7/5/23, 10:35 AM Etiology of atrioventricular block - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Etiology of atrioventricular block : William H Sauer, MD : Mark S Link, MD : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Dec 06, 2022. INTRODUCTION Atrioventricular (AV) block is defined as a delay or interruption in the transmission of an impulse from the atria to the ventricles due to an anatomical or functional impairment in the conduction system. The conduction disturbance can be transient or permanent, with conduction that is delayed, intermittent, or absent. Commonly used terminology includes: First-degree AV block Delayed conduction from the atrium to the ventricle (defined as a prolonged PR interval of >200 milliseconds) without interruption in atrial to ventricular conduction. Second-degree AV block Intermittent atrial conduction to the ventricle, often in a regular pattern (eg, 2:1, 3:2, or other pattern), which are further classified into Mobitz type I (Wenckebach) and Mobitz type II second degree AV block. Third-degree (complete AV) block No atrial impulses conduct to the ventricle. High-grade AV block Intermittent atrial conduction to the ventricle with two or more consecutive blocked P waves but without complete AV block. AV block has a variety of causes ( table 1). The various etiologies of AV block will be reviewed here. The management of the specific types of AV block is discussed separately. (See "First- degree atrioventricular block" and "Second-degree atrioventricular block: Mobitz type I (Wenckebach block)" and "Second-degree atrioventricular block: Mobitz type II" and "Third- degree (complete) atrioventricular block".) https://www.uptodate.com/contents/etiology-of-atrioventricular-block/print 1/15 7/5/23, 10:35 AM Etiology of atrioventricular block - UpToDate PHYSIOLOGIC AV BLOCK AV block can result from physiologic slowing of cardiac conduction in response to increased parasympathetic nervous system output. Enhanced vagal tone due to athletic training, sleep, pain, carotid sinus massage, or carotid sinus hypersensitivity syndrome can result in slowing of the sinus rate and/or the development of AV conduction disturbances. In general, enhanced vagal tone leads to lower degrees of AV block (ie, first degree or Mobitz type I second degree); higher degree AV block that occurs in the setting of enhanced vagal tone could suggest other pathologic contributions to AV conduction disturbance. (See "Sinus node dysfunction: Epidemiology, etiology, and natural history" and "Carotid sinus hypersensitivity and carotid sinus syndrome".) PATHOPHYSIOLOGIC AV BLOCK Fibrosis and sclerosis of the conduction system, which appears idiopathic, accounts for about one-half of cases of AV block. Conduction system fibrosis and sclerosis may be induced by several different conditions that often cannot be distinguished clinically [1]. Additionally, some degree of fibrosis and sclerosis occurs as part of the normal aging process, with the prevalence increasing progressively with age with approximately a 2:1 male:female predominance. Among a prospective cohort of more than half a million United Kingdom residents, the prevalence of conduction system disease (which included all levels of AV block, as well as bundle branch blocks) was approximately 11 per 10,000 persons under age 55 and increased to between 55 per 10,000 persons 65 years of age [2]. Idiopathic Apparently idiopathic progressive cardiac conduction defects are the most common cause of AV block, occurring in approximately 50 percent of cases. Idiopathic AV conduction abnormalities are characterized by progressive impairment of the conduction system which occurs gradually over decades: Lenegre disease The term Lenegre disease has been traditionally used to describe a progressive, fibrotic, sclerodegenerative affliction of the conduction system in younger (age <60 years) individuals. Lenegre disease is frequently associated with slow progression to complete heart block and may be hereditary. (See 'Familial disease' below.) Lev disease The term Lev disease has been used to refer to "sclerosis of the left side of the cardiac skeleton" in older patients (age >70 years old), such as that associated with calcific involvement of the aortic and mitral rings [3-5]. Lev disease is caused by fibrosis or https://www.uptodate.com/contents/etiology-of-atrioventricular-block/print 2/15 7/5/23, 10:35 AM Etiology of atrioventricular block - UpToDate calcification extending from any of the fibrous structures adjacent to the conduction system into the conduction system [4,5]. Depending upon the anatomic location of the areas of fibrosis and sclerosis, various conduction abnormalities can result: Fibrosis of the superior and basal aspect of the muscular septum is a common cause of right bundle branch block (RBBB) with left anterior fascicular block in the older adult. Involvement of the mitral ring or the central fibrous body, for example, may be the most common cause of complete heart block with a narrow QRS complex in the older adult. Aortic valve calcification, on the other hand, can invade the bundle of His, the right and/or left bundle branch as well as the left anterior fascicle. Thus, the QRS complex may be prolonged. Associated with other cardiac disease Ischemic heart disease Ischemic heart disease accounts for about 40 percent of cases of AV block [1]. Conduction can be disturbed with either chronic ischemic heart disease or during an acute myocardial infarction (MI) [6-10]. Up to 20 percent of patients with an acute MI develop some degree of AV block, with the likelihood and severity related to the area and extent of ischemia/infarction [8-10]. While restoration of perfusion in the setting of acute MI frequently leads to improved conduction, coronary revascularization in stable patients with AV block rarely if ever improves AV conduction. Intraventricular conduction disturbances (IVCDs), including bundle and fascicular blocks, also occur in 10 to 20 percent of cases of acute MI [11-17]. Left bundle branch block (LBBB) and RBBB with left anterior fascicle block are most common. (See "Conduction abnormalities after myocardial infarction".) Cardiomyopathies and myocarditis AV block can be seen in patients with cardiomyopathies, including hypertrophic obstructive cardiomyopathy and infiltrative processes such as amyloidosis and sarcoidosis, and in patients with myocarditis due to a variety of causes including rheumatic fever, Lyme disease, diphtheria, viruses, systemic lupus erythematosus, toxoplasmosis, bacterial endocarditis, and syphilis [4,5,18-29]. Patients with COVID-19-associated myocarditis have been observed to have varying degrees of AV block [30,31]. The development of AV block in myocarditis is often a poor prognostic sign. (See "Clinical manifestations and diagnosis of myocarditis in adults" and "Lyme carditis", section on 'Atrioventricular conduction abnormalities'.) https://www.uptodate.com/contents/etiology-of-atrioventricular-block/print 3/15 7/5/23, 10:35 AM Etiology of atrioventricular block - UpToDate Congenital heart disease AV block of varying degrees can be associated with a variety of congenital heart defects that result in structural abnormalities (eg, congenitally corrected transposition of the great arteries, large primum atrial septal defects, and large AV septal defects [AV canal defects]). Additionally, complete heart block may be an isolated lesion (ie, with no associated structural heart disease), most commonly associated with neonatal lupus, which results from transplacental passage of anti-Ro/SSA or anti-La/SSB antibodies from the mother. (See "Atrial arrhythmias (including AV block) in congenital heart disease", section on 'Congenital AV block' and "Congenital third-degree (complete) atrioventricular block" and "Neonatal lupus: Epidemiology, pathogenesis, clinical manifestations, and diagnosis".) Familial disease Familial AV block, characterized by a progression in the degree of AV block in association with a variable apparent site of block, may be transmitted as an autosomal dominant trait. One form of AV conduction block has been mapped to a genetic locus at chromosome 19q13 and the other to chromosome 3p21, where the cardiac sodium channel, SCN5A, is encoded [32]. Several SCN5A mutations have been associated with AV conduction block [33-39]. Some patients with hereditary AV block are identified in childhood due to the presents of bundle branch disease (ie, RBBB, LBBB, left anterior fascicular block [LAFB], or left posterior fascicular block [LPFB]), while others present in middle-age and have been called hereditary Lenegre disease [33,34,36,40]. In the latter setting, it has been proposed that haploinsufficiency combined with aging leads to a progressive decline in conduction [41]. (See 'Idiopathic' above.) Different SCN5A mutations are associated with other cardiac abnormalities including congenital long QT syndrome, the Brugada syndrome, familial sinus node dysfunction, and familial dilated cardiomyopathy with conduction defects and susceptibility to atrial fibrillation. (See "Congenital long QT syndrome: Pathophysiology and genetics" and "Sinus node dysfunction: Epidemiology, etiology, and natural history" and "Genetics of dilated cardiomyopathy" and "Brugada syndrome: Epidemiology and pathogenesis", section on 'SCN5A'.) Other genetic forms of familial AV block have been described, including a form of progressive cardiac conduction system disease mapped to a locus on chromosome 19q13 and a form associated with congenital heart disease for which a point mutation has been identified in the cardiac transcription factor CSX/NKX2-5 [40,42-47]. (See 'Associated with other cardiac disease' above.) Miscellaneous causes AV block can also occur in a variety of other disorders: Hyperkalemia, usually when the plasma potassium concentration is above 6.3 meq/L [48- 50]. (See "Clinical manifestations of hyperkalemia in adults", section on 'Conduction https://www.uptodate.com/contents/etiology-of-atrioventricular-block/print 4/15 7/5/23, 10:35 AM Etiology of atrioventricular block - UpToDate abnormalities and arrhythmias'.) Additive effects of hyperkalemia and AV blocking agents are discussed below. (See 'Medications' below.) Hyperthyroidism and hypothyroidism, myxedema, and thyrotoxic periodic paralysis [4,5,51]. (See "Cardiovascular effects of hypothyroidism", section on 'Rhythm disturbances' and "Thyrotoxic periodic paralysis", section on 'Clinical features'.) Hereditary neuromuscular heredodegenerative disease such as myotonic dystrophy, Kearns-Sayre syndrome, and Erb's dystrophy [52-54]. (See "Inherited syndromes associated with cardiac disease".) Cardiac tumors, cysts, myocardial bridging, and trauma [3-5,55-57]. (See "Cardiac tumors" and "Myocardial bridging of the coronary arteries", section on 'Clinical relevance'.) Rheumatologic disorders including dermatomyositis [3-5]. (See "Clinical manifestations of dermatomyositis and polymyositis in adults", section on 'Cardiac involvement'.) IATROGENIC AV BLOCK Iatrogenic AV block, which can result from either medications or invasive procedures, is common. As with physiologic AV block, iatrogenic AV block can occur in isolation, but can also exacerbate underlying pathophysiologic AV block. Medications A variety of drugs can impair AV conduction, resulting in AV block. The common medications which can result in AV block include: Beta blockers Non-dihydropyridine calcium channel blockers (especially verapamil and to a lesser extent diltiazem) Digoxin Adenosine Antiarrhythmic medications, commonly amiodarone but also drugs that modulate the sodium channel (eg, quinidine, procainamide, disopyramide, etc) Most patients with AV block who are taking drugs that can impair conduction probably have some degree of underlying conduction system disease, although toxicity may result from medication overdose (either intentional or as a result of decreased clearance in the setting of renal or hepatic dysfunction). The association between medications altering AV conduction and https://www.uptodate.com/contents/etiology-of-atrioventricular-block/print 5/15 7/5/23, 10:35 AM Etiology of atrioventricular block - UpToDate underlying conduction system disease was suggested by a study of 169 patients with second or third degree AV block not related to acute MI, digitalis toxicity, or vasovagal syncope [58]. Of these, 92 (54 percent) were receiving beta blockers and/or verapamil or diltiazem. Drug discontinuation resulted in resolution of AV block in 32 of 79 cases; however, AV block later recurred in the absence of therapy in 18 of these patients. In patients receiving one or more AV blockers, a syndrome involving bradycardia (sinus arrest), renal failure, AV block, shock, and hyperkalemia (BRASH), has been described. In patients with BRASH, the severity of bradycardia (caused by sinus arrest and/or AV block) may be greater than generally caused by either the dose/level of AV blocker or level of hyperkalemia alone. This syndrome is discussed further separately. (See "Sinoatrial nodal pause, arrest, and exit block", section on 'Etiology'.) A 2020 scientific statement from the American Heart Association details drugs associated with AV block [59]. Cardiac procedures AV conduction abnormalities may result from a variety of invasive cardiac procedures. Open heart surgery AV block may occur following replacement of either the aortic or mitral valve, closure of a ventricular septal defect, or other surgical procedures [5,60-65]. In many instances, this is a transient phenomenon related to periprocedural edema which resolves in the hours to days following surgery and can be managed with temporary pacing. However, surgery may result in a permanent conduction abnormality requiring a permanent pacemaker. Transcatheter aortic valve implantation (TAVI) Between 2 and 8 percent of patients who undergo percutaneous TAVI develop AV block following the procedure. Pre-existing disturbances of cardiac conduction (particularly right bundle branch block), a narrow left ventricular outflow tract, and the severity of mitral annular calcification appear to be predictors of this complication. There may also be a higher rate of heart block observed with self-expanding implanted aortic valves compared with balloon expandable versions [66,67]. (See "Transcatheter aortic valve implantation: Complications", section on 'High degree heart block'.) Catheter ablation for arrhythmias AV block is a potential complication of catheter ablation of reentrant arrhythmias when the reentrant pathway lies within or near the AV node. As an example, catheter ablation for AV nodal reentrant tachycardia typically involves areas of the atrium very close to the AV node, with a resulting 1.4 percent risk of heart https://www.uptodate.com/contents/etiology-of-atrioventricular-block/print 6/15 7/5/23, 10:35 AM Etiology of atrioventricular block - UpToDate block following this procedure [68]. (See "Overview of catheter ablation of cardiac arrhythmias", section on 'Complications'.) Transcatheter closure of VSD A variety of devices have been used to percutaneously close muscular ventricular septal defects (VSDs), both congenital and those that occur after myocardial infarction. The Amplatzer ventricular septal defect occluder, for example, completely occluded 28 of 30 VSDs in one report [69]. One patient with complete left bundle branch block after the procedure progressed to complete heart block at one year. The presumed mechanism is that the right ventricular retention disk overlaps the ventricular conduction system as it passes above or anterosuperiorly to the defect. (See "Management and prognosis of congenital ventricular septal defect in adults", section on 'Arrhythmias and AV block'.) Alcohol (ethanol) septal ablation Percutaneous transluminal alcohol (ethanol) septal ablation is an invasive septal reduction therapy for patients with hypertrophic cardiomyopathy and significant left ventricular outflow tract obstruction. This intervention consists of infarction and thinning of the proximal interventricular septum via infusion of alcohol into the first septal perforating branch of the left anterior descending coronary artery through an angioplasty catheter. Complete heart block is seen in approximately 8 to 10 percent of patients after this procedure. (See "Hypertrophic cardiomyopathy: Management of patients with outflow tract obstruction", section on 'Septal reduction therapy'.) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Heart block in adults (The Basics)") https://www.uptodate.com/contents/etiology-of-atrioventricular-block/print 7/15 7/5/23, 10:35 AM Etiology of atrioventricular block - UpToDate SUMMARY AND RECOMMENDATIONS Atrioventricular (AV) block is defined as a delay or interruption in the transmission of an impulse from the atria to the ventricles due to an anatomical or functional impairment in the conduction system. The conduction disturbance can be transient or permanent, and it can have many causes ( table 1). (See 'Introduction' above.) Fibrosis and sclerosis of the conduction system accounts for about 50 percent of cases of AV block and may be induced by several different conditions that often cannot be distinguished clinically. When fibrosis and sclerosis of the conduction system are present, they are frequently progressive and may ultimately progress to complete heart block. (See 'Idiopathic' above.) Ischemic disease accounts for about 40 percent of cases of AV block. Conduction can be disturbed with either chronic ischemic heart disease or during an acute myocardial infarction. AV block can be seen in patients with cardiomyopathies and in the setting of congenital heart disease. (See 'Associated with other cardiac disease' above.) Familial AV block, characterized by a progression in the degree of AV block in association with a variable apparent site of block, may be transmitted as an autosomal dominant trait. (See 'Familial disease' above and "Congenital third-degree (complete) atrioventricular block", section on 'Etiology'.) A variety of drugs, including beta blockers, non-dihydropyridine calcium channel blockers (especially verapamil and to a lesser extent diltiazem), digitalis, adenosine, and antiarrhythmic medications, can impair AV conduction, occasionally resulting in AV block. In most cases, the resulting AV block is at least partially reversible following withdrawal of the offending medication(s). (See 'Medications' above.) A variety of procedures performed on the heart may result in AV block, including most commonly open heart surgery, but also following transcatheter aortic valve implantation, catheter ablation of arrhythmias, transcatheter closure of a ventricular septal defect, and alcohol septal ablation. (See 'Cardiac procedures' above.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Leonard Ganz, MD, FHRS, FACC, who contributed to earlier versions of this topic review. https://www.uptodate.com/contents/etiology-of-atrioventricular-block/print 8/15 7/5/23, 10:35 AM Etiology of atrioventricular block - UpToDate Use of UpToDate is subject to the Terms of Use. REFERENCES 1. ZOOB M, SMITH KS. THE AETIOLOGY OF COMPLETE HEART-BLOCK. Br Med J 1963; 2:1149. 2. Khurshid S, Choi SH, Weng LC, et al. Frequency of Cardiac Rhythm Abnormalities in a Half Million Adults. Circ Arrhythm Electrophysiol 2018; 11:e006273. 3. LENEGRE J. ETIOLOGY AND PATHOLOGY OF BILATERAL BUNDLE BRANCH BLOCK IN RELATION TO COMPLETE HEART BLOCK. Prog Cardiovasc Dis 1964; 6:409. 4. LEV M. ANATOMIC BASIS FOR ATRIOVENTRICULAR BLOCK. Am J Med 1964; 37:742. 5. LEV M. THE PATHOLOGY OF COMPLETE ATRIOVENTRICULAR BLOCK. Prog Cardiovasc Dis 1964; 6:317. 6. Begg FR, Magovern GJ, Cushing WJ, et al. Selective cine coronary arteriography in patients with complete heart block. J Thorac Cardiovasc Surg 1969; 57:9. 7. Simon AB, Zloto AE. Atrioventricular block: natural history after permanent ventricular pacing. Am J Cardiol 1978; 41:500. 8. LEVINE SA, MILLER H, PENTON GB. Some clinical features of complete heart block. Circulation 1956; 13:801. 9. HEJTMANCIK MR, HERRMANN GR, SHIELDS AH, WRIGHT JC. A clinical study of complete heart block. Am Heart J 1956; 52:369. 10. ROWE JC, WHITE PD. Complete heart block: a follow-up study. Ann Intern Med 1958; 49:260. 11. Killip T 3rd, Kimball JT. Treatment of myocardial infarction in a coronary care unit. A two year experience with 250 patients. Am J Cardiol 1967; 20:457. 12. Godman MJ, Lassers BW, Julian DG. Complete bundle-branch block complicating acute myocardial infarction. N Engl J Med 1970; 282:237. 13. Sugiura T, Iwasaka T, Hasegawa T, et al. Factors associated with persistent and transient fascicular blocks in anterior wall acute myocardial infarction. Am J Cardiol 1989; 63:784. 14. Mullins CB, Atkins JM. Prognoses and management of venticular conduction blocks in acute myocardial infarction. Mod Concepts Cardiovasc Dis 1976; 45:129. 15. Hindman MC, Wagner GS, JaRo M, et al. The clinical significance of bundle branch block complicating acute myocardial infarction. 1. Clinical characteristics, hospital mortality, and one-year follow-up. Circulation 1978; 58:679. 16. Scheinman MM, Gonzalez RP. Fascicular block and acute myocardial infarction. JAMA 1980; 244:2646. https://www.uptodate.com/contents/etiology-of-atrioventricular-block/print 9/15 7/5/23, 10:35 AM Etiology of atrioventricular block - UpToDate 17. Dubois C, Pi rard LA, Smeets JP, et al. Short- and long-term prognostic importance of complete bundle-branch block complicating acute myocardial infarction. Clin Cardiol 1988; 11:292. 18. Harris A, Davies M, Redwood D, et al. Aetiology of chronic heart block. A clinico-pathological correlation in 65 cases. Br Heart J 1969; 31:206. 19. Bernstein, M . Auriculoventricular dissociation following scarlet fever: Report of a case. Am Heart J 1938; 16:582. 20. Rantz, LA, Spink, et al. Abnormalities in the electrocardiogram following hemolytic streptococcus sore throat. Arch Intern Med 1946; 77:66. 21. Lev M, Bharati S, Hoffman FG, Leight L. The conduction system in rheumatoid arthritis with complete atrioventricular block. Am Heart J 1975; 90:78. 22. CLARK NS. Complete heart block in children; report of three cases possibly attributable to measles. Arch Dis Child 1948; 23:156. 23. Rosenberg, DH . Electrocardiographic changes in epidemic parotitis (mumps). Proc Soc Exp Biol Med 1945; 58:9. 24. ENGLE MA. Recovery from complete heart block in diphtheria. Pediatrics 1949; 3:222. 25. Menon TB, Rao CK. Tuberculosis of the Myocardium Causing Complete Heart Block. Am J Pathol 1945; 21:1193. 26. SHEE JC. STOKES-ADAMS ATTACKS DUE TO TOXOPLASMA MYOCARDITIS. Br Heart J 1964; 26:151. 27. Lim CH, Toh CC, Chia BL, Low LP. Stokes-Adams attacks due to acute nonspecific myocarditis. Am Heart J 1975; 90:172. 28. Wray R, Iveson M. Complete heart block and systemic lupus erythematosus. Br Heart J 1975; 37:982. 29. Kleid JJ, Kim ES, Brand B, et al. Heart block complicating acute bacterial endocarditis. Chest 1972; 61:301. 30. Kir D, Mohan C, Sancassani R. Heart Brake: An Unusual Cardiac Manifestation of COVID-19. JACC Case Rep 2020; 2:1252. 31. Sardana M, Scheinman MM, Moss JD. Atrioventricular block after COVID-19: What is the mechanism, site of block, and treatment? Heart Rhythm 2021; 18:489. 32. Schott JJ, Alshinawi C, Kyndt F, et al. Cardiac conduction defects associate with mutations in SCN5A. Nat Genet 1999; 23:20. 33. Tan HL, Bink-Boelkens MT, Bezzina CR, et al. A sodium-channel mutation causes isolated https://www.uptodate.com/contents/etiology-of-atrioventricular-block/print 10/15 7/5/23, 10:35 AM Etiology of atrioventricular block - UpToDate cardiac conduction disease. Nature 2001; 409:1043. 34. Wang DW, Viswanathan PC, Balser JR, et al. Clinical, genetic, and biophysical characterization of SCN5A mutations associated with atrioventricular conduction block. Circulation 2002; 105:341. 35. Herfst LJ, Potet F, Bezzina CR, et al. Na+ channel mutation leading to loss of function and non-progressive cardiac conduction defects. J Mol Cell Cardiol 2003; 35:549. 36. Probst V, Kyndt F, Potet F, et al. Haploinsufficiency in combination with aging causes SCN5A- linked hereditary Len gre disease. J Am Coll Cardiol 2003; 41:643. 37. McNair WP, Ku L, Taylor MR, et al. SCN5A mutation associated with dilated cardiomyopathy, conduction disorder, and arrhythmia. Circulation 2004; 110:2163. 38. Olson TM, Michels VV, Ballew JD, et al. Sodium channel mutations and susceptibility to heart failure and atrial fibrillation. JAMA 2005; 293:447. 39. Makiyama T, Akao M, Tsuji K, et al. High risk for bradyarrhythmic complications in patients with Brugada syndrome caused by SCN5A gene mutations. J Am Coll Cardiol 2005; 46:2100. 40. https://www.ncbi.nlm.nih.gov/gtr/conditions/C1879286/ (Accessed on January 04, 2017). 41. Royer A, van Veen TA, Le Bouter S, et al. Mouse model of SCN5A-linked hereditary Len gre's disease: age-related conduction slowing and myocardial fibrosis. Circulation 2005; 111:1738. 42. Brink PA, Ferreira A, Moolman JC, et al. Gene for progressive familial heart block type I maps to chromosome 19q13. Circulation 1995; 91:1633. 43. Schott JJ, Benson DW, Basson CT, et al. Congenital heart disease caused by mutations in the transcription factor NKX2-5. Science 1998; 281:108. 44. Ikeda Y, Hiroi Y, Hosoda T, et al. Novel point mutation in the cardiac transcription factor CSX/NKX2.5 associated with congenital heart disease. Circ J 2002; 66:561. 45. Jay PY, Harris BS, Maguire CT, et al. Nkx2-5 mutation causes anatomic hypoplasia of the cardiac conduction system. J Clin Invest 2004; 113:1130. 46. Pashmforoush M, Lu JT, Chen H, et al. Nkx2-5 pathways and congenital heart disease; loss of ventricular myocyte lineage specification leads to progressive cardiomyopathy and complete heart block. Cell 2004; 117:373. 47. Gray B, Behr ER. New Insights Into the Genetic Basis of Inherited Arrhythmia Syndromes. Circ Cardiovasc Genet 2016; 9:569. 48. Arnsdorf MF, Schreiner E, Gambetta M, et al. Electrophysiological changes in the canine atrium and ventricle during progressive hyperkalaemia: electrocardiographical correlates and the in vivo validation of in vitro predictions. Cardiovasc Res 1977; 11:409. https://www.uptodate.com/contents/etiology-of-atrioventricular-block/print 11/15 7/5/23, 10:35 AM Etiology of atrioventricular block - UpToDate 49. Surawicz B. Relationship between electrocardiogram and electrolytes. Am Heart J 1967; 73:814. 50. Fisch C. Relation of electrolyte disturbances to cardiac arrhythmias. Circulation 1973; 47:408. 51. Hsu YJ, Lin YF, Chau T, et al. Electrocardiographic manifestations in patients with thyrotoxic periodic paralysis. Am J Med Sci 2003; 326:128. 52. Roberts NK, Perloff JK, Kark RA. Cardiac conduction in the Kearns-Sayre syndrome (a neuromuscular disorder associated with progressive external ophthalmoplegia and pigmentary retinopathy). Report of 2 cases and review of 17 published cases. Am J Cardiol 1979; 44:1396. 53. Sanyal SK, Johnson WW. Cardiac conduction abnormalities in children with Duchenne's progressive muscular dystrophy: electrocardiographic features and morphologic correlates. Circulation 1982; 66:853. 54. Komajda M, Frank R, Vedel J, et al. Intracardiac conduction defects in dystrophia myotonica. Electrophysiological study of 12 cases. Br Heart J 1980; 43:315. 55. James TN, Carson DJ, Marshall TK. De subitaneis mortibus. I. Fibroma compressing His bundle. Circulation 1973; 48:428. 56. den Dulk K, Brugada P, Braat S, et al. Myocardial bridging as a cause of paroxysmal atrioventricular block. J Am Coll Cardiol 1983; 1:965. 57. Rosen KM, Heller R, Ehsani A, Rahimtoola SH. Localization of site of traumatic heart block with His bundle recordings: electrophysiologic observations regarding the nature of "split" H potentials. Am J Cardiol 1972; 30:412. 58. Zeltser D, Justo D, Halkin A, et al. Drug-induced atrioventricular block: prognosis after discontinuation of the culprit drug. J Am Coll Cardiol 2004; 44:105. 59. Tisdale JE, Chung MK, Campbell KB, et al. Drug-Induced Arrhythmias: A Scientific Statement From the American Heart Association. Circulation 2020; 142:e214. 60. Sanoudos G, Reed GE. Late heart block in aortic valve replacement. J Cardiovasc Surg (Torino) 1974; 15:475. 61. Rosen KM, Mehta A, Rahimtoola SH, Miller RA. Sites of congenital and surgical heart block as defined by His bundle electrocardiography. Circulation 1971; 44:833. 62. Furman S, Young D. Cardiac pacing in children and adolescents. Am J Cardiol 1977; 39:550. 63. Hofschire PJ, Nicoloff DM, Moller JH. Postoperative complete heart block in 64 children treated with and without cardiac pacing. Am J Cardiol 1977; 39:559. https://www.uptodate.com/contents/etiology-of-atrioventricular-block/print 12/15 7/5/23, 10:35 AM Etiology of atrioventricular block - UpToDate 64. Berdajs D, Schurr UP, Wagner A, et al. Incidence and pathophysiology of atrioventricular block following mitral valve replacement and ring annuloplasty. Eur J Cardiothorac Surg 2008; 34:55. 65. Murray LE, Smith AH, Flack EC, et al. Genotypic and phenotypic predictors of complete heart block and recovery of conduction after surgical repair of congenital heart disease. Heart Rhythm 2017; 14:402. 66. Roten L, Wenaweser P, Delacr taz E, et al. Incidence and predictors of atrioventricular conduction impairment after transcatheter aortic valve implantation. Am J Cardiol 2010; 106:1473. 67. El-Sabawi B, Welle GA, Cha YM, et al. Temporal Incidence and Predictors of High-Grade Atrioventricular Block After Transcatheter Aortic Valve Replacement. J Am Heart Assoc 2021; 10:e020033. 68. Kesek M, Lindmark D, Rashid A, Jensen SM. Increased risk of late pacemaker implantation after ablation for atrioventricular nodal reentry tachycardia: A 10-year follow-up of a nationwide cohort. Heart Rhythm 2019; 16:1182. 69. Thanopoulos BD, Rigby ML. Outcome of transcatheter closure of muscular ventricular septal defects with the Amplatzer ventricular septal defect occluder. Heart 2005; 91:513. Topic 907 Version 30.0 https://www.uptodate.com/contents/etiology-of-atrioventricular-block/print 13/15 7/5/23, 10:35 AM Etiology of atrioventricular block - UpToDate GRAPHICS Major causes of atrioventricular (AV) block Physiologic and pathophysiologic Increased vagal tone Progressive cardiac conduction system disease With fibrosis and/or sclerosis (Lenegre disease) With calcification (Lev disease) Ischemic heart disease, including acute myocardial infarction Cardiomyopathy Infiltrative processes (eg, sarcoidosis, amyloidosis, hemochromatosis, malignancy, etc) Other non-ischemic cardiomyopathies (eg, idiopathic, infectious, etc) Infections (eg, viral myocarditis, Lyme carditis) Congenital AV block Related to structural congenital heart disease As part of neonatal lupus syndrome Other Hyperkalemia, severe hypo- or hyperthyroidism, trauma, degenerative neuromuscular diseases Iatrogenic Drugs Beta blockers, calcium channel blockers, digoxin, adenosine, antiarrhythmic drugs Cardiac surgery Post valvular surgery, post surgical correction of congenital heart disease Transcatheter aortic valve implantation Catheter ablation of arrhythmias Transcatheter closure of VSD Alcohol septal ablation for HCM VSD: ventricular septal defect; HCM: hypertrophic cardiomyopathy. Graphic 62885 Version 6.0 https://www.uptodate.com/contents/etiology-of-atrioventricular-block/print 14/15 7/5/23, 10:35 AM Etiology of atrioventricular block - UpToDate Contributor Disclosures William H Sauer, MD Grant/Research/Clinical Trial Support: Biosense-Webster [Catheter ablation]; Boston Scientific [Catheter ablation]. All of the relevant financial relationships listed have been mitigated. Mark S Link, MD No relevant financial relationship(s) with ineligible companies to disclose. Susan B Yeon, MD, JD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/etiology-of-atrioventricular-block/print 15/15