G. Buheitel

Monosomy 22q11 in patients with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries

Objective To describe the morphology of the pulmonary arteries in patients with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries with and without monosomy 22q11. Design A retrospective analysis of all patients with this congenital heart defect who are being followed at the University Children’s Hospital Erlangen. Setting A tertiary referral centre for paediatric cardiology and paediatric cardiac surgery. Patients 21 patients with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries. Monosomy 22q11 was diagnosed by fluorescent in situ hybridisation using the D22S75 probe (Oncor). The morphology of the pulmonary arteries was assessed on the basis of selective angiograms. Results 10 patients (48%) were shown to have a microdeletion in 22q11 (group I). There was no difference with respect to the presence of confluent central pulmonary arteries between these patients (80%) and the remaining 11 patients (group II) without monosomy 22q11 (91%). Patients of group I, however, more often had arborisation anomalies of the pulmonary vascular bed (90% in group Iv 27% in group II). Because of the more severe abnormalities of the pulmonary arteries, a biventricular repair had not been possible in any of the children with monosomy 22q11, though repair had been carried out in 64% of the children in group II. Conclusions The developmental disturbance caused by monosomy 22q11 seems to impair the connection of the peripheral pulmonary artery segments to the central pulmonary arteries in patients with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries, resulting in a lower probability of biventricular repair.

Safety and efficacy of interventional occlusion of patent ductus arteriosus with detachable coils: a multicentre experience.

Abstract In order to define the safety and efficacy of Cook detachable coils for interventional closure of patent ductus arteriosus, we performed a retrospective analysis of all patients who underwent cardiac catheterization in seven centres for intended interventional occlusion of patent arterial duct. From January 1995 until March 1998, cardiac catheterization for intended interventional occlusion of patent arterial duct was performed in 317 consecutive children. Successful placement of at least one coil was achieved in 282 children (89%). The mean diameter of the ductus in children treated with Cook detachable coils was 1.65 mm, mean fluoroscopy time was 10.7 min. Occlusion rates were 62% 10 min after the procedure, 82% at the time of discharge, 91% at 4 months and 95% at late follow-up (2 years). In children with a ductus diameter of ≤ 2.5 mm the rate of successful coil deployment was 94% with a 98% occlusion rate at late follow-up. Complications occurred in 11 procedures (3.5%) including haemolysis (3 patients), embolization of a coil to the pulmonary artery (7 patients, 2.3%) and inability to release a coil (1 patient). Conclusion In our opinion, Cook detachable coils are safe and effective especially in the treatment of persistent ductus arteriosus with a diameter ≤ 2.5 mm. Due to the low costs these coils appear to be superior to other devices in this subgroup of patients.

Circumscribed intestinal protein loss with deficiency in CD4+ lymphocytes after the Fontan procedure

Abstract Protein-losing enteropathy is an important complication after right heart bypass operations (Fontan procedure). Laboratory examinations usually reveal hypoalbuminaemia, hypoproteinaemia, elevated α1-antitrypsin clearance, and lymphocytopenia. A case of protein-losing enteropathy after Fontan procedure is reported with a circumscribed protein loss in the region of the terminal ileum despite good haemodynamics. The patient developed only mild hypoalbuminaemia and no diarrhoea but severe cellular and humoral immune abnormalities, namely a markedly decreased proportion of CD4+ lymphocytes but normal proportion of CD8+ lymphocytes (CD4+ 14%, CD8+ 23%) and decreased serum levels of immunoglobulin G. Intestinal biopsies revealed normal mucosa. This report is unique as it is the first to describe a ratio of CD4+ to CD8+ lymphocytes <1 due to an almost selective loss of CD4+ lymphocytes and a circumscribed intestinal protein loss in a patient who developed protein-losing enteropathy after Fontan operation. Conclusion There is a severe decrease of CD4+ lymphocytes of unknown origin in a patient with circumscribed intestinal protein loss after Fontan operation. Passive leakage of lymph fluid due to abnormal systemic venous pressure is not a sufficient explanation of the almost selective loss of CD4+ lymphocytes. Primary or secondary activation of the immune system may influence structural integrity and permeability of the intestinal wall and may play a triggering role in protein-losing enteropathy after the Fontan procedure.

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

Abstract 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 Fishers 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.

Fortschritte beim interventionellen Verschluss des persistierenden Ductus arteriosus: Vergleich der Ergebnisse mit unterschiedlichen Verschlusssystemen

This report describes our results with transcatheter closure of patent ductus arteriosus between March 1993 and May 2000 including our early experience with the Amplatzer duct occluder. One hundred and sixty-six consecutive procedures were performed in 160 patients. The mean age was 6.8 years (range 0.8 to 26.2), mean weight 24.3 kg (range 7.7 to 84.0). Single or multiple coils were implanted successfully in 114 cases, a Rashind double umbrella in 35 patients, and an Amplatzer duct occluder in 16 patients. After failure to implant coils in one patient, a second attempt with a Rashkind double umbrella was successful. Complete closure of the patent ductus arteriosus was achieved in a total of 148 patients (92.5%), mean fluoroscopy time was 13.7 min (range 3.1 to 126 min). In 144 patients (90.0%), occlusion without residual shunting was achieved by the first interventional approach. Angiography showed immediate closure in 44%, echocardiography within 48 h revealed complete closure in additional 28%. In a further 18%, a residual shunt disappeared spontaneously in the following months. In five patients a second procedure was performed to terminate residual shunting after placement of a Rashkind occluder system by coils. In three patients, the residual shunt resolved. In 12 patients (7.5%) echocardiography showed a residual shunt 2–1259 days after interventional approach. Occlusion rates of the different devices were 83% for the Rashkind occluder, 92% for detachable coils, and 100% for the Amplatzer duct occluder. Coil embolisation into the pulmonary artery occured in two patients, interventional removal was successful in one of them. There were no further complications.    According to our experience interventional occlusion of patent ductus arteriosus is highly effective and associated with a low complication rate. Transcatheter closure using the Amplatzer duct occluder seems to be safe and effective also in small children with a body weight of 8 kg and a large ductus diameter. Compared to the total group of patients, the occlusion rate of the Amplatzer duct occluder was significantly higher (p=0.005), and of the Rashkind occluder system significantly lower (p=0.026). Therefore, we recommend the use of detachable coils in patients with small ductus (diameter ≤2mm) and the Amplatzer duct occluder in those with a larger ductus. Transcatheter closure of the patent ductus arteriosus according to this regimen should achieve occlusion rates above 95%. Zwischen 3/1993 und 5/2000 führten wir bei 160 Patienten zwischen 0,8 und 26,2 Jahren 166 Interventionen zum Verschluss eines persistierenden Ductus arteriosus durch. 115 Interventionen wurden mit Metallspiralen, 35 mit einem Rashkind-Okkluder-System und 16 mit einem Amplatzer-Ductokkluder-System durchgeführt. Bei insgesamt 148 Patienten (92,5%) gelang der restshuntfreie Verschluss des Ductus arteriosus, bei 144 Patienten (90,0%) konnte der Ductus mit einer Intervention komplett verschlossen werden.    Bei 12 Patienten (7,5%) ist 2–1259 Tage nach der Intervention echokardiographisch noch ein Restshunt nachweisbar. Ein kompletter Verschluss mit dem Rashkind-Okkluder-System allein gelang bei 83%, mit einer oder mehreren Metallspiralen in 92% der Fälle. Bei allen 16 Patienten mit Amplatzer-Ductokkluder-System gelang ein kompletter Verschluss. Schwere Komplikationen traten nicht auf, in 2 Fällen kam es zu einer Embolisation von Metallspiralen in die Pulmonalgefäße. Die Verschlussrate des Amplatzer-Ductokkluder-Systems (100% nach 2 Tagen) war signifikant besser (p=0,005) und die des Rashkind-Ductokkluder-Systems (81% nach 2 Jahren) signifikant schlechter (p=0,026) als die des Gesamtkollektivs.    Der interventionelle Verschluss des persistierenden Ductus arteriosus stellt eine komplikationsarme Behandlungsmethode mit hoher Erfolgsrate dar. Mit dem Amplatzer-Ductokkluder steht auch für Kinder mit einem Körpergewicht von 8 kg und relativ großem Ductus ein sicheres Verschlusssystem zur Verfügung. Durch eine differenzierte interventionelle Therapie lassen sich weitere Verbesserungen der Verschlussraten auf über 95% erzielen. Für Patienten mit einem minimalen Ductusdiameter ≤2mm empfehlen wir die Verwendung von replazierbaren Metallspiralen, für größere Ductus das Amplatzer-Okkluder-System.

Search for somatic 22q11.2 deletions in patients with conotruncal heart defects

A wide range of clinical variability in patients with 22q11.2 deletions has been demonstrated in numerous studies. Nevertheless, it is still an open question if major genetic factors contribute to clinical expression. Therefore one aim of this study was to investigate, if patients with 22q11.2 deletion and conotruncal heart defects show a “second hit” somatic 22q11.2 deletion in tissue from the conotruncus, heart vessels or thymus. The second aim was to analyse patients with conotruncal heart defects without 22q11.2 deletion in blood cells for somatic deletion mosaicism. We were able to study tissue samples from heart surgery from 23 patients, 9 of whom had 22q11 deletions by FISH analysis on metaphase spreads from peripheral lymphocytes. Analysis of 18 polymorphic markers from the 22q11.2 region in DNA prepared from thymus and/or heart vessels and/or conotruncus tissue and peripheral lymphocytes in each patient did not show any allelic loss. Thus somatic 22q11.2 deletions apparently do not play a major role in conotruncal heart defects in patients with or without germ line 22q11.2 deletion.

Balloon dilatation of critical left heart stenoses in low birthweight infants

We describe the results of balloon angioplasty in 5 infants with body weights of 850‐2400 g. Three patients with severe aortic valve stenosis and two patients with isthmic coarctation of the aorta experienced relief of stenosis. Two patients with aortic valve stenosis developed thrombosis of the femoral artery; however, complete resolution of the compromised pulse occurred following thrombolytic therapy. In both patients with isthmic coarctation, pulses on the right leg remained diminished. All patients are doing well 0.28 to 3.32 y after the procedure; none has required additional therapy. Our results in a limited number of consecutive low birthweight infants show that balloon dilatation is feasible and can be performed successfully even in neonates with body weights <1500g. According to our experience, balloon dilatation in infants with body weights >2000 g does not differ significantly from standard procedures. In very small infants, however, balloon angioplasty requires special precautions to avoid temperature loss. Arterial access is the major problem in small children, and requires further improvement.

Spätpostoperative Herzrhythmusstörungen nach totaler cavopulmonaler Anastomose und ihre Beziehung zum Operationsalter der Patienten

Late postoperative arrhythmias are a common problem associated with significant morbidity following Fontan operations. We analyzed in our patients whether age at the time of a modified Fontan procedure (total cavopulmonary connection) has an influence on the frequency of late postoperative arrhythmias.¶   We examined all 66 long-term surviving patients who underwent a total cavopulmonary connection (TCPC) in our center during a nine year period. At the time of TCPC, 31 children were younger (group I) and 35 children were older than 4years (group II). The follow-up period was almost identical in both groups (group I: 4.29 years, group II: 4.52 years). We evaluated all ecgs performed at maximum intervals of 6 months and all Holter ecgs performed at intervals of 12 months.¶   Atrial tachyarrhythmias (supraventricular tachycardias, atrial flutter) were registered in six patients (9%). All of these patients belonged to group II (17%). Ventricular arrhythmias (couplets, ventricular tachycardia) were found in 3% of the younger and 17% of the older patients. Abnormalities of sinus node function were registered in equal frequency in younger and older children (group I: 35%, group II: 31%), while pauses with a duration of >2s where present only in older children (group II: 14%). Pacemaker implantation or antiarrhythmic therapy became necessary in 10/66 patients (15%) affecting none of the children who underwent the TCPC <4 years (group I) but 10/35 children (group II) who underwent the TCPC at an older age (29%).¶   According to our findings in the medium-term follow-up after TCPC, atrial tachyarrhythmias and complex ventricular arrhythmias are registered less frequently in children who underwent the modified Fontan procedure at an age of less than 4years. Although further studies will have to show whether these differences persist in the long-term follow-up, these findings represent an additional argument for the elective performance of modified Fontan operations at an age of less than 4 years. Spätpostoperative Herzrhythmusstörungen haben wesentlichen Anteil an der Morbidität im Langzeitverlauf nach Fontan-Operationen. Wir untersuchten in unserem Krankengut, ob das Alter zum Zeitpunkt einer modifizierten Fontan-Operation (totale cavopulmonale Anastomose) einen Einfluss hat auf die Häufigkeit spätpostoperativer Dysrhythmien.¶   Erfasst wurden alle 66 langzeitüberlebenden Patienten, bei denen in einem Zeitraum von 9 Jahren in unserem Zentrum eine totale cavopulmonale Anastomose (TCPC) durchgeführt worden war. 31 Kinder waren zum Zeitpunkt der TCPC jünger (Gruppe I), 35 älter als 4Jahre (Gruppe II). Der Nachbeobachtungszeitraum beider Gruppen war nahezu identisch (Gruppe I: 4,29Jahre, Gruppe II: 4,52 Jahre). Ausgewertet wurden sämtliche EKGs, die postoperativ in Abständen von maximal 6 Monaten und alle Langzeit-EKGs, die im Abstand von 12 Monaten erfolgten.¶   Tachykarde atriale Rhythmusstörungen (supraventrikuläre Tachykardien, Vorhofflattern) traten bei 6 Patienten (9%) auf. Dies betraf keines der Kinder in Gruppe I und 17% der Kinder in Gruppe II. Ventrikuläre Arrhythmien (Couplets, Salven) fanden sich bei 3% der jüngeren und 17% der älteren Patienten. Auffälligkeiten der Sinusknotenfunktion bestanden in gleicher Häufigkeit bei jüngeren und älteren Patienten (Gruppe I: 35%, Gruppe II: 31%), Pausen mit einer Dauer von >2 Sekunden zeigten jedoch ausschließlich ältere Kinder (Gruppe II: 14%). Eine Schrittmacherimplantation oder eine medikamentöse antiarrhythmische Therapie wurde bei 10/66 Pat. (15%) notwendig. Dies betraf kein Kind mit Anlage einer TCPC vor dem Alter von 4 Jahren (Gruppe I), jedoch 10/35 Patienten bei denen die TCPC später erfolgte (GruppeII: 29%).¶   Aufgrund unserer Ergebnisse finden sich im mittelfristigen Verlauf nach TCPC bei Kindern mit einem OP-Alter <4 Jahre weniger tachykarde atriale und ventrikuläre Herzrhythmusstörungen als bei Kindern mit höherem Op-Alter. Obwohl abzuwarten bleibt, ob diese Unterschiede auch im Langzeitverlauf erhalten bleiben, sprechen diese Ergebnisse für die elektive Durchführung der Operation vor dem Alter von 4 Jahren.

Aortic Root Abscess Complicated by Fistulization and Intracerebral Hemorrhagic Infarction

We report an unusual case of a 12-year-old male with aortic root abscess complicated by fistulization and intracerebral hemorrhagic infarction. Transesophageal echocardiography provided exact information about the location and dimension. Color-flow mapping demonstrated fistulous communication between the abscess and both the aorta and the left ventricle, causing severe diastolic regurgitation through the paravalvular leak. Pulmonary autograft aortic root replacement was performed with good result.

Die Ballondilatation der Pulmonalklappe Kurz-, mittel- und langfristige Ergebnisse

Background Immediate and long-term results after balloon dilatation of pulmonary valve stenosis in our unit. Methods and patients All 111 patients (1 day–18 years) who have had balloon dilatation of a pulmonary valvar stenosis between 12/1987 and 8/1997 were divided into 4 groups: Typical valvar pulmonary stenosis (group A; n=78), stenosis with dysplastic pulmonary valve (group B; n=10), critical pulmonary stenosis (group C; n=16) and pulmonary atresia after transcatheter or operative opening of the valve (group D; n=7). Patients with pulmonary stenosis and complex congenital heart disease were excluded. Results The average systolic transvalvular gradient was reduced from 68.5 to 27.2mmHg (60%) immediately after balloon dilatation. After a follow up of 48.8±37 months 101 patients could be reevaluated. In group A (n=69 at FU) and C (n=16 at FU) 81% showed a systolic transvalvular gradient <30mmHg after one and 83% (A) respective 94% (C) after two balloon dilatations. In group B (n=9 at FU) 44% exhibited a systolic gradient <30mmHg after one and 56% after two balloon dilatations. In group D (n=7 at FU) 57% showed a systolic gradient <30mmHg with no further improvement by a second dilatation. Over all, 80% of our patients could be treated sufficiently by transcatheter means. The rate of major complications was 7.3% with no lasting residuals at follow up and no deaths. Conclusion Balloon dilatation of the pulmonary valve is secure and effective. Best results are obtained in patients with typical pulmonary valve stenosis and in newborns and infants with critical pulmonary valve stenosis. Fragestellung Unmittelbare Ergebnisse und Langzeitverlauf nach Ballondilatation einer Pulmonalklappenstenose in unserer Klinik. Methode und Patienten Alle 111 Patienten (1 Tag bis 18 Jahre), die sich zwischen 12/1987 und 8/1997 einer Ballondilatation der Pulmonalklappe unterzogen, wurden in 4 Gruppen eingeteilt: Typische valvuläre Pulmonalstenose (Gruppe A; n=78), dysplastische Pulmonalklappe mit Stenose (Gruppe B; n=10), kritische Pulmonalklappenstenose (Gruppe C; n=16) und Pulmonalklappenatresie nach interventioneller oder operativer Eröffnung der Klappe (Gruppe D; n=7). Patienten mit Pulmonalstenose in Verbindung mit einem komplexen Herzfehler wurden ausgeschlossen. Ergebnisse Der mittlere systolische transvalvuläre Gradient wurde von 68,5 auf 27,2mmHg (60%) unmittelbar nach der Dilatation reduziert. Nach einer Nachbeobachtungszeit von 48,8±37 Monaten wurden 101 Patienten nachuntersucht. In Gruppe A (n=69 bei NU) und C (n=16 bei NU) zeigten je 81% einen systolischen transvalvulären Gradienten unter 30mmHg nach einer und 83% (A) bzw. 94% (C) nach zwei Ballondilatationen. In Gruppe B (n=9 bei NU) wiesen 44% einen systolischen Gradienten unter 30mmHg nach einer und 56% nach zwei Ballondilatationen auf. In Gruppe D (n=7 bei NU) zeigten 57% einen systolischen Gradienten unter 30mmHg, ohne weitere Verbesserung durch eine 2. Dilatation. Insgesamt konnten 80% unserer Patienten ausreichend durch interventionelle Maßnahmen behandelt werden. Die Rate an ernsten Komplikationen lag bei 7,3%, die alle bei der Nachuntersuchung keine dauerhaften Schäden hinterlassen hatten. Es traten keine Todesfälle auf. Schlussfolgerung Die Ballondilatation der Pulmonalklappe ist sicher und effektiv. Die besten Ergebnisse werden bei Patienten mit typischer valvulärer Pulmonalstenose und bei Neugeborenen und Säuglingen mit kritischer Pulmonalstenose erreicht.