Pediatric Cardiology

, Volume 34, Issue 8, pp 2040–2043

Maternal Antibody-Associated Fetal Second-Degree Heart Block and Atrial Flutter: Case Report and Review

Authors

  • Jeffrey H. Sacks
    • Emory University School of Medicine
    • Children’s Healthcare of Atlanta
  • Cyrus Samai
    • Emory University School of Medicine
    • Children’s Healthcare of Atlanta
  • Kevin Gomez
    • Atlanta Perinatal Consultants
    • Emory University School of Medicine
    • Children’s Healthcare of Atlanta
    • Sibley Heart Center
Case Report

DOI: 10.1007/s00246-012-0588-x

Cite this article as:
Sacks, J.H., Samai, C., Gomez, K. et al. Pediatr Cardiol (2013) 34: 2040. doi:10.1007/s00246-012-0588-x

Abstract

Exposure to maternal anti-Ro (SS-A) and anti-La (SS-B) antibodies is a well-described risk factor for the development of fetal atrioventricular (AV) block. The role of maternal fluorinated steroids in the treatment and prevention of antibody-mediated fetal AV block is controversial. Fetal atrial flutter has rarely been described in association with maternal antibodies. This report describes a case of fetal exposure to maternal anti-Ro antibodies with associated second-degree AV block and atrial flutter. Interestingly, the reported patient had 2:1 AV conduction during both normal atrial rates (consistent with AV node conduction disease) and episodes of flutter (consistent with physiologic AV node functionality). The fetus was treated with transplacental digoxin and dexamethasone, which resolved both rhythm disturbances. The case report is followed by a brief discussion of AV block and atrial flutter associated with maternal antibody exposure.

Keywords

Anti-La (SS-B) antibodiesAnti-Ro (SS-A) antibodiesAtrial flutterFetal arrhythmiaHeart block

Abbreviations

AV

Atrioventricular

AF

Atrial flutter

BPM

Beats per minute

EFE

Endocardial fibroelastosis

Case Report

A 41-year-old G3P1 woman presented with fetal bradycardia at 28 weeks gestation. The fetal heart rhythm showed a 2:1 atrioventricular (AV) block, with an atrial rate of 140 beats per minute (bpm) and a ventricular rate of 70 bpm. (Fig. 1). The atrial rhythm was regular, excluding nonconducted premature atrial contractions as a possible explanation. Rare 1:1 AV conduction was seen, with an AV interval of 117 ms shown by the left ventricular (LV) inflow/outflow technique. A small, 1.5-mm pericardial effusion along the right ventricular free wall was noted, as was a tiny muscular ventricular septal defect, but no other abnormalities of cardiac anatomy or function were seen.
https://static-content.springer.com/image/art%3A10.1007%2Fs00246-012-0588-x/MediaObjects/246_2012_588_Fig1_HTML.jpg
Fig. 1

A 2:1 atrioventricular block demonstrated by (a) M-mode through the right atrium and left ventricle (b) a ventricular rate measured at 64 beats per minute (bpm) (V–V interval of 0.94 s), and (c) an atrial rate of 128 bpm (A–A interval of 0.47 s)

The patient subsequently had positive test results for anti-Ro antibodies (>8 U) and negative results for anti-La antibodies (0.2 U) (normal range <1, Mayo Clinic Jacksonville clinical lab) but showed no signs or symptoms of connective tissue disease. Based on previous reports describing regression of first- and second-degree AV block with the use of fluorinated steroids, dexamethasone was administered at a daily dose of 4 mg by mouth.

At 29 weeks gestation, the fetus showed atrial flutter, with an atrial rate of 480 bpm and a 2:1 AV block resulting in a ventricular rate of 240 bpm (Fig. 2). The patient was admitted for fetal heart rhythm monitoring and arrhythmia treatment.
https://static-content.springer.com/image/art%3A10.1007%2Fs00246-012-0588-x/MediaObjects/246_2012_588_Fig2_HTML.jpg
Fig. 2

Atrial flutter with a 2:1 atrioventricular (AV) block demonstrated by (a) M-mode through the right atrium and left ventricle (b) an atrial rate of 480 bpm (A–A interval of 0.125 s), and (c) a ventricular rate measured at 240 bpm (V–V interval of 0.25 s)

Over the next several days, the fetal heart rhythm varied between normal atrial rates, with a 2:1 AV block (atrial rate, 140–150 bpm; ventricular rate, 70–75 bpm), brief intervals of 1:1 conduction (atrial and ventricular rates, 140–150 bpm), and periods of atrial flutter (atrial rates, 480 bpm; ventricular rates, 240 bpm). The mechanical AV interval during brief episodes of normal sinus rhythm measured 133 ms by the superior vena cava–aorta Doppler technique.

Due to a significant fetal tachycardia burden, transplacental antiarrhythmic therapy was started after a maternal electrocardiogram and echocardiogram were found to be normal. Sotalol, typically first-line monotherapy for uncomplicated fetal atrial flutter at our institution, was not prescribed in this case due to concern for worsening AV conduction when the atria was not in flutter due to the drug’s beta-blocking effects. Despite reports describing questionable effectiveness of digoxin as monotherapy in atrial flutter, transplacental digoxin was administered due to its low risk for significant adverse effects on the patient and the fetus [4, 5, 8].

Sinus rhythm, atrial flutter, and 2:1 AV block all were noted during inhospital observation for approximately 2 weeks (atrial flutter up to 50 % of the time), but the cardiovascular evaluation demonstrated stable biventricular systolic function without progression of heart enlargement, AV valve regurgitation, or pericardial effusion, and biophysical profiles were normal. The patient’s digoxin dose was titrated to a serum concentration of 1.5–2 ng/ml. By 31 weeks gestation, the fetal heart rhythm converted entirely to sinus, with 1:1 AV conduction at rates of 130–150 bpm and with an AV interval of 108 ms. However, mild oligohydramnios developed. The pericardial effusion resolved, and the patient was discharged receiving digoxin and dexamethasone, which she continued for the duration of the pregnancy.

Over the next 2 months, the fetal heart rhythm and cardiovascular status remained normal. The AV interval was noted by two different techniques to be within normal limits, at approximately 130 ms. Oligohydramnios progressed gradually, and the fetus experienced growth retardation, presumably because of adverse reactions to the steroids, and placenta previa was diagnosed. Delivery by cesarean section ensued at 36 5/7 weeks gestation.

As always in similar cases, the boy’s cardiac anatomy, electrocardiograms, and PR intervals and function were normal 3 years postnatally, except for a tiny muscular ventricular septal defect (VSD), which closed spontaneously in his first year of life.

Discussion

Maternal anti-Ro (SS-A) and anti-La (SS-B) antibodies have been implicated in a number of fetal and neonatal cardiovascular diseases. These antibodies can be seen in mothers with Sjogren’s syndrome, systemic lupus erythematosus, and other rheumatologic diseases, but most often occur in otherwise healthy individuals, as in the reported case [12]. Fetal cardiovascular disease can be the presenting manifestation for mothers who subsequently go on to experience the development of clinical autoimmune disease, although this is debated in the literature [3, 6, 9].

The incidence of fetal cardiac involvement for those exposed to maternal anti-Ro/anti-La antibodies is quite variable. Depending on the study, 1–25 % of fetuses exposed to these antibodies have subsequent fibrosis or inflammation of the conduction system or myocardium [2, 7].

Heart Block

Fetal AV block in the presence of maternal antibodies typically presents at gestation weeks 20–24, as in the reported case [7]. Although an exact mechanism has not been elucidated, antibody-mediated inflammation, necrosis, and fibrosis of the conduction system are suspected to be the cause [2]. Maternal antibodies are believed to cross the placenta and bind to fetal cardiac structures, triggering activation of the fetal immune response. In a small retrospective analysis of anti-Ro and anti-La antibody-exposed infants with fetal AV block and endocardial fibroelastosis, immunohistochemistry on the pathologic assessment of explanted hearts was performed to identify deposition of immunoglobulin-G (IgG) and IgM as well as T cell infiltrates in the cardiac tissue suggesting an antibody-mediated inflammatory etiology [11].

Furthermore, it has been recognized that the antibody burden correlates with the degree of cardiac complications [6]. At autopsy, a macrophage infiltrate often can be seen affecting fetal cardiac structures. In vitro studies suggest that tumor necrosis factor alpha may contribute to inflammation, resulting in fibrosis and necrosis [3].

The significance of varying degrees of fetal AV block is debated in the literature. Although progression of first-degree fetal AV block to higher-grade heart block has been described, in the majority of cases, it does not progress and may resolve spontaneously [1, 7]. Second- and third-degree fetal AV block is less common and associated with a worse outcome. In one report, none of the 35 fetuses (61 %) presenting with third-degree heart block reverted to normal rhythm. Of the 39 % presenting with second-degree fetal AV block, 41 % had progression of their block, 41 % remained in second-degree block, and 18 % regressed to normal AV conduction. Fetuses with progression of fetal AV block tended to have poorer prognoses [10]. Fetal bradycardia is a significant risk factor for demise because of the reliance on chronotropy to maintain cardiac output given the relative inability of fetal hearts to increase stroke volume [4, 10].

Atrial Flutter

In addition to AV block, the reported case was complicated by fetal atrial flutter. Atrial flutter is a tachyarrhythmia caused by intra-atrial reentry with varying degrees of adaptive AV block. In this context, AV block is protective because it prevents ventricular rates from tracking with atrial rates, which can be as fast as 400–600 bpm.

Fetal atrial flutter may lead to hydrops fetalis and intrauterine fetal demise [5]. In a retrospective review of 45 fetuses with a prenatal diagnosis of atrial flutter, 9 % died or experienced severe neurologic dysfunction [8].

Fetal atrial flutter has rarely been reported in association with maternal auto-antibodies and never, to our knowledge, in association with second-degree fetal AV block [8]. The mechanism of atrial flutter in maternal antibody-exposed fetuses is unknown, but it is postulated that atrial inflammation may be the substrate for intra-atrial reentry [6].

The Reported Patient

The reported case demonstrated a unique fetal cardiac disturbance in the presence of maternal anti-Ro antibodies. Whereas atrial flutter has been described in the setting of complete fetal AV block, the reported case was unique in that second-degree fetal AV block and atrial flutter occurred in a fetus exposed to maternal antibodies. Additionally, both rhythm disturbances resolved after treatment with dexamethasone and digoxin.

Finally, the reported patient presented with a puzzling AV conduction abnormality: when the fetus was in sinus rhythm (i.e., normal atrial rates), the fetal AV node conducted 2:1, whereas, when the fetus was in atrial flutter (i.e., very fast atrial rates), the fetal AV node also conducted 2:1. The 2:1 fetal AV block with normal atrial rates suggests the presence of AV nodal disease because a healthy fetal AV node should be able to conduct at rates of 150–170 bpm. A 2:1 AV block during episodes of atrial flutter, however, demonstrates a physiologic and protective function of the AV node and relatively robust AV node performance.

Why the AV node was capable of conducting at a rate of 235 bpm during atrial flutter but could not conduct at a rate of 150 bpm when the atrial rate was normal is unknown. We hypothesize that fetal atrial flutter may have led to a high catecholamine state (perhaps in response to low output), which enhanced AV nodal conduction but only during the stress of atrial flutter.

Due to the poor prognosis associated with both atrial flutter and fetal AV block, dexamethasone was administered to reduce inflammation of the conduction system and atria. In an effort to control the ventricular rate during atrial flutter and potentially convert to sinus rhythm, digoxin was administered. The fetal AV block and atrial flutter both resolved during a 3-week period, although a causative link cannot be proved. The remainder of the fetus’s prenatal course was unremarkable except for oligohydramnios and intrauterine growth retardation.

The reported case demonstrates the potential benefits of both dexamethasone for fetal atrial flutter and AV block in the context of maternal anti-Ro antibodies as well as two of the well-described risks. Further prospective study on the therapy for these fetal arrhythmias is needed.

Copyright information

© Springer Science+Business Media New York 2012