Should We Limit Antiarrhythmic Drug Choice in Patients

Employing New Criteria for Confirmation of Conduction Pacing – Achieving True Left Bundle Branch Pacing May Be Harder Than Meets the EyeJoshua Sink, MD1, Nishant Verma, MD, MPH2Northwestern University, Feinberg School of Medicine, Department of Internal MedicineNorthwestern University, Feinberg School of Medicine, Division of CardiologyCorresponding Author:Nishant Verma, MD, MPH251 East Huron Street, Feinberg 8-503Chicago, IL [email protected]: NoneDisclosures: Dr. Sink has nothing to disclose. Dr. Verma receives speaker honoraria from Medtronic, Biotronik and Baylis Medical and consulting fees from Boston Scientific, Biosense Webster, AltaThera Pharmaceuticals and Knowledge 2 Practice.Word Count: 1200In recent years, conduction system pacing (CSP) has garnered significant attention from the electrophysiology (EP) community. This movement has been driven by the hypothesis that using the natural conduction system activation is desirable and clinically beneficial in patients with advanced conduction disease and ventricular desynchrony. Permanent His-bundle pacing (PHBP) is generally seen as the purest form of conduction system activation. (Figure 1) PHBP was first described over 20 years ago but the idea has attracted substantial investigative effort in recent years. When successfully achieved, His bundle pacing has been associated with reduction in mortality, reduction in heart failure (HF) admissions, and improvement in left ventricular (LV) function compared to right ventricular (RV) pacing.1 Despite this, consistent achievability in real-world practice remains limited due to a variety of factors including narrow anatomic targetability, lead stability, high pacing thresholds, low ventricular sensing, and inability to correct the QRS in bundle branch block.2Thus, while waiting for the next iteration of improved delivery techniques, pacing leads and programming algorithms,, alternative methods of conductive system pacing have emerged, with the potential to surmount the challenges described.Left bundle branch pacing (LBBP) has recently emerged as an alternative method of CSP. The technique was first described by Huang et al. in 2017 and has seen a momentous rise in interest since.3 In 2019, Huang et al. produced a user manual for a successful LBBP procedure, and in it they attempted to develop the first iteration of criteria for the confirmation of LBBP.4 Utilizing these criteria, or close variations of them, a number of studies were published afterwards that demonstrated preliminary safety, feasibility, and efficacy of LBBP.5,6,7 LBBP became an attractive alternative to His bundle pacing because of the lower thresholds, improved lead stability, and higher procedural success rates. When compared against RV pacing in patients requiring a high burden of pacing, LBBP has demonstrated reduced mortality, HF admissions, and need for upgrade to a BiV device.8 In a small, non-randomized patient sample, LBBP showed greater improvement in LV ejection fraction (EF) compared to BiV pacing.9 Most notably, perhaps, is the astonishing rate of lead placement success, with achievement rates reported as high as 98% in sizable studies.6Differences between the two forms of CSP were apparent from the beginning, including in the appropriate QRS morphology after a successful case. Unlike PHBP, LBBP did not reproduce the native QRS and the QRS duration was often greater than at baseline (Figure 2). The arena of LBBP underwent a notable shift in the Fall of 2021 when Wu et al. proposed new criteria to prove LBBP.10 In this study, they presented an exquisite display of fundamental electrophysiologic principles by using mapping catheters positioned on the His and LV septum during LBB lead placement. Through this painstaking work, they clarified the difference between true LBBP and left bundle branch area pacing (LBBAP), which can incorporate both LBBP and left ventricular septal pacing (LVSP). In their proposed framework, without the presence of a His or LV septum mapping catheter, output dependent QRS transition from non-selective (NS-LBBP) to selective-LBBP (S-LBBP) or LVSP is necessary to prove LBBP and had a sensitivity and specificity of 100%.The present study by Shimeno et al, published in the current issue of the Journal of Cardiovascular Electrophysiology , is the first known effort to document achievement rates of LBBP by utilizing the modified criteria proposed by Wu et al.11 The primary finding of the study is that achieving true LBBP with an acceptable pacing threshold is likely harder than previously realized. As expected, there was improvement after a learning curve, but even in the last third of patients enrolled, the achievement rate of LBBP was only 50%. This is dramatically lower than previously reported achievement rates using the original Huang et al. criteria, and it suggests that not all patients in the previously described studies were actually achieving true LBBP. An unknown subset of patients in these studies was likely only achieving LVSP. This is probably due to a prior reliance on indicators such as a paced right bundle branch block (RBBB) pattern, identification of an intrinsic LBB potential, and/or use of V6 R-wave peak time cutoffs (RWPT) without clear output-dependent QRS transition. It is also worth noting that a variety of RWPT cutoffs have been used seemingly arbitrarily as ‘evidence of LBBP’. This presents a major dilemma and highlights the need for a clear set of LBBP criteria to be defined by the collective EP community. Despite these caveats, many of these previous studies did not fully confirm LBBP in their patients, yet the outcomes from these studies were still clinically promising. This raises the obvious question, does obtaining true LBBP matter? Future studies will need to explore the differences in clinical outcomes between true LBBP and LVSP.Secondarily, Shimeno et al. have provided a useful tool in identifying that LBB potential to QRS-onset ≥ 22ms had a specificity of 98% in predicting LBBP.11 This target measure can help future operators ensure proximal enough engagement of the LBB conduction system. Additionally, the group took a close look at validating a RWPT cutoff time for the prediction of LBBP. Unfortunately, a RWPT cutoff of 68 ms (in non-LBBB patients), determined by the ROC curve, was not highly predictive. This runs contrary to previous reports by Wu et al. and Jastrzebski et al., which reported higher predictive value of RWPT cutoffs10,12 Looking at the data surrounding RWPT cutoffs as a collective, it likely should not be used as a primary metric for confirming LBBP due to imperfect sensitivity and specificity, but it may be an alternative if output dependent QRS transition or change in RWPT of ≥10 ms is not observed. Additionally, in the event that capture thresholds are similar between the LBB and the adjacent myocardium, programmed stimulation is an option to try to reveal a QRS transition by exploiting differences in refractory periods.This study also highlighted one of the unique complications of LBBP by demonstrating a high rate of septal perforation. Paradoxically, more perforations were seen with increased experience, likely highlighting that deeper penetration into the septum is often sought as operators become more familiar with the procedure. The long-term clinical implications of this complication are, thus far, unknown.Looking forward, clear guidelines for confirmation of LBBP need to be defined. This is necessary to ensure quality before undertaking multi-center randomized controlled trials to assess LBBP in comparison to current pacing methods. To date, Wu et al. seem to have provided the best framework to achieve this.10 That said, there are concerns given that this has only been validated in 30 patients (and only 9 with LBBB). In an ideal world, these criteria would be validated in a larger population, though the work to accomplish this would be meticulous given the current gold standard of using an LV septal mapping catheter to prove conduction system capture. Shimeno et al. should be congratulated for their effort in putting this framework to practice. In their work, they have demonstrated that achieving true LBBP as defined by Wu et al. may be harder than meets the eye, and this is very important in assessing the practicality of using LBBP as a widespread alternative to other pacing methods.References:Abdelrahman M, Subzposh FA, Beer D, et al. Clinical Outcomes of His Bundle Pacing Compared to Right Ventricular Pacing. J Am Coll Cardiol . 2018;71(20):2319-2330. doi:10.1016/j.jacc.2018.02.048Zanon F, Abdelrahman M, Marcantoni L, et al. Long term performance and safety of His bundle pacing: A multicenter experience. J Cardiovasc Electrophysiol . 2019;30(9):1594-1601. doi:10.1111/jce.14063Huang W, Su L, Wu S, et al. A Novel Pacing Strategy With Low and Stable Output: Pacing the Left Bundle Branch Immediately Beyond the Conduction Block. Can J Cardiol . 2017;33(12):1736.e1-1736.e3. doi:10.1016/j.cjca.2017.09.013Huang W, Chen X, Su L, Wu S, Xia X, Vijayaraman P. A beginner’s guide to permanent left bundle branch pacing. Heart Rhythm . 2019;16(12):1791-1796. doi:10.1016/j.hrthm.2019.06.016Padala SK, Master VM, Terricabras M, et al. Initial Experience, Safety, and Feasibility of Left Bundle Branch Area Pacing: A Multicenter Prospective Study. JACC Clin Electrophysiol . 2020;6(14):1773-1782. doi:10.1016/j.jacep.2020.07.004Su L, Wang S, Wu S, et al. Long-Term Safety and Feasibility of Left Bundle Branch Pacing in a Large Single-Center Study. Circ Arrhythm Electrophysiol . 2021;14(2):e009261. doi:10.1161/CIRCEP.120.009261Huang W, Wu S, Vijayaraman P, et al. Cardiac Resynchronization Therapy in Patients With Nonischemic Cardiomyopathy Using Left Bundle Branch Pacing. JACC Clin Electrophysiol . 2020;6(7):849-858. doi:10.1016/j.jacep.2020.04.011Sharma PS, Patel NR, Ravi V, et al. Clinical outcomes of left bundle branch area pacing compared to right ventricular pacing: Results from the Geisinger-Rush Conduction System Pacing Registry. Heart Rhythm . 2022;19(1):3-11. doi:10.1016/j.hrthm.2021.08.033Wu S, Su L, Vijayaraman P, et al. Left Bundle Branch Pacing for Cardiac Resynchronization Therapy: Nonrandomized On-Treatment Comparison With His Bundle Pacing and Biventricular Pacing. Can J Cardiol . 2021;37(2):319-328. doi:10.1016/j.cjca.2020.04.037Wu S, Chen X, Wang S, et al. Evaluation of the Criteria to Distinguish Left Bundle Branch Pacing From Left Ventricular Septal Pacing. JACC Clin Electrophysiol . 2021;7(9):1166-1177. doi:10.1016/j.jacep.2021.02.018Shimeno K, Tamura S, Hayashi Y, et al. Achievement Rate and Learning Curve of Left Bundle Branch Capture in Left Bundle Branch Area Pacing Procedure Performed to Demonstrate Output-Dependent QRS Transition.J Cardiovasc Electrophysiol . 2022Jastrzębski M, Kiełbasa G, Curila K, et al. Physiology-based electrocardiographic criteria for left bundle branch capture. Heart Rhythm . 2021;18(6):935-943. doi:10.1016/j.hrthm.2021.02.021Figure LegendsFigure 1: Permanent His Bundle PacingPanel A: A 12-lead electrocardiogram (EKG) shows baseline conduction in a patient with exertional intolerance. The PR interval is markedly prolonged and, with exercise, this patient developed AV block. A permanent His-bundle pacemaker was implantedPanel B: An EKG demonstrating permanent His-bundle pacing in the same patient as panel A. Selective His-bundle capture results in reproduction of the intrinsic QRS complex.Figure 2: Non-Selective Left Bundle Branch PacingA 12-Lead electrocardiogram showing non-selective left bundle branch pacing. The paced QRS morphology is not a direct match for native conduction and the QRS duration is longer than at baseline. However, conduction system capture was confirmed with an output dependent QRS morphology change.FiguresFigure 1: Permanent His-Bundle Pacing

Sudden Cardiac Death (SCD) remains a global threat.1The most common causes of SCD are ischemic heart diseases and structural cardiomyopathies in the elderly. Additional causes can be arrhythmogenic, respiratory, metabolic, or even toxigenic.2,3,4 Despite the novel diagnostic tools and our deeper understanding of pathologies and genetic associations, there remains a subset of patients for whom a trigger is not identifiable. When associated with a pattern of Ventricular Fibrillation, the diagnosis of exclusion is deemed Idiopathic Ventricular Fibrillation (IVF).2,5 IVF accounts for 5% of all SCDs6 – and up to 23% in the young male subgroup5 – and has a high range of recurrence rates (11-45%).7,8,9 There are still knowledge gaps in the initial assessment, follow-up approach, risk stratification and subsequent management for IVF.1,10,11 While subsets of IVF presentations have been better characterized into channelopathies, such as Brugada’s syndrome (BrS), Long QT Syndrome (LQTS), Early Repolarization Syndrome (ERS), Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), much remains to be discovered.12,13 Implantable Cardioverter Device (ICD) placement as secondary prevention for IVF is the standard of care. This is warranted in the setting of high recurrence rates of arrhythmias (11-43%). Multiple studies have shown potential complications from ICDs and a significant number of cases experiencing inappropriate shock after ICD placement.14In their article, Stampe et al. aim to further understand clinical presentation and assessment, and risk factors for recurrent ventricular arrhythmias in IVF patients. Using a single-centered retrospective study, they followed a total of 84 Danish patients who were initially diagnosed with IVF and received a secondary ICD placement between December 2007 and June 2019. Median follow-up time was 5.2 years (ICR=2-7.6). To ensure detection of many possible underlying etiologies ranging from structural, ischemic, arrhythmogenic, metabolic, or toxicologic, the researchers found that a wide array of diagnostic tools were necessary: standard electrocardiograms (ECGs), high-precordial leads ECGs, standing ECGs, Holter monitoring, sodium-channel blocker provocation tests, exercise stress tests, echocardiograms, cardiac magnetic resonance imaging, coronary angiograms, cardiac computed tomography, electrophysiological studies, histological assessment, blood tests, toxicology screens, and genetic analysis.The study by Stampe et al. highlights the importance of thorough and continuous follow-up with rigorous evaluation: Three (3.6%) patients initially diagnosed with IVF were later found to have underlying cardiac abnormalities (LQTS and Dilated Cardiomyopathy) that explained their SCA. Like other studies, the burden of arrhythmia was found to be high, but unlike reported data, the overall prognosis of IVF was good. Despite the initial pattern of ventricular fibrillation in those who experienced appropriate ICD placement (29.6%), ventricular tachycardia and ventricular fibrillation had a comparable predominance. As for patients with inappropriate ICD placements, atrial fibrillation was a commonly identified pathological rhythm (16.7%). Recurrent cardiac arrest at presentation (19.8%) was a risk factor for appropriate ICD therapy (HR=2.63, CI=1.08-6.40, p=0.033). However, in contrast to previous studies, early repolarization detected on baseline ECG (12.5%), was not found to be a risk factor (p=0.842).The study by Stampe et al. has few limitations. First, the study design, a retrospective cohort, precluded standardized follow-up frequencies and diagnostic testing. Second, while the study was included many of the cofounders tested in previous studies (baseline characteristics, baseline ECG patterns, comorbidities), medication use was not included. Third, the follow-up period may have been insufficient to detect effect from some of the confounding factors. Finally, the sample size was small and it was from a single center.There are several strengths of the Stampe et al. study. Firstly, the wide range of diagnostic tests used at index presentation and during the follow-up period ensured meticulous detection of most underlying etiologies. Secondly, appropriate and well-defined inclusion and exclusion criteria were used. Thirdly, funding by independent parties ensured no influence on study design, result evaluation, and interpretation. Finally, the study has succeeded in improving our understanding of IVF. Future studies should include though a larger population size and a more diverse population.References:1.AlJaroudi WA, Refaat MM, Habib RH, Al-Shaar L, Singh M, et al. Effect of Angiotensin Converting Enzyme Inhibitors and Receptor Blockers on Appropriate Implantable Cardiac Defibrillator Shock: Insights from the GRADE Multicenter Registry. Am J Cardiol Apr 2015; 115 (7): 115(7):924-31.2. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: executive summary. J Am Coll Cardiol 2018;72:e91–e220.3. Refaat MM, Hotait M, London B: Genetics of Sudden Cardiac Death. Curr Cardiol Rep Jul 2015; 17(7): 6064. Priori SG, Wilde AA, Horie M, Cho Y, Behr ER, Berul C, et al. HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013. Heart Rhythm 2013;10:1932–1963.5. Priori SG, Blomström-Lundqvist C, Mazzanti A, et al. ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC). Eur Heart J 2015;36(41):2793-2867.6. Zipes DP, Wellens HJ. Sudden cardiac death. Circulation. 1998;98:2334–2351.7. Ozaydin M, Moazzami K, Kalantarian S, Lee H, Mansour M, Ruskin JN. Long-term outcome of patients with idiopathic ventricular fibrillation: a meta-analysis. J Cardiovasc Electrophysiol 2015;26:1095–1104.8. Herman AR, Cheung C, Gerull B, Simpson CS, Birnie DH, Klein GJ, et al. Outcome of apparently unexplained cardiac arrest: results from investigation and follow-up of the prospective cardiac arrest survivors with preserved ejection fraction registry. Circ Arrhythm Electrophysiol 2016;9:e003619.9. Siebermair J, Sinner MF, Beckmann BM, Laubender RP, Martens E, Sattler S, et al.Early repolarization pattern is the strongest predictor of arrhythmia recurrence in patients with idiopathic ventricular fibrillation: results from a single centre long-term follow-up over 20 years. Europace 2016;18:718-25.10. Refaat MM, Hotait M, Tseng ZH: Utility of the Exercise Electrocardiogram Testing in Sudden Cardiac Death Risk Stratification. Ann Noninvasive Electrocardiol 2014; 19(4): 311-318.11. Gray B, Ackerman MJ, Semsarian C, Behr ER. Evaluation after sudden death in the young: a global approach. Circ Arrhythm Electrophysiol 2019;12: e007453.12. Herman AR, Cheung C, Gerull B, Simpson CS, Birnie DH, Klein GJ, et al. Response to Letter Regarding Article, Outcome of apparently unexplained cardiac arrest: results from investigation and follow-up of the prospective cardiac arrest survivors with preserved ejection fraction registry”. Circ Arrhythm Electrophysiol 2016;9:e004012.13. Chen Q, Kirsch GE, Zhang D, Brugada R, Brugada J, Brugada P, Potenza D, et al. Genetic basis and molecular mechanism for idiopathic ventricular fibrillation. Nature 1998;392:293–296.14. Baranchuk A, Refaat M, Patton KK, Chung M, Krishnan K, et al. What Should You Know About Cybersecurity For Cardiac Implantable Electronic Devices? ACC EP Council Perspective. J Am Coll Cardiol Mar 2018; 71(11):1284-1288.

Background: A computational model demonstrated that atrial fibrillation (AF) rotors could be distributed in patchy fibrotic tissue and play an important role in AF drivers. However, this was not validated in humans. Objective: The purpose of this study was to evaluate the fibrotic tissue properties of AF rotors in patients with persistent AF. Methods: A total of 287 segments in 15 patients with persistent AF (longstanding persistent AF in 9 patients) that underwent AF ablation were assessed. Non-passively activated areas (NPAs), where rotational activation (AF rotor) was frequently observed, were detected by the novel real-time phase mapping (ExTRa Mapping). Atrial fibrosis was detected by late-gadolinium enhancement magnetic resonance imaging (LGE-MRI), and the fibrotic heterogeneity and density were assessed by the entropy (LGE-entropy) and volume ratio of the enhancement voxel (LGE-volume ratio), respectively. Results: NPAs were found in 61 (21%) of 287 segments and were mostly found around the pulmonary vein antrum. A receiver operating characteristic curve analysis yielded an optimal cutoff value of 5.7 and 10% for the LGE-entropy and LGE-volume ratio, respectively. The incidence of NPAs was significantly higher at segments with an LGE-entropy of >5.7 and LGE-volume ratio of >10% than at the other segments (38 [30%] of 126 vs. 23 [14%] of 161 segments, p = 0.001). No NPAs were found at segments with an LGE-volume ratio of >50% regardless of the LGE-entropy. Conclusion: AF rotors are mostly distributed in relatively weak and much more heterogenous fibrotic tissue.

Background: Transvenous lead extraction (TLE) is standard of care for the management of patients with cardiac implantable electronic device infection or lead related complications. Currently, objective data on TLE in Latin America is lacking. Objective: To describe the current practice standards in Latin American centers performing TLE. Methods: An online survey was sent through the mailing list of the Latin American Heart Rhythm Association (LAHRS). Online reminders were sent through the mailing list; duplicate answers were discarded. The survey was available for one month, after which no more answers were accepted. Results: A total of 48 answers were received, from 44 different institutions (39.6% from Colombia, 27,1% from Brazil), with most respondents (83%) being electrophysiologists. Twenty-nine institutions (66%) performed less than 10 lead extractions/year, with 7 (15%) institutions not performing lead extraction. Although most institutions in which lead extraction is performed reported using several tools, mechanical rotating sheaths were cited as the main tool (73%), 13.5% reported the use of mechanical extraction sheaths and only 13.5% reporting the use of laser sheaths. Management of infected leads was performed according to current guidelines. Conclusion: This survey is the first attempt to provide information on TLE procedures in Latin America and could provide useful information for future prospective registries. According to our results, the number of centers performing high volume lead extraction in Latin America is smaller than that reported in other continents, with most interventions performed using mechanical tools. Future prospective registries assessing acute and long-term success are needed.

Background: Outcomes of catheter ablation (CA) among patients with non-paroxysmal atrial fibrillation (AF) are largely disappointing. Objective: We sought to evaluate the feasibility, effectiveness, and safety of a single-stage stepwise endo-/epicardial approach in patients with persistent/longstanding-persistent AF. Methods: We enrolled 25 consecutive patients with symptomatic persistent (n=4) or longstanding-persistent (n=21) AF and at least one prior endocardial procedure, who underwent CA using an endo-/epicardial approach. Our anatomical stepwise protocol included multiple endocardial as well as epicardial (Bachmann’s bundle [BB] and ligament of Marshall ablations) components, and entailed ablation of atrial tachycardias emerging during the procedure. The primary outcome was freedom from any AF/atrial tachycardia episode after a 3-month blanking period. The secondary outcome was patients’ symptom status during follow-up. Results: The stepwise endo-/epicardial approach allowed sinus rhythm restoration in 72% of patients, either directly (n=6, 24%) or after AF organization into atrial tachycardia (n=12, 48%). BB’s ablation was commonly implicated in arrhythmia termination. After a median follow-up of 266 days (interquartile range, 96 days), survival free from AF/atrial tachycardia was 88%. Antiarrhythmic drugs could be discontinued in 22 patients (88%). As compared to baseline, more patients were asymptomatic at 9-month follow-up (0% vs- 56%, p=0.02). Five patients (20%) developed mild medical complications, whereas one subject (4%) had severe kidney injury requiring dialysis. Conclusion: a single-stage endo-/epicardial CA resulted in favorable rhythm and symptom outcomes in a cohort of patients with symptomatic persistent/longstanding-persistent AF and one or more prior endocardial procedures. Epicardial ablation of BB was commonly implicated in procedural success.

The pandemic caused by SARS-CoV-2 has affected communities throughout the world. The global nature of health care disparities is exacerbated by COVID-19. Patients in Low-and Middle-Income Countries have limited health care resources and marginal support for the evaluation and treatment of cardiac rhythm disorders. Heart Rhythm Societies and their members need to advocate for increased subsidies and assistance for these patients.

Abstract Introduction: Therapies for substrate-related arrhythmias include ablation or drugs targeted at altering conductive properties or disruption of slow zones in heterogeneous myocardium. Conductive compounds such as carbon nanotubes may provide a novel personalizable therapy for arrhythmia treatment by allowing tissue homogenization. Methods: A nanocellulose-carbon nanotube conductive hydrogel was developed to have conduction properties similar to normal myocardium. Ex vivo perfused canine hearts were studied. Electroanatomic activation mapping of the epicardial surface was performed at baseline, after radiofrequency ablation, and after uniform needle injections of the conductive hydrogel through the injured tissue. Gross histology was used to assess distribution of conductive hydrogel in the tissue. Results: The conductive hydrogel viscosity was optimized to decrease with increasing shear rate to allow expression through a syringe. The DC conductivity under aqueous conduction was 4.3·10-1 S/cm. In 4 canine hearts, when compared to the homogeneous baseline conduction, isochronal maps demonstrated sequential myocardial activation with a shift in direction of activation to surround the edges of the ablated region. After injection of conductive hydrogel, isochrones demonstrated conduction through the ablated tissue with activation similar to baseline in all 4 hearts. Gross specimen examination demonstrated retention of the hydrogel within the tissue. Conclusions: This proof-of-concept study demonstrates that conductive hydrogel can be injected into acutely disrupted myocardium to restore conduction. Future experiments should focus on evaluating long-term retention and biocompatibility of the hydrogel through in vivo experimentation.

Dr. Rahul George Muthalaly MBBS, MPH1,2, Dr. Roy M John MBBS, PhD, FRCP3Monash Heart, Monash Health, Melbourne VICVictorian Heart Institute, Monash University, Melbourne VICStanford University, Palo Alto, CA 94304 USACorresponding Author:Dr. Rahul G MuthalalyPh: [email protected] information for all other authors:[email protected] Count: 1238 wordsFunding: NoneConflict of Interest: NoneAblation for atrial fibrillation (AF) is an established therapy that continues to grow in scope and indication(1). The benefits of AF ablation are well recognized in heart failure and symptomatic paroxysmal AF. Additionally, the recent EAST-AFNET4 trial demonstrated benefit for an early AF rhythm control strategy even in asymptomatic patients (2). This change in paradigm from rate and rhythm control equivalence may be partially related to the increasing use of AF ablation for rhythm control. As ablation therapy continues to proliferate, questions of how to optimise procedural outcomes at a health service level arise. A key component of this optimisation is defining predictors of outcomes related to ablation procedures.One such predictor is procedural case volume. Studies outside of AF ablation have demonstrated complex relationships between institutional size, procedural volume, case difficulty and outcomes. Published data on transcatheter aortic valve replacement (TAVR) for example, suggest a durable link between hospital case volume and mortality even after adjusting for institutional learning curves and known risk factors for poor outcomes (3). These insights have relevance for AF ablation for which there is wide-ranging procedural variation across factors such as lesion sets and type of ablation energy. The relationship between AF ablation volume and outcomes have been explored in previous studies(4, 5). Tonchev and colleagues, in a meta-analysis, demonstrated a significantly lower risk of complications in centres performing >100 procedures per year (OR 0.62, 95%CI 0.53 to 0.73) (4). This carried over to mortality, which was significantly lower in high volume centres (OR 0.33, 95% CI 0.26-0.43). Ablation efficacy was also greater in higher volume centres. Importantly, the majority of procedures included in this meta-analysis of real-world data were undertaken in low volume centres (70.9% in centres with <100 procedures/year) alerting to the reality that high-volume centers are not readily available to most patients.The influence of energy types (cryoballoon ablation versus catheter based radiofrequency ablation) on the relationship between procedural volume and outcomes is less well defined. This is of relevance as cryoablation appears to have a gentler learning curve than radiofrequency ablation for centres that are newly introducing AF ablation(6). In this issue of the journal , Kanaoka and colleagues present data on the relationship between procedural volume, energy type and acute procedural outcomes based on analysis of the Japanese National Database of Insurance Claims and Specific Health Check-ups. The authors identified 270,116 patients from this database undergoing first-time AF ablation with cryoablation or radiofrequency energy. A small subset of patients who underwent hot balloon and laser ablation were excluded as the numbers were too low. Complications were identified using administrative coding for the most common diagnoses associated with ablation risks. Ablation success could only be defined using coding for repeat AF ablation or initiation of anti-arrhythmic drug within 1 year.The authors split hospitals into quartiles using case volume resulting in groups with medians of 69 (very low), 157 (low), 252 (high) and 469 (very high) procedures per year. They found that the relative risk of peri-procedural complications was approximately 10-20% lower in all other groups when compared with the very low procedural volume hospitals. Cubic spline plots demonstrated a plateau effect, with no further reduction in complications when hospitals approach 150-200 cases per year. Similarly, when considering AF recurrence assessed by repeat ablation or initiation of anti-arrhythmic drugs up to 1 year, there was approximately a 10% relative risk reduction in the low, high and very high-volume hospitals when compared to very low-volume centres. Of note, there appeared to be a similar plateau volume of approximately 150-200 cases per year above which the benefit attenuated. The relationship between procedural volume and outcomes was however, only seen with RF ablation. Among the more than 56,000 cryoablation cases, there were no significant differences in complications or recurrence in the low, high or very high procedural volume hospitals when compared with the very low volume hospitals. Of note, there was a similar burden of AF related comorbidities in the radiofrequency and cryoablation populations.These results of Kanoaka and colleagues add further evidence to the notion that, when it comes to AF ablation, there appears to be a threshold of hospital procedural volume above which the risk of complications and recurrence decreases. The finding of a threshold in the range of 150-200 procedures per year, is in keeping with previous work suggesting benefits in excess of 100 procedures per year(5). Additionally, the present study sheds new light on the effect of ablation type on this relationship. In keeping with the recognition that cryoablation appears to offer an easier learning curve, the effect of procedural volume on both safety and efficacy outcomes was eliminated when considering only cryoablation cases.Limitations of the study have to be recognized. The study is observational, retrospective and derived from a national database. These factors admit the potential for unmeasured confounders and imperfect assessment of outcomes. The definition of ablation success was based on coding for repeat ablation or use of antiarrhythmic drugs within the first year. This definition, although pragmatic, does not account for recurrence occurring outside of 1 year or recurrence that did not result in repeat ablation or anti-arrhythmic drug therapy. Furthermore, complications were defined using administrative coding. Notably, this coding was not able to identify phrenic nerve injury, which occurs in approximately 5-6% of patients undergoing cryoablation(7). In addition, significant differences existed between the RF and cryoablation groups. There was a greater proportion of paroxysmal AF in the cryoablation compared to RF group (74% versus 46%). Because RF ablation allows for more flexibility in ablation lesion set, this energy form tends to be used in those with more advanced atrial remodelling. Hence, it is very likely that the RF group comprised a more complex patient group with a greater dependence on operator experience and case volume. The observed differences in learning curve between the two energy sources may have been less striking or even absent, had the groups been matched. The study however, has the advantage of the use of a database that covers of 98% of the Japanese population and magnitude of case volume included, allow for valuable insights.Abundant work has now demonstrated that hospital procedural volume is a key component of optimising outcomes from any complex interventional procedure(3, 5). The improved outcomes observed as a result of hospital procedural volume are likely due to a wide-range of additional factors that include appropriate patient selection, an experienced electrophysiology laboratory team and standardized, guideline-directed pre- and post-procedural management(8). The Heart Rhythm Society’s 2020 AF Centres of Excellence whitepaper outlines the rationale and guidance for key components of an AF Centre of Excellence(8). However, as the increasing benefit of AF ablation creates an increasing demand for the procedure, a balance must be struck between having very few centres of excellence and abundant centres with limited experience. In this context, the results of the current study by Kanoaka and colleagues are valuable and raises the possibility of a two-tiered approach. That of lower volume centres providing less complex procedures such as cryoablation for simpler cases of AF and higher volume ‘Centres of Excellence’ providing advanced ablation procedures for more complex AF cases. Such a division of labor may strike the balance between ablation availability and optimal outcomes. This differentiation, based on the characteristics of procedure offered and type of patients treated, will likely achieve greater importance as future technologies such as pulsed field ablation emerge and promise faster, safer and easier ablation strategies for AF(9).References1. Hindricks G, Potpara T, Dagres N, Arbelo E, Bax JJ, Blomström-Lundqvist C, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. European Heart Journal. 2020;42(5):373-498.2. Kirchhof P, Camm AJ, Goette A, Brandes A, Eckardt L, Elvan A, et al. Early Rhythm-Control Therapy in Patients with Atrial Fibrillation. New England Journal of Medicine. 2020;383(14):1305-16.3. Vemulapalli S, Carroll JD, Mack MJ, Li Z, Dai D, Kosinski AS, et al. Procedural Volume and Outcomes for Transcatheter Aortic-Valve Replacement. New England Journal of Medicine. 2019;380(26):2541-50.4. Cheung JW, Yeo I, Cheng EP, Ip JE, Thomas G, Liu CF, et al. Inpatient hospital procedural volume and outcomes following catheter ablation of atrial fibrillation. J Cardiovasc Electrophysiol. 2020;31(8):1908-19.5. Tonchev IR, Nam MCY, Gorelik A, Kumar S, Haqqani H, Sanders P, et al. Relationship between procedural volume and complication rates for catheter ablation of atrial fibrillation: a systematic review and meta-analysis. Europace. 2021;23(7):1024-32.6. Velagic V, Prepolec I, Pasara V, Puljevic M, Puljevic D, Planinc I, et al. Learning curves in atrial fibrillation ablation – A comparison between second generation cryoballoon and contact force sensing radiofrequency catheters. Indian Pacing and Electrophysiology Journal. 2020;20(6):273-80.7. Heeger C-H, Sohns C, Pott A, Metzner A, Inaba O, Straube F, et al. Phrenic Nerve Injury During Cryoballoon-Based Pulmonary Vein Isolation: Results of the Worldwide YETI Registry. Circulation: Arrhythmia and Electrophysiology. 2022;15(1):e010516.8. Piccini JP, Sr., Allred J, Bunch TJ, Deering TF, Di Biase L, Hussein AA, et al. Rationale, considerations, and goals for atrial fibrillation centers of excellence: A Heart Rhythm Society perspective. Heart Rhythm. 2020;17(10):1804-32.9. Reddy VY, Dukkipati SR, Neuzil P, Anic A, Petru J, Funasako M, et al. Pulsed Field Ablation of Paroxysmal Atrial Fibrillation: 1-Year Outcomes of IMPULSE, PEFCAT, and PEFCAT II. JACC: Clinical Electrophysiology. 2021;7(5):614-27.

Introduction: Presence of preferential pathway conduction is mostly detected as fractionated presystolic potentials preceding the QRS onset during premature ventricular contractions (PVCs) and late potentials during sinus rhythm (SR), but the electrophysiologic mechanisms and significance of these potentials have not been fully clarified. We describe a PVC case series in which the preferential pathway conduction was 3-dimensionaly visualized by coherent mapping with the conduction velocity vector. Methods: Five PVCs (2 from the left coronary cusp, 2 from the commissure of the left and right coronary cusps, and 1 from the pulmonary artery) in 4 patients for which a fractionated presystolic potential during the PVCs and late potential during SR were recorded at the successful ablation site were reviewed, and 3-dimensional coherent activation maps with the conduction velocity vector during the PVCs and SR were reconstructed. Results: At the successful ablation site, an “M”-shaped discrete presystolic-potential and “W”-shaped discrete late-potential were recorded in all patients. The configuration of the flipped electrogram of the presystolic-potential nearly matched that of the electrogram exhibiting the late-potential. We created coherent activation maps annotating the onset of the presystolic potentials during the PVCs, and the offset of the late potentials during SR, which suggested bidirectional conduction of the preferential pathway connecting the PVC origin to the myocardium. Conclusion: In this case series, the M-shaped presystolic potential and W-shaped late potential were reversely matched. These reverse potentials, and the coherent activation vector maps during PVCs and SR suggested bidirectional conduction of the preferential pathway in opposite directions.

Introduction: Chemical ablation by retrograde infusion of ethanol into the vein of Marshall (VOM-EI) can facilitate achievement of mitral isthmus block. This study sought to describe efficacy and safety of this technique. Methods and Results: Twenty-two consecutive patients (14 male, median age 71 years) with attempted VOM-EI for mitral isthmus ablation were included in the study. VOM-EI was successfully performed with a median of 4 ml of 96% ethanol in 19 patients (86%) and mitral isthmus was successfully blocked in all (100%). Touch up endocardial and/or epicardial ablation after VOM-EI was necessary in 12 patients (63%). Perimitral flutter was present in 12 patients (63%) during VOM-EI and terminated or slowed by VOM-EI in four and three patients, respectively. Low-voltage area of the mitral isthmus region increased from 3.1 cm2 (IQR 0-7.9) before to 13.2 cm2 (IQR 8.2-15.0) after VOM-EI and correlated significantly with the volume of ethanol injected (P = 0.03). Median high-sensitive cardiac troponin-T increased significantly from 330 ng/L (IQR 221-516) the evening of the procedure to 598 ng/L (IQR 382-769; P=0.02) the following morning. A small pericardial effusion occurred in three patients (16%), mild pericarditis in one (5%) and uneventful VOM dissection in two (11%). After a median follow-up of 3.5 months (IQR 3.0-11.0), 10 of 18 patients (56%) with VOM-EI and available follow-up had arrhythmia recurrence. Repeat ablation was performed in five patients (50%) and peri-mitral flutter diagnosed in three (60%). Conclusion: VOM-EI is feasible, safe and effective to achieve acute mitral isthmus block

Aggressive Treatment of Atrial Fibrillation in Hypertrophic Cardiomyopathy

Introduction: Early recurrence (ER) of atrial fibrillation (AF) is defined as the recurrence of atrial tachyarrhythmias within 3 months after AF ablation, however, this definition is based on data from the era of radiofrequency catheter ablation (RFCA), without contact force (CF) technology. We investigated the significance of ER as a risk factor for late recurrence (LR) in paroxysmal AF (PAF) patients treated with CF and non-CF-guided ablation. Methods and Results: We studied 395 patients with PAF who underwent RFCA. Of these, 97 patients underwent RFCA without CF technology (Non-CF group) and 298 underwent with CF technology (CF group). Over a 2-year post-ablation follow-up period, LR occurred in 54 of 97 (55.7%) patients in the Non-CF group, and in 105 of 298 (35.2%) patients in the CF group. ER had a more significant relationship with LR in the CF than in the Non-CF group, and all patients in the CF group with ER in the 3rd month developed LR. Conclusion: ER in PAF patients who have undergone CF-guided ablation have a greater risk of LR than those who have undergone non-CF-guided ablation. ER in the 3rd month after CF-guided ablation may indicate an absolute risk of LR. Blanking period could be defined as 2 months in the CF era.

Catheter Ablation of Ventricular Arrhythmias in patients with Prior Mitral Valve Surgery: Challenging, but Feasible and Effective!Amrish Deshmukh, MD; Frank Bogun, MD; Jackson J. Liang, DOElectrophysiology Section, Division of Cardiology; University of Michigan, Ann Arbor, MIFunding: NoneDisclosures: None

A document by Youssef Jalloul. Click on the document to view its contents.

Atrial fibrillation (AF) is the most common cardiac arrhythmia and often occurs with heart failure (HF) [1]. AF prevalence increases with increasing severity of HF: for instance its prevalence ranges from 5 percent in patients with New York Heart Association (NYHA) functional class I HF to 40 percent in patients with NYHA class IV HF [2]. Its presence with HF plays a significant prognostic role and increases morbidity and mortality. Heart Failure with reduced ejection fraction (HFrEF) is associated with cardiac arrhythmias [3]. HFrEF is also one of the indications for Cardiac resynchronization therapy (CRT) placement [4]. Therefore, many patients undergoing CRT implantation will concomitantly have HF and AF. As the benefit from CRT in HF patients has been established, the data on patients with both HF and AF is limited, because patients with atrial arrhythmias were excluded from most of the major CRT trials, such as CARE-HF and COMPANION [5]. However, a number of observational studies and small randomized clinical trials suggest a benefit from CRT in AF and HF patients such as a CRT-mediated ejection fraction (EF) increase [6, 7]. Other studies showed a high non-response rate in patients with AF as compared to those in sinus rhythm (SR) [8]. Thus, it is important to determine whether CRT has a beneficial role in these patients to decide on adding an atrial lead at the time of CRT implantation especially in patients with longstanding-persistent AF.In their published study, Ziegelhoeffer et al. investigated the outcomes of CRT placement with an atrial lead in patients with HF and AF. This was done by conducting a retrospective analysis of all patients with AF who received CRT for HF at the Kerckhoff Heart Center since June 2004 and were observed until July 2018- completing a 5-year follow-up. The authors identified 328 patients and divided them into 3 subgroups: paroxysmal (px) AF, persistent (ps) AF, and longstanding-persistent (lp) AF, with all patients receiving the same standard operative management. During the observation period, the authors analyzed the rhythm course of the patients, cardiac parameters (NYHA class, MR, LVEF, left atrial diameter) and performed a subgroup analysis for patients who received an atrial lead. The study showed that all groups had a high rate of sinus rate (SR) conversion and rhythm maintenance at 1 and 5 years. Specifically, the patients who received an atrial lead among the lp AF group were shown to have a stable EF, less pronounced  left ventricular end-systolic diameter (LVESD) and  left ventricular end diastolic diameter (LVEDD) and lower mitral regurgitation (MR) rates at one year follow-up as compared to the group without atrial lead placement. Moreover, the results of the lp group were similar to the ps-AF group, although the latter had a lower number of participants (n=4) without initial implantation of the atrial lead. The authors attributed the improvement in cardiac function and SR conversion to CRT and the implantation of an additional atrial lead.Although some studies showed that CRT therapy reduced secondary MR in HF [9, 10], this study additionally suggests that CRT with an atrial lead was associated with improved myocardial function and improvement of interventricular conduction delay triggering cardiac remodeling in patients with HF and AF. Although the results showed better cardiac function in the subgroup analysis of the patients with an additional atrial lead, these results were reported as percentages with no level of significance specified, hence statistical significance of the difference in the described parameters (such as LVESD, LVEDD) could not be determined. Further investigation via prospective studies is needed with larger sample size in the future to further support the results of the study especially that it was done in a single center and had a relatively small sample size.References:1. Chung MK, Refaat M, Shen WK, et al. Atrial Fibrillation: JACC Council Perspectives. J Am Coll Cardiol. Apr 2020; 75 (14): 1689-1713.2. Maisel, W.H. and L.W. Stevenson, Atrial fibrillation in heart failure: epidemiology, pathophysiology, and rationale for therapy. Am J Cardiol, 2003. 91 (6a): p. 2d-8d.3. AlJaroudi WA, Refaat MM, Habib RH, et al. Effect of Angiotensin Converting Enzyme Inhibitors and Receptor Blockers on Appropriate Implantable Cardiac Defibrillator Shock: Insights from the GRADE Multicenter Registry. Am J Cardiol Apr 2015; 115 (7): 115(7):924-31.4. Yancy, C.W., et al., 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol, 2013. 62 (16): p. e147-239.5. Cleland, J.G., et al., The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med, 2005.352 (15): p. 1539-49.6. Leclercq, C., et al., Comparative effects of permanent biventricular and right-univentricular pacing in heart failure patients with chronic atrial fibrillation. Eur Heart J, 2002. 23 (22): p. 1780-7.7. Upadhyay, G.A., et al., Cardiac resynchronization in patients with atrial fibrillation: a meta-analysis of prospective cohort studies. J Am Coll Cardiol, 2008. 52 (15): p. 1239-46.8. Wilton, S.B., et al., Outcomes of cardiac resynchronization therapy in patients with versus those without atrial fibrillation: a systematic review and meta-analysis. Heart Rhythm, 2011. 8 (7): p. 1088-94.9. van Bommel, R.J., et al., Cardiac resynchronization therapy as a therapeutic option in patients with moderate-severe functional mitral regurgitation and high operative risk. Circulation, 2011.124 (8): p. 912-9.10. Breithardt, O.A., et al., Acute effects of cardiac resynchronization therapy on functional mitral regurgitation in advanced systolic heart failure. J Am Coll Cardiol, 2003. 41 (5): p. 765-70.

Background: Computer simulation model demonstrated that atrial fibrillation (AF) driver attached to the patchy fibrosis assessed by late gadolinium enhancement magnetic resonance imaging (LGE-MRI). However, it has not been well elucidated in patients with persistent AF. The aim of this study is to investigate whether radiofrequency (RF) application on the patchy LGE site (PLS) could terminate AF or convert to atrial tachycardia (AT) and improve the rhythm outcome. Methods: A total of 31consecutive persistent AF patients with PLS were enrolled (PLS ablation group, mean age: 69 ± 8 years, mean left atrial diameter: 42 ± 6 mm). AF direct termination or AT conversion during RF application on the PLS were defined as favorable response. The rhythm outcome was compared between the PLS ablation group and the propensity matched conventional ablation group. Results: Favorable response was found in 15 (48%) of 31 patients (AF termination in 7, AT conversion in 8 patients). AF recurrence at 12 months follow-up was significantly less in the PLS group as compared to the control group (4 (13%) of 31 patients vs. 11 (35%) of 31 patients, log-rank p = 0.019). In patients with favorable response, AT recurred in 1 (7%) of 15 patients but AF. Conclusions: The PLS ablation could terminate AF or convert to AT in half of the patients and improve the rhythm outcome as compared to the conventional ablation. No AF recurrence was documented in patients with a favorable response.

Abstract Introduction: Linear ablation in addition to pulmonary vein antrum isolation (PVAI) has failed to improve the success rate for persistent atrial fibrillation (PeAF), due to incomplete block of ablation lines, especially in the mitral isthmus (MI). Methods and results: The study enrolled 191 patients (66 in group 1 and 125 in group 2). In group 1, EI-VOM was firstly performed, followed by radiofrequency (RF) applications targeting bilateral PVAI and bidirectional block in the roofline, cavotricuspid isthmus, and MI. In group 2, PVAI and the three linear ablations were completed using only RF energy. MI block was achieved in 63(95.5%) and 101(80.8%) patients in group 1 and 2, respectively (p=0.006). Patients in group 1 had shorter ablation time for left pulmonary vein antrum (8.15 min vs 12.59 min, p<0.001) and MI (7.0 min vs 11.8 min, p<0.001) and required less cardioversion (50(78.5%) vs 113(90.4%), p=0.007). During the 12-month follow-up, 58 (87.9%) patients were free from AF/AT in group 1 compared with 81 (64.8%) in group 2 (p<0.001). In multivariate cox regression, the ‘upgraded 2C3L’ procedure is associated with a lower recurrence rate (HR 0.27, 95%CI 0.12-0.59). Conclusion: Compared with the conventional ‘2C3L’ approach, the ‘upgraded 2C3L’ approach has higher effectiveness for ablation of PeAF.