-
Birth Defects Research May 2019Congenital complete heart block (CCHB) is a life-threatening medical condition in the unborn fetus with insufficiently validated prenatal interventions. Maternal... (Review)
Review
Congenital complete heart block (CCHB) is a life-threatening medical condition in the unborn fetus with insufficiently validated prenatal interventions. Maternal administration of medications aimed at decreasing the immune response in the fetus and beta-agonists intended to increase fetal cardiac output have shown only marginal benefits. Anti-inflammatory therapies cannot reverse CCHB, but may decrease myocarditis and improve heart function. Advances in prenatal diagnosis and use of strict surveillance protocols for delivery timing have demonstrated small improvements in morbidity and mortality. Ambulatory surveillance programs and wearable fetal heart rate monitors may afford early identification of evolving fetal heart block allowing for emergent treatment. There is also preliminary data suggesting a roll for prevention of CCHB with hydroxychloroquine, but the efficacy and safety is still being studied. To date, intrauterine fetal pacing has not been successful due to the high-risk invasive placement techniques and potential problems with lead dislodgement. The development of a fully implantable micropacemaker via a minimally invasive approach has the potential to pace fetal patients with CCHB and thus delay delivery and allow fetal hydrops to resolve. The challenge remains to establish accepted prenatal interventions capable of successfully managing CCHB in utero until postnatal pacemaker placement is successfully achieved.
Topics: Female; Fetal Heart; Heart Block; Humans; Pregnancy; Prenatal Care; Prenatal Diagnosis; Reproducibility of Results
PubMed: 30821931
DOI: 10.1002/bdr2.1459 -
Indian Pediatrics May 2013Congenital Heart Block (CHB) is the most serious complication of neonatal lupus erythematosus. Transplasental transfer of maternal anti SSA/Ro or antiSSB/La antibodies... (Review)
Review
Congenital Heart Block (CHB) is the most serious complication of neonatal lupus erythematosus. Transplasental transfer of maternal anti SSA/Ro or antiSSB/La antibodies around 12th week of gestation is associated with development of CHB. This may lead to inflammation, fibrosis and scarring of fetal conduction system in the early second trimester. Different degrees of atrioventricular (AV) block may be seen in the affected fetus. First and second-degree AV blocks may change in severity; however, third degree AV block is irreversible. CHB is mostly diagnosed between 18 - 24th weeks of gestation. Even if most of the mothers carrying autoantibodies of several rheumatic diseases such as systemic lupus erythematosus or Sjogrens syndrome are not aware of their diseases until their children are born with CHB, it is recommended that antibody-positive mothers or the mothers having babies with neonatal lupus erythematosus should be referred for close fetal echocardiographic surveillance beginning from the early second trimester. Although their utility is still controversial, various therapeutic regimes such as sympathomimetic, plasmapheresis, steroids, intravenous immunoglobulin, digoxin, diuretic and in utero pacing have been used for intrauterine treatment of CHB. Aggressive medical treatment is coupled with pacing in infants who do not respond to medical therapy alone.
Topics: Heart Block; Humans; Infant, Newborn; Lupus Erythematosus, Systemic
PubMed: 23778728
DOI: 10.1007/s13312-013-0156-3 -
Scandinavian Journal of Immunology Jan 2021Autoimmune congenital heart block (CHB) may develop in foetuses of women carrying anti-Ro/SSA and La/SSB autoantibodies and is characterized by disruption of signal...
Autoimmune congenital heart block (CHB) may develop in foetuses of women carrying anti-Ro/SSA and La/SSB autoantibodies and is characterized by disruption of signal conduction at the atrioventricular (AV) node, resulting in partial or complete AV block. If not fatal in utero, complete CHB typically requires lifelong cardiac pacing. No treatment has so far been unequivocally demonstrated to prevent or treat autoimmune CHB, and the relatively low incidence (1%-5%) and recurrence (12%-16%) rates of second/third-degree AV block add to the complexity of managing pregnancies in women with anti-Ro/La antibodies. Altogether, a better understanding of events leading to development of autoimmune CHB is needed to improve surveillance and treatment strategies. In the past decade, studies have started to look beyond the role of maternal autoantibodies in disease pathogenesis to assess other contributing factors such as foetal genetics and, more recently, immune responses in foetuses and neonates of anti-Ro/La antibody-positive women. In this review, we provide an update on the epidemiology, clinical presentation and current treatment approaches of autoimmune CHB, summarize the previously proposed pathogenic mechanisms implicating maternal autoantibodies, and discuss the recent findings of type I interferon (IFN) and innate immune activation in foetuses with autoimmune CHB and in neonates of anti-Ro/La antibody-positive mothers, and how these may contribute to autoimmune CHB pathogenesis.
Topics: Autoantibodies; Autoantigens; Autoimmune Diseases; Autoimmunity; Disease Management; Disease Susceptibility; Fibrosis; Heart Block; Humans; Immunity, Innate; Immunotherapy; Incidence; Interferons; Macrophages; Recurrence
PubMed: 33188653
DOI: 10.1111/sji.12995 -
Cardiology in Review 2014Transplacental transfer of maternal anti-Ro and/or anti-La autoantibodies can result in fetal cardiac disease, including congenital heart block and cardiomyopathy,... (Review)
Review
Transplacental transfer of maternal anti-Ro and/or anti-La autoantibodies can result in fetal cardiac disease, including congenital heart block and cardiomyopathy, called cardiac neonatal lupus (NL). Thousands of women are faced with the risk of cardiac NL in their offspring, which is associated with significant morbidity and mortality. There are no known therapies to permanently reverse third-degree heart block in NL, although several treatments have shown some effectiveness in incomplete heart block and disease beyond the atrioventricular node. Fluorinated steroids taken during pregnancy have shown benefit in these situations, although adverse effects may be concerning. Published data are discordant on the efficacy of fluorinated steroids in the prevention of mortality in cardiac NL. β-agonists have been used to increase fetal heart rates in utero. The endurance of β-agonist effect and its impact on mortality are in question, but when used in combination with other therapies, they may provide benefit. No controlled experiments regarding the use of plasmapheresis in cardiac NL have been performed, despite its theoretical benefits. Intravenous immunoglobulin was not shown to prevent cardiac NL at a dose of 400 mg/kg, although it has shown effectiveness in the treatment of associated cardiomyopathy both in utero and after birth. Retrospective studies have shown that hydroxychloroquine may prevent the recurrence of cardiac NL in families with a previously affected child, and a prospective open-label trial is currently recruiting patients in order to fully evaluate this relationship.
Topics: Adrenergic beta-Agonists; Female; Heart Block; Humans; Hydroxychloroquine; Immunoglobulins, Intravenous; Lupus Erythematosus, Systemic; Plasmapheresis; Pregnancy; Prenatal Care; Prenatal Diagnosis; Secondary Prevention; Steroids, Fluorinated
PubMed: 25050975
DOI: 10.1097/CRD.0000000000000026 -
Chinese Medical Journal Dec 2017Congenital heart block (CHB) is a rare but life-threatening disorder. More than half of CHB cases are associated with maternal autoimmune, which are termed as... (Review)
Review
OBJECTIVE
Congenital heart block (CHB) is a rare but life-threatening disorder. More than half of CHB cases are associated with maternal autoimmune, which are termed as autoimmune-associated CHB. This review summarized the recent research findings in understanding autoimmune-associated CHB, discussed the current diagnostic approaches and management strategies, and summarized the problems and future directions for this disorder.
DATA SOURCES
We retrieved the articles published in English from the PubMed database up to January 2017, using the keywords including "Autoimmune-associated", "Autoimmune-mediated", and "Congenital heart block".
STUDY SELECTION
Articles about autoimmune-associated CHB were obtained and reviewed.
RESULTS
Observational studies consistently reported that transplacental maternal antibodies might recognize fetal or neonatal antigens in various tissues and result in immunological damages, but the molecular mechanisms underlying CHB pathogenesis still need illuminated. Multiple factors were involved in the process of atrioventricular block development and progression. While several susceptibility genes had been successfully defined, how these genes and their protein interact and impact each other remains to be explored. With currently available diagnostic tools, fetal ultrasound cardiography, and fetal magnetocardiography, most of CHB could be successfully diagnosed and comprehensively evaluated prenatally. The efficacy of current approaches for preventing the progression and recurrence of CHB and other autoimmune-mediated damages was still controversial.
CONCLUSIONS
This review highlighted the relationships between autoimmune injuries and CHB and strengthened the importance of perinatal management and therapy for autoimmune-associated CHB.
Topics: Autoimmune Diseases; Female; Heart Block; Humans; Pregnancy; Prenatal Care
PubMed: 29176145
DOI: 10.4103/0366-6999.219160 -
Scandinavian Journal of Immunology Sep 2010
Topics: Autoantibodies; Autoimmune Diseases; Female; Fetal Diseases; Heart Block; Humans; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications
PubMed: 20696012
DOI: 10.1111/j.1365-3083.2010.02446.x -
Nature Reviews. Rheumatology May 2015Autoimmune congenital heart block (CHB) is an immune-mediated acquired disease that is associated with the placental transference of maternal antibodies specific for Ro... (Review)
Review
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.
Topics: Autoantibodies; Autoantigens; Autoimmune Diseases; Female; Heart Block; Humans; Infant; Pregnancy
PubMed: 25800217
DOI: 10.1038/nrrheum.2015.29 -
JACC. Clinical Electrophysiology Apr 2021
Topics: Bundle of His; Bundle-Branch Block; Heart Block; Humans
PubMed: 33888270
DOI: 10.1016/j.jacep.2020.12.008 -
European Review For Medical and... Feb 2021The present article aims at describing a rare case of an RP patient who evolved with heart block and was successfully treated with corticoid pulse therapy, without the...
OBJECTIVE
The present article aims at describing a rare case of an RP patient who evolved with heart block and was successfully treated with corticoid pulse therapy, without the need for pacemaker insertion.
PATIENTS AND METHODS
A systematic research on relapsing polychondritis (RP) and heart block (HB) published in PubMed/MEDLINE, Web of Sciences, LILACS, and Scielo from 1966 to August 2020 was performed.
RESULTS
It was found 10 studies on RP associated with HB, and we added a case. Most were male (7/10) with ages 30 to 66 years old. RP disease duration was 1 week-6 years. In most cases (7/10), the RP was active when the HB occurred. A complete HB was observed in 4/7, followed by type II degree block in 3/7, and one patient had a sinus node dysfunction. Most patients received glucocorticoids. A pacemaker was inserted in 4/9 cases. Good outcome was observed in 3/9 patients and mortality in 2/10.
CONCLUSIONS
We report the first case of an RP patient who had a heart block and was successfully treated with methylprednisolone pulse therapy. The authors suggest that in these RP cases, an attempt with a glucocorticoid pulse therapy may be offered to treat the heart block and prevent the insertion of a pacemaker.
Topics: Adult; Female; Heart Block; Humans; Methylprednisolone; Polychondritis, Relapsing
PubMed: 33660817
DOI: 10.26355/eurrev_202102_25109 -
Arthritis Research & Therapy Apr 2012During pregnancy in autoimmune conditions, maternal autoantibodies are transported across the placenta and may affect the developing fetus. Congenital heart block (CHB)... (Review)
Review
During pregnancy in autoimmune conditions, maternal autoantibodies are transported across the placenta and may affect the developing fetus. Congenital heart block (CHB) is known to associate with the presence of anti-Ro/SSA and anti-La/SSB antibodies in the mother and is characterized by a block in signal conduction at the atrioventricular (AV) node. The mortality rate of affected infants is 15% to 30%, and most live-born children require lifelong pacemaker implantation. Despite a well-recognized association with maternal anti-Ro/La antibodies, CHB develops in only 1% to 2% of anti-Ro-positive pregnancies, indicating that other factors are important for establishment of the block. The molecular mechanisms leading to complete AV block are still unclear, and the existing hypotheses fail to explain all aspects of CHB in one comprehensive model. In this review, we discuss the different specificities of maternal autoantibodies that have been implicated in CHB as well as the molecular mechanisms that have been suggested to operate, focusing on the evidence supporting a direct pathogenic role of maternal antibodies. Autoantibodies targeting the 52-kDa component of the Ro antigen remain the antibodies most closely associated with CHB. In vitro experiments and animal models of CHB also point to a major role for anti-Ro52 antibodies in CHB pathogenesis and suggest that these antibodies may directly affect calcium regulation in the fetal heart, leading to disturbances in signal conduction or electrogenesis or both. In addition, maternal antibody deposits are found in the heart of fetuses dying of CHB and are thought to contribute to an inflammatory reaction that eventually induces fibrosis and calcification of the AV node, leading to a complete block. Considering that CHB has a recurrence rate of 12% to 20% despite persisting maternal autoantibodies, it has long been clear that maternal autoantibodies are not sufficient for the establishment of a complete CHB, and efforts have been made to identify additional risk factors for this disorder. Therefore, recent studies looking at the influence of genetic and environmental factors will also be discussed.
Topics: Animals; Autoantibodies; Female; Heart Block; Humans; Maternal-Fetal Exchange; Pregnancy
PubMed: 22546326
DOI: 10.1186/ar3787