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PubMedDate not supplied

[Isolated congenital heart block in undifferentiated connective tissue disease and in primary Sjögren's syndrome: a clinical study of 81 pregnancies in 41 patients].

OBJECTIVE: To study the incidence and the features of congenital heart block (CHB) in patients with undifferentiated connective tissue disease (UCTD) and primary Sjögren's syndrome (pSS). METHODS: We studied 81 pregnancies of 41 women attending the Outpatients' Clinic of the Rheumatology Unit of University Hospital of Padova from July 1989 to March 2004. Twenty five of these (61%) were affected with UCTD and 16 (39%) with pSS. Serologic inclusion criteria was anti-Ro/La positivity, assessed by counterimmunoelectrophoresis and ELISA. RESULTS: CHB was found in 2 out of the 46 (4.3%) pregnancies followed by our Staff and in 2 out of the 35 (5.7%) included in the retrospective part of the study. In 3 cases CHB was a 3rd degree block, causing pregnancy termination in 2. The only 2nd degree block was identified in one patient at the 22nd week of gestation and treated with dexamethasone and plasma-exchange. All of the women were positive to 52 kd and 60 kd Ro autoantibodies. CHB mothers had higher titer antibodies to 52 kd Ro protein than did the mothers with healthy infants (P = 0.026). Electrocardiographic abnormalities at birth were found in 3 out of 29 asymptomatic infants. One presented sinus bradycardia, the second abnormalities of ventricular repolarization, both regressed spontaneously, while the third ventricular extrasystoles which continue even now at 5 months. CONCLUSIONS: These results showed that in UCTD and pSS there is a higher incidence of CHB than that reported in Systemic Lupus Erythematosus. Electrocardiographic screening in all infants born to mothers with anti-Ro/La antibodies would seem an important measure to identify those with irreversible heart conduction abnormalities.

Adult↗
PubMed1995

Complete heart block and severe tricuspid regurgitation after radiotherapy. Case report and review of the literature.

Cardiac complications can occur long after chest radiotherapy. We describe a patient who developed both valve disease and complete heart block at different intervals following radiotherapy for Hodgkin's disease. The combined presentation of these two very rare cardiac complications and surgery for radiation-induced tricuspid valve disease have not been described before.

Adult↗
PubMed1978

[Long term electrophysiological study on patients with acute myocardial infarction and complete heart block. Is cardiac pacing always necessary? (author's transl)].

UNLABELLED: Of 335 consecutive patients (pts) admitted to the coronary care unit (CCU) for acute myocardial infarction (AMI), 34 (10%) evidenced complete heart block (HB). The overall inhospital mortality was 14% (47 pts) versus 39% of the HB group (13 pts). No previous conduction disturbances were documented in 58% of pts before appearance of complete HB. Complete HB was preceded in 52% of pts by first or second degree HB or bundle branch block. Of 21 pts with HB discharged from the hospital, 5 (23%) died between 5 and 24 months (mean 12): no patients had sudden death; 16 pts (76%) are still alive after 13 to 45 months (mean 30). His bundle electrophysiologic (HBE) study was performed in 10 pts of the HB group after 4 to 40 months: 4 pts with anterior versus 6 with inferior AMI. Conduction disturbances were no longer present in all but one pt who had H-V 60 msec. Ajmaline (50 + 50 mg iv) prolonged A-H over 130 msec in 4 pts; H-V was not significantly increased in 8 of the 10 pts, while in two pts was 100 msec. One pt in the acute phase and one pt 12 months later, required pacemaker (PM) implant (both had inferior MI). IN CONCLUSION: no sudden death was documented during the follow-up period. The late HBE study, before and after ajmaline, did not allow to recognize critical conduction abnormalities suggessting prophylactic PM implantation.

Adult↗
PubMed1998

Immune-mediated congenital heart block (CHB): identifying and counseling patients at risk for having children with CHB.

OBJECTIVE: To identify patterns of maternal antibodies associated with an increased risk of having a child with congenital heart block (CHB) and to provide a basis for counseling women with a previously affected child. METHODS: This retrospective clinical study of the obstetric histories of 46 Finnish women with a CHB child compared the strength and specificity of the immune response to SS-A/Ro and SS-B/La, as determined by immunoblot and ELISA, in 44 affected women with 85 women with systemic lupus erythematosus (SLE) and 32 women with primary Sjögren's syndrome (SS) with healthy children. RESULTS: High levels of anti-SS-A/Ro and anti-SS-B/La by practically all assays were associated with a significantly increased risk of having a CHB child. The best single test to identify high-risk mothers was anti-52 kd SS-A/Ro by immunoblot (OR 18.9), and it was the only assay to detect mothers at increased risk of CHB as compared with controls with primary SS. Low risk of CHB was indicated by undetectable or low levels of antibodies in the ELISA assays and no reactivity on immunoblot. Mothers with a previous child with CHB had a history of fetal loss (mostly spontaneous abortions) or a history of recurrent fetal losses (> or = 3) slightly more often than controls. Late-trimester obstetric complications in non-CHB pregnancies were insignificant. The relative risk for a female child compared with a male child to have CHB was 1.9 (1.2-2.9, P = .009), and the risk of the mother having another child with CHB was 12% (4 of 34). CONCLUSION: Although there is no unique antibody profile specific for CHB, mothers with a high or low risk of having a child with CHB can be identified. Female children appear to have an increased risk of CHB, but the risk of the mother having another child with CHB is low.

Abortion, Spontaneous↗
PubMed1998

Autoimmune-associated congenital heart block: demographics, mortality, morbidity and recurrence rates obtained from a national neonatal lupus registry.

OBJECTIVES: The present study describes the demographics, mortality, morbidity and recurrence rates of autoimmune-associated congenital heart block (CHB) using information from the Research Registry for Neonatal Lupus. BACKGROUND: Isolated CHB detected at or before birth is strongly associated with maternal autoantibodies to 48-kD SSB/La, 52-kD SSA/Ro and 60-kD SSA/Ro ribonucleoproteins and is a permanent manifestation of the neonatal lupus syndromes (NLS). Available data are limited by the rarity of the disease. RESULTS: The cohort includes 105 mothers whose sera contain anti-SSA/Ro or anti-SSB/La antibodies, or both, and their 113 infants diagnosed with CHB between 1970 and 1997 (56 boys, 57 girls). Of 87 pregnancies in which sufficient medical records were available, bradyarrhythmia confirmed to be CHB was initially detected before 30 weeks of gestation in 71 (82%) (median time 23 weeks). There were no cases in which major congenital cardiac anatomic defects were considered causal for the development of CHB; in 14 there were minor abnormalities. Twenty-two (19%) of the 113 children died, 16 (73%) within 3 months after birth. Cumulative probability of 3-year survival was 79%. Sixty-seven (63%) of 107 live-born children required pacemakers: 35 within 9 days of life, 15 within 1 year, and 17 after 1 year. Forty-nine of the mothers had subsequent pregnancies: 8 (16%) had another infant with CHB and 3 (6%) had a child with an isolated rash consistent with NLS. CONCLUSIONS: Data from this large series substantiate that autoantibody-associated CHB is not coincident with major structural abnormalities, is most often identified in the late second trimester, carries a substantial mortality in the neonatal period and frequently requires pacing. The recurrence rate of CHB is at least two- to three-fold higher than the rate for a mother with anti-SSA/Ro-SSB/La antibodies who never had an affected child, supporting close echocardiographic monitoring in all subsequent pregnancies, with heightened surveillance between 18 and 24 weeks of gestation.

Autoimmune Diseases↗
PubMedDate not supplied

Cardiac 5-HT(4) serotoninergic receptors, 52kD SSA/Ro and autoimmune-associated congenital heart block.

It was recently reported that sera from patients with systemic lupus erythematosus contain antibodies reactive with the second extracellular loop of the serotoninergic 5-HT(4) receptor expressed in the human heart. This antibody response was associated with antibodies to 52kD SSA/Ro, a reactivity prevalent in mothers of children with congenital heart block (CHB). The current study was undertaken to determine whether the 5-HT(4) receptor is a target of the immune response in these mothers. Initial experiments demonstrated mRNA expression of the 5-HT(4) receptor in the human foetal atrium. Electrophysiologic studies established that human foetal atrial cells express functional 5-HT(4) receptors. Sera from 116 mothers enrolled in the Research Registry for Neonatal Lupus, whose children have CHB, were evaluated. Ninety-nine (85%) of these maternal sera contained antibodies to SSA/Ro, 84% of which were reactive with the 52kD SSA/Ro component by immunoblot. None of the 116 sera were reactive with the peptide spanning aa165-185 of the serotoninergic receptor. Rabbit antisera which recognized this peptide did not react with 52kD SSA/Ro or peptide aa365-382 in the C terminus. Although 5-HT(4) receptors are present and functional in the human foetal heart, maternal antibodies to the 5-HT(4) receptor are not associated with the development of CHB.

Antibodies↗
PubMed1995

Anti-La (SS-B) but not anti-Ro52 (SS-A) antibodies cross-react with laminin--a role in the pathogenesis of congenital heart block?

Cross-reactions between maternally derived autoantibodies and fetal cardiac antigens have been postulated to play a role in the pathogenesis of congenital heart block (CHB). We have explored the cross-reactivity of autoantibodies to the small ribonuclear autoantigens, La/SS-B and Ro/SS-A, with laminin, the major component of cardiac sarcolemmal membrane using affinity-purified antibodies from patients with Sjögren's syndrome (SS). Anti-La antibodies purified from eight of 10 patients cross-reacted significantly with mouse laminin by ELISA. In contrast, purified antibodies to Ro52 from the same 10 patients showed little or no binding to laminin. Laminin inhibited up to 70% binding of anti-La antibodies to La antigen, and La inhibited up to 65% binding of anti-La antibodies to laminin. The cross-reaction was further examined on cryosections of 10 human fetal hearts aged from 8.7 to 14.9 weeks of gestation, two normal adult hearts, and one pathological adult heart with a diagnosis of dilated cardiomyopathy. Anti-Ro52 antibodies did not bind to the surface of cardiac cells. However, anti-La antibodies from seven of 10 patients tested bound to the surface of fetal myocytes from hearts aged 9.4 to 14.9 weeks of gestation, and also to the myocytes from the pathological adult heart but not to normal adult hearts. Preincubation with La antigen abolished the binding of anti-La antibodies to the surface of adult heart myocytes with dilated cardiomyopathy, and pre-incubation with mouse laminin could partially block this binding. These results suggest that molecular mimicry between laminin and La, but not Ro52, may act as a target for specific maternal autoantibodies, and contribute to the pathogenesis of CHB at a critical stage during fetal cardiac development.

Adult↗
PubMed1996

The expression of human endogenous retrovirus-3 in fetal cardiac tissue and antibodies in congenital heart block.

Endogenous retrovirus-3 (ERV-3) is an endogenous retrovirus encoding an open reading frame for an envelope protein expressed in placenta. In this study we also found high levels of expression in fetal heart, with peak expression occurring between 11 and 17 weeks of gestation. Antibodies to a peptide corresponding to a predicted epitope of ERV-3 were studied by ELISA in sera from 32 healthy women, 47 women during pregnancy, 19 post-partum, 34 with Sjogren's syndrome (SS), 28 with systemic lupus erythematosus (SLE) and 48 mothers of babies with congenital heart block (CHB). Elevated levels of antibodies to ERV-3 were found in normal pregnancy and in patients with SS or SLE. Compared with normal sera the highest levels occurred in mothers of CHB babies (P < 0.001). Antibodies from sera from three CHB mothers bound to recombinant transmembrane protein of ERV-3 on immunoblots, and to sections of fetal cardiac tissue and placenta. This study has shown evidence of autoimmunization to ERV-3 during pregnancy, with particularly high levels of antibodies in mothers of CHB babies. The expression of ERV-3 in fetal heart and the presence of antibodies in maternal sera suggest a possible role in the pathogenesis of CHB.

Adult↗