John deHeide Contem poraryClinicalPractice in Electrophysiology Focuson com plicationsand post-dischargee-Health
Contemporary Clinical Practice in Electrophysiology: Focus on complications and post-discharge e-Health Hedendaagse klinische praktijk in de elektrofysiologie: Focus op complicaties en e-Health na ontslag John de Heide
COLOFON ISBN 978-94-6506-734-6 Design / layout John de Heide Printing Ridderprint, www.ridderprint.nl © 2025 John de Heide, Vlaardingen, the Netherlands All rights are reserved. No part of this book may be reproduced, distributed, stored in a retrieval system, used for training generative AI tools or transmitted in any form or by any means, without prior written permission of the author.
Contemporary Clinical Practice in Electrophysiology Focus on complications and post-discharge e-Health Hedendaagse klinische praktijk in de elektrofysiologie: Focus op complicaties en e-Health na ontslag Proefschrift ter verkrijging van de graad van doctor aan de Erasmus Universiteit Rotterdam op gezag van de rector magnificus Prof. dr. ir. A.J. Schuit volgens besluit van het College voor Promoties. De openbare verdediging zal plaatsvinden op op woensdag 5 februari 2025 om 15.30 uur door John de Heide geboren te Vlaardingen.
PROMOTIECOMMISSIE Promotor: Prof. dr. F. Zijlstra Overige leden: Prof. dr. J.W. Roos-Hesselink Dr. O.C. Manintveld Prof. dr. R.E. Knops Copromotoren: Dr. S.C. Yap Dr. M.J. Lenzen Financial support by the Dutch Heart Foundation for the publication of this thesis is gratefully acknowledged. Financial support by the Dutch Society of Cardiovascular Nursing (NVHVV) for the publication of this thesis is gratefully acknowledged.
5 TABLE OF CONTENTS CHAPTER 1 General introduction and outline of the thesis Part I: Evaluation of complications in atrial fibrillation management CHAPTER 2 Efficacy and safety of direct oral anticoagulants in patients undergoing elective electrical cardioversion: A real-world patient population International Journal of Cardiology 2021;326:98-102 (first author) CHAPTER 3 Minimally interrupted novel oral anticoagulant versus uninterrupted vitamin K antagonist during atrial fibrillation ablation Journal of Interventional Cardiac Electrophysiology 2018;53:3416 (first author) CHAPTER 4 Impact of undiagnosed obstructive sleep apnea on atrial fibrillation recurrence following catheter ablation IJC Heart&Vasculature 2022;40:101014 (first author) EDITORIAL Undiagnosed sleep apnea in patients with atrial fibrillation: an underutilized opportunity for antiarrhythmic management IJC Heart&Vasculature 2022;40:101050 Part II: Evaluation of complications in device therapy CHAPTER 5 Pocket hematoma after pacemaker or defibrillator surgery: Direct oral anticoagulants versus vitamin K antagonists IJC Heart&Vasculature 2022;39:101005 (first author) CHAPTER 6 Device infection in patients undergoing pacemaker or defibrillator surgery: risk stratification using the PADIT-score Journal of Interventional Cardiac Electrophysiology 2024 (first author) CHAPTER 7 Efficacy and safety of transvenous lead extraction using a liberal combined superior and femoral approach Journal of Interventional Cardiac Electrophysiology 2021;62:23948 (fifth author)
6 Part III: Patient empowerment: Use of eHealth as discharge aid CHAPTER 8 A quality improvement initiative for patient knowledge comprehension during the discharge procedure using a novel computer-generated patient-tailored discharge document in cardiology Digital Health 2022 (second author) CHAPTER 9 Get the picture. A Pilot Feasibility Study of Telemedical Wound Assessment Using a Mobile Phone in Cardiology Patients Journal of Cardiovascular Nursing 2017;32:E9-15 (first author) Epilogue CHAPTER 10 Summary and general discussion Dutch summary | Nederlandse samenvatting German summary | Zusammenfassung in Deutsch CHAPTER 11 List of publications CHAPTER 12 PhD portfolio CHAPTER 13 About the author | Curriculum Vitae CHAPTER 14 Acknowledgement | Dankwoord
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General introduction 9 Cardiac electrophysiology is a rapidly evolving subspecialty of cardiology. Its main focus is to treat cardiac arrhythmias and prevent sudden cardiac death. Within the Erasmus MC there is a dedicated team of cardiac electrophysiologists, fellows, nurse practitioners, nurses, technicians and researchers who are actively involved in the care and cure of patients with a heart rhythm disorder. Over the last decades the treatment of heart rhythm disorders has evolved from exclusive anti-arrhythmic drug therapy to a broad spectrum of invasive and noninvasive therapies. The invasive treatment arsenal includes pacemakers, implantable cardioverter-defibrillators (ICDs), and catheter ablation of cardiac arrhythmias (1). Furthermore, patient centred care with emphasis on shared decision making has entered the clinical arena. Currently, there is an enhanced emphasis on risk factor management, which inherently optimizes therapy outcomes and as such is the underlying principle of this thesis. 1.1 Evaluation of complications in atrial fibrillation Atrial fibrillation (AF) is a supraventricular tachyarrhythmia with uncoordinated atrial electrical activation (2). It is the most common cardiac arrhythmia in adults and constitutes a significant burden to patients, communal health and health economy. The lifetime risk of AF in Europe is as high as 40% (2). In 2021 approximately 123,400 newly diagnosed AF cases were documented in the Netherlands (3). In recent years a paradigm shift in the management of AF was observed with a change from prescribing anti-arrhythmic drugs and electrical cardioversions (ECVs) to comprehensive AF care (1). Comprehensive AF care includes a focus on patient engagement, participation, and shared decision making in a treatment plan and involves a combination of lifestyle management, risk factor management, antiarrhythmic drugs, ECV and AF catheter ablation (1). Currently, the first aim is to improve lifestyle management and initiate a more aggressive risk factor management. Secondly, a choice will be made between rate or rhythm control depending on patient preferences, symptoms, comorbidity, and anticipated benefits and risks of invasive catheter ablation. Rate control is achieved using atrioventricular blocking agents (i.e., betablockers, digoxin, verapamil) or a “pace and ablate” strategy. Rhythm control is achieved using a combination of anti-arrhythmic drugs, ECVs, and AF catheter ablation. Inherent to every medical procedure, there are 1
Chapter 1 10 certain risks associated with electrophysiology procedures. Both ECVs and AF catheter ablation can be associated with the risk of bleeding and thrombo-embolic events (2, 4, 5). For example, AF catheter ablation requires the introduction of catheters in the left atrium. This introduces the risk of air emboli or blood clots resulting in cerebral lesions. Furthermore, vascular access complications and cardiac perforation can occur in patients who are fully anticoagulated. In addition, AF in itself is associated with an elevated risk of ischemic stroke. Preventing the risk of an ischemic stroke usually implies the use of oral anticoagulation, which in turn induces a higher risk of bleeding. In recent years, the use of anticoagulation has shifted from the use of vitamin K anticoagulants (VKAs) to direct oral anticoagulants (DOACs). Several large randomized studies (RE-LY, ROCKET-AF, ARISTOTLE and ENGAGE AF-TIMI) have demonstrated that DOACs have a more favourable risk-benefit profile regarding stroke, intracranial haemorrhage, and mortality (6). Consequently, the use of DOACs has increased considerably over recent years. In the Netherlands there was a slow uptake of its use before 2016, due to limited clinical experience and data on peri-procedural efficacy and safety, lack of an antidote, combined with a lack of reimbursement for patients with AF (7, 8). Since 2016 there was a clear shift from the use of VKA to DOAC in AF patients. This was also observed in the patients who presented for an ECV or AF ablation. In this thesis we evaluated the impact of the increased use of DOACs in our AF population. To improve the outcome of AF ablation, there should not only be a focus on improved technologies. Addressing modifiable risk factors is equally important. A potentially modifiable risk factor for AF is sleep apnoea, and shares the same risk factors, such as overweight and hypertension (1, 9, 10). This may be mitigated by lifestyle management such as losing weight and exercise. Preferably lifestyle management and treatment of sleep apnoea should be initiated before catheter ablation, as it can improve outcome (2). Importantly, sleep apnoea is not easily recognized and may thus be undertreated. In this thesis we evaluated the effect of undiagnosed sleep apnoea on the outcome of AF ablation.
General introduction 11 1.2 Evaluation of complication rates in device therapy Cardiac implantable electronic devices (CIED) are used to treat impulse and conduction abnormalities, ventricular arrhythmias and heart failure. CIEDs include pacemakers, ICDs, cardiac resynchronization therapy (CRT). Furthermore, diagnostic CIEDs like implantable loop recorders are used to detect the cause of unexplained syncope. Many new innovations have been introduced in the past decade and include subcutaneous ICDs, leadless pacemakers, and conduction system pacing to achieve CRT (11, 12). Growing numbers of pacemaker and ICD implantations can be observed due to increasing life expectancy and growing age of the population (11, 12). This can also be observed in the Netherlands, with 14,570 pacemaker interventions in 2022. However, the number of ICD interventions has remained stable with 5,664 ICD interventions in 2022, with up to 40% for secondary prevention (13). The indications for a pacemaker most commonly are sinus node dysfunction and high-degree atrioventricular block. Over 80% of implanted pacemakers are in patients >65 years of age. An ICD is usually indicated in patients for secondary prevention of sudden cardiac death, or for primary prevention in heart failure patients with a left ventricular ejection fraction of ≤35% (12). Finally, CRT therapy is indicated in patients with chronic heart failure with severe LV dysfunction and left bundle branch block (LBBB). By correcting the electromechanical desynchrony caused by LBBB, positive LV remodelling is possible. This has resulted in significant improvement in morbidity and mortality in patients with heart failure and LBBB (11). Both pacemakers and ICDs are considered low-risk procedures, but unfortunately are still associated with complications such as bleeding, infection and lead dislocation (11, 12). To minimize risks, preventive measures such as antibiotics prophylaxis, experienced and certified staff, sterile environment, periprocedural haemostatic agents, antibacterial envelopes and post-procedural pressure bandages are essential (14). Prevention of pocket hematoma is important and this also requires meticulous attention to modifiable risk factors, including older age, renal failure, congestive heart failure, low operator experience, concomitant antiplatelet therapy, device replacement, lead revision, and heparin bridging (15, 16). Periprocedural oral anticoagulation is associated with a higher likelihood for pocket hematoma (17). 1
Chapter 1 12 Discontinuing DOACs 24–48 h before surgery depending on their renal function, or targeting an international normalized ratio of 2.0 to 2.5, and avoiding heparin bridging were important changes in anticoagulation regimen over the last decade (2013-2023) (18). The increased use of DOACs may have further influenced the risk profile in CIED procedures in our center. In this thesis we evaluated this change in anticoagulation regimen for CIED related surgery in our patient population. Another key complication is the risk of a pocket infection. It is associated with increased mortality risk and substantial morbidity (19, 20). A pocket infection may necessitate device and lead extraction to prevent endocarditis, which leads to higher costs, a higher risk profile and a significant burden to the patient. In reducing the risk of infections the use of antibiotic prophylaxis, chlorhexidine skin preparation, delaying the procedure in case of fever, avoidance of heparin bridging, avoidance of pocket hematoma, the use of strict sterile techniques, and having experienced operators are important preventive measures (21). Antibacterial envelopes may be used in highrisk patients. However, they are associated with high costs (22). Currently, there is no reimbursement for the antibacterial envelope in the Netherlands. Risk stratification with risk score calculators can be useful in identifying these high-risk patients (2325). The identification of patients may be aided using risk calculators such as the PADIT (Prevention of Arrhythmia Device Infection Trial)-score (26, 27). In this thesis we evaluated the usefulness of the PADIT score in clinical practice. 1.3 Patient empowerment: Use of eHealth as discharge aid Finally, in this thesis we would like to address the importance of involving the patient in his or her treatment strategy. Patient centred care models encourage shared decision-making between patients and healthcare providers (1, 28). Patient empowerment may be impacted by knowledge about early recognition of possible complications. Patients who are engaged in their care are more likely to adhere therapy, helping identification of irregularities or complications promptly (28). Health literacy and disease self-management can benefit from eHealth applications (29, 30). In this thesis we evaluated a computer generated personalized discharge letter as a discharge aid in comparison to the standard discharge information. As a result of advances in therapy and changes in care pathways a reduction in (re)hospitalizations was observed in the Erasmus MC. The Erasmus MC, being a
General introduction 13 tertiary referral hospital, has a wider adherence area than other hospitals and referred patients are at risk for a gap in their follow-up. Use of eHealth may facilitate a reduction of patient time spent in clinical assessments, and reduced travel times (31). Early recognition of complications may also be possible using telemedicine. In our clinical practice we offer teleconsultation for our patients until their first outpatient clinic visit. In this thesis we evaluated the feasibility of patient initiated mobile phone photography in assessing a possible complication. 1.4 Aims and outline of this thesis This thesis has two aims: First, to focus on various strategies on reducing complication rates in electrophysiology procedures (part I and II). Secondly, to improve patient empowerment via the use of eHealth innovations with a focus on prevention, identifying and early reduction of complications (part III). In the first part of this thesis (chapters 2 - 4) the focus will be on evaluating the complication rates in ECV and catheter ablation of AF in the Erasmus MC after changes in anticoagulant regimen, but also identifying the proportion of patients with sleep apnoea after catheter ablation of AF. The second part of this thesis (chapters 5 - 7) focuses on evaluating the complication rates in device therapy. We focused on identifying complication rates in CIED therapy. We explored thromboembolic and bleeding complications in CIED related surgery procedures, being implantation, device change or upgrade, but also in a novel lead extraction technique. Furthermore, we evaluated the use of the PADIT score in identifying patients at risk for infection. In the third part of this thesis (chapters 8 and 9), the development of an eHealth and mHealth intervention by the nurse practitioner as a discharge aid in our center is being explored. Both interventions may have furthered patient participation and empowerment. Finally, in chapter 10, the main results of the previous chapters are integrated and interpreted in the summary and final discussion focusing on the clinical implications of the presented studies and directions for future research. 1
Chapter 1 14 References 1. Hendriks JM, Gallagher C, Middeldorp ME, Lau DH, Sanders P. Risk factor management and atrial fibrillation. Europace. 2021;23(23 Suppl 2):ii52-ii60. 2. 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. 3. VZinfo.nl. Hart- en vaatziekten | Leeftijd en geslacht. In: RIVM, editor. Den Haag: Ministerie van Volksgezondheid, Welzijn en Sport ( VWS (Ministerie van Volksgezondheid, Welzijn en Sport)); 2022. 4. Hansen ML, Jepsen RM, Olesen JB, Ruwald MH, Karasoy D, Gislason GH, et al. Thromboembolic risk in 16 274 atrial fibrillation patients undergoing direct current cardioversion with and without oral anticoagulant therapy. Europace. 2015;17(1):18-23. 5. Ghzally Y AI, Gerasimon G. Catheter Ablation. Treasure Island (FL): StatPearls Publishing; 2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470203/. 6. Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet. 2014;383(9921):955-62. 7. ten Cate V, ten Cate H, Verheugt FWA. The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF). Netherlands Heart Journal. 2016;24(10):574-80. 8. NVVC. Richtlijn Antitrombotisch beleid. Federatie Medisch Specialisten2016. 9. Ariyaratnam JP, Middeldorp M, Thomas G, Noubiap JJ, Lau D, Sanders P. Risk Factor Management Before and After Atrial Fibrillation Ablation. Card Electrophysiol Clin. 2020;12(2):141-54. 10. Pathak RK, Middeldorp ME, Meredith M, Mehta AB, Mahajan R, Wong CX, et al. Long-Term Effect of Goal-Directed Weight Management in an Atrial Fibrillation Cohort: A Long-Term Follow-Up Study (LEGACY). J Am Coll Cardiol. 2015;65(20):2159-69. 11. Glikson M, Nielsen JC, Kronborg MB, Michowitz Y, Auricchio A, Barbash IM, et al. 2021 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy: Developed by the Task Force on cardiac pacing and cardiac resynchronization therapy of the European Society of Cardiology (ESC) With the special contribution of the European Heart Rhythm Association (EHRA). EP Europace. 2021;24(1):71-164. 12. Zeppenfeld K, Tfelt-Hansen J, de Riva M, Winkel BG, Behr ER, Blom NA, et al. 2022 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: Developed by 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 the Association for European Paediatric and Congenital Cardiology (AEPC). European Heart Journal. 2022;43(40):3997-4126. 13. NHR H. Jaarcijfers pacemaker en ICD. Den Haag: Hartstichting & NHR; 2023. 14. Blomstrom-Lundqvist C, Traykov V, Erba PA, Burri H, Nielsen JC, Bongiorni MG, et al. European Heart Rhythm Association (EHRA) international consensus document on how to prevent, diagnose, and treat cardiac implantable electronic device infections-endorsed by the Heart Rhythm Society (HRS), the Asia Pacific Heart Rhythm Society (APHRS), the Latin American Heart Rhythm Society (LAHRS), International Society for Cardiovascular Infectious Diseases (ISCVID), and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2020;41(21):2012-32. 15. Birnie DH, Healey JS, Wells GA, Verma A, Tang AS, Krahn AD, et al. Pacemaker or defibrillator surgery without interruption of anticoagulation. N Engl J Med. 2013;368(22):2084-93. 16. Ahmed I, Gertner E, Nelson WB, House CM, Zhu DW. Chronic kidney disease is an independent predictor of pocket hematoma after pacemaker and defibrillator implantation. J Interv Card Electrophysiol. 2010;29(3):203-7.
General introduction 15 17. Ferretto S, Mattesi G, Migliore F, Susana A, De Lazzari M, Iliceto S, et al. Clinical predictors of pocket hematoma after cardiac device implantation and replacement. J Cardiovasc Med (Hagerstown). 2020;21(2):123-7. 18. Birnie DH, Healey JS, Wells GA, Ayala-Paredes F, Coutu B, Sumner GL, et al. Continued vs. interrupted direct oral anticoagulants at the time of device surgery, in patients with moderate to high risk of arterial thrombo-embolic events (BRUISE CONTROL-2). European Heart Journal. 2018;39(44):3973-9. 19. Ahsan SY, Saberwal B, Lambiase PD, Koo CY, Lee S, Gopalamurugan AB, et al. A simple infection-control protocol to reduce serious cardiac device infections. Europace. 2014;16(10):1482-9. 20. Brough CEP, Rao A, Haycox AR, Cowie MR, Wright DJ. Real-world costs of transvenous lead extraction: the challenge for reimbursement. Europace. 2019;21(2):290-7. 21. Blomström-Lundqvist C, Traykov V, Erba PA, Burri H, Nielsen JC, Bongiorni MG, et al. European Heart Rhythm Association (EHRA) international consensus document on how to prevent, diagnose, and treat cardiac implantable electronic device infections-endorsed by the Heart Rhythm Society (HRS), the Asia Pacific Heart Rhythm Society (APHRS), the Latin American Heart Rhythm Society (LAHRS), International Society for Cardiovascular Infectious Diseases (ISCVID) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Eur J Cardiothorac Surg. 2020;57(1):e1-e31. 22. Wilkoff BL, Boriani G, Mittal S, Poole JE, Kennergren C, Corey GR, et al. Cost-Effectiveness of an Antibacterial Envelope for Cardiac Implantable Electronic Device Infection Prevention in the US Healthcare System From the WRAP-IT Trial. Circ Arrhythm Electrophysiol. 2020;13(10):e008503. 23. Birnie DH, Wang J, Alings M, Philippon F, Parkash R, Manlucu J, et al. Risk Factors for Infections Involving Cardiac Implanted Electronic Devices. Journal of the American College of Cardiology. 2019;74(23):2845-54. 24. Mittal S, Shaw RE, Michel K, Palekar R, Arshad A, Musat D, et al. Cardiac implantable electronic device infections: incidence, risk factors, and the effect of the AigisRx antibacterial envelope. Heart Rhythm. 2014;11(4):595-601. 25. Shariff N, Eby E, Adelstein E, Jain S, Shalaby A, Saba S, et al. Health and economic outcomes associated with use of an antimicrobial envelope as a standard of care for cardiac implantable electronic device implantation. Journal of cardiovascular electrophysiology. 2015;26(7):783-9. 26. Birnie DH, Wang J, Alings M, Philippon F, Parkash R, Manlucu J, et al. Risk Factors for Infections Involving Cardiac Implanted Electronic Devices. J Am Coll Cardiol. 2019;74(23):2845-54. 27. Correction. J Am Coll Cardiol. 2020;76(6):762. 28. Barry MJ, Edgman-Levitan S. Shared decision making—The pinnacle patient-centered care. 2012. 29. Arsad FS, Soffian SSS, Kamaruddin PSNM, Nordin NR, Baharudin MH, Baharudin UM, et al. The impact of eHealth applications in healthcare intervention: a systematic review. J Health Res. 2023;37. 30. Leclercq C, Witt H, Hindricks G, Katra RP, Albert D, Belliger A, et al. Wearables, telemedicine, and artificial intelligence in arrhythmias and heart failure: Proceedings of the European Society of Cardiology Cardiovascular Round Table EP Europace. 2022;24(9):1372-83. 31. Giacalone A, Marin L, Febbi M, Franchi T, Tovani-Palone MR. eHealth, telehealth, and telemedicine in the management of the COVID-19 pandemic and beyond: Lessons learned and future perspectives. World J Clin Cases. 2022;10(8):2363-8. 1
19 CHAPTER 2 Efficacy and safety of direct oral anticoagulants in patients undergoing elective electrical cardioversion: A real-world patient population John de Heide, André de Wit, Rohit E. Bhagwandien, Amira Assaf, Jaleesa GrosBisdom, Koen C. van der Meer, Sip A. Wijchers, Felix Zijlstra, Tamas Szili-Torok, Mattie J. Lenzen, Sing-Chien Yap The Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands International Journal of Cardiology, March 2021, Volume 326, p. 98–102, https://doi.org/10.1016/j.ijcard.2020.10.070
Chapter 2 20 Abstract Background: Direct oral anticoagulants (DOACs) have emerged as the preferred choice of oral anticoagulation in patients with atrial fibrillation. Randomized trials have demonstrated the efficacy and safety of DOAC in patients undergoing electrical cardioversion (ECV); however, there is limited real-world data. Objective: To evaluate the outcome of patients undergoing an elective ECV for atrial tachyarrhythmia in a tertiary referral center who were treated with DOAC or vitamin K antagonist (VKA) without routine trans oesophageal echocardiography (TEE). Methods: This was a retrospective single-center cohort study of consecutive patients undergoing an elective ECV for atrial tachyarrhythmia from January 2013 to February 2020. The primary endpoints were thromboembolism (composite of stroke, transient ischemic attack or systemic embolism) and major bleeding events within 60 days. Results: A total of 1431 ECV procedures were performed in 920 patients. One-third of the procedures were performed under DOAC (N=488, 34%) and the remainder of the procedures was performed under VKA (N=943, 66%). There were no differences between groups with regard to demographic variables (mean age 62.4±11.7, 72% men) and mean CHA2DS2-VASc score (2.3±1.6); however, the VKA group had a higher proportion of patients with co-morbidity. Thromboembolism occurred in 0.41% in the DOAC group versus 0.64% in the VKA group (P=0.72). Major bleeding events occurred in 0.41% in the DOAC group versus 0.11% in the VKA group (P=0.27). Conclusion: In a real-world population, the rates of thromboembolism and major bleeding events were low after elective ECV in patients using DOAC or VKA, even without routine TEE.
DOACs in elective electrical cardioversion 21 1. Introduction Direct oral anticoagulants (DOACs) are currently the preferred choice of oral anticoagulation in patients with atrial fibrillation (AF) for long-term stroke prevention (1). Electrical cardioversion (ECV) play an important role in a rhythm control strategy, therefore it is not surprising that many patients undergoing ECV are treated with a DOAC. For patients with AF of >48 hours duration, it is recommended to use therapeutic oral anticoagulation at least 3 weeks before and 4 weeks after ECV (2). An advantage of DOAC is that therapeutic oral anticoagulation can be achieved rapidly, which is especially relevant for anticoagulation naïve patients. However, it is important to ensure adherence to the DOAC intake, as there is no coagulation assay available providing information on effective anticoagulation over the past 3 weeks. Post-hoc subgroup analysis from large phase 3 stroke prevention trials have shown a good safety profile of DOACs pericardioversion with a thromboembolic risk of <1% (3-6). Furthermore, prospective randomized controlled trials (RCTs) in patients requiring elective ECV demonstrated low and similar thromboembolic and bleeding rates when comparing factor Xa inhibitors to vitamin K antagonists (VKA) (7-9). It is important to note that all RCTs were not powered to demonstrate noninferiority. In addition, the majority (>50%) of patients in the RCTs underwent transoesophageal echocardiography (TEE) to guide cardioversion, which is not routine practice in many centers. There is limited real-world data of DOACs in patients undergoing elective ECV outside the scope of highly controlled RCT (10-18). The availability of real-world data is important as it reflects actual clinical practice. For example, in many centers it is not common practice to have a preprocedural TEE before an elective ECV. We evaluated the efficacy and safety of DOACs versus VKA in patients undergoing elective ECV for atrial tachyarrhythmia in a large tertiary referral center without routine preprocedural TEE. 2
Chapter 2 22 2. Methods 2.1 Study cohort We retrospectively evaluated all consecutive adult patients who underwent an elective ECV for sustained atrial tachyarrhythmia (>48 hours) from January 2013 to February 2020 at the department of Cardiology of the Erasmus MC, University Medical Center Rotterdam, the Netherlands. Atrial tachyarrhythmias comprised atrial fibrillation, atrial flutter and atrial tachycardia. Patients who had an emergency ECV or received an ECV for an atrial tachyarrhythmia with a duration <48 hours were not included in the study. Patients were identified by screening all scheduled ECV procedures in the study period. If the patient did not undergo an ECV for any reason, then this patient was excluded from the final analysis. Furthermore, patients who had <60 days of follow-up after the procedure, except when death occurred, were excluded. Data were collected from the electronic medical records. 2.2 Anticoagulation regimen All patients required therapeutic oral anticoagulation for at least 3 weeks prior to ECV. In patients using VKA, the International Normalized Ratio (INR) level had to be in the therapeutic range (≥2.0) in the 3 weeks prior to the procedure. The INR was rechecked on the day of the procedure. Patients using DOAC had to use them continuously for at least 3 weeks. Compliance was evaluated by asking the patient whether they did not miss a dose in the previous 3 weeks. If abovementioned conditions were not met, we usually postponed the procedure. If required (e.g., inadequate INR, doubt about DOAC adherence, symptom-driven), a TEE-guided ECV was performed. Thus, not all patients with an inadequate oral anticoagulation received a TEE. Patients continued their oral anticoagulation for a minimum of 4 weeks after the ECV procedure. Continuation of oral anticoagulation after this 4-week period was based on the CHADS-VASc score or other indication for oral anticoagulation (e.g., mechanical heart valves). 2.3 Electrical cardioversion Electrical cardioversion was performed in the holding area or on the ward under the supervision of a nurse practitioner or cardiologist. The procedures were performed under monitored anaesthesia care. The placement of the external patches was usually posterior-anterior. For patients in atrial fibrillation a synchronized ECV was
DOACs in elective electrical cardioversion 23 performed with a biphasic shock of 200 Joules. For patients in atrial flutter a lower dose was used (usually 100 Joules). A cardioversion was repeated when necessary. 2.4 Study endpoints The primary efficacy endpoint was a composite of stroke, transient ischemic attack (TIA), and systemic embolic event (SEE) within 60 days. The primary safety endpoint was major bleeding within 60 days. Major bleeding was defined according to the International Society of Thrombosis and Haemostasis (ISTH) criteria and included clinically overt bleeding accompanied by a decrease in the haemoglobin level of at least 20 g/L (1.24 mmol/L) or transfusion of at least 2 units of packed red cells, occurring at a critical site, or resulting in death (19). TIA and stroke were diagnosed by a neurologist. The secondary efficacy endpoints were death from any cause, stroke, TIA, SEE, and a composite of stroke and SEE (excluding TIA). 2.5 Statistical analysis Continuous parameters were tested for normality before analysis and are expressed as mean ± standard deviation (SD) or median [interquartile range], as appropriate. Categorical data are presented as frequencies and percentages. Comparisons between groups were performed with an independent Student t test, chi-square tests, Fisher exact test, or a Mann-Whitney U test, as appropriate. All analyses were twotailed; a p-value<0.05 was considered statistically significant. Statistical analyses were performed using SPSS software (SPSS, version 25; IBM, Chicago, Illinois). 2.6 Ethics The Medical Ethics Committee reviewed the study (MEC-2019-0405), and this retrospective single-center study was not subjected to the Dutch Medical Research Involving Human Subjects Act. The study was carried out according to the ethical principles for medical research involving human subjects established by Declaration of Helsinki, protecting the privacy of all the participants and the confidentiality of their personal information. 2
Chapter 2 24 3. Results 3.1 Patient population and cardioversion A total 1570 elective ECV procedures were scheduled in the study period. In 94 cases (6.0%) no ECV was performed and 45 cases (2.9%) had insufficient follow-up after an ECV (Fig. 1). Preprocedural TEE was performed in 23 patients (1.5%) and a left atrial thrombus was suspected in 5 cases resulting in postponement of the procedure (Appendix A). Final analysis was performed in the remaining 1431 ECV procedures among 920 patients. Almost two-third of the patients received one ECV procedure during the study period (n=610), while the remaining one-third received ≥2 ECV procedures (n=310). These 310 patients with multiple ECV procedures had a total of 511 repeat ECV procedures. Repeat ECV procedures were performed more often in the VKA group in comparison to the DOAC group (39% versus 28%, P<0.001). The reason for a repeat ECV was recurrence of atrial tachyarrhythmia (n=450, 88%) or a prior not successful ECV (n=61, 12%), this was similar for both groups. Periprocedural DOAC was used in 488 (34%) procedures, while in the remainder of the procedures (n=943, 66%) periprocedural VKA was used. Of the 488 cardioversions performed on DOAC, dabigatran was used in 225 of 488 procedures (46%); apixaban in 114 procedures (23%); rivaroxaban in 81 procedures (17%); and edoxaban in 68 procedures (14%). Periprocedural VKAs used were acenocoumarol (n=846) or phenprocoumon (n=97). The use of DOAC increased steadily over the years during the study period, increasing from 5% in 2013 to 73% in 2020 (Fig. 2). Since 2018, DOAC was used in more than half of the procedures. There were differences in baseline characteristics between the VKA and DOAC group (Table 1). The VKA group comprised a more complex patient population with a higher proportion of patients with congenital heart disease, congestive heart failure, coronary heart disease, diabetes mellitus, LV dysfunction and renal insufficiency. This is also reflected by a higher proportion of patients with a HAS-BLED bleeding score ≥3 and American Society of Anaesthesiologists (ASA) physical status classification system score ≥3. However, the thromboembolic risk as reflected by the mean CHA2DS2-VASc score was similar between groups. The acute cardioversion success was similar between groups (92% for both groups, P=0.70).
DOACs in elective electrical cardioversion 25 3.2 Primary endpoints In total, 8 patients (0.56%) had a thromboembolic event and 3 patients (0.21%) had an ISTH major bleeding event during the 60-day follow-up period. There were no differences in the primary efficacy and safety endpoints between both groups (Table 2). A detailed overview of endpoints is presented in Appendix B. A thromboembolic event occurred in 6 (0.64%) and 2 (0.41%) patients in the VKA and DOAC group, respectively (P=0.72). The timing of thromboembolic events was similar between groups (VKA: median 19 [10, 25] days; DOAC: 13 [4, 22] days, P=0.64). In the 8 patients with a thromboembolic event, 5 patients (63%) had a medical history of prior stroke or TIA (Appendix B). All patients with a TIA after ECV had an uneventful recovery. The patients who had experienced a stroke had a modified Rankin scale (20) ranging from 0 to 2. No SEE occurred in the study population. Major bleeding occurred in 1 (0.11%) and 2 (0.41%) patients in the VKA and DOAC group, respectively (P=0.27) (Table 2, Appendix B). One patient had a trauma-related subdural hematoma and had a modified Rankin scale of 4. The two other patients experienced a gastro-intestinal bleeding requiring blood transfusion and had an uneventful recovery. 3.3 Secondary endpoints In total, 8 patients (0.56%) died within 60 days after the ECV procedure. There were no differences in the all-cause mortality rate between both groups (Table 2, Appendix B). Also, when looking at the individual endpoints there was no difference between groups with regard to stroke, TIA or SEE. For comparison with RCTs, the composite endpoint of stroke and SEE was also presented. The 30-day rate of the composite endpoint of stroke and SEE and major bleeding after ECV was comparable to the results of the 3 RCTs focusing on the efficacy and safety of pericardioversion DOAC (Appendix C). 4. Discussion The present study demonstrates that DOACs are associated with low thromboembolic and bleeding rates (both <0.5%) in patients undergoing elective ECV for atrial tachyarrhythmia in the setting of a tertiary referral center. Furthermore, the study period was a transition time in our center where DOAC use pericardioversion increased from 5% in 2013 to 73% in 2020. 2
Chapter 2 26 In non-anticoagulated patients, ECV is associated with an increased risk of stroke (5-7%) (21). This risk is mitigated (<1%) if patients use oral anticoagulation. The 2016 ESC AF guidelines recommends the use of therapeutic oral anticoagulation at least 3 weeks before and 4 weeks after ECV (2). The use of VKA has its limitations, the most important being its narrow therapeutic window requiring regular INR assessments, delayed onset of action and certain drug-drug interactions (11, 22). Considering these limitations, DOACs has become an attractive alternative for VKA (1). In the Netherlands, there was initially a conservative policy with regard to DOAC mainly due to concerns about the lack of an antidote, patient adherence, lack of monitoring and increased health care costs (23). In the Netherlands there was a slower uptake of DOAC use in comparison to other Western European countries (24). Since 2016 there is a steady increase in the use of DOAC in the Netherlands and this is reflected in a higher proportion of patients with DOAC undergoing an elective ECV in our center in the second half of the study period. Nowadays, DOAC is the most commonly used oral anticoagulant pericardioversion. An advantage of the use of DOAC in the setting of ECV is that it can avoid delays or postponement of ECV due to inadequate INR levels with VKA (9, 11). Avoiding postponement and rescheduling of ECV procedures by using DOAC has been shown to be costeffective in comparison to VKA (25). RCTs and meta-analysis have demonstrated the safety and efficacy of DOAC in patients undergoing ECV (7-9, 26-28). Our results are in line with the outcome of the 3 RCTs focusing on pericardioversion DOAC (Appendix C). The mean CHA2DS2VASc score and the proportion of patients with moderate to high thromboembolic risk (CHA2DS2-VASc score ≥2) in our study population was comparable to the RCTs (Appendix C). These randomized trials are important, but the study populations and pre-procedural work-up do not always reflect clinical practice. For example, the EMANATE trial only included anticoagulation naïve patients (<48 hours of anticoagulation before randomization) (8). Furthermore, >50% of patients in the RCTs underwent cardiac imaging to rule out thrombus in the left atrial appendage before ECV. Previous observational studies have shown that in 1.4-3.6% of therapeutically anticoagulated patients a TEE prior to ECV or AF ablation revealed a LAA thrombus (29, 30). The incidence of LAA thrombus seems to correlate with the CHADS-VASc score (29). In many centers, however, preprocedural imaging is not standard practice. Therefore, availability of real-world studies of pericardioversion
DOACs in elective electrical cardioversion 27 DOAC is important (10-18). Of these real-world studies, 2 single-center studies had a larger sample size than our study, however, in both studies approximately one-fifth of procedures were guided by TEE (11, 17). Coleman et al. retrospectively evaluated 4,647 cardioversions in the Cleveland Clinic (USA) in the period 2009 to 2013, of which only 20% were performed under DOAC (17). The thromboembolic event rate under DOAC was relatively high, 1.62% within 8 weeks of follow-up, but this was similar to the VKA group (0.97%, P=0.16). Frederiksen et al. retrospectively evaluated 2,150 cardioversions from the Regional Hospital Central Jutland (Denmark) in the period 2011 to 2016 (11). This study showed a low thromboembolic event rate within 60 days with either DOAC or VKA (0.15% versus 0.14%). Our study also demonstrates a low thromboembolic event rate in procedures performed under DOAC and VKA in a routinely non-TEE-guided strategy. 5. Study limitations The present study has the known limitations inherent to an observational study. Selection bias may play a role, as DOAC are not used in patients with severe renal dysfunction or mechanical valves. This is partly reflected by a higher proportion of patients with comorbidity in the VKA group. Furthermore, the low event rates precluded a thorough statistical analysis between groups. 6. Conclusions During the past years, DOAC has replaced VKA as the most commonly used oral anticoagulant in patients undergoing elective ECV for atrial tachyarrhythmias. The use of pericardioversion DOAC was associated with low rates of thromboembolic and bleeding complications (both <0.5%) and was comparable to the use of VKA in a real-world population without routine TEE. 2
Chapter 2 28 References 1. J. Steffel, P. Verhamme, T.S. Potpara, et al., The 2018 European heart rhythm association practical guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation, Eur. Heart J. 39 (16) (2018) 1330–1393. 2. P. Kirchhof, S. Benussi, D. Kotecha, et al., 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS, Eur. Heart J. 37 (38) (2016) 2893–2962. 3. G. Flaker, R.D. Lopes, S.M. Al-Khatib, et al., Efficacy and safety of apixaban in patients after cardioversion for atrial fibrillation: insights from the ARISTOTLE trial (Apixaban for reduction in stroke and other thromboembolic events in atrial fibrillation), J. Am. Coll. Cardiol. 63 (11) (2014) 1082–1087. 4. R. Nagarakanti, M.D. Ezekowitz, J. Oldgren, et al., Dabigatran versus warfarin in patients with atrial fibrillation: an analysis of patients undergoing cardioversion, Circulation. 123 (2) (2011) 131–136. 5. J.P. Piccini, S.R. Stevens, Y. Lokhnygina, et al., Outcomes after cardioversion and atrial fibrillation ablation in patients treatedwith rivaroxaban andwarfarin in the ROCKET AF trial, J. Am. Coll. Cardiol. 61 (19) (2013) 1998–2006. 6. A. Plitt, M.D. Ezekowitz, R. De Caterina, et al., Cardioversion of atrial fibrillation in ENGAGE AFTIMI 48, Clin. Cardiol. 39 (6) (2016) 345–346. 7. R. Cappato, M.D. Ezekowitz, A.L. Klein, et al., Rivaroxaban vs. vitamin K antagonists for cardioversion in atrial fibrillation, Eur. Heart J. 35 (47) (2014) 3346–3355. 8. M.D. Ezekowitz, C.V. Pollack Jr., J.L. Halperin, et al., Apixaban compared to heparin/vitamin K antagonist in patients with atrial fibrillation scheduled for cardioversion: the EMANATE trial, Eur. Heart J. 39 (32) (2018) 2959–2971. 9. A. Goette, J.L. Merino, M.D. Ezekowitz, et al., Edoxaban versus enoxaparin-warfarin in patients undergoing cardioversion of atrial fibrillation (ENSURE-AF): a randomised, open-label, phase 3b trial, Lancet. 388 (10055) (2016) 1995–2003. 10. S. Itainen, M. Lehto, T. Vasankari, et al., Non-vitamin K antagonist oral anticoagulants in atrial fibrillation patients undergoing elective cardioversion, Europace. 20 (4) (2018) 565–568. 11. A.S. Frederiksen, A.E. Albertsen, A.M.S. Christesen, N. Vinter, L. Frost, D.S. Moller, Cardioversion of atrial fibrillation in a real-world setting: non-vitamin K antagonist oral anticoagulants ensure a fast and safe strategy compared to warfarin, Europace. 20 (7) (2018) 1078–1085. 12. G. Femia, T. Fetahovic, P. Shetty, A. Lee, Novel Oral anticoagulants in direct current Cardioversion for atrial fibrillation, Heart Lung Circ. 27 (7) (2018) 798–803. 13. A.K. Johansson, T. Juhlin, J. Engdahl, et al., Is one month treatment with dabigatran before cardioversion of atrial fibrillation sufficient to prevent thromboembolism? Europace. 17 (10) (2015) 1514–1517. 14. R.M. Kaplan, C.L. Diaz, T. Strzelczyk, et al., Outcomes with novel Oral anticoagulants in obese patients who underwent electrical Cardioversion for atrial Tachyarrhythmias, Am. J. Cardiol. 122 (7) (2018) 1175–1178. 15. S. Itainen-Stromberg, A.M. Hekkala, A.L. Aro, T. Vasankari, K.E.J. Airaksinen,M. Lehto, Real-life experience with non-vitamin K antagonist oral anticoagulants versus warfarin in patients undergoing elective cardioversion of atrial fibrillation, Ann. Noninvasive Electrocardiol. 25 (2020) (e12766). 16. N. Shibata, I.Morishima, K. Okumura, et al., Non-vitamin K antagonist oral anticoagulants versus warfarin for cardioversion of atrial fibrillation in clinical practice: a single-center experience, J. Arrhythm. 33 (1) (2017) 7–11. 17. C.M. Coleman, S. Khalaf, S.Mould, et al., Novel Oral anticoagulants for DC Cardioversion procedures: utilization and clinical outcomes compared with warfarin, Pacing Clin. Electrophysiol. 38 (6) (2015) 731–737. 18. S. Kochhauser, Y. Khaykin, J. Beardsall, et al., Comparison of outcomes after cardioversion or atrial fibrillation ablation in patients with differing periprocedural anticoagulation regimens, Can. J. Cardiol. 30 (12) (2014) 1541–1546. 19. S. Schulman, C. Kearon, Subcommittee on control of anticoagulation of the S, standardization Committee of the International Society on T, Haemostasis. Definition of major bleeding in clinical
DOACs in elective electrical cardioversion 29 investigations of antihemostatic medicinal products in non-surgical patients, J. Thromb. Haemost. 3 (4) (2005) 692–694. 20. J.C. van Swieten, P.J. Koudstaal, M.C. Visser, H.J. Schouten, J. van Gijn, Interobserver agreement for the assessment of handicap in stroke patients, Stroke. 19 (5) (1988) 604–607. 21. M.L. Hansen, R.M. Jepsen, J.B. Olesen, et al., Thromboembolic risk in 16 274 atrial fibrillation patients undergoing direct current cardioversion with and without oral anticoagulant therapy, Europace. 17 (1) (2015) 18–23. 22. A. Goette, H. Heidbuchel, Practical implementation of anticoagulation strategy for patients undergoing Cardioversion of atrial fibrillation, Arrhythmia Electrophysiol. Rev. 6 (2) (2017) 50–54. 23. L.A. de Jong, M. Koops, J.J. Gout-Zwart, et al., Trends in direct oral anticoagulant (DOAC) use: health benefits and patient preference, Neth. J. Med. 76 (10) (2018) 426–430. 24. V. Ten Cate, H. Ten Cate, F.W. Verheugt, The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) : Exploring the changes in anticoagulant practice in patients with nonvalvular atrial fibrillation in the Netherlands, Neth. Hear. J. 24 (10) (2016) 574–580. 25. S.H. Hohnloser, R. Cappato, M.D. Ezekowitz, et al., Patient-reported treatment satisfaction and budget impact with rivaroxaban vs. standard therapy in elective cardioversion of atrial fibrillation: a post hoc analysis of the X-VeRT trial, Europace. 18 (2) (2016) 184–190. 26. C.M. Gibson, A.N. Basto, M.L. Howard, Direct Oral anticoagulants in Cardioversion: a review of current evidence, Ann. Pharmacother. 52 (3) (2018) 277–284. 27. S.A. Di Fusco, F. Colivicchi, N. Aspromonte, M. Tubaro, A. Aiello, M. Santini, Direct oral anticoagulants in patients undergoing cardioversion: insight from randomized clinical trials, Monaldi Arch. Chest Dis. 87 (1) (2017) 805. 28. R.I. Mincu, A.A.Mahabadi,M. Totzeck, T. Rassaf, Novel anticoagulants versus vitamin K antagonists for cardioversion of non- valvular atrial fibrillation – a meta-analysis of more than 17000 patients, Sci. Rep. 9 (1) (2019) 3011. 29. E. Bertaglia, M. Anselmino, A. Zorzi, et al., NOACs and atrial fibrillation: incidence and predictors of left atrial thrombus in the real world, Int. J. Cardiol. 249 (2017) 179–183. 30. G. Stabile, V. Russo, A. Rapacciuolo, et al., Transesophageal echocardiograpy in patients with persistent atrial fibrillation undergoing electrical cardioversion on new oral anticoagulants: a multi center registry, Int. J. Cardiol. 184 (2015) 283–284. 2
Chapter 2 30 Tables Table 1. Baseline characteristics Characteristic Total n=1,431 VKA group n=943 DOAC group n=488 p-value Age (years), mean ± SD 62.4 ± 11.7 62.1 ± 11.6 62.8 ± 12.0 0.32 Male gender 1032 (72.1) 669 (70.9) 363 (74.4) 0.17 BMI, mean ± SD 28.3 ± 5.4 28.3 ± 5.5 28.3 ± 5.1 0.98 TEE 18 (1.3) 13 (1.4) 5 (1.0) 0.80 Medical history Prior TIA 111 (7.8) 71 (7.5) 40 (8.2) 0.65 Prior stroke 106 (7.4) 72 (7.6) 34 (7.0) 0.65 Prior intracranial bleeding 17 (1.2) 15 (1.6) 2 (0.4) 0.069 Prior extracranial bleeding 64 (4.5) 48 (5.1) 16 (3.3) 0.14 Arterial hypertension 612 (42.8) 402 (42.6) 210 (43.0) 0.88 Renal insufficiency* 342 (23.9) 266 (28.2) 76 (15.6) <0.001 Congestive heart failure 333 (23.3) 250 (26.5) 83 (17.0) <0.001 Coronary artery disease 323 (22.6) 239 (25.3) 84 (17.2) <0.001 LVEF ≤40% 304 (21.3) 227 (24.1) 77 (15.8) <0.001 Diabetes mellitus 209 (14.6) 151 (16.0) 58 (11.9) 0.036 Vascular disease 175 (12.2) 119 (12.6) 56 (11.5) 0.53 Congenital heart disease 114 (8.0) 90 (9.5) 24 (4.9) 0.002 Type of atrial tachyarrhythmia Atrial fibrillation 1094 (77.2) 724 (77.7) 370 (76.3) 0.55 Atrial flutter 262 (18.5) 163 (17.5) 99 (20.4) 0.18 Atrial tachycardia 61 (4.3) 45 (4.8) 16 (3.3) 0.22 Scores ASA ≥3 774 (56.3) 543 (59.2) 231 (50.4) 0.002 CHA2DS2-VASc, mean ± SD 2.3 ± 1.6 2.4 ± 1.7 2.2 ± 1.6 <0.001 CHA2DS2-VASc ≥2 935 (65.3) 625 (66.3) 310 (63.5) 0.30 HAS-BLED, mean ± SD 1.3 ± 1.1 1.4 ± 1.1 1.1 ± 1.0 <0.001 HAS-BLED ≥3 176 (12.3) 132 (14.0) 44 (9.0) 0.007 Antiplatelet therapy Acetylsalicylic acid 105 (7.3) 81 (8.6) 24 (4.9) 0.12 Clopidogrel 53 (3.7) 35 (3.7) 18 (3.7) 0.98 Persantin 2 (0.1) 2 (0.2) - 0.55 Ticagrelor 1 (0.1) 1 (0.1) - 1.00 Triple therapy 14 (1.0) 10 (1.1) 4 (0.8) 0.78 Antiarrhythmic therapy Amiodaron 356 (24.9) 271 (28.7) 85 (17.4) <0.001 Sotalol 335 (23.4) 208 (22.1) 127 (26.0) 0.093 Digoxin 286 (20.0) 210 (22.3) 76 (15.6) 0.003 Flecainide 95 (6.6) 53 (5.6) 42 (8.6) 0.031 Verapamil 30 (2.1) 24 (2.5) 6 (1.2) 0.10 Diltiazem 15 (1.0) 9 (1.0) 6 (1.2) 0.63 Propafenone 3 (0.2) 3 (0.3) - 0.56 All data depicted as n (%) unless stated otherwise. * eGFR <60 ml/min/m2. Abbreviations: ASA= American Society of Anaesthesiologists physical status classification system, DOAC = direct-acting oral anticoagulation; LVEF= left ventricular ejection fraction, TEE = transesophageal echocardiogram; VKA= vitamin K antagonist
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