Clinical relevance of monosomy 22q11.2 in children with pulmonary atresia and ventricular septal defect

The purpose of our study was to describe the prevalence and the clinical spectrum of monosomy 22q11.2 in a population of patients with pulmonary atresia and ventricular septal defect. We examined all 44 patients with this conotruncal cardiac malformation who presented to our institution from January 1994 until December 1997. The type of collateral lung perfusion was recorded including anomalies of the pulmonary arteries as well as facial and immunological abnormalities. Molecular-cytogenetic testing for a 22q11.2 microdeletion was performed using the probes D22S75 and cHKAD26. Statistical differences were evaluated with the Fisher's Exact Test. Monosomy 22q11.2 was present in ten children (23%) with major aortopulmonary collateral arteries (group 1). The remaining 13 children (29%) with major aortopulmonary collateral arteries (group 2) and all 21 children (48%) with ductus arteriosus (group 3) were negative for this microdeletion. All children in group 1 had facial anomalies, six had mild immunological abnormalities including decreased CD 4+ or CD 8+ cells. Anomalies of the pulmonary vascular bed were significantly more frequent in children of group 1 (9/10) than in children of group 2 (4/13) or group 3 (0/21). Due to these pulmonary vascular anomalies, corrective surgery had been accomplished in fewer children with monosomy 22q11.2 (none in group 1) as compared to 7/13 children in group 2 and 14/21 children in group 3. Conclusion In children with pulmonary atresia and ventricular septal defect, monosomy 22q11.2 is preferentially associated with major aortopulmonary collateral arteries. Due to the higher incidence of pulmonary arterial abnormalities, successful surgical repair will require a different therapeutic approach in most patients with this microdeletion. Received: 3 June 1998 / Accepted in revised form: 11 September 1998     

Hypoplasia of the intrapulmonary arteries in children with right ventricular outflow tract obstruction,ventricular septal defect,and major aortopulmonary collateral arteries

Summary Postmortem injection studies have been carried out on the pulmonary vasculature of four children dying with pulmonary atresia and ventricular septal defect or severe tetralogy of Fallot with major aortopulmonary collateral arteries, in which nearly all bronchopulmonary segments had more than one source of blood supply. Despite regional variations in the source of blood supply, there was remarkable uniformity of arterial size and number within the respiratory unit throughout each case. In all cases, there was a normal number of arterial pathways, but both pre- and intraacinar arteries were considerably smaller than normal. The need for early operative intervention to ensure growth of pre- and particularly intraacinar arteries is emphasized.     

肺动脉闭锁合并室间隔缺损的临床病理分析

目的 研究肺动脉闭锁合并室间隔缺损的解剖类型和血流动力学改变,并探讨其适宜的手术方式.方法 回顾性分析233例肺动脉闭锁合并室间隔缺损的造影结果,分析肺血来源、肺动脉发育情况和合并畸形及其与手术预后的影响.结果 233例中中央肺动脉存在,肺血单纯由未闭的动脉导管供应者112例(48.1%),其中1例为双侧动脉导管(0.5%);中央肺动脉和大的主一肺动脉侧支血管(MAPCA)均存在者104例(44.6%);无中央肺动脉,仅有MAPCA供应肺血者17例(7.3%).肺动脉闭锁部位以右室流出道和瓣膜闭锁最多见(48.1%).侧支血管的来源包括直接的主动脉一肺侧支动脉,间接的主动脉一肺侧支动脉和支气管动脉.合并畸形包括心脾综合征、房室连接不一致、心室大动脉连接不一致、多发室间隔缺损、右位主动脉弓、房间隔缺损、左上腔静脉残存、内脏异位症、上下心室、肺静脉异位引流和冠状动脉起源异常等.结论 肺动脉闭锁合并室间隔缺损患者肺血来源多样化,肺动脉发育程度不一,并可合并多种心内、心外畸形,影响手术方法的选掸和手术结果.     

Dual-Catheter Balloon Occlusion Aortography in Pulmonary Atresia with Ventricular Septal Defect and Major Aorto-Pulmonary Collaterals

Angiography remains the gold standard in the preoperative evaluation of complex pulmonary blood supply in patients with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries. In neonates, balloon occlusion aortography using a Berman balloon catheter is a very effective technique. However, in older patients this method is frequently limited due to failure to achieve distal balloon occlusion. A novel technique using a balloon valvuloplasty catheter and a standard angiographic catheter in combination is described. The technique allowed enhanced visualization of the complex anatomy in three patients scheduled for surgical intervention.     

圆锥动脉干畸形与染色体22q11.2微缺失之间的关系

染色体22q11.2微缺失综合征患儿中约80％合并有先天性心血管畸形.研究发现,染色体22q11.2区内基因(TBX1、CRKL、ERK2)参与染色体22q11.2微缺失的发生.合并染色体22q11.2微缺失最常见的心血管畸形是圆锥动脉干畸形,包括法洛四联症、室间隔缺损型肺动脉闭锁、永存动脉干以及主动脉弓中断.主要表型...     

Aortic Arch Anomalies Associated with Chromosome 22q11 Deletion (CATCH 22)

Chromosome 22q11 deletion or CATCH 22 is associated with DiGeorge syndrome, conotruncal anomaly face syndrome, and velocardiofacial syndrome. Associated congenital heart diseases include tetralogy of Fallot, truncus arteriosus, and ventricular septal defect. Associated anomalies of the aortic arch, aortic branches, ductus arteriosus, and pulmonary arteries are more frequent in patients with the deletion than in those without the deletion. Associated anomalies include right aortic arch, cervical aorta, aberrant origin or isolation of the subclavian artery, the absence of the ductus arteriosus, major aortopulmonary collateral arteries, isolation of the left pulmonary artery, and vascular ring formed by the right aortic arch, retroesophageal aortic arch, and left descending aorta.     

肺动脉闭锁合并室间隔缺损104例诊断分析

目的　分析肺动脉闭锁合并室间隔缺损 (PA/VSD)的解剖类型及血流动力学改变 ,探讨其适宜的手术方式。方法　对 1992年 6月至 2 0 0 2年 5月在广东省心血管病研究所儿科住院的PA/VSD患儿共 10 4例 ,采用超声心动图结合心血管造影术 ,确定闭锁的部位、肺动脉的发育情况及血供来源。结果　右室流出道及瓣膜闭锁、有肺动脉总干 31例 ;肺动脉总干闭锁、左右肺动脉有汇合 5 0例 ;左肺动脉闭锁 10例 ,右肺动脉闭锁 8例 ;左右肺动脉均闭锁 5例。肺动脉的血供来源 :大的主肺动脉侧支血管 5 1例 ,动脉导管未闭 2 7例 ,多支小的侧支血管 2 6例。合并畸形有卵圆孔未闭、房间隔缺损、大动脉转位、完全性房室间隔缺损、右室双出口、镜面右位心、右旋心及左旋心。结论　合并室间隔缺损的肺动脉闭锁可发生在不同部位 ,肺动脉的血供来源多样化     

肺动脉闭锁合并室间隔缺损与大型主肺侧支动脉的外科治疗及研究进展

肺动脉闭锁合并室间隔缺损与大型主肺侧支动脉是一类少见的先天性心脏病.目前,随着外科治疗的不断进步以及对该疾病的更深入的认识,分期手术的治疗方案已经得到了越来越多外科医生的认同.     

Unifocalization and repair of pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries

Aim: To correlate anatomic and genetic features of paediatric patients with pulmonary atresia, ventricular septal defect (VSD) and multiple aortopulmonary collateral arteries with surgical outcome.
Methods: 44 consecutive patients aged 33±40 mo underwent either primary one-stage unifocalization ( n =32) or palliative right ventricular outflow tract reconstruction ( n =12) followed by secondary unifocalization and repair ( n =10) based on preoperative morphometric and functional evaluation of pulmonary blood sources. Chromosome 22q11.2 microdeletion occurred in 41% of cases. Combined VSD closure during one-stage procedures was guided by an intraoperative pulmonary flow study. Complete repair was accomplished in 35 cases (83%, 95% CI 72–95%). Variables examined included occurrence of confluent intrapericardial pulmonary arteries, central pulmonary arteries, confluent intraparenchymal pulmonary arteries, dominant collateral or pulmonary arteries, and chromosome 22q11.2 microdeletion. The sensitivity and specificity of the pulmonary flow study in predicting postoperative pulmonary haemodynamics were also tested.
Results: Eight-year actuarial survival and freedom from reoperation were 85% and 63%, respectively. Sensitivity and specificity of the pulmonary flow study were 94% and 100%, respectively. None of the anatomical variables examined was significantly related to the outcome of treatment. The only statistically relevant association was detected between survival and occurrence of 22q11.2 microdeletion ( p <0.003). Logistic analysis showed an increased likelihood of positive outcome in relation to first- ( p <0.02) or second-stage ( p <0.04) complete correction.
Conclusion: Morphology of pulmonary blood supply has no major impact on surgical outcome. Pulmonary flow study is a highly specific and sensitive intraoperative test. Chromosome 22q11.2 microdeletion remains the only variable significantly affecting survival.     

Unifocalization and repair of pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries

AIM: To correlate anatomic and genetic features of paediatric patients with pulmonary atresia, ventricular septal defect (VSD) and multiple aortopulmonary collateral arteries with surgical outcome. METHODS: 44 consecutive patients aged 33 +/- 40 mo underwent either primary one-stage unifocalization (n = 32) or palliative right ventricular outflow tract reconstruction (n = 12) followed by secondary unifocalization and repair (n = 10) based on preoperative morphometric and functional evaluation of pulmonary blood sources. Chromosome 22q11.2 microdeletion occurred in 41% of cases. Combined VSD closure during one-stage procedures was guided by an intraoperative pulmonary flow study. Complete repair was accomplished in 35 cases (83%, 95% CI 72-95%). Variables examined included occurrence of confluent intrapericardial pulmonary arteries, central pulmonary arteries, confluent intraparenchymal pulmonary arteries, dominant collateral or pulmonary arteries, and chromosome 22q11.2 microdeletion. The sensitivity and specificity of the pulmonary flow study in predicting postoperative pulmonary haemodynamics were also tested. RESULTS: Eight-year actuarial survival and freedom from reoperation were 85% and 63%, respectively. Sensitivity and specificity of the pulmonary flow study were 94% and 100%, respectively. None of the anatomical variables examined was significantly related to the outcome of treatment. The only statistically relevant association was detected between survival and occurrence of 22q11.2 microdeletion (p < 0.003). Logistic analysis showed an increased likelihood of positive outcome in relation to first- (p < 0.02) or second-stage (p < 0.04) complete correction. CONCLUSION: Morphology of pulmonary blood supply has no major impact on surgical outcome. Pulmonary flow study is a highly specific and sensitive intraoperative test. Chromosome 22q11.2 microdeletion remains the only variable significantly affecting survival.     

Outcome of pulmonary atresia and ventricular septal defect during infancy

We evaluated 54 patients with pulmonary atresia and ventricular septal defect who were referred during the first year of life between 1972 and 1992. Particular emphasis was given to the nature of the pulmonary blood supply and its influence on outcome. Ductal supply of confluent pulmonary arteries was present in 30 patients (55.6%, group I), whereas 24 patients (44.4%, group II) had a pulmonary blood supply that was entirely (31.4%) or predominantly (13.0%) dependent on systemic collateral arteries. Over the 20 years these was no significant difference in actuarial survival between the two groups. Corrective surgery was performed in 8 of 30 patients in group I (26.7%)-significantly more than in group II (4 of 24, 16.7%). Arborization abnormalities of the pulmonary arteries (stenosis of unbranched and intrapulmonary arteries) were almost exclusively present in patients with systemic collateral arteries (p<0.03), accounting for the lower probability of undergoing corrective surgery in group II patients. During the first decade of this study (1973–1983) corrective surgery was attempted in 9.6% of patients, with 42% mortality; and during the second decade (1983–1993) surgery was performed in 39.1% of patients, with 26% mortality, a significantly lower figure. Improving surgical results, complete preoperative demarcation of the pulmonary blood supply, and a more aggressive approach with early unifocalization of the pulmonary blood supply may invalidate comparison with retrospective data on the advisability of attempting to correct this anomaly. The present paper provides data against which treatment of infants with pulmonary atresia and ventricular septal defect presenting during the next decade can be compared.     

Imaging of aortopulmonary collateral arteries with high-resolution multidetector CT

Background Precise visualization of the pulmonary vasculature is mandatory for adequate treatment of patients with pulmonary atresia and ventricular septal defect (PA-VSD). Aortopulmonary collateral arteries (APCs) can be visualized by selective injections of contrast agent in the catheterization laboratory.Objective To evaluate multidetector CT (MDCT) and different image postprocessing methods for analysis of complex pulmonary blood supply in patients with PA-VSD.Materials and methods Eight patients (6 weeks to 27.8 years of age) with PA-VSD and APCs underwent MDCT and cardiac catheterization. Using multiplanar reformatting, volume rendering and semiautomatic segmentation algorithms, the aorta, pulmonary arteries and APCs were displayed. MDCT and cardiac catheterization were analyzed by two independent observers.Results MDCT accurately imaged central pulmonary arteries (n=8), aortopulmonary shunts (n=2), right ventricular to pulmonary artery conduits (n=2) and origin, course and intrapulmonary connections of APCs (n=25), compared to X-ray angiography. A high correlation was found between the MDCT vessel diameter measurements by two independent observers (n=70, r=0.96, P<0.01) and between MDCT and angiographic vessel diameter measurements (n=68, r=0.96, P<0.01).Conclusions Using three-dimensional imaging software, a complex pulmonary blood supply can be non-invasively and accurately imaged with high-resolution MDCT. This technique may help to reduce the number of cardiac catheterizations or guide interventional or surgical therapy.Electronic supplementary material Supplementary material is available for this article at     

Pulmonary Atresia with Intact Ventricular Septum and Major Aortopulmonary Collaterals: Association with Deletion 22q11.2

We describe the first association of pulmonary atresia, intact ventricular septum, and absent central pulmonary arteries with deletion 22q11.2. The pulmonary blood flow was derived from major aortopulmonary collaterals. The role of the deletion in pulmonary arborization is discussed.     

不伴体-肺动脉侧支和动脉导管未闭的婴幼儿肺血减少型复杂先天性心脏病的肺组织病理改变

目的：婴幼儿肺发育过程中,肺循环血量的改变影响肺外周血管的发育,导致肺组织的结构出现病理性改变。该研究利用形态半定量分析方法,了解不伴体-肺动脉侧支和动脉导管未闭的肺血减少型复杂先天性心脏病的婴幼儿肺细小动脉和肺泡间质的病理改变特点。方法选择有肺组织病理切片资料的56例婴幼儿不伴体-肺动脉侧支和动脉导管未闭的肺血减少型复杂先心病患儿作为病变组,年龄4～36月,包括法洛四联症34例和合并肺动脉狭窄的右室双出口7例、单心室9例、三尖瓣闭锁4例和完全性心内膜垫缺损2例。5例年龄4～18月非心、肺源性疾病死亡的婴幼儿作为对照组。采用显微镜形态半定量分析技术测量肺细小动脉内、外弹力板间距,计算平均中膜厚度百分比（MT%）和中膜面积百分比（MS%）,单位面积肺细小动脉数目（APSC）,单位面积肺泡数（MAN）,平均肺泡内衬间隔(MLI),肺实质占同切片肺总面积比例(PPA%)和单位面积肺泡数/肺细小动脉数比（AAR）。结果：先心病组的MT%,MS%,APSC和MAN降低,肺细小动脉内弹力板间距、AAR和MLI升高,与对照组比较差异有显著性,其余参数差异没有显著性。先心病组多数肺细小动脉形状不规则。结论：不伴体-肺动脉侧支和动脉导管未闭的肺血减少型复杂先心病的婴幼儿外周肺细小动脉中膜变薄、管腔扩张,单位面积肺细小动脉数目和单位面积肺泡数目减少,肺泡内径增大。     

Różne postaci zespołu Fallota – aspekty morfologiczne diagnostyki i terapii wady

Tetralogy of Fallot (ToF) is a congenital heart defect caused by antero-cephalad deviation of the insertion of the muscular outlet septum. Because of the abnormal position of the outlet septum, specific phenotypic combination is observed: right ventricle outflow tract obstruction, ventricular septal defect, biventricular origin of the overriding aorta and secondary right ventricular hypertrophy. The degree of outlet septum deviation determines the type of tetralogy – from discreet right ventricle outflow tract obstruction with no clinical significance to pulmonary atresia with hypotrophy of the pulmonary trunk and arteries. The decreased pulmonary flow causes the major aorta-to-pulmonary collateral arteries formation. They arise from descending aorta mainly as the bronchial arteries and feed different segments of the lungs. One of the most problematic type of ToF is absent pulmonary valve syndrome coexisting with the absence of the ductus arteriosus. The abnormalities of the leaflets of the pulmonary valves results in wideness of the pulmonary arteries and secondary bronchial and oesophageal destruction. The coronary arteries anomalies are well-known as associated to abnormal outflow tract rotation in ToF. It is of great importance in surgical correction of the malformation. The septal defects are the most common heart anomalies associated to ToF, but other ones are also observed. In those cases we have to remember about possibility of chromosomal aberration co-existing that the Down syndrome and chromosome 22^nd microdeletion are most common. ToF is also known as a component of the visceral heterotaxy syndromes.     

Aortic Valvar Atresia, Interrupted Aortic Arch, and Quadricuspid Pulmonary Valve: A Rare Combination

Aortic atresia and interrupted aortic arch is a rare cardiac combination. Review of the literature revealed nine cases. We present two patients with this combination and the additional finding of quadricuspid pulmonary valves, one of which was severely stenotic. In the latter patient, an aortopulmonary window was present. The other had a unique blood supply to the brachiocephalic arteries and ascending aorta from systemic collateral arteries. To the best of our knowledge, the association of a quadricuspid pulmonary valve with this combination has not been previously reported.     

Unusual Differential Diagnosis of Common Arterial Trunk

Common arterial trunk is relatively a straightforward diagnosis on echocardiography. We describe a neonate who was referred to our centre as a case of common arterial trunk but on evaluation was found to have pulmonary atresia with ventricular septal defect and aortopulmonary window, for which he underwent repair with Barbero-Marcial technique. These two conditions differ anatomically and embryologically, and careful echocardiographic evaluation will help in diagnosis and appropriate management.     

Surgical Repair for D-Transposition of the Great Arteries Associated With an Aortopulmonary Window Using the Fenestrated Ventricular Septal Defect Patch as a Safety Adjunct

Transposition of the great arteries with a ventricular septal defect and an associated aortopulmonary window is a rare anatomic combination having a high risk for pulmonary hypertension. Arterial switch with closure of the ventricular septal defect and repair of the aortopulmonary window is the procedure of choice, but a postoperative pulmonary hypertensive crisis is a common occurrence associated with significant morbidity and mortality. This report describes one case of such an anatomic lesion, which was repaired successfully with a fenestrated ventricular septal defect patch as an adjunct to decrease the risk of a postoperative pulmonary hypertensive crisis.     

Pulmonary Arteriography with Retrograde Injection of Contrast Medium via Radial Artery: Efficacy in Neonates with Ductus-Dependent Decreased Pulmonary Flow

In an attempt to visualize the pulmonary arterial trees of neonates and infants with ductus-dependent decreased pulmonary flow, the efficacy of retrograde injection of contrast from the radial arteries of 11 consecutive patients was tested. All patients had pulmonary atresia and patent ductus arteriosus. A 22- or 24-gauge needle was inserted into the radial artery and contrast medium of 2 ml/kg was injected at flow rates of 3 to 4 ml/sec. The pulmonary arteries were filled by retrograde flow through the ductus arteriosus. This method provided clear visualization of the pulmonary arteries, especially by ductus-sided injections. Developmental anomalies of the pulmonary trunk, localized stenosis at the ductus, and aortopulmonary collateral arteries were demonstrated. No complications occurred during angiography, and all the procedures were completed within 30 minutes. This method appears to be useful in detecting anatomical abnormalities of the pulmonary arteries in neonates and infants with ductus-dependent decreased pulmonary flow.     

Concomitant One-Stage Unifocalization and Bidirectional Glenn Procedure

A concomitant one-stage unifocalization and bidirectional Glenn procedure was performed in a patient with a functionally single ventricle, pulmonary atresia, and major aortopulmonary collateral arteries (MAPCAs). Reconstruction of the absent central pulmonary artery was achieved using the MAPCAs as well as the autologous pericardium. After 1 year, cineangiography and cardiac catheterization showed an excellent result: well-developed pulmonary arteries as well as low pressure in the superior vena cava. To the best of our knowledge, this is the first report of a successful concomitant one-stage unifocalization and bidirectional Glenn procedure.