Background
Most of congenital heart block without structural heart anomaly is induced by maternal anti-Sjögren’s syndrome-associated antibody. Approximately 2% of fetuses of anti-Sjögren’s syndrome-associated antibody-positive mothers are affected. Once heart block develops to complete atrioventricular block, it becomes irreversible. However, it can be reversed if therapeutic intervention is early performed before developing to complete atrioventricular block. The irreversible nature of complete atrioventricular block and its high mortality rate rationalise early detection and fetal therapeutic interventions. Reference Cuneo, Sonesson and Levasseur1 Accumulating evidence suggested that among the antibodies observed in the patients with Sjögren’s syndrome, a fraction of 52 kDa in the anti-Ro/SSA antibody was responsible for fetal heart block, whereas a fraction of 60 kDa was rather independent of it. Reference Salomonsson, Dorner, Theander, Bremme, Larsson and Wahren-Herlenius2,Reference Miyasato-Isoda, Waguri, Yamada, Miyano and Wada3 Meanwhile, advanced atrioventricular block in adults positive for a 60-kDa fraction of anti-Ro/SSA antibody has been increasingly reported. Reference Santos-Pardo, Martinez-Morillo, Villuendas and Bayes-Genis4,Reference Jobling, Rajabally and Ng5 Herein, we report the case of a neonate who developed reversible complete atrioventricular block and whose mother was solely positive for a 60-kDa anti-Ro/SSA antibody.
Case presentation
The fetus was referred to our hospital at 39 weeks of gestation with a diagnosis of fetal bradycardia and hydrops. His mother was healthy without a history of autoimmune diseases. In addition, the gestation period was uneventful until 38 weeks of gestation for both the mother and fetus. The heart rate of fetus was 140–160 bpm at 38 weeks of gestation, which became less than 60 bpm at 39 weeks of gestation (Fig. 1).
Figure 1. Fetal heart rate monitoring. Fetal heart rate monitoring at gestational age of 38 weeks (left panel) and 39 weeks (right panel) is shown. While the fetal heart rate at 38 weeks of gestation age is 140–160 bpm with reasonable variability, it was less than 60 bpm at 39 weeks of gestation, which temporarily increased up to 80 bpm. Dotted line: baseline heart rate, which is less than 60 bpm. Solid line: temporal increase of heart rate.
Bradycardia with suppressed left ventricular ejection fraction of 38% necessitated a semi-urgent caesarian section. Upon arrival at the neonatal ICU, the fetus’s heart rate was 70 bpm, by which a diagnosis of complete atrioventricular block was established (Fig. 2). Blood test results revealed no signs of disseminated intravascular coagulation or viral infection, as indicated by the absence of antibodies against viruses (parvovirus, coxsackievirus, or echovirus). Since markedly high maternal and fetal anti-Sjögren’s syndrome-associated antibody titres were identified (> 1200 U/ml), he was diagnosed with immune mediated atrioventricular block at this point. However, the development of complete atrioventricular block at 39 weeks of gestational age was atypical. Due to an acute decline in the general condition, temporary ventricular pacing was urgently implanted, and intravenous steroids were administered. Atrioventricular conduction gradually recovered to first-degree atrioventricular block. Additionally, left ventricular contractility was improved to an ejection fraction of more than 60%. Temporary pacing was terminated within 3 days. The infant was discharged 45 days after birth. He had been followed up as an outpatient for more than 3 years without signs of atrioventricular block. Electrocardiogram indicated left-anterior fascicular block and right bundle branch block without any signs of heart failure. Since his clinical course was distinct from that of the fetuses and neonates with typical autoimmune congenital complete atrioventricular block, the fraction of his mother’s anti-Sjögren’s syndrome-associated antibody was analysed to further delineate the mechanism underlying the atrioventricular block. A markedly high titre of anti-Ro/SSA 60 kDa antibody was identified, whereas anti-Ro/SSA 52 kDa and anti-La/SSB antibody were negative.
Figure 2. Electrocardiogram at neonatal ICU arrival and before discharge. A: Electrocardiogram at neonatal ICU arrival. B: Electrocardiogram before discharge.
Discussion
Although neonatal lupus syndrome is caused by maternal anti-Ro/SSA and anti-La/SSB antibody, the mechanism underlying development of various symptoms is not clearly understood. Our patient developed a complete atrioventricular block during fetal life which was atypical in two aspects. First, he developed fetal complete atrioventricular block and reduced contractility as late as 39 weeks of gestation. This is in sharp contrast to a previous prospective report in which no fetus without atrioventricular block until 26 weeks of gestation developed conduction disease between the last clinical observation and birth. Reference Cuneo, Sonesson and Levasseur1 Second, his complete atrioventricular block recovered within a few days after steroids administration and temporary pacing, despite the fact that fetal immune-mediated complete atrioventricular block is generally irreversible. Reference Saleeb, Copel, Friedman and Buyon6
Accumulating knowledge suggests that anti-Sjögren’s syndrome-associated antibody could develop into immune-mediated complete atrioventricular block even in adults, of which two mechanisms are implied. Reference Lazzerini, Capecchi and Laghi-Pasini7 One is the acquired immune heart block, in which the newly developed antibody could induce cardiac inflammation, and the other mechanism could involve a transplacental maternal antibody that might cause an insult to the heart during fetal life. Considering the two types of cardiac neonatal lupus, the neonatal and late-onset types, these mechanisms might be similarly possible. Reference Morel, Levesque and Maltret8 However, the recovery of cardiac contractility in our case was also distinct from that observed in neonatal lupus-associated cardiomyopathy.
A plausible explanation for the atypical manifestation in our patient was that he developed acute myocarditis during fetal life, which was supported by both the rapid resolution of complete atrioventricular block and suppressed but reversible cardiac contractility. Regarding the other pertinent conditions for developing conduction disorder, including viral or other infectious myocarditis, thyroid disorders and electrolyte abnormalities, laboratory findings as well as postnatal conditions, suggested that they were unlikely. Furthermore, his mother was negative for symptoms or sick contact. Electrocardiography indicated a two-branch bundle block, which was suggestive of a post-myocarditis condition rather than immune-mediated complete atrioventricular block in the fetus. Although typical immune-mediated fetal atrioventricular block stems from an insult to the atrioventricular node, Reference Lazzerini, Capecchi and Laghi-Pasini7 the immune target in this case appeared to be the myocardium and Purkinje fibre, similar to complete atrioventricular block that develops in adults with Sjögren’s syndrome-associated antibody. Reference Villuendas, Olive and Junca9 Indeed, the fraction of 52-kDa anti-Ro/SSA antibody, not the fraction of 60 kDa, has been focused on as a culprit of fetal complete atrioventricular block. However, an increasing number of reports of adults have emphasised that the anti-Sjögren’s syndrome-associated antibody, regardless of its fraction, might be responsible for complete atrioventricular block, where infra-Hisian block is observed and is reversible if immunosuppressants are prescribed. Reference Villuendas, Olive and Junca9
The lower frequency of adult complete atrioventricular block associated with anti-Sjögren’s syndrome-associated antibody compared with fetus is explained by reserve of the L-type Ca channel, which is sensitive to the anti-Sjögren’s syndrome-associated antibody, in the myocardium. Lazzarini et al suggested that immune-acquired complete atrioventricular block in adults was reversible. Reference Lazzerini, Capecchi and Laghi-Pasini7 Consequently, despite the development of complete atrioventricular block in the fetus, similarity with the immune complete atrioventricular block detected in adults was notable, as it was reversible and the affected site was the fascicular bundle. In addition, the maternal anti-Ro/SSA antibody was a fraction of 60 kDa and negative for 52 kDa, which implied a low probability of typical fetal complete atrioventricular block developing during the second trimester of pregnancy.
Taken together, our case highlighted the importance of suspecting reversible complete atrioventricular block if the clinical course was atypical of fetal autoimmune congenital complete atrioventricular block.
Acknowledgements
The authors thank Drs. Takuya Takahashi, Yumi Sato, Yurie Takizawa, Satoshi Nakano, and Kotaro Oyama, Iwate Medical University, for their helpful discussion and assistance with the treatment. The authors also thank Dr Yoichiro Ishii, Osaka Women’s and Children’s Hospital, for helpful advice on diagnosis and patient management.
Financial support
JSPS KAKENHI Grant Number JP20K08191 (Dr Saiki), grant from the Miyata Cardiac Research Promotion Foundation (Dr. Saiki).
Competing interests
None.
Ethical standard
The patient’s family provided informed consent for treatment of the child and presenting clinical course.
