Prediction of outcome in fetal autoimmune complete heart block.

Assessing cardiac function and risk stratification in a fetal anti-Sjögren syndrome type A (SSA) or anti-Sjögren syndrome type B (SSB) complete atrioventricular block (CAVB) is challenging. We aimed to evaluate the cardiovascular profile score (CVP) and its components in surveillance of fetuses with autoimmune CAVB. METHODS: Retrospective cohort review of CAVB pregnancies, excluding fetuses with significant cardiac anomalies. RESULTS: CAVBs are in 17 fetuses, diagnosed at mean gestational age of 23 ± 5 weeks. Overall mortality is 18%: 1 termination, 1 fetal demise (intrauterine fetal demise [IUFD]), and 1 postnatal death. Both mortalities had intrauterine growth restriction; IUFD had placental infarction. Presenting CVP 8.7 ± 1. No fetus had CVP <7; the score correlated with increased risk of perinatal death. The 2 mortalities had initial CVP scores of 8 and 9; both increased to 10 on subsequent exams. 30% of fetuses had low middle cerebral artery pulsatility (MCA-PI) on the last study. All had high umbilical artery pulsatility (UA-PI) throughout gestation. The 2 deaths had the lowest MCA-PI. CONCLUSION: Despite low heart rates, high CVP scores in our cohort remained high and were not predictive of mortality. Abnormalities in MCA flow reflects fetal cerebral vasodilation that may indicate altered hemodynamics and be predictive of outcomes, but data is limited. Abnormal umbilical artery (UA) flow suggests that perinatal mortality may also be related to placental disease.

Immune-Mediated Fetal Complete Atrioventricular Block: Can Dexamethasone Therapy Revert the Process?

BACKGROUND: Fetal complete atrioventricular block (CAVB) is usually autoimmune mediated. The risk of developing CAVB is 2% to 3% in anti-Ro/SS-A seropositive pregnancies and it increases 10 times after previous CAVB in siblings. Despite being a rare complication, CAVB carries a 20% mortality rate and substantial morbidity, as about 65% of newborns will eventually need life-long pacing. Once found, fetal CAVB is almost always irreversible, despite aggressive immunotherapy. This poor outcome prompted some research groups to address this situation. All groups followed anti-Ro/SS-A seropositive pregnancies on a weekly basis during the second trimester of pregnancy and tried to detect first degree atrioventricular block (AVB) using accurate echocardiographic tools, assuming they may characterize the initiation of the immune damage to the A-V conduction system, at which point the process might still be reversible. Some of the groups treated fetuses with first degree AVB with maternal oral fluorinated steroids. We summarized the results of all groups, including our group. We describe a case of a fetus that developed CAVB 6 days after normal sinus rhythm (NSR), who under aggressive dexamethasone therapy gradually reverted to NSR. This fetus had a previous sibling with CAVB. We assumed the immune damage to the conduction system in this small group of fetuses with a previous CAVB sibling may have occurred more quickly than usual. We therefore recommend a twice-weekly follow-up with these fetuses.

Maternal steroid therapy for fetuses with second-degree immune-mediated congenital atrioventricular block: a systematic review and meta-analysis.

INTRODUCTION: The aim of this study was to explore the effect of maternal fluorinated steroid therapy on fetuses affected by second-degree immune-mediated congenital atrioventricular block. MATERIAL AND METHODS: Studies reporting the outcome of fetuses with second-degree immune-mediated congenital atrioventricular block diagnosed on prenatal ultrasound and treated with fluorinated steroids compared with those not treated were included. The primary outcome was the overall progression of congenital atrioventricular block to either continuous or intermittent third-degree congenital atrioventricular block at birth. Meta-analyses of proportions using random effect model and meta-analyses using individual data random-effect logistic regression were used. RESULTS: Five studies (71 fetuses) were included. The progression rate to congenital atrioventricular block at birth in fetuses treated with steroids was 52% (95% confidence interval 23-79) and in fetuses not receiving steroid therapy 73% (95% confidence interval 39-94). The overall rate of regression to either first-degree, intermittent first-/second-degree or sinus rhythm in fetuses treated with steroids was 25% (95% confidence interval 12-41) compared with 23% (95% confidence interval 8-44) in those not treated. Stable (constant) second-degree congenital atrioventricular block at birth was present in 11% (95% confidence interval 2-27) of cases in the treated group and in none of the newborns in the untreated group, whereas complete regression to sinus rhythm occurred in 21% (95% confidence interval 6-42) of fetuses receiving steroids vs. 9% (95% confidence interval 0-41) of those untreated. CONCLUSIONS: There is still limited evidence as to the benefit of administered fluorinated steroids in terms of affecting outcome of fetuses with second-degree immune-mediated congenital atrioventricular block.

Reversible complete atrioventricular block in patient with wegener's granulomatosis - a report on fortunate outcome with long term follow-up.

Reversible complete atrioventricular block in patient with Wegener's granulomatosis - a report on a positive outcome with long term follow-up. Atrioventricular (AV) block is a rare complication of Wegener's granulomatosis (WG), thus there are no standards of management in such cases. We present a case of a patient with a dual-chamber pacemaker (DDD) implanted due to complete AV block in the course of Wegener's granulomatosis (WG). An immunosuppressive therapy resulted in the resolution of non-cardiac and AV conduction disorders. The diagnostic functions of the pacemaker enabled us to evaluate AV conduction over a five-year follow-up period. The resolution of AV conduction disorders, which accompanied WG remission, suggests that careful monitoring with temporary cardiac pacing may be considered in some patients before permanent pacemaker implantation.

Fetal magnetocardiography (fMCG) to monitor cardiac time intervals in fetuses at risk for isoimmune AV block.

OBJECTIVE: The objective of this report is to detect cardiac time intervals (CTIs) in fetuses exposed to SSA/Ro-SSB/La antibodies in relation to gestational age (GA) and fetal weight and compared them with a control cohort. METHODS: Fetal magnetocardiography (fMCG) recordings were conducted on a biomagnetic device dedicated to obstetrical measurement starting in the second trimester. Fetal cardiac time intervals of 87 healthy fetuses of normal gestation (control group) were compared to 11 fetuses exposed to maternal SSA/Ro-SSB/La antibodies (study group). RESULTS: fCTIs were analyzed starting at 17 weeks of GA. Atrial and ventricular depolarization times increased with GA in both groups. PQ segments were significantly longer in the study group (50.8 ms vs. 60.2 ms; p < 0.001) independent of GA or fetal weight. PQ segment prolongation was more obvious in the study group prior to 30 weeks of GA. CONCLUSION: PQ segment prolongation can be interpreted as early AV-node involvement caused by maternal SSA/Ro-SSB/La antibodies. The age dependency of the PQ segment should be taken into account in further studies.

Outcomes of fetal echocardiographic surveillance in anti-SSA exposed fetuses at a large fetal cardiology center.

BACKGROUND: Echocardiography screening in anti-SSA antibody exposed fetuses is controversial. OBJECTIVE: The aim of this study is to evaluate utility of fetal echocardiography in anti-SSA exposure. METHODS: Echocardiograms performed over 9 years for maternal anti-SSA exposure were reviewed for atrioventricular (AV) block, cardiomyopathy, arrhythmias, effusion, valve abnormalities, or other abnormalities identified by the echocardiographer. Fetuses with AV block referred to our institution and subsequently found to be anti-SSA exposed were also identified. RESULTS: Six hundred thirty six echocardiograms were performed on 140 fetuses (Cohort 1) of 134 women screened for maternal anti-SSA +/- anti-SSB antibodies. No fetuses developed second or third-degree AV block or cardiomyopathy (odds ratio 0.1, CI 0.0051 to 1.9410, p = 0.13). Dexamethasone was administered to three fetuses for sinus bradycardia, echogenicity near AV node, and ventricular systolic dysfunction with valve regurgitation; all normalized. Screening echocardiograms identified: sinus bradycardia (n = 1), PR prolongation (n = 5), premature atrial contractions (n = 3), valve regurgitation (n = 24), echogenic myocardium (n = 4), and pericardial effusion (n = 1). Isolated tricuspid regurgitation and first-degree AV block did not progress. Nine cases of SSA-mediated AV block (Cohort 2) were referred after heart block developed. CONCLUSIONS: Serial fetal echocardiography in anti-SSA exposed fetuses did not detect AV block. In rare cases, dexamethasone treatment may have affected disease course.

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

AIM: To investigate the correlation between maternal autoantibodies and age at diagnosis of isolated complete atrioventricular (AV) block (CAVB) and to study signs of late progression of foetal immune-mediated insults in cases of postnatally diagnosed CAVB. METHODS: Patients with CAVB (n = 190) identified in a population-based manner were included. Maternal autoantibody profile was correlated with age at CAVB diagnosis. A structured review of medical records was performed if a late CAVB diagnosis (>27 days post-partum) was associated with a sero-positive mother. RESULTS: Maternal Ro/La autoantibodies were observed in 88% of cases with a congenital diagnosis. Thirteen cases with a sero-positive mother and late CAVB diagnosis were found (age-range: 4 months-43 years). In two cases, CAVB was diagnosed in conjunction with infections, one case had a family history of cardiomyopathy and two cases had nontypical clinical presentations, indicating alternative pathogenetic mechanisms. In the remaining eight cases, no likely factors inducing CAVB, other than maternal autoantibodies, could be identified. CONCLUSION: Our observations support the hypothesis that late progression to CAVB can be the result of an immune-mediated pathogenetic mechanism during foetal life. An autoantibody-associated diagnosis after the neonatal period is therefore possible, and testing of maternal serology at the time of diagnosis is recommended.

Advanced Atrioventricular Block in Athletes: Prevalence and Role of Anti-Ro/Sjögren Syndrome-Related Antigen A Antibodies.

BACKGROUND: Advanced atrioventricular block (AVB), that is, higher than second-degree Mobitz-1, is an abnormal finding in athletes. Despite intensive investigation, in several cases the pathogenesis remains unknown, but frequently pacemaker implantation is still indicated. Increasing evidence points to circulating anti-Ro/Sjögren syndrome-related antigen A (SSA) antibodies cross-reacting with L-type calcium channel and inhibiting the related current as an epidemiologically relevant and potentially reversible cause of isolated AVB in adults. The aim of the study was to determine the prevalence of anti-Ro/SSA-associated advanced AVBs in a large sample of young athletes. METHODS AND RESULTS: A total of 2536 consecutive athletes aged <40 years without a history of cardiac diseases/interventions were enrolled in a cross-sectional study. Resting and exercise electrocardiography was performed, and those presenting any AVB were further evaluated by 24-hour Holter ECG. Athletes with second-degree AVBs and their mothers underwent anti-Ro/SSA testing. Moreover, purified immunoglobulin G from subjects with anti-Ro/SSA-positive and anti-Ro/SSA-negative advanced AVB were tested on L-type calcium current and L-type-calcium channel expression using tSA201 cells. The global prevalence of advanced AVB in the overall sample was ≈0.1%, but the risk considerably increased (2%) when intensely trained postpubertal male subjects were selectively considered. While none of the athletes with advanced AVB showed heart abnormalities, in 100% of cases anti-Ro/SSA antibodies were detected. Ex vivo experiments showed that immunoglobulin G from anti-Ro/SSA-positive but not -negative subjects with advanced AVB acutely inhibit L-type calcium current and chronically downregulate L-type-calcium channel expression. CONCLUSIONS: Our study provides evidence that advanced AVB occurs in young athletes, in most cases associated with anti-Ro/SSA antibodies blocking L-type calcium channels. These findings may open new avenues for immunomodulating therapies to reduce the risk of life-threatening events in athletes, avoiding or delaying pacemaker implantation.

Risk of cardiac conduction disorders, and pacemaker implantations among individuals tested for serum Borrelia burgdorferi antibodies, a nationwide, matched, population-based cohort study.

OBJECTIVES: To investigate the short- and long-term risks of atrioventricular block and other cardiac conduction disorders associated with being tested for Borrelia burgdorferi (Bb) antibodies or Bb seropositivity as measures of confounding by indication and Bb infection, respectively. METHODS: We performed a nationwide population-based matched cohort study (Denmark, 1993-2021). We included 52 200 Bb-seropositive individuals (stratified as only Bb-IgM-seropositive [n = 26 103], only Bb-IgG-seropositive [n = 18 698], and Bb-IgM-and-IgG-seropositive [n = 7399]) and two age- and sex-matched comparison cohorts: 104 400 Bb-seronegative individuals and 261 000 population controls. We investigated the risk associated with being tested for serum Bb antibodies and being Bb seropositive. Outcomes were atrioventricular block and other conduction disorders. We calculated short-term odds ratios (aOR) (within 1 month), and long-term hazard ratios (aHR) (after 1 month) adjusted for age, sex, diabetes, chronic heart failure, and kidney disease with 95% CI. RESULTS: Compared with population controls, individuals tested for Bb antibodies had increased short- and long-term risks of atrioventricular block (aOR 47.9, 95% CI: 30.0-76.7, aHR 1.3, 95% CI:1.2-1.3), and other conduction disorders (aOR 18.2, 95% CI: 10.1-32.8, aHR 1.2, 95% CI: 1.1-1.4). Compared with Bb-seronegative individuals, only Bb-IgM-and-IgG-seropositive individuals had increased short-term risk of atrioventricular block (aOR: 2.1, 95% CI: 1.5-3.1). DISCUSSION: The results suggest that Bb antibody testing is included in the diagnostic work-up of conduction disorders. Finally, that Bb seropositivity is not associated with other conduction disorders than atrioventricular block or with increased long-term risk of conduction disorders.

Dual challenge inside the womb: a case report of concomitant fetal atrio-ventricular block associated with maternal anti-SSA antibodies and fetal tachyarrhythmia diagnosed as Wolff-Parkinson-White syndrome after birth.

Fetal autoimmune atrioventricular block (AVB) is a rare but potentially life-threatening condition. It results from the passage of maternal anti-SSA/Ro or Anti SSB/La auto-antibodies into the fetal circulation, leading to inflammation and fibrosis of the AV node and often to irreversible damage. Besides AVB, these antibodies can also cause cardiomyopathies, but there is no evidence linking them to tachyarrhythmias. We present the case of a patient with significant risk factors for fetal AVB: a prior history of hydrops fetalis, high anti-SSA/Ro antibody levels and hypothyroidism. In this case, the use of dexamethasone and intravenous immunoglobulin may have contributed to reversing the first-degree atrioventricular block detected at 19 weeks of gestation. Additionally, at 21 weeks, the fetus developed a tachyarrhythmia that needed treatment with flecainide. Soon after the birth, the newborn underwent ECG Holter and Wolff-Parkinson-White Syndrome (WPWS) was diagnosed. To our knowledge, the coexistence of fetal AVB and WPWS has never been described.

Subclinical maternal autoimmune disease leading to congenital high degree atrioventricular block: Case report and review of the literature.

Maternal autoimmune disease is the most common cause of congenital heart block (CHB), a rare illness characterized by fibrosis and calcification of the fetal atrioventricular (AV) node due to maternal autoantibodies anti-SSA/Ro and anti-SSB/La. We report the full autopsy and clinical information on a female neonate with high degree AV block and calcification in the AV node, atrial approaches to the AV node, and both right and left bundle branches, born to a 27-year-old female with subclinical autoimmune disease.

Isolated atrioventricular block in the fetus: a retrospective, multinational, multicenter study of 175 patients.

BACKGROUND: Isolated complete atrioventricular block in the fetus is a rare but potentially lethal condition in which the effect of steroid treatment on outcome is unclear. The objective of this work was to study risk factors associated with death and the influence of steroid treatment on outcome. METHODS AND RESULTS: We studied 175 fetuses diagnosed with second- or third-degree atrioventricular block (2000-2007) retrospectively in a multinational, multicenter setting. In 80% of 162 pregnancies with documented antibody status, atrioventricular block was associated with maternal anti-Ro/SSA antibodies. Sixty-seven cases (38%) were treated with fluorinated corticosteroids for a median of 10 weeks (1-21 weeks). Ninety-one percent were alive at birth, and survival in the neonatal period was 93%, similar in steroid-treated and untreated fetuses, regardless of degree of block and/or presence of anti-Ro/SSA. Variables associated with death were gestational age < 20 weeks, ventricular rate ≤ 50 bpm, fetal hydrops, and impaired left ventricular function at diagnosis. The presence of ≥ 1 of these variables was associated with a 10-fold increase in mortality before birth and a 6-fold increase in the neonatal period independently of treatment. Except for a lower gestational age at diagnosis in treated than untreated (23.4 ± 2.9 versus 24.9 ± 4.9 weeks; P=0.02), risk factors were distributed equally between treatment groups. Two-thirds of survivors had a pacemaker by 1 year of age; 8 children developed cardiomyopathy. CONCLUSIONS: Risk factors associated with a poor outcome were gestation < 20 weeks, ventricular rate ≤ 50 bpm, hydrops, and impaired left ventricular function. No significant effect of treatment with fluorinated corticosteroids was seen.

Anti-Ro52 monoclonal antibodies specific for amino acid 200-239, but not other Ro52 epitopes, induce congenital heart block in a rat model.

BACKGROUND: Congenital heart block (CHB) may develop in fetuses of women with anti-Ro/La autoantibodies following placental transfer of maternal autoantibodies and disruption of the fetal atrioventricular (AV) conduction system. Animal models of CHB currently rely on immunisation or transfer of anti-Ro/La antibodies purified from mothers of children with CHB, which does not allow precise identification of the disease-inducing antibody specificity. OBJECTIVE: To determine the ability of different anti-Ro52 monoclonal antibodies to induce cardiac electrophysiological abnormalities in vivo and affect the calcium homoeostasis of cardiomyocytes in vitro. METHODS: Monoclonal antibodies recognising different domains of Ro52 were generated and injected into pregnant rats, and ECG was recorded on newborn pups. Cultures of rat neonatal cardiomyocytes were established to assess the effect of the different anti-Ro52 monoclonal antibodies on calcium homoeostasis. RESULTS: First-degree AV block and bradycardia developed after maternal transfer of antibodies specific for amino acids 200-239 of Ro52 (p200), while pups exposed to antibodies targeting N- or C-terminal epitopes of Ro52 did not show any electrocardiogram abnormalities. Addition of an anti-p200 antibody to cultured cardiomyocytes induced calcium dyshomoeostasis in a time- and dose-dependent manner, while addition of other Ro52 antibodies had no effect. CONCLUSION: These data for the first time show unambiguously that antibodies specific for amino acids 200-239 of Ro52 can induce cardiac conduction defects in the absence of other autoantibodies, and may therefore be the main initiators of cardiac pathology in the pool of anti-Ro52 antibodies in mothers of children with CHB.

Maternal MHC regulates generation of pathogenic antibodies and fetal MHC-encoded genes determine susceptibility in congenital heart block.

Congenital heart block develops in fetuses of anti-Ro52 Ab-positive women. A recurrence rate of 20%, despite the persistence of maternal autoantibodies, indicates that there are additional, yet unidentified, factors critical for development of congenital heart block. In this study, we demonstrate that besides the maternal MHC controlling Ab specificity, fetal MHC-encoded genes influence fetal susceptibility to congenital heart block. Using MHC congenic rat strains, we show that heart block develops in rat pups of three strains carrying MHC haplotype RT1(av1) (DA, PVG.AV1, and LEW.AV1) after maternal Ro52 immunization, but not in LEW rats (RT1(l)). Different anti-Ro52 Ab fine specificities were generated in RT1(av1) versus RT1(l) animals. Maternal and fetal influence was determined in an F(2) cross between LEW.AV1 and LEW strains, which revealed higher susceptibility in RT1(l) than RT1(av1) pups once pathogenic Ro52 Abs were present. This was further confirmed in that RT1(l) pups more frequently developed heart block than RT1(av1) pups after passive transfer of RT1(av1) anti-Ro52 sera. Our findings show that generation of pathogenic Ro52 Abs is restricted by maternal MHC, whereas the fetal MHC locus regulates susceptibility and determines the fetal disease outcome in anti-Ro52-positive pregnancies.

A population-based investigation of the autoantibody profile in mothers of children with atrioventricular block.

The objective of the study was to investigate the antigen specificity and occurrence of individual autoantibodies in mothers of children diagnosed with atrioventricular (AV) block in a nation-wide setting. Patients with AV block detected before 15 years of age were identified using national quality registries as well as a network of pediatric and adult cardiologists and rheumatologists at the six university hospitals in Sweden. Patients with gross heart malformations, surgically or infectiously induced blocks were excluded. Blood samples were obtained from the mothers and maternal autoantibody profile, including the occurrence of antibodies against Ro52, Ro60, La, SmB, SmD, RNP-70k, RNP-A, RNP-C, CENP-C, Scl-70, Jo-1, ribosomal RNP and histones was investigated in 193 mothers of children with AV block by immunoblotting and ELISA. Autoantibody reactivity was detected in 48% (93/193) of the mothers of children with AV block. In autoantibody-positive mothers, the vast majority, 95% (88/93), had antibodies against Ro52, while 63% (59/93) had autoantibodies to Ro60 and 58% (54/93) had autoantibodies to La. In addition, 13% (12/93) of the autoantibody-positive mothers had antibodies to other investigated antigens besides Ro52, Ro60 and La, and of these anti-histone antibodies were most commonly represented, detected in 8% (7/93) of the mothers. In conclusion, this Swedish population-based study confirms that maternal autoantibodies may associate with heart block in the child. Further, our data demonstrate a dominant role of Ro52 antibodies in association with AV block.

The benefits of transplacental treatment of isolated congenital complete heart block associated with maternal anti-Ro/SSA antibodies: a review.

Isolated congenital complete atrio-ventricular block (CAVB) is associated with the transplacental passage of maternal autoantibodies directed to foetal Ro/SSA ribonucleoproteins. Their interactions most likely trigger the inflammation of the atrio-ventricular node and the myocardium in susceptible foetuses. The inflamed tissues may then heal with fibrosis that may cause heart block, endocardial fibroelastosis, and dilated cardiomyopathy. CAVB, the most common cardiac complication, typically develops between 18 and 24 gestational weeks. Untreated, the condition carries a significant mortality risk as the foetus needs to overcome the sudden drop in ventricular rate, the loss of normal atrial systolic contribution to ventricular filling, and perhaps concomitant myocardial inflammation and fibrosis. The rationale to treat a foetus at the stage of CAVB is primarily to mitigate myocardial inflammation and to augment foetal cardiac output. Maternal dexamethasone administration has been shown to improve incomplete foetal AV block, myocardial dysfunction, and cavity effusions. Beta-sympathomimetics may be useful to increase the foetal heart rate and myocardial contractility. Published data from our institution suggest an improved survival >90% if maternal high-dose dexamethasone was initiated at the time of CAVB detection and maintained during the pregnancy and if a beta-adrenergic drug was added at foetal heart rates below 55 beats/min. Despite the improvement in outcome, there is an ongoing debate about treatment-related risks. In this review, we will appraise the natural history of untreated CAVB, discuss currently available management options, and examine the results and risks of in-utero treatment of antibody-mediated CAVB.

Arrhythmias presenting in neonatal lupus.

Perfusion of human foetal heart with anti-Ro/SSA antibodies induces transient heart block. Anti-Ro/SSA antibodies may cross-react with T- and L-type calcium channels, and anti-p200 antibodies may cause calcium to accumulate in rat heart cells. These actions may explain a direct electrophysiological effect of these antibodies. Congenital complete heart block is the more severe manifestation of so-called "Neonatal Lupus". In clinical practice, it is important to distinguish in utero complete versus incomplete atrioventricular (AV) block, as complete AV block to date is irreversible, while incomplete AV block has been shown to be potentially reversible after fluorinated steroid therapy. Another issue is the definition of congenital AV block, as cardiologists have considered congenital blocks detected months or years after birth. We propose as congenital blocks detected in utero or within the neonatal period (0-27 days after birth). The possible detection of first degree AV block in utero, with different techniques, might be a promising tool to assess the effects of these antibodies. Other arrhythmias have been described in NL or have been linked to anti-Ro/SSA antibodies: first degree AV block, in utero and after birth, second degree (i.e. incomplete block), sinus bradycardia and QT prolongation, both in infants and in adults, ventricular arrhythmias (in adults). Overall, these arrhythmias have not a clinical relevance, but are important for research purposes.

Spectrum of cardiac involvement in neonatal lupus.

'Neonatal' lupus erythematosus (NLE) describes a clinical spectrum of cardiac and non-cardiac abnormalities observed in neonates and foetuses whose mothers have the auto-antibodies anti-SSA/Ro (anti-Ro) and anti-SSB/La (anti-La). Of the cardiac abnormalities, congenital AVB is the most common cardiovascular abnormality found in affected foetuses and infants. Many other cardiovascular manifestations of NLE have been more recently recognized including atrial and ventricular arrhythmias and other conduction abnormalities, myocarditis, cardiomyopathy often with endocardiofibroelastosis and structural heart disease, particularly valvar lesions. In this report, the spectrum of cardiovascular manifestations observed in foetuses and infants with NLE are reviewed and the pathogenesis, diagnosis and clinical outcomes are briefly discussed.

Anti-Ro52/SSA antibody-exposed fetuses with prolonged atrioventricular time intervals show signs of decreased cardiac performance.

OBJECTIVE: To investigate if anti-Ro/SSA antibody-exposed fetuses with prolonged atrioventricular (AV) time intervals also have prolongation of the isovolumetric contraction time (ICT). METHODS: Seventy-eight anti-Ro/SSA (including 70 anti-Ro52) antibody-exposed fetuses at risk for congenital heart block (CHB) were followed weekly, between 18 and 24 weeks of gestation, with two Doppler echocardiographic methods designed to detect signs of first-degree AV block. One of these AV time measurements, using hemodynamic events from the mitral valve and aortic outflow as indirect markers of atrial and ventricular depolarization (MV-Ao), was also used to calculate a time interval representing an early phase of systolic cardiac performance, i.e. the ICT. Two hundred and eighty-four women with normal pregnancies served as controls for AV time intervals and another 106 were used to establish an ICT reference range. RESULTS: Strong positive relationships were found between ICT and MV-Ao time intervals (r = 0.91, P < 0.001), as well as between ICT and time intervals obtained from the superior vena cava and aorta (r = 0.85, P < 0.001). The ICT was estimated to contribute more than 50% of the total AV time prolongation. Abnormal AV time and ICT intervals were only seen in anti-Ro52 positive pregnancies. CONCLUSIONS: The ICT is an important contributor to prolongation of AV time intervals. This observation suggests that anti-Ro52/SSA antibody-exposed fetal hearts have not only disturbed electrical conduction but also decreased mechanical performance. Moreover, our findings have implications for the interpretation of AV time intervals used for surveillance of fetuses at risk for developing CHB.