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  • Review Article
  • Published:

The clinical spectrum of autoimmune congenital heart block

Nature Reviews Rheumatology volume 11, pages 301–312 (2015)Cite this article

Subjects

Key Points

  • Autoimmune congenital heart block (CHB) is part of a cluster of fetal and neonatal manifestations associated with placental transference of autoantibodies

  • Maternal autoantibodies specific for Ro and La, and diagnosis in utero or neonatally, are key features of CHB

  • Irreversible complete atrioventricular (AV) block is the principal cardiac manifestation in >80% of reported cases

  • Some babies might develop other, more severe, cardiac complications, including endocardial fibroelastosis or valvular insufficiency

  • 20% of cases of autoimmune CHB are fatal and 64% of live births require a pacemaker

  • 1.7% of pregnant women positive for anti-Ro or anti-La antibodies have a baby with autoimmune CHB, but the risk climbs to 16% for mothers who have had previous CHB-affected pregnancies

Abstract

Autoimmune congenital heart block (CHB) is an immune-mediated acquired disease that is associated with the placental transference of maternal antibodies specific for Ro and La autoantigens. The disease develops in a fetal heart without anatomical abnormalities that could otherwise explain the block, and which is usually diagnosed in utero, but also at birth or within the neonatal period. Autoantibody-mediated damage of fetal conduction tissues causes inflammation and fibrosis and leads to blockage of signal conduction at the atrioventricular (AV) node. Irreversible complete AV block is the principal cardiac manifestation of CHB, although some babies might develop other severe cardiac complications, such as endocardial fibroelastosis or valvular insufficiency, even in the absence of cardiac block. In this Review, we discuss the epidemiology, classification and management of women whose pregnancies are affected by autoimmune CHB, with a particular focus on the autoantibodies associated with autoimmune CHB and how we should test for these antibodies and diagnose this disease. Without confirmed effective preventive or therapeutic strategies and further research on the aetiopathogenic mechanisms, autoimmune CHB will remain a severe life-threatening disorder.

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Figure 1: Maternal and fetal factors associated with the development of CHB.
Figure 2: Ratios of autoantibody positivity and negativity amongst CHB-affected mothers.14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52
Figure 3: Proportions of isolated and multiple autoantibody positivity.
Figure 4: Maternal autoimmune diseases associated with CHB.
Figure 5: Demographics of autoimmune CHB.
Figure 6: Autoantibody sequential studies and clinical evaluation of women who have babies with CHB of any degree, EFE or congenital valvular disease in an otherwise structurally-normal fetal heart.
Figure 7: Electrocardiogram.

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Acknowledgements

M.R.-C. is supported by Grants La Marató de TV3 (071810) and Fondo de Investigaciones Sanitarias (080103/1201009). J.P.B. is supported by NIH Grants 3R37AR042455 and 3R03HD069986. P.B.-Z. is supported by 'Ajut per a la Recerca Josep Font' from Hospital Clinic-Barcelona.

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Authors and Affiliations

  1. Department of Autoimmune Diseases, Josep Font Laboratory of Autoimmune Diseases, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Calle Villarroel 170, Barcelona, 08036, Spain

    Pilar Brito-Zerón & Manuel Ramos-Casals

  2. Division of Rheumatology, Department of Medicine, New York University School of Medicine, 550 First Avenue, New York, 10016, NY, USA

    Peter M. Izmirly & Jill P. Buyon

  3. Division of Women's Health, Graham Hughes Lupus Research Laboratory, King's College London, The Rayne Institute, Lambeth Wing, 4th Floor, St Thomas' Hospital, London, SE1 7EH, UK

    Munther A. Khamashta

Authors
  1. Pilar Brito-Zerón
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  2. Peter M. Izmirly
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  3. Manuel Ramos-Casals
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  4. Jill P. Buyon
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  5. Munther A. Khamashta
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Contributions

P.B.-Z., M.R.-C. and M.A.K. contributed to the conception and design of the Review. All authors contributed to acquisition and/or analysis of the systematic review data, and to writing the article and to review and/or editing of the manuscript before submission.

Corresponding author

Correspondence to Munther A. Khamashta.

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The authors declare no competing financial interests.

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Case-control studies that have evaluated anti-Ro/La titers in affected and non-affected pregnancies with CHB (DOCX 33 kb)

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Brito-Zerón, P., Izmirly, P., Ramos-Casals, M. et al. The clinical spectrum of autoimmune congenital heart block. Nat Rev Rheumatol 11, 301–312 (2015). https://doi.org/10.1038/nrrheum.2015.29

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