Fetal Congenital Heart Block

    

    

    Figure 8: Resolution of congenital heart block at 35 weeks and 3 days in
Case 3.
    

Discussion

Fetal congenital heart block is associated with pronounced morbidity and mortality such that a high index of suspicion is necessary to diagnose this condition early in gestation. The prognosis of these fetuses will depend on the following factors: first, the presence or absence of structural heart disease; second; the rate of ventricular activation (the critical value being less than 55 bpm); and third, the presence or absence of physiologic disturbances in cardiac function (such as congestive heart failure or the presence of hydrops fetalis) which is associated with the poorest prognosis [1]. Mortality rates reported depending on the developmental period of first appearance of CHB symptoms are 43% in fetuses, 6% in neonates and 0% in children, thus, the later CHB develops, the better is the chance of survival. On the other hand, based on symptoms, fetuses with hydrops fetalis or endocardial fibroelastosis incur a 100% rate of mortality [10]. Therefore, accurate prenatal diagnosis cannot be overemphasized in such circumstances where it is a matter of definitive rather than palliative treatment after birth. The crux of electrocardiography is the intimate relationship between the cardiac nerve conduction system and the structural morphology of the heart [11]. This theme is vividly captured in the classification of CHB. Congenital heart block is categorized into two types depending on the presence of structural heart disease (Figure 9). CHB with congenital heart disease confers a 14% chance of survival in the neonatal period. The most common structural anomalies involved include left atrial isomerism and discordant atrioventricular connections. On the other hand, CHB without structural heart disease, also referred to as isolated CHB, confers an 85% chance of survival in the neonatal period. This second category is further subdivided into those associated with maternal autoantibodies or those associated with other diseases such as the storage disorders (Hurler’s Syndrome and Hunter’s Syndrome) [12]. Our first case illustrated CHB with structural heart disease. CHB develops directly as there is disruption of the conduction network from the onset. On Fetal Electrocardiography (fECG), severity of CHB would range from a first degree block in the form of a simple PR prolongation to a second degree block in the forms of Mobitz Type I (Wenkebach) or Mobitz Type II phenomena, or as seen in our patient, to a third degree block which is defined as either of the following: (a) regular RR intervals at a >1000 ms cycle length; or (b) regular PP intervals at <1000 ms cycle length; or (c) irregular PR intervals [13]. In our patient, a septal defect was suspected at the onset with symptoms of pericardial effusion, and although 2D-echocardiography did not confirm a structural anomaly, this could not be totally ruled out. Our second case illustrated CHB without structural heart disease and was secondary to maternal autoantibodies, otherwise known as isolated CHB. The peak onset of this type of CHB is at 18-24 weeks of gestation since maternal autoantibodies only begin to pass through the placenta at 12 weeks and symptoms will usually manifest only after 6 weeks of fetal exposure. The autoantibodies linked to CHB include increased levels of the antinuclear antibodies Sjogren Syndrome A (SSa) or Sjogren Syndrome B (SSb), both also known as Ro and La antibodies respectively after the initials of the patients from whom these were first detected. In this scenario, the hypothesized pathogenesis of CHB is due to the direct effect of these autoantibodies on calcium regulation in the fetal heart leading to cross reactive disturbances in signal conduction or electrogenesis or both [14-16] Another hypothesis postulates that inflammatory immune reactions caused by the transfer of maternal autoantibodies initiate scarring and fibrosis via apoptosis in myocytes of the fetal heart eventually leading to disruption of the conduction system [17]. Our second case is a typical example of neonatal lupus, which is the passive acquisition of maternal autoantibodies in the fetus. As in the case of our index patient, half of mothers at diagnosis are usually asymptomatic for autoimmune disease and may only become aware of their illness because of this fetal manifestation. CHB in neonatal lupus will be at least of the second degree to third degree types. Moreover, only 1-7.5% of fetuses with neonatal lupus will develop CHB while the rest may have skin rashes (annular lesions mostly on the face around the eyes), liver abnormalities (elevated liver enzymes and jaundice), blood dyscrasias (such as cytopenias) and photosensitivity. These non-cardiac manifestations are transient and will subside once maternal autoantibodies are cleared beginning at the 8th month of life. Unfortunately, for those who develop conduction system disease, this manifestation is irreversible. For mothers known to carry these autoantibodies and with a previously affected child, there is a 15-18% recurrence rate of neonatal lupus in subsequent pregnancies [17,18]. Finally, our third case exemplifies the common clinical scenario of transient in utero CHB. At this stage of development, both genetic and environmental insults may still undergo remodeling and repair due to the plasticity of the fetal heart. This immense ability to reengineer itself remains a mystery as much as the true underlying etiology of congenital heart block still remains unknown leading researchers struggling with questions such as “is heart block a normal phenomenon in development towards structural normalcy?” Among the possible causes of transient in utero CHB are genetic ion channelopathies involving sodium and potassium ion channel unit defects. Whether transient or irreparable, these channelopathies have been linked to fetal intrauterine demise and sudden infant deaths. Current studies aim to identify genetic loci that carry these mutations [19]. The significance of reporting cases of CHB, although incidentally rare and most probably underreported, lies in the need for promoting awareness of the signs and symptoms of the disease. For CHB, universal screening is not advocated but a high index of suspicion should lead to proper diagnosis using ultrasound as the gold standard followed by fECG, MRI, autoantibody testing and genome arrays as confirmatory tests. Ongoing studies concerning perinatal management persist amidst their limited usefulness. The most recognized therapeutic approach is the use of transplacental treatments such as beta stimulants and steroids. The former includes ritodrine, terbutaline and salbutamol, all of which may effectively increase fetal ventricular rate by 10-20% and reverse hydrops, but their effects are short lived due to their brief duration of action [18]. On the other hand, the use of steroids, namely dexamethasone and betamethasone, is the most widely studied mode of therapy, especially in cases of CHB secondary to maternal autoantibodies. Steroids are known to directly effect treatment of AV block. Prompt administration of steroids after AV block onset may even improve the degree of AV block. Another target of steroid action is the prevention of myocarditis, which leads to fibrosis of the fetal heart. Steroid therapy though is not without its disadvantages. Chronic use may lead to increased infection, loss of bone density, diabetes, hypertension and cataracts in the mother, while fetal effects include oligohydramnios, adrenal suppression, intrauterine growth restriction and risk to the developing fetal brain. Furthermore, in various studies, the most famous of which being the PRIDE study (PR Interval and Dexamethasone Evaluation), results showed that there were no differences in mortality, prematurity, degree of final heart block or need for pacemakers in fetuses treated with steroids, but it was noted that the presence of pericardial or pleural effusions as well as ascites and hydrops seemed to improve with their use [4]. Other modes of therapy include Immunoglobulin (IVIG) administration and early delivery with direct pacing of the ventricle [2]. At present, therapeutic management in utero still remains controversial. First, CHB prophylaxis in SSa/Ro and SSb/La mothers is deemed impractical because only 1-7.5% of fetuses will develop CHB. Second, due to the low incidence of the disease, there is no singularly accepted standard protocol and third, most cases of CHB either transiently resolve or are detected at such advanced stages leaving no room for therapeutic benefits [20]. Carpenter et al. attempted the first fetal ventricular pacing in utero for hydrops secondary to complete atrioventricular block in 1986 [21]. Despite fetal death four hours after placement, the investigators concluded that such a procedure would lead to better chances of fetal survival if placed earlier in the course of fetal hydrops. Further attempts and research along this line of therapy have focused on sheep experiments [22]. Surviving cases of CHB will eventually require pacemaker insertion. The risk factors for requirement of a pacemaker are as follows: (1) mean resting heart rate below a determined number per age group (55 bpm in newborns); (2) symptomatic bradycardia (sudden presentation or limited exercise capability); (3) presence of significant structural heart disease; (4) significant pauses on 24-hr ambulatory electrocardiographic monitoring; and (5) a prolonged QTc interval or a wide QRS escape rhythm with complex ventricular ectopy [1]. Prognosis after pacemaker insertion is very good, therefore specialist care once diagnosed with CHB is imperative In summary, three cases illustrating the different presenting scenarios of fetal CHB were reported and clearly, it is of utmost importance that understanding electrocardiac physiology is vital to the clinician whether in fetal, pediatric or adult medicine. In cases of fetal CHB, prompt diagnosis is key to direct a complete evaluation of both maternal and fetal conditions. Although sometimes vigilance alone and no intervention is required, continued investigation of the exact etiology and mechanism of development from all levels, molecular to anatomical, will lead to the discovery of a more effective mode of management.

    

    

    Figure 9: Classification of Congenital Heart Block.