Home monitoring of fetal heart rhythm: Lived experiences of women with anti-SSA/Ro52 autoantibodies and their co-parents.

OBJECTIVE: The aim of this study was to explore the parents' experiences of home monitoring of the fetal heart rhythm. Women with anti-SSA/Ro52 autoantibodies carry a 2%-3% risk of giving birth to a child with congenital heart block (CHB), following transplacental transfer and antibody-mediated inflammation in the fetal conduction system during 18th to 24th gestational week. Early detection and subsequent treatment have been reported to decrease morbidity and mortality. Therefore, home monitoring of the fetal heart rhythm by Doppler has been offered at our fetal cardiology center. This study was undertaken to explore the lived experience of the routine. METHODS: Participants were recruited from a single fetal cardiology center. Consecutive sampling was used. The inclusion criteria were women with SSA/Ro52 antibodies who had undergone Doppler examinations within the last two and a half years at the hospital and had monitored the fetal heartbeat at home. A semi-structured questionnaire was created, and the participants were interviewed individually. The interviews were transcribed verbatim and analyzed according to qualitative content analysis. RESULTS: The overall theme was defined as "walking on thin ice," with six underlying categories: reality, different strategies, gain and loss, healthcare providers, underlying tension, and conducting the examinations again, all with a focus on how to handle the home monitoring during the risk period. CONCLUSION: Both the mother and the co-parent expressed confidence in their own abilities and that the monitoring provided them with the advantage of growing a bond with the expected child. However, all the participants described a feeling of underlying tension during the risk period. The results show that home monitoring is not experienced as complicated or a burden for the parents-to-be and should be considered a vital part of the chain of care for mothers at risk for giving birth to a child with CHB. However, explaining the teamwork between the different caregivers, for the patients involved, their areas of expertise, and how they collaborate with the patient continues to be a pedagogic challenge and should be developed further.

Isolated non-immune mediated second-degree atrioventricular block in fetus: natural history and predictive factors for spontaneous recovery.

OBJECTIVES: To uncover the clinical course of fetal isolated non-immune mediated second-degree AVB and determine the factors associated with the spontaneous recovery for fetal non-immune second-degree atrioventricular block (AVB). METHODS: A total of 20 fetuses with isolated, non-immune mediated second-degree AVB were prospectively recruited between 2014 and 2022. These fetuses were divided into the spontaneous recovery group (n=12) and the non-spontaneous recovery group (n=8). Maternal and fetal basic characteristics, intrauterine and postnatal outcomes were compared between groups. RESULTS: Twelve fetuses restored 1:1 atrioventricular conduction in utero and did not recur during the postnatal follow-up period. The residual eight fetuses maintained as second-degree AVB and six of them were aborted due to parental request in utero. Of the two live children with second-degree AVB, one of them progressed to complete AVB at the latest follow up at the age of 34 months, but without any symptoms, heart enlargement or dysfunction. The residual one progressed to complete AVB and was finally diagnosed with type 2 long-QT syndrome. Fetuses in the spontaneous recovery group presented with earlier gestational age at diagnosis (20.0[17.0-26.0] vs. 24.5[18.0-35.0] weeks, p=0.004) and higher atrial rate (147[130-160] vs 138.00[125.00-149.00] bpm, p=0.006) in comparison with the non-spontaneous recovery group. A cut-off value of 22.5 weeks of gestational age and 144 bpm of atrial rate at diagnosis could predict the failure of spontaneous recovery, with sensitivities of 87.5%, 75%, and specificities of 92.0%, 87.5%, respectively. CONCLUSIONS: The outcome of fetal non-immune second-degree AVB was favorable. Earlier gestational age at diagnosis and higher atrial rate were related to spontaneous reversion for isolated non-immune-mediated second-degree AVB. However, prenatal gene test should be performed for those with persistent AVB to exclude the heritable disorders including LQTS. These findings may provide important references for clinical management and prenatal counseling. This article is protected by copyright. All rights reserved.

Molecular Mechanisms of Fetal and Neonatal Lupus: A Narrative Review of an Autoimmune Disease Transferal across the Placenta.

This study, conducted by searching keywords such as "maternal lupus", "neonatal lupus", and "congenital heart block" in databases including PubMed and Scopus, provides a detailed narrative review on fetal and neonatal lupus. Autoantibodies like anti-Ro/SSA and anti-La/SSB may cross the placenta and cause complications in neonates, such as congenital heart block (CHB). Management options involve hydroxychloroquine, which is able to counteract some of the adverse events, although the drug needs to be used carefully because of its impact on the QTc interval. Advanced pacing strategies for neonates with CHB, especially in severe forms like hydrops, are also assessed. This review emphasizes the need for interdisciplinary care by rheumatologists, obstetricians, and pediatricians in order to achieve the best maternal and neonatal health in lupus pregnancies. This multidisciplinary approach seeks to improve the outcomes and management of the disease, decreasing the burden on mothers and their infants.

Ventricular Functional Analysis in Congenital Complete Heart Block Using Speckle Tracking: Left Ventricular Epicardial Compared to Right Ventricular Septal Pacing.

BACKGROUND: Chronic right ventricular (RV) apical pacing in patients with congenital complete atrioventricular block (CCAVB) is associated with left ventricle (LV) dyssynchrony and dysfunction. Hence, alternative pacing sites are advocated. The aim of this study was to compare LV function using STE in selected patients with LV epicardial pacing (LVEp) vs. RV transvenous pacing (RVSp). METHODS: This was a single-center, retrospective study in patients with CCAVB who underwent permanent pacemaker implant at age ≤ 18 years. Age- and gender-matched patients with a normal heart anatomy and function served as the control group. LV function was comprehensively assessed by conventional 2D Echocardiography and speckle-tracking echocardiography (STE). RESULTS: We included 24 patients in the pacemaker group [27.6% male, mean age of 17.1 at last follow-up, follow-up duration of 8.7 years, RVSp (n = 9; 62.5%)] compared to 48 matched healthy controls. Shortening fraction (SF) and ejection fraction (EF) were normal and similar between cases and controls. However, STE detected abnormal LV function in the pacemaker group compared to controls. The former demonstrated lower/abnormal, Peak Longitudinal Strain myocardial (PLS Myo) [- 12.0 ± 3.3 vs. - 18.1 ± 1.9, p < 0.001] and Peak Longitudinal Strain endocardial (PLS endo) [- 16.1 ± 4.1 vs. 1.7 ± 1.7, p < 0.001]. STE parameters of LV function were significantly more abnormal in LVEp vs. RVSp subgroup as demonstrated by lower values for PLS Myo (- 10.1 ± 3.2 vs. - 13.1 ± 2.9, p = 0.03) and PLS Endo (- 13.8 ± 4.4 vs. - 17.5 ± 3.3, p = 0.03). CONCLUSION: STE was more sensitive in detecting subtle differences in LV function relative to standard conventional 2D echocardiography (SF and EF) in selected patients with CCAVB and a permanent pacemaker. Furthermore, STE demonstrated that transvenous RV septal pacing was associated with better LV systolic function preservation than LV epicardial pacing for comparable post-implant intervals.

Favourable outcome of a severe bradyarrhythmia in a neonate: a case report.

We report the case of a term neonate with severe fetal bradycardia with an unusually benign clinical course with follow-up till infancy.

Cohort study of congenital complete heart block among preterm neonates: a single-center experience over a 15-year period.

Congenital complete heart block (CCHB) is a very rare condition, with high risk of mortality. Prematurity is associated with immaturity of the cardiovascular system. Morbidity related to CCHB and prematurity has never been described. We describe a tertiary perinatal center experience over a 15-year period on CCHB management and complications in preterm infants. This is a single-center observational cohort study. All neonates admitted to neonatal intensive care unit with a diagnosis of isolated CCHB between January 2006 and January 2021 were identified. All preterm neonates (< 37 weeks) were compared with a control cohort of term neonates (≥ 37 weeks). Antenatal data, complications of prematurity, medical, and surgical management of CCHB were recorded. Twenty-four neonates with isolated CCHB (16 preterm and 8 term) were born during the study period, including 5 very preterm (< 32 weeks) and 11 preterm (32 to 37 weeks). All very preterm were born via emergency caesarian section without antenatal steroid administration. They had multiple severe morbidities including chronic lung disease, necrotizing enterocolitis, grades 3-4 intraventricular hemorrhage, cystic periventricular leukomalacia, and longer periods of mechanical and non-invasive ventilatory support than preterm. Thirteen out of sixteen preterm infants had permanent pacemakers inserted, compared to 1/8 for term newborns. All babies born before 35-week gestation were either paced or died.Conclusion: Premature neonates with CCHB have high risk of mortality and morbidity especially if undiagnosed and born by unnecessary emergency caesarian section without antenatal steroids. Prematurity below 35 weeks may be associated with death or pacemaker insertion. This supports better antenatal screening to avoid induced prematurity. What is Known: • Congenital complete heart block is a very rare condition associated with high morbidity and mortality. • Antenatal risk factors for poor outcome include fetal hydrops, low ventricular rate (HR <55 beats per minute), and congenital heart defect. What is New: • Infants born <32 weeks with CCHB had no antenatal steroid administration, and sustained high burden of morbidity (chronic lung disease, intraventricular hemorrhage, and cystic periventricular leukomalacia). • Birth <35 weeks is strongly associated with requiring pacing prior to discharge or death.

Third Trimester Fetal Heart Rates in Antibody-Mediated Complete Heart Block Predict Need for Neonatal Pacemaker Placement.

Congenital complete heart block (CCHB) affects 1 in 20,000 newborns. This study evaluates fetal and neonatal risk factors predictive of neonatal pacemaker placement in antibody-mediated complete heart block. The Children's Hospital Los Angeles institutional fetal, pacemaker, and medical record databases were queried for confirmed SSA/SSB cases of CCHB between January 2004 and July 2019. Cases excluded were those with a diagnosis beyond the neonatal period, diagnosis of a channelopathy, or if maternal antibody status was unknown. We recorded the gestational age (GA), birth weight (BW), fetal heart rates (FHRs) of the last echocardiogram before delivery, specific neonatal ECG and echocardiogram findings, age at pacemaker placement, and mortality. Of 43 neonates identified with CCHB, 27 had confirmed maternal antibody exposure. Variables associated with neonatal pacemaker implantation were FHRs < 50 bpm (p = 0.005), neonatal heart rates < 52 bpm (p = 0.015), and neonatal left ventricular fractional shortening (FS) percentages < 34% (p = 0.03). On multivariate analysis, FHR remained significant (p = 0.03) and demonstrated an increased risk of neonatal pacemaker placement by an odds ratio of 12.5 (95% CI 1.3-116, p = 0.05). The median GA at which the FHR was obtained was 34 weeks (IQR 26-35 weeks). Neonatal pacemaker placement was highly associated with a FHR < 50 bpm, neonatal HR < 52 bpm, and neonatal FS < 34%. FHRs at 34 weeks GA (IQR 26-35 weeks) correlated well with postnatal heart rates and were predictive of neonatal pacemaker placement.

Histological finding of maternal antibody-associated congenital heart block accompanied by large atrial septal defect and severe cardiac dysfunction.

Cardiac dysfunction commonly occurs in congenital heart block associated with maternal anti-SSA antibodies, especially after pacemaker implantation. We report the case of a 4-year-old girl with antibody-associated congenital heart block and a large secundum atrial septal defect who presented with significant cardiac dysfunction 4 years after pacemaker implantation. Histological findings were useful for determining the course of treatment and perioperative risk of intracardiac repair.

Neonatal lupus erythematosus - prevention is better than cure.

Neonatal lupus erythematosus (NLE) is a congenital autoimmune condition in which the transplacental passage of immunoglobulin G (IgG) directed against auto-antigens causes clinical symptoms in the foetus or neonate. Anti-Ro/SS-A, anti-La/SS-B, and to a lesser extent, anti-U1RNP autoantibodies (aAbs) have the strongest association with NLE. However, ~ 50% of affected mothers are asymptomatic despite carrying those aAbs. The clinical picture of the disease is very diverse. Cardiac manifestations are the most severe, including congenital heart block (CHB), with a mortality rate of ~18%. Preventative therapy with hydroxychloroquine (HCQ) reduces the recurrence rate of CHB in subsequent pregnancies by ~50%.

Ventricular pacing and myocardial function in patient with congenital heart block.

INTRODUCTION: Pacing-induced cardiomyopathy (PICM) is a potential complication of chronic right ventricular (RV) pacing, but its characterization in adult patients is often complicated by pre-existing cardiomyopathy. This study investigated the incidence of PICM in patients with congenital heart block (cHB) who have conduction disease from birth without confounding pre-existing cardiac conditions. METHODS AND RESULTS: This retrospective cohort analysis included 42 patients with cHB and baseline left ventricular ejection fraction (LVEF) ≥50%. Kaplan-Meier analysis was used to assess freedom from cardiomyopathy (defined as LVEF <50%) between paced and nonpaced patients. Patients were 26 ± 3 years old at first presentation, 64% were women and baseline LVEF was 60.0 ± 0.2%. Median follow-up from birth was 35 (interquartile range [IQR]: 20-42) years with a median of 6.7 years (IQR: 3.6-9.2) at our institution. Thirty-two patients received pacing at mean age 21 ± 3 years. Patients receiving a pacemaker (PM) were significantly more likely to develop a cardiomyopathy (p = .021) and no patient developed a cardiomyopathy in the absence of a PM. Four patients who developed a new cardiomyopathy were upgraded to biventricular pacing, leading to stabilization or improvement of LVEF. CONCLUSION: In a relatively young and healthy cHB cohort, RV pacing is associated with a higher risk of developing a cardiomyopathy. These data confirm the deleterious effects of RV pacing on myocardial function in patients without pre-existing structural cardiac disease and has clinical implications to the management of patients with cHB.

Interferons and innate immune activation in autoimmune congenital heart block.

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.

Neonatal lupus erythematosus - practical guidelines.

BACKGROUND: Neonatal lupus erythematosus is an autoimmune disease acquired during fetal life as a result of transplacental passage of maternal anti-Sjögren's-syndrome-related antigen A (anti-SSA/Ro), anti-Sjögren's-syndrome-related antigen B (anti-SSB/La) or anti-U1 ribonucleoprotein (anti-U1-RNP) antinuclear autoantibodies. CONTENTS: Clinical manifestations include skin lesions, congenital heart block, hepatobiliary involvement and cytopenias. Most of the disorders disappear spontaneously after clearance of maternal antibodies. Cardiac symptoms, however, are not self-resolving and often pacemaker implantation is required. Diagnosis is based on clinical presentation and the presence of typical antibodies in the mother's or infant's serum. OUTLOOK: Neonatal lupus erythematosus may develop in children born to anti-SSA/Ro or anti-SSB/La women with various systemic connective tissue diseases. However, in half of the cases, the mother is asymptomatic, which may delay the diagnosis and have negative impact on the child's prognosis. Testing for antinuclear antibodies should be considered in every pregnant woman since early treatment with hydroxychloroquine or intravenous immunoglobulin (IVIG) has proven to be effective in preventing congenital heart block.

False Asystole Alarms Post-Temporary Pacemaker Placement Due to Pseudo-fusion.

An infant with congenital heart block and hemodynamically significant bradycardia underwent therapeutic temporary pacing wires placement. Post-operatively, frequent "asystole" alarms were observed on telemetry causing distress to both the family and the nursing staff. Investigation of these alarms showed that pacemaker malfunction led to monitor pseudo-malfunction. The alarms were alleviated with mindful setting of the pacemaker and telemetry monitor parameters. This case highlights the challenges of pacemaker placement and monitoring of very small infants in the intensive care setting. Awareness of these challenges would help in troubleshooting pacemaker and telemetry monitor issues.

Temporary pacemaker implantation through umbilical vein in a low birth weight neonate with congenital complete heart block.

Congenital heart block is a rare and lethal condition in paediatric population associated with maternal connective tissue disorders and rarely with structural cardiac disease like atrioventricular canal defects with or without left isomerism and congenitally corrected transposition of great arteries. Pacing in neonate if indicated is generally accomplished by epicardial pacing systems. However, in cases of significant bradycardia and haemodynamic instability, temporary pacemaker implantation via transvenous approach remains as a suitable option. Despite the advances in percutaneous catheter interventions, use of transvenous pacing in newborn is extremely challenging due to inadvertent risk of vessel injury, thrombus formation and mortality, and most of the time technical inability to place the lead within the right ventricular cavity. We report a case of congenital complete atrioventricular block in a premature male with birth weight of 1.51 kg who was managed with temporary pacemaker implantation through umbilical vein.

A multicentre study of 244 pregnancies in undifferentiated connective tissue disease: maternal/fetal outcomes and disease evolution.

OBJECTIVES: To investigate fetal/perinatal and maternal outcomes from a large multicentre cohort of women diagnosed with UCTD. METHODS: This multicentre retrospective cohort study describes the outcomes of 224 pregnancies in 133 consecutive women with a diagnosis of UCTD, positive for ANA and aged <45 years old at study inclusion. RESULTS: Of the 224 pregnancies analysed, 177 (79%) resulted in live births, 45 (20.1%) in miscarriages (defined as pregnancy loss before 12 weeks' gestation), 2 (0.9%) in stillbirths (pregnancy loss after 20 weeks' gestation) and 6 (2.7%) cases showed intrauterine growth restriction. Miscarriages and stillbirths were strongly associated with the presence of aPL and ENA antibodies (P < 0.05). Maternal pregnancy complications were as follows: 5 (2.2%) cases developed pre-eclampsia, 11 (4.9%) cases gestational hypertension and 12 (5.4%) cases gestational diabetes. Joint involvement represented the most frequent clinical manifestation of the cohort (57.9%), followed by RP (40.6%), photosensitivity (32.3%) and haematological manifestations (27.1%). The rate of disease evolution of our cohort from a diagnosis of UCTD to a diagnosis of definite CTD was 12% within a mean time of 5.3 ± 2.8 years. With a total follow-up after first pregnancy of 1417 patient-years, we observed the evolution to a defined CTD in one out of every 88 patient- years. CONCLUSION: In our multicentre cohort, women with UCTD had a live birth rate of 79%. Women with UCTD should be referred to specialist follow-up when planning a pregnancy. ENA profiling and aPL testing should be mandatory in this setting, and further therapeutic approaches and management should be planned accordingly.

Geoepidemiology and clinical characteristics of neonatal lupus erythematosus: a systematic literature review of individual patients' data

Background/aim: Neonatal lupus erythematosus (NLE) is an autoimmune syndrome caused by transplacental transmission of maternal autoantibodies, often with devastating consequences. The objective of this systematic literature review was to analyze the demographic data, geoepidemiology, clinical, and serological characteristics associated with NLE. Materials and methods: We performed a systematic literature search of the Pubmed database covering the period from 1976 to August 2015, using the MeSH terms "neonatal lupus" or "congenital heart block". To be included in the study, articles of any type (original articles, case series, and case reports) had to report on infants with NLE on an individualized (i.e. patient-by-patient) basis. Results: A total of198 studies were included in the review, reporting on a total of 755 NLE patients. The most frequently reported clinical manifestations of NLE were congenital heart block (CHB, 65.2%), cutaneous lupus (33.1%), and cytopenias (15.5%). We found differences in NLE characteristics based on study geographical origin, with CHB being much more frequent in patients of European or American descent (49.4% and 35%, respectively), while reports originating from Asia reported a higher prevalence of skin involvement (45.2%). Most CHB cases (72.9%) were diagnosed between the 18th and 26th week of gestation. Conclusions: Phenotypic differences of NLE depending on race and country may reflect true pathophysiologic differences or methodologic discrepancies. While maternal autoimmune disease is not a prerequisite for the development of NLE, the existence of a truly "immunonegative" CHB is questionable.

Comorbidity and long-term outcome in patients with congenital heart block and their siblings exposed to Ro/SSA autoantibodies in utero.

OBJECTIVE: Congenital heart block (CHB) may develop in fetuses of Ro/SSA autoantibody-positive women. Given the rarity of CHB, information on comorbidity and complications later in life is difficult to systematically collect for large groups of patients. We therefore used nation-wide healthcare registers to investigate comorbidity and outcomes in patients with CHB and their siblings. METHODS: Data from patients with CHB (n= 119) and their siblings (n= 128), all born to anti-Ro/SSA-positive mothers, and from matched healthy controls (n= 1,190) and their siblings (n= 1,071), were retrieved from the Swedish National Patient Register. Analyses were performed by Cox proportional hazard modelling. RESULTS: Individuals with CHB had a significantly increased risk of cardiovascular comorbidity, with cardiomyopathy and/or heart failure observed in 20 (16.8%) patients versus 3 (0.3%) controls, yielding a HR of 70.0 (95% CI 20.8 to 235.4), and with a HR for cerebral infarction of 39.9 (95% CI 4.5 to 357.3). Patients with CHB also had a higher risk of infections. Pacemaker treatment was associated with a decreased risk of cerebral infarction but increased risks of cardiomyopathy/heart failure and infection. The risk of systemic connective tissue disorder was also increased in patients with CHB (HR 11.8, 95% CI 4.0 to 11.8), and both patients with CHB and their siblings had an increased risk to develop any of 15 common autoimmune conditions (HR 5.7, 95% CI 2.83 to 11.69 and 3.6, 95% CI 1.7 to 8.0, respectively). CONCLUSIONS: The data indicate an increased risk of several cardiovascular, infectious and autoimmune diseases in patients with CHB, with the latter risk shared by their siblings.

Pregnancy outcomes in mixed connective tissue disease: a multicentre study.

OBJECTIVES: In this study we aimed to investigate foetal and maternal pregnancy outcomes from a large multicentre cohort of women diagnosed with MCTD and anti-U1RNP antibodies. METHODS: This multicentre retrospective cohort study describes the outcomes of 203 pregnancies in 94 consecutive women ever pregnant who fulfilled the established criteria for MCTD with confirmed U1RNP positivity. RESULTS: The foetal outcomes in 203 pregnancies were as follows: 146 (71.9%) live births, 38 (18.7%) miscarriages (first trimester pregnancy loss of <12 weeks gestation), 18 (8.9%) stillbirths (pregnancy loss after 20 weeks gestation) and 11 (5.4%) cases with intrauterine growth restriction. Maternal pregnancy outcomes were as follows: 8 (3.9%) developed pre-eclampsia, 2 (0.9%) developed eclampsia, 31 (15.3%) developed gestational hypertension and 3 (1.5%) developed gestational diabetes. Women with MCTD and aPL and pulmonary or muscular involvement had worse foetal outcomes compared with those without. Moreover, we report a case of complete congenital heart block (0.45%) and a case of cutaneous neonatal lupus, both born to a mother with positive isolated anti-U1RNP and negative anti-Ro/SSA antibodies. CONCLUSION: In our multicentre cohort, women with MCTD had a live birth rate of 72%. While the true frequency of heart block associated with anti-U1RNP remains to be determined, this study might raise the consideration of echocardiographic surveillance in this setting. Pregnancy counselling should be considered in women with MCTD.

Aetiologies and temporal trends of atrioventricular block in young patients: a 20-year nationwide study.

AIMS: To describe aetiologies and temporal trends in young patients with atrioventricular block (AVB). METHODS AND RESULTS: We identified all patients in Denmark, receiving their first pacemaker because of AVB before the age of 50 years between 1996 and 2015. Medical records were reviewed and clinical information and diagnostic work-up results were obtained to evaluate the aetiology. We used Poisson regression testing for temporal trends. One thousand and twenty-seven patients were identified, median age at time of implantation was 38 (interquartile range 25-45) years, 584 (56.9%) were male. The aetiologies were complications to cardiac surgery [n = 157 (15.3%)], congenital AVB [n = 93 (9.0%)], cardioinhibitory reflex [n = 52 (5.0%)], congenital heart disease [n = 43 (4.2%)], complication to radiofrequency ablation [n = 35 (3.4%)], cardiomyopathy [n = 31 (3.0%)], endocarditis [n = 18 (1.7%)], muscular dystrophy [n = 14 (1.4%)], ischaemic heart disease [n = 14 (1.4%)], sarcoidosis [n = 11 (1.1%)], borreliosis [n = 9 (0.9%)], hereditary [n = 6 (0.6%)], side-effect to antiarrhythmics [n = 6 (0.6%)], planned His-ablation [n = 5 (0.5%)], complication to alcohol septal ablation [n = 5 (0.5%)], and other known aetiologies [n = 11 (1.1%)]. The aetiology remained unknown in 517 (50.3%) cases. While the number of patients with unknown aetiology increased during the study period (P < 0.001), we observed no significant change in the number of patients with identified aetiology (P = 0.35). CONCLUSION: In a nationwide cohort, the aetiology of AVB was identified in only half the patients younger than 50 years referred for first-time pacemaker implantation. The number of patients with unknown aetiology increased during the study period. These findings indicate need for better insight into aetiologies of AVB and improved diagnostic work-up guidelines.

Benefits of fetal echocardiographic surveillance in pregnancies at risk of congenital heart block: single-center study of 212 anti-Ro52-positive pregnancies.

OBJECTIVES: Assuming that autoimmune congenital heart block (CHB) is a progressive disease amenable to therapeutic modulation, we introduced a surveillance program for at-risk pregnancies with the dual aim of investigating if fetal atrioventricular block (AVB) could be detected and treated before becoming complete and irreversible, and to establish the incidence of AVB I, II and III in a large prospective cohort. METHODS: This was a prospective study of 212 anti-Ro52 antibody-exposed pregnancies at risk of fetal AVB that were followed weekly between 18 and 24 weeks' gestation at our tertiary fetal cardiology center from 2000 to 2015. A 12-lead electrocardiogram (ECG) was recorded within 1 week after birth. Fetal Doppler atrioventricular (AV) intervals were converted to Z-scores using reference standard values derived from normal pregnancies. Each fetus was represented by the average value of the two recordings, obtained at two consecutive visits, which resulted in the longest AV interval. AV interval values were classified into normal AV conduction (Z-score ≤ 2.0) and three levels of delayed AV conduction: Z-score > 2.0 and ≤ 3.0, Z-score > 3.0 and ≤ 4.0, and Z-score > 4.0. RESULTS: AVB II or III developed in 6/204 (2.9%) pregnancies without a CHB history and 1/8 (12.5%) of those with a CHB history. AV intervals > 2 and ≤ 3, > 3 and ≤ 4, and > 4 were detected in 16.0%, 7.5% and 2.8% of cases, respectively, and were related to the PR interval on 185 available ECGs. Three of the five cases with AVB III and one of two cases with 2:1 AVB II developed within 1 week of AV interval Z-score of 1.0, 1.9, 2.8 and 1.9, respectively. Transplacental treatment with betamethasone was associated with restoration of 1:1 AV conduction in the two fetuses with AVB II, with a better long-term result (normal ECG vs AVB I or II) observed in the case in which treatment was started within 1 week after AVB developed. Betamethasone treatment did not reverse AVB III, although a temporary effect on AV conduction was observed in 1/5 cases. Notably, the three cases in which treatment was started within 1 week after AVB III development responded with a higher ventricular rate than the other two cases and did not require pacemaker implantation until a later age (2-5 years vs 1.5-2 months). CONCLUSION: Fetal AV interval is a poor predictor of CHB progression, but CHB surveillance still allows detection of fetuses with AVB II or III shortly after its development, allowing for timely treatment initiation and potentially better outcome. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.