

An editorial is presented to the article the way in which heuristic biases influence medical decisionmaking has an area of focus especially physicians, charged with the public trust to provide the best care for a given patient. Topics include visibility and full transparency to the myriad of factors contribute to that decision‐making process has preferred and an often demanded regulatory strategy for the globe; and the number of payments for time period increased by 19% for general payments.

Aims: The objective of the study was to conduct a systematic review to describe and compare the different approaches for performing cardiac electrophysiology (EP) procedures in patients with interrupted inferior vena cava (IVC) or equivalent entities causing IVC obstruction., Methods: We conducted a structured search to identify manuscripts reporting EP procedures with interrupted IVC or IVC obstruction of any aetiology published up until August 2020. No restrictions were applied in the search strategy. We also included seven local cases that met inclusion criteria., Results: The analysis included 142 patients (mean age 48.9 years; 48% female) undergoing 143 procedures. Obstruction of the IVC was not known before the index procedure in 54% of patients. Congenital interruption of IVC was the most frequent cause (80%); and, associated congenital heart disease (CHD) was observed in 43% of patients in this setting. The superior approach for ablation was the most frequently used strategy (52%), followed by inferior approach via the azygos or hemiazygos vein (24%), transhepatic approach (14%), and retroaortic approach (10%). Electroanatomical mapping (58%), use of long sheaths (41%), intracardiac echocardiography (19%), transesophageal echocardiography (15%) and remote controlled magnetic navigation (13%) were used as adjuncts to aid performance. Ablation was successful in 135 of 140 procedures in which outcomes were reported. Major complications were only reported in patients undergoing AF ablation, including two patients with pericardial effusion, one of whom required surgical repair, and another patient who died after inadvertent entry into an undiagnosed atrioesophageal fistula from a previous procedure., Conclusion: The superior approach is most frequent approach for performing EP procedures in the setting of obstructed IVC. Transhepatic approach is a feasible alternative, and may provide a "familiar approach" for transseptal access when it is required. Adjunctive use of long sheaths, intravascular echocardiography, electro-anatomical mapping and remote magnetic navigation may be helpful, especially if there is associated complex CHD. With careful planning, EP procedures can usually be successfully performed with a low risk of complications., (© 2022 The Authors. Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

The optimal strategy for ablation of persistent atrial fibrillation (PsAF) remains to be defined. Established substrate-based ablation techniques, particularly techniques targeting complex electrograms, with complementary linear ablation for organized atrial tachycardias, have been associated with modest success rates. Recently, the development of VoM ethanol ablation (Et-VoM) has facilitated ablation of previously inaccessible arrhythmogenic substrate. This has allowed comparison of a standardized anatomically-guided protocol with Et-VOM to a traditional electrophysiology-guided approach for PsAF ablation., (© 2022 Wiley Periodicals LLC.)

Introduction: The optimal strategy after a failed ablation for persistent atrial fibrillation (perAF) is unknown. This study evaluated the value of an anatomically guided strategy using a systematic set of linear lesions with adjunctive ethanol infusion into the vein of Marshall (Et-VOM) in patients referred for second perAF ablation procedures., Methods and Results: Patients with perAF who underwent a second procedure were grouped according to the two strategies. The first strategy was an anatomically guided approach using systematic linear ablation with adjunctive Et-VOM, with bidirectional blocks at the posterior mitral isthmus (MI), roof, and cavotricuspid isthmus (CTI) as the procedural endpoint (Group I). The second one was an electrophysiology-guided strategy, with atrial tachyarrhythmia termination as the procedural endpoint (Group II). Arrhythmia behavior during the procedure guided the ablation strategy. Groups I and II consisted of 96 patients (65 ± 9 years; 71 men) and 102 patients (63 ± 10 years; 83 men), respectively. Baseline characteristics were comparable. In Group I, Et-VOM was successfully performed in 91/96 (95%), and procedural endpoint (bidirectional block across all three anatomical lines) was achieved in 89/96 (93%). In Group II, procedural endpoint (atrial tachyarrhythmia termination) was achieved in 80/102 (78%). One-year follow-up demonstrated Group I (21/96 [22%]) experienced less recurrence compared to Group II (38/102 [37%], Log-rank p = .01). This was driven by lower AT recurrence in Group I (Group I: 10/96 [10%] vs. Group II: 29/102 [28%]; p = .002)., Conclusion: Anatomically guided strategy with adjunctive Et-VOM is superior to an electrophysiology-guided strategy for second procedures in patients with perAF at 1-year follow-up., (© 2022 Wiley Periodicals LLC.)

Cellular Electrophysiology of Vanoxerine. Introduction: There remains an unmet need for safe and effective antiarrhythmic drugs, especially for the treatment of atrial fibrillation. Vanoxerine is a drug that is free of adverse cardiac events in normal volunteers, yet is a potent blocker of the hERG (hKv11.1) cardiac potassium channel. Consequently,we hypothesized that vanoxerine might also be a potent blocker of cardiac calcium (Ca) and sodium (Na) currents, and would not affect transmural dispersion of repolarization. Methods: The whole cell patch clamp technique was used to measure currents from cloned ion channels overexpressed in stable cell lines and single ventricular myocytes. We measured intracellular action potentials from canine ventricular wedges and Purkinje fibers using sharp microelectrode technique. Results: We found that vanoxerine was a potent hKv11.1 blocker, and at submicromolar concentrations, it blocked Ca and Na currents in a strongly frequency-dependent manner. In the canine ventricular wedge preparation vanoxerine did not significantly affect transmural action potential waveforms, QT interval or transmural dispersion of repolarization. Conclusions: Vanoxerine (1) is a potent blocker of cardiac hERG, Na and Ca channels; (2) block is strongly frequency-dependent especially for Na and Ca channels; and (3) transmural dispersion of ventricular repolarization is unaffected. The multichannel block and repolarization uniformity resemble the effects of amiodarone, the exemplar atrial fibrillation drug. Vanoxerine is a completely different chemical and has none of amiodarone's toxic effects. Vanoxerine has characteristics of a potentially effective and safe antiarrhythmic. [ABSTRACT FROM AUTHOR]

Introduction: Muscarinic receptor antagonists are proposed to prevent atrial fibrillation (AF), but also facilitate AV conduction, limiting clinical usefulness. Methods: Cisatracurium, a neuromuscular blocker, was administered to anesthetized dogs (0.05–0.8 mg/kg IV) and was administered to superfused pulmonary vein (PV) tissues in vitro. Results: Dose-dependent suppression of AF induced by premature atrial stimuli was observed under control conditions (n = 3), right vagus nerve stimulation (n = 7), and anterior right ganglionated plexus stimulation (n = 3). AF was prevented (P < 0.0001) concurrent with suppression of the decreased atrial MAP duration/ERP accompanying vagus nerve stimulation without altering AH intervals or sinus cycle length. Although atropine (0.001–0.016 mg/kg, n = 4) suppressed AF (P < 0.04) in association with suppression of atrial MAP shortening induced by vagus nerve stimulation, atropine also prevented sinus cycle length and AH interval prolongation with vagus nerve stimulation, and decreased AV effective and functional refractory periods. In vitro, both cisatracurium and atropine prevented (1) action potential shortening produced by acetylcholine administration and (2) action potential shortening and arrhythmia triggering within PV sleeves produced by local autonomic nerve stimulation, atropine producing competitive inhibition, and cisatracurium producing noncompetitive M2 muscarinic receptor blockade. Conclusions: Cisatracurium demonstrates a dose-dependent (1) suppression of AF and atrial action potential shortening accompanying vagus nerve stimulation without facilitating sinus or atrioventricular nodal function and (2) noncompetitive blockade of action potential shortening and triggered firing induced in isolated PVs by local autonomic nerve stimulation. The data are consistent with allosteric binding of cisatracurium to the M2 muscarinic receptor in canine atrium. [ABSTRACT FROM AUTHOR]

Background: Humans are more similar in transmural Purkinje and cardiac ion channel distributions to dogs than pigs. The Purkinje network in pigs is transmural but confined to the endocardium in dogs. Little is known about intramural activation during long-duration ventricular fibrillation (LDVF) given these differences. We tested the hypothesis that the transmural activation sequence is similar in sinus rhythm (SR) and LDVF in dogs as well as pigs, but different between species. Methods and Results: In six pigs and seven dogs, 50–60 plunge needles (six electrodes, 2-mm spacing) were placed throughout the left ventricle. Unipolar recordings were made for >10 minutes of LDVF. SR and LDVF activation times were grouped into waves by linking activations along each needle. Origin (earliest activation) and propagation direction were determined for each wave. The mean wave origin was significantly more endocardial in dogs than pigs for SR and 1 through 10 minutes of LDVF. Predominant propagation direction in LDVF and SR was endocardial to epicardial in dogs, but the opposite or equal in both directions in pigs. Fastest activation rate was epicardial in pigs, but endocardial in dogs with an increasing endocardial-to-epicardial activation rate gradient as LDVF progressed in dogs but not pigs. Conclusions: The transmural activation sequence in SR and LDVF is markedly different between pigs and dogs. These differences may be related to differences in Purkinje fiber and ion channel distributions and suggest that dogs are a better model for investigating activation sequences during LDVF, given the similarities with humans. [ABSTRACT FROM AUTHOR]

Introduction: Rapid firing originating within pulmonary veins (PVs) initiates atrial fibrillation (AF). The following studies were performed to evaluate spontaneous PV firing in patients with AF to distinguish focal versus reentrant mechanisms. Methods: Intracardiac recordings were obtained in 18 patients demonstrating paroxysmal AF. Microelectrode (ME) recordings were obtained from superfused canine PV sleeves (N = 48). Results: Spontaneous PV firing (566 ± 16 bpm; 127 ± 6 ms cycle length) giving rise to AF (52 episodes) was observed. Tachycardia-pause initiation was present in 132 of 200 episodes of rapid PV firing and 34 of 52 AF episodes. The pause cycle length preceding PV firing was 1,039 ± 86 ms following tachycardia (420 ± 40 ms cycle length). The remaining episodes were initiated following a 702 ± 32 ms pause during sinus rhythm (588 ± 63 ms). Spontaneous firing recorded with a multipolar mapping catheter did not detect electrical activity bridging the diastolic interval between the initial ectopic and preceding post-pause sinus beat. Tachycardia-pause initiated PV firing (138 ± 7 ms coupling interval) in patients correlated with tachycardia-pause enhanced isometric force, early afterdepolarization (EAD) amplitude, and triggered firing within canine PVs. Rapid firing (1,172 ± 134 bpm; 51 ± 8 ms cycle length) following an abbreviated coupling interval (69 ± 12 ms) was initiated in 13 of 18 canine PVs following tachycardia-pause pacing during norepinephrine + acetylcholine superfusion. Stimulation selectively activating local autonomic nerve terminals facilitated tachycardia-pause triggered firing in canine PVs (5 of 15 vs 0 of 15; P < 0.05). Conclusions: The studies demonstrate (1) tachycardia-pause initiation of rapid, short-coupled PV firing in AF patients and (2) tachycardia-pause facilitation of isometric force, EAD formation, and autonomic-dependent triggered firing within canine PVs, suggestive of a common arrhythmia mechanism. [ABSTRACT FROM AUTHOR]

An editorial is presented on impact of Civid-19 pandemic on Heart Rhythm Societies and their members. Topics discussed include attending cutting edge presentations and being introduced to new concepts given by emerging and known leaders in the field of cardiac electrophysiology; and Cardiac electrophysiologists have followed many of those patients; like other health care workers, they are also at risk of acquiring coronavirus disease 2019 (COVID‐19).

Background: Earliest postshock activation following failed defibrillation shocks slightly lower than the defibrillation threshold (DFT) in large animals appears to arise from a focus. We tested the hypothesis that these foci are caused by early or delayed afterdepolarizations (EADs or DADs) by performing epicardial electrical mapping and giving the EAD inhibitor pinacidil or the DAD inhibitor flunarizine to see if the foci were extinguished or altered in timing or location. Methods and Results: A sock containing 504 electrodes was placed over the entire ventricular epicardium of 12 open-chested pigs. After the DFT was determined and additional shocks given, pinacidil was administered to 6 pigs and flunarizine to 6 pigs. Then, the DFT was again determined and additional shocks were given. Pinacidil significantly shortened the effective refractory period (ERP) (162 ± 16 vs 130 ± 28 msec) and action potential duration (APD90) (179 ± 6 vs 149 ± 19 msec) and significantly increased the peak frequency of the power spectrum of a left ventricle (LV) electrode during ventricular fibrillation (VF) (9.3 ± 0.6 vs 10.5 ± 1.0 Hz), while flunarizine did not significantly alter the ERP (162 ± 8 vs 167 ± 18 msec) or APD90 (187 ± 12 vs 191 ± 20) but significantly reduced the peak frequency (9.2 ± 0.5 vs 7.5 ± 1.0 Hz). These findings suggest the drugs had their expected electrophysiological effects. However, the DFT was not significantly changed by either drug. Following the same strength shock 10% below the predrug DFT, earliest postshock activation arose in a focal epicardial pattern from the anterior-apical LV both before and after the drugs. The time from the shock until the appearance of this activation was not significantly different before and after either drug. Conclusion: The lack of change in DFT as well as the lack of change in the incidence, location, and timing of the postshock focus with sub-DFT strength shocks before and after pinacidil and flunarizine provide evidence that these foci are not caused by triggered activity. [ABSTRACT FROM AUTHOR]

Introduction: We hypothesize that local modifications in electrophysiological properties, when confined to zones of limited extent, induce few changes in the global activation process during ventricular fibrillation (VF). To test this hypothesis, we produced local electrophysiological modifications by stretching a circumscribed zone of the left ventricular wall in an experimental model of VF. Methods and Results: In 23 Langendorff-perfused rabbit hearts frequency, time–frequency and time-domain techniques were used to analyze the VF recordings obtained with two epicardial multiple electrodes before, during, and after local stretching produced with a left intraventricular device. Acute local stretching accelerated VF in the stretched zone reversibly and to a variable degree, depending on the magnitude of stretch and the time elapsed from its application. In the half time (5 minutes) of the analyzed period, a longitudinal lengthening of 12.1 ± 4.5% (vertical axis) and 11.8 ± 6.2% (horizontal axis) in the stretched zone produced an increase in the dominant frequency (DFr) (15.2 ± 1.9 versus 18.8 ± 2.5 Hz, P < 0.0001), a decrease in mean VV interval (63 ± 8 versus 53 ± 6 msec, P < 0.001), and an increase in the complexity of the activation maps—with more areas of conduction block and more breakthrough patterns (23% versus 37%, P < 0.01), without significant changes in the percentages of complete reentry patterns (9% versus 9%, ns). Simultaneously, in the nonstretched zone, no variations were observed in the DFr (15.2 ± 2.1 versus 15.3 ± 2.5 Hz, ns), mean VV intervals (66 ± 8 versus 65 ± 8 msec, ns), or types and percentages of maps with breakthrough (25% versus 20%, ns) or reentry patterns (12% versus 8%, ns). No significant correlation was observed between the DFr in the two zones (R = 0.24, P = 0.40). Conclusion: Local stretching increases the electrophysiological heterogeneity of myocardium and accelerates and increases the complexity of VF in the stretched area, without significantly modifying the occurrences of the types of VF activation patterns in the nonstretched zone. [ABSTRACT FROM AUTHOR]

Introduction: We hypothesized that the transgenic mice expressing a dominant-negative form of the CREB transcription factor (CREB[sub A133] ) under the control of the cardiac myocyte-specific α-MHC promoter and displaying dilated cardiomyopathy would exhibit electrophysiologic abnormalities similar to those observed in human cardiomyopathy. Methods and Results: Invasive electrophysiologic studies were performed on two age groups of mice: 11-week-old mice (n = 20, 9 transgenic mice and 11 wild-type controls) and 17-week-old mice (n = 16, 7 transgenic mice and 9 wild-type controls). Five additional transgenic mice underwent ambulatory ECG monitoring to determine the cause of death. The 11-week-old CREB[sub A133] transgenic mice had longer PR and AH intervals than 11-week-old wild-type controls (P < 0.001), whereas at 17 weeks of age the transgenic mice also demonstrated increased HV intervals and widened QRS duration (P < 0.05). At both 11 weeks and 17 weeks of age, AV Wenckebach cycle length, 2:1 AV cycle length, and AV nodal functional and effective refractory periods were significantly longer in transgenic mice than in controls (P < 0.05). Although no ventricular arrhythmias were inducible at 11 weeks of age, at 17 weeks of age, ventricular tachycardia was induced in 4 of the 7 CREB[sub A133] transgenic mice but in none of the 9 wild-type controls. All 5 CREB[sub A133] transgenic mice that underwent ambulatory ECG monitoring revealed high-grade AV block, but not ventricular arrhythmia, at the time of death. Conclusion: These data suggest that CREB[sub A133] transgenic mice manifest abnormalities of AV nodal and infra-Hisian conduction and inducibility of ventricular arrhythmia, which are characteristics of human dilated cardiomyopathy. (J Cardiovasc Electrophysiol, Vol. 14, pp. 982-989, September 2003) [ABSTRACT FROM AUTHOR]

Introduction: Reliable detection of drug-induced proarrhythmia, especially the potential for polymorphic ventricular tachycardia, is of great importance in the development of new compounds that are safe for the heart and was evaluated in a blinded study.. Methods and Results: In 142 female rabbits, the monophasic action potential was used to determine intraventricular conduction, action potential duration (APD), triangulation (APD[sub 30] to APD[sub 90] ), reverse use-dependence, instability and presence of chaotic behavior, early afterdepolarizations, torsades de pointes (TdP), and ventricular fibrillation. In addition, 31 coded drugs were tested in a blinded fashion in another 150 hearts. Prototype cardiovascular agents [quinidine (IA), lidocaine (IB), flecainide (IC), propranolol (II), sotalol (IIIB), amiodarone (IIIAB) and verapamil (IV)] were correctly characterized in terms of their effects upon conduction and APD. Agents documented in clinical practice to have proarrhythmic potential (droperidol, sotalol, mibefradil, bepridil, lidoflazine, ketanserin, sertindole, terfenadine, haloperidol, astemizole, cisapride, ziprasidone, lubeluzole, dofetilide, quinidine, ibutilide) were identified as such. Pimozide is reported to rarely produce TdP and was also found to elicit Class III action with few adverse effects. Equally important, agents believed not to be proarrhythmic (two solvents, atenolol, propranolol, fenoximone, cetirizine, verapamil, sildenafil, lidocaine, diltiazem) were identified as having no proarrhythmic activity.. Conclusion: The SCREENIT method properly characterized and quantified prototype cardiovascular drugs and correctly identified proarrhythmic noncardiovascular agents of various mechanisms, but it did not produce false-positive results.(J Cardiovasc Electrophysiol, Vol. 14, pp. 287-294, March 2003). [ABSTRACT FROM AUTHOR]

Introduction: Experimental evidence suggests a major role for Fas receptor activation in a wide range of myocardial pathologies. Because clinical situations, which are likely to be associated with Fas activation, are accompanied by a variety of ventricular arrhythmias, the major goal of this study was to investigate the ionic mechanisms responsible for these phenomena. Methods and Results: To delineate the origin of Fas-mediated electrophysiologic perturbations, the transient outward K+ current Ito and the L-type Ca2+ current ICa,L were studied in murine ventricular myocytes treated with the Fas-activating monoclonal antibody Jo2. Jo2 decreased Ito (4.36 ± 1.2 pA/pF vs 17.48 ± 2.36 pA/pF in control, VM, = -H50 mV; P < 0.001) and increased ICa,L (-13.17 ± 1.38 pA/pF vs -3.94 ± 0.78 pA/pF in control, VM, = 0 mV; P < 0.001). Pretreatment of ventricular myocytes with ryanodine or thapsigargin prevented the electrophysiologic effects of Jo2, suggesting that [Ca2+], elevation is important for Fas-mediated action. In agreement with our previous studies demonstrating dependence of Fas-based myocyte dysfunction on an intact inositol trisphosphate (1,4,5-IP3) pathway, the effects of Jo2 on Ito and ICa,L were prevented by the phospholipase C (generates 1,4,5-IP3) blocker U73122, and by xestospongin C (tested with Ito), a specific blocker of IP3-operated sarcoplasmic reticulum Ca2+ release channels. Furthermore, intracellular perfusion with 1,4,5-IP3, but not with 1,3,4-IP3, caused electrophysiologic effects resembling those of Jo2. Conclusion: Decreased Ito and increased ICa,L underlie Fas-induced action potential alterations and arrhythmias in murine ventricular myocytes, effects that appear to be mediated by 1,4,5-IP3-induced intracellular calcium release. [ABSTRACT FROM AUTHOR]

Background: Left bundle branch pacing (LBBP) is a new near-physiological pacing modality. Distinguishing left ventricular septal only pacing (LVSP) from nonselective LBBP still needs clarification. This prospective study sought to establish a differentiation algorithm to confirm LBBP., Methods and Results: LBBP was attempted in consecutive patients. If direct LBB capture (LBBP) could not be confirmed, LVSP was considered to have been achieved. Intracardiac left ventricular (LV) activation sequence and activation time were analyzed using coronary sinus (CS) electrogram mapping. Electrophysiological parameters including S-CSmax, S-CSmin, LV lateral wall activation time, ΔLV, and LBB potential were compared between LBBP and LVSP. Stimulated LV activation time (S-LVAT) and stimulated QRS duration (S-QRSd) were also compared between the two groups. Multivariate logistic regression analysis was used to develop a prediction algorithm for LBBP. Of the 43 prospectively enrolled patients, 27 underwent LBBP and 16 underwent LVSP. All LBBP patients showed identical LV activation sequences to their intrinsic rhythm while no LVSP patients maintained their intrinsic sequence. S-CSmax, ΔLV, LV lateral wall activation time, and S-LVAT during LBBP were significantly shorter than those during LVSP. Combining LBB potential with S-LVAT had the largest area under the curve (AUC) of 0.985 for confirming LBBP with a sensitivity of 95.2% and a specificity of 93.7%., Conclusions: Compared with LVSP, LBBP preserves a normal LV activation sequence and better electrical synchrony. A combination of LBB potential with S-LVAT can be an effective and practical model to distinguish LBBP from LVSP during implantation in patients with normal LBB activation., (© 2022 Wiley Periodicals LLC.)

Background: Pulsed-field ablation (PFA) yields a novel ablation technology for atrial fibrillation (AF). PFA lesions promise to be highly durable, however clinical data on lesion characteristics are still limited., Objective: This study sought to investigate PFA lesion creation with ultrahigh-density (UHDx) mapping., Methods: Consecutive AF patients underwent PFA-based pulmonary vein isolation (PVI) using a multispline catheter (Farwave, Farapulse Inc.). Additional ablation, including left atrial posterior wall isolation (LAPWI) and mitral isthmus ablation (MI) were performed in a subset of persistent AF patients. The extent of PFA-lesions and decrease of LA-voltage were assessed with pre- and post PFA UHDx-mapping (Orion™ catheter and Rhythmia™ 3D-mapping system, Boston Scientific)., Results: In 20 patients, acute PVI was achieved in 80/80 PVs, LAPW isolation in 9/9 patients, MI ablation in 2/2 (procedure time: 123 ± 21.6 min, fluoroscopy time: 19.2 ± 5.5 min). UHDx-mapping subsequent to PVI revealed early PV-reconnection in five case (5/80, 6.25%). Gaps were located at the anterior-superior PV ostia and were successfully targeted with additional PFA. Repeat UHDx mapping after PFA revealed a significant decrease of voltage along the PV ostia (1.67 ± 1.36 mV vs. 0.053 ± 0.038 mV, p < .0001) with almost no complex electrogram-fractionation at the lesion border zones. PFA-catheter visualization within the mapping system was feasible in 17/19 (84.9%) patients and adequate in 92.9% of ablation sites., Conclusion: For the first time illustrated by UHDx mapping, PFA creates wide antral circumferential lesions and homogenous LAPW isolation with depression of tissue voltage to a minimum. Although with a low incidence, early PV reconnection can still occur also in the setting of PFA., (© 2022 Wiley Periodicals LLC.)

Introduction: Standard two-dimensional (2D), phased-array intracardiac echocardiography (ICE) is routinely used to guide interventional electrophysiology (EP) procedures. A novel four-dimensional (4D) ICE catheter (VeriSight Pro, Philips) can obtain 2D and three-dimensional (3D) volumetric images and cine-videos in real-time (4D). The purpose of this study was to determine the early feasibility and safety of this 4D ICE catheter during EP procedures., Methods: The 4D ICE catheter was placed from the femoral vein in ten patients into various cardiac chambers to guide EP procedures requiring transseptal catheterization, including ablation for atrial fibrillation and left atrial appendage closure. 2D- and 3D-ICE images were acquired in real-time by the electrophysiologist. A dedicated imaging expert performed digital steering to optimize and postprocess 4D images., Results: Eight patients underwent pulmonary vein isolation (cryoballoon in seven patients, pulsed field ablation in one, additional radiofrequency left atrial ablation in one). Two patients underwent left atrial appendage closure. High quality images of cardiac structures, transseptal catheterization equipment, guide sheaths, ablation tools, and closure devices were acquired with the ICE catheter tip positioned in the right atrium, left atrium, pulmonary vein, coronary sinus, right ventricle, and pulmonary artery. There were no complications., Conclusion: This is the first experience of a novel deflectable 4D ICE catheter used to guide EP procedures. 4D ICE imaging is safe and allows for acquisition of high-quality 2D and 3D images in real-time. Further use of 4D ICE will be needed to determine its added value for each EP procedure type., (© 2021 Wiley Periodicals LLC.)

Background: Intracardiac electrogram data remain one of the primary diagnostic inputs guiding complex ablation procedures. However, the technology to collect, process, and display intracardiac signals has known shortcomings and has not advanced in several decades., Objective: The purpose of this study was to evaluate a new signal processing platform, the PURE EP™ system (PURE), in a multi-center, prospective study., Methods: Intracardiac signal data of clinical interest were collected from 51 patients undergoing ablation procedures with PURE, the signal recording system, and the 3D mapping system at the same time stamps. The samples were randomized and subjected to blinded, controlled evaluation by three independent electrophysiologists to determine the overall quality and clinical utility of PURE signals when compared to conventional sources. Each reviewer assessed the same (92) signal sample sets and responded to (235) questions using a 10-point rating scale. If two or more reviewers rated the PURE signal higher than the control, it was deemed superior., Results: A total of 93% of question responses showed consensus amongst the blinded reviewers. Based on the ratings for each pair of signals, a cumulative total of 164 PURE signals out of 218 (75.2%) were statistically rated as Superior for this data set (p < .001). Only 14 PURE signals out of 218 were rated as Inferior (6.4%)., Conclusion: The PURE intracardiac signals were statistically rated as superior when compared to conventional systems., (© 2021 The Authors. Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

Introduction: The initiation of ventricular arrhythmias is in part associated with autonomic nervous tone. We Investigated the effects of sympathetic and parasympathetic stimulation on the monophasic action potentials (MAPs) of the epicardium (EPi), mid!myocardial (M) region, and endocardium (Endo) in vivo. Methods and Results: In 12 mongrel open chest anesthetized dogs, both sides of the cervical vagus nerves and stellate ganglia were crushed with a tight ligature. Right atrial pacing at 600 msec cycle length was begun after the sinus nodal area had been crushed. MAPs from the NI region were measured by two needle electrodes that were supported by a W-shaped plastic frame. The epicardial, M region, and endocardial MAP durations at 90% repolarizatlon (MAPD90) were 287 ± 7, 315 ± 7, and 290 ± 8 msec, respectively. The MAPD90 from M cells was longer than that from Epi or Endo. Sympathetic stimulation shortened MAPD90 more In the M region (53 ± 4 msec) than that in the Epi (27 ± 3 msec) or Endo (26 ± 4 msec). The transmural dispersion of repolarization during sympathetic stimulation was shorter than that of the control. Parasympathetic stimulation did not significantly affect any of the MAPD90 values. Simultaneous sympathetic and parasympathetic stimulation produced changes not significantly to those produced by sympathetic stimulation alone. Conclusion: Our results suggest that sympathetic activity can reduce transmural dispersion of repolarization under autonomic control in the canine heart under baseline conditions. [ABSTRACT FROM AUTHOR]

Introduction: While it is now understood that the tissue geometry and the electric field distribution are important in generating virtual electrodes, the effects of interaction between a collection of electrodes have not been examined. To develop a basis for understanding such interactions, we have studied a single pair of oppositely polarized virtual sources. Although such oppositely polarized pairs of virtual electrodes can be generated by a variety of field distributions and tissue geometries, we examine one simple system that incorporates the salient features of source interaction. Met/sods and Results: Our model system is a homogeneous tissue strip stimulated by a uniform extracellular field. To clarify virtual source interaction, we show that field stimulated tissue can be equivalently polarized by a set of intracellular current sources with magnitude and distribution defined by the generalized activating function. In our model system, an intracellular current source is produced at one edge of the tissue and an intracellular current sink at the other. Therefore, the tissue length acts to modulate the overlap, or interaction, between the polarizations arising from each source. To quantify the effects of source interaction, the chronaxie and rheobase values of the strength-duration relation were determined for source separations varying between 1.0 cm and 100 μm (active membrane dynamics were modeled with the Luo-Rudy phase I formulation). At all separations > 3.0 mm, the chronaxie was constant at 3.09 msec and the rheobase was 0.38 V/cm. Under 0.2 mm, the chronaxie decreased to 0.55 msec while the rheobase increased linearly with the inverse of source separation. The dependence of these parameters on separation primarily reflects passive electrotonic interactions between the two virtual electrodes. However, the exact values are strongly dependent upon active tissue properties-largely the inward rectifier potassium channel and activation of the sodium current. conclusion: Tissue excitation in response to field stimulation is strongly modulated by the proximity of, and therefore the interaction between, oppositely polarized virtual electrode sources. [ABSTRACT FROM AUTHOR]