7/5/23, 10:35 AM Congenital third-degree (complete) atrioventricular block - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Congenital third-degree (complete) atrioventricular block : William H Sauer, MD, Edward P Walsh, 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: May 16, 2023. 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 higher degrees of block, 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 Two or more consecutive blocked P waves. Atrioventricular block is considered to be "congenital" when it occurs spontaneously in a fetus or young child. Congenital complete heart block (CHB) was first described in 1901 by Morquio, who also noted the familial occurrence and the association with Stokes-Adams attacks and death [1]. The presence of fetal bradycardia (40 to 80 beats per minute) as a manifestation of CHB was first noted in 1921 and is the initial sign of this disorder in many cases [2]. https://www.uptodate.com/contents/congenital-third-degree-complete-atrioventricular-block/print 1/20 7/5/23, 10:35 AM Congenital third-degree (complete) atrioventricular block - UpToDate The epidemiology, etiologies, clinical presentation, diagnosis, treatment, and prognosis associated with congenital CHB will be presented here. Discussions of noncongenital complete AV block are presented separately. (See "Etiology of atrioventricular block" and "Third-degree (complete) atrioventricular block".) EPIDEMIOLOGY The incidence of congenital CHB in the general population varies between 1 in 15,000 to 1 in 22,000 live-born infants [3,4]. Injury to fetal conduction tissues caused by transplacental exposure to maternal autoantibodies related to systemic lupus erythematosus or Sj gren's disease is responsible for 60 to 90 percent of cases of congenital CHB overall [5-7]. Among women with anti-Ro/SSA and/or anti-La/SSB antibodies, fetal/neonatal CHB occurs in approximately 2 percent of pregnancies [8,9]. However, once a woman has given birth to an infant with autoimmune CHB block, the recurrence rate in subsequent pregnancies rises to approximately 15 percent. (See "The anti-Ro/SSA and anti-La/SSB antigen-antibody systems".) As many as 40 percent of cases of congenital CHB do not present until later in childhood (mean age five to six years) [7]. Only rarely do these patients (5 percent) have proven autoimmune etiology [7]. ETIOLOGY The etiologies of congenital CHB include the following [10]: Autoimmune antibodies. Structural heart abnormalities due to congenital heart disease (eg, congenitally corrected transposition of the great arteries, endocardial cushion defects). Idiopathic familial congenital CHB. Complete heart block may also be seen in the fetus or young child as a consequence of myocarditis or mechanical trauma from surgical or transcatheter interventions; however, these acquired forms are not considered "congenital." Autoimmune congenital CHB Autoimmune heart block typically begins in utero, though clinical detection may occasionally be delayed until after birth or during early childhood [11]. In most cases, the block is third degree, with lower-grade block seen only occasionally. The mechanism is understood to involve damage to developing specialized conduction tissue from https://www.uptodate.com/contents/congenital-third-degree-complete-atrioventricular-block/print 2/20 7/5/23, 10:35 AM Congenital third-degree (complete) atrioventricular block - UpToDate passive transplacental passage of maternal autoantibodies to Ro/SSA and/or La/SSB intracellular ribonuclear proteins [10]. The risk of CHB in an individual fetus does not correlate directly with the maternal autoantibody titer. Importantly, the majority of mothers who give birth to a child with autoimmune CHB have never had symptoms of connective tissue disease up to time of delivery despite their positive serology. Some affected newborns may present with a multisystem neonatal lupus syndrome that can include skin rash, hepatobiliary disease, and thrombocytopenia [12]. (See "Neonatal lupus: Epidemiology, pathogenesis, clinical manifestations, and diagnosis", section on 'Clinical manifestations'.) Congenital CHB related to congenital heart defects Certain forms of congenital heart disease are associated with developmental abnormalities of the AV conduction tissues [13]. L-looped transposition of the great arteries (L-TGA) In L-TGA (also called "congenitally corrected" transposition of the great arteries) ( figure 1), the compact AV node develops outside of Koch's triangle in an unusual anterior location near the base of the right atrial appendage. This displaced node is often feeble and can deteriorate over time so that complete heart block is seen in as many as 5 percent of these patients at birth, and in more than 25 percent by adulthood. (See "L-transposition of the great arteries (L-TGA): Anatomy, clinical features, and diagnosis".) Endocardial cushion defects Displacement of the AV node also occurs in patients with endocardial cushion defects (ie, primum atrial septal defects or complete AV canal defects) ( figure 2). These hearts do not have a proper triangle of Koch, and the compact node is consequently displaced in a posterior direction beneath the mouth of coronary sinus. Similar to L-TGA, AV nodal function can be suboptimal in endocardial cushion defects, with complete heart block at birth in some individuals, and a significant risk of surgically- induced block following repairs. (See "Clinical manifestations and diagnosis of atrioventricular (AV) canal defects".) Syndromes with simple atrial septal defects Congenitally impaired AV nodal function can also be observed in some simple cases of atrial septal defect among patients with Holt- Oram syndrome, an autosomal dominant disorder causing cardiac and upper-limb abnormalities that involves a mutation on the TBX5 gene [14]. (See "Isolated atrial septal defects (ASDs) in children: Classification, clinical features, and diagnosis", section on 'Genetic disorders'.) Idiopathic familial congenital CHB Non-immune CHB in patients with a structurally normal heart has also been described as an idiopathic disorder with a strong familial tendency. In a https://www.uptodate.com/contents/congenital-third-degree-complete-atrioventricular-block/print 3/20 7/5/23, 10:35 AM Congenital third-degree (complete) atrioventricular block - UpToDate retrospective cohort of 141 children with AV block diagnosed in utero or up to age 15 years (51 percent female, 84 percent asymptomatic, 71 percent with complete AV block on presentation, with an additional 21 percent progressing from incomplete to complete AV block), 112 patients (79 percent) received permanent pacemakers, most prophylactically in asymptomatic patients (70 of 112 patients [63 percent]) [15]. Familial screening electrocardiograms (ECGs) were obtained from 130 parents of patients in the cohort and were compared with 130 matched healthy controls [16]. Parents of the children with AV block were significantly more likely to have conduction abnormalities compared with healthy controls, including complete or incomplete right bundle branch block (39 versus 2 percent), complete or incomplete left bundle branch block (15 versus 3 percent), and PR prolongation (19 versus 0 percent). Progressive AV block has also been reported in association with an extracardiac phenotype that includes a brachyfacial abnormality, finger deformity, and dental dysplasia [17]. Members of these two unrelated families shared a common mutation in the third exon of the gene encoding for connexin-45, a gap junction channel involved in electrical signal propagation in the sinoatrial (SA) node, AV node, and His-Purkinje system. PATHOPHYSIOLOGY Most cases of congenital CHB are immune-mediated and are characterized pathologically by fibrous tissue that either replaces the atrioventricular (AV) node and its surrounding tissue or by an interruption between the atrial myocardium and the AV node [18-26]. The net effect is that the block is usually at the level of the AV node [20,22,24,27,28], allowing junctional escape rhythms that can usually support the fetal and neonatal circulation, at least temporarily [12,29]. The primary injury is caused by the binding of anti-Ro/SSA and/or anti-La/SSB antibodies to the developing AV node and its surrounding tissue [9,18,30]. Both Ro/SSA and La/SSB antigens are abundant in fetal heart tissue between 18 and 24 weeks [30]. Apoptosis induces translocation of Ro/SSA and La/SSB to the surface of fetal cardiomyocytes; anti-Ro and anti-La antibodies then bind to the surface of the fetal cardiocytes and induce the release of tumor necrosis factor by macrophages, which then results in fibrosis [31]. In addition to inducing tissue damage, anti-Ro/SSA and/or anti-La/SSB antibodies inhibit calcium channel activation or the cardiac L- and T- type calcium channels themselves; L-type channels are crucial to action potential propagation and conduction in the AV node [32,33]. Congenital CHB in patients with congenital heart defects is directly related to abnormalities in the embryologic development of the specialized atrioventricular conduction tissues that lead to displacement and functional impairment of the AV node and/or His bundle. https://www.uptodate.com/contents/congenital-third-degree-complete-atrioventricular-block/print 4/20 7/5/23, 10:35 AM Congenital third-degree (complete) atrioventricular block - UpToDate CLINICAL MANIFESTATIONS The manifestations of congenital CHB vary according to the age at presentation, underlying etiology, ventricular rate of the escape rhythm, and ventricular function. Patients with autoimmune congenital CHB tend to present earlier than those with CHB due to other causes [34]. In addition to atrioventricular conduction defects, in a small number of cases autoimmune CHB can be associated with sinoatrial node dysfunction as well as a more diffuse cardiomyopathy that can result in depressed ventricular function and endocardial fibroelastosis [7,9,18,35,36]. (See "Neonatal lupus: Epidemiology, pathogenesis, clinical manifestations, and diagnosis", section on 'Other cardiac abnormalities'.) Autoimmune heart block typically begins in utero, though clinical detection may occasionally be delayed until after birth or during early childhood. In most cases, the block is third degree, with lower-grade block seen only occasionally. The noncardiac manifestations of neonatal lupus resolve as maternal antibodies dissipate in the infant, but cardiac damage tends to be irreversible. In utero presentation Congenital heart block may present with fetal bradycardia between 18 and 28 weeks of gestation [7,11,12]. The clinical manifestations, diagnosis, and approach to management of intrauterine congenital CHB are discussed separately. (See "Neonatal lupus: Epidemiology, pathogenesis, clinical manifestations, and diagnosis" and "Fetal arrhythmias", section on 'Heart block'.) Neonatal presentation The primary finding in neonates with congenital CHB is a slow heart rate that is usually less than 100 beats per minute. Neonates with congenital CHB otherwise have few specific physical examination findings, although they may appear pale or diaphoretic related to the reduction in cardiac output. Other clinical clues in the neonate may include: Intermittent cannon waves in the neck Variable intensity of the first heart sound (see "Auscultation of heart sounds") Intermittent gallops and murmurs Signs of congestive heart failure (eg, crackles on lung examination, elevated jugular venous pulsations, peripheral edema, etc) As with cases presenting in utero, almost all presenting in the neonatal period (90 percent in one series) are due to maternal autoantibodies [7,37]. First- or second-degree AV block found in infants at birth can progress to CHB and should be followed carefully [35,38]. https://www.uptodate.com/contents/congenital-third-degree-complete-atrioventricular-block/print 5/20 7/5/23, 10:35 AM Congenital third-degree (complete) atrioventricular block - UpToDate Presentation in later childhood Up to 40 percent of patients with congenital CHB present later in childhood. Reasons for the late presentation are speculative, but likely relate to an intermittent early course or a higher ventricular rate of the escape rhythm [39]. The primary finding in children with congenital CHB is a slow heart rate with or without bradycardia-related symptoms, including reduced exercise tolerance and presyncope or syncope (Stokes-Adams attacks) [7,40]. Sudden death has also rarely been described [29,41,42]. Although congenital CHB may be intermittent when first detected, it usually becomes persistent over time [7]. While congenital CHB diagnosed for the first time later in childhood may be congenital in origin, escaping notice because of a higher ventricular rate and the absence of symptoms, patients who present later in childhood likely have preserved AV conduction at birth and acquire progressive AV nodal disease thereafter [7]. In a single-center study of 102 patients with congenital CHB diagnosed over a 34-year period, the number of presentations later in childhood remained constant from 1980 to 1998 despite the introduction of fetal echocardiography and the wide availability of heart rate monitoring during pregnancy and labor, suggesting that AV conduction is preserved at birth and becomes abnormal at a later time in a subset of patients [7]. Maternal autoantibody exposure accounts for almost all cases presenting in utero or the neonatal period, but for only a few cases occurring at older ages (5 percent in one report) [7]. (See 'Epidemiology' above and "Neonatal lupus: Epidemiology, pathogenesis, clinical manifestations, and diagnosis".) DIAGNOSIS In nearly all cases, the diagnosis of complete heart block can be made by obtaining a surface ECG, ideally a full 12-lead ECG, though a single-lead rhythm strip is sometimes adequate if a full 12-lead ECG cannot be obtained. The diagnosis is usually suspected when a slow pulse is detected and heart block is confirmed by ECG or by ambulatory ECG monitoring [7,40,41]. DIFFERENTIAL DIAGNOSIS Complete heart block has a relatively unique appearance on the ECG, with evidence of atrial (P waves) and ventricular (QRS complexes) activity that are independent of each other, and an atrial rate faster than the ventricular rate. Rarely, complete AV block can occur in which the atrial rate is exactly twice the ventricular rate (eg, atrial rate of 80 beats per minute with a ventricular rate of 40 beats per minute), in which case the appearance on ECG could be similar to that of second- https://www.uptodate.com/contents/congenital-third-degree-complete-atrioventricular-block/print 6/20 7/5/23, 10:35 AM Congenital third-degree (complete) atrioventricular block - UpToDate degree AV (ie, 2:1) block. However, any slight variation in the exact multiples should result in variations on the ECG that allow the distinction between third-degree (complete) AV block and second-degree AV block. In utero CHB must be differentiated from benign bradycardia caused by frequent blocked premature atrial complexes (also referred to a premature atrial beat, premature supraventricular complex, or premature supraventricular beat), which can be reliably distinguished on the basis of the fetal echocardiogram. TREATMENT In utero treatment The management options for congenital CHB in utero are limited, and treatment of the fetus with CHB is primarily expectant. Fortunately, the fetus will tolerate the slow escape rhythm in the majority of cases. If hydrops fetalis or other signs of fetal distress should develop, early delivery and emergency pacing may be needed. The approach to in utero treatment of fetal CHB is discussed in detail separately. (See "Neonatal lupus: Management and outcomes", section on 'In utero management' and "Fetal arrhythmias", section on 'Heart block'.) Postnatal treatment For neonates and children who present later with congenital CHB, the principal therapeutic decision involves the need for, and the potential timing of, permanent pacemaker insertion. For older children who are able to express themselves about symptoms, the presence or absence of symptoms will help guide the decision. Patients with an adequate ventricular heart rate and no symptoms can usually be followed with serial observation, while symptomatic patients (typically those with a slower ventricular heart rate) will require a permanent pacemaker [43]. Most patients (approximately 90 percent or greater) ultimately have a pacemaker inserted ( figure 3), regardless of when CHB developed (ie, in utero or following delivery) [7,41]. Our approach to pacemaker implantation is in general agreement with the professional society guidelines for management of bradycardia, which specifically address the population of patients with congenital CHB [43-45]. Pacemaker implantation was recommended (class I) or felt to be reasonable (class IIa) for patients with congenital CHB and the following characteristics: Symptomatic bradycardia or low cardiac output (class I). Wide QRS escape rhythm, complex ventricular ectopy, or ventricular dysfunction (class I). Asymptomatic adults with congenital CHB (class IIa). Infants with normal anatomy and a ventricular rate less than 55 beats per minute (class I). https://www.uptodate.com/contents/congenital-third-degree-complete-atrioventricular-block/print 7/20 7/5/23, 10:35 AM Congenital third-degree (complete) atrioventricular block - UpToDate Infants with other structural congenital heart disease and a ventricular rate less than 70 beats per minute (class I). Children beyond the first year of life with an average heart rate less than 50 beats per minute, or abrupt pauses two to three times the basic R-R cycle length (class IIa). The type of pacemaker implanted is based primarily upon patient age/size, as well as the presence or absence of congenital heart defects. Implants for infants and very young children will usually require epicardial leads due to small caliber of the standard insertion veins used for transvenous devices, as well as the expectation for thoracic growth that may eventually place tension on transvenous leads [46]. Epicardial leads are also used in patients of any age with septal defects that allow intracardiac shunting and thus increase the risk of thromboembolic complications [47]. A transvenous dual-chamber pacemaker is preferred at most centers when there are no significant size constraints or other contraindications. When feasible, consideration should be given to techniques for ventricular lead placement that activate the native His bundle or left bundle branch [48]. (See "Modes of cardiac pacing: Nomenclature and selection".) PROGNOSIS CHB presenting in utero or the neonatal period, which is mostly due to maternal autoantibodies, is associated with a high early mortality [10,49-51]. The outcome for patients diagnosed as neonates is better than for those diagnosed in utero. Infants and young children with complete heart block who are asymptomatic usually remain so until later childhood, adolescence, or adulthood [3,52]. (See "Neonatal lupus: Management and outcomes".) Among 175 cases of congenital CHB diagnosed in the fetus, 29 (17 percent) died either in utero or within the first three months of life [7,12]. Survival appears to relate to gestational age at birth, with offspring born before 34 weeks having a higher mortality rate than those born later (52 versus 9 percent) [12]. Infants with first- or second-degree heart block at birth can progress to complete heart block [12,35,38]. (See 'Clinical manifestations' above.) In a single-center cohort of 33 patients who presented in the neonatal period, five had signs of heart failure, but none had hydrops fetalis [7]. None died within the first six months, but two died at 0.9 and 1.5 years of age. Prognosis is generally excellent among infants and those diagnosed later in childhood [10]. However, exercise limitation and even mortality in childhood are not negligible [40,53,54]. Children with a mean heart rate below 50 beats per minute and evidence of an unstable junctional escape rhythm may be at particular risk [37,40]. Even patients who have been https://www.uptodate.com/contents/congenital-third-degree-complete-atrioventricular-block/print 8/20 7/5/23, 10:35 AM Congenital third-degree (complete) atrioventricular block - UpToDate asymptomatic throughout childhood are at increased risk of sudden death. In a review of 102 patients who were without symptoms through age 15, 27 (26 percent) had a subsequent syncopal episode, eight of which were fatal [41]. Those patients who do not experience symptoms or syncopal attacks may still suffer physiologic consequences of bradycardia. The ventricular rate tends to fall slowly with age [41]. To compensate for the slow heart rate, the heart enlarges to produce a higher stroke volume; in some cases, this can lead to voltage criteria for left ventricular enlargement and nonspecific ST-T wave changes [55] as well as to heart failure [56,57]. In general, the prognosis following pacemaker implantation is excellent [37,58,59]. However, a significant number of patients (5 to 11 percent) develop heart failure over the long-term, even if a pacemaker is inserted [56,57,60]. In a study of 149 patients followed for 10 years, 6 percent developed a dilated cardiomyopathy by 6.5 years of age; risk factors included anti-Ro/SSA or anti-La/SSB antibodies, increased heart size at initial evaluation, and the absence of improvement with a pacemaker [57]. Patients diagnosed prior to one month of age are more likely to have left ventricular systolic dysfunction both prior to permanent pacemaker implantation and over the long-term [37]. In another study of 114 subjects followed over a period of 40 years, 26 subjects (23 percent) reached the primary composite outcome of death, LV systolic dysfunction, heart failure, cardiomyopathy, or use of cardiac resynchronization therapy, with an incidence rate of 2.2 per 100 person-years [60]. The primary outcome occurred at a median of 3.1 years after diagnosis. While the development of heart failure in such patients may be a consequence of myocardial fibrosis associated with CHB [56], heart failure is also a well-recognized long-term consequence of right ventricular pacing with consequent ventricular asynchrony [61] (see "Modes of cardiac pacing: Nomenclature and selection", section on 'Modes to minimize ventricular pacing'). Patients with congenital heart block who develop ventricular dysfunction in the setting of chronic right ventricular pacing will usually benefit from upgrading to cardiac resynchronization with addition of a left ventricular pacing lead [62]. An alternative for this patient group is His bundle pacing as a method to mitigate detrimental effects of asynchronous right ventricular pacing [63]. (See "Cardiac resynchronization therapy in heart failure: Indications and choice of system".) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cardiac implantable https://www.uptodate.com/contents/congenital-third-degree-complete-atrioventricular-block/print 9/20 7/5/23, 10:35 AM Congenital third-degree (complete) atrioventricular block - UpToDate electronic devices".) 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)" and "Patient education: Heart block in children (The Basics)") SUMMARY AND RECOMMENDATIONS Congenital third-degree (complete) heart block (CHB), a relatively rare disorder affecting between 1 in 15,000 to 1 in 22,000 live-born infants, may result from autoimmune antibodies, structural heart abnormalities due to congenital heart disease, or may be idiopathic. Autoimmune CHB due to maternal auto antibodies that cross the placenta is responsible for 60 to 90 percent of cases of congenital CHB overall. (See 'Epidemiology' above and 'Etiology' above.) The manifestations of congenital CHB vary according to the age at presentation, underlying etiology, ventricular rate of the escape rhythm, and ventricular function. The primary finding in neonates with congenital CHB is a slow heart rate that is usually less than 100 beats per minute. Neonates with congenital CHB otherwise have few specific physical examination findings, although they may appear pale or diaphoretic related to the reduction in cardiac output. (See 'Clinical manifestations' above.) In nearly all cases, the diagnosis of complete heart block can be made by obtaining a surface ECG. The diagnosis is usually suspected when a slow pulse is detected and heart https://www.uptodate.com/contents/congenital-third-degree-complete-atrioventricular-block/print 10/20 7/5/23, 10:35 AM Congenital third-degree (complete) atrioventricular block - UpToDate block is confirmed by ECG or by ambulatory ECG monitoring. (See 'Diagnosis' above.) For neonates and children who present later with congenital CHB, the principal therapeutic decision involves the need for and the potential timing of permanent pacemaker insertion. For older children who are able to express themselves about symptoms, the presence or absence of symptoms will help guide the decision. Patients with an adequate ventricular heart rate and no symptoms can usually be followed with serial observation, while symptomatic patients (typically those with a slower ventricular heart rate) will require a permanent pacemaker. In general, the prognosis following pacemaker implantation is excellent. 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