Late development of complete atrioventricular block may be immune mediated and congenital in origin

Bergman, Gunnar; Skog, Amanda; Tingström, Joanna; Ottosson, Vijole; Hoxha, Ariela; Ambrosi, Aurélie; Salomonsson, Stina; Wahren‐Herlenius, Marie

doi:10.1111/apa.12483

Cited by 22 publications

(17 citation statements)

References 20 publications

(32 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, a recent report from the Swedish cardiac NL cohort identified 13 anti-SSA/Ro-exposed cases diagnosed after birth (age 4 months to 43 years of age), 11 with normal heart rates in utero (42). These findings support the hypothesis that immune-mediated inflammation and fibrosis in cardiac tissues can continue postnatally, resulting in late progression to cardiac NL.…”

Section: Discussionmentioning

confidence: 99%

Serum Biomarkers of Inflammation, Fibrosis, and Cardiac Function in Facilitating Diagnosis, Prognosis, and Treatment of Anti-SSA/Ro–Associated Cardiac Neonatal Lupus

Saxena

Izmirly

Han

et al. 2015

Journal of the American College of Cardiology

View full text Add to dashboard Cite

BACKGROUND Cardiac manifestations of neonatal lupus (cardiac NL) include congenital heart block and cardiomyopathy. Several candidate biomarkers were evaluated in cases at risk for cardiac NL on the basis of potential roles in inflammation, fibrosis, and cardiac dysfunction: C-reactive protein (CRP); NT-pro-B-type natriuretic peptide (NT-proBNP); troponin I; matrix metalloproteinase (MMP)-2; urokinase plasminogen activator (uPA); urokinase plasminogen activator receptor (uPAR); plasminogen; and vitamin D. OBJECTIVES Identification of maternal and fetal biomarkers associated with development and morbidity of cardiac NL should provide clues to pathogenesis with translational implications for management. METHODS Cord and maternal blood samples (139 each) collected during pregnancies at risk for cardiac NL were available for study. Levels of cord and maternal CRP, cord NT-proBNP, and cord troponin I were evaluated using multiplex assays. Cord and maternal vitamin D were assessed by liquid chromatography-mass spectrometry. MMP-2, uPA, uPAR, and plasminogen were evaluated using ELISA. RESULTS Cord CRP, NT-proBNP, MMP-2, uPA, uPAR, and plasminogen levels were higher in cardiac NL-affected fetuses than in unaffected cases, independent of maternal rheumatic disease, season at highest risk of cardiac NL development, and medications taken during pregnancy. These biomarkers were positively associated with a disease severity score derived from known risk factors for mortality in cardiac NL. Maternal CRP and cord troponin I levels did not differ between the groups. Cord and maternal vitamin D levels were not significantly associated with cardiac NL, but average maternal vitamin D level during pregnancy was positively associated with longer time to postnatal pacemaker placement. CONCLUSIONS These data support the association of fetal reactive inflammatory and fibrotic components with development and morbidity of cardiac NL. Following CRP and NT-proBNP levels after birth can potentially monitor severity and progression of cardiac NL. MMP-2 and the uPA/uPAR/plasminogen cascade provide therapeutic targets to decrease fibrosis. Although decreased vitamin D did not confer increased risk, given the positive influence on postnatal outcomes, maternal levels should be optimized.

show abstract

Section: Discussionmentioning

confidence: 99%

Serum Biomarkers of Inflammation, Fibrosis, and Cardiac Function in Facilitating Diagnosis, Prognosis, and Treatment of Anti-SSA/Ro–Associated Cardiac Neonatal Lupus

Saxena

Izmirly

Han

et al. 2015

Journal of the American College of Cardiology

View full text Add to dashboard Cite

show abstract

“…26 Starting with this body of evidence, in a Swedish nationwide retrospective study, 53 cases of isolated III1AVB of unknown origin were identified in whom the diagnosis was made after the cutoff period of 27 days of life (range 4 months-43 years, median 9 years, mean 13.6 years) and whose mothers were available for blood sampling. 29 Among these cases, 13 (24.5%) had a seropositive mother. All these 13 subjects were anti-Ro/SSA-negative.…”

Section: Late Progressive Congenital Formmentioning

confidence: 99%

“…In the Swedish nationwide retrospective study, 2 of 13 reported cases were diagnosed in relation to infections, suggesting that microbes may be a triggering factor. 29 In the other patients who had no evident pathogenic factor other than maternal autoantibodies, milder infections cannot be excluded. Moreover, 1 subject had a family history of cardiomyopathy, which may have contributed to the late progression of the conduction defect.…”

Section: Putative Mechanismsmentioning

confidence: 99%

See 1 more Smart Citation

Isolated atrioventricular block of unknown origin in adults and anti-Ro/SSA antibodies: Clinical evidence, putative mechanisms, and therapeutic implications

2015

View full text Add to dashboard Cite

“…In contrast, maternal autoantibodies have been detected in only a minority of children, in whom AV block was diagnosed beyond the neonatal period, a different, distinct clinical entity [15, 34, 95]. However, some isolated AV blocks diagnosed beyond the neonatal period are also immune-mediated, even with late detection of maternal anti-Ro/SSA autoantibodies [12]. This condition, emerging in childhood or even in the adult age, represents a late progressive congenital form of immune AV block with the late development of a subclinical anti-Ro/SSA-induced congenital damage of the conduction system, related to a not fully understood autoantibody-independent worsening with age [51].…”

Section: Atrioventricular Conduction Disorders In Structurally Normalmentioning

confidence: 99%

Congenital and childhood atrioventricular blocks: pathophysiology and contemporary management

Baruteau¹,

Pass²,

Thambo³

et al. 2016

Eur J Pediatr

102

View full text Add to dashboard Cite

Atrioventricular block is classified as congenital if diagnosed in utero, at birth, or within the first month of life. The pathophysiological process is believed to be due to immune-mediated injury of the conduction system, which occurs as a result of transplacental passage of maternal anti-SSA/Ro-SSB/La antibodies. Childhood atrioventricular block is therefore diagnosed between the first month and the 18th year of life. Genetic variants in multiple genes have been described to date in the pathogenesis of inherited progressive cardiac conduction disorders. Indications and techniques of cardiac pacing have also evolved to allow safe permanent cardiac pacing in almost all patients, including those with structural heart abnormalities.Conclusion: Early diagnosis and appropriate management are critical in many cases in order to prevent sudden death, and this review critically assesses our current understanding of the pathogenetic mechanisms, clinical course, and optimal management of congenital and childhood AV block. What is Known: • Prevalence of congenital heart block of 1 per 15,000 to 20,000 live births. AV block is defined as congenital if diagnosed in utero, at birth, or within the first month of life, whereas childhood AV block is diagnosed between the first month and the 18th year of life. As a result of several different etiologies, congenital and childhood atrioventricular block may occur in an entirely structurally normal heart or in association with concomitant congenital heart disease. Cardiac pacing is indicated in symptomatic patients and has several prophylactic indications in asymptomatic patients to prevent sudden death. • Autoimmune, congenital AV block is associated with a high neonatal mortality rate and development of dilated cardiomyopathy in 5 to 30 % cases. What is New: • Several genes including SCN5A have been implicated in autosomal dominant forms of familial progressive cardiac conduction disorders. • Leadless pacemaker technology and gene therapy for biological pacing are promising research fields. In utero percutaneous pacing appears to be at high risk and needs further development before it can be adopted into routine clinical practice. Cardiac resynchronization therapy is of proven value in case of pacing-induced cardiomyopathy.

show abstract

Late development of complete atrioventricular block may be immune mediated and congenital in origin

Cited by 22 publications

References 20 publications

Serum Biomarkers of Inflammation, Fibrosis, and Cardiac Function in Facilitating Diagnosis, Prognosis, and Treatment of Anti-SSA/Ro–Associated Cardiac Neonatal Lupus

Serum Biomarkers of Inflammation, Fibrosis, and Cardiac Function in Facilitating Diagnosis, Prognosis, and Treatment of Anti-SSA/Ro–Associated Cardiac Neonatal Lupus

Isolated atrioventricular block of unknown origin in adults and anti-Ro/SSA antibodies: Clinical evidence, putative mechanisms, and therapeutic implications

Congenital and childhood atrioventricular blocks: pathophysiology and contemporary management

Contact Info

Product

Resources

About