15 Complete Heart Block—Third-Degree Heart Block

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Complete Heart Block—Third-Degree Heart Block

Mohamad Al-Ahdab

Complete atrioventricular (AV) block can be deﬁned as interruption in the transmission of the cardiac impulse from the atria to the ventricles due to an anatomical or functional impairment in the AV conduction system.

The conduction disturbance can be transient or permanent.

Congenital complete heart block (CHB), the most common and important form in chil- dren, was ﬁrst described in 1901 by Morquio, who also noted a familial occurrence and an association with Stokes-Adams attacks and death. The presence of fetal bradycardia (40–

80 bpm) as a manifestation of CHB was ﬁrst noted in 1921. The incidence of congeni- tal CHB in the general population varies be- tween 1 in 15,000 to 1 in 22,000 live-born infants.

ETIOLOGY

In the absence of congenital heart dis- ease, neonatal lupus is responsible for 60%

to 90% of cases of congenital CHB. Antibod- ies from a mother with an autoimmune con- nective tissue disorder, most frequently lupus erythematosus, cross the placenta to the fe- tus during the ﬁrst trimester and account for

almost all cases presenting in utero or dur- ing the neonatal period. Rarely it may explain a few cases occurring later (5% in one re- port). Other causes include myocarditis and various structural cardiac defects, particularly congenitally corrected transposition of the great arteries, AV discordance, or polysplenia with AV canal defect. Several genetic disor- ders such as familial atrial septal defect and Kearns-Sayre syndrome (Chapter 18) have been identiﬁed (Table 1). In most cases, CHB is characterized pathologically by ﬁbrous tis- sue that either replaces the AV node and its surrounding tissue or by an interruption be- tween the atrial myocardium and the AV node;

other lesions that can occur include congen- ital absence of the AV node. The net effect is that the block is usually at the level of the AV node. The heart is otherwise structurally normal in these children.

Neonatal Lupus

Complete heart block, hepatobiliary dis-

ease, malar rash, thrombocytopenia and, less

frequently, myocarditis comprise the neona-

tal lupus primarily presenting in utero or in

the neonate. Frequently the only manifesta-

tion of neonatal lupus, and by extension an

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TABLE 1. Congenital Complete Heart Block (1 in 20,000 to 25,000 Live Births)

No associated structural heart disease Accounts for 67% to 75% of affected infants Immune-mediated complete heart block

Accounts for 80% of congenital complete heart block in the absence of structural defect

Associated with maternal autoantibodies (anti-SSA/Ro antibodies and anti-SSB/La antibodies) which are the putative etiologic agents

Because the mentioned antibodies are of the IgG class, transplacental passage and complete heart block do not appear until after 16 to 20 weeks of gestation

High fetal wastage

At least 80% of mothers with affected infants will have autoantibodies; most mothers will either have or develop overt symptoms of a systemic connective tissue disorder

Discontinuity within the cardiac conduction tissue at level of the atrial axis, within the nodal-ventricular conduction tissue, or within the intraventricular conduction tissue^∗

Other associations: (applies to complete heart block at birth as well as letter) Tumors and neoplasia

Myocarditis and infections Familial, genetic, and metabolic Long QT syndrome

Congestive heart failure occurs but less commonly Fair to good postnatal prognosis

Pacemaker in the newborn period indicated by presence of congestive heart failure or a very slow heart rate (<50 to 55 bpm), or at an older age by symptoms

Associated with complex structural heart disease Accounts for 25% to 33% of affected infants Most common forms of cardiac malformations:

Corrected (I-loop) transposition of the great arteries Single ventricle

Defects in atrial and ventricular septation and looping

Guarded prognosis: high fetal and newborn mortality (even with pacemaker) Usually with congestive heart failure

Early permanent cardiac pacemaker frequently necessary

∗See Ho et al., Am J Cardiol 1986, 58:291–294.

autoimmune abnormality in the mother, is CHB in the newborn.

Neonatal lupus is due to transplacental passage of maternal anti-Ro/SSA and/or anti- La/SSB antibodies. Among women with such antibodies, CHB occurs in approximately 2%

of pregnancies. Once such a woman has given birth to an infant with CHB, the recurrence rate of CHB in subsequent pregnancies is about 15%; another 6% have an isolated rash consistent with neonatal lupus.

Anti-Ro/SSA and/or anti-La/SSB anti- bodies bind to fetal cardiac tissue, leading to immune-mediated injury to the AV node and its surrounding tissue. Both Ro/SSA and La/SSB antigens are abundant in fetal heart tissue between 18 and 24 weeks. 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 cardiomyocytes and in- duce the release of tumor necrosis factor by macrophages, resulting in ﬁbrosis. In addi- tion to inducing tissue damage, anti-Ro/SSA and/or anti-La/SSB antibodies inhibit calcium channel activation of the cardiac L- and T-type calcium channels themselves; L-type chan- nels are crucial to action potential propagation and conduction in the AV node. The sinoatrial (SA) node also may be involved; sinus brady- cardia has been described in 3.8% percent of fetuses but is usually not permanent.

CLINICAL MANIFESTATION

The manifestations of CHB vary with

the age at presentation. Patients with the

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neonatal lupus syndrome tend to present ear- lier than those with CHB not due to neonatal lupus.

Presentation in Utero

Congenital heart block may present with fetal bradycardia between 18 and 28 weeks of gestation. Almost all of these cases (95% in one series) are due to neonatal lupus, demon- strated by the presence of anti-Ro/SSA and/or anti-La/SSB antibodies in the maternal serum.

In utero detection is made by echocardiogra- phy, which can estimate the fetal PR interval (Chapter 19). Complications in utero include hydrops fetalis, myocarditis, endocardial ﬁ- broelastosis, pericardial effusion, and sponta- neous intrauterine fetal death. In one report, among 29 cases diagnosed in utero, there was one therapeutic abortion and six intrauterine fetal deaths; a lower rate of intrauterine death (6 of 87) was seen in another study. Second- degree block detected in utero can progress to CHB.

Infants who present with heart block in utero, but who survive until birth, have a high neonatal mortality rate. In one report, 6 of 22

II

I

III

HBE

AVF V

H H

V

P P P

V

V H

V

P P

FIGURE 1. Leads II, I, III, and aVF with a His bundle electrogram (HBE) and ventricular (V) electrogram demon- strating CHB with a His bundle (H) escape rhythm. The ventricular rate is 45 bpm. Reprinted with permission from Ho SY et al. The anatomy of congenital heart block. J Am Cardiol 1986;58(3):292–294 and Elsevier.

such infants (27%) died within one week of birth. In another series, 10 of 107 (9%) died within the ﬁrst three months. Infants born be- fore 34 weeks have a higher mortality rate than those born later (52% vs. 9%). Infants with ﬁrst- or second-degree heart block at birth can progress to CHB.

Presentation in the Neonate

As in the fetus, the cardinal ﬁnding in CHB in the neonate is a slow heart rate. In addition to bradycardia, other clinical clues in the neonate include intermittent cannon waves in the neck, a ﬁrst heart sound that varies in in- tensity, and intermittent gallops and murmurs.

As with cases presenting in utero, almost all

presenting in the neonatal period (90% in one

series) are due to neonatal lupus. The newborn

at greatest risk has a rapid atrial rate, often

150 bpm or faster, and a ventricular rate less

than 50 bpm. Similar to acquired CHB, the

ECG most commonly shows a narrow QRS

complex due to a junctional or AV nodal es-

cape or ectopic rhythm (Figure 1). First- or

second-degree heart block found in infants at

birth can progress to CHB. The outcome for

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FIGURE 2. Monitor electrocardiographic tracing in a 10-year-old boy presenting with syncope. The tracing shows intermittent CHB with long pauses. A pacemaker was implanted although his AV conduction improved. Myocarditis was presumed but unproven (negative cardiac biopsy). Reprinted with permission from Ho SY et al. The anatomy of congenital heart block. J Am Cardiol 1986;58(3):292–294 and Elsevier.

patients diagnosed as neonates is better than for those diagnosed in utero. In the above cited review, 33 patients presented in the perinatal period; ﬁve had signs of heart failure, but none had hydrops fetalis. None died within the ﬁrst six months, but two died at 0.9 and 1.5 years of age. Our experience has been not as grave.

Presentation in Childhood

As many as 40% of cases of congeni- tal heart block do not present until childhood (mean age ﬁve to six years) (Figure 2). Few of

these patients (5%) have neonatal lupus. The diagnosis is usually made when by presenta- tion such as syncope or by detecting a slow pulse. Heart block is conﬁrmed by ECG or by ambulatory ECG monitoring.

Complete heart block may be intermit-

tent when ﬁrst detected, but usually becomes

persistent in later childhood. It has been sug-

gested that most unexplained CHB diagnosed

for the ﬁrst time beyond infancy is congeni-

tal in origin and has escaped notice because

of a higher ventricular rate and the absence

of symptoms. However, given that prenatal

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TABLE 2. Disorders that Can Cause Third-Degree Heart Block

Fibrosis and Sclerosis: Fibrosis and sclerosis of the conduction system accounts for about one-half of cases of AV block.

Lenegre’s disease has been traditionally used to describe a progressive, ﬁbrotic, sclerodegenerative afﬂiction of the conduction system in younger individuals associated with slow progression to CHB and may be hereditary.

Lev’s disease has referred to “sclerosis of the left side of the cardiac skeleton” in older patients, such as that associated with calciﬁc involvement of the aortic and mitral rings.

Familial Disease: Familial AV conduction block (Chapter 18).

Valvular Disease: Calciﬁcation and ﬁbrosis of the aortic or mitral valve rings can extend into the conducting system.

Cardiomyopathies: Includes hypertrophic obstructive cardiomyopathy and inﬁltrative processes such as amyloidosis and sarcoidosis.

Hyperthyroidism, myxedema, and thyrotoxic periodic paralysis.

Neuromuscular heredodegenerative disease, dermatomyositis, rheumatoid disease, and Paget’s disease.

Infections: Myocarditis due to rheumatic fever, diphtheria, viruses, systemic lupus erythematosus, toxoplasmosis, bacterial endocarditis, syphilis, and Lyme disease.

Malignancies: Such as Hodgkin’s disease and other lymphomas; multiple myeloma; and cardiac tumors.

Drugs: A variety of drugs can impair conduction and cause AV block (Chapter 21).

Ischemic heart disease.

ultrasound is now well-developed and in wide use, it may be that cases currently missed in fetal life have preserved AV conduction at birth and acquire progressive AV nodal dis- ease thereafter. Consistent with this notion are two observations. First, in a report from one center, the number of childhood case referrals remained constant from 1980 to 1998 despite the introduction of fetal echocardiography and the wide availability of heart rate mon- itoring during pregnancy and labor. Second, in a series of 102 patients who were asymp- tomatic through age 15 and were followed for 7 to 30 years thereafter, a slow decline in ven- tricular rate was noted with increasing age, with a mean heart rate at age 15 of 46 bpm and a mean heart rate after age 40 of 39 bpm.

Some patients present with bradycardia- related symptoms, including reduced exercise tolerance, presyncope, or syncope. Sudden death has also been described. In the above re- view of 102 patients who were without symp- toms through age 15, 27 (26%) had a subse- quent syncopal episode, eight of which were fatal. Six of these eight episodes represented a ﬁrst syncopal episode.

Many other disorders can disrupt the AV conduction system (Table 2). These disorders are rare in the young.

TREATMENT

Management of congenital heart block in utero and in the perinatal period can include steroid therapy if associated with anti-Ro/SSA and anti-La/SSB antibodies, and isoproterenol and/or pacemaker insertion im- mediately postpartum.

The principal therapeutic decision af- ter the immediate perinatal period involves the need for pacemaker placement. Most pa- tients ultimately have a pacemaker inserted, regardless of the time of onset of the syn- drome. In one study, by 20 years of age, only 11% of neonatal and 12% of child- hood cases had not required pacemaker im- plantation. In another report that included 40 patients free of symptoms at age 15, pace- makers were required in 90% by age 60 (Chapter 17).

The Report of the American College of Cardiology/American Heart Association/

North American Society for Pacing and

Electrophysiology Task Force on Practice

Guidelines (Committee on Pacemaker Im-

plantation) outlines management of third-

degree AV block in children, adoles-

cents, and patients with congenital heart

disease.

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TABLE 3. Class I Indications for Pacemaker Implant in Children

Symptomatic bradycardia (syncope or presyncope) Moderate to marked exercise intolerance Heart failure thought related to the bradycardia Left ventricular dysfunction or low cardiac output A wide QRS escape rhythm or block below the His

bundle

Complex ventricular arrhythmias

In an infant, ventricular rates<50−55 bpm or <70 bpm when associated with congenital heart disease Sustained pause-dependent VT, with or without

prolonged QT, in which the efﬁcacy of pacing is thoroughly documented

Advanced second- or third-degree AV block persisting at least seven days after cardiac surgery

Class I Conditions: Class I conditions are those for which there is evidence and/or general agreement that a permanent pacemaker should be implanted. This class includes patients with ad- vanced second- or third-degree heart block, which is permanent or intermittent (Table 3).

These guidelines are reasonable but should be tailored to the patients needs. Infants with CHB but otherwise a normally structural heart may be followed without a pacemaker even if the heart rate is in the 40s when asleep.

Equally important is the variation in the heart rate and the overall status of the child. In contrast, an infant with CHB (congenital or surgical) and structural heart disease should receive a pacemaker. Other useful guidelines are outlined in Table 4.

Class II Conditions: Class II conditions are those for which permanent pacemakers are

TABLE 4. Other Customized Guidelines

Cardiac enlargement

QT interval prolongation, which may represent a substrate for ventricular arrhythmias (Class II by the ACC/AHA/NASPE guidelines)

Ventricular arrhythmias related to a slow rate or that can be abolished by a more rapid heart rate

Ectopic rhythms or other medical conditions are present that require drugs that suppress the automaticity of escape pacemakers and result in symptomatic bradycardia

frequently used, but there is divergence of opin- ion with respect to the necessity of their insertion (Table 5). Some of these conditions reﬂect ad- vanced but not complete heart block.

LONG-TERM PROGNOSIS

Complete heart block, as noted, pre- senting in utero or the neonatal period due to neonatal lupus, is associated with a sig- nificant early mortality. Of 175 cases de- scribed in two reports, 29 (17%) died either in utero or within the first three months of life. Infants and young children with CHB who are asymptomatic usually remain so until later childhood, adolescence, or adult- hood. Children with a mean heart rate below 50 bpm and evidence of an unstable junctional escape rhythm may benefit from early pace- maker implant. One particular risk related to the AV block and the ventricular bradycar- dia is the development of torsades de pointes (Figure 3).

Those patients who do not experience symptoms or syncopal attacks may nonethe- less experience physiologic consequences of bradycardia. The ventricular rate tends to fall slowly with age. 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 as well as to heart failure.

In general, the prognosis for the major-

ity of young patients following pacemaker

implantation for isolated congenital CHB is

excellent. However, one report evaluated 16

patients (10 with neonatal lupus) in whom

a pacemaker was implanted within the ﬁrst

two weeks of life; 12 developed heart fail-

ure before age 24. The major ﬁndings on

myocardial biopsy were hypertrophy and in-

terstitial ﬁbrosis. During follow-up, four pa-

tients died from progressive heart failure

and seven required transplantation. In another

study of 149 patients followed for 10 years,

6% developed a dilated cardiomyopathy by

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TABLE 5. Class II Indications

Second- or third-degree AV block within the bundle of His in an asymptomatic patient (consider as Class I) Prolonged subsidiary pacemaker recovery time with a pause greater than three seconds

Transient surgical second- or third-degree AV block that reverts to bifascicular block

Asymptomatic second- or third-degree AV block and a ventricular rate below 50 bpm when awake beyond the ﬁrst year of life

Complete AV block with double or triple rest cycle length pauses or minimal heart rate variability Asymptomatic neonate with congenital CHB and bradycardia in relation to age

Long QT syndrome (especially with ventricular arrhythmias)

Congenital heart disease and impaired hemodynamics due to sinus bradycardia or loss of AV synchrony

Neuromuscular disease with any degree of AV block (including ﬁrst-degree AV block), with or without symptoms, because there may be unpredictable progression of AV conduction disease

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.

While the development of heart fail- ure in such patients may be a consequence of myocardial ﬁbrosis associated with CHB, another factor may be the long-term con- sequences of right ventricular pacing with consequent ventricular asynchrony. Recently, a report compared 23 patients with con-

FIGURE 3. Eight-year-old boy with congenital CHB developed ventricular extrasystoles and torsades de pointes. He spontaneously converted and a dual-chamber pacemaker was implanted. Reprinted with permission from Ho SY et al. The anatomy of congenital heart block. J Am Cardiol 1986;58(3):292–294 and Elsevier.

genital CHB, each of whom had a pace- maker, to 30 matched healthy control subjects.

Echocardiography was performed before

pacemaker implantation and after at least ﬁve

years of right ventricular pacing in the CHB

patients. The CHB patients with pacemakers,

not surprisingly when compared to perfectly

normal controls, developed asynchronous left

ventricular contraction, an increase in left ven-

tricular end-diastolic diameter, a decrease in

cardiac output, and a decrease in exercise

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performance. When pacemaker therapy is ini- tially placed in children, there are often lim- ited choices. Biventricular pacing, when the patient is of sufﬁcient size, may, in part, ad- dress this observation (Chapter 17).