Background: Rheumatic diseases (RDs) are associated with increased cardiovascular morbidity, including a 40% higher risk of atrial fibrillation (AF). While ablation has become the cornerstone of rhythm control, its safety in patients with rheumatic diseases remains poorly defined. Methods: Adults with a primary admission diagnosis of AF catheter ablation from 2016 to 2022 were identified using the National Inpatient Sample. We excluded patients with other forms of supraventricular tachycardia, pacemaker/defibrillator procedures, and atrioventricular junction ablations. Sociodemographic, clinical characteristics, and outcomes were compared between groups. Multivariate logistic regression adjusted for age, race, sex, and potential comorbid confounders was used to assess for independent associations. Results: A weighted total of 48,855 patients were included, 2.5% of which had RD. These patients were predominantly female, older, and had higher rates of renal dysfunction, hypertension, heart failure, history of stroke, ischemic heart disease, heart failure, and obstructive sleep apnea (all p < 0.001). Patients with RD had higher complication rates (12.9% vs. 8.8%, p < 0.001); specifically, bleeding (p < 0.001), infection (p = 0.008), pericardial (p = 0.003), and respiratory complications (p < 0.001). RDs were not found to be an independent predictor of complications, though there was a trend towards more complications (odds ratio 1.43, 95% confidence interval 0.97-2.11, p = 0.070). Conclusions: Patients with RD undergoing AF ablation were older, female, and had higher rates of comorbidities. This translated to higher unadjusted periprocedural complications in patients with rheumatic diseases. While RDs were not independently associated with adverse outcomes, a trend towards increased complications was observed.

BACKGROUND:Atriofascicular fibers (AFFs) are rare accessory pathways that have higher rates of recurrence after ablation because of either failure to identify AFF (M) potentials or mechanical termination with contact. OBJECTIVE:We aimed to evaluate whether electroanatomic mapping (EAM) using multielectrode, high-density nonlinear catheters can reliably localize AFF potentials and determine a site for ablation without causing mechanical termination. METHODS:Seven patients underwent electrophysiology studies (EPS) and EAM using high-density, multielectrode catheters for antidromic tachycardia using AFFs. RESULTS:Mean age at ablation was 15.5 ± 7.4 years, and 2 (29%) were female. Two had Ebstein's anomaly. Three of 7 (43%) had previous ablation attempts. Of the previous attempts, 3 (60%) were complicated by mechanical termination during mapping. None of the previous ablation attempts was performed using high-density mapping catheters. HD Grid with Ensite NavX (Abbott Cardiovascular, Abbott Park, IL) was used in 3; the remainder used the PentaRay (3) or Optrell (1) catheters with CARTO (Biosense Webster, Irvine, CA). The AFF course was mapped to the lateral tricuspid annulus in all. Four of 7 had oblique courses with atrial insertion superior to the ventricular insertion. Multielectrode mapping catheters did not result in mechanical termination in any of these cases, whereas mechanical termination with ablation catheters occurred in 4 (57%). Successful ablation was performed in all with no recurrence over a 15 ± 6-month follow-up. CONCLUSION:EAM using high-density multielectrode mapping catheters allow localization of atriofascicular pathways without causing mechanical termination and may improve long-term success of ablation. Majority of the pathways had oblique courses with atrial insertion superior to the ventricular insertion.

Background/Objectives: Atrial fibrillation (AF) and flutter (AFL) are the most common cardiac arrhythmias worldwide. Cardiovascular complications are a common manifestation of acute and post-acute COVID-19 infection. We aimed to analyze the nationwide trends in clinical characteristics and outcomes of patients hospitalized for AF/AFL before and during the COVID-19 outbreak in the U.S. Methods: This study is a retrospective analysis of patients, aged 18 and older, hospitalized for AF/AFL in the U.S. between 2016 and 2020. We drew data from the National Inpatient Sample (NIS) database. Baseline sociodemographic and clinical data, as well as outcomes including stroke, acute coronary syndrome (ACS), and mortality, were analyzed. Multivariable analysis was performed to identify independent associations between the different clinical and demographic characteristics and the composite endpoint of Mortality/ACS/Stroke. Results: An estimated total of 2,163,699 hospitalizations for AF/AFL were identified. The hospitalization volume between 2016 and 2019 was stable, averaging 465,176 a year, followed by a significant drop to 302,995 in 2020. Patients’ median age was 72 years (IQR 62–80), 50.9% were male, and 81.5% were white. The composite endpoint steadily increased from 6.5% in 2016 to 11.8% in 2020 (Ptrend < 0.001). In a multivariable regression analysis, age > 75 (OR: 1.35; 95% CI 1.304–1.399, p < 0.001), ischemic heart disease (OR: 1.466; 95% CI: 1.451–1.481; p < 0.001), and chronic kidney disease (OR: 1.635; 95% CI: 1.616–1.653; p < 0.001) were associated with the composite endpoint. COVID-19 was associated with the composite endpoint outcome in the year 2020 (OR: 1.147; 95% CI: 1.037–1.265; p = 0.007). Conclusions: Hospitalization for AF/AFL dropped significantly during the first year of the COVID-19 pandemic outbreak, possibly due to patients’ avoidance of hospital visits. The composite endpoint of Mortality/ACS/Stroke uptrended significantly during the study period. COVID-19 was shown to be independently associated with the adverse composite outcome Mortality/ACS/Stroke.

Cardiac arrhythmia ablation was first performed in 1981 by Dr. Scheinman in a patient with atrial fibrillation and multiple comorbidities that prohibited the then usual treatment of surgical ablation via sternotomy and cardiotomy.1 After intense research, the treatment of atrial fibrillation moved on to radiofrequency ablation of the pulmonary veins and shifted away from nodal techniques in this patient population.1 Over more than four decades, these giant leaps in treatment technology have dramatically reduced the need for sternotomy and other highly invasive techniques and revolutionized the treatment of atrial fibrillation. In recent years, the treatment of atrial fibrillation using ablation strategies has again seen an expansion in use to the heart failure population. As perioperative physicians, anesthesiologists must be cognizant of the nuances of the expanded use of this technology to the high-risk heart failure population. Recently, in their manuscript “Catheter Ablation in End-Stage Heart Failure with Atrial Fibrillation” (CASTLE HTx), Sohns et al demonstrated an impressive mortality benefit with the application of catheter based atrial fibrillation ablation in patients with atrial fibrillation and left ventricular ejection fraction (LVEF) ≤ 35%.2 In this investigation, the authors randomized patients with reduced LVEF and symptomatic atrial fibrillation (persistent or paroxysmal) to catheter ablation (pulmonary vein isolation +/- other) and goal-directed medical therapy (GDMT), or GDMT alone. After enrolling 97 patients per arm, and following an 18-month median follow-up period, the study was halted due to significant outcome differences between the groups, with a dramatic reduction in mortality (6% vs 20%, hazard ratio 0.29, intention-to-treat analysis) noted for the ablation group. Alone, this would be a remarkable finding, but it must also be noted that there was significant crossover of patients from the GDMT to the ablation arm. This raises the possibility that the true differences in outcomes between GDMT and ablation may be even more pronounced. This work has the potential to significantly alter the routine management of this patient population, and it stands to reason that anesthesiologists will increasingly encounter this complex group in the electrophysiology lab. The findings of CASTLE-HTx raise important questions about which specific populations and demographics may benefit most from catheter ablation and which require special attention to optimize outcomes. As always, the devil is in the details, and care must be taken when interpreting and applying the findings. Upon review of the supplemental data from CASTLE HTx, a few interesting results emerge. First, the demonstrated mortality and outcome differences are far more robust in patients with higher baseline LVEF in the range of 25-35% (HR 0.13 CI 0.04-0.45), when compared with <25% (HR 0.49, CI 0.17-1.41).2 Although underpowered to demonstrate outcome differences with this level of stratification, the confidence interval for patients with LVEF <25 suggests that there may not be as much benefit to the intervention in this group. Similarly, though there were trends towards significance, the study was underpowered to demonstrate outcome differences in women (HR 0.33, CI 0.07-1.50), patients ≥65 years of age (HR 0.41, CI 0.16-1.04) and patients with paroxysmal atrial fibrillation (HR 0.50, CI 0.17-1.48). 2 As with many other invasive interventions, there may be a tipping point where benefits do not justify procedural risks. In Castle-HTx, the authors publish very low rates of procedural complications 4/194 (2%), all of which were described as “minor” vascular issues. This contrasts with previously published literature, where complication rates are similar overall (2.9-3.6%), but significant complications such as tamponade, effusion and stroke were more frequently reported (nearly 50% of overall).2,3 Further, female sex has been identified by multiple authors as a predictor of complications in this population.1,4,5 Given these important limitations, a thoughtful approach is important when considering the broad applications of these findings. It is also important to consider how these findings fit into the landscape of perioperative and procedural management of atrial fibrillation. The American Association for Thoracic Surgery (AATS) consensus guidelines list concomitant surgical ablation for atrial fibrillation during cardiac surgery as a Class I indication for improving short term (<30 day) survival, and a Class IIa indication for improving longer term (>30 day) survival.6 A multicenter retrospective analysis from 2019 found an association between improved short- and long-term survival in cardiac surgical patients that underwent surgical ablation as part of a variety of primary operations. 7 In their study, after risk adjustment, patients undergoing surgical ablation had improved 5-year survival (HR 0.69, CI 0.51-0.92), and the effect was observed across all concomitant operations.7 Though this trial did include patients with depressed LVEF (<40%), no sub-analysis of this population was performed, and to date there is a lack of high-quality evidence corroborating the mortality benefits of surgical ablation specifically in the reduced LVEF population. Given both the surgical as well as the medical data, it appears that prospective investigation of surgical ablation in this population is warranted. Anesthesiologists must be aware of the effects of all commonly prescribed goal direct medical therapy (GDMT) agents in this patient population. For example, in the Castle HTx intervention arm: 68% of patients were being treated with sacubitril-valsartan (Entrestoâ, Novartis AG, Basel, Switzerland), 32% of patients with either an angiotensin converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB), and 24% were being treated with a sodium glucose transport protein 2 (SGLT2) inhibitor.1 ACEi and ARB use has been inconsistently associated with perioperative vasoplegia after cardiac and non-cardiac surgical procedures.8-11 Patients presenting for catheter-based procedures are a relatively unexplored area with regard to this topic. The decision to withhold afterload reduction in end stage heart failure patients is complex given that increased afterload can precipitate decompensated heart failure while perioperative hypotension can contribute to acute kidney injury. A thoughtful approach that includes a review of institutional protocols regarding perioperative administration of these agents should be followed in patients presenting for atrial fibrillation ablation. Given its relatively recent release, data regarding the association between sacubitril-valsartan and perioperative hypotension is mostly limited to case reports and case series, with no definitive conclusions that can be made in the catheter-based population.12 SGLT2 inhibitors, which function by blocking the reabsorption of glucose in the nephron, have seen a rapidly growing list of indications for use in the heart failure population.13,14,15 The notable side effects with this class of medications, euglycemic ketoacidosis as well as genital infections and an initial concern for urinary tract infections (due to the resultant glycosuria), have important implications in the perioperative period.16,17,18 In one large meta-analysis, an association with urinary tract infections was disproven but genital infections seem to be more frequent in the SGLT2 inhibitor group.18 Most organizations recommend withholding SGLT2 inhibitors 3-4 days before surgery and restarting them when oral intake has normalized to reduce the risk of euglycemic DKA.16,17,19 Though the incidence of hypoglycemia with SGLT2 inhibitors is low, anesthesiologists may consider assessing glucose levels during longer ablation procedures, particularly because patients receiving these agents are frequently diabetic and often receiving other glucose lowering medications. Finally, the rise of glucagon-like peptide-1 receptor agonists (GLP-1) like semaglutide will likely further complicate management of these patients. There is increasing evidence that weight loss in the overweight/obese patient population plays an important role in the management of this population.20,21 Glucagon like peptides-1 agonists are being widely used to achieve this goal in this patient population. Emerging evidence in the preserved LVEF heart failure population suggests that GLP-1 agonists may have a role in symptom reduction and quality of life improvement and future work may translate this to low LVEF patients presenting for anesthetic management.22,23 Notably, GLP-1 agonists delay gastric emptying, and may predispose patients to aspiration events at the time of anesthetic induction. Though high-quality evidence is still lacking on this topic, the American Society of Anesthesiologists has recommended holding the oral forms for a day preoperatively, and the weekly injectable for a week preoperatively. 24 A notable finding in the supplemental index of CASTLE HTx trial was the very low procedure time.1 Specifically, “skin-to-skin” or procedure start to finish time was 96 ± 20 minutes, which is dramatically faster than that seen in large observational studies which found an average procedure time of 180 minutes (interquartile range, 25th to 75th percentile, of 140-230).25 This discrepancy could be due to a number of factors including two experienced providers per case with ≥ 400 procedures each. Some of the aforementioned differences in procedural complications in CastleHTx may be partially attributable to these shorter procedural durations and experienced providers. The far shorter procedure times (nearly 50%) has several important implications with regard to the widespread use of this procedure in the end stage heart failure population. First, contemporary ablation catheters continuously infuse fluid in order to achieve better current delivery to the cardiac tissue and achieve more durable lesions through the irrigant's cooling effect. This will often result in volumes of up to 30 milliliters/minute during ablation, which could have important implications in the heart failure population and necessitate the use of diuretic therapy to avoid heart failure exacerbation.26 Second, duration of anesthesia is also likely associated with increased fluid administration due to the need for infusions and medication administration, a modifiable risk with vigilant care, in addition to the inherent risks of anesthetizing the heart failure population. As an extension of the results of this trial, it may be possible that in non-compliant heart failure patients who otherwise meet criteria, ablation could be part of a staged procedure to reduce long term morbidity. Though both arms of Castle-HTx received GDMT, it would be interesting to study whether ablation alone could provide mortality benefit in the non-compliant population. Further, patients unwilling to continue anticoagulation (or those with a contraindication) may benefit from a combined ablation and left atrial appendage occlusion device, followed with a shorter duration of anticoagulation. This would require a case-by-case evaluation given that stopping anticoagulation after atrial fibrillation ablation is not consistent with current guidelines.27 Perhaps in the future, a hybrid structural heart and atrial fibrillation ablation approach may assist patients that would prefer to avoid long term anticoagulation. Retrospective reviews do suggest that this approach is possible, but further research is needed to assess safety and efficacy in the heart failure population.28,29 As the treatment of atrial fibrillation finds expanding use in ever more high-risk populations, anesthesiologists are tasked with not only understanding the nature of the procedures patients will receive, but also the growing body of literature surrounding the care of advanced heart failure patients. Additionally, the impact of SGLT-2 inhibitors, afterload reducing medications such as sacubitril-valsartan, and novel anticoagulants in the perioperative period has not yet been fully appreciated and requires both vigilance and research from the anesthesia community. Combined ablation-structural interventions are likely to play a larger role in certain patient cohorts and cardiac anesthesiologists are likely to be called upon for imaging guidance. Anesthesiologists will play a central role in meeting the needs of the growing heart failure population and it is imperative that our community engages in the meaningful delivery of high-level care, research, patient safety advocacy. 1Scheinman MA, Rutherford JD. The Development of Cardiac Arrhythmia Ablation: A Conversation With Melvin A. Scheinman, MD. Circulation. 2017 Mar 28;135(13):1191-1193. doi: 10.1161/CIRCULATIONAHA.117.027956. PMID: 28348089.2Sohns C, Fox H, Marrouche NF, Crijns HJGM, Costard-Jaeckle A, Bergau L, Hindricks G, Dagres N, Sossalla S, Schramm R, Fink T, El Hamriti M, Moersdorf M, Sciacca V, Konietschke F, Rudolph V, Gummert J, Tijssen JGP, Sommer P; CASTLE HTx Investigators. Catheter Ablation in End-Stage Heart Failure with Atrial Fibrillation. N Engl J Med. 2023 Aug 27.3Mol D, Houterman S, Balt JC, Bhagwandien RE, Blaauw Y, Delnoy PH, van Driel VJ, Driessen AH, Folkeringa RJ, Hassink RJ, van Huysduynen BH, Luermans JG, Ouss AJ, Stevenhagen YJ, van Veghel D, Westra SW, de Jong JS, de Groot JR; Netherlands Heart Registration Ablation Registration Committee. Complications in pulmonary vein isolation in the Netherlands Heart Registration differ with sex and ablation technique. Europace. 2021 Feb 5;23(2):216-225. doi: 10.1093/europace/euaa255. Erratum in: Europace. 2021 Aug 6;23(8):1332. PMID: 33141152.4Gupta A, Perera T, Ganesan A, Sullivan T, Lau DH, Roberts-Thomson KC, Brooks AG, Sanders P. Complications of catheter ablation of atrial fibrillation: a systematic review. Circ Arrhythm Electrophysiol. 2013 Dec;6(6):1082-8. doi: 10.1161/CIRCEP.113.000768. Epub 2013 Nov 15. PMID: 24243785.5Yves De Greef, Edwin Ströker, Bruno Schwagten, Kaspars Kupics, Jeroen De Cocker, Gian-Battista Chierchia, Carlo de Asmundis, Dirk Stockman, Ian Buysschaert, Complications of pulmonary vein isolation in atrial fibrillation: predictors and comparison between four different ablation techniques: Results from the MIddelheim PVI-registry, EP Europace, Volume 20, Issue 8, August 2018, Pages 1279–1286, https://doi.org/10.1093/europace/eux2336Ad N, Damiano RJ Jr, Badhwar V, Calkins H, La Meir M, Nitta T, Doll N, Holmes SD, Weinstein AA, Gillinov M. Expert consensus guidelines: Examining surgical ablation for atrial fibrillation. J Thorac Cardiovasc Surg. 2017 Jun;153(6):1330-1354.e1. doi: 10.1016/j.jtcvs.2017.02.027. Epub 2017 Mar 2. PMID: 28390766.7Iribarne A, DiScipio AW, McCullough JN, Quinn R, Leavitt BJ, Westbrook BM, Robich MP, Sardella GL, Klemperer JD, Kramer RS, Weldner PW, Olmstead EM, Ross CS, Malenka DJ; Northern New England Cardiovascular Disease Study Group. Surgical Atrial Fibrillation Ablation Improves Long-Term Survival: A Multicenter Analysis. Ann Thorac Surg. 2019 Jan;107(1):135-142. doi: 10.1016/j.athoracsur.2018.08.022. Epub 2018 Oct 6. PMID: 30300644.8Noubiap JJ, Nouthe B, Sia YT, Spaziano M. Effect of preoperative renin-angiotensin system blockade on vasoplegia after cardiac surgery: A systematic review with meta-analysis. World J Cardiol. 2022 Apr 26;14(4):250-259.9Milne B, Gilbey T, Ostermann M, Kunst G. Pro: We Should Stop ACE Inhibitors Early Before Cardiac Surgery to Prevent Postoperative Acute Kidney Injury. J Cardiothorac Vasc Anesth. 2020 Oct;34(10):2832-2835.10Disque A, Neelankavil J. Con: ACE Inhibitors Should Be Stopped Prior to Cardiovascular Surgery. J Cardiothorac Vasc Anesth. 2016 Jun;30(3):820-2. doi: 10.1053/j.jvca.2016.01.016.11Roshanov PS, Rochwerg B, Patel A, Salehian O, Duceppe E, Belley-Côté EP, Guyatt GH, Sessler DI, Le Manach Y, Borges FK, Tandon V, Worster A, Thompson A, Koshy M, Devereaux B, Spencer FA, Sanders RD, Sloan EN, Morley EE, Paul J, Raymer KE, Punthakee Z, Devereaux PJ. Withholding versus Continuing Angiotensin-converting Enzyme Inhibitors or Angiotensin II Receptor Blockers before Noncardiac Surgery: An Analysis of the Vascular events In noncardiac Surgery patIents cOhort evaluatioN Prospective Cohort. Anesthesiology. 2017 Jan;126(1):16-27.12Haider L, Hugon-Vallet E, Constantin JP, Riad Z, Sebbag L, Mewton N. ARNI Pre-Operative Use and Vasoplegic Syndrome in Patients Undergoing Heart Transplantation or Left Ventricular Assist Device Surgery. Med Sci (Basel). 2021 Dec 21;10(1):2.13McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Anand IS, Bělohlávek J, Böhm M, Chiang CE, Chopra VK, de Boer RA, Desai AS, Diez M, Drozdz J, Dukát A, Ge J, Howlett JG, Katova T, Kitakaze M, Ljungman CEA, Merkely B, Nicolau JC, O'Meara E, Petrie MC, Vinh PN, Schou M, Tereshchenko S, Verma S, Held C, DeMets DL, Docherty KF, Jhund PS, Bengtsson O, Sjöstrand M, Langkilde AM; DAPA-HF Trial Committees and Investigators. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019 Nov 21;381(21):1995-2008.14Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, Januzzi J, Verma S, Tsutsui H, Brueckmann M, Jamal W, Kimura K, Schnee J, Zeller C, Cotton D, Bocchi E, Böhm M, Choi DJ, Chopra V, Chuquiure E, Giannetti N, Janssens S, Zhang J, Gonzalez Juanatey JR, Kaul S, Brunner-La Rocca HP, Merkely B, Nicholls SJ, Perrone S, Pina I, Ponikowski P, Sattar N, Senni M, Seronde MF, Spinar J, Squire I, Taddei S, Wanner C, Zannad F; EMPEROR-Reduced Trial Investigators. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N Engl J Med. 2020 Oct 8;383(15):1413-1424.15Solomon SD, McMurray JJV, Claggett B, de Boer RA, DeMets D, Hernandez AF, Inzucchi SE, Kosiborod MN, Lam CSP, Martinez F, Shah SJ, Desai AS, Jhund PS, Belohlavek J, Chiang CE, Borleffs CJW, Comin-Colet J, Dobreanu D, Drozdz J, Fang JC, Alcocer-Gamba MA, Al Habeeb W, Han Y, Cabrera Honorio JW, Janssens SP, Katova T, Kitakaze M, Merkely B, O'Meara E, Saraiva JFK, Tereshchenko SN, Thierer J, Vaduganathan M, Vardeny O, Verma S, Pham VN, Wilderäng U, Zaozerska N, Bachus E, Lindholm D, Petersson M, Langkilde AM; DELIVER Trial Committees and Investigators. Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction. N Engl J Med. 2022 Sep 22;387(12):1089-1098.16Thiruvenkatarajan V, Jesudason D, Nanjappa N, Meyer EJ, Van Wijk RM. Perioperative Management of Glucose-lowering Drugs: Comment. Anesthesiology. 2021 Feb 1;134(2):349-350.17Preiser JC, Provenzano B, Mongkolpun W, Halenarova K, Cnop M. Perioperative Management of Oral Glucose-lowering Drugs in the Patient with Type 2 Diabetes. Anesthesiology. 2020 Aug;133(2):430-438.18Puckrin R, Saltiel MP, Reynier P, Azoulay L, Yu OHY, Filion KB. SGLT-2 inhibitors and the risk of infections: a systematic review and meta-analysis of randomized controlled trials. Acta Diabetol. 2018 May;55(5):503-514.19FDA Revises Labels of SGLT2 Inhibitors for Diabetes to Include Warnings About Too Much Acid in the Blood and Serious Urinary Tract Infections. FDA; (2021). Available online at: https://www.fda.gov/drugs/drug-safety-and-availability/fda-revises-labels-sglt2-inhibitors-diabetes-include-warnings-about-too-much-acid-blood-and-serious accessed: 10/8/202320Heidenreich, PA et al 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines J Am Coll Cardiol. 2022 May, 79 (17) e263–e42121Hindricks G 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, Volume 42, Issue 5, 1 February 2021, Pages 373–49822Kosiborod MN, Abildstrøm SZ, Borlaug BA, Butler J, Rasmussen S, Davies M, Hovingh GK, Kitzman DW, Lindegaard ML, Møller DV, Shah SJ, Treppendahl MB, Verma S, Abhayaratna W, Ahmed FZ, Chopra V, Ezekowitz J, Fu M, Ito H, Lelonek M, Melenovsky V, Merkely B, Núñez J, Perna E, Schou M, Senni M, Sharma K, Van der Meer P, von Lewinski D, Wolf D, Petrie MC; STEP-HFpEF Trial Committees and Investigators. Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity. N Engl J Med. 2023 Sep 21;389(12):1069-1084. doi: 10.1056/NEJMoa2306963. Epub 2023 Aug 25. PMID: 37622681.23Pérez-Belmonte LM, Sanz-Cánovas J, García de Lucas MD, Ricci M, Avilés-Bueno B, Cobos-Palacios L, Pérez-Velasco MA, López-Sampalo A, Bernal-López MR, Jansen-Chaparro S, Miramontes-González JP, Gómez-Huelgas R. Efficacy and Safety of Semaglutide for the Management of Obese Patients With Type 2 Diabetes and Chronic Heart Failure in Real-World Clinical Practice. Front Endocrinol (Lausanne). 2022 Jun 24;13:851035. doi: 10.3389/fendo.2022.851035. PMID: 35813629; PMCID: PMC9263111.24https://www.asahq.org/about-asa/newsroom/news-releases/2023/06/patients-taking-popular-medications-for-diabetes-and-weight-loss-should-stop-before-elective-surgery accessed: 10/8/2325Loring Z, Holmes DN, Matsouaka RA, Curtis AB, Day JD, Desai N, Ellenbogen KA, Feld GK, Fonarow GC, Frankel DS, Hurwitz JL, Knight BP, Joglar JA, Russo AM, Sidhu MS, Turakhia MP, Lewis WR, Piccini JP. Procedural Patterns and Safety of Atrial Fibrillation Ablation: Findings From Get With The Guidelines-Atrial Fibrillation. Circ Arrhythm Electrophysiol. 2020 Sep;13(9):e007944.26Chopra N, Amin AK, Gupta A, Fu EY, Nichols AJ, Nelson SD, Kleman JM, Kleman JM, Kidwell GA, Billakanty SR. Clinical Impact of Saline Volume Infused Through Irrigated-Tip Ablation Catheter in Low Acuity Paroxysmal Atrial Fibrillation Ablation Patients. J Atr Fibrillation. 2018 Dec 31;11(4):2093. doi: 10.4022/jafib.2093.27Kadire SR, Al-Khatib SM, Calkins H. Anticoagulation after Ablation for Atrial Fibrillation. N Engl J Med. 2021 Jul 29;385(5):466-468.28Phillips KP, Walker DT, Humphries JA. Combined catheter ablation for atrial fibrillation and Watchman® left atrial appendage occlusion procedures: Five-year experience. J Arrhythm. 2016 Apr;32(2):119-26. doi: 10.1016/j.joa.2015.11.001.29Ke JY, Jin LS, Lin YN, Xu J, Liu WK, Fu JY, Li L, Chen YL, Qiu YX, Li YC. Combined atrial fibrillation ablation and left atrial appendage closure: Watchman vs. LAmbre devices. Front Cardiovasc Med. 2022 Nov 2;9:1011037. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

HomeJournal of the American Heart AssociationVol. 12, No. 17Ablation for Persistent Atrial Fibrillation: Is There a Light at the End of the Tunnel? Open AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citations ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toOpen AccessEditorialPDF/EPUBAblation for Persistent Atrial Fibrillation: Is There a Light at the End of the Tunnel? Munther Homoud Munther HomoudMunther Homoud *Correspondence to: Munther Homoud, MD, FACP, FACC, FHRS, Section of Pacing and Electrophysiology, Tufts Medical Center, 800 Washington St., Boston, MA 02111. Email: E-mail Address: [email protected] https://orcid.org/0009-0008-4719-0717 , Section of Pacing and Electrophysiology, , Tufts Medical Center, , Boston, , MA, , USA, Search for more papers by this author Originally published29 Aug 2023https://doi.org/10.1161/JAHA.123.031258Journal of the American Heart Association. 2023;12:e031258This article is a commentary on the followingLong‐Term Impact of Additional Ablation After Pulmonary Vein Isolation: Results From EARNEST‐PVI TrialOther version(s) of this articleYou are viewing the most recent version of this article. Previous versions: August 29, 2023: Ahead of Print Compared with patients with paroxysmal atrial fibrillation, the optimal ablation strategy to reduce or eliminate atrial fibrillation in patients with persistent atrial fibrillation remains elusive.1 This is probably due to electroanatomical changes that have now set in the left atrium promoting the perpetuation of atrial fibrillation even after isolation of the pulmonary veins has been successfully performed. To improve the outcomes of patients with atrial fibrillation undergoing ablation, investigators have targeted structures such as the posterior wall, the left atrial appendage, ganglionated plexi, rotors, and complex fractionated electrograms with mixed results. Furthermore, studies such as the STAR AF II (Substrate and Trigger Ablation for Reduction of Atrial Fibrillation Trial Part II) failed to demonstrate that the addition of ablation targeting complex atrial electrograms or linear ablation lines across the left atrial roof and mitral valve isthmus to pulmonary vein isolation reduced the recurrence rate when compared with pulmonary vein isolation alone.2 Although widely performed, ablation of atrial fibrillation carries inherent risks.3 Ablation strategies that extend beyond isolation of the pulmonary vein carry short‐ and long‐term consequences. Striking the right balance of ablation to favor better long‐term outcomes without exposing the patient to serious complications is a topic of feverish research.In this context, Masuda et al in this issue of the Journal of the American Heart Association (JAHA) report on the long‐term impact of their strategy in approaching persistent atrial fibrillation.4 The EARNEST‐PVI (Effect of Extensive Ablation on Recurrence in Patients With Persistent Atrial Fibrillation Treated with Pulmonary Vein Isolation) trial was a multicenter prospective randomized controlled study comparing the 3‐year recurrence of atrial fibrillation in patients with persistent atrial fibrillation randomized to pulmonary vein isolation alone (PVI) or pulmonary vein isolation with additional ablation (PVI‐plus). Persistent atrial fibrillation was defined as a sustained episode lasting ≥7 days and <5 years at enrollment.5 Patients with valvular atrial fibrillation (AF), left atrium ≥5 cm, heart failure, and a history of prior cardiac surgery were excluded. Patients in both groups also underwent nonpulmonary vein trigger ablation. In the PVI‐plus group, 85.1% underwent linear ablations, and 15.3% underwent complex fractionated atrial electrogram ablation.6 Patients randomized to linear lesions required at least 2 linear lesions: a roof line connecting the right and left encircling PV lesions together as well as a mitral isthmus ablation line, either an anterior line or a posterior line. Isolation of the posterior wall by adding a floor line was left to the discretion of the operators. The identification of complex fractionated atrial electrogram was performed according to an automated proprietary algorithm used in the 3‐dimensional mapping system employed for that case. The decision to perform linear lesions or target complex fractionated atrial electrogram was left to the discretion of the operator.Analysis of long‐term results demonstrated a significantly lower AF recurrence rate in patients randomly assigned to PVI‐plus and in patients who received on‐treatment PVI‐plus. The lower AF recurrence rate was seen only in patients who underwent linear ablation and not in patients where ablation targeted complex fractionated atrial electrogram. There was no difference in AF recurrence based on the type of linear ablation created. However, atrial tachycardia recurrences were more frequent in patients who underwent linear ablation and were mostly macroreentrant (89%) and iatrogenic due to gaps in linear ablation (62%), the remaining were focal.On balance, the authors concluded that patients with persistent AF had a better outcome with PVI and linear ablation. They do caution that the risk of iatrogenic atrial tachycardia should prompt the operator to consider an individualized approach and cite several studies targeting low‐voltage areas. The authors attribute the better outcomes in their study to the durability of the PVI and linear lesions seen in their repeat ablation cases, attributed to the use of contact force sensing ablation catheters and employing strict criteria to determine block across linear ablation. The limitations of the study were identified: methods for determining recurrences, the lack of a uniform ablation strategy to address recurrences, and not including unmappable atrial tachycardia recurrences in the analysis of results.In a recently published study addressing the suboptimal outcomes of ablation in persistent atrial fibrillation, the ERASE‐AF (Low‐Voltage Myocardium‐Guided Ablation Trial of Persistent Atrial Fibrillation) randomized 324 patients into a PVI onlyversus a PVI+substrate modification targeting areas of left atrial myocardial low‐voltage using a threshold of 0.5 mV.7 The 12‐month risk of recurrence of AF was significantly lower in patients randomized to PVI+substrate modification. Patients with low‐voltage myocardium who underwent PVI alone had the highest risk of AF recurrence (63%) whereas patients with low‐voltage myocardium who underwent PVI+substrate modification had an AF recurrence rate similar to that of patients with no low‐voltage myocardium who underwent PVI alone. Patients who underwent PVI+substrate modification had a trend for higher adverse events, mainly vascular.The EARNEST‐PVI and the ERASE‐AF studies seem to indicate that modification of the left atrium by creating linear lesions or homogenizing scar tissue, not unlike ablation for ventricular tachycardia in the setting of scar tissue, can yield favorable results. This assumption has to be reconciled with the recent finding from the DECAAF II (Efficacy of Delayed Enhancement MRI‐Guided Ablation Vs Conventional Catheter Ablation of Atrial Fibrillation) trial, which failed to demonstrate that targeting left atrial scar defined by magnetic resonance imaging, in addition to PVI, lowers the recurrence rate of AF when compared with PVI alone.8 The EARNEST‐PVI trial is one of a few emerging trials that not only herald an improvement in the outcomes of patients with persistent AF undergoing ablation but also shed light on the pathophysiology of persistent atrial fibrillation.DisclosuresNone.Footnotes*Correspondence to: Munther Homoud, MD, FACP, FACC, FHRS, Section of Pacing and Electrophysiology, Tufts Medical Center, 800 Washington St., Boston, MA 02111. Email: mhomoud@tuftsmedicalcenter.orgThis article was sent to Kevin F. Kwaku, MD, PhD, Associate Editor, for editorial decision and final disposition.See Editorial by Masuda et al.For Disclosures, see page 2.References1 Hindricks G, Potpara T, Dagres N, Arbelo E, Bax JJ, Blomström‐Lundqvist C, Boriani G, Castella M, Dan GA, Dilaveris PE, 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. Eur Heart J. 2021; 42:373–498. doi: 10.1093/eurheartj/ehaa612CrossrefMedlineGoogle Scholar2 Verma A, Jiang CY, Betts TR, Chen J, Deisenhofer I, Mantovan R, Macle L, Morillo CA, Haverkamp W, Rukshen R, et al. Approaches to catheter ablation for persistent atrial fibrillation. N Engl J Med. 2015; 372:1812–1822. doi: 10.1056/NEJMoa1408288CrossrefMedlineGoogle Scholar3 Obeid MJ, Zhou J, Sale AJ, Longacre C, Zeitler EP, Andrade J, Mittal S, Piccini JP. Early mortality after inpatient versus outpatient catheter ablation in patients with atrial fibrillation. Heart Rhythm. 2023; 20:833–841. doi: 10.1016/j.hrthm.2023.02.016CrossrefMedlineGoogle Scholar4 Masuda M, Inoue K, Tanaka N, Watanabe T, Makino N, Egami Y, Oka T, Minamiguchi H, Miyoshi M, Okada M, et al. Long‐term impact of additional ablation after pulmonary vein isolation: results from EARNEST‐PVI trial. J Am Heart Assoc. 2023; 12:e029651. doi: 10.1161/JAHA.123.029651LinkGoogle Scholar5 Dohi T, Nakatani D, Inoue K, Hikoso S, Oka T, Hayashi K, Masuda M, Furukawa Y, Kawasaki M, Egami Y, et al. Effect of Extensive Ablation on Recurrence in Patients with Persistent Atrial Fibrillation Treated with Pulmonary Vein Isolation (EARNEST‐PVI) trial: design and rationale. J Cardiol. 2019; 74:164–168. doi: 10.1016/j.jjcc.2019.01.010CrossrefMedlineGoogle Scholar6 Inoue K, Hikoso S, Masuda M, Furukawa Y, Hirata A, Egami Y, Watanabe T, Minamiguchi H, Miyoshi M, Tanaka N, et al. Pulmonary vein isolation alone vs. more extensive ablation with defragmentation and linear ablation of persistent atrial fibrillation: the EARNEST‐PVI trial. Europace. 2021; 23:565–574. doi: 10.1093/europace/euaa293CrossrefMedlineGoogle Scholar7 Huo Y, Gaspar T, Schönbauer R, Wójcik M, Fiedler L, Roithinger FX, Martinek M, Piorkowski C. Low‐voltage myocardium‐guided ablation trial of persistent atrial fibrillation. NEJM Evid. 2022; 1:1–10. doi: 10.1056/EVIDoa2200141CrossrefGoogle Scholar8 Marrouche NF, Wazni O, McGann C, Greene T, Dean JM, Dagher L, Kholmovski E, Mansour M, Marchlinski F, Wilber D, et al. Effect of MRI‐guided fibrosis ablation vs conventional catheter ablation on atrial arrhythmia recurrence in patients with persistent atrial fibrillation: the DECAAF II randomized clinical trial. JAMA. 2022; 327:2296–2305. doi: 10.1001/jama.2022.8831.5CrossrefMedlineGoogle Scholar eLetters(0)eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.Sign In to Submit a Response to This Article Previous Back to top Next FiguresReferencesRelatedDetailsRelated articlesLong‐Term Impact of Additional Ablation After Pulmonary Vein Isolation: Results From EARNEST‐PVI TrialMasaharu Masuda, et al. Journal of the American Heart Association. 2023;12 September 5, 2023Vol 12, Issue 17 Article InformationMetrics Copyright © 2023 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley BlackwellThis is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.https://doi.org/10.1161/JAHA.123.031258PMID: 37642025 Manuscript receivedJune 24, 2023Manuscript acceptedJune 30, 2023Originally publishedAugust 29, 2023 Keywordsleft atrial ablationpersistent atrial fibrillationrecurrenceEditorialslinear ablationPDF download SubjectsAtrial Fibrillation

Introduction: Interatrial block (IAB) from disruption of conduction through Bachmann’s bundle results in atrial electromechanical dysfunction. Delay in conduction and alteration in the pattern of atrial activation causes P-wave lengthening (≥120 ms) and characteristic biphasic P-waves in the inferior ECG leads. IAB has been associated with atrial arrhythmia and risk of stroke. Generally, the anatomic substrate for IAB is a fibrotic atrial myopathy; however, intertrial masses have also been associated with IAB. Lipomatous hypertrophy of the interatrial septum (LHIS) constitutes an anatomical barrier that could similarly lead to IAB. Hypothesis: The presence of LHIS is associated with an increased prevalence of IAB. Methods: A query of the echocardiography database at our institution from 2017 to present revealed 312 subjects with LHIS. Data collection included demographic characteristics, ECG and echocardiographic parameters. Prevalence of IAB and associated clinical variables were assessed. Results: The mean age was 72 years (56% male). In the total group IAB was present in 131 patients (42%). Comparison between the group with IAB versus without IAB was notable for a higher prevalence of stroke in those with IAB (24 subjects versus 16; p value = 0.013). The prevalence of atrial fibrillation was not statistically different between the two groups, but atrial flutter was noted to be more prevalent in those with IAB (16 subjects vs 9; p value = 0.018). Hypertension and male sex were also associated with IAB. Conclusions: Subjects with LHIS have a high prevalence of IAB, likely consequent to localized disruption in conduction through Bachmann’s bundle. We demonstrate a higher prevalence of atrial flutter and stroke in those with LHIS and IAB. These results highlight the importance of LHIS as a potential cause of IAB that can contribute to atrial structural remodeling and electromechanical dysfunction associated with atrial arrhythmia and stroke.

Hypertrophic cardiomyopathy (HCM) is a common inherited cardiovascular disorder affecting 1 in 500 people in the general population. Characterized by asymmetric left ventricular hypertrophy, cardiomyocyte disarray and cardiac fibrosis, HCM is a highly complex disease with heterogenous clinical presentation. While mutations in sarcomere genes can account for a substantial proportion of familial cases, 40-50% of HCM patients do not carry such sarcomere variants and the causal mutations for their diseases remain elusive. Recently, we identified a novel variant of the alpha-crystallin B chain (CRYAB R123W ) in a pair of homozygotic twins who developed concordant HCM phenotypes that manifested over a nearly identical time course. Yet, how CRYAB R123W promotes HCM phenotype remains unclear. Here, we generated mice carrying the Cryab R123W -knockin allele and demonstrated that hearts from these animals exhibit increased maximal elastance, reduced diastolic function and are more susceptible to ventricular tachycardia with programmed stimulation. Upon transverse aortic constriction, mice carrying the Cryab R123W allele developed pathogenic left ventricular hypertrophy with substantial cardiac fibrosis and progressively decreased ejection fraction. In contrast to another well-characterized CRYAB variant (R120G) which induced Desmin aggregation, no evidence of protein aggregation was observed in hearts expressing CRYAB R123W despite its potent effect on driving cellular hypertrophy. Unexpectedly, CRYAB R123W appears to enhance calcium signaling by promoting nuclear localization of NFAT through direct interaction with calcineurin. Studies on isolated adult cardiomyocytes reveal altered fractional shortening, calcium dyshomeostasis, prolonged action potential duration, and T-wave alternans. Crossing of CRYAB R123W mice with a mybpc3 knock-in model of HCM did not potentiate pathological hypertrophy in compound heterozygotes, indicating that the pathological mechanisms in this model are independent of the sarcomere. Thus, our data establish the Cryab R123W allele as a novel genetic model of HCM that potentially unveils additional sarcomere-independent mechanisms of cardiac pathological hypertrophy and sudden cardiac death.