Catheter based cardioneuroablation is increasingly being utilized to improve outcomes in patients with vasovagal syncope and functional atrioventricular block. There is now increasing convergence amongst enthusiasts on its various aspects, including patient selection, technical steps, and procedural end-points. This pragmatic review aims to take the reader through a step-by-step approach to cardioneuroablation: we begin with a brief overview of the anatomy of intrinsic cardiac autonomic nervous system, before focusing on the indications, pre- and post-procedure management, necessary equipment, and its potential limitations.

Radiofrequency Ablation: Four Decades Later, Still Optimizing Lesion Characterization Alan D. Enriquez, M.D.1,2; Sharma Kattel MD, PhD11Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, CT2VA Connecticut Healthcare System, West Haven, CTFunding: NoneDisclosures: Boston Scientific – HonorariaWord count: 1304Corresponding Author:Alan D. Enriquez, MDCardiovascular MedicinePO Box 208017New Haven, CT [email protected] catheter ablation was first introduced in the early 1980s with a direct current shock used as the energy source. (1) Titration of energy delivery was difficult, and extensive tissue damage could occur. Radiofrequency (RF) ablation was first reported by Huang and colleagues in 1985 and has since become the cornerstone of catheter ablation. The technique and delivery of RF energy application has undergone significant modifications over the last two decades with the introduction of irrigated tip and contact force sensing catheters.The current standard RF generator produces 300-750 kHz of alternating sinusoidal current. During RF application, the current that transverses from the tip of the ablation catheter through intervening tissue to a dispersive electrode attached to patient’s body surface results in lesion formation through resistive and conductive heating, with tissue temperatures \(\geq\) 50o Celsius resulting in irreversible injury. (2) As higher current delivery may be limited due to char formation from rapid temperature rise in the tissue-catheter interface, irrigated RF was developed to overcome this limitation. Introduction of contact force sensing catheters has provided an additional tool to continuously assess catheter stability during RF delivery, thereby improving safety and efficacy. (3)Despite these advances, assessment of lesion quality during RF ablation remains challenging, and inadequate lesion formation plays a substantial role in the relatively high recurrence rates after atrial fibrillation and ventricular tachycardia ablation.(4,5) Current density is a primary determinant of lesion size and is dependent on multiple factors including RF power, size of the electrode tip, tissue contact, impendence, tissue-electrode interface temperature, tissue characteristics, and duration of energy delivery. Irrigated RF has rendered tip temperature unreliable as a predictor of tissue temperature, and accounting for all of these variables to reliably determine lesion size has been problematic.As a result, there has been significant interest in developing algorithms to predict the size of lesion formation to improve efficacy and safety of catheter ablation. Force Time Integral (FTI) and Lesion Size Index (LSI) have been developed for use with the TactiCathTM contact force sensing catheter and EnsiteTM Precision 3D mapping system (Abbott Medical, St. Paul, MN).FTI is defined as total contact force integrated over the time of RF delivery. While targeting FTI > 400 grams has been associated with improved outcomes in atrial fibrillation ablation (6,7), FTI does not account for power. LSI is calculated by aggregating contact force as well as current data across time with the intent to provide a more precise assessment of lesion formation. However, data regarding the accuracy of LSI in predicting lesion size and quality is sparse.In this issue, Themistoclakis et al evaluated lesion size for pre-specified values of LSI reached during RF delivery in vivo in a porcine heart. Using 3D electro-anatomical mapping as a reference, 64 RF lesions targeting LSI values of 4-6 using a fixed power output of 30 W in temperature control mode at 42° C and contact force of 10-30 grams were created in 7 porcine hearts using a TactiCath contact force sensing catheter. The hearts were then explanted, and lesions were examined histologically. Only 25 non-transmural lesions were used for complete analysis with the remainder excluded due to transmurality, macroscopically unidentifiable lesions, or inability to measure lesion width or depth because of unfavorable anatomic location of the lesions. Of note, all atrial lesions were transmural with LSI \(\geq\) 4, and only lesions in the right and left ventricles were included in the final analysis. The authors were able to show a strong linear correlation with LSI values and lesion width (r=0.87, p<0.00001) and depth (r=0.89, p<0.00001). At LSI values of 4, 5 and 6, lesion width corresponded to 4.6±0.6 mm, 7.3±0.8 mm and 8.6±1.2 mm respectively. Similarly, lesion depth at LSI values of 4, 5, and 6 corresponded to 2.6±0.8 mm, 4.7±0.6 mm and 7.2±1.1 mm respectively. Furthermore, compared with other lesion parameters (FTI, RF duration, impedance drop, average temperature, contact force, and power), LSI was the only independent predictor of lesion width and depth in multivariable regression analysis. Also, steam pops, char formation, and damage to surrounding structures were not observed in this study.This is the first in vivo study examining LSI and lesion width and depth, and the authors have demonstrated that LSI is highly correlated with lesion width and depth. Moreover, these findings are consistent with prior studies. A prior in vitro study using a porcine myocardial slab model also showed that LSI was predictive of lesion width and depth and was a stronger predictor compared to FTI (8). Another in vivo study by Whitaker et al showed that when a LSI of 5 is targeted in the right atrium of porcine hearts, a LSI(interlesion distance – LSI) \(\leq\) 1.5 was associated with contiguous lesions and no gaps in the ablation line. (9) Thus, this study supports LSI as a strong predictor of lesion size.Achieving adequate lesion depth and width during RF application is important to obtain transmurality and contiguous lesions respectively and to improve efficacy of radiofrequency ablation. In some situations, it may also be important to limit lesion depth to prevent collateral damage to adjacent structures, such as avoiding esophageal damage when ablating in the posterior left atrium. Hence, LSI is a potentially powerful tool to assess lesion size during ablation in real-time. The authors proposed formulas for estimation of lesion width and depth using LSI based on their linear regression model (W(mm)= -4.21+2.17*LSI, and D(mm)=-7.54+2.54* LSI ). Using these equations, they proposed LSI values to achieve transmural lesions at different locations in the left atrium (LA) during pulmonary vein isolation (PVI) based on average human LA thickness (posterior wall = 4.1 mm, LSI ≥ 4.8; ridge between appendage and pulmonary vein = 5.0 mm, LSI ≥ 5.2; or interatrial septum = 5.5 mm, LSI ≥ 5.4) . There are clinical data supporting targeting pre-specified LSI values during PVI. There are small studies showing improved outcomes with PVI when the mean LSI achieved Is > 5.0. (10,11) Kanamori et al showed that an LSI < 5.25 anteriorly and < 4.0 posteriorly was associated with conduction gaps after PVI and suggested target LSI values of\(\geq\ \)5.2 anteriorly and \(\geq\) 4.0 posteriorly (areas adjacent to the espohagus) to obtain durable pulmonary vein isolation. (12) Adverse events were also not more frequent in patients with higher LSI values.While the findings of this study are compelling, there are limitations in applying these LSI findings to clinical practice. There were a relatively small number of lesions included in the study, and there are inherent differences in tissue heterogeneity, thickness, blood flow, body surface, and impedance values in porcine hearts compared to human hearts. In addition, these findings are most applicable to ablation in the ventricles since atrial lesions were excluded from the final analysis due to transmurality, though LSI had similar correlation with lesion width in the atrial lesions. It is also important to note that these LSI values were obtained at a fixed power of 30 W and using saline irrigation. These correlations may not hold true for different power settings or other irrigation fluids (e.g. half-normal saline), especially with the use of high power due to nonlinear behavior of tissue heating from an initial rapid resistive heating in early phase to more conductive heating in the later phase.The findings of this study combined with the existing literature support LSI as a clinically relevant surrogate for lesion size. Targeting LSI values of 4-6 appears to be safe, and LSI may be used as an adjunctive tool in conjunction with other parameters of RF ablation to estimate lesion size. However, caution must still be exercised, and there are no established LSI targets for atrial fibrillation and ventricular tachycardia ablation. While progress is being made in characterizing lesions during ablation, further studies are required to confirm the efficacy of using LSI and to establish optimal LSI target values.References1. Andrade JG, Rivard L, Macle L. The past, the present, and the future of cardiac arrhythmia ablation. Can J Cardiol 2014;30:S431-41.2. Nath S, DiMarco JP, Haines DE. Basic aspects of radiofrequency catheter ablation. J Cardiovasc Electrophysiol 1994;5:863-76.3. Yokoyama K, Nakagawa H, Shah DC, Lambert H, Leo G, Aeby N, Ikeda A, Pitha JV, Sharma T, Lazzara R, Jackman WM. Novel contact force sensor incorporated in irrigated radiofrequency ablation catheter predicts lesion size and incidence of steam pop and thrombus. Circ Arrhythm Electrophysiol 2008;1:354-62.4. Packer DL, Mark DB, Robb RA, Monahan KH, Bahnson TD, Poole JE, Noseworthy PA, Rosenberg YD, Jeffries N, Mitchell LB, Flaker GC, Pokushalov E, Romanov A, Bunch TJ, Noelker G, Ardashev A, Revishvili A, Wilber DJ, Cappato R, Kuck KH, Hindricks G, Davies DW, Kowey PR, Naccarelli GV, Reiffel JA, Piccini JP, Silverstein AP, Al-Khalidi HR, Lee KL, Investigators C. Effect of Catheter Ablation vs Antiarrhythmic Drug Therapy on Mortality, Stroke, Bleeding, and Cardiac Arrest Among Patients With Atrial Fibrillation: The CABANA Randomized Clinical Trial. JAMA 2019;321:1261-1274.5. Sapp JL, Wells GA, Parkash R, Stevenson WG, Blier L, Sarrazin JF, Thibault B, Rivard L, Gula L, Leong-Sit P, Essebag V, Nery PB, Tung SK, Raymond JM, Sterns LD, Veenhuyzen GD, Healey JS, Redfearn D, Roux JF, Tang AS. Ventricular Tachycardia Ablation versus Escalation of Antiarrhythmic Drugs. N Engl J Med 2016;375:111-21.6. Neuzil P, Reddy VY, Kautzner J, Petru J, Wichterle D, Shah D, Lambert H, Yulzari A, Wissner E, Kuck KH. Electrical reconnection after pulmonary vein isolation is contingent on contact force during initial treatment: results from the EFFICAS I study. Circ Arrhythm Electrophysiol 2013;6:327-33.7. Kautzner J, Neuzil P, Lambert H, Peichl P, Petru J, Cihak R, Skoda J, Wichterle D, Wissner E, Yulzari A, Kuck KH. EFFICAS II: optimization of catheter contact force improves outcome of pulmonary vein isolation for paroxysmal atrial fibrillation. Europace 2015;17:1229-35.8. Calzolari V, De Mattia L, Indiani S, Crosato M, Furlanetto A, Licciardello C, Squasi PAM, Olivari Z. In Vitro Validation of the Lesion Size Index to Predict Lesion Width and Depth After Irrigated Radiofrequency Ablation in a Porcine Model. JACC Clin Electrophysiol 2017;3:1126-1135.9. Whitaker J, Fish J, Harrison J, Chubb H, Williams SE, Fastl T, Corrado C, Van Zaen J, Gibbs J, O’Neill L, Mukherjee R, Rittey D, Thorsten J, Donskoy E, Sohal M, Rajani R, Niederer S, Wright M, O’Neill MD. Lesion Index-Guided Ablation Facilitates Continuous, Transmural, and Durable Lesions in a Porcine Recovery Model. Circ Arrhythm Electrophysiol 2018;11:e005892.10. Dello Russo A, Fassini GM, Casella M, Romanelli E, Pala S, Riva S, Catto V, Moltrasio M, Tundo F, Zucchetti M, Majocchi B, Dessanai MA, Pizzamiglio F, Vettor G, Ribatti V, Gasperetti A, Cellucci S, Negro G, Sicuso R, Carbucicchio C, Tondo C. Lesion index: a novel guide in the path of successful pulmonary vein isolation. J Interv Card Electrophysiol 2019;55:27-34.11. Mattia L, Crosato M, Indiani S, Causin E, Licciardello C, Maria Squasi PA, De Leo A, Calzolari V. Prospective Evaluation of Lesion Index-Guided Pulmonary Vein Isolation Technique in Patients with Paroxysmal Atrial Fibrillation: 1-year Follow-Up. J Atr Fibrillation 2018;10:1858.12. Kanamori N, Kato T, Sakagami S, Saeki T, Kato C, Kawai K, Chikata A, Takashima SI, Murai H, Usui S, Furusho H, Kaneko S, Takamura M. Optimal lesion size index to prevent conduction gap during pulmonary vein isolation. J Cardiovasc Electrophysiol 2018;29:1616-1623.

Title: Looking for Lead Adhesions While Planning for Transvenous Lead ExtractionAuthor: Callahan, Thomas DAuthor Expanded:Thomas D. Callahan, IV, MD, FACC, FHRSDirector, Inpatient Inpatient ServiceAssociate Program Director, Cardiovascular Medicine FellowshipCleveland ClinicClinical Assistant Professor of MedicineCleveland Clinic Lerner College of MedicineCleveland [email protected] 216-444-2267Fax: 216-636-6953Corresponding Author: Thomas D. Callahan, IV, MD, FACC, FHRSFunding: NoneDisclosures:Thomas D. Callahan, IV, MD serves as a consultant to Biotronik. (modest)Key words:Transvenous lead extraction, TLE, adhesion, planning, predictionAcknowledgements: None

Aims: Iatrogenic cardiac perforation is an uncommon but potentially fatal complication of invasive cardiac procedures. When non-surgical management fails, urgent cardiac surgery is required. Standard surgical approach is usually through full sternotomy. However, we propose a less invasive and equally effective technique with video-assisted thoracoscopic surgery (VATS).  Methods: This single-center retrospective study in a tertiary hospital identified all patients requiring surgical intervention due to iatrogenic cardiac perforation over a period of 5 years. Patients were grouped by surgical approach, being either sternotomy or VATS. Primary endpoints were length of ICU stay, hospital stay, 30-day mortality and all round mortality. Results: 25 patients were identified: 11 in the sternotomy-group and 14 in the VATS-group. Preoperative baseline characteristics were equal. Significant difference was found for 30-day mortality (p < 0.05). There was no difference for the other endpoints. Conclusions: Video-assisted thoracoscopic surgery is a promising alternative to standard sternotomy for iatrogenic cardiac perforations after invasive cardiac procedures.

Is there a need for a novel algorithm for accessory pathways localization?Malek Nayfeh MD, Marwan M. Refaat MDDivision of Cardiology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, LebanonRunning Title: Is there a need for a novel algorithm for WPW localization?Words: 572 (excluding the title page and references)Keywords: accessory pathways, Wolff-Parkinson-white, WPW, cardiac arrhythmias, cardiovascular diseases, heart diseases, Inferior Lead DiscordanceFunding: NoneDisclosures: NoneCorresponding Author:Marwan M. Refaat, MD, FACC, FAHA, FHRS, FASE, FESC, FACP, FRCPAssociate Professor of MedicineDirector, Cardiovascular Fellowship ProgramDepartment of Internal Medicine, Cardiovascular Medicine/Cardiac ElectrophysiologyDepartment of Biochemistry and Molecular GeneticsAmerican University of Beirut Faculty of Medicine and Medical CenterPO Box 11-0236, Riad El-Solh 1107 2020- Beirut, LebanonUS Address: 3 Dag Hammarskjold Plaza, 8th Floor, New York, NY 10017, USAOffice: +961-1-350000/+961-1-374374 Extension 5353 or Extension 5366 (Direct)Wolff Parkinson White Syndrome (WPW) affects between 0.1% and 0.2% of the population, causes morbidity due to supraventricular tachycardia (SVT) and can lead to sudden cardiac arrest [1-3]. The management involves localizing the accessory pathway, and then ablating it, by using either radiofrequency (RF) ablation or cryoablation. The electrocardiogram has been useful over the last decades in the localization of accessory pathways, premature ventricular contractions site of origin and pacing sites [4]. Regarding localization of the pathway, following a large study of RF ablation, Fitzpatrick et al described eight anatomical locations of different pathways using fluoroscopic landmarks: Right anteroseptal (RAS), right midseptal (RMS), right posteroseptal (RPS), right anterolateral (RAL), right posterolateral (RPL), left anterolateral (LAL), left posterolateral (LPL) and left posteroseptal (LPS) [5]. Other algorithms such as the Arruda algorithm or the D’Avila algorithm are also used by clinicians [6, 7]. Most of the accessory pathways’ localization algorithms involve assessment of the delta wave vector (Figure 1), some focus more on QRS morphology (Figure 2), and others combine both methods (Figure 3) [8-12]. By using these algorithms, differentiating between right sided and left sided accessory pathways does not generally pose a problem. However, determining the exact location of right and left sided pathways appears to be more challenging.The study of Bera et al. is a retrospective cohort. Twenty-two patients met the inclusion criteria. The aim was to assess the value of inferior lead discordance (meaning a positive QRS in lead II and a negative QRS in lead III) as a predictor of right anterior (RA) and RAL pathway. The authors included participants who had undergone RF ablation and were found to have right sided pathways. They then separated them in two groups based on if they had RA and RAL pathway (group 1) vs other pathways (group 2). The study found that all patients who had RA and RAL pathway had an ECG showing ILD, while 17 out of 18 patients who were in the other locations did not have an ECG with ILD. The sensitivity and specificity of ILD for predicting RAL location are 100% and 95% respectively.The findings in this study are highly relevant because they represent a clear and simple way of localizing RA/RAL pathways. Other algorithms are also extremely helpful but have their limitations especially if they rely on the delta wave polarity and the electrocardiogram is not fully pre-excited. Another advantage to the algorithm used in this study is that it focuses on limb leads, instead of pericardial leads, which are highly susceptible to variability due to possible displacement.This was a well conducted study, but has some limitations, most notably the small sample size of 22, with only 4 being RA and RAL pathways. There are many algorithms that help cardiologists and cardiac electrophysiologists in localizing accessory pathways before ablation, however, none has specifically focused on RA and RAL pathways. With the advances in artificial intelligence and machine learning, more algorithms using them might be developed in the future.Figure LegendsFigure 1: Examples of algorithms that rely on delta wave polarity such as Fitzpatrick (top) [5], Chiang (bottom left) [8] and Arruda (bottom right) [6]Figure 2: Example of algorithms that rely on QRS morphology such as D’Avilla (top left) [7], Taguchi (top right) [9] and St George’s (bottom) [10].Figure 3: Examples of algorithms that rely both on delta waves and QRS morphology, such as Pambrun (top) [11] and Baek (bottom) [12].References:1. Refaat MM, Hotait M, Tseng ZH (2014). Utility of the Exercise Electrocardiogram Testing in Sudden Cardiac Death Risk Stratification. Ann Noninvasive Electrocardiol, 19(4): 311-318.2. Lu, C. W., Wu, M. H., Chen, H. C., Kao, F. Y., & Huang, S. K. (2014). Epidemiological profile of Wolff-Parkinson-White syndrome in a general population younger than 50 years of age in an era of radiofrequency catheter ablation. International journal of cardiology, 174(3), 530–534. https://doi.org/10.1016/j.ijcard.2014.04.1343. Arai, A., & Kron, J. (1990). Current management of the Wolff-Parkinson-White syndrome. The Western journal of medicine, 152(4), 383–391.4. Refaat M, Mansour M, Singh JP, Ruskin JN, Heist EK (2011). Electrocardiographic Characteristics in Right Ventricular Versus Biventricular Pacing in Patients With Paced Right Bundle Branch Block QRS Pattern. J Electrocardiol, 44 (2): 289-95.5. Fitzpatrick, A. P., Gonzales, R. P., Lesh, M. D., Modin, G. W., Lee, R. J., & Scheinman, M. M. (1994). New algorithm for the localization of accessory atrioventricular connections using a baseline electrocardiogram. Journal of the American College of Cardiology, 23(1), 107–116. https://doi.org/10.1016/0735-1097(94)90508-86. Arruda, M. S., McClelland, J. H., Wang, X., Beckman, K. J., Widman, L. E., Gonzalez, M. D., Nakagawa, H., Lazzara, R., & Jackman, W. M. (1998). Development and validation of an ECG algorithm for identifying accessory pathway ablation site in Wolff-Parkinson-White syndrome. Journal of cardiovascular electrophysiology, 9(1), 2–12. https://doi.org/10.1111/j.1540-8167.1998.tb00861.x7. d’Avila, A., Brugada, J., Skeberis, V., Andries, E., Sosa, E., & Brugada, P. (1995). A fast and reliable algorithm to localize accessory pathways based on the polarity of the QRS complex on the surface ECG during sinus rhythm. Pacing and clinical electrophysiology : PACE, 18(9 Pt 1), 1615–1627. https://doi.org/10.1111/j.1540-8159.1995.tb06983.x8. Chiang, C. E., Chen, S. A., Teo, W. S., Tsai, D. S., Wu, T. J., Cheng, C. C., Chiou, C. W., Tai, C. T., Lee, S. H., & Chen, C. Y. (1995). An accurate stepwise electrocardiographic algorithm for localization of accessory pathways in patients with Wolff-Parkinson-White syndrome from a comprehensive analysis of delta waves and R/S ratio during sinus rhythm. The American journal of cardiology, 76(1), 40–46. https://doi.org/10.1016/s0002-9149(99)80798-x9. Taguchi, N., Yoshida, N., Inden, Y., Yamamoto, T., Miyata, S., Fujita, M., Yokoi, K., Kyo, S., Shimano, M., Hirai, M., &amp; Murohara, T. (2013, December 22). A simple algorithm for localizing accessory pathways in patients with Wolff-Parkinson-White syndrome using only the R/S ratio. Journal of Arrhythmia. Retrieved February 10, 2022, from https://www.sciencedirect.com/science/article/pii/S188042761300165810. Xie, B., Heald, S. C., Bashir, Y., Katritsis, D., Murgatroyd, F. D., Camm, A. J., Rowland, E., & Ward, D. E. (1994). Localization of accessory pathways from the 12-lead electrocardiogram using a new algorithm. The American journal of cardiology, 74(2), 161–165. https://doi.org/10.1016/0002-9149(94)90090-611. Pambrun, T., El Bouazzaoui, R., Combes, N., Combes, S., Sousa, P., Le Bloa, M., Massoullié, G., Cheniti, G., Martin, R., Pillois, X., Duchateau, J., Sacher, F., Hocini, M., Jaïs, P., Derval, N., Bortone, A., Boveda, S., Denis, A., Haïssaguerre, M., & Albenque, J. P. (2018). Maximal Pre-Excitation Based Algorithm for Localization of Manifest Accessory Pathways in Adults. JACC. Clinical electrophysiology, 4(8), 1052–1061. https://doi.org/10.1016/j.jacep.2018.03.01812. Baek, S. M., Song, M. K., Uhm, J. S., Kim, G. B., & Bae, E. J. (2020). New algorithm for accessory pathway localization focused on screening septal pathways in pediatric patients with Wolff-Parkinson-White syndrome. Heart rhythm, 17(12), 2172–2179. https://doi.org/10.1016/j.hrthm.2020.07.016.

Symphony to Leadless pacing – An Ode to JoyHassan Khan1, Larry A Chinitz1*1Leon H. Charney Division of Cardiology. New York University Langone Health. New York, NY, USA*Larry A Chinitz MD, FACC, FACP Benjamin and Coyle Family Professor of Medicine and Cardiac Electrophysiology Director, Cardiac Electrophysiology and the NYU Heart Rhythm CenterClinical Director, Leon H Charney Division of CardiologyNYU School of Medicine 212-263-7149 (O)[email protected] count, text: 1222 (excluding references) Number of tables/figures: 1COI; L.Chinitz- Speakers Honoraria; Medtronic,AbbottCoi; H. Khan- NoneLudwig van Beethoven’s 9th Symphony is regarded by many musicologists as one of the finest works in the history of music. It is notable for several reasons, particularly being the first example of a composer using voices, with words sung by a chorus and vocal soloist in the final movement. These words were adapted from the poem ”Ode to Joy”, written by Friedrich Schiller, and to date symbolize the celebration of music, making all who hear it feel better about life.Leadless pacing has also made a transformational effect on the lives of patients with bradyarrhythmias. Introduced to overcome the complications and adverse effects associated with conventional transvenous pacemakers, leadless pacing is observed to be safe, with a low risk of both short and long-term adverse events and high rates of successful implantation1, 2. To further the role of leadless pacing, the MARVEL (Micra Atrial TRacking Using a Ventricular AccELerometer) 23 prospective non-randomized multicenter clinical trial, tested the ability of an enhanced AV synchronous pacing algorithm utilizing the device’s three axis accelerometer, to attain mechanical sensing of atrial contractility. The MICRA AV TPS (Medtronic, MN) was released in 2020 with a ventricular pacing and atrial tracking mode (VDD), and achieved mechanical atrial sensing resulting in AV-synchronous pacing of >70% at rest in 95% participants (38 of the 40 with complete heart block) within the trial. Significant benefits to AV synchrony include avoidance of pacemaker syndrome, improvement of quality of life and as seen in these patients, improvement in left ventricle stroke volume and function3-5.The study observed that AV synchrony varied with physical activity and posture, with best results achieved at rest. Patient selection is crucial for optimal use of this algorithm as it is difficult to track atrial rates >105 bpm. At higher sinus rates, i.e. during exercise, the A3 and A4 signals fuse, along with encroachment of A4 on PVAB as the sinus rate increases further. Patient characteristics remain crucial and as seen in a subsidiary analysis of the MARVEL 2, individuals with markers of diastolic dysfunction (higher E/A ratios) and /or atrial myopathy (atrial strain) were found to be at higher risk of reduced mechanical atrial sensing of A46. Moreover, those with weak atrial contractions may not provide adequate A4 signals to the accelerometer. Therefore, performances of the algorithm in a real-world setting may not mirror those seen in the clinical trial arena. Further complicating the issue remains the ideal threshold for AV synchrony, which is assigned to >70% in research studies. In practice however, the AV synchrony cut-off required to achieve meaningful clinical benefit, avoid pacemaker syndrome and improve quality of life remains uncertain, though is certainly not 100%Recognizing that optimal AV synchrony in routine clinical practice may be challenging, Kowgli et al. in this issue of the Journal of Cardiovascular Electrophysiology , describe their multicenter institutional experience of outpatient programming optimization of the AV-synchronous MICRA leadless pacing system7. They included 43 patients with MICRA AV following exclusion of those with persistent atrial fibrillation or reduced follow-up. They describe the frequency of AV synchrony (defined as the ratio of atrial mechanically sensed (AM)-ventricular pacing to total ventricular paced percentage) at device interrogation done at 3 months of follow up. They report an overall mean AV synchronous pacing (AsVP) of 62.9%. In 65% of the patients adequate AV synchrony with AsVP >70% was found. Those with inadequate AsVP (<70%) had a higher body mass index, higher prevalence of congestive heart failure and prior history of cardiac surgery. Authors note that a small A4-wave amplitude, high ventricular pacing burden, and inadequate device reprogramming (over-use of auto A4 threshold, or lack of initiation of VDD mode at initialization) were main considerations for suboptimal AV synchronous pacing.Most importantly, their data confirms and is in line with recent reports,8, 9 that the success in achieving AV synchrony in a real-world setting may be lower than the MARVEL 2 clinical trial. The results also emphasize the importance of active programming changes which can significantly improve AV synchrony following an optimization post implantation. As identified in this report, MICRA AV optimization may require a learning curve, noted by an improvement in AsVP from 55% earlier, to 68% later in the study. Critical programming changes made by performing a manual atrial mechanical (MAM) test while disabling the features that automatically affect these, include adjusting the post ventricular atrial blanking (PVAB), A3/A4 windows and A3/A4 thresholds, and turning off the AV conduction mode (VVI +) in those with complete heart block and escape >40 bpm. The authors and others8, 9 have identified helpful examples of troubleshooting these interval timings and thresholds for optimizing AV synchrony, which an implanter must be familiar with in order to successfully manage patients with leadless AV synchronous devices. Critically, while performing a MAM test, a key prerequisite for successful interpretation of device tracings is the inclusion of an optimal ECG tracing. In cases where standard leads do not show a discernable P wave, the Lewis lead method can be helpful10. Several key steps towards successful optimization of AV synchrony are summarized in Figure 1.Kowgli et al. evaluated AV synchrony at device interrogation 3 months post implant whereas MARVEL 2 limited the analysis duration to about 30 minutes immediately after pacemaker optimization. This is a somewhat artificial setting and would be expected to be different from observations made at 3 months and longer periods of follow-up. Real world settings are also associated with changes in heart rate, patient movement, atrial or ventricular arrhythmias, as well as changes in lifestyle and medications. Therefore, an optimization session both at post-op (prior to discharge) and in the clinic at follow-up, with prior Holter monitoring and exercise testing in younger patients, may help detect AV dysynchrony earlier and allow recognition and correction of atrial mechanical under or oversensing.The current study acknowledges the complexity of leadless pacing and the need for optimization at follow-up to achieve higher levels of AV synchrony. It also reflects on patient selection being crucial to reap the full benefits of leadless technology. In patients with fast baseline sinus rates, in younger and physically active patients, or those who may have a greater reliance on AV synchrony at peak heart rates, this device may not be optimal. In addition, P wave amplitude, frequent atrial and ventricular arrhythmias, and sinus bradycardia will adversely affect the ability to achieve AV Synchrony. With appropriate patient selection, monitoring and best practices of device programming, leadless pacemakers will undoubtedly achieve clinically relevant AV synchrony. The true marvel of leadless technology can be seen as an impressive reduction in complication rates and better patient satisfaction compared to current transvenous devices. Further improvements in design, technology and best practices will deliver symphony to pacing and afford those who use it an experience that is safe and reminiscent of normal cardiovascular physiology.

An 82-year old woman with third degree atrioventricular block underwent left bundle branch area pacing (LBBAP) lead implantation

Title: The Fa(r)st or the Spurious - Pulmonary vein cycle length – Is it the fuel driving persistent AF, or simply just fumes?Authors: Sandeep Prabhu1,2,3 and Louise Segan1,2,3

Recently receiving FDA approval, the Amplatzer Amulet™ LAA occluder device (Abbott Medical Inc) provides a dual seal mechanism alternative to the commercially available Watchman FLX or Watchman 2.5 device for embolic stroke prevention in patients with non-valvular atrial fibrillation (NVAF). This Step-by-Step review will cover patient selection, pre-procedure imaging assessment, device sizing, device preparation, implant target position assessment, implant technique and troubleshooting, and immediate post implant follow-up.

A document by Matthew Hanson. Click on the document to view its contents.

Introduction: The surface EKG of typical atrioventricular nodal reentrant tachycardia (AVNRT) shows simultaneous ventricular-atrial (RP) activation with pseudo R’ in V1 and typical heart rates ranging from 150-220/min. Slower rates are suspicious for junctional tachycardia (JT). However, occasionally we encounter typical AVNRT with slow ventricular rates. We describe a series of typical AVNRT cases with heart rates under 110/min. Methods: A total of 1972 patients with AVNRT who underwent slow pathway ablation were analyzed. Typical AVNRT was diagnosed when; 1) evidence of dual atrioventricular nodal conduction, 2) tachycardia initiation by atrial drive train with A-H-A response, 3) septal ventriculoatrial (VA) time < 70 ms, and 4) ventricular-atrial-ventricular (V-A-V) response to ventricular overdrive (VOD) pacing with post pacing interval-tachycardia cycle length (PPI-TCL) > 115ms. JT was excluded by either termination or advancement of tachycardia by atrial extrastimuli (AES) or atrial overdrive (AOD) pacing. Results: We found 11 patients (Age 20-78 years old, 6 female) who met the above-mentioned criteria. The TCL ranged from 560ms to 782ms. Except for one patient showing tachycardia termination, all patients demonstrated a V-A-V response and PPI-TCL over 115ms with VOD. AES or AOD pacing successfully excluded JT by either advancing the tachycardia in 10 patients or by tachycardia termination in one patient. Slow pathway was successfully ablated, and tachycardia was not inducible in all patients. Conclusions: This case series describes patients with typical AVNRT with slow ventricular rate (less than 110/min) who may mimic JT. We emphasize the importance of using pacing maneuvers to exclude JT.

Atrial fibrillation (AF) is the most common atrial arrhythmia and is subcategorized into numerous clinical phenotypes. Given its heterogeneity, investigations into the genetic mechanisms underlying AF have been pursued in recent decades, with predominant analyses focusing on early onset or lone AF. Linkage analyses, genome wide association studies (GWAS), and single gene analyses have led to the identification of rare and common genetic variants associated with AF risk. Significant overlap with genetic variants implicated in dilated cardiomyopathy syndromes, including truncating variants of the sarcomere protein titin, have been identified through these analyses, in addition to other genes associated with cardiac structure and function. Despite this, widespread utilization of genetic testing in AF remains hindered by the unclear impact of genetic risk identification on clinical outcomes and the high prevalence of variants of unknown significance (VUS). However, genetic testing is a reasonable option for patients with early onset AF and in those with significant family history of arrhythmia. While many knowledge gaps remain, emerging data support genotyping to inform selection of AF therapeutics. In this review we highlight the current understanding of the complex genetic basis of AF and explore the overlap of AF with inherited cardiomyopathy syndromes. We propose a set of criteria for clinical genetic testing in AF patients and outline future steps for the integration of genetics into AF care.

What is Different About Pulsed Field Ablation … Everything?David E. Haines, MDBeaumont Health System, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan, USAFunding: NoneDisclosures: Dr. Haines is a consultant for Ablacon, Inc., Affera, Inc., Biosense Webster, Inc., Boston Scientific Corporation, Inc., Medtronic, Inc., and Philips Healthcare, Inc. He has equity interest in Ablacon, Inc. and Affera, Inc.Corresponding author:David E. Haines, MD Director, Heart Rhythm Center Professor, Cardiovascular Medicine Oakland University William Beaumont School of Medicine 3601 West 13 Mile Road Royal Oak, MI 48073 248-898-4176 [email protected] the time of early preclinical reports of the efficacy, speed and safety of pulsed field ablation (PFA), the interventional electrophysiology community has been waiting in anxious anticipation for its clinical approval and release. As most people actively engaged in interventional electrophysiology know, PFA is the technology that creates myocardial lesions with trains of very high voltage pulses that are nanoseconds or microseconds in duration.1 This form of ablation is nonthermal, and cell injury/death is created by electroporation of the organelles and sarcolemmal membrane, with cell death occurring via apoptosis as well as other mechanisms.2 Because myocardial ablation is the result of an electrical field effect, electrode-tissue proximity is important but contact force is not. The physiological effect of acute PFA is striking in that there is immediate loss of electrical signal so that acute pulmonary vein isolation is achieved from a single shot catheter in under one second (figure 1). Preclinical animal studies have demonstrated effective chronic lesions that have been reliably transmural for atrial ablations.3 But the most compelling aspect of PFA is the apparent tissue selectivity of this energy form. At doses sufficient to create reliable transmural lesions in animals, there is little or no discernable injury to the esophagus, phrenic nerves, coronary arteries or distal pulmonary veins, in contrast to ablation with thermal techniques such as radiofrequency or cryoballoon ablation, where thermal collateral injury to contiguous structures can lead to substantial morbidity and death.4,5So, what is the catch? Is there any downside to PFA compared to other ablation technologies? The answer is that we do not know. Despite a substantial body of preclinical experience published to date, clinical outcomes with PFA are just starting to be reported. In this issue of theJournal , Neven et al describe the acute pathological effects of PFA in a swine model over the first 60 minutes and compare them to findings from chronic animals at 3 weeks and 3 months.6 For their study, they mostly employed a suction electrode for epicardial delivery (some lesions created with a circular catheter under blood) and delivered a single unipolar cathodal pulse of mostly 200 J (some dose ranging performed with chronic lesions between 30 – 200 J) at various sites on the right and left ventricles. Pathology on acute specimens was examined 0 to 60 minutes post ablation, and chronic specimens were examined after 3 weeks and 3 months. They reported that acute lesions showed contraction band necrosis and interstitial edema, and at >/= 3 weeks, there was sharply demarcated connective tissue that evolved into scar.What new insights have we gained from the present study that we can now apply to the burgeoning field of clinical PFA? Unfortunately, despite considerable effort put forth by these investigators, their results are not generalizable to the wider field of PFA. No study reporting outcomes using one proprietary PFA system will be necessarily applicable to results from a competing proprietary system. The field of catheter ablation has become accustomed to interchangeability of one RF generator or catheter for another. That is because the thermodynamics of electrical resistive heating of tissue is predictable, and there are limited operator parameters (power, time, contact force) and design parameters (electrode size, convective cooling) that affect tissue heating. The biological effects of hyperthermia are straightforward and reproducible; thus, it is possible for scientists and clinicians to compare experiences from one proprietary RFA system to another and draw some generalizable conclusions. 7 Not so with PFA. To paraphrase an old saying, “When you’ve seen one PFA system, you’ve seenone PFA system.” The operator-controlled parameters are familiar (energy level, catheter-tissue position), but the design parameter variations are dizzying and most importantly unknown to us . A precedent was set early in the development of this field that the PFA waveform was proprietary, and that the commercialized product was a “black box”. A few of the parameters that can be modulated by the manufacturer include pulse amplitude, pulse duration, unipolar/bipolar, monophasic/biphasic, interpulse delay, interphase delay, pulse train number, pulse train duration and more. For example, the waveform used by Neven et al. was a milliseconds duration, monophasic damped sine wave generated by an external defibrillator (Lifepak 9, Physio-Control, Inc; Redmond, WA) and delivered in a unipolar cathodal fashion to an indifferent dispersive skin electrode. In contrast, most PFA systems deliver pulses are nanoseconds to microseconds in duration with a range of variation of the other parameters listed above (figure 2). Thus, the outcomes from ablation with a proprietary PFA system cannot and should not be extrapolated to different proprietary systems that may have dramatically different waveforms that result in different procedural outcomes.One of the major unanswered questions in the field of PFA is what is the time course of clinical effect after energy delivery? The hope and anticipation has been that lesions created by PFA will be more durable than those created with thermal ablation techniques (RFA or cryoablation). A dramatic features of catheter ablation with PFA is that disappearance of the local electrograms is seen immediately after pulse delivery (figure 1). Unfortunately, this does not necessarily indicate that a permanent lesion has been created. Beyond the border of irreversible electroporation there is a penumbra of reversible electroporation manifested by loss of the electrical signal but maintenance of viability. In the heart, this has been described pathologically as a rim of tissue with enhanced with hematoxylin and eosin staining, and maintenance of mitochondrial activity as delineated by cytochrome C oxidase staining.8 Thus, the acute end point of conduction block and loss of local electrogram signal employed in RF ablation does not indicate that a permanent lesion has been made with PFA. With myocardial ablation, the extent of reversible electroporation beyond the border of permanent injury has not been fully characterized, nor has the time course of recovery of normal function. There are many anecdotal reports of pulmonary vein reconnection after acute PVI with PFA in patients with atrial fibrillation. Unfortunately, the present study did not report mapping data and compare the extent of acute physiological effect to the acute pathological lesions.Therefore, a challenge for operators performing PFA is that acute electrogram voltage mapping cannot be used as a metric to assess therapeutic effect. The strategy adopted for PVI with PFA is to deliver a very large ablation dose, since injury to collateral structures is rare.9 The larger the energy delivery, the more likely it will be that permanent block is achieved. One experienced operator concluded “Go big or go home”. Once again, the pulse wave morphology, pulse width and pulse train number are proprietary features of the system that are preselected. The operator can choose different pulse amplitudes, but in almost all cases the maximum setting is selected. Is there such a thing as too much energy delivery with PFA? In preclinical studies, very high energy delivery has been associated with large volume microbubble production and evidence of thermal effects (charring) at the electrode-tissue interface. Creating a large uncontrolled lesion may be appropriate for a narrowly defined anatomical target like the pulmonary vein antrum but may not be appropriate for targeting other arrhythmogenic substrates because of concern about excessive injury to the surrounding myocardium. The consequences of very high PFA energy delivery in the clinical setting are unknown but most experts believe that there should be an upper safe limit established for each unique PFA system. So, the manufacturers will decide the dosing that the clinician will use. Will the recommended dose be safe and effective for all patients going forward? Time will tell. Ideally, we should have a method to assess myocardial viability after PFA prior to removing catheters from the heart, so that touch up ablations with improved catheter-tissue proximity can be performed. With RFA, promising technologies like real time magnetic resonance imaging,10 near field ultrasound imaging11 and NADH fluorescence12 have been explored, but their utility in assessing acute PFA lesions is unknown.The era of PFA is exciting and full of promise, but there are many unanswered questions that remain. As we gain more clinical experience with PFA, the benefits and limitations of the various commercial systems will become more obvious. Because of its speed and safety, PFA is likely to become the dominant mode of ablation for PVI, but we need to move forward in this field cautiously with recognition that all of the consequences of this ablation mode are still unknown.References:Verma A, Asivatham SJ, Deneke T, Castellvi Q, Neal RE. Primer on pulsed electrical field ablation: understanding the benefits and limitations. Circulation Arrhythm Electrophysiol. 2021; 14: e010086. doi.org/10.1161/CIRCEP.121.010086.Napotnik TB, Polajzer T, Miklavcic D. Cell death due to electroporation – A review. Bioielectrochemistry. 2021; 141:107871.Stewart MT, Haines DE, Verma A, Kirchhof N, Barka N, Grassl E, Howard B. Intracardiac pulsed field ablation: Proof of feasibility in a chronic porcine model. Heart Rhythm. 2019; 16:754-764. doi: 10.1016/j.hrthm.2018.10.030.Bradley CJ, Haines DE. Pulsed field ablation for pulmonary vein isolation in the treatment of atrial fibrillation. J Cardiovasc Electrophysiol. 2020 Aug;31(8):2136-2147. doi: 10.1111/jce.14414.Koruth J.S., Kuroki K., Kawamura I., et. al.: Pulsed field ablation vs radiofrequency ablation: esophageal injury in a novel porcine model. Circ Arrhythm Electrophysiol 2020; 13:Neven K, van Driel VJHM, Vink A, du Pre BC, van Wessel H, Futing A, Doevendans PA, Wittkampf FHM, van Es R. Characteristics and time course of acute and chronic myocardial lesion formation after electroporation ablation in the porcine model. J Cardiovasc Electrophysiol. 2022 (in press).Haines DE. Biophysics and Pathophysiology of Radiofrequency Lesion Formation. In: Catheter Ablation of Cardiac Arrhythmias, 4th Edition. Huang SKS, Miller JM, editors. Philadelphia, PA: Elsevier Saunders Publishing, 2020.Nakagawa H, Castellvi, Neal R, Girouard S, Kuroda S, Hussein AA, Saliba WI, Wazni OM. Histological characterization of reversible and irreversible ventricular lesion boundaries produced by pulsed field ablation. Heart Rhythm 2021; 18: S151-S152. doi: 0.1016/j.hrthm.2021.06.386Reddy VY, Neuzil P, Koruth JS, Petru J, Funosako M, Cochet H, Sediva L, Chovanec M, Dukkipati SR, Jais P. Pulsed field ablation for pulmonary vein isolation in atrial fibrillation. J Am Coll Cardiol 2019; 74: pp. 315-326. doi: 10.1016/j.jacc.2019.04.021.Mukherjee RK, Roujol S, Chubb H, Harrison J, Williams S, Whitaker J, O’Neill L, Silberbauer J, Neji R, Schneider R, Pohl T, Lloyd T, O’Neill M, Razavi R. Epicardial electroanatomical mapping, radiofrequency ablation, and lesion imaging in the porcine left ventricle under real-time magnetic resonance imaging guidance-an in vivo feasibility study. Europace. 2018 Sep 1;20(FI2):f254-f262. doi: 10.1093/europace/eux341.Haines DE, Wright M, Harks E, Deladi S, Fokkenrood S, Brink R, Belt H, Kolen AF, Mihajlovic N, Zuo F, Rankin D, Stoffregen W, Cockayne D, Cefalu J. Near-Field Ultrasound Imaging During Radiofrequency Catheter Ablation: Tissue Thickness and Epicardial Wall Visualization and Assessment of Radiofrequency Ablation Lesion Formation and Depth. Circ Arrhythm Electrophysiol. 2017 Dec;10(12):e005295. doi: 10.1161/CIRCEP.117.005295.Swift L, Gil DA, Jaimes R 3rd, Kay M, Mercader M, Sarvazyan N. Visualization of epicardial cryoablation lesions using endogenous tissue fluorescence. Circ Arrhythm Electrophysiol. 2014 Oct;7(5):929-37. doi: 10.1161/CIRCEP.114.001750.Figures:Figure 1 – A circular ablation catheter is positioned in the right superior pulmonary vein antrum (PV 1 thorugh 9) and high frequency near field pulmonary vein potentials were recorded. Immediately after delivery of a PFA pulse, the pulmonary vein potentials are eliminated.Figure 2 – A. Irreversible electroporation waveform similar to that employed by Neven et al. from a Lifepak 9 defibrillator (Physio-control Service Manual No. 803763-06, Physio-control, Redmond, WA). B. Representative waveform from a pulsed field ablation generator using a train of biphasic microsecond duration pulses.

Although uncommonly encountered, dual atrioventricular nodal non-reentrant tachycardia (DAVNNRT) is a well described arrhythmia that can manifest in patients with dual atrioventricular nodal pathways physiology. This arrhythmia is characterized on ECG by a single P wave followed by two conducted QRS complexes, and on intracardiac EGMs by a single atrial electrogram followed by two separate His deflections and ventricular electrograms. Our case demonstrates a rare case of “triple atrioventricular non-reentrant tachycardia” in which a patient was found to have 3 distinct AV nodal pathways and multiple “triple fire responses”, both on surface ECG and intracardiac electrograms.

Transseptal left atrial catheterization is routinely used for many common catheter-based interventions. Tools for transseptal catheterization have advanced over the recent years. Such tools include imaging advances with intracardiac echocardiology as well as an array of needles, wires, and dilators to achieve transseptal access with greater ease and safety. This review will discuss the contemporary tools for transseptal catheterization and guidance for difficult cases.

Background: Infection remains a major complication of cardiac implantable electronic devices (CIEDs) and can lead to significant morbidity and mortality. Extrathoracic devices that avoid epicardial or transvenous leads, such as the subcutaneous implantable cardioverter-defibrillator (S-ICD), can reduce the risk of serious infection-related complications, such as bloodstream infection and infective endocarditis. While the 2017 AHA/ACC/HRS guidelines include recommendations for S-ICD use for patients at high risk of infection, currently, there are no clinical trial data that address best practices for the prevention of S-ICD infections. Therefore, an expert panel was convened to develop consensus on these topics. Methods: An expert process mapping methodology was used to achieve consensus on the appropriate steps to minimize or prevent S-ICD infections. Two face-to-face meetings of high-volume S-ICD implanters and an infectious diseases specialist, with expertise on cardiovascular implantable electronic device infections, were conducted to develop consensus on useful strategies pre-, peri-, and post-implant to reduce S-ICD infection risk. Results: Expert panel consensus of recommended steps for patient preparation, S-ICD implantation, and post-operative management were developed to provide guidance in individual patient management. Conclusion: Achieving expert panel consensus by process mapping methodology for S-ICD infection prevention was attainable, and the results should be helpful to clinicians in adopting interventions to minimize risks of S-ICD infection.

In the context of atrial fibrillation (AF), traditional clinical practices have thus far fallen short in several domains such as identifying patients at risk of incident AF or patients with concomitant undetected paroxysmal AF. Novel approaches leveraging artificial intelligence have the potential to provide new tools to deal with some of these old problems. In this review we focus on the roles of artificial intelligence-enabled ECG pertaining to AF, potential roles of deep learning (DL) models in the context of current knowledge gaps, as well as limitations of these models. One key area where DL models can translate to better patient outcomes is through automated ECG interpretation. Further, we overview some of the challenges facing AF screening and the harms and benefits of screening. In this context, a unique model was developed to detect underlying hidden AF from sinus rhythm and is discussed in detail with its potential uses. Knowledge gaps also remain regarding the best ways to monitor patients with ESUS and who would benefit most from oral anticoagulation. The AI-enabled AF model is one potential way to tackle this complex problem as it could be used to identify a subset of high-risk ESUS patients likely to benefit from empirical oral anticoagulation. Role of DL models assessing AF burden from long duration ECG data is also discussed as a way of guiding management. There is a trend towards the use of consumer-grade wristbands and watches to detect AF from photoplethysmography data. However, ECG currently remains the gold standard to detect arrythmias including AF. Lastly, role of adequate external validation of the models and clinical trials to study true performance is discussed.

Subcutaneous implantable cardioverter defibrillators (S-ICDs) are currently indicated for patients who meet ICD implantation criteria for the prevention of sudden cardiac death (SCD). In December 2020, a unique cardiac implantable electronic device (CIED) situation arose as both the S-ICD generator and electrode were under a device advisory. We would recommend all future CIED implantation guidelines receive a caveat regarding checking current CIED advisories, in order to avoid future similar scenarios.