Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 1.736
5-Year Impact Factor – 2.135
Index Copernicus  – 168.52
MEiN – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

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Advances in Clinical and Experimental Medicine

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doi: 10.17219/acem/157239

Publication type: review

Language: English

License: Creative Commons Attribution 3.0 Unported (CC BY 3.0)

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Wu Y, Xu H, Tu X, Gao Z. Review of the epidemiology, pathogenesis and prevention of atrial fibrillation after pacemaker implantation [published online as ahead of print on January March 6, 2023]. Adv Clin Exp Med. 2023. doi:10.17219/acem/157239

Review of the epidemiology, pathogenesis and prevention of atrial fibrillation after pacemaker implantation

Yeshun Wu1,A,B,C,D, Hongqing Xu1,A,B,C, Xiaoming Tu1,E, Zhenyan Gao1,E,F

1 Department of Cardiology, Quzhou Affiliated Hospital of Wenzhou Medical University – Quzhou People’s Hospital, China


Cardiac pacemaker implantation is an important treatment for symptomatic bradycardia. However, epidemiological data show that the incidence of atrial fibrillation (AF) is significantly higher in patients with implanted pacemakers than in the general population, which may be related to the preoperative presence of multiple risk factors for AF, improvement of diagnostic sensitivity and the pacemaker itself. The pathogenesis of AF after the implantation of pacemaker is related to cardiac electrical remodeling, structural remodeling, inflammation, and autonomic nervous disorder, which are induced by the pacemaker. Moreover, different pacing modes and pacing sites have various effects on the pathogenesis of postoperative AF. Recent studies have reported that reducing the proportion of ventricular pacing, improving the pacing site and setting up special pacing procedures might be highly useful in prevention of AF after pacemaker implantation. This article reviews the epidemiology, pathogenesis, influencing factors, and preventive measures regarding AF after pacemaker surgery.

Key words

pathogenesis, atrial fibrillation, pacemaker implantation, pacing modes, pacing sites

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References (137)

  1. Biffi M, Capobianco C, Spadotto A, et al. Pacing devices to treat bradycardia: Current status and future perspectives. Exp Rev Med Devices. 2021;18(2):161–177. doi:10.1080/17434440.2021.1866543
  2. Bukari A, Wali E, Deshmukh A, et al. Prevalence and predictors of atrial arrhythmias in patients with sinus node dysfunction and atrial pacing. J Interv Card Electrophysiol. 2018;53(3):365–371. doi:10.1007/s10840-018-0463-7
  3. Chu SY, Jiang J, Wang YL, Sheng QH, Zhou J, Ding YS. Pacemaker-detected atrial fibrillation burden and risk of ischemic stroke or thromboembolic events: A cohort study. Heart Lung. 2020;49(1):66–72. doi:10.1016/j.hrtlng.2019.07.007
  4. Tayal B, Riahi S, Sogaard P, et al. Risk of atrial fibrillation after pacemaker implantation: A nationwide Danish registry-based follow-up study. J Electrocardiol. 2020;63:153–158. doi:10.1016/j.jelectrocard.2019.09.021
  5. Boriani G, Sakamoto Y, Botto G, et al. Prevention of long‐lasting atrial fibrillation through antitachycardia pacing in DDDR pacemakers. Int J Clin Pract. 2021;75(3):e13820. doi:10.1111/ijcp.13820
  6. Kornej J, Börschel CS, Benjamin EJ, Schnabel RB. Epidemiology of atrial fibrillation in the 21st century: Novel methods and new insights. Circ Res. 2020;127(1):4–20. doi:10.1161/CIRCRESAHA.120.316340
  7. Chen XL, Ren XJ, Liang Z, Han ZH, Zhang T, Luo Z. Analyses of risk factors and prognosis for new-onset atrial fibrillation in elderly patients after dual-chamber pacemaker implantation. J Geriatr Cardiol. 2018;15(10):628–633. doi:10.11909/j.issn.1671-5411.2018.10.008
  8. Nielsen JC. Mortality and incidence of atrial fibrillation in paced patients. J Cardiovasc Electrophysiol. 2002;13(S1):S17–S22. doi:10.1111/j.1540-8167.2002.tb01948.x
  9. Connolly SJ, Kerr CR, Gent M, et al. Effects of physiologic pacing versus ventricular pacing on the risk of stroke and death due to cardiovascular causes. N Engl J Med. 2000;342(19):1385–1391. doi:10.1056/NEJM200005113421902
  10. Nielsen JC, Thomsen PEB, Hojberg S, et al. A comparison of single-lead atrial pacing with dual-chamber pacing in sick sinus syndrome. Eur Heart J. 2011;32(6):686–696. doi:10.1093/eurheartj/ehr022
  11. Stambler BS, Ellenbogen KA, Orav EJ, et al. Predictors and clinical impact of atrial fibrillation after pacemaker implantation in elderly patients treated with dual chamber versus ventricular pacing. Pacing Clin Electrophysiol. 2003;26(10):2000–2007. doi:10.1046/j.1460-9592.2003.00309.x
  12. Sweeney MO, Bank AJ, Nsah E, et al. Minimizing ventricular pacing to reduce atrial fibrillation in sinus-node disease. N Engl J Med. 2007;357(10):1000–1008. doi:10.1056/NEJMoa071880
  13. Sweeney MO, Hellkamp AS, Ellenbogen KA, et al. Adverse effect of ventricular pacing on heart failure and atrial fibrillation among patients with normal baseline QRS duration in a clinical trial of pacemaker therapy for sinus node dysfunction. Circulation. 2003;107(23):2932–2937. doi:10.1161/01.CIR.0000072769.17295.B1
  14. Toff WD, Camm AJ, Skehan JD. Single-chamber versus dual-chamber pacing for high-grade atrioventricular block. N Engl J Med. 2005;353(2):145–155. doi:10.1056/NEJMoa042283
  15. Khan AA, Boriani G, Lip GYH. Are atrial high rate episodes (AHREs) a precursor to atrial fibrillation? Clin Res Cardiol. 2020;109(4):409–416. doi:10.1007/s00392-019-01545-4
  16. Simu G, Rosu R, Cismaru G, et al. Atrial high-rate episodes: A comprehensive review. Cardiovasc J Afr. 2021;32(2):48–53. doi:10.5830/CVJA-2020-052
  17. Kaufman ES, Israel CW, Nair GM, et al. Positive predictive value of device-detected atrial high-rate episodes at different rates and durations: An analysis from ASSERT. Heart Rhythm. 2012;9(8):1241–1246. doi:10.1016/j.hrthm.2012.03.017
  18. Sanna T. Long-term monitoring to detect atrial fibrillation with the indwelling implantable cardiac monitors. Int J Stroke. 2018;13(9):893–904. doi:10.1177/1747493018790023
  19. Bertaglia E, Blank B, Blomström-Lundqvist C, et al. Atrial high-rate episodes: Prevalence, stroke risk, implications for management, and clinical gaps in evidence. EP Europace. 2019;21(10):1459–1467. doi:10.1093/europace/euz172
  20. Camm AJ, Simantirakis E, Goette A, et al. Atrial high-rate episodes and stroke prevention. EP Europace. 2017;19(2):169–179. doi:10.1093/europace/euw279
  21. January CT, Wann LS, Calkins H, et al. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society in Collaboration With the Society of Thoracic Surgeons. Circulation. 2019;140(2):e125–e151. doi:10.1161/CIR.0000000000000665
  22. Hindricks G, Potpara T, Dagres N, 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). Eur Heart J. 2021;42(5):373–498. doi:10.1093/eurheartj/ehaa612
  23. Andrade JG, Aguilar M, Atzema C, et al. The 2020 Canadian Cardiovascular Society/Canadian Heart Rhythm Society Comprehensive Guidelines for the Management of Atrial Fibrillation. Can J Cardiol. 2020;36(12):1847–1948. doi:10.1016/j.cjca.2020.09.001
  24. Uittenbogaart SB, Lucassen WAM, van Etten-Jamaludin FS, de Groot JR, van Weert HCPM. Burden of atrial high-rate episodes and risk of stroke: A systematic review. EP Europace. 2018;20(9):1420–1427. doi:10.1093/europace/eux356
  25. Van Gelder IC, Healey JS, Crijns HJGM, et al. Duration of device-detected subclinical atrial fibrillation and occurrence of stroke in ASSERT. Eur Heart J. 2017;38(17):1339–1344. doi:10.1093/eurheartj/ehx042
  26. Healey JS, Connolly SJ, Gold MR, et al. Subclinical atrial fibrillation and the risk of stroke. N Engl J Med. 2012;366(2):120–129. doi:10.1056/NEJMoa1105575
  27. Kawakami H, Nagai T, Saito M, et al. Clinical significance of atrial high-rate episodes for thromboembolic events in Japanese population. Heart Asia. 2017;9(2):e010954. doi:10.1136/heartasia-2017-010954
  28. Nishinarita R, Niwano S, Oikawa J, et al. Novel predictor for new-onset atrial high-rate episode in patients with a dual-chamber pacemaker. Circ Rep. 2021;3(9):497–503. doi:10.1253/circrep.CR-21-0096
  29. Ogino Y, Ishikawa T, Ishigami T, et al. Characteristics and prognosis of pacemaker-identified new-onset atrial fibrillation in Japanese people. Circ J. 2017;81(6):794–798. doi:10.1253/circj.CJ-16-1018
  30. Tanawuttiwat T, Lande J, Smeets P, et al. Atrial fibrillation burden and subsequent heart failure events in patients with cardiac resynchronization therapy devices. J Cardiovasc Electrophysiol. 2020;31(6):1519–1526. doi:10.1111/jce.14444
  31. Brandenburg S, Arakel EC, Schwappach B, Lehnart SE. The molecular and functional identities of atrial cardiomyocytes in health and disease. Biochim Biophys Acta. 2016;1863(7):1882–1893. doi:10.1016/j.bbamcr.2015.11.025
  32. Liaquat MT, Ahmed I, Alzahrani T. Pacemaker malfunction. In: StatPearls. Treasure Island, USA: StatPearls Publishing; 2022. Accessed December 7, 2022.
  33. Saito Y, Nakamura K, Ito H. Cell-based biological pacemakers: Progress and problems. Acta Med Okayama. 2018;72(1):1–7. doi:10.18926/AMO/55656
  34. Ni H, Zhang H, Grandi E, Narayan SM, Giles WR. Transient outward K+ current can strongly modulate action potential duration and initiate alternans in the human atrium. Am J Physiol Heart Circ Physiol. 2019;316(3):H527–H542. doi:10.1152/ajpheart.00251.2018
  35. Greiser M, Schotten U. Dynamic remodeling of intracellular Ca2+ signaling during atrial fibrillation. J Mol Cell Cardiol. 2013;58:134–142. doi:10.1016/j.yjmcc.2012.12.020
  36. Nattel S, Dobrev D. Electrophysiological and molecular mechanisms of paroxysmal atrial fibrillation. Nat Rev Cardiol. 2016;13(10):575–590. doi:10.1038/nrcardio.2016.118
  37. Nattel S, Heijman J, Zhou L, Dobrev D. Molecular basis of atrial fibrillation pathophysiology and therapy: A translational perspective. Circ Res. 2020;127(1):51–72. doi:10.1161/CIRCRESAHA.120.316363
  38. Dzeshka MS, Lip GYH, Snezhitskiy V, Shantsila E. Cardiac fibrosis in patients with atrial fibrillation. J Am Coll Cardiol. 2015;66(8):943–959. doi:10.1016/j.jacc.2015.06.1313
  39. Lai D, Xu L, Cheng J, et al. Stretch current-induced abnormal impulses in CaMKIIδ knockout mouse ventricular myocytes. J Cardiovasc Electrophysiol. 2013;24(4):457–463. doi:10.1111/jce.12060
  40. Walters TE, Lee G, Spence S, et al. Acute atrial stretch results in conduction slowing and complex signals at the pulmonary vein to left atrial junction: Insights into the mechanism of pulmonary vein arrhythmogenesis. Circ Arrhytm Electrophysiol. 2014;7(6):1189–1197. doi:10.1161/CIRCEP.114.001894
  41. Yang S, Mei B, Liu H, et al. A modified beagle model of inducible atrial fibrillation using a right atrium pacemaker. Braz J Cardiovasc Surg. 2020;35(5):713–721. doi:10.21470/1678-9741-2019-0363
  42. Ferrari ADL, Borges AP, Albuquerque LC, et al. Cardiac pacing induced cardiomyopathy: Myth or reality sustained by evidence? Rev Bras Cir Cardiovasc. 2014;29(3):402–413. doi:10.5935/1678-9741.20140104
  43. Merchant FM, Mittal S. Pacing induced cardiomyopathy. J Cardiovasc Electrophysiol. 2020;31(1):286–292. doi:10.1111/jce.14277
  44. Xu H, Gao J, Wang F. Altered mitochondrial expression genes in patients receiving right ventricular apical pacing. Exp Mol Pathol. 2016;100(3):469–475. doi:10.1016/j.yexmp.2016.05.005
  45. Deshmukh A, Lakshmanadoss U, Deshmukh P. Hemodynamics of His bundle pacing. Card Electrophysiol Clin. 2018;10(3):503–509. doi:10.1016/j.ccep.2018.05.014
  46. Zhang YY, Wu DY, Fu NK, Lu FM, Xu J. Neuroendocrine and haemodynamic changes in single-lead atrial pacing and dual-chamber pacing modes. J Int Med Res. 2013;41(4):1057–1066. doi:10.1177/0300060513489798
  47. Jalife J, Kaur K. Atrial remodeling, fibrosis, and atrial fibrillation. Trends Cardiovasc Med. 2015;25(6):475–484. doi:10.1016/j.tcm.2014.12.015
  48. Reese-Petersen AL, Olesen MS, Karsdal MA, Svendsen JH, Genovese F. Atrial fibrillation and cardiac fibrosis: A review on the potential of extracellular matrix proteins as biomarkers. Matrix Biol. 2020;91–92:188–203. doi:10.1016/j.matbio.2020.03.005
  49. Merchant FM. Pacing-induced cardiomyopathy: Just the tip of the iceberg? Eur Heart J. 2019;40(44):3649–3650. doi:10.1093/eurheartj/ehz715
  50. Khurshid S, Frankel DS. Pacing-induced cardiomyopathy. Card Electro­physiol Clin. 2021;13(4):741–753. doi:10.1016/j.ccep.2021.06.009
  51. Fanari Z, Hammami S, Hammami MB, Hammami S, Shuraih M. The effects of right ventricular apical pacing with transvenous pacemaker and implantable cardioverter defibrillator on mitral and tricuspid regurgitation. J Electrocardiol. 2015;48(5):791–797. doi:10.1016/j.jelectrocard.2015.07.002
  52. Iscan S, Eygi B, Besir Y, et al. Inflammation, atrial fibrillation and cardiac surgery: Current medical and invasive approaches for the treatment of atrial fibrillation. Curr Pharm Des. 2018;24(3):310–322. doi:10.2174/1381612824666180131120859
  53. Olsen FJ, Møgelvang R, Jensen GB, Jensen JS, Biering-Sørensen T. Relationship between left atrial functional measures and incident atrial fibrillation in the general population. JACC Cardiovasc Imaging. 2019;12(6):981–989. doi:10.1016/j.jcmg.2017.12.016
  54. Scott L, Li N, Dobrev D. Role of inflammatory signaling in atrial fibrillation. Int J Cardiol. 2019;287:195–200. doi:10.1016/j.ijcard.2018.10.020
  55. Vyas V, Hunter RJ, Longhi MP, Finlay MC. Inflammation and adiposity: New frontiers in atrial fibrillation. EP Europace. 2020;22(11):1609–1618. doi:10.1093/europace/euaa214
  56. Pacheco KA. Allergy to surgical implants. Clinic Rev Allerg Immunol. 2019;56(1):72–85. doi:10.1007/s12016-018-8707-y
  57. Liew R, Khairunnisa K, Gu Y, et al. Role of tumor necrosis factor-α in the pathogenesis of atrial fibrosis and development of an arrhythmogenic substrate. Circ J. 2013;77(5):1171–1179. doi:10.1253/circj.CJ-12-1155
  58. Acampa M, Lazzerini PE, Guideri F, Tassi R, Lo Monaco A, Martini G. Inflammation and atrial electrical remodelling in patients with embolic strokes of undetermined source. Heart Lung Circ. 2019;28(6):917–922. doi:10.1016/j.hlc.2018.04.294
  59. da Silva RMFL. Influence of inflammation and atherosclerosis in atrial fibrillation. Curr Atheroscler Rep. 2017;19(1):2. doi:10.1007/s11883-017-0639-0
  60. Wijesurendra RS, Casadei B. Mechanisms of atrial fibrillation. Heart. 2019;105(24):1860–1867. doi:10.1136/heartjnl-2018-314267
  61. Yongjun Q, Huanzhang S, Wenxia Z, Hong T, Xijun X. From changes in local RAAS to structural remodeling of the left atrium: A beautiful cycle in atrial fibrillation. Herz. 2015;40(3):514–520. doi:10.1007/s00059-013-4032-7
  62. Carnagarin R, Kiuchi MG, Ho JK, Matthews VB, Schlaich MP. Sympathetic nervous system activation and its modulation: Role in atrial fibrillation. Front Neurosci. 2019;12:1058. doi:10.3389/fnins.2018.01058
  63. Qin M, Zeng C, Liu X. The cardiac autonomic nervous system: A target for modulation of atrial fibrillation. Clin Cardiol. 2019;42(6):644–652. doi:10.1002/clc.23190
  64. Chiladakis JA, Kalogeropoulos A, Manolis AS. Autonomic responses to single- and dual-chamber pacing. Am J Cardiol. 2004;93(8):985–989. doi:10.1016/j.amjcard.2003.12.052
  65. Elder DH, Lang CC, Choy AM. Pacing-induced heart disease: Understanding the pathophysiology and improving outcomes. Exp Rev Cardiovasc Ther. 2011;9(7):877–886. doi:10.1586/erc.11.82
  66. DeForge WF. Cardiac pacemakers: A basic review of the history and current technology. J Vet Cardiol. 2019;22:4–50. doi:10.1016/j.jvc.2019.01.001
  67. Mulpuru SK, Madhavan M, McLeod CJ, Cha YM, Friedman PA. Cardiac pacemakers: Function, troubleshooting, and management. J Am Coll Cardiol. 2017;69(2):189–210. doi:10.1016/j.jacc.2016.10.061
  68. Kerr CR, Connolly SJ, Abdollah H, et al. Canadian trial of physiological pacing: Effects of physiological pacing during long-term follow-up. Circulation. 2004;109(3):357–362. doi:10.1161/01.CIR.0000109490.72104.EE
  69. Reiffel JA. Intra-atrial block: Definition and relationship to atrial fibrillation and other adverse outcomes. J Atrial Fibril. 2019;12(2):2234. doi:10.4022/jafib.2234
  70. Spies F, Knecht S, Zeljkovic I, et al. First-degree atrioventricular block in patients with atrial fibrillation and atrial flutter: The prevalence of intra-atrial conduction delay. J Interv Card Electrophysiol. 2021;61(2):421–425. doi:10.1007/s10840-020-00838-3
  71. Bohm A. Prolonged PR interval despite a programmed short sensed AV delay: The role of intra-atrial conduction time. Europace. 2002;4(3):329–331. doi:10.1053/eupc.2002.0244
  72. Khaykin Y, Exner D, Birnie D, Sapp J, Aggarwal S, Sambelashvili A. Adjusting the timing of left-ventricular pacing using electrocardiogram and device electrograms. EP Europace. 2011;13(10):1464–1470. doi:10.1093/europace/eur146
  73. Kim WH, Joung B, Shim J, et al. Long-term outcome of single-chamber atrial pacing compared with dual-chamber pacing in patients with sinus-node dysfunction and intact atrioventricular node conduction. Yonsei Med J. 2010;51(6):832. doi:10.3349/ymj.2010.51.6.832
  74. Statescu C, Sascau RA, Maciuc V, Arsenescu Georgescu C. Programming an optimal atrioventricular interval in a dual chamber pacemaker regional population. Maedica (Bucur). 2011;6(4):272–276. PMID:22879840. PMCID:PMC3391943.
  75. Cheung JW, Keating RJ, Stein KM, et al. Newly detected atrial fibrillation following dual chamber pacemaker implantation. J Cardiovasc Electrophysiol. 2006;17(12):1323–1328. doi:10.1111/j.1540-8167.2006.00648.x
  76. Wu Z, Chen X, Ge J, Su Y. The risk factors of new-onset atrial fibrillation after pacemaker implantation. Herz. 2021;46(S1):61–68. doi:10.1007/s00059-019-04869-z
  77. Roithinger FX, Abou-Harb M, Pachinger O, Hintringer F. The effect of the atrial pacing site on the total atrial activation time. Pacing Clin Electrophysiol. 2001;24(3):316–322. doi:10.1046/j.1460-9592.2001.00316.x
  78. Kliś M, Sławuta A, Gajek J. Antiarrhythmic properties of atrial pacing. Adv Clin Exp Med. 2017;26(2):351–357. doi:10.17219/acem/61429
  79. Verlato R, Botto GL, Massa R, et al. Efficacy of low interatrial septum and right atrial appendage pacing for prevention of permanent atrial fibrillation in patients with sinus node disease: Results from the Electrophysiology-Guided Pacing Site Selection (EPASS) Study. Circ Arrhytm Electrophysiol. 2011;4(6):844–850. doi:10.1161/CIRCEP.110.957126
  80. Sławuta A, Kliś M, Skoczyński P, Bańkowski T, Moszczyńska-Stulin J, Gajek J. Bachmann’s bundle pacing not only improves interatrial conduc-tion but also reduces the need for ventricular pacing. Adv Clin Exp Med. 2016;25(5):845–850. doi:10.17219/acem/63351
  81. Hettrick DA, Mittelstadt JR, Kehl F, et al. Atrial pacing lead location alters the hemodynamic effects of atrial‐ventricular delay in dogs with pacing induced cardiomyopathy. Pacing Clin Electrophysiol. 2003;26(4 Pt 1):853–861. doi:10.1046/j.1460-9592.2003.t01-1-00150.x
  82. Watabe T, Abe H, Kohno R, et al. Atrial pacing site and atrioventricular conduction in patients paced for sinus node disease: Atrial pacing site and AV conduction. J Cardiovasc Electrophysiol. 2014;25(11):1224–1231. doi:10.1111/jce.12476
  83. Akerström F, Pachón M, Puchol A, et al. Chronic right ventricular apical pacing: Adverse effects and current therapeutic strategies to minimize them. Int J Cardiol. 2014;173(3):351–360. doi:10.1016/j.ijcard.2014.03.079
  84. Iqbal AM, Jamal SF. Pacemaker syndrome. In: StatPearls. Treasure Island, USA: StatPearls Publishing; 2022. Accessed December 7, 2022.
  85. Liu T, Li G. Pulmonary vein dilatation: Another possible crosslink between left atrial enlargement and atrial fibrillation? Int J Cardiol. 2008;123(2):193–194. doi:10.1016/j.ijcard.2006.11.135
  86. Ratanasit N, Karaketklang K, Krittayaphong R. Left atrial volume index as an independent determinant of pulmonary hypertension in patients with chronic organic mitral regurgitation. BMC Cardiovasc Disord. 2016;16(1):141. doi:10.1186/s12872-016-0306-3
  87. Kodama Y, Kuraoka A, Ishikawa Y, et al. Outcome of patients with functional single ventricular heart after pacemaker implantation: What makes it poor, and what can we do? Heart Rhythm. 2019;16(12):1870–1874. doi:10.1016/j.hrthm.2019.06.019
  88. Ståhlberg M, Nakagawa R, Bedja D, et al. Chronic atrial and ventricular pacing in the mouse: Application to model cardiac dyssynchrony and resynchronization in heart failure. Circ Heart Fail. 2019;12(2):e005655. doi:10.1161/CIRCHEARTFAILURE.118.005655
  89. Tayal B, Fruelund P, Sogaard P, et al. Incidence of heart failure after pacemaker implantation: A nationwide Danish registry-based follow-up study. Eur Heart J. 2019;40(44):3641–3648. doi:10.1093/eurheartj/ehz584
  90. Abedin Z. Incidence of new onset atrial fibrillation in patients with permanent pacemakers and the relation to the pacing mode. Med Sci Monit. 2014;20:268–273. doi:10.12659/MSM.890052
  91. Jankelson L, Bordachar P, Strik M, Ploux S, Chinitz L. Reducing right ventricular pacing burden: Algorithms, benefits, and risks. EP Europace. 2019;21(4):539–547. doi:10.1093/europace/euy263
  92. Boriani G, Tukkie R, Manolis AS, et al. Atrial antitachycardia pacing and managed ventricular pacing in bradycardia patients with paroxysmal or persistent atrial tachyarrhythmias: The MINERVA randomized multicentre international trial. Eur Heart J. 2014;35(35):2352–2362. doi:10.1093/eurheartj/ehu165
  93. Shurrab M, Healey JS, Haj-Yahia S, et al. Reduction in unnecessary ventricular pacing fails to affect hard clinical outcomes in patients with preserved left ventricular function: A meta-analysis. Europace. 2016;19(2):282–288. doi:10.1093/europace/euw221
  94. Frisch DR, Kenia AS, Walinsky P, Balog J. Managed ventricular pacing facilitating atrioventricular nodal reentrant tachycardia. Pacing Clin Electrophysiol. 2014;37(11):1568–1571. doi:10.1111/pace.12318
  95. Das A. Electrocardiographic features: Various atrial site pacing. Indian Heart J. 2017;69(5):675–680. doi:10.1016/j.ihj.2017.08.030
  96. Ramdjan TT, van der Does LJ, Knops P, Res JC, de Groot NM. Right versus left atrial pacing in patients with sick sinus syndrome and paroxysmal atrial fibrillation (Riverleft study): Study protocol for randomized controlled trial. Trials. 2014;15(1):445. doi:10.1186/1745-6215-15-445
  97. Minamiguchi H, Nanto S, Onishi T, Watanabe T, Uematsu M, Komuro I. Low atrial septal pacing with dual-chamber pacemakers reduces atrial fibrillation in sick sinus syndrome. J Cardiol. 2011;57(2):223–230. doi:10.1016/j.jjcc.2010.11.002
  98. Zhang L, Jiang H, Wang W, et al. Interatrial septum versus right atrial appendage pacing for prevention of atrial fibrillation: A meta-analysis of randomized controlled trials. Herz. 2018;43(5):438–446. doi:10.1007/s00059-017-4589-7
  99. Burri H, Bennani I, Domenichini G, et al. Biatrial pacing improves atrial haemodynamics and atrioventricular timing compared with pacing from the right atrial appendage. Europace. 2011;13(9):1262–1267. doi:10.1093/europace/eur099
  100. Rubaj A, Rucinski P, Kutarski A, et al. Cardiac hemodynamics and proinflammatory cytokines during biatrial and right atrial appendage pacing in patients with interatrial block. J Interv Card Electrophysiol. 2013;37(2):147–154. doi:10.1007/s10840-013-9792-8
  101. Nagarakanti R, Slee A, Saksena S. Left atrial reverse remodeling and prevention of progression of atrial fibrillation with atrial resynchronization device therapy utilizing dual-site right atrial pacing in patients with atrial fibrillation refractory to antiarrhythmic drugs or catheter ablation. J Interv Card Electrophysiol. 2014;40(3):245–254. doi:10.1007/s10840-014-9931-x
  102. Lewicka-Nowak E, Kutarski A, Dabrowska-Kugacka A, Rucinski P, Zagozdzon P, Raczak G. A novel method of multisite atrial pacing, incorporating Bachmann’s bundle area and coronary sinus ostium, for electrical atrial resynchronization in patients with recurrent atrial fibrillation. Europace. 2007;9(9):805–811. doi:10.1093/europace/eum152
  103. Hayashi K, Kohno R, Fujino Y, et al. Pacing from the right ventricular septum and development of new atrial fibrillation in paced patients with atrioventricular block and preserved left ventricular function. Circ J. 2016;80(11):2302–2309. doi:10.1253/circj.CJ-16-0640
  104. Chen X, Qian Z, Zou F, et al. Differentiating left bundle branch pacing and left ventricular septal pacing: An algorithm based on intracardiac electrophysiology. Cardiovasc Electrophysiol. 2022;33(3):448–457. doi:10.1111/jce.15350
  105. Heckman LIB, Luermans JGLM, Curila K, et al. Comparing ventricular synchrony in left bundle branch and left ventricular septal pacing in pacemaker patients. J Clin Med. 2021;10(4):822. doi:10.3390/jcm10040822
  106. Vetta F, Marinaccio L, Vetta G. Alternative sites of ventricular pacing: His bundle pacing. Monaldi Arch Chest Dis. 2020;90(2). doi:10.4081/monaldi.2020.1251
  107. Weizong W, Zhongsu W, Yujiao Z, et al. Effects of right ventricular nonapical pacing on cardiac function: A meta-analysis of randomized controlled trials. Pacing Clin Electrophysiol. 2013;36(8):1032–1051. doi:10.1111/pace.12112
  108. Curila K, Jurak P, Halamek J, et al. Ventricular activation pattern assessment during right ventricular pacing: Ultra‐high‐frequency ECG study. J Cardiovasc Electrophysiol. 2021;32(5):1385–1394. doi:10.1111/jce.14985
  109. Pastore G, Zanon F, Baracca E, et al. The risk of atrial fibrillation during right ventricular pacing. Europace. 2016;18(3):353–358. doi:10.1093/europace/euv268
  110. Zhu H, Li X, Wang Z, et al. New-onset atrial fibrillation following left bundle branch area pacing vs. right ventricular pacing: A two-centre prospective cohort study [published online as ahead of print on August 9, 2022]. EP Europace. 2022. doi:10.1093/europace/euac132
  111. Sharma PS, Patel NR, Ravi V, et al. Clinical outcomes of left bundle branch area pacing compared to right ventricular pacing: Results from the Geisinger–Rush Conduction System Pacing Registry. Heart Rhythm. 2022;19(1):3–11. doi:10.1016/j.hrthm.2021.08.033
  112. Su L, Wang S, Wu S, et al. Long-term safety and feasibility of left bundle branch pacing in a large single-center study. Circ Arrhytm Electrophysiol. 2021;14(2):e009261. doi:10.1161/CIRCEP.120.009261
  113. Knight BP, Gersh BJ, Carlson MD, et al. Role of permanent pacing to prevent atrial fibrillation: Science advisory From the American Heart Association Council on Clinical Cardiology (Subcommittee on Electrocardiography and Arrhythmias) and the Quality of Care and Outcomes Research Interdisciplinary Working Group, in Collaboration With the Heart Rhythm Society. Circulation. 2005;111(2):240–243. doi:10.1161/01.CIR.0000151800.84945.47
  114. Mitchell A. How do atrial pacing algorithms prevent atrial arrhythmias? Europace. 2004;6(4):351–362. doi:10.1016/j.eupc.2004.03.005
  115. Lewalter T, Yang A, Pfeiffer D, et al. Individualized selection of pacing algorithms for the prevention of recurrent atrial fibrillation: Results from the VIP registry. Pacing Clin Electrophysiol. 2006;29(2):124–134. doi:10.1111/j.1540-8159.2006.00305.x
  116. Carlson MD, Ip J, Messenger J, et al. A new pacemaker algorithm for the treatment of atrial fibrillation. J Am Coll Cardiol. 2003;42(4):627–633. doi:10.1016/S0735-1097(03)00780-0
  117. Gold MR, Adler S, Fauchier L, et al. Impact of atrial prevention pacing on atrial fibrillation burden: Primary results of the Study of Atrial Fibrillation Reduction (SAFARI) trial. Heart Rhythm. 2009;6(3):295–301. doi:10.1016/j.hrthm.2008.11.033
  118. Hohnloser SH, Healey JS, Gold MR, et al. Atrial overdrive pacing to prevent atrial fibrillation: Insights from ASSERT. Heart Rhythm. 2012;9(10):1667–1673. doi:10.1016/j.hrthm.2012.06.012
  119. Kantharia BK, Freedman RA, Hoekenga D, et al. Increased base rate of atrial pacing for prevention of atrial fibrillation after implantation of a dual-chamber pacemaker: Insights from the Atrial Overdrive Pacing Study. Europace. 2007;9(11):1024–1030. doi:10.1093/europace/eum170
  120. Lau CP, Tachapong N, Wang CC, et al. Prospective randomized study to assess the efficacy of site and rate of atrial pacing on long-term progression of atrial fibrillation in sick sinus syndrome: Septal Pacing for Atrial Fibrillation Suppression Evaluation (SAFE) Study. Circulation. 2013;128(7):687–693. doi:10.1161/CIRCULATIONAHA.113.001644
  121. Dézsi CA, Szentes V. The real role of β-blockers in daily cardiovascular therapy. Am J Cardiovasc Drugs. 2017;17(5):361–373. doi:10.1007/s40256-017-0221-8
  122. Vinereanu D, Spinar J, Pathak A, Kozlowski D. Role of metoprolol succinate in the treatment of heart failure and atrial fibrillation: A systematic review. Am J Ther. 2020;27(2):e183–e193. doi:10.1097/MJT.0000000000001043
  123. Lan Q, Wu F, Han B, Ma L, Han J, Yao Y. Intravenous diltiazem versus metoprolol for atrial fibrillation with rapid ventricular rate: A meta-analysis. Am J Emerg Med. 2022;51:248–256. doi:10.1016/j.ajem.2021.08.082
  124. Bonora BM, Raschi E, Avogaro A, Fadini GP. SGLT-2 inhibitors and atrial fibrillation in the Food and Drug Administration adverse event reporting system. Cardiovasc Diabetol. 2021;20(1):39. doi:10.1186/s12933-021-01243-4
  125. De Vecchis R, Paccone A, Di Maio M. Upstream therapy for atrial fibrillation prevention: The role of sacubitril/valsartan. Cardiol Res. 2020;11(4):213–218. doi:10.14740/cr1073
  126. Shao Q, Meng L, Lee S, et al. Empagliflozin, a sodium glucose co-transporter-2 inhibitor, alleviates atrial remodeling and improves mitochondrial function in high-fat diet/streptozotocin-induced diabetic rats. Cardiovasc Diabetol. 2019;18(1):165. doi:10.1186/s12933-019-0964-4
  127. Okutucu S, Fatihoglu SG, Sabanoglu C, et al. Effects of angiotensin receptor neprilysin inhibition on P-wave dispersion in heart failure with reduced ejection fraction. Herz. 2021;46(Suppl 1):69–74. doi:10.1007/s00059-019-04872-4
  128. Suo Y, Yuan M, Li H, et al. Sacubitril/valsartan improves left atrial and left atrial appendage function in patients with atrial fibrillation and in pressure overload-induced mice. Front Pharmacol. 2019;10:1285. doi:10.3389/fphar.2019.01285
  129. Rodriguez A, Hunter CL, Premuroso C, et al. Safety and efficacy of prehospital diltiazem for atrial fibrillation with rapid ventricular response. Prehosp Disaster Med. 2019;34(3):297–302. doi:10.1017/S1049023X19004278
  130. Shi S, Chu Y, Jia Q, Hu Y. Comparative efficacy and safety of wenxin granule combined with antiarrhythmic drugs for atrial fibrillation: A protocol for a systematic review and network meta-analysis. Medicine (Baltimore). 2021;100(3):e24434. doi:10.1097/MD.0000000000024434
  131. Tian G, Sun Y, Liu S, et al. Therapeutic effects of Wenxin Keli in cardiovascular diseases: An experimental and mechanism overview. Front Pharmacol. 2018;9:1005. doi:10.3389/fphar.2018.01005
  132. Arnold DD, Yalamanoglu A, Boyman O. Systematic review of safety and efficacy of IL-1-targeted biologics in treating immune-mediated disorders. Front Immunol. 2022;13:888392. doi:10.3389/fimmu.2022.888392
  133. Capucci A, Cipolletta L, Guerra F, Giannini I. Emerging pharmacotherapies for the treatment of atrial fibrillation. Expert Opin Emerg Drugs. 2018;23(1):25–36. doi:10.1080/14728214.2018.1446941
  134. Nomani H, Saei S, Johnston TP, Sahebkar A, Mohammadpour AH. The efficacy of anti-inflammatory agents in the prevention of atrial fibrillation recurrences. Curr Med Chem. 2020;28(1):137–151. doi:10.2174/1389450121666200302095103
  135. Scott L, Li N, Dobrev D. Role of inflammatory signaling in atrial fibrillation. Int J Cardiol. 2019;287:195–200. doi:10.1016/j.ijcard.2018.10.020
  136. Bashir M, Bhagra A, Kapa S, MacLeod C. Modulation of the autonomic nervous system through mind and body practices as a treatment for atrial fibrillation. Rev Cardiovasc Med. 2019;20(3):129. doi:10.31083/j.rcm.2019.03.517
  137. Wang S, Zhou X, Huang B, et al. Spinal cord stimulation suppresses atrial fibrillation by inhibiting autonomic remodeling. Heart Rhythm. 2016;13(1):274–281. doi:10.1016/j.hrthm.2015.08.018