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     

Diagnosis and treatment of pulmonary atresia and ventricular septal defect

Surgical repair of the intracardiac anatomy in patients with pulmonary atresia and ventricular septal defect can be performed today with a low operative mortality. Diagnostic and therapeutic problems in these patients are almost exclusively related to the nature of collateral lung perfusion and associated anomalies of the pulmonary vascular bed. These anomalies are frequently found in patients with major aortopulmonary collateral arteries and include multifocal pulmonary blood supply, hypoplasia, stenosis, or arborization anomalies of the pulmonary arteries. Diagnostic methods must focus on an exact identification of the collateral pulmonary blood supply, the presence and size of central pulmonary arteries, and the connections of the arterial segments. Recent genetic studies have shown that monosomy 22q11.2 is found in 25–32% of children with pulmonary atresia and ventricular septal defect. This microdeletion is significantly more frequent in patients with major aortopulmonary collateral arteries and it seems to be associated with a higher percentage of pulmonary arterial anomalies. During recent years, efforts have concentrated on earlier treatment of patients with pulmonary atresia with ventricular septal defect with combined catheter and surgical interventions. Early establishment of antegrade flow to the central pulmonary arteries stimulates growth of the pulmonary arteries, optimizes the angiographic diagnosis of abnormalities of the pulmonary vascular bed, and allows for the possibility of balloon angioplasty or stenting of the central pulmonary arteries.     

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     

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.     

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.     

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.     

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.     

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。     

Pulmonary arterial changes in patients with ventricular septal defects and severe pulmonary hypertension

Summary In 25 patients, aged eight months to 31 years, with ventricular septal defect (VSD; isolated in 15, the others with atrial septal defect, PDA, coarctation or patent ductus arteriosus + coarctation), each with severe pulmonary artery hypertension (pulmonary artery systolic pressure [Ppa] at least 75% of systemic and an elevated pulmonary vascular resistance), we related morphologic and morphometric data from open-lung biopsy to hemodynamic measurements obtained at cardiac catheterization during the same hospital admission. Of the hemodynamic features measured, only the ratios of pulmonary-to-systemic flow and pulmonary-to-systemic resistance correlated significantly with structure. Neither pulmonary artery pressure (Ppa) nor pulmonary vascular resistance correlated significantly with any structural feature studied. The increased external diameter of respiratory bronchiolar arteries in those with the more advanced Heath-Edwards grades reflects dilatation and suggests that it is in the small arteries of the distal arterial bed that the changes of pulmonary hypertension are most significant. Neither age nor body weight correlated significantly with the degree of structural or hemodynamic abnormality. In the ten patients who underwent VSD closure, Ppa was measured postoperatively. The Heath-Edwards grade (no more than one grade-III lesion) and arterial density (at least one-half that normal for age) were the best correlates of the difference between preoperative Ppa and Ppa immediately after corrective surgery. The presurgical catheterization data, including pulmonary resistance and the resistance ratio, did not correlate significantly with change in Ppa following VSD closure. Lung biopsy is an important diagnostic aid because it helps in predicting the early response in postoperative Ppa in patients with VSD and elevated pulmonary vascular resistance.     

An overview of pulmonary atresia, ventricular septal defect, and multiple aorta pulmonary collateral arteries

The management of infants and children with pulmonary atresia, ventricular septal defect, and multiple aorta pulmonary collateral arteries has proven to be challenging. Therapeutic approaches have included unifocalization, shunting, coiling of collateral vessels, and heart/lung transplantation. Results have been variable and frustrating. This review will cover the anatomy, physiology, initial medical management, subsequent surgical management, and controversies surrounding various therapeutic approaches. The evolving understanding of genetic considerations in this condition will also be explored.     

Pulmonary hypertension in patients with complete transposition of the great arteries: Midterm results after surgery

Postoperative results of surgical repair of complete transposition of the great arteries (TGA) with pulmonary hypertension (PH) in 19 patients in whom mean pulmonary arterial pressure was >50 mmHg or the pulmonary/systemic arterial pressure ratio was >0.8 were examined. TGA with intact ventricular septum was diagnosed in 10 patients and TGA with ventricular septal defect in 9. At the time of corrective surgery (arterial switch 10, atrial switch 9), patients ranged in age from 7 months to 14 years (mean 2.4 years). Seventeen patients (89%) survived with New York Heart Association functional class I. Seven patients in whom calculated pulmonary vascular resistance was 10–20 U · m² after surgery survived with subsequent regression of PH. Residual PH was diagnosed in 36% of survivors. Two patients in whom pulmonary vascular resistance was 26 and 36 U · m², respectively, died after surgery. In patients with TGA, severe PH was not necessarily fatal and was potentially reversible after successful surgery.     

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     

Stenting of Bilateral Arterial Ducts in Complex Congenital Heart Disease

Bilateral arterial ducts serving nonconfluent pulmonary arteries is a very rare pattern of pulmonary blood flow in congenital heart disease with pulmonary atresia. In this setting, neonatal ductal closure might result in abrupt pulmonary hypoperfusion and life-threatening systemic hypoxia, thereby indicating emergent surgical palliation or repair. However, percutaneous arterial duct stenting might be an alternative to surgery, especially in high-risk patients. This article reports on two critical neonates with complex heart disease and discontinuous pulmonary arteries dependent on bilateral arterial ducts who successfully underwent transcatheter ductal stenting as first-step palliation toward lower-risk corrective surgery.     

Chronic Outpatient Sildenafil Therapy for Pulmonary Hypertension in a Child After Cardiac Surgery

We report the case of a 14-month-old male with d-transposition of the great arteries, ventricular septal defect, and pulmonary hypertension successfully treated with long-term sildenafil following cardiac surgery. To our knowledge, this is the first published report of long-term sildenafil treatment in a child after corrective cardiac surgery.     

Pulmonary atresia and ventricular septal defect with coronary artery to pulmonary artery fistula: Case report and review of the literature

The pulmonary blood supply in patients with pulmonary atresia and ventricular septal defect is highly variable. Several cases have been reported in the literature in which a coronary artery to pulmonary artery fistula, alone or in combination with additional vessels, supplies the pulmonary circulation. We report a case of successful repair during early infancy, with unique hemodynamic, clinical, and anatomic features. The literature is reviewed.     

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.     

Necrotizing arteritis in uncorrected tetralogy of fallot with pulmonary atresia

Summary A 10-year-old girl with uncorrected tetralogy of Fallot with pulmonary atresia presented with fevers of unknown origin and left lung infiltrates. At autopsy, necrotizing vascular changes resembling those of severe pulmonary hypertension (grade VI in the Heath-Edwards classification) were confined to the left lung. Pulmonary blood flow and pressure were greater in the left lung and were provided by an enlarged collateral artery arising directly from the descending thoracic aorta. To our knowledge, this is the first report of necrotizing arteritis of the pulmonary arteries in uncorrected tetralogy of Fallot with pulmonary atresia.The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or reflecting the views of the Department of the Army or the Department of Defense.     

Balloon Atrial Septostomy Under Two-Dimensional Echocardiographic Control: A New Outlook

Between January 1989 and February 1995 a group of 47 consecutive infants aged 31–180 days (mean 83.5 ± 48.8 days) with various cyanotic heart diseases and poor intracardiac mixing underwent balloon atrial septostomy (BAS) under two-dimensional (2D) echocardiographic control in the procedure room or intensive care unit. Diagnoses were 27 cases of transposition of the great arteries (TGA), 1 mitral atresia, 9 tricuspid atresia, 7 critical pulmonary stenosis with hypoplastic right ventricle, 3 pulmonary atresia with intact interventricular septum, and 1 total anomalous pulmonary venous return. A standard subcostal view was used mainly to delineate the interatrial septum and to guide the balloon catheter. The creating (tearing) of the atrial septal defect was seen clearly during the procedure, and the 2D echocardiographic imaging was helpful for assessing the adequacy of the BAS at the end of the procedure. The results were good (5–9 mm in diameter) with no significant complications. The 2D echocardiographic scans showed no significant changes in the created atrial hole sizes during the follow-up of 1–6 months. We conclude that BAS under 2D echocardiographic control can be performed successfully and safely in infants with cyanotic congenital heart disease up to 6 months of age. This method should be considered for palliation, avoidance of surgery, or allowing the patient to survive until an appropriate time for corrective surgery.     

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.