Permanent pacemaker implantation in complete congenital fetal atrioventricular (AV) block: a case report / Implantación de marcapasos permanente en bloqueo atrioventricular (AV) fetal congénito completo: reporte de caso

Abstract: One of the most common pathologies attributed to lupus neonatal refers to atrioventricular (AV) congenital block, which diagnosis can be made between 16 and 30 weeks of gestation due to persistent fetal bradycardia. The development of this disease is mostly related to maternal anti-Ro/SSA and anti-Smith autoantibodies. Currently, there are a number of alternatives for prenatal and postnatal treatment, with some controversy about their viability. The placement of a permanent pacemaker is presented as one of the most appropriate procedures currently, even with the risks awarded. This case report describes the placement of a permanent pacemaker to a two-month-old newborn with high maternal contents of anti-Ro/SSA and anti-Smith nuclear autoantibodies, with a favorable outcome.(AU)

Resumen: Una de las patologías más comunes atribuidas al lupus neonatal se refiere al bloqueo congénito atrioventricular (AV), diagnóstico que se puede realizar entre 16 y 30 semanas de gestación debido a bradicardia fetal persistente. El desarrollo de esta enfermedad se relaciona principalmente con los anticuerpos anti-Ro/SSA materno y anti-Smith. Actualmente, existen varias alternativas para el tratamiento prenatal y postnatal, con cierta controversia sobre su viabilidad. La colocación de un marcapasos permanente se presenta como uno de los procedimientos más adecuados actualmente, incluso con los riesgos adjudicados. Este relato de caso describe la colocación de un marcapasos permanente en un recién nacido de dos meses con alto contenido materno de autoanticuerpos anti-Ro/SSA y anti-Smith, con un resultado favorable.(AU)

A prospective observational cohort study of exposure to womb-like sounds to stabilize breathing and cardiovascular patterns in preterm neonates.

PURPOSE: We exposed premature infants to womb-like sounds to evaluate such exposure on breathing and cardiovascular patterns. We hypothesized that these sounds would reduce apnea and intermittent hypoxemia, enhance parasympathetic outflow, and improve cardiovascular patterns. METHODS: A total of 20 cases and 5 control infants at ≤32-36 weeks corrected gestational age participated in a prospective observational cohort study. Twenty-four hours of continuous ECG, respiratory and oxygen saturation data were collected in all infants. Womb-like sounds were played intermittently in 6-hour blocks. Salivary samples were collected at study beginning and end for cortisol. Apnea, intermittent hypoxemia, and bradycardia were evaluated, and heart rate variability was assessed by time domain and spectral techniques. RESULTS: Intermittent hypoxemia and bradycardia significantly declined after sound exposure. No significant differences in apnea, cortisol levels, or heart rate variability were evident among the study infants. CONCLUSIONS: Exposing premature infants to womb-like sounds has the potential to reduce hypoxemic and bradycardic events, and be used as an intervention to stabilize breathing and cardiac control in preterm infants.

Genetic Determinants of Hereditary Bradyarrhythmias: A Contemporary Review of a Diverse Group of Disorders.

Bradyarrhythmia is a common clinical presentation. Although the majority of cases are acquired, genetic screening of families with bradyarrhythmia has led to the discovery of a growing number of causative hereditary mutations. These mutations can interfere with any of the steps required for the occurrence of each cardiac cycle, including generation of an action potential in the sinoatrial node, successful exit of the action potential from the node, propagation of the action potential throughout the atria until the depolarization waves reach the atrioventricular node, and finally transmission of the action potential to the ventricles through the His-Purkinje system. As expected, channelopathies are the predominant culprit for hereditary bradyarrhythmias, because they play a crucial role in action potential generation and propagation. Interestingly, there are an increasing number of genes that encode for various regulatory or structural cellular components that have been linked to hereditary bradyarrhythmias. Furthermore, population-based genetic screening has revealed that age-related conduction defects may in fact be caused by genetic predispositions rather than the simple process of aging. With recent advances in genetic testing and the creation of animal models, not only have we discovered new culprit genes but it has also has become evident that there are still significant gaps in our knowledge of cardiac pathophysiology. In this review, we discuss the clinical presentations of known hereditary bradyarrhythmias and their associated conditions in addition to detailing our current molecular understanding of the mechanisms by which they are manifested.

The Phosphorylation State of GSK3ß Serine 9 Correlated to the Development of Valproic Acid-Associated Fetal Cardiac Teratogenicity, Fetal VPA Syndrome, Rescued by Folic Acid Administration.

The effects of the phosphorylation state of the glycogen synthase kinase 3ß involved in the cardiac myocytes (jelly-like cells) epithelial-mesenchymal transition-associated migration during heart-valve formation were examined through the valproic acid-induced cardiac teratogenicity of transgenic line A34 of Tg in a the Brachydanio rerio embryo model. Valproic acid is an effective anti-epileptic drug; however, when taken by pregnant women to treat epilepsy, it can produce cardiac developmental defects in fetuses. In this study, the role of glycogen synthase kinase 3ß in valproic acid-induced cardiac teratogenicity was investigated. Transgenic line A34 of zebrafish embryos was used at 3 days postfertilization. The results show that 78% (18/23) of the embryos treated with 0.10 mM valproic acid (group A) had incomplete chamber formation with normal looping and 22 % (5/23) had abnormal looping. Bradycardia was also found in comparison with control embryos (P < 0.001). For the embryos treated with 0.25 mM valproic acid (group B), 92% (22/24) demonstrated chamber formation failure and looping abnormality. Pericardial effusion, noncontracting ventricles, and enlarged, slowly beating atriums were observed at 6 days postfertilization. Valproic acid inhibited phosphorylation of serine 9 in glycogen synthase kinase 3ß in a dose-dependent manner. According to immunochemical staining results, valproic acid was shown to inhibit the mass migration and proliferation of cardiomyocytes in the development of the heart-valve region through inhibition of the GSK3ß Ser 9 phosphorylation. Folic acid rescued the GSK3ß Ser 9 phosphorylation and reversed the valproic acid-induced cardiac morphological, functional, and biochemical defects.

[Autonomic regulation and bradycardia during the neonatal period]. / Régulation autonomique et bradycardies néonatales.

The high frequency of bradycardia observed during the neonatal period requires cardiac monitoring but also understanding its intrinsic mechanisms, including responsiveness of the autonomic nervous system (ANS). Heart rate variability and spontaneous baroreflex analysis can help understand the autonomic dysregulation of cardiorespiratory control, possibly responsible for sudden infant death. In clinical neonatology practice, neonatal bradycardia does not warrant continuation of monitoring if it remains isolated, asymptomatic, and short (<10 s), followed by a rapid cardiac acceleration indicating an adapted sympathetic response. Further evaluation of ANS responsiveness is possible for newborns including analyzing the complexity of the heart rate and respiratory variability. This allows better targeting children with high risk after discharge. The real-time evaluation of autonomic regulation could become a valuable tool in clinical practice.

Voriconazole induced bradycardia.

Voriconazole is a triazole antifungal drug that is used to treat invasive fungal infections, especially aspergillus. Here, we report two children who had severe bradycardia associated with voriconazole at a dose of 12 mg/kg per day. Bradycardia resolved in 24 hours in both after decreasing the dose to 10 mg/kg per day. Heart rates were in normal limits on follow-up. Bradycardia may be a side effect of voriconazole treatment in children under immunosuppressive treatment. Heart rate should be monitored in patients receiving voriconazole and other triazole treatments.

Predisposing factors and effects of fetal bradycardia following cordocentesis at mid-pregnancy.

OBJECTIVES: To identify predisposing factors of fetal bradycardia following cordocentesis at mid-pregnancy and to compare the pregnancy outcomes to those without bradycardia. METHODS: All cordocenteses performed at 18-22 weeks of gestation were prospectively enrolled. The inclusion criteria consisted of: (i) singleton pregnancies; (ii) no fetal structural or chromosomal abnormalities; (iii) the procedures done by experienced operators. They were divided into two groups; procedures with fetal bradycardia (Group 1) and those without bradycardia (Group 2). Factors related to bradycardia were identified and pregnancy outcomes between the two groups were also compared. RESULTS: Of 6147 cordocenteses recruited, 2829 met the inclusion criteria. Of these,152 had fetal bradycardia whereas the remaining 2677 did not. The procedures involving placenta penetration, and umbilical cord bleeding were significantly related to a higher rate of fetal bradycardia. On the other hand, cordocenteses with fetal bradycardia had a significantly higher rate of fetal loss (11.8 vs. 1.9%, respectively, p = 0.001) as well as a higher rate of low birth weight and preterm birth. CONCLUSIONS: Cordocentesis with placenta penetration and umbilical cord bleeding carries a higher risk for fetal bradycardia and fetal bradycardia was an independent factor for a higher rate of fetal loss, preterm birth and low birth weight.

Bloqueo cardiaco fetal debido a lupus materno / Fetal heart block due to maternal lupus erythematosus

El lupus eritematoso neonatal se caracteriza por la aparición de lesiones cutáneas y bloqueo cardiaco congénito. Presentamos un caso de bloqueo aurículo-ventricular fetal en una primigesta de 23 años, observado en la ecografía de la semana 20. Diagnosticamos el lupus materno por la existencia de anticuerpos anti-Ro y anti-La en sangre materna. Optamos por una conducta expectante de vigilancia sin tratamiento prenatal. Nacido en un hospital de referencia, al neonato se le implantó un marcapasos, siendo la evolución satisfactoria. La madre no ha presentado brote puerperal (AU)

Neonatal lupus erythematosus is characterized by the development of cutaneous injuries and congenital heart block. We describe a case of fetal atrioventricular block in a 23-year-old primigravida, detected in the ultrasound scan at 20 weeks. Maternal lupus was diagnosed on the basis of anti-Ro and anti-La antibodies in the mother's blood. Expectant management was carried out with close monitoring without prenatal treatment. The neonate was born in the referral hospital. A pacemaker was implanted with satisfactory outcome. The mother showed no puerperal outbreak (AU)

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.

[Successful outcome of a pregnancy with an extremely low fetal heart rate (34 bpm) due to isolated complete heart block--case report]. / Pomyslne zakonczenie ciazy u plodu ze skrajnie wolna czynnoscia komór (34/min.) w przebiegu izolowanego calkowitego bloku przedsionkowo-komorowego--opis przypadku.

Isolated complete congenital heart block (CHB) in the majority of cases is associated with the presence of autoantibodies to SSA (Ro) and SSB (La) antigens in the maternal serum. The prognosis is less favorable in fetuses with a ventricular rate < 55bpm. We have reported a case of a fetus with an isolated non-autoimmune CHB with an extremely low ventricular rate (34bpm) in which the outcome was favorable. In the neonate the non-compaction of the myocardium was diagnosed.

Congenital heart block not associated with anti-Ro/La antibodies: comparison with anti-Ro/La-positive cases.

OBJECTIVE: To study anti-Ro/La-negative congenital heart block (CHB). METHODS: Forty-five fetuses with CHB were evaluated by analysis of anti-Ro/La antibodies using sensitive laboratory methods. RESULTS: There were 9 cases of anti-Ro/La-negative CHB; 3 died (33.3%). Only 3 (33.3%) were complete in utero and 5 (55.5%) were unstable. No specific etiology was diagnosed. Six infants (66.6%) were given pacemakers. There were 36 cases of anti-Ro/La-positive CHB. All except 2 infants (94.4%) had complete atrioventricular block in utero. Ten died (27.8%), one (2.7%) developed severe dilated cardiomyopathy, and 26 (72.2%) were given pacemakers. CONCLUSION: Nine of the 45 consecutive CHB cases (20%) were anti-Ro/La-negative with no known cause. They were less stable and complete than the anti-Ro/La positive cases.

Extremely low ventricular rate in a fetus with an isolated non-autoimmune complete congenital heart block. Case report.

Congenital complete heart block (CCHB) is an uncommon disorder with an incidence of about 1/20,000 in liveborn infants. It can occur in the setting of structurally normal heart or with structural disease; it is associated with high mortality and morbidity and requires a high index of suspicion for early diagnosis and therapy. Isolated CCHB in a fetus is usually associated with the presence of autoantibodies to SSA (Ro) and SSB (La) antigens in the maternal circulation. Such antibodies cross into the fetal circulation and cause inflammation of the conduction tissues; the causal mechanism is not known. Although the prognosis for the majority of fetuses is good, it is less favourable in fetuses with a ventricular rate <55 bpm in early pregnancy or with a decrease in the ventricular rate by >5 bpm during pregnancy. It is not known if the same prognostic criteria apply for fetuses with isolated non-autoimmune CCHB. This article reports authors' experience in managing a pregnancy with an extremely low fetal heart rate (47 bpm) in a single fetus with an isolated non-autoimmune CCHB in which the outcome was favorable.

A new syndrome with noncompaction cardiomyopathy, bradycardia, pulmonary stenosis, atrial septal defect and heterotaxy with suggestive linkage to chromosome 6p.

We report a three-generation family with nine patients affected by a combination of cardiac abnormalities and left isomerism which, to our knowledge, has not been described before. The cardiac anomalies include non-compaction of the ventricular myocardium, bradycardia, pulmonary valve stenosis, and secundum atrial septal defect. The laterality sequence anomalies include left bronchial isomerism, azygous continuation of the inferior vena cava, polysplenia and intestinal malrotation, all compatible with left isomerism. This new syndrome is inherited in an autosomal dominant pattern. A genome-wide linkage analysis suggested linkage to chromosome 6p24.3-21.2 with a maximum LOD score of 2.7 at marker D6S276. The linkage interval is located between markers D6S470 (telomeric side) and D6S1610 (centromeric side), and overlaps with the linkage interval in another family with heterotaxy reported previously. Taken together, the genomic region could be reduced to 9.4 cM (12 Mb) containing several functional candidate genes for this complex heterotaxy phenotype.

Transient heart block in a neonate associated with previously undiagnosed maternal anti-Ro/SSA and anti-La/SSB antibodies.

This report presents the case of an infant who was born with transient complete heart block. The cardiac rhythm converted to normal sinus rhythm within 12 hours of life. Following the diagnosis in this infant of congenital heart block, both the mother and the infant were tested for autoantibodies. Both were found to be strongly positive for anti-Ro/SSA antibodies. The infant was also weakly positive for the anti-La/SSB antibodies and her mother moderately positive for the same. Congenital heart block associated with these maternal antibodies is well documented in the literature; however, this is the only reported case that documents a transient nature of the complete heart block.

Long-term follow-up after pacemaker implantation in neonates and infants.

BACKGROUND: Pacemaker (PM) system implantation in neonates and infants is often complicated by hemodynamic instability, small vessel size, and abnormal cardiovascular anatomy. Thus, an open surgical approach for epicardial lead insertion is often required. We assessed the long-term outcomes after epicardial PM implantation in this age group. METHODS: Between 1992 and 2004, 22 consecutive patients underwent PM implantation within the first year of life. Bipolar steroid-eluting epicardial leads (Medtronic CapSure Epi 10366 and 4968) were inserted through median sternotomy, the sybxyphoid approach, or thoracotomy, and connected to various pulse generators. RESULTS: Pacemakers were implanted at a median age of 35 days (range, 1 to 300). Intracardiac anatomy was abnormal in 17 patients. Indications for PM therapy were heart block in 18 patients and sinus node dysfunction in 4 patients. During a median follow-up of 4.6 years (range, 4 days to 12.8 years), 7 devices were replaced owing to end of battery life (n = 6) or elective device repositioning (n = 1), at a median of 4.1 years (range, 1 to 7.8). One dislodged ventricular lead and 2 atrial lead sensing failures were observed. Sensing, pacing thresholds, and lead impedances showed good implant and stable follow-up values. CONCLUSIONS: Pacemaker-associated morbidity is low. Pacemaker system complications with epicardial leads are rare. Battery life is relatively shorter compared with children and adults because of the fast heart rate and complete PM dependency in most of these children. Even for neonates and infants, modern pacemaker therapy is feasible, safe, and effective.

Prenatal diagnosis of Bartter syndrome with biochemical examination of amniotic fluid: case report.

Antenatal Bartter syndrome typically presents with marked fetal polyuria that leads to polyhydramnios and premature delivery. In our case, polyhydramnios was detected at 26 weeks of gestation and amniotic fluid chloride level was high. Serial amnion-drains were performed. During indomethacine treatment, fetal bradycardia developed. The mother was given daily oral potassium to maintain normal serum level and prevent fetal arrhythmias. After birth, hypokalaemic alkalosis, low chloride, hyper-reninemia and hyperaldosteronemia were detected.

Interstitial deletion of a proximal 3p: a clinically recognisable syndrome.

Interstitial deletions of the proximal short arm of chromosome 3 occurring as constitutional aberrations are rare and a defined clinical phenotype is not established yet. We report on a 30-months-old girl with distinct facial features (square facies, plagiocephaly, broad forehead, broad nasal bridge, long philtrum and low set ears) and psychomotor/speech delay associated with an interstitial deletion of 3p12 chromosomal band, del(3)(p12p12). Clinical manifestations of our child were compared with those of other eight patients with the same deletion previously described to further delineate the proximal 3p deletion syndrome.

Dilated cardiomyopathy masquerading as long QT syndrome.

Atrioventricular block has been described in association with cases of long QT syndrome and mortality is increased in this subgroup. We describe an infant with congenital QT prolongation and atrioventricular block with normal cardiac function, leading to the initial diagnosis of long QT syndrome. She subsequently developed dilated cardiomyopathy requiring cardiac transplantation. We postulate that the presenting electrocardiograph abnormalities were early manifestations of the myocardial disease, preceding the development of myocardial dysfunction by several months. The need for heightened surveillance in cases of QT prolongation with atrioventricular block is amplified by the possibility of an evolving cardiomyopathy.