RESUMEN
Inferior sinus venosus atrial septal defect (SVASD) is the rarest form of the atrial septal defect (ASD) and can sometimes go unnoticed. Although this defect can be associated with other congenital anomalies, its association with hypoplasia of the posterior mitral leaflet is extremely rare. In this case, we present a woman with a history of surgery for an ostium secundum ASD who exhibited persistent right heart chamber dilation. Echocardiography revealed hypoplasia of the posterior mitral leaflet, and cardiac magnetic resonance (CMR) imaging confirmed the presence of a previously undetected inferior sinus venosus ASD.
Asunto(s)
Defectos del Tabique Interatrial , Válvula Mitral , Humanos , Defectos del Tabique Interatrial/complicaciones , Defectos del Tabique Interatrial/diagnóstico , Defectos del Tabique Interatrial/diagnóstico por imagen , Femenino , Válvula Mitral/anomalías , Válvula Mitral/diagnóstico por imagen , Ecocardiografía/métodosRESUMEN
INTRODUÇÃO A mutação do fator V de Leiden é uma condição genética que acomete um ponto único no sítio de inativação do fator V impedindo a ligação com a proteína C ativada, resultando em um estado pró-trombótico. A fibrilação atrial (FA) é a arritmia mais comum do mundo com predomínio na população idosa, e está relacionada com elevado risco de eventos tromboembólicos. A oclusão do apêndice atrial esquerdo (OAA) é um procedimento minimamente invasivo, visando a tromboprofilaxia em pacientes com FA e contraindicação de anticoagulação oral (ACO). DESCRIÇÃO DO CASO Paciente M.S.F.R.S., octogenária com fragilidade severa, dependente para atividades básicas e instrumentais da vida diária, portadora da mutação heterozigótica do fator V de Leiden, dislipidêmica, ex-tagabista, obesidade sarcopênica e apresenta FA permanente em uso inicial de varfarina. Antecedentes de trombose venosa profunda em membro inferior direito, comunicação interatrial corrigida por atriosseptoplastia, quatro eventos prévios de acidente vascular encefálico (AVE) com sequela motora à direita, e osteoporose associado a múltiplas fraturas de vértebras com correção cirúrgica. Além disso, apresentava má adesão ao uso de varfarina com acompanhamento irregular do controle de INR, associado com episódios de sangramentos gastrointestinais. Por isso, optou-se pela realização da oclusão do apêndice atrial esquerdo para prevenção secundária de eventos tromboembólicos. A paciente fez uso de ácido acetilsalicílico (AAS) 100mg e clopidogrel 75mg durante 6 meses pós-procedimento, seguido da suspensão dessas medicações e introdução da rivaroxabana 15mg, devido ao risco elevado de eventos tromboembólicos propiciados pela trombofilia. Atualmente em uso de metoprolol 200mg/dia; digoxina 0,125mg/dia; omeprazol 20mg/dia; clonazepam 2mg/dia e rivaroxabana 15mg/dia. CONCLUSÃO Segundo ensaios clínicos randomizados, a OAA não mostrou-se inferior ao uso de ACO quanto a ocorrência de AVE e embolismo sistêmico, como também demonstrou superioridade quanto a menores taxas de mortalidade cardiovascular. O estudo PROTECT-AF recomenda o uso de ACO associado ao AAS por 45 dias, seguido da dupla antiagregação plaquetária durante 6 meses e após isso, uso indeterminado de AAS isolado. Porém a anticoagulação ideal pós-intervenção permanece um desafio. O futuro da OAA está relacionado com a experiência do operador, evolução da tecnologia dos dispositivos, consenso da terapia antitrombótica e manejo das principais complicações.
Asunto(s)
Humanos , Femenino , Anciano de 80 o más Años , Fibrilación Atrial , Factor V , Apéndice Atrial , Arritmias Cardíacas , Ensayos Clínicos Controlados Aleatorios como Asunto , Accidente Cerebrovascular , Defectos del Tabique InteratrialRESUMEN
This 10-minute video aims at improving skills for the structural assessment of the interatrial septum using 2-dimensional transthoracic echocardiography (TTE) to increase the ability to diagnose-or rule out-the different types of interatrial communications. Of the five types of lesions, this video focuses on ostium secundum atrial septal defect. This is the first video in our MicroLearning Video Series, designed to help a target audience of sonographers, general cardiologists, general practitioners who want to gain knowledge on fundamental cardiology, and technicians. View the video at https://vimeo.com/989145537/4898c3c590.
Asunto(s)
Tabique Interatrial , Defectos del Tabique Interatrial , Valor Predictivo de las Pruebas , Humanos , Defectos del Tabique Interatrial/diagnóstico por imagen , Defectos del Tabique Interatrial/fisiopatología , Tabique Interatrial/diagnóstico por imagen , EcocardiografíaRESUMEN
Pulmonary arterial hypertension (PAH) is a well-known complication of congenital heart disease (CHD). The lack of a satisfactory animal model for PAH associated with CHD (PAH-CHD) has limited progress in understanding the pathogenesis of PAH and the development of therapeutic agents. The development of a rat model for PAH associated with atrial septal defect (ASD) was achieved through atrial septal puncture and thermal ablation. Two and 4 weeks after modeling, hematoxylin and eosin staining showed that the vascular thickness, vascular thickness index, vascular area, and vascular area index in pulmonary arteries with an outer diameter of 50-300 µm in the PAH-ASD 2 and 4 weeks group were higher than those in the sham group (all P < 0.05). Alpha-smooth muscle actin (É-SMA) staining showed that the medial thickness, medial thickness index, medial area, and medial area index in pulmonary arteries with an outer diameter of 50-300 µm at 2 and 4 weeks after modeling were significantly higher than those in the sham group (all P < 0.05). Additionally, mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR) in the PAH-ASD 2 and 4 weeks groups were significantly higher than those in the sham group (both P < 0.05). Elastin van Gieson staining showed that the vascular obstruction score in the PAH-ASD 2 and 4 weeks group was significantly higher than that in the sham group (both P < 0.05). The PAH-ASD rats were successfully generated. These findings suggest that our model would be useful for further research into the pathogenesis, prevention, and treatment of PAH-ASD.
Asunto(s)
Modelos Animales de Enfermedad , Defectos del Tabique Interatrial , Hipertensión Arterial Pulmonar , Arteria Pulmonar , Animales , Defectos del Tabique Interatrial/complicaciones , Defectos del Tabique Interatrial/patología , Defectos del Tabique Interatrial/fisiopatología , Ratas , Arteria Pulmonar/patología , Arteria Pulmonar/fisiopatología , Masculino , Hipertensión Arterial Pulmonar/etiología , Hipertensión Arterial Pulmonar/patología , Hipertensión Arterial Pulmonar/fisiopatología , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/patología , Hipertensión Pulmonar/fisiopatología , Ratas Sprague-Dawley , Resistencia VascularRESUMEN
BACKGROUND: Cleft in the mitral valve leaflet is a primary cause of congenital mitral regurgitation, stemming from developmental anomalies in the mitral valve and frequently associated with other congenital heart defects. Concurrent presence of cleft in mitral valve leaflet with atrial septal defect and ventricular septal defect is relatively rare. Echocardiography, especially transesophageal echocardiography, is essential in diagnosing cleft mitral valve leaflet and related congenital heart defects, providing critical, detailed imagery for accurate assessment. This study presents a young female patient whose anterior mitral cleft, along with atrial septal defect and ventricular septal defect, was revealed through three-dimensional transesophageal echocardiography. CASE PRESENTATION: A 25-year-old Iranian female, experiencing progressive dyspnea and diminished physical capacity over 3 months, was referred to our hospital. Initial examination and transthoracic echocardiography indicated severe mitral regurgitation. Further evaluation with transesophageal echocardiography corroborated these findings and identified a cleft in the anterior mitral valve leaflet, coupled with mild left ventricular enlargement and significant left atrial enlargement. The complexity of the patient's condition was heightened by the diagnosis of cleft mitral valve leaflet in conjunction with atrial septal defect and ventricular septal defect, showing the complex nature of congenital defects. CONCLUSION: This case emphasizes the critical role of transthoracic echocardiography in diagnosing cleft of mitral valve leaflet and associated cardiac anomalies, showcasing its superiority over transthoracic echocardiography for detailed visualization of cardiac structures. The identification of multiple congenital defects highlights the necessity for a comprehensive diagnostic approach to manage and treat patients with complex congenital heart diseases effectively. Future research should aim to refine diagnostic methodologies to enhance patient outcomes for cleft of mitral valve leaflets and related congenital conditions.
Asunto(s)
Ecocardiografía Tridimensional , Ecocardiografía Transesofágica , Defectos del Tabique Interatrial , Defectos del Tabique Interventricular , Insuficiencia de la Válvula Mitral , Válvula Mitral , Humanos , Femenino , Ecocardiografía Transesofágica/métodos , Defectos del Tabique Interatrial/diagnóstico por imagen , Defectos del Tabique Interatrial/complicaciones , Defectos del Tabique Interventricular/diagnóstico por imagen , Defectos del Tabique Interventricular/complicaciones , Adulto , Ecocardiografía Tridimensional/métodos , Insuficiencia de la Válvula Mitral/diagnóstico por imagen , Válvula Mitral/diagnóstico por imagen , Válvula Mitral/anomalíasRESUMEN
BACKGROUND: Extensive research has recognized the significant roles of non-coding RNAs (ncRNAs) in various cellular pathophysiological processes and their association with diverse diseases, including atrial septal defect (ASD), one of the most prevalent congenital heart diseases. This systematic review aims to explore the intricate involvement and significance of ncRNAs in the pathogenesis and progression of ASD. METHODS: Four databases (PubMed, Embase, Scopus, and the Web of Science) were searched systematically up to June 19, 2023, with no year restriction. The risk of bias assessment was evaluated using the Newcastle-Ottawa scale. RESULTS: The present systematic review included thirteen studies with a collective study population of 874 individuals diagnosed with ASD, 21 parents of ASD patients, and 22 pregnant women carrying ASD fetuses. Our analysis revealed evidence linking five long ncRNAs (STX18-AS1, HOTAIR, AA709223, BX478947, and Moshe) and several microRNAs (hsa-miR-19a, hsa-miR-19b, hsa-miR-375, hsa-miR-29c, miR-29, miR-143/145, miR-17-92, miR-106b-25, and miR-503/424, miR-9, miR-30a, miR-196a2, miR-139-5p, hsa-let-7a, hsa-let-7b, and hsa-miR-486) to ASD progression, corresponding to previous studies. CONCLUSIONS: NcRNAs play a crucial role in unraveling the underlying mechanisms of ASD, contributing to both biomarker discovery and therapeutic advancements. This systematic review sheds light on the mechanisms of action of key ncRNAs involved in ASD progression, providing valuable insights for future research in this field.
Asunto(s)
Defectos del Tabique Interatrial , MicroARNs , Humanos , Defectos del Tabique Interatrial/genética , MicroARNs/genética , Femenino , ARN no Traducido/genética , ARN Largo no Codificante/genética , EmbarazoRESUMEN
In this case report, we illustrate the minimally invasive endoscopic repair of an atrial septal defect via a right minithoracotomy in a young patient with a dislocated Amplatzer Septal Occluder.
Asunto(s)
Defectos del Tabique Interatrial , Dispositivo Oclusor Septal , Humanos , Defectos del Tabique Interatrial/cirugía , Defectos del Tabique Interatrial/diagnóstico , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Toracotomía/métodos , Masculino , Femenino , Resultado del TratamientoRESUMEN
Atrial Septal Defect closure in childhood and early adulthood has a good prognosis, but in older individuals the risk-benefit ratio is not as straightforward. We report a 57-year-old man who was easily fatigued when exercising. The cardiac examination revealed a wide and fixed splitting of S2, a pulmonary ejection systolic murmur grade III/VI, and increased jugular venous pressure. The transesophageal echocardiography showed Atrial Septal Defect secundum with a diameter of 20 mm, L-to-R shunt, and 5 mm, a thin and floppy inferior rim. The patient underwent surgical Atrial Septal Defect closure. The deficient posteroinferior rim occurs only in 3.3% of patients with secundum Atrial Septal Defect. This condition will enhance the likelihood of occluder dislodgement in the transcatheter closure approach. We learn from this case that surgical Atrial Septal Defect closure may be an option for elderly patients if there is an inadequate, thin, and floppy inferior rim or no comorbidities.
Asunto(s)
Ecocardiografía Transesofágica , Defectos del Tabique Interatrial , Humanos , Defectos del Tabique Interatrial/cirugía , Defectos del Tabique Interatrial/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Cateterismo Cardíaco/métodos , Dispositivo Oclusor SeptalRESUMEN
Congenital heart disease (CHD) accounts for nearly one-third of all major congenital anomalies, with atrial septal defect (ASD) and ventricular septal defect (VSD) being the most common forms of simple CHD, which involve a large number of susceptibility genes. However, despite extensive research, the etiology of ASD and VSD remains unclear. Yunnan Province has advantages in exploring CHD pathogenesis due to its unique genetic background. Therefore, we aimed to evaluate the association between single nucleotide polymorphisms (SNPs) of genes and susceptibility to simple CHD in a specific population by means of a case-control study. A total of 337 healthy controls and 767 patients with simple CHD (501 ASD and 266 VSD) from China were recruited. Candidate SNPs were identified through whole-genome sequencing of pooled CHD patients and controls (pool-seq). Genotyping from 1,104 samples was performed, and stratified analysis was conducted to explore the association between positive SNPs and CHD subtypes. χ2 tests and logistic regression were used to analyze the relationship between each SNP and simple CHD. Of 11 SNPs identified, SOD2 rs62437333 (P = 0.005) and POU5F1 rs3130504 (P = 0.017) showed differences between the control and ASD cohorts. In the dominant inheritance model hypothesis, rs62437333 allele C carriers had increased ASD (odds ratio (OR) = 2.04, P = 0.005) and combined simple CHD risk (OR = 2.33, P = 0.012) compared to DD genotype, while rs3130504 allele C carriers had increased ASD risk (OR = 1.121, P = 0.045) compared to DD genotype.
Asunto(s)
Pueblo Asiatico , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Superóxido Dismutasa , Humanos , Masculino , Femenino , China/epidemiología , Estudios de Casos y Controles , Superóxido Dismutasa/genética , Pueblo Asiatico/genética , Cardiopatías Congénitas/genética , Niño , Adulto , Preescolar , Adolescente , Defectos del Tabique Interatrial/genética , Defectos del Tabique Interventricular/genética , Defectos del Tabique Interventricular/epidemiología , Genotipo , Pueblos del Este de AsiaRESUMEN
Iatrogenic inferior vena cava (IVC)-left atrium (LA) shunt is a rare complication in atrial septal defect (ASD) surgery, caused by mistaking the Eustachian valve for the lower margin of the ASD. In this report, we describe the case of a 45-year-old woman who experienced circulatory collapse at termination of cardiopulmonary bypass during surgical IVC-LA shunt repair. Transesophageal echocardiography helped identify stenosis between the IVC and the right atrium, caused by a residual original incorrectly placed ASD patch. Removal of most of the patch led to improvement in circulatory failure.
Asunto(s)
Ecocardiografía Transesofágica , Atrios Cardíacos , Defectos del Tabique Interatrial , Reoperación , Vena Cava Inferior , Humanos , Femenino , Defectos del Tabique Interatrial/cirugía , Defectos del Tabique Interatrial/diagnóstico por imagen , Persona de Mediana Edad , Vena Cava Inferior/cirugía , Vena Cava Inferior/diagnóstico por imagen , Atrios Cardíacos/cirugía , Atrios Cardíacos/diagnóstico por imagen , Choque/etiologíaRESUMEN
The evolution of percutaneous procedures that use transseptal puncture to treat left-sided structural heart disease has led to the emergence of iatrogenic atrial septal defects as a potential complication. These defects can result in hemodynamic decompensation and worsening clinical outcomes. Some iatrogenic atrial septal defects require immediate closure, others do not. This case report presents 2 patients who underwent transcatheter edge-to-edge mitral valve repair with transseptal puncture and required iatrogenic atrial septal defect closure (1 immediate and 1 delayed). The goal of this report is to highlight iatrogenic atrial septal defect assessment and the possible need for closure after transseptal puncture.
Asunto(s)
Cateterismo Cardíaco , Ecocardiografía Transesofágica , Defectos del Tabique Interatrial , Enfermedad Iatrogénica , Insuficiencia de la Válvula Mitral , Válvula Mitral , Humanos , Cateterismo Cardíaco/métodos , Cateterismo Cardíaco/efectos adversos , Cateterismo Cardíaco/instrumentación , Defectos del Tabique Interatrial/cirugía , Defectos del Tabique Interatrial/diagnóstico , Insuficiencia de la Válvula Mitral/cirugía , Insuficiencia de la Válvula Mitral/diagnóstico , Válvula Mitral/cirugía , Válvula Mitral/diagnóstico por imagen , Masculino , Anciano , Femenino , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Implantación de Prótesis de Válvulas Cardíacas/métodos , Implantación de Prótesis de Válvulas Cardíacas/instrumentación , Lesiones Cardíacas/etiología , Lesiones Cardíacas/diagnóstico , Lesiones Cardíacas/cirugía , Resultado del Tratamiento , Anciano de 80 o más Años , PuncionesAsunto(s)
Insuficiencia Cardíaca , Defectos del Tabique Interatrial , Corazón Auxiliar , Dispositivo Oclusor Septal , Humanos , Defectos del Tabique Interatrial/cirugía , Defectos del Tabique Interatrial/diagnóstico por imagen , Insuficiencia Cardíaca/cirugía , Cateterismo Cardíaco/métodos , Cateterismo Cardíaco/instrumentación , Implantación de Prótesis/métodos , Implantación de Prótesis/instrumentaciónRESUMEN
Background: Cardiac electronic device implantation may be associated with complications. Case Summary: This is a report of inadvertent implantation of implantable cardioverter-defibrillator lead through an unrecognized sinus venosus atrial septal defect into the left ventricle that was not diagnosed early after implantation. Six months later chest x-ray showed an abnormal lead course that was confirmed with echocardiography as to be in the left ventricle. Surgical removal of the implantable cardioverter-defibrillator lead, repair of atrial septal defect, and correction of abnormal pulmonary venous connections were performed. Meanwhile, follow-up of the patient receiving a new dual chamber permanent pacemaker from the contralateral side and discussion of the aforementioned complication are addressed. Conclusion: Early diagnosis of device implantation complication is of paramount importance and prevents potential catastrophic complications.
This is a report of a middle-aged woman who received a heart battery (pacemaker) without proper initial indication and faced unnecessary consequences/complications. The wire was supposed to be implanted in the right side of the heart, but due to the congenital heart disease of the patient (that was not diagnosed), the wire was erroneously passed through the congenital defect to the left side of the heart. After the diagnosis of the problem, we referred her to a heart surgeon to correct the congenital heart defect and also pull the wire out. After open surgery, a new pacemaker (with two wires) was implanted in the patient without any additional complications.
Asunto(s)
Desfibriladores Implantables , Ventrículos Cardíacos , Humanos , Desfibriladores Implantables/efectos adversos , Ventrículos Cardíacos/diagnóstico por imagen , Ecocardiografía/métodos , Remoción de Dispositivos/métodos , Defectos del Tabique Interatrial/cirugía , Defectos del Tabique Interatrial/diagnóstico , Masculino , Femenino , Marcapaso Artificial/efectos adversos , Persona de Mediana EdadRESUMEN
We report a compressed air worker who had diffuse cutaneous decompression sickness with pain in his left shoulder and visual disturbance characteristic of migraine aura after only his third hyperbaric exposure. The maximum pressure was 253 kPa gauge with oxygen decompression using the Swanscombe Oxygen Decompression Table. He was found to have a very large right-to-left shunt across a 9 mm atrial septal defect. He had transcatheter closure of the defect but had some residual shunting with release of a Valsalva manoeuvre. Thirty-two other tunnel workers undertook the same pressure profile and activities in the same working conditions during the maintenance of a tunnel boring machine for a total of 233 similar exposures and were unaffected. As far as we are aware this is the first report of shunt-mediated decompression sickness in a hyperbaric tunnel worker in the United Kingdom and the second case reported worldwide. These cases suggest that shunt-mediated decompression sickness should be considered to be an occupational risk in modern compressed air working. A right-to-left shunt in a compressed air worker should be managed in accordance with established clinical guidance for divers.
Asunto(s)
Enfermedad de Descompresión , Defectos del Tabique Interatrial , Enfermedades Profesionales , Humanos , Enfermedad de Descompresión/etiología , Enfermedad de Descompresión/terapia , Masculino , Defectos del Tabique Interatrial/cirugía , Enfermedades Profesionales/etiología , Aire Comprimido/efectos adversos , Adulto , Oxigenoterapia Hiperbárica/métodos , Maniobra de Valsalva , Persona de Mediana Edad , Buceo/efectos adversosRESUMEN
BACKGROUND: Atrial septal defects (ASD) are the most common type of adult congenital heart disease (ACHD) associated with a high risk developing of pulmonary arterial hypertension (PAH). ASD closure is not recommended in patients with PAH and Pulmonary Vascular Resistance (PVR) ≥ 5 Wood Unit (WU). Noninvasive methods have been proposed to measure PVR; however, their accuracy remains low. Right Ventricle (RV) - Pulmonary Artery (PA) coupling is defined as the ability of the RV to adapt to high-resistance conditions. Tricuspid Annular Plane Systolic Excursion (TAPSE)/estimated pulmonary artery systolic pressure (ePASP) calculation using echocardiography is a noninvasive technique that has been proposed as a surrogate equation to evaluate RV-PA coupling. Currently, no research has demonstrated a relationship between RV-PA coupling and PVR in patients with ASD. METHODS: The study participants were consecutive eligible patients with ASD who underwent right heart catheterization (RHC) and echocardiography at Hasan Sadikin General Hospital, Bandung. Both the procedures were performed on the same day. RV-PA Coupling, defined as TAPSE/ePASP > 0.31, was assessed using echocardiography. The PVR was calculated during RHC using the indirect Fick method. RESULTS: There were 58 patients with ASD underwent RHC and echocardiography. Among them, 18 had RV/PA Coupling and 40 had RV/PA Uncoupling. The PVR values were significantly different between the two groups (p = 0.000). Correlation test between TAPSE/ePASP with PVR showed moderate negative correlation (r= -0.502, p = 0.001). TAPSE/ePASP ≤ 0.34 is the cutoff point to predict PVR > 5 WU with sensitivity of 91.7% and specificity 63.6%. CONCLUSION: This study showed a moderate negative correlation between TAPSE/ePASP and PVR. TAPSE/ePASP ≤ 0.34 could predict PVR > 5 WU with good sensitivity.
Asunto(s)
Cateterismo Cardíaco , Defectos del Tabique Interatrial , Arteria Pulmonar , Resistencia Vascular , Función Ventricular Derecha , Humanos , Defectos del Tabique Interatrial/fisiopatología , Defectos del Tabique Interatrial/diagnóstico por imagen , Defectos del Tabique Interatrial/complicaciones , Arteria Pulmonar/fisiopatología , Arteria Pulmonar/diagnóstico por imagen , Masculino , Femenino , Adulto , Persona de Mediana Edad , Presión Arterial , Hipertensión Arterial Pulmonar/fisiopatología , Hipertensión Arterial Pulmonar/diagnóstico , Hipertensión Arterial Pulmonar/diagnóstico por imagen , Valor Predictivo de las PruebasRESUMEN
Atrial septal defects (ASDs) occur in 1 of 1500 live births and constitute 6-10% of congenital heart defects. There is a female-to-male predominance of 2 to 1. According to their embryological origins, we can differentiate five different types of ASDs (see Fig. 23.1).
Asunto(s)
Defectos del Tabique Interatrial , Humanos , Defectos del Tabique Interatrial/terapia , Defectos del Tabique Interatrial/diagnóstico , Femenino , MasculinoRESUMEN
The relative simplicity of the clinical presentation and management of an atrial septal defect belies the complexity of the developmental pathogenesis. Here, we describe the anatomic development of the atrial septum and the venous return to the atrial chambers. Experimental models suggest how mutations and naturally occurring genetic variation could affect developmental steps to cause a defect within the oval fossa, the so-called secundum defect, or other interatrial communications, such as the sinus venosus defect or ostium primum defect.
Asunto(s)
Modelos Animales de Enfermedad , Defectos del Tabique Interatrial , Defectos del Tabique Interatrial/genética , Defectos del Tabique Interatrial/patología , Defectos del Tabique Interatrial/fisiopatología , Animales , Humanos , Mutación , Tabique Interatrial/patología , Transducción de Señal/genéticaRESUMEN
The development of a fully functional four-chambered heart is critically dependent on the correct formation of the structures that separate the atrial and ventricular chambers. Perturbation of this process typically results in defects that allow mixing of oxygenated and deoxygenated blood. Atrioventricular septal defects (AVSD) form a class of congenital heart malformations that are characterized by the presence of a primary atrial septal defect (pASD), a common atrioventricular valve (cAVV), and frequently also a ventricular septal defect (VSD). While AVSD were historically considered to result from failure of the endocardial atrioventricular cushions to properly develop and fuse, more recent studies have determined that inhibition of the development of other components of the atrioventricular mesenchymal complex can lead to AVSDs as well. The role of the dorsal mesenchymal protrusion (DMP) in AVSD pathogenesis has been well-documented in studies using animal models for AVSDs, and in addition, preliminary data suggest that the mesenchymal cap situated on the leading edge of the primary atrial septum may be involved in certain situations as well. In this chapter, we review what is currently known about the molecular mechanisms and animal models that are associated with the pathogenesis of AVSD.
Asunto(s)
Modelos Animales de Enfermedad , Defectos de los Tabiques Cardíacos , Animales , Defectos de los Tabiques Cardíacos/genética , Defectos de los Tabiques Cardíacos/fisiopatología , Defectos de los Tabiques Cardíacos/patología , Humanos , Transducción de Señal , Defectos del Tabique Interatrial/genética , Defectos del Tabique Interatrial/fisiopatología , Defectos del Tabique Interatrial/patología , Defectos del Tabique Interventricular/genética , Defectos del Tabique Interventricular/fisiopatología , Defectos del Tabique Interventricular/patologíaRESUMEN
Although atrial septal defects (ASD) can be subdivided based on their anatomical location, an essential aspect of human genetics and genetic counseling is distinguishing between isolated and familiar cases without extracardiac features and syndromic cases with the co-occurrence of extracardiac abnormalities, such as developmental delay. Isolated or familial cases tend to show genetic alterations in genes related to important cardiac transcription factors and genes encoding for sarcomeric proteins. By contrast, the spectrum of genes with genetic alterations observed in syndromic cases is diverse. Currently, it points to different pathways and gene networks relevant to the dysregulation of cardiomyogenesis and ASD pathogenesis. Therefore, this chapter reflects the current knowledge and highlights stable associations observed in human genetics studies. It gives an overview of the different types of genetic alterations in these subtypes, including common associations based on genome-wide association studies (GWAS), and it highlights the most frequently observed syndromes associated with ASD pathogenesis.