CONGENITAL HEART DISEASE IN CYANOTIC CHILDREN

Cyanosis is often the only apparent symptom of congenital heart disease for which a child is brought to a physician. Some of the more common anomalies can be diagnosed from this and other symptoms by a general practitioner. Squatting after exertion is a sign of tetralogy of Fallot; severe disability with relatively mild cyanosis may indicate pure pulmonary stenosis. A brisk, short, rasping systolic murmur is characteristic of these conditions and of tricuspid atresia.Tetralogy of Fallot is further symptomatized by a boot-shaped heart, not greatly enlarged, and right axis deviation on electrocardiograms. Typically the lung fields are clear. The author''s treatment of choice is aortic-pulmonary or subclavian-pulmonary anastomosis as indicated, preferably done after the child is three years old if the condition is not so severe as to require earlier operation.Pure pulmonary stenosis, which in some cases cannot be distinguished from tetralogy of Fallot except by cardiac catheterization and angiocardiography, may in more typical cases be diagnosed by convexity rather than concavity in the pulmonary segment and by differences in electrocardiograms. An expanding valvulotome is used to open the stenosed pulmonary valve, which is then dilated.A systolic murmur, a round heart and left axis deviation are usually found in tricuspid atresia. Shunt operations performed for relief of this condition may lead to later heart failure because of the devious rerouting of blood through the heart.The operations here outlined and others are statistically evaluated.     

法洛四联症合并肺动脉闭锁的手术治疗分析

目的：探讨法洛四联症合并肺动脉闭锁的手术治疗,对其各型手术时机、手术方法进行概述。方法：在我院就诊的21例法洛四联症合并肺动脉闭锁患者,15例患者在全身廓醉中度低温体外循环下实行一期根治术,6例患者实行分期手术。结果：3例发生术后早期死亡,Ⅲ患者2例,Ⅳ型患者1例,死亡原因：低心排血量综合征1例,灌注肺1例,严重感染1例。16例保持长期随访,随访0．6．4年,NYHA心功能都达到Ⅰ或Ⅱ级标准。结论：法洛四联症合并肺动脉闭锁确诊后,根据肺动脉发育情况选择合适的手术方式尽快手术,能提高患者的治愈率,降低病死率。     

Per-operative stent placement in the right pulmonary artery; a hybrid technique for the management of pulmonary artery branch stenosis at the time of pulmonary valve replacement in adult Fallot patients

After having undergone surgical correction at an early age, many patients with tetralogy of Fallot develop long-term complications including progressive pulmonary regurgitation and peripheral pulmonary stenosis. A high percentage of these patients need to undergo a second operation in their adolescence or early adulthood. If simultaneous treatment of both pulmonary regurgitation and peripheral pulmonary stenosis is warranted, a complete surgical approach has several disadvantages. We describe four cases of Fallot patients with severe pulmonary regurgitation and peripheral pulmonary stenosis who were treated using a hybrid approach involving surgical implantation of a pulmonary homograft and peroperative stenting of the pulmonary artery.     

Pregnancy after surgical correction of tetralogy of Fallot.

Forty pregnancies have been documented in 27 patients with surgically corrected tetralogy of Fallot. Infertility was uncommon and there were no premature births and few abortions or small-for-dates babies; this suggests that surgery that corrects cyanosis improves the outcome of pregnancy by correcting the fetal environment. Pregnancy was well tolerated and there were no serious cardiac complications. Thirty of the 31 infants examined were normal, the one abnormal infant having pulmonary atresia. A patient with no major residual defects after surgery for tetralogy of Fallot may be reassured that pregnancy will be well tolerated and that delivery may be managed in the normal manner.     

Epidemiology of congenital heart disease in Louisiana: an association between race and sex and the prevalence of specific cardiac malformations.

We hypothesized that susceptibility to the genetic and environmental factors that disrupt cardiac development is associated with race and sex. To evaluate this hypothesis, we asked whether the prevalence of specific cardiac malformations differs by race and sex. We attempted to include all infants born alive in the State of Louisiana from January 1, 1988, through December 31, 1989, and diagnosed by echocardiography, catheterization and/or autopsy within a year of birth as having one of ten specific cardiac malformations. The prevalence of atrioventricular canal defects (AVCD) per 1,000 live births was significantly higher for black females (.744) compared to black males (.198) and for white females (.414) compared to white males (.116). Complete transposition of the great arteries (TGA) was significantly higher for white males (.559) compared to white females (.122); in contrast, TGA was not significantly different for black males (.198) and black females (.169). Obstructive left heart syndrome (OLHS)--aortic stenosis and/or coarctation of the aorta--was significantly higher for white males (.652) compared to white females (.317); in contrast, OLHS was not significantly different for black males (.264) and black females (.169). Single ventricle (SV) was significantly higher for whites (.202) compared to blacks (.067). We did not find that race and sex were associated with differences in the prevalence of tetralogy of Fallot and hypoplastic left heart syndrome. The numbers of infants with anomalous pulmonary venous return, tricuspid atresia, double outlet right ventricle, or truncus arteriosus were too small to measure an association with race and sex. These results demonstrate that the prevalence of a subset of cardiac malformations differs by race and sex.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acquired left coronary artery fistula to right ventricular outflow tract

A 59-year-old asymptomatic male was referred to our hospital for evaluation 44 years after surgical correction of a Fallot’s tetralogy. Transthoracic echocardiography showed a good surgical result with only a mild subvalvular pulmonary stenosis and mild pulmonary regurgitation. However, in the parasternal short axis a diastolic colour Doppler flow was seen in the right ventricular outflow tract with a maximum velocity over 4 m/s (figure 1). Pulmonary regurgitation seemed very unlikely because of the high velocity in the absence of elevated pulmonary artery pressure. Because a fistula was suspected, a multislice computer tomography scan was performed.     

Les sténoses pulmonaires périphériques congénitales: Présentation de 16 observations et revue de la littérature

Sixteen cases of peripheral pulmonary stenosis have been studied clinically and by cardiac catheterization. Diagnosis has been proved in all cases by manometric measurements and/or cineangiocardiography. All patients except two were below 2 years of age. Ten cases were of type I, i.e. the stenosis was localized to the pulmonary trunk or its main branches. Six patients were of type III, i.e. they had diffuse stenosis of the pulmonary arterial tree. The physical findings, which in many cases are typical and include the presence of a systolic murmur over both lung fields, should alert the physician to the diagnosis at the bedside. At cardiac catheterization the configuration of the pressure tracing in the main pulmonary artery is typical, showing an abrupt rise and fall of the systolic wave followed by a low situated dicrotic notch. There is no doubt that in the past many cases of peripheral pulmonary stenosis have been wrongly diagnosed as “essential pulmonary hypertension”.     

小儿法洛四联症根治术后氨基末端脑钠肽前体水平变化及其临床意义分析

目的：探讨小儿法洛四联症根治术后血浆氨基末端脑钠肽前体（N—terminal pro-brain natriuretic peptide,NT-proBNP）水平变化及其临床意义。方法：选择我院2011年10月～2013年4月收治的法洛四联症患儿52例,所有患儿行法洛四联症根治术治疗,并于术前、术后3h、12h、48h、1周、1个月和3个月测定患儿血浆NT-proBNP水平,应用心脏彩超机检查肺动脉跨瓣压差、右室舒张末期容积（rightventricularend．diastolicvolume,RVEDV）、左室射血分数（Leftventricular ejection fraction,LVEF）和右心Tei指数（Teiindex）。结果：①术后3hNT—proBNP水平开始逐渐升高,术后48h达最高,明显高于术前水平（P〈0．01）,术后1个月、3个月明显低于治疗前水平（P〈0．05）。②术后1周,右心功能不全组血浆NT．proBNP水平、肺动脉跨瓣压差、RVEDV明显高于右心功能正常组,LVEF明显低于右心功能正常组（P〈0．05）。③术后3个月,重度返流组、中度返流组患儿术后48h、1周、3个月血浆NT—proBNP明显高于轻度返流组（P〈0．05）;重度返流组患儿术后1周、3个月血浆NT—proBNP明显高于轻度返流组（P〈0．05）。结论：NT．proBNP在小儿法洛四联症根治术后早期的变化水平与右心功能的变化一致,可以作为评估右心功能的客观指标。     

Sonic hedgehog maintains proliferation in secondary heart field progenitors and is required for normal arterial pole formation

The Sonic hedgehog (Shh)-null mouse was initially described as a phenotypic mimic of Tetralogy of Fallot with pulmonary atresia (Washington Smoak, I., Byrd, N.A., Abu-Issa, R., Goddeeris, M.M., Anderson, R., Morris, J., Yamamura, K., Klingensmith, J., and Meyers, E.N. 2005. Sonic hedgehog is required for cardiac outflow tract and neural crest cell development. Dev. Biol. 283, 357–372.); however, subsequent reports describe only a single outflow tract, leaving the phenotype and its developmental mechanism unclear. We hypothesized that the phenotype that occurs in response to Shh knockdown is pulmonary atresia and is directly related to the abnormal development of the secondary heart field. We found that Shh was expressed by the pharyngeal endoderm adjacent to the secondary heart field and that its receptor Ptc2 was expressed in a gradient in the secondary heart field, with the most robust expression in the caudal secondary heart field, closest to the Shh expression. In vitro culture of secondary heart field with the hedgehog inhibitor cyclopamine significantly reduced proliferation. In ovo, cyclopamine treatment before the secondary heart field adds to the outflow tract reduced proliferation only in the caudal secondary heart field, which coincided with the region of high Ptc2 expression. After outflow tract septation should occur, embryos treated with cyclopamine exhibited pulmonary atresia, pulmonary stenosis, and persistent truncus arteriosus. In hearts with pulmonary atresia, cardiac neural crest-derived cells, which form the outflow tract septum, migrated into the outflow tract and formed a septum. However, this septum divided the outflow tract into two unequal sized vessels and effectively closed off the pulmonary outlet. These experiments show that Shh is necessary for secondary heart field proliferation, which is required for normal pulmonary trunk formation, and that embryos with pulmonary atresia have an outflow tract septum.     

应用同种带瓣管道重建右室流出道的危险因素分析

目的：评价采用同种带瓣管道行右室流出道重建术的临床效果,探讨影响手术效果及临床预后的因素。方法：回顾2002年11月至2010年11月期间应用同种带瓣管道行右室流出道重建患者的临床资料,分析患者手术前后的一般信息、血流动力学表现与临床预后的关系。结果：行右室流出道重建术后49例痊愈出院,5例死亡,存活率90．7％,死亡率9-3％。手术前后比较右室流出道内径较术前明显增加,右室一左室收缩压比值、右室-肺动脉压差较术前明显降低,三尖瓣反流、肺动脉瓣反流较术前加重,肺动脉瓣狭窄较术前减轻。统计分析表明患者死亡的危险因素有术后右室平均压、术后肺动脉-主动脉收缩压比值、术后二尖瓣反流。术后心胸比、术后肺动脉收缩压、术后肺动脉一主动脉收缩压比值、术后三尖瓣反流可能和术后患者ICU时间延长有关。McGoon指数、术后心胸比、术后肺动脉收缩压、术后右室平均压、术后肺动脉一主动脉收缩压比值、合并动脉导管未闭、术后三尖瓣反流可能和术后患者呼吸机时间延长有关。结论：复杂先天性心脏病患者采用同种带瓣管道重建右室流出道可以取得较满意的临床效果,术后流出道梗阻矫正满意,可以防止肺动脉返流导致的心脏损害。     

Further phenotypic delineation of subtelomeric (terminal) 4q deletion with emphasis on intracranial and reproductive anatomy

Hypoplastic left heart syndrome(HLHS) refers to the abnormal development of the left-sided cardiac structures, resulting in obstruction to blood flow from the left ventricular outflow tract. In addition, the syndrome includes underdevelopment of the left ventricle, aorta, and aortic arch, as well as mitral atresia or stenosis. HLHS has been reported to occur in approximately 0.016 to 0.036% of all live births. Newborn infants with the condition generally are born at full term and initially appear healthy. As the arterial duct closes, the systemic perfusion becomes decreased, resulting in hypoxemia, acidosis, and shock. Usually, no heart murmur, or a non-specific heart murmur, may be detected. The second heart sound is loud and single because of aortic atresia. Often the liver is enlarged secondary to congestive heart failure. The embryologic cause of the disease, as in the case of most congenital cardiac defects, is not fully known. The most useful diagnostic modality is the echocardiogram. The syndrome can be diagnosed by fetal echocardiography between 18 and 22 weeks of gestation. Differential diagnosis includes other left-sided obstructive lesions where the systemic circulation is dependent on ductal flow (critical aortic stenosis, coarctation of the aorta, interrupted aortic arch). Children with the syndrome require surgery as neonates, as they have duct-dependent systemic circulation. Currently, there are two major modalities, primary cardiac transplantation or a series of staged functionally univentricular palliations. The treatment chosen is dependent on the preference of the institution, its experience, and also preference. Although survival following initial surgical intervention has improved significantly over the last 20 years, significant mortality and morbidity are present for both surgical strategies. As a result pediatric cardiologists continue to be challenged by discussions with families regarding initial decision relative to treatment, and long-term prognosis as information on long-term survival and quality of life for those born with the syndrome is limited.     

Phenotypic variability in <Emphasis Type="Italic">Hey2 −/−</Emphasis> mice and absence of <Emphasis Type="Italic">HEY2</Emphasis> mutations in patients with congenital heart defects or Alagille syndrome

The genetic alterations leading to congenital heart defects (CHD) are still poorly understood. We and others have recently shown that in mice loss of Hey2 results in a high incidence of fatal ventricular and atrial septal defects, combined with tricuspid stenosis or atresia in some cases. The phenotype has been postulated to resemble human tetralogy of Fallot. Our analysis of CD1 outbred mice suggests that phenotypic consequences of Hey2 loss can be quite variable and dependent on modifier genes as we detected only isolated VSDs with lower prevalence and a significantly reduced mortality rate in this strain. Since Hey2 is one of the few Notch target genes, it is also conceivable that HEY2 mutations may account for cases of Alagille syndrome (AGS: variable combinations of heart, skeleton, eye, and facial malformations and cholestasis), in which the typical mutations of the Notch ligand JAG1 cannot be found. To clarify the role of HEY2 in human CHD and AGS, we screened by direct sequencing 23 children with CHD and 38 patients diagnosed with AGS, which lack mutations in the JAG1 gene. We found two types of silent changes in the coding region: a CTTCTG transition in exon 3 and a CTGCTC polymorphism in exon 5. Furthermore, a heterozygous SNP in the splice donor site of exon 4 was detected that is unlikely to disrupt splicing. Although the high incidence and variability of human congenital heart defects implies a multifactorial genetic basis, our results suggest that mutation of HEY2 is not a major contributing factor.     

PHONOCARDIOGRAPHY

In phonocardiography the second heart sound is important in appraisal of congenital heart disease and pulmonary hypertension because it reflects the duration of right ventricular systoles.The systolic murmur in patients with intracardiac shunt decreases as pulmonary hypertension develops, and may eventually disappear completely as the pulmonary pressure reaches systemic level.Reference tracings in phonocardiography are useful for showing the interrelationship of the various cardiac sounds and murmurs.     

Congenital Aortic Stenosis: Some Observations on the Natural History and Clinical Assessment

Three hundred patients, 30 years of age or under, with the clinical diagnosis of aortic stenosis were reviewed to provide information on the accuracy of clinical assessment and the natural history of the condition when left untreated. Sudden death was uncommon and occurred only in patients with clinical evidence of severe obstruction. In infants, the early presentation and lethal nature of aortic stenosis appeared to result from the presence of additional cardiac lesions. Correlation of clinical assessment with hemodynamic data in 83 patients indicated that important stenosis was present if the systolic murmur was accompanied by a thrill and associated with an increased left ventricular impulse, decreased brachial artery pulse pressure, or left ventricular hypertrophy on the electrocardiogram. The site of obstruction could not be established with certainty by clinical examination, but an early systolic ejection click was strong evidence against subvalvular stenosis.     

Disturbed morphogenesis of cardiac outflow tract and increased rate of aortic arch anomalies in the offspring of diabetic rats

BACKGROUND: Maternal diabetes (MD) is a risk factor for offspring to develop cardiovascular anomalies; this is of growing clinical concern since the number of women in childbearing age with compromised glucose homeostasis is increasing. Hyperglycemia abrogates cardiovascular development in vitro; however, a link to cardiovascular defects in diabetic offspring remains to be investigated. METHODS: We have studied cardiovascular development in offspring of MD rats by examining serial histological sections of GD 12.0-18.0 offspring. Development of pharyngeal arch artery malformations was analyzed and related to intracardiac anomalies. RESULTS: Pharyngeal arch artery and intracardiac defects were present in 27 of 37 MD GD 13.0-18.0 offspring. Early sixth arch arteries showed abrogated arteriogenesis, whereas fourth arch artery defects developed as a result of abnormal remodeling. Morphometrical analysis showed increased apoptosis in regressing artery segments and reduced apoptosis in persisting artery segments. Double outlet right ventricle with infundibular stenosis (tetralogy of Fallot) was predominantly found in combination with sixth artery defects and pulmonary atresia. As confirmed by morphometric analysis and three-dimensional (3D)-reconstructions, outflow tract defects coincided with endocardial cushion hypoplasia. Cases with teratology of Fallot additionally showed a shorter outflow tract. No relation with apoptosis or disturbed neural crest cell migration was found. CONCLUSIONS: Our data uniquely demonstrate mechanistic differences involved in the development of sixth and fourth artery anomalies. Whereas increased apoptosis induces fourth artery anomalies, pulmonary outflow obstruction abrogates sixth artery differentiation independent of apoptosis. The model presented allows analysis of diabetic conditions on cardiovascular development in vivo, essential for elucidating this teratology.     

Mutations of the GATA4 and NKX2.5 genes in Chinese pediatric patients with non-familial congenital heart disease

A number of mutations in GATA4 and NKX2.5 have been identified to be causative for a subset of familial congenital heart defects (CHDs) and a small number of sporadic CHDs. In this study, we evaluated common GATA4 and NKX2.5 mutations in 135 Chinese pediatric patients with non-familial congenital heart defects. Two novel mutations in the coding region of GATA4 were identified, namely, 487C >T (Pro163Ser) in exon 1 in a child with tetralogy of Fallot and 1220C >A (Pro407Gln) in exon 6 in a pediatric patient with outlet membranous ventricular septal defect. We also found 848C >A (Pro283Gln) in exon 2 of the NKX2.5 gene in a pediatric patient with ventricular septal defect, patent ductus arteriosus and aortic isthmus stenosis. None of the mutations was detected in healthy control subjects (n = 114). This study suggests that GATA4 and NKX2.5 missense mutations may be associated with congenital heart defects in pediatric Chinese patients. Further clinical studies with large samples are warranted.     

Evaluation of late results of surgical treatment of congenital heart disease.

Operative mortality from surgical treatment of congenital heart disease has been steadily reduced over the past 20 years. During the same period it has become clear that a proportion of survivors have residual clinical problems. Some of these are due to imperfect repair, a number being due to factors beyond present surgical control, and some are the consequence of associated cardiovascular defects. The chief problems can be elucidated by an analysis of the results of surgical treatment of six cardiac malformations: simple pulmonary valve stenosis, coarctation of the aorta, secundum atrial septal defect, isolated ventricular septal defect, tetralogy of Fallot and transposition of the great arteries. Recognition of the sequelae of preoperative hemodynamic strain and apparently minor associated malformations is important, and it is possible to anticipate such factors. Long-term follow-up of patients after operation is particularly important.     

L'Anastomose cavo-pulmonaire dans les malformations tricuspidiennes: Evolution de 10 cas opérés

Certain congenital malformations affecting the rightsided cavities of the heart and accompanied by a diminished pulmonary blood flow can be improved by an end-to-side anastomosis between the right pulmonary artery and the superior vena cava. Nine out of the 10 patients who underwent the operation survived. The results have been very impressive in six patients with tricuspid atresia who were critically ill. The anoxemic episodes ceased completely and cyanosis has disappeared. Three cases of Ebstein''s anomaly have also been improved. This clinical study has given us the opportunity to review the physiological consequences of the anastomosis, its complications and its surgical indications. We believe that this type of shunt is especially indicated in cases of tricuspid atresia, in which only a palliative form of surgery can be performed.