Congenital Atrioventricular Block Research Articles

Permanent epicardial pacing : a first line strategy in children

Abstract Background Permanent cardiac pacing in paediatric patients remains a challenge. According to the European Paediatric and Congenital Society (AEPC) recommendations, below 20 kg epicardial implantation is preferred, while above 20 kg endocardial implantation is given priority unless specific contraindication. In the literature, a weight at 15 kg is also found to be the minimal weight above which an endovascular implantation is considered. However, endovascular systems have been reported to be associated with a high risk of complications. Recent improvements in epicardial leads technology have significantly improved pacing thresholds (1-3), battery life and reduced the risk of re-intervention for epicardial lead dysfunction (4,5). Purpose The aim of the study is to evaluate the long-term results and efficacy of epicardial pacing in children and to investigate risk factors for epicardial lead dysfunction. Method We performed a retrospective, single-centre analysis of consecutive patients aged ˂18 years implanted with an epicardial PM between 2004 and 2020. The data collection included initial pacing parameters, at 1 month, 1 year, 2 years, and at last follow-up, as well as occurrence of early and late complications. Results A total of 101 patients (93 atrial and 131 ventricular epicardial) were analysed. The mean follow-up time was 6.2 years (range 2 days to 16.9 years). Median age at implantation was 4.2 years (IQ 0.3-8.8 years), median weight was 15.2 kg (IQ 5.2-28.0 kg). Congenital heart disease (CHD) was recorded in 59,4% of patients. Reasons for implantation were postoperative complete atrioventricular block (AVB) (40.6%), congenital AVB (37.6%), sinus dysfunction (7.9%), complete AVB with heart disease without surgery (7.9%), others (4%). Four patients had a system infection resulting in device extraction and reimplantation. The mortality rate was 15.8%, but no deaths was directly related to PM implantation or dysfunction. Detection values, impedances were stable over time, and the and average pacing thresholds remained ˂0,98±0,81 volt in the atrium and ˂ 1.57±0,89 volt in the ventricle. Lead survival was 96,7%, 90,7%, 82,3%, 74,5% at 1, 5, 8 and 10 years. The presence of CHD, weight ˂15kg, dual chamber implantation, implantation for postoperative BAV were not significant risk factors for lead dysfunction. In the group of patients implanted above 15kg the presence of a CHD significantly increased the risk of lead dysfunction (p=0.037) and all-cause reimplantation (p=0.010). In the group implanted above 15kg without any cardiopathy, the survival rate without lead dysfunction at 5 and 10 years was 100% and 90.9% respectively. Conclusion Epicardial pacing in children with steroid-eluting leads shows good long-term results with stable pacing parameters and good survival from lead dysfunction. For children implanted at a weight above 15 kg and without cardiopathy results with epicardial stimulation were excellent.Epicardial lead survival

Conduction System Pacing in Pediatrics and Congenital Heart Disease: A Case Report and Literature Review.

Conduction system pacing involving either His bundle pacing (HBP) or left bundle branch pacing (LBBP) is a modality that has been introduced as a safe and effective alternative to right ventricular (RV) pacing to help prevent pacemaker-associated cardiomyopathy. While HBP has been employed in the pediatric and congenital populations, several small studies have shown LBBP to be safe and effective in the pediatric population. We present a patient with congenital atrioventricular block and postoperative ventricular septal defect repair cardiomyopathy with subsequent left ventricular function improvement following a transition from an RV epicardial pacemaker system to an LBBP system. This case report serves as a foundation for a review of the current state of LBBP in pediatrics and congenital heart disease.

Abstract 15739: Fetal Echocardiographic Predictors of Perinatal Outcome in Congenital Atrioventricular Block

Background: Congenital atrioventricular block (AVB) is a rare disease with poor outcomes. Heart rate (HR) is a major prognostic factor. To date, no study has evaluated the contribution of cardiac output (CO), stroke volume (SV), and HR on outcomes. Methods: In this retrospective study we evaluated associations between fetal echocardiographic parameters and risk of a composite severe fetal adverse event (AE) in patients with congenital AVB. Results: Of the 58 cases of congenital AVB, 21 (36%) had the composite AE, defined as fetal hydrops (8/58, 14%), ≥ moderate ventricular dysfunction (LV 3/58, 5%; RV 6/58 11%), fetal demise (2/57, 4%), or premature birth at ≤ 35 weeks (17/55, 31%). Of the 55 live births, 3/55 (5%) patients died and 35/55 (64%) had a pacemaker placed in the neonatal period. In univariate analysis, lower HR z-score was associated with the composite AE (p = 0.002) and all individual components of the composite AE. Higher LV end diastolic volume was associated with the composite AE (p = 0.004), premature birth (p = 0.006) and neonatal pacemaker placement (p = 0.009). Higher LV SV was associated with the composite AE (p = 0.003) and with fetal hydrops (p = 0.031) and premature birth (p = 0.002). Higher combined CO (p = 0.038), presence of structural heart defect (p = 0.038) and heterotaxy (p = 0.01) were associated with fetal hydrops. In multivariate analysis, lower HR z-score (p = 0.044) and higher LV SV (p = 0.037) were associated with the composite AE. Longitudinal analysis showed the AE group had lower HR and higher SV throughout gestation and trends towards a greater decline in SV and CO (particularly RV CO) in the third trimester. Conclusions: Heart rate, not CCO, is the primary determinant of perinatal outcome in fetuses with high grade AVB. The compensatory increase in LV volume and SV in the patients with the lowest HR (and worst outcomes) maintains CCO in most fetuses with AVB and reflects the ability for fetal cardiac adaptation in the setting of prolonged severe bradycardia.

Reversible complete atrioventricular block in a neonate with maternal anti-Sjögren's syndrome-associated antibody: atypical phenotype of autoimmune congenital heart block.

The fetus of anti-Sjögren's syndrome-associated antibody-positive mother developed complete atrioventricular block at 39 weeks of gestation and required urgent ventricular pacing after birth. Unexpectedly, the patient recovered from the atrioventricular block within a few days. Fraction analysis of maternal anti-Sjögren's syndrome-associated antibody revealed positivity for isolated anti-Ro/SSA 60 kDa antibody, which is abnormal as most patients with complete atrioventricular block present with anti-Ro/SSA52 kDa positivity, which may indicate a potentially atypical late and reversible manifestation of an autoimmune congenital atrioventricular block in this patient.

Pacemaker Management and In-Hospital Outcomes in Neonatal Congenital Atrioventricular Block

BackgroundNeonatal congenital atrioventricular block (nCAVB) is rare, causes bradycardia, confers high mortality, and frequently requires pacing. In-hospital outcomes and pacemaker management in nCAVB are limited. ObjectivesThe purpose of this study was to analyze pacing and outcomes of nCAVB with and without congenital heart disease (CHD) using a multicenter database. MethodsA Pediatric Health Information System database review from January 1, 2004, to June 30, 2022. Patients <31 days of age with a nCAVB International Classification of Diseases-9th/10th Revision diagnosis code and no cardiac surgeries except pacemaker were included. Pacing and in-hospital mortality were analyzed using univariate and multivariable logistic statistics and competing risk and event-free survival models. ResultsOf 1,146 patients with nCAVB, 659 (57.5%) were girls and 506 (44.2%) were premature. Among the 326 (28.4%) with CHD, 134 (41.1%) underwent pacemaker insertion as initial intervention and 56 (17.2%) had temporary pacing wires. In-hospital mortality occurred in 118 (36.2%), with increased adjusted odds with temporary pacing wires placed at 0 to 1 or 2 to 7 days of age relative to no wires, and with decreased odds among pacemakers placed at 2 to 7 or 8+ days of age relative to no pacemaker. Of 820 (71.6%) without CHD, 334 (40.7%) underwent pacemaker insertion as the initial intervention and 81 (9.9%) had temporary pacing wires. In-hospital mortality occurred in 69 (8.4%) with increased adjusted odds in prematurity and decreased odds among pacemaker placement at 2 to 7 days of age relative to no pacemaker. ConclusionsOver 18.5 years, in-hospital mortality occurred in 36.2% of nCAVB patients with CHD and 8.4% with non-CHD. Associations with increased in-hospital mortality included CHD and prematurity and decreased with pacemaker placement. Prospective registries are needed to better characterize and standardize management of this rare but high-mortality disease.

The Success of a New Protocol for Early Diagnosis and Management of Congenital Atrioventricular Block: A Follow-up Study of 15 Fetuses from November 2007 to August 2022

Background: Congenital atrioventricular heart block (CAVB) is a relatively rare condition that can lead to long-term complications. Early diagnosis and management of CAVB is currently the ideal goal, particularly in high-risk pregnancies. Methods: The Fetal Heart Center at Kurdistan University serves as the primary referral center for pregnant mothers residing in the western region of Iran. Fifteen fetuses with CAVB were admitted between November 2007 and August 2022. They were referred for one or more of the following reasons: Fetal bradycardia or arrhythmia, abnormal ultrasound findings, and previous maternal or fetal risk factors. After obtaining a complete medical history, we conducted fetal echocardiography and ordered testing for maternal Lo/Ra autoantibodies. Our therapeutic approach was based on the type of atrioventricular block (AVB), serum titer of Lo/Ra antibodies, and specific risk factors associated with each type of AVB. Consequently, we used a combination of different medications, including dexamethasone, Hydroxychloroquine (HCQ), IVIG, beta-agonists, and inotropes. Results: We admitted 15 fetuses with CAVB, including seven females (47%) and eight males (53%). Most of our cases had positive tests for Lo and Ra autoantibodies, with varying degrees of AVB. A previous fetal death was common in our case series, accounting for 47% of cases. Moderate and high antibody titers were present in 80% of our cases. Mild bradycardia was a relatively common finding in our cases of first and second-degree atrioventricular block (AVB), occurring in 33% of patients. All of the above-mentioned findings, commonly referred to as major risk factors, were used for either early evaluation or therapeutic goals. No cases with first-degree AVB developed a higher grade of AVB after our therapeutic approach. One fetus with second-degree AVB developed CCHB, and another with mixed second/third-degree AVB reverted to second-degree AVB with the use of appropriate medications. Conclusions: Our therapeutic approach for the current cases yielded satisfactory results. Subsequently, we attempted to develop a rudimentary approach for early managing and treating fetuses with various types of CAVB. We are looking forward to future multicenter studies.

Complete Heart Block In Pregnancy And Manual Removal Of The Placenta After Vaginal Delivery

Management of the risk for cardiovascular and obstetrical complications is difficult in pregnant women with complete heart block. Complete congenital or acquired atrioventricular block can detected for the first time during pregnancy and delivery but only few cases have been reported in the literature. The first case was reported in 1914 by Nanta [1]. The acquired variety is very rare during pregnancy as this type is mostly seen after 50 years of age[2].During pregnancy acquired heart block may be due to myocarditis, collagen vascular diseases ,following infective endocarditis of aortic valve with root abscess or as a complication of cardiac surgery. In acquired heart block, heart rate is usually 40 or less per minute with wide QRS in ECG. They are usually symptomatic with temporary loss of consciouness in the form of presyncope or syncope[3]. The prognosis is generally worse, but ultimately depends on the underlying cause [4]. Complete atrioventricular block detected for the first time during pregnancy is usually congenital. With an incidence of 1 in 20,000 live born infants [5],congenital complete atrioventricular block is a rare disease. The aetiology is not completely understood. However, complete atrioventricular block may be isolated or combined with congenital heart diseases in up to 53% of affected individuals[6] It may be caused by cardiac malformations or damaged by maternal antibodies .Family history of complete atrioventricular block is one of the risk factor for congenital atrioventricular block [7-8].

Pacemaker Implantation in the Pediatric Population

Introduction: The development of pediatric arrhythmology, as a segment of pediatric cardiology, is conditioned by surgical correction of congenital heart diseases (CHD). The beginning of pediatric cardiosurgery is also the time of pacemaker implantation. The aim of this article is to present indications and results of pacemaker implantation in children in our conditions from April 1997 to April 2020 in the Clinical Center University of Sarajevo (CCUS). Patients and Methods: The article is descriptive and includes the period from April 1997 to April 2020. The data were extracted from the official medical documentation of patients hospitalized at the Paediatric Clinic, CCUS (protocol of operated CHD in children, register of continuous electrocardiogram [ECG] Holter monitoring, register of implanted pacemakers in children). Results: During this period, 46 pacemakers were implanted, 29 (63%) in male patients, of which 13 (28%) were due to congenital atrioventricular (AV) block, and 33 (71.7%) were mostly in children with a postoperative block. Postoperative block occurred in 28 children (84.8%). Given that 771 children with CHD were operated on in the same period, a complication of postoperative complete heart block arose in 3.6% of children, which had to be tackled immediately after surgery in seven patients (21.2%), and later in 26 patients (78.8%). In regard to the age of pacemaker implantation, the interval was between 7 days and 18 years. The local team implanted 37 (80.4%) pacemakers. Reimplantation was done in four patients (8.7%). In April 2020, we followed 42 patients, four of whom died (three after surgery and one child due to congenital heart block). With the help of continuous ECG Holter monitoring (5,839 registrations and analysis), we recognized second- or third-degree or high-degree AV block, which was the indication for pacemaker implantation in 8.2% of all performed ECG Holter monitorings, with a respective indication for control of implanted pacemaker in 3.2% of ECG Holters. Conclusion: Children with implanted pacemakers require close monitoring, frequent medical examinations, recognition of the right time for generator exchange, as well as reimplantation of the pacemaker. This can be achieved principally with the help of continuous ECG Holter monitoring, with an adequately developed pediatric cardiology/cardiosurgery.

Immediate single-chamber pacemaker implantation in a 2-hour-old infant with complete congenital atrioventricular block.

Immediate single-chamber pacemaker implantation in a 2-hour-old infant with complete congenital atrioventricular block.

Association of anti-Ro seropositivity with cardiac rhythm and conduction disturbances.

Anti-Ro/La autoantibodies are especially prevalent in autoimmune diseases but are also relatively frequent in healthy adults. Their arrhythmogenic effect on the immature cardiac conductive system is well established, with substantial evidence demonstrating an increased risk for congenital atrioventricular block in neonates of seropositive mothers. Despite their wide distribution and their arrhythmogenic potential effect, there are no large population studies conducted in seropositive adults. Thus, this is the first large population-based study to examine the association of anti-Ro/La seropositivity with cardiac rhythm and conduction disturbances. This cross-sectional designed study involved the electronic health records of the largest health maintenance organization in Israel. All subjects that were tested positive for anti-Ro/anti-La antibodies between the years 2002 and 2019 were included and were matched by age, gender, and place of residence, with controls. Rates of different cardiac rhythm and conduction disturbances were compared between groups. Sensitivity analyses were performed using propensity score matching. The study population included 17 231 anti-Ro/La seropositive subjects and 84 368 controls. Anti-Ro seropositive patients had higher rates of conduction disturbances (3.0 vs. 1.7%, P < 0.001) and rhythm disturbances (10.5 vs. 7.0%, P < 0.001). Patients who tested positive for anti-La alone did not demonstrate a significant association with arrhythmias. Multivariate logistic regression analysis, controlling for possible confounders, showed an increased risk for cardiac conduction disturbances [odds ratio (OR) 1.44, 95% confidence interval (CI) 1.25-1.66, P < 0.001], as well as for cardiac rhythm disturbances (OR 1.21, 95% CI 1.11-1.31, P < 0.001) among anti-Ro seropositive patients. However, the association with rhythm disturbances was more robust in certain subgroup analyses. Anti-Ro seropositivity is positively associated with adult cardiac conduction disturbances and, to a lesser extent, cardiac rhythm disturbances, regardless of the presence of concurrent autoimmune disease.

Fetal cardiofibroelastosis - a consequence of anti-Ro maternal transfer during pregnancy. Case report and review of the literature

With scarcely any reports published on the association of fetal endocardial fibroelastosis and Ro antibodies maternal transfer during pregnancy, this subject continues to raise concern among health care providers around the world, especially when neonatal lupus syndrome is taken into consideration as the main diagnosis. Fetuses with congenital atrioventricular block have a risk of intrauterine fetal demise and the concern comes from a variety of factors that show significant association between the presence of maternal antibodies to SS-A/Ro during pregnancy and their children serum level of these antibodies. Nevertheless, fetal endocardial fibroelastosis plays an important role in altering ventricular diastolic function and ventricular development in children and neonates. Methods. Medical literature was searched on PubMed and Medline using key words such as fetal endocardial fibroelastosis, anti-Ro antibodies in pregnancy and neonatal lupus syndrome and over 200 articles were taken into consideration, with 17 of them included in the final review. The clinical case included in this paper was referred to the Department of Maternal Fetal Medicine, Filantropia Clinical Hospital in Bucharest, during the second pregnancy after a first pregnancy that resulted in stillbirth with congenital heart block and fibroelastosis as a result of the maternal diagnosis of Sjogren’s syndrome with transplacental transfer of SS-A/Ro antibodies.

Conduction System Pacing in Pediatrics and Congenital Heart Disease, a Single Center Series of 24 Patients.

His-bundle pacing has demonstrated feasibility in numerous adult studies to reverse and prevent pacing-induced cardiomyopathy, however, is met with higher capture thresholds with deployment sheaths designed for adults with his-bundles in the typical location. To describe 24 pediatric and adult congenital patients post-physiologic pacing. Patients at the University of Minnesota Masonic Children's Hospital with congenital complete heart block or congenital heart disease and atrioventricular block presented for pacemaker placement between November 2019 and January 2021. Twenty-four patients had attempted his-bundle placement using either Medtronic's C315 or C308 sheaths and 3830 leads except for 3 patients who had Boston Scientific's His system with the Shape 3 sheath and 7842 leads. Twenty-four total patients underwent physiologic pacing (23 his-bundle, 13 female, 11 male) with median age of 14years (range 8-39years) with median weight of 51kg (range 21.2-81kg) with five right-sided implants performed. Twelve patients had congenital heart disease including atrioventricular canal defects, tetralogy of Fallot, and ventricular septal defect repairs (nine patients with ventricular septal defect repairs). Twelve patients had selective His-bundle pacing (six with congenital heart disease). Median threshold to capture was 0.5V at 0.4ms (range 0.4 to 1.1V at 0.4ms), impedance 570ohms (range 456-1140ohms), and sensing median of 9.7mV (range 1.5-13.8mV if present). The median follow-up time was 610days (range 240-760days). No complications occurred peri-procedurally or during follow-up. His-bundle pacing is feasible in pediatric and congenital heart disease patients.

Complete Congenital Atrioventricular Block Found by Ultrasound in Pregnancy

A 27-year-old woman at 7 months of pregnancy presented to the obstetric emergency department with a history of fetal bradycardia for 3 days. Her vital signs were within normal limits. Autoimmune disease screening revealed positive antinuclear antibodies and weakly positive anti–Sjögren's syndrome A antibodies. Color Doppler ultrasound of the fetal 4-chamber view showed low pulse rates, mitral regurgitation, and increased cardiothoracic ratio (Video E1 [available at http://www.annemergmed.com]), which might have certain clinical significance.

Complex cyanotic congenital heart disease presenting as congenital heart block in a Nigerian infant: case report and literature review

Background: The prevalence of cyanotic congenital heart diseases (CCHD) varies world wide. It accounts for a third of all congenital heart diseases. The common CCHD includes Tetralogy of Fallot(TOF), transposition of the great arteries (TGA), total anomalous pulmonary venous return (TAPVR), truncus arteriosus, and tricuspid atresia (TA). Less common variants include Ebstein’s anomaly, Hypoplastic left heart syndrome, pulmonary atresia, and single ventricle. Children of all ages can be are affected. The commonest presentation is cyanosis. Bradycardia and/or congenital heart block are rare presentations and mostly occur in the presence of an associated congenital atrioventricular block. Case report: We report a case of a 3-month-old female presenting with congenital heart block and bradycardia at 3 months of age and found to have complex cyanotic congenital heart disease on echocardiography. Conclusion: An infant presenting with bradycardia clinically should be screened for congenital heart defect as bradycardia may be an ominous sign of serious underlying cardiac defect.

Quand penser à un syndrome de Sjögren primitif ?

Primary Sjögren's syndrome (SS) or Sjögren disease is an autoimmune disorder with a high female ratio (9:1) with a peak of frequency around 50-year-old, but there are also cases with early onset before the age of 20. Forms with the classic triad of dryness, fatigue and pain are a common mode of entry into the disease and account for about 30% of patients with primary SS. Systemic involvement with one or more visceral manifestations is seen in about 70% of cases. Late Raynaud's phenomenon, bronchiolar involvement, interstitial lung disease, synovitis, neuropathies (particularly sensory neuropathies), tubulointerstitial nephritis, and parotid enlargement are all possible entry points to the disease since the dryness may be in the background. Finally, SS should also be considered in cases of cryoglobulinemic vasculitis, which often combines membranoproliferative glomerulonephritis, purpura, livedo and multiple mononeuropathy. More rarely, it is the discovery of a MALT lymphoma or the occurrence of a congenital atrioventricular heart block that will lead to the diagnosis of SS.

A Case Series of Concomitant Cardiac Electrical Disease among Takotsubo Syndrome Patients and Literature Review.

The pathophysiology of Takotsubo Syndrome (TTS) is not completely understood and the trigger of sudden cardiac death (SCD) in TTS is not clear either. We therefore sought to find an association between TTS and primary electrical diseases. A total of 148 TTS patients were analyzed between 2003 and 2017 in a bi-centric manner. Additionally, a literature review was performed. The patients were included in an ongoing retrospective cohort database. The coexistence of TTS and primary electrical diseases was confirmed in five cases as the following: catecholaminergic polymorphic ventricular tachycardia (CPVT, 18-year-old female) (n = 1), LQTS 1 (72-year-old female and 65-year-old female) (n = 2), LQTS 2 (17-year-old female) (n = 1), and LQTS in the absence of mutations (22-year-old female). Four patients suffered from malignant tachyarrhythmia and recurrent syncope after TTS. Except for the CPVT patient and one LQTS 1 patient, all other cases underwent subcutaneous ICD implantation. An event recorder of the CPVT patient after starting beta-blocker did not detect arrhythmias. The diagnosis of primary electrical disease was in 80% of cases unmasked on a TTS event. This diagnosis triggered a family clinical and genetic screening confirming the diagnosis of primary electrical disease. A subsequent literature review identified five cases as the following: a congenital atrioventricular block (n = 1), a Jervell and Lange-Nielsen Syndrome (n = 1), and a family LQTS in the absence of a mutation (n = 2), LQTS 2 (n = 1). A primary electrical disease should be suspected in young and old TTS patients with a family history of sudden cardiac death. In suspected cases, e.g., ongoing QT interval prolongation, despite recovery of left ventricular ejection fraction a family screening is recommended.

A Male Infant with Cholestatic Jaundice, Hemolytic Anemia, and Thrombocytopenia.

A Male Infant with Cholestatic Jaundice, Hemolytic Anemia, and Thrombocytopenia.

Cardiac resynchronisation therapy in a pace-dependent infant with tetralogy of Fallot.

We present the case of a 5-month-old infant with tetralogy of Fallot and congenital atrio-ventricular block that developed severe left ventricular dysfunction during apical left ventricular pacing, in which cardiac resynchronisation therapy was used as an emergency procedure due to persistent low cardiac output syndrome.

Minimally invasive permanent pacemaker implantation immediately after birth: from delivery room to heart surgery.

Congenital atrioventricular block is diagnosed in uterine life, at birth, or early in life. Atrioventricular blocks can be life threatening immediately at birth so urgent pacemaker implantation techniques are requested. Reasons can be cardiac or non-cardiac, but regardless of the reason, operations are challenging. We aimed to present technical procedure and operative results of pacemaker implantation in neonates. Between June 2014 and February 2021, 10 neonates who had congenital atrioventricular block underwent surgical operation to implant permanent epicardial pacemaker by using minimally invasive technique. Six of the patients were female and four of them were male. Mean age was 4.3 days (0-11), while three of them were operated on the day of birth. Mean weight was 2533 g (1200-3300). Operations were achieved through subxiphoidal minimally skin incision. Epicardial 25 mm length dual leads were implanted on right ventricular surface and generators were fixed on the right (seven patients) or left (three patients) diaphragmatic surface by incising pleura. There were no complication, morbidity, and mortality related to surgery. Few studies have characterised the surgical outcomes following epicardial permanent pacemaker implantation in neonates. The surgical approach is attractive and compelling among professionals so we aimed to present the techniques and results in patients who required permanent pacemaker implantation in the first month of life.

How Cardiac Embryology Translates into Clinical Arrhythmias.

The electrophysiological signatures of the myocardium in cardiac structures, such as the atrioventricular node, pulmonary veins or the right ventricular outflow tract, are established during development by the spatial and temporal expression of transcription factors that guide expression of specific ion channels. Genome-wide association studies have shown that small variations in genetic regions are key to the expression of these transcription factors and thereby modulate the electrical function of the heart. Moreover, mutations in these factors are found in arrhythmogenic pathologies such as congenital atrioventricular block, as well as in specific forms of atrial fibrillation and ventricular tachycardia. In this review, we discuss the developmental origin of distinct electrophysiological structures in the heart and their involvement in cardiac arrhythmias.