Pediatric Congenital Atrioventricular Block

Third-degree or complete congenital atrioventricular block (CAVB) is seen either in the fetal life or any time after birth with complete atrioventricular (AV) dissociation and bradycardia and is called congenital heart block to differentiate it from acquired third-degree heart block. It can occur in the fetal life due to maternal disease or due to a congenital heart defect in the fetus and can manifest at any given time before or after birth. CAVB can occur in a structurally normal heart (isolated CAVB) or in association with congenital heart disease (complex CAVB with congenital heart defects). (See Etiology.)

More recently, it has been recognized that the association and prognosis of CAVB differ depending on whether the block is identified in the fetus, newborn, or older child.

Isolated CAVB occurs in the absence of other congenital heart defects. It usually is seen in association with certain autoimmune antibodies in the mother that cross the placenta and damage the atrioventricular (AV) node of the fetus. The mother can be completely asymptomatic in presence of these autoimmune antibodies or may have a diagnosis of an autoimmune disorder (eg, systemic lupus erythematosus, Sjögren syndrome). (See Etiology, Presentation, and Workup.)

Isolated CAVB can also occur due to myocarditis and rare hereditary conditions, such as storage disorders (eg, Hurler syndrome, Hunter syndrome). Often, no etiology is found for an isolated CAVB.

CAVB can also be seen with certain congenital heart defects, most often complex defects, such as heterotaxy with accompanying AV canal defects and L-transposition of the great arteries.

Congenital atrioventricular block (CAVB) with structural heart disease is considered to be caused by failure of the AV conduction system to develop during heart development. This may be a result of increased distance between the AV node and the ventricular conduction tissues, as when associated with structural congenital heart disease or damage related to the passage of maternal autoantibodies.

Isolated CAVB was first described in 1901. In the early 1970s, the association with maternal connective-tissue disease was recognized.

Autoimmune CAVB is presumed to be caused by injury from the placental passage of maternal anti-Ro and anti-La (or related) antibodies, which are present in more than 90% of mothers during pregnancy or at the time of delivery. The mothers may or may not have a diagnosis of an autoimmune disease made at that time. Once these autoantibodies have developed, they can be detected in the mother lifelong, although the titers may vary. These autoantibodies damage the AV conduction tissue possibly by inflammation or direct ion channel interaction in the early stage and later by fibrosis.[1, 2, 3]  There is a population-based recurrence rate of 12%, although factors other than maternal autoantibodies also contribute to the risk of congenital heart block in the neonates, including major histocompatibility class (MHC) I and II.[4]  Further studies should be undertaken to elucidate the molecular pathways involved in the development of CAVB.[5]

CAVB occurs in as many as 5% of children born to mothers with anti-Ro antibody, which can be seen with subclinical or clinical maternal lupus erythematosus, maternal Sjögren syndrome, or other maternal autoimmune diseases.[6] After birth, the children may present with varying degrees of heart block, including CAVB, cardiomyopathy, and other manifestations of neonatal lupus syndrome.[7] However, the majority of infants who are born to these mothers do not manifest AV block. Owing to the high incidence of anti-Ro/SSA and anti-p200 antibodies in female patients with connective tissue diseases, screening for congenital heart block-associated autoantibodies during pregnancy may be a strong consideration.[8]

In a Japanese retrospective study comprising 52,124 clinical records of pregnancies from a single center, there were 183 anti-Ro/SSA antibody-positive women, in whom titers of anti-Ro/SSA, anti-Ro52, and anti-Ro60 antibodies were independent risk factors for fetal congenital heart block, and the use of corticosteroids before 18 weeks’ gestation was an independent protective factor.[9] The investigators indicated that measurement of anti-Ro52 antibody levels (area under the receiver-operating characteristic [ROC] = 0.84) may aid in identifying anti-Ro/SSA antibody-positive women at risk for delivering infants with congenital heart block. Interestingly, two cases of fetal congenital heart block occurred in women without known risk factors (eg, positive anti-Ro/SSA antibody, previous pregnancy with congenital heart block).[9]

Many times, no clear etiology is determined for isolated CAVB. Rarely, it can occur as a result of myocarditis, infiltrative disease, or cardiomyopathy. Hereditary diseases such as Hurler cardiomyopathy and Hunter cardiomyopathy may be associated with CAVB.

Complex CAVB is associated with congenital heart defects that have structural abnormality of the conduction system. These heart defects are usually complex, such as L-transposition of the great arteries.

The majority of the congenital atrioventricular block (CAVB) cases are autoimmune AV blocks.[10] Autoimmune AV block occurs in approximately 1 per 14,000-20,000 live births. However, because significant fetal loss is thought to result from this disease, the true incidence of the disease (per conception) may be significantly higher. Structural congenital heart block is also rare, but with a higher proportion of fetal loss. The prevalence of isolated CAVB may be slightly higher in females than in males.

The prognosis in isolated complete congenital atrioventricular block (CAVB) is relatively good but may be influenced by the patient's age at presentation. Patients presenting as fetuses or at birth have significantly higher morbidity and mortality rates than do patients presenting later in childhood.[11]

Fetal bradyarrhythmia associated with congenital heart defects has a poor prognosis.[12]  Patients with L-transposition of the great arteries and other complex structural cardiac defects have a worse prognosis unless detected and treated early.[13]

According to a long-term follow-up study by Michaelsson and colleagues, adults with complete CAVB who did not have pacemaker implantation had a poorer prognosis than those who did because of multiple complications related to their disease.[14] Therefore, in the adolescent who has not yet developed indications for pacing (an unusual case), recommendations for pacemaker implantation should be considered, regardless of symptoms or underlying escape rate.

Morbidity and mortality

The fetal mortality rate of isolated CAVB may be as much as 30%-50%. Patients who are diagnosed and treated in the neonatal period have a survival rate of 94%, and patients who are diagnosed and treated in childhood have a survival rate of 100%.

Risk factors for death in patients with isolated CAVB include fetal diagnosis, very low heart rate, low birth weight, premature gestation, male gender, hydrops fetalis, endocardial fibroelastosis, and diminished ventricular function.

Hydrops fetalis is the risk factor for patients with structural heart disease and CAVB. Fetal and newborn mortality rates in congenital heart block with structural heart disease remain high, even if effective pacing is used.

Complications

Long-term potential complications in all patients include development of ventricular dilatation and dysfunction. Children with autoimmune CAVB may also have frequent ectopy and primary or secondary long QT syndrome. Patients without a pacemaker may develop AV valve regurgitation, atrial rhythm disorders, thromboembolism, congestive failure, or sudden death.[14]  Patients with a pacemaker may develop pacing system–related complications, including lead fracture, mal-sensing, and pacing system infections. Replacement of pacemakers is required at intervals and can lead to complications from the procedure. Congenital complete heart block is an increasingly recognized cause of fetal loss. (See Treatment.)

Parents who are at risk of having a child with congenital atrioventricular block (CAVB) must be informed that this disease is easily identifiable and relatively easily treated after birth. The stigma of pacing as a therapy associated with elderly persons should be avoided. Parents should recognize that their affected offspring are likely to receive and benefit from pacing therapy at some point during childhood but that pacemaker therapy is intentionally deferred until indications are present to preserve lifelong access for pacing systems.

Patients and their families should be instructed to avoid medications that can cause AV block (eg, calcium channel blockers, beta blockers).

Congenital atrioventricular block (CAVB) may be identified during prenatal examinations, in the perinatal period, or during childhood or adulthood. Historical and other features widely vary and particularly depend on the timing of presentation and accompanying structural heart disease.

Isolated CAVB

Many of the mothers confirmed to have a fetus with autoimmune AV block may have no symptoms. The fetus in whom isolated CAVB is identified during the perinatal period usually presents with an incidental finding of bradycardia or hydrops fetalis.

Occasionally, these mothers may have a history of recurrent fetal loss. Fetuses of such mothers should be routinely evaluated for CAVB.

The mother is often completely asymptomatic. In addition to fetuses who are incidentally identified, siblings of children with known isolated heart block are at a higher risk with a recurrence rate for heart block of 17%-22%.

In the perinatal period, fetal bradycardia may have myriad causes. However, when persistent bradycardia is identified in the third trimester, emergency delivery is sometimes inappropriately carried out without differentiating acute causes of bradycardia related to fetal distress from the more chronic condition of isolated CAVB.

Newborns with congenital heart block may present with a hydropic appearance secondary to fetal heart failure or may develop signs of low cardiac output within hours to days after birth. However, affected newborns often appear asymptomatic and may have accelerated ventricular rates approaching those of healthy newborns. Congenital heart block is not likely to be identified in many such infants until well after birth. An associated finding of neonatal lupus may be present.

In older infants or children, signs of low cardiac output due to bradycardia, such as pallor, mottling, lethargy, exercise intolerance, palpitations, dizziness, or syncope, may occur. Children may have sleep disturbances or be asymptomatic.

CAVB with structural heart disease

The diagnosis of a congenital heart defect in one child or first-degree relative is an indication for fetal echocardiography to check for cardiac malformations.

Children with structural heart defects may present with cyanosis, murmur, failure to thrive, or recurrent pneumonias or may be completely asymptomatic in childhood (such as children with L-transposition of the great arteries and intact ventricular septum).

The fetus may be monitored with ultrasonography for varying degrees of heart block and hydrops fetalis. In the newborn, the findings may range from asymptomatic to signs of congestive heart failure and low cardiac output.

The most typical physical finding is a low heart rate for age. Because the block is usually complete and the escape rhythm is usually junctional in origin, a regular rhythm at 60-80 beats per minute (bpm) is often found. Auscultation demonstrates a variable first heart sound caused by the AV asynchrony.

Congenital atrioventricular block (CAVB) may be associated with findings of low cardiac output or congestive heart failure. Low cardiac output may manifest with physical findings of irritability or lethargy, cool skin, mottling, or cyanosis.

Congestive heart failure may manifest with tachypnea and hepatomegaly. If congestive heart failure has been present prenatally, marked edema may be part of the complex of hydrops fetalis.

Children with neonatal lupus can present with rash, as well as with neurologic and hepatic manifestations. The rash can occur some days after birth and is worsened with sun exposure. Annular or elliptical erythematous plaques can be present on the skin of face, scalp, and extremities. It usually resolves without scarring but can be associated with residual hypopigmentation or, rarely, telangiectasias.

Children with structural heart disease may manifest symptoms and signs related to the specific congenital heart defect. Patients with heterotaxia syndrome may be cyanotic. Patients with L-transposition of the great arteries may be completely asymptomatic or may demonstrate a murmur.

After birth, electrocardiography (ECG) is recommended to assess for congenital atrioventricular block (CAVB) and to assess the QT interval that can be prolonged. ECG and Holter ambulatory ECG monitoring are routinely performed initially and periodically in patients with complete CAVB.

All children, regardless of fetal findings, should undergo an electrocardiogram after birth to check the conduction intervals. Children with first-degree or second-degree AV block have been known to progress to third-degree CAVB.

Holter monitoring (ambulatory ECG) is recommended to determine if the AV block is intermittent or persistent and to evaluate for associated arrhythmias.

Exercise testing is performed on a regular basis in patients who are capable, usually in patients older than age 7 years. Electrophysiologic testing is not routinely performed in patients with CAVB, although it provides information regarding pathophysiology and prognosis in certain cases.

Chest radiography may reveal cardiomegaly and pleural effusions. Heterotaxia may be suspected in presence of visceroatrial discordance. One should look for a midline liver, rightward stomach bubble, and dextrocardia. Looking at lead placement in temporary and permanent pacemakers is helpful.

Consultations

The mother should consult with a rheumatologist to begin monitoring for possible autoimmune disease. Consultation with a rheumatologist is also advised for the infant, particularly if other manifestations of neonatal lupus erythematosus are present.

Genetic consultation is recommended for children with first-degree relatives with structural heart disease or those with storage disorder or cardiomyopathy.

Pediatric cardiology consultation is necessary for every case.

In patients with congenital atrioventricular block (CAVB), routine electrolyte assays should be performed to assess for metabolic derangements (especially hyperkalemia), and a complete blood count (CBC) should be obtained to assess for anemia, neutropenia, and thrombocytopenia.

Neonatal assessment should include a measurement of anti-Ro and anti-La antibody levels, preferably using a line immunoassay[3] in the mother. Assessment for other organ and/or tissue damage should include a platelet assessment to rule out thrombocytopenia and an assessment of liver enzymes to rule out alloimmune hepatitis.

If inflammatory disease is suspected, workup for various infectious etiologies (eg, human immunodeficiency virus [HIV]) should be performed. Cardiac troponins and pro-brain natriuretic peptide (BNP) levels can be helpful in assessing the severity of the disease.

If hypertrophic cardiomyopathy is suspected, evaluation for lysosomal storage diseases should be included.

Preductal and post-ductal saturations by pulse oximetry should be performed. Check for hypoxemia and acidosis using arterial blood gas (ABG) findings. Also, check lactic acid for perfusion. A hyperoxia test is very helpful in differentiating lung disease–related hypoxemia versus hypoxemia due to a cyanotic heart disease. One can evaluate for Howell-Jolly/Heinz bodies on peripheral smear for evaluation of asplenia that is seen with heterotaxia syndromes.

Echocardiography should be performed initially and during periodic follow-up care in affected fetuses, infants, and children in order to assess ventricular function and size and to rule out congenital or acquired cardiac malformations or valve dysfunction.[16]

Children of mothers with the anti-Ro and anti-La antibodies should undergo regular fetal ultrasonographic assessments, including detailed fetal echocardiography to identify conduction delay, bradycardia, and ventricular function.

Mothers with the autoimmune antibodies or those with one affected child should undergo regular fetal ultrasonographic assessments,[15] including detailed fetal echocardiography, to identify subsequent affected pregnancies starting early, at 16 weeks' gestation. Fetal echocardiography may reveal varying degrees of AV block. Fetal monitoring should be performed to look for bradycardia, fetal distress, and hydrops fetalis.

Fetal echocardiography is geared towards looking for early heart block, bradycardia, arrhythmias, pericardial effusion, cardiomegaly, valvular insufficiency (especially tricuspid regurgitation), decreasing contractile function, and abnormal venous and arterial pulsations.

Myocardial biopsies are not routinely performed in patients with congenital atrioventricular block (CAVB). However, histologic findings have been reported from experimental studies and autopsy specimens; these findings demonstrated various stages of fibrosis and calcification of the AV conduction area, depending on the timing of the specimen.

Immune deposition is also a frequent finding, although whether this is specific for the conduction system or occurs throughout the myocardium in general is unclear. The mechanisms of cell death and fibrosis are unclear. Hypotheses include alloimmune-mediated inflammatory responses and immune-triggered apoptosis.

In some cases, the sinoatrial node has also been found to be affected and may be hypoplastic, fibrotic, or completely absent.

Pharmacologic therapy

Little evidence suggests that the administration of steroids or immunoglobulins or the performance of plasmapheresis in the mother can reverse third-degree atrioventricular (AV) block in the fetus. However, these therapies may be helpful in early first- and second-degree heart block and in reducing associated myocardial dysfunction.

Regular and close monitoring for heart block and transplacental therapy with fluorinated steroids (dexamethasone) and beta sympathomimetics have been used by some centers with satisfactory results at the first evidence of heart block and bradycardia with hydrops, respectively. However, current evidence doesn’t support the use of fluorinated steroids in the treatment of complete AV block.[17]  Prophylactic therapy is not currently indicated, because these medications can have maternal and fetal side effects.[18]

Children with complete congenital atrioventricular block (CAVB) due to heart disease, if associated with pulmonary atresia or severe stenosis, may need to be on prostaglandin therapy to keep the ductus patent.

In patients with CAVB, prophylactic antibiotic therapy during and following surgery appears to reduce the incidence of pacemaker system infections, although current studies do not reach statistical significance because of the relative rarity of this complication (approximately 1%).

Hydrops fetalis

Therapy for hydrops fetalis can be challenging in utero and after birth. A staged approach with stabilization of the patient, drainage of the effusions, the use of intravenous inotropes (dopamine) and chronotropes (isoproterenol), and placement of a pacemaker has shown some success. Some centers recommend cesarean and preterm delivery for fetuses with CAVB and hydrops fetalis.

Bradycardia

In the perinatal period, fetal bradycardia may be an incidental finding. However, when persistent bradycardia is identified in the third trimester, emergency delivery is sometimes inappropriately carried out without differentiating acute causes of bradycardia related to fetal distress from the more chronic condition of isolated CAVB.

The medical care of congenital atrioventricular block (CAVB) is currently focused on identifying the optimal timing of pacemaker therapy to ensure a positive outcome. Additional care is aimed at identifying and treating the associated conditions that arise. Patients who present with symptoms as fetuses or newborns may require earlier pacing than do those who present with symptoms later in childhood. Fetuses with hydrops fetalis secondary to maternal autoimmune disease have successfully received pacing in utero; however, this has not prevented fetal demise.

Symptoms referable to bradycardia are an indication for pacing in complete CAVB. Because severe symptoms (eg, syncope) occasionally arise suddenly or sudden cardiac death can occur, additional risk factors identified from monitoring have been recommended as indications for pacing.[19]

Temporary pacing can be achieved transcutaneously, transesophageally, or transvenously. However, permanent pacemaker placement is eventually needed in most children with CAVB. Major criteria for pacing based on ECG or Holter monitoring in children include an average heart rate of less than 50 bpm, a nighttime or sleeping average heart rate of less than 45 bpm, or pauses secondary to AV block that are longer than 3 seconds.

In the setting of borderline major criteria, other criteria that may influence the decision for timing of pacemaker implantation include cardiomegaly, a high atrial rate, junctional instability (eg, junctional exit block), a broad complex escape rhythm, diminished ventricular response to exercise, QT prolongation, and complex ventricular ectopy.

When criteria are met, surgical implantation of an epicardial pacemaker should be performed, with knowledge of the implications of pacing in children and recognition of the lifelong need for pacing and pacemaker lead access. Multiple backup pacing systems at the time of surgery (eg, temporary transvenous pacing, transthoracic pacing units) are helpful to avoid the extremes of bradycardia that may be associated with anesthesia and pacemaker surgery.

Venous obstruction, small patient size, and actual or potential right-left shunting are relative contraindications for transvenous pacing. Fortunately, epicardial pacing leads have greatly improved and allow for successful pacing system insertion under these conditions. Some centers are using neonatal endocardial pacing systems.

In children beyond the neonatal period, an endocardial pacing with transvenous approach or robot-assisted thoracoscopic implantation of left ventricular leads is possible. The risk of venous occlusion appears to correlate with the ratio of available transvenous lead body sizes and the patient's body surface area.[20] Exceeding this ratio may lead to a high incidence of venous obstruction. Robot-assisted minimally invasive surgery has the advantage of avoiding intravascular endocarditis and thrombosis.

In addition, imaging of the subclavian-innominate venous channels before pacemaker lead placement is helpful for transvenous lead placement. The course of the lead should be evaluated in 2 planes to avoid inadvertent lead placement into the foramen ovale, an unroofed left superior vena cava to coronary sinus, or left-sided circulation via the subclavian artery. Either a subcutaneous or subpectoral pocket may be formed inferior to the clavicle.

Major lawsuits related to pacing in congenital atrioventricular block (CAVB) have arisen primarily because of inadvertent placements of pacing leads into the left-sided circulation. This complication can be recognized at or immediately following system placement using complementary radiographic views, usually lateral and posteroanterior (PA) or anteroposterior (AP).

Numerous pacing strategies are used in the management of congenital complete heart block in children; the interested reader is referred to the 2017 review by Chandler et al.[21]

Follow-up

Routine pacemaker follow-up visits should be maintained according to national or international guidelines. Transtelephonic pacemaker monitoring may allow for improved follow-up care and longer intervals between outpatient visits.

Activity

Patients with permanent pacing systems should be restricted from activities that result in repeated intentional direct trauma to the pacemaker area (eg, martial arts). Patients with permanent pacing systems should be restricted from exposure to high magnetic fields, such as direct magnetic resonance imaging (MRI) exposure.

Intrauterine treatments used for congenital atrioventricular block (CAVB) include chronotropic agents, inotropic agents, steroids, and plasmapheresis. In general, medications are not necessary in children with complete CAVB. Emergency use of chronotropic medications, with or without inotropic agents, may be helpful in fetuses and newborns with hydrops fetalis, congestive heart failure, or low cardiac output.

Some investigators have suggested the use of immunosuppressive agents in fetuses and newborns to potentially slow or halt progressive CAVB in utero. This is currently being evaluated as a prospective study.

The use of steroids or immunoglobulins may be helpful in early first- and second-degree heart block and in reducing associated myocardial dysfunction.

Class Summary

Corticosteroids have anti-inflammatory properties and cause profound and varied metabolic effects. They modify the body's immune response to diverse stimuli.

Dexamethasone (Baycadron, Dexamethasone Intensol)

Dexamethasone may produce significant clinical responses in some patients. It may be helpful in early first- and second-degree heart block and in reducing associated myocardial dysfunction.

Class Summary

These agents are used to improve the clinical aspect of the disease. It may reduce associated myocardial dysfunction.

Immune globulin intravenous (Gamunex, Octagam, Gammaplex, Gammagard)

This provides an antibody-mediated blockade of Fas-Fas ligand interactions involved in the epidermal necrosis of toxic epidermal necrolysis–like cutaneous lupus erythematosus.