RESUMO
We sought to examine current practices and changes in practice regarding initial counseling for families of patients with hypoplastic left heart syndrome (HLHS) given the evolution of options and outcomes over time. Counseling (Norwood with Blalock-Taussig-Thomas shunt (NW-BTT), NW with right ventricle to pulmonary artery conduit (NW-RVPA), hybrid palliation, heart transplantation, or non-intervention/hospice (NI)) for patients with HLHS were queried via questionnaire of pediatric care professionals in 2021 and compared to identical questionnaire from 2011. Of 322 respondents in 2021 (39% female), 299 respondents were cardiologists (92.9%), 17cardiothoracic surgeons (5.3%), and 6 were nurse practitioners (1.9%). Respondents were largely from North America (96.9%). In 2021, NW-RVPA procedure was the preferred palliation for standard risk HLHS patient (61%) and was preferred across all US regions (p < 0.001). NI was offered as an option by 71.4% of respondents for standard risk patients and was the predominant strategy for patients with end-organ dysfunction, chromosomal abnormality, and prematurity (52%, 44%, and 45%, respectively). The hybrid procedure was preferred for low birth-weight infants (51%). In comparison to the identical 2011 questionnaire (n = 200), the NW-RVPA was endorsed more in 2021 (61% vs 52%, p = 0.04). For low birth-weight infants, hybrid procedure was more recommended than in 2011 (51% vs 21%, p < 0.001). The NW-RVPA operation is the most recommended strategy throughout the US for infants with HLHS. The hybrid procedure for low birth-weight infants is increasingly recommended. NI continues to be offered even in standard risk patients with HLHS.
Assuntos
Procedimento de Blalock-Taussig , Transplante de Coração , Síndrome do Coração Esquerdo Hipoplásico , Procedimentos de Norwood , Lactente , Criança , Humanos , Feminino , Masculino , Síndrome do Coração Esquerdo Hipoplásico/cirurgia , Procedimento de Blalock-Taussig/métodos , Artéria Pulmonar/cirurgia , Ventrículos do Coração , Aconselhamento , Resultado do Tratamento , Procedimentos de Norwood/métodos , Estudos RetrospectivosRESUMO
Substantial progress has been made in the standardization of nomenclature for paediatric and congenital cardiac care. In 1936, Maude Abbott published her Atlas of Congenital Cardiac Disease, which was the first formal attempt to classify congenital heart disease. The International Paediatric and Congenital Cardiac Code (IPCCC) is now utilized worldwide and has most recently become the paediatric and congenital cardiac component of the Eleventh Revision of the International Classification of Diseases (ICD-11). The most recent publication of the IPCCC was in 2017. This manuscript provides an updated 2021 version of the IPCCC.The International Society for Nomenclature of Paediatric and Congenital Heart Disease (ISNPCHD), in collaboration with the World Health Organization (WHO), developed the paediatric and congenital cardiac nomenclature that is now within the eleventh version of the International Classification of Diseases (ICD-11). This unification of IPCCC and ICD-11 is the IPCCC ICD-11 Nomenclature and is the first time that the clinical nomenclature for paediatric and congenital cardiac care and the administrative nomenclature for paediatric and congenital cardiac care are harmonized. The resultant congenital cardiac component of ICD-11 was increased from 29 congenital cardiac codes in ICD-9 and 73 congenital cardiac codes in ICD-10 to 318 codes submitted by ISNPCHD through 2018 for incorporation into ICD-11. After these 318 terms were incorporated into ICD-11 in 2018, the WHO ICD-11 team added an additional 49 terms, some of which are acceptable legacy terms from ICD-10, while others provide greater granularity than the ISNPCHD thought was originally acceptable. Thus, the total number of paediatric and congenital cardiac terms in ICD-11 is 367. In this manuscript, we describe and review the terminology, hierarchy, and definitions of the IPCCC ICD-11 Nomenclature. This article, therefore, presents a global system of nomenclature for paediatric and congenital cardiac care that unifies clinical and administrative nomenclature.The members of ISNPCHD realize that the nomenclature published in this manuscript will continue to evolve. The version of the IPCCC that was published in 2017 has evolved and changed, and it is now replaced by this 2021 version. In the future, ISNPCHD will again publish updated versions of IPCCC, as IPCCC continues to evolve.
Assuntos
Cardiopatias Congênitas , Classificação Internacional de Doenças , Criança , Feminino , Humanos , Sistema de Registros , Sociedades Médicas , Organização Mundial da SaúdeRESUMO
Elastic fiber fragmentation (EFF) is a hallmark of aortic valve disease (AVD), and neovascularization has been identified as a late finding related to inflammation. We sought to characterize the relationship between early EFF and aberrant angiogenesis. To examine disease progression, regional anatomy and pathology of aortic valve tissue were assessed using histochemistry, immunohistochemistry, and electron microscopy from early-onset (<40 yo) and late-onset (≥40 yo) non-syndromic AVD specimens. To assess the effects of EFF on early AVD processes, valve tissue from Williams and Marfan syndrome patients was also analyzed. Bicuspid aortic valve was more common in early-onset AVD, and cardiovascular comorbidities were more common in late-onset AVD. Early-onset AVD specimens demonstrated angiogenesis without inflammation or atherosclerosis. A distinct pattern of elastic fiber components surrounded early-onset AVD neovessels, including increased emilin-1 and decreased fibulin-5. Different types of EFF were present in Williams syndrome (WS) and Marfan syndrome (MFS) aortic valves; WS but not MFS aortic valves demonstrated angiogenesis. Aberrant angiogenesis occurs in early-onset AVD in the absence of inflammation, implicating EFF. Elucidation of underlying mechanisms may inform the development of new pharmacologic treatments.
RESUMO
Substantial progress has been made in the standardization of nomenclature for paediatric and congenital cardiac care. In 1936, Maude Abbott published her Atlas of Congenital Cardiac Disease, which was the first formal attempt to classify congenital heart disease. The International Paediatric and Congenital Cardiac Code (IPCCC) is now utilized worldwide and has most recently become the paediatric and congenital cardiac component of the Eleventh Revision of the International Classification of Diseases (ICD-11). The most recent publication of the IPCCC was in 2017. This manuscript provides an updated 2021 version of the IPCCC.The International Society for Nomenclature of Paediatric and Congenital Heart Disease (ISNPCHD), in collaboration with the World Health Organization (WHO), developed the paediatric and congenital cardiac nomenclature that is now within the eleventh version of the International Classification of Diseases (ICD-11). This unification of IPCCC and ICD-11 is the IPCCC ICD-11 Nomenclature and is the first time that the clinical nomenclature for paediatric and congenital cardiac care and the administrative nomenclature for paediatric and congenital cardiac care are harmonized. The resultant congenital cardiac component of ICD-11 was increased from 29 congenital cardiac codes in ICD-9 and 73 congenital cardiac codes in ICD-10 to 318 codes submitted by ISNPCHD through 2018 for incorporation into ICD-11. After these 318 terms were incorporated into ICD-11 in 2018, the WHO ICD-11 team added an additional 49 terms, some of which are acceptable legacy terms from ICD-10, while others provide greater granularity than the ISNPCHD thought was originally acceptable. Thus, the total number of paediatric and congenital cardiac terms in ICD-11 is 367. In this manuscript, we describe and review the terminology, hierarchy, and definitions of the IPCCC ICD-11 Nomenclature. This article, therefore, presents a global system of nomenclature for paediatric and congenital cardiac care that unifies clinical and administrative nomenclature.The members of ISNPCHD realize that the nomenclature published in this manuscript will continue to evolve. The version of the IPCCC that was published in 2017 has evolved and changed, and it is now replaced by this 2021 version. In the future, ISNPCHD will again publish updated versions of IPCCC, as IPCCC continues to evolve.
Assuntos
Cardiopatias Congênitas , Classificação Internacional de Doenças , Criança , Feminino , Humanos , Sistema de Registros , Sociedades MédicasRESUMO
The definition and classification of ventricular septal defects have been fraught with controversy. The International Society for Nomenclature of Paediatric and Congenital Heart Disease is a group of international specialists in pediatric cardiology, cardiac surgery, cardiac morphology, and cardiac pathology that has met annually for the past 9 years in an effort to unify by consensus the divergent approaches to describe ventricular septal defects. These efforts have culminated in acceptance of the classification system by the World Health Organization into the 11th Iteration of the International Classification of Diseases. The scheme to categorize a ventricular septal defect uses both its location and the structures along its borders, thereby bridging the two most popular and disparate classification approaches and providing a common language for describing each phenotype. Although the first-order terms are based on the geographic categories of central perimembranous, inlet, trabecular muscular, and outlet defects, inlet and outlet defects are further characterized by descriptors that incorporate the borders of the defect, namely the perimembranous, muscular, and juxta-arterial types. The Society recognizes that it is equally valid to classify these defects by geography or borders, so the emphasis in this system is on the second-order terms that incorporate both geography and borders to describe each phenotype. The unified terminology should help the medical community describe with better precision all types of ventricular septal defects.
Assuntos
Cardiopatias Congênitas/classificação , Comunicação Interventricular/classificação , Melhoria de Qualidade , Terminologia como Assunto , Pré-Escolar , Consenso , Feminino , Cardiopatias Congênitas/cirurgia , Comunicação Interventricular/cirurgia , Humanos , Lactente , Recém-Nascido , Classificação Internacional de Doenças , Masculino , Pediatria , Sociedades MédicasRESUMO
An internationally approved and globally used classification scheme for the diagnosis of CHD has long been sought. The International Paediatric and Congenital Cardiac Code (IPCCC), which was produced and has been maintained by the International Society for Nomenclature of Paediatric and Congenital Heart Disease (the International Nomenclature Society), is used widely, but has spawned many "short list" versions that differ in content depending on the user. Thus, efforts to have a uniform identification of patients with CHD using a single up-to-date and coordinated nomenclature system continue to be thwarted, even if a common nomenclature has been used as a basis for composing various "short lists". In an attempt to solve this problem, the International Nomenclature Society has linked its efforts with those of the World Health Organization to obtain a globally accepted nomenclature tree for CHD within the 11th iteration of the International Classification of Diseases (ICD-11). The International Nomenclature Society has submitted a hierarchical nomenclature tree for CHD to the World Health Organization that is expected to serve increasingly as the "short list" for all communities interested in coding for congenital cardiology. This article reviews the history of the International Classification of Diseases and of the IPCCC, and outlines the process used in developing the ICD-11 congenital cardiac disease diagnostic list and the definitions for each term on the list. An overview of the content of the congenital heart anomaly section of the Foundation Component of ICD-11, published herein in its entirety, is also included. Future plans for the International Nomenclature Society include linking again with the World Health Organization to tackle procedural nomenclature as it relates to cardiac malformations. By doing so, the Society will continue its role in standardising nomenclature for CHD across the globe, thereby promoting research and better outcomes for fetuses, children, and adults with congenital heart anomalies.
Assuntos
Cardiopatias Congênitas/classificação , Classificação Internacional de Doenças/história , Pediatria , Sociedades Médicas/normas , Terminologia como Assunto , Cardiopatias Congênitas/diagnóstico , História do Século XIX , História do Século XX , História do Século XXI , Humanos , Organização Mundial da SaúdeRESUMO
Upon detection of foreign-body embolization to the central nervous system (CNS) following a specific invasive cardiovascular procedure in 1 autopsied child, we undertook a quality assurance analysis to determine whether other patients had had similar events. Autopsies of all infants and children with history of cardiac catheterization, heart surgery on cardiopulmonary bypass, and/or extracorporeal membrane oxygenation over a 5-year period at a single tertiary care institution were reviewed for light-microscopic evidence of foreign material. Of the 24 patients meeting clinical criteria (13 females, 11 males; ages 6 days to 20 years, median age 7.5 months), 8 (33%) had foreign embolic material to the CNS. The material was associated with a cellular inflammatory reaction in all cases, with a subset associated with infarcts. No embolic foreign material was detected in 14 age-matched patients without history of cardiovascular procedures. Particles acquired from ex vivo manipulation of a catheter type utilized in at least 1 of the affected patients demonstrated similar histologic characteristics. We conclude that, in addition to recognized risks of hypoxic-ischemic brain damage in congenital cardiopulmonary disease, potential brain insult exists in the form of instrumentation-related foreign emboli to the cerebral vasculature. Cardiac catheters are a potential source of foreign embolic material.
Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Sistema Nervoso Central , Embolia/etiologia , Corpos Estranhos , Adolescente , Autopsia , Criança , Feminino , Corpos Estranhos/complicações , Corpos Estranhos/etiologia , Corpos Estranhos/patologia , Cardiopatias/cirurgia , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE: Fetal cardiac interventions are performed via direct cardiac puncture and are associated with significant fetal morbidity. The feasibility of utilizing magnetic navigation to maneuver a guide wire and balloon across a fetal aortic valve without direct cardiac puncture is tested. METHODS: A fetal heart model was manufactured and placed in a catheterization laboratory equipped with magnetic navigation. Magnetically steerable guide wires along with commercially available coronary balloons were inserted into the model at a site mimicking a hepatic vein. RESULTS: Passage of the wire and balloon was achieved on every attempt. The model was suitable for testing although the structural characteristics of the model made wire passage from the right to the left atrium the most challenging aspect. Once the wire was positioned in the left ventricle, it was easily maneuvered 180 degrees towards the left ventricular outflow tract and then the descending aorta. Advancement of a coronary balloon over this wire was uncomplicated. CONCLUSION: In a fetal heart model, it is feasible to deliver a wire and balloon from abdominal venous access antegrade across the aortic valve. Progression to fetal lamb models is planned and may advance fetal cardiac interventions by reduction of fetal morbidity.
Assuntos
Valvuloplastia com Balão , Procedimentos Cirúrgicos Cardíacos/métodos , Coração Fetal/cirurgia , Fetoscopia/métodos , Cardiopatias Congênitas/cirurgia , Traumatismos Cardíacos/prevenção & controle , Modelos Anatômicos , Animais , Valvuloplastia com Balão/instrumentação , Valvuloplastia com Balão/métodos , Cateterismo/instrumentação , Cateterismo/métodos , Estudos de Viabilidade , Feminino , Fluoroscopia/instrumentação , Fluoroscopia/métodos , Humanos , Magnetismo , Punções , Cirurgia Assistida por Computador/instrumentação , Cirurgia Assistida por Computador/métodosRESUMO
OBJECTIVES: Aortic atresia (AA) in hypoplastic left heart syndrome (HLHS) has been associated with increased mortality in several prior studies. We reviewed our autopsy series to explore the relationship of coronary abnormalities to anatomic subsets of HLHS with AA. METHODS: We retrospectively reviewed all pathology specimens with AA/MS (mitral stenosis) and AA/MA (mitral atresia) in the Cardiac Registry of Children's Hospital Boston between 1955 and 2009 including autopsy reports, operative notes, and imaging studies. Formalin-fixed hearts were examined, and cases found to have macroscopic coronary artery abnormalities were sectioned at mid-left ventricular level in the transverse plane and at mid-right ventricular level in the longitudinal plane for histologic analysis of coronary arteries using tissue sections stained with hematoxylin and eosin. RESULTS: A total of 216 autopsy cases were identified with AA/MS (134) and AA/MA (82). Coronary anomalies were found in 49 cases, left ventricle-coronary fistula in 39, all in AA/MS, and 10 other coronary abnormalities, all in AA/MA. Histologic study confirmed fistulas only in the AA/MS group with no evidence of fistulas in the AA/MA group. CONCLUSIONS: The occurrence of left ventricle-coronary fistulas appears limited to the AA/MS group, and coronary fistula specimens were disproportionately more prevalent in postoperative specimens. Further clinical studies are required to validate this finding and to identify subgroups that carry a higher mortality risk.
Assuntos
Anormalidades Múltiplas , Valva Aórtica/anormalidades , Anomalias dos Vasos Coronários/mortalidade , Fístula/mortalidade , Síndrome do Coração Esquerdo Hipoplásico/mortalidade , Valva Aórtica/patologia , Autopsia , Boston , Distribuição de Qui-Quadrado , Anomalias dos Vasos Coronários/patologia , Fístula/patologia , Ventrículos do Coração/anormalidades , Ventrículos do Coração/patologia , Humanos , Síndrome do Coração Esquerdo Hipoplásico/patologia , Valva Mitral/anormalidades , Valva Mitral/patologia , Estenose da Valva Mitral/mortalidade , Estenose da Valva Mitral/patologia , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de RiscoRESUMO
OBJECTIVE: To determine the safety and efficacy of the chemotherapeutic agents vinblastine and methotrexate in the treatment of children with progressive multivessel intraluminal pulmonary vein stenosis (PVS). METHODS: Children received weekly vinblastine and methotrexate for a period of 1 year. Outcomes (for patients receiving ≥1 month of chemotherapy) were classified separately for patients with isolated PVS and PVS with congenital heart disease (CHD). Primary efficacy outcome was "response to treatment" categorized by echocardiographic criteria of response. Survival to 1 year was also evaluated. All adverse events were classified according to Cancer Therapy Evaluation Program, Common Terminology Criteria version 3.0. Events were further classified as related to chemotherapy, cardiac, or other causes. RESULTS: Among 29 patients enrolled, 28 received at least one dose of chemotherapy and were evaluable for toxicity, while 23 were evaluable for response (21 CHD, 2 isolated). Both patients in the isolated group had progressive disease and died. Overall, 33% (7/21) of patients with PVS and CHD had stable disease; 1-year survival of 38%; and four patients continue in remission (93, 96, 124, and 125 months after treatment initiation). While both cardiac-related (19%) and chemotherapy-related (53%) toxicities were common, most were asymptomatic laboratory changes. Grade 3 (13%) and grade 4 (4%) toxicities were reversible, and no treatment-related grade 5 toxicities were observed. CONCLUSION: We report on the first prospective trial of chemotherapy for infants and children targeting the presence of myofibroblastic cells within the lesions of PVS based on myofibroblastic proliferation associated with desmoid tumors of infancy. The toxicity profile resulted in numerous treatment delays and interruptions that, combined with limited information on the natural history of PVS in this patient population, hampered our ability to determine the true efficacy of this approach. These results will be important as a baseline for clinical trials in this patient population.
Assuntos
Metotrexato/uso terapêutico , Veias Pulmonares/efeitos dos fármacos , Pneumopatia Veno-Oclusiva/tratamento farmacológico , Vimblastina/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Pré-Escolar , Esquema de Medicação , Quimioterapia Combinada , Humanos , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Miofibroblastos/efeitos dos fármacos , Miofibroblastos/patologia , Estudos Prospectivos , Veias Pulmonares/patologia , Pneumopatia Veno-Oclusiva/diagnóstico por imagem , Pneumopatia Veno-Oclusiva/mortalidade , Pneumopatia Veno-Oclusiva/patologia , Taxa de Sobrevida , Texas , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia , Vimblastina/administração & dosagem , Vimblastina/efeitos adversosRESUMO
OBJECTIVES: The objective of this article is to review anatomic, physiologic, and clinical features of fetuses and neonates with severe mitral regurgitation (MR) in conjunction with aortic stenosis (AS) and left ventricular (LV) and left atrial (LA) dilation and to present preliminary results of pre-natal intervention for this condition. BACKGROUND: Severe fetal valvar AS with an abnormal mitral valve (MV) and MR can lead to left heart dilation, with consequent compression of the right ventricle (RV); hydrops and low cardiac output are often associated. METHODS: This is a retrospective review of fetuses diagnosed with AS, severe MR, and LA dilation (2002 to 2009) and neonates with the same combination of abnormalities (1988 to 2009). RESULTS: Fourteen fetuses and 7 neonates were investigated. Eleven fetuses had severe hydrops; all had polyhydramnios and a structurally abnormal MV, abnormal MV inflow pattern, restrictive/intact atrial septum, retrograde flow in the transverse aortic arch, and compression of the right heart. The mean indexed RV output was 326 ± 160 ml/kg/min, lower than the normal average fetal combined ventricular output of 550 ± 150 ml/kg/min. Ten fetuses underwent pre-natal cardiac intervention: aortic valvuloplasty (n = 8) and/or atrial septal dilation/stenting (n = 5). Seven of these, and 11 overall, were live born. Nine patients died (median age 6 days), and 2 patients are currently alive. All 7 patients diagnosed in the neonatal period died (median age 1 day). CONCLUSIONS: Aortic stenosis associated with significant MR in the fetus can cause severe LA and LV enlargement, leading to low cardiac output and hydrops. Despite the potential advantages of early pre-natal diagnosis and both fetal and neonatal interventions, this rare complex of anomalies carries a poor prognosis.
Assuntos
Estenose da Valva Aórtica/diagnóstico por imagem , Átrios do Coração/anormalidades , Átrios do Coração/diagnóstico por imagem , Hidropisia Fetal/diagnóstico por imagem , Insuficiência da Valva Mitral/diagnóstico por imagem , Ultrassonografia Pré-Natal/métodos , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/terapia , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Hidropisia Fetal/terapia , Recém-Nascido , Insuficiência da Valva Mitral/complicações , Insuficiência da Valva Mitral/terapia , Gravidez , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The hemodynamics after Fontan surgery are notable for hypertension and dilation of the right atrium (RA). The effect of this stress on atrial cytoarchitecture has not been systematically studied and might be relevant to arrhythmias and their treatment. Morphologic and histopathologic analyses were performed on tissue from the RA and left atrium (LA) from autopsy specimens of Fontan hearts (n = 47). The findings were compared to those from control samples from young patients with normal atrial hemodynamics (n = 15). Most Fontan specimens were from young patients who died after a relatively short duration of Fontan physiology. The tissues were analyzed for wall thickness, fibrosis content, and fibrosis pattern. The mean wall thickness for the RA (3.0 +/- 1.0 mm) and LA (2.3 +/- 0.6 mm) in the Fontan hearts was significantly greater than that in the control hearts (RA, 1.8 +/- 0.4 mm; LA, 1.8 +/- 0.5 mm; p <0.001 and p = 0.024, respectively). The predictors for thickening of the RA included (1) older age at Fontan surgery, (2) older age at death, and (3) longer duration of Fontan circulation. The Fontan hearts and control hearts exhibited nearly identical fibrosis patterns in the RA and LA. Neither wall thickness nor fibrosis varied with the underlying heart defect or style of Fontan connection. In conclusion, atrial remodeling after Fontan surgery for univentricular heart physiology involves increased wall thickness in both the RA and LA. Interstitial fibrosis was also observed in the Fontan atria; however, because a similar pattern was present in the control tissue, this likely represented normal fibroelastic atrial structure, rather than a specific response to Fontan hemodynamics. The degree of wall thickening observed in the Fontan atria was not so excessive as to preclude transmural lesions during catheter or surgical ablation of reentrant arrhythmias.
Assuntos
Técnica de Fontan/efeitos adversos , Átrios do Coração/patologia , Átrios do Coração/fisiopatologia , Criança , Pré-Escolar , Feminino , Hemodinâmica , Humanos , MasculinoRESUMO
OBJECTIVE: To describe and characterize morphological characteristics of endocardial irregularities in the roof of the left atrium as seen on coronary CT angiography. METHODS: We retrospectively evaluated the left atrium in 50 consecutive coronary CT patients with multiplanar reformatting, volume rendering, and virtual endoscopy. RESULTS: Twenty-one of the 50 patients had an endocardial irregularity at the roof of the left atrium. The most common finding (n = 14) was a smooth diverticulum, arising near the venoatrial junction of the right superior pulmonary vein. CONCLUSION: Endocardial irregularities of the left atrium can be identified on coronary CT and may be more common than previously considered. The findings probably represent remnants of the cardinal venous system during embryological development. Further work should focus on the true prevalence and potential clinical significance.
Assuntos
Angiografia Coronária/métodos , Divertículo/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Feminino , Átrios do Coração/anormalidades , Átrios do Coração/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Vascular rings are a rare form of congenital malformation that completely encircle the trachea and esophagus with vascular structures. The two most common forms are double aortic arch and right aortic arch with an aberrant left subclavian artery and a left-sided ligamentum arteriosum. Patients may present with symptoms of airway or esophageal impingement, including "noisy breathing," stridor, respiratory distress, difficulty feeding, or dysphagia. Typically, the more severe the airway or esophageal compression, the earlier the age at presentation. Diagnosis was traditionally made by posterior compression of the esophagus demonstrated by barium swallow; in the current era, CT angiography or magnetic resonance angiography is used. Although helpful to delineate intracardiac anatomy and associated structural heart defects, echocardiography is less useful for imaging vascular structures when atretic segments comprise part of the vascular ring. Management includes surgical division of the structures contributing to the vascular ring. Some centers also perform surgical remodeling of Kommerell's diverticulum because this structure may contribute to continuing tracheal or esophageal compression even after the ring has been released. Patients with associated tracheomalacia may continue to have symptoms that can last for months, but ultimately resolve with time. Long-term results are generally excellent with minimal morbidity and mortality.
RESUMO
Bilateral atresia of the coronary artery ostia in patients with pulmonary atresia and intact ventricular septum is a rare condition with no reported survivors beyond early infancy. We report the first case of diagnosis by echocardiography followed by successful cardiac transplantation.
Assuntos
Anomalias dos Vasos Coronários/diagnóstico por imagem , Anomalias dos Vasos Coronários/cirurgia , Transplante de Coração , Atresia Pulmonar/diagnóstico por imagem , Atresia Pulmonar/cirurgia , Septos Cardíacos/diagnóstico por imagem , Septos Cardíacos/cirurgia , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/cirurgia , Humanos , Recém-Nascido , Resultado do Tratamento , UltrassonografiaRESUMO
BACKGROUND: Primary pulmonary vein stenosis (PVS) is a progressive disorder of infants. Although catheter based intervention and chemotherapy are used to manage the disorder, the benefit of these approaches is reduced considerably by restenosis. The nature of the intimal cells causing the occlusive lesions in PVS is poorly understood. METHODS: Seven PVS cases were studied with antibodies for smooth muscle actin (SMA), muscle-specific actin (MSA), monoclonal desmin, S100 protein, CD31, CD34, CD45RO, CD68, CD99, Ki-67 (MIB-I), and with antibodies directed against several receptor tyrosine kinases (RTK), including platelet-derived growth factor alpha and beta receptor (PDGFR-alpha and -beta), epidermal growth factor receptor (EGFR), fibroblast growth factor receptor (FGFR), vascular endothelial growth factor 1 and 2 receptor (VEGFR), and stem cell factor receptor (c-kit). RESULTS: Lesional cells stained strongly and diffusely with SMA and MSA, but not for macrophage, lymphocyte, endothelial markers, or for Ki-67. RTK expression was strong and diffuse for PDGFR-alpha and -beta, FGFR, and VEGFR-2. Lesional cells stained for VEGF and PDGF beta receptor was phosphorylated. CONCLUSIONS: The histologic appearance, and the strong diffuse immunoreactivity for smooth muscle markers, indicates that the intimal lesional cells are myofibroblast-like. Expression of various receptor tyrosine kinases and some ligands suggests an autocrine or paracrine role of these proteins in the pathogenesis of the intimal occlusive lesion in PVS.
Assuntos
Veias Pulmonares/patologia , Receptores Proteína Tirosina Quinases/metabolismo , Animais , Constrição Patológica/enzimologia , Feminino , Humanos , Imuno-Histoquímica , Lactente , Recém-Nascido , Masculino , Coelhos , Túnica Íntima/patologia , Doenças Vasculares/enzimologia , Doenças Vasculares/patologiaRESUMO
Mutations in developmental regulatory genes have been found to be responsible for some cases of congenital heart defects. One such regulatory gene is Gata4, a zinc finger transcription factor. In order to circumvent the early embryonic lethality of Gata4-null embryos and to investigate the role of myocardial Gata4 expression in cardiac development, we used Cre/loxP technology to conditionally delete Gata4 in the myocardium of mice at an early and a late time point in cardiac morphogenesis. Early deletion of Gata4 by Nkx2-5Cre resulted in hearts with striking myocardial thinning, absence of mesenchymal cells within the endocardial cushions, and selective hypoplasia of the RV. RV hypoplasia was associated with downregulation of Hand2, a transcription factor previously shown to regulate formation of the RV. Cardiomyocyte proliferation was reduced, with a greater degree of reduction in the RV than in the LV. Late deletion of Gata4 by Cre recombinase driven by the alpha myosin heavy chain promoter did not selectively affect RV development or generation of endocardial cushion mesenchyme but did result in marked myocardial thinning with decreased cardiomyocyte proliferation, as well as double-outlet RV. Our results demonstrate a general role of myocardial Gata4 in regulating cardiomyocyte proliferation and a specific, stage-dependent role in regulating the morphogenesis of the RV and the atrioventricular canal.
Assuntos
Proteínas de Ligação a DNA/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Ventrículos do Coração/embriologia , Morfogênese/fisiologia , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Fatores de Transcrição/metabolismo , Animais , Proliferação de Células , Proteínas de Ligação a DNA/genética , Fator de Transcrição GATA4 , Cardiopatias Congênitas/genética , Cardiopatias Congênitas/metabolismo , Cardiopatias Congênitas/patologia , Ventrículos do Coração/citologia , Proteína Homeobox Nkx-2.5 , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Integrases/genética , Mesoderma/citologia , Mesoderma/fisiologia , Camundongos , Camundongos Transgênicos , Morfogênese/genética , Miocárdio/citologia , Miócitos Cardíacos/citologia , Fatores de Transcrição/genética , Proteínas Virais/genéticaRESUMO
Normal heart development is orchestrated by a set of highly conserved transcription factors that includes GATA4, Nkx2-5, and Tbx5. Heterozygous mutation of each of these genes causes congenital heart disease in humans. In mouse models, haploinsufficiency for Nkx2-5 or Tbx5 resulted in an increased incidence of structural heart disease, confirming that normal heart development is sensitive to small changes in expression levels of Nkx2-5 and Tbx5. However, mice haploinsufficient for GATA4 have not been reported to have cardiac abnormalities. We generated two new GATA4 alleles, GATA4(H) and GATA4(flox). GATA4(flox/flox) embryos expressed 50% less GATA4 protein in the heart and survived normally. In contrast, GATA4(H/H) embryos expressed 70% less GATA4 protein in the heart and died between days 13.5 and 16.5 of gestation. These embryos had common atrioventricular canal (CAVC), double outlet right ventricle (DORV), hypoplastic ventricular myocardium, and normal coronary vasculature. Myocardial hypoplasia was associated with diminished cardiomyocyte proliferation. Hemodynamic measurements demonstrated that these embryos had normal systolic function, severe diastolic dysfunction, and atrioventricular regurgitation. Surprisingly, expression levels of the putative GATA4 target genes ANF, BNP, MEF2C, Nkx2-5, cyclin D2, and BMP4 were unchanged in mutant hearts, suggesting that GATA4 is not a dose-limiting regulator of the expression of these genes during later stages of embryonic cardiac development. These data demonstrate that multiple aspects of embryonic cardiac morphogenesis and function are exquisitely sensitive to small changes in GATA4 expression levels.
Assuntos
Coração/embriologia , Animais , Divisão Celular/fisiologia , Quimera , Proteínas da Membrana Plasmática de Transporte de GABA , Marcação de Genes , Coração/fisiologia , Proteínas de Membrana Transportadoras , Camundongos , Miócitos Cardíacos/citologia , Fatores de TempoRESUMO
The mouse is the animal of choice for the study of molecular mechanisms involved in the regulation of cardiovascular morphogenesis and function. Recently, a series of genetically engineered mouse models have been reported (e.g. cGATA6/lacZ, MinK/lacZ knock-in/knock-out, engrailed2/lacZ, Cardiac troponin I/lacZ) that provide new and exciting information on the development of the atrioventricular conduction system (AVCS). On the basis of these and ongoing studies, concepts for the formation of the AVCS are continuously being adjusted. A proper understanding of the normal developmental mechanisms underlying the cardiac remodelling leading to the formation of the AVCS is imperative for the interpretation of cardiac abnormalities, including conduction disturbances, as observed in some genetically perturbed (knockout) mice. In this paper information on murine AVCS development will be integrated with published and unpublished results from studies in other vertebrates, including human and rabbit. We will illustrate that although many pieces of the puzzle still remain to be gathered, the outline of a very complex and critical event in cardiac morphogenesis is slowly emerging. Specifically, we will re-evaluate the concept of the 'primary ring' in the context of the new insights in the development of the AV junction as provided by the respective mouse models described above.
Assuntos
Sistema de Condução Cardíaco/embriologia , Sistema de Condução Cardíaco/crescimento & desenvolvimento , Coração/crescimento & desenvolvimento , Animais , Coração/anatomia & histologia , Coração/fisiologia , Sistema de Condução Cardíaco/fisiologia , Humanos , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Morfogênese , Miocárdio/citologia , Miocárdio/metabolismo , Canais de Potássio/genética , Canais de Potássio/metabolismo , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , TransgenesRESUMO
We identified a GATA6 gene enhancer that selectively marks the developing atrioventricular conduction system (AVCS) in transgenic mice. This enhancer reads anterior/posterior and medial/lateral positional information early in the cardiogenic programme and remains active in progressively more restricted subsets of heart cells leading up to AVCS formation. Additional experiments will be required to determine if the potential to be recruited into the AVCS is similarly restricted to a subset of myocardial cells early in the cardiogenic programme or if this enhancer can also be activated de novo in cells that initially reside outside this field. We are using several strategies to identify factors that regulate this and other AVCS enhancers and hence govern AVCS function. We are also using this enhancer to make transgenic mice that express Cre, or an inducible form of Cre, to track lineages and to delete floxed genes in the developing or mature AVCS. This Cre/lox approach provides a means to deconstruct complex congenital heart phenotypes that involve the conduction system and to test whether genes are required to form the AVCS or to maintain AVCS function. Lastly, we are exploring strategies to isolate and analyse AVCS cells from normal and affected hearts.