Renate Kaulitz

Comprehensive genotype–phenotype analysis in 230 patients with tetralogy of Fallot

Background Tetralogy of Fallot (ToF), the most frequent cyanotic congenital heart disease, is associated with a wide range of intra- and extracardiac phenotypes. In order to get further insight into genotype–phenotype correlation, a large cohort of 230 unselected patients with ToF was comprehensively investigated. Methods and results 230 patients with ToF were studied by karyotyping, comprehensive 22q11.2 deletion testing and sequencing of TBX1, NKX2.5 and JAG1, as well as molecular karyotyping in selected patients. Pathogenic genetic aberrations were found in 42 patients (18%), with 22q11.2 deletion as the most common diagnosis (7.4%), followed by trisomy 21 (5.2%) and other chromosomal aberrations or submicroscopic copy number changes (3%). Mutations in JAG1 were detected in three patients with Alagille syndrome (1.3%), while NKX2.5 mutations were seen in two patients with non-syndromic ToF (0.9%). One patient showed a recurrent polyalanine stretch elongation within TBX1 which represents a true mutation resulting in loss of transcriptional activity due to cytoplasmatic protein aggregation. Conclusion This study shows that 22q11.2 deletion represents the most common known cause of ToF, and that the associated cardiac phenotype is distinct for obstruction of the proximal pulmonary artery, hypoplastic central pulmonary arteries and subclavian artery anomalies. Atrioventricular septal defect associated with ToF is very suggestive of trisomy 21 and almost excludes 22q11.2 deletion. We report a further patient with a recurrent polyalanine stretch elongation within TBX1 and for the first time link TBX1 cytoplasmatic protein aggregation to congenital heart defects.

Fontan-type procedures: residual lesions and late interventions

BACKGROUND The purpose of this study was to determine the type and incidence of hemodynamic and electrophysiological abnormalities requiring surgical or catheter-based interventions in a single-center long-term experience. METHODS Eighty-eight patients with a follow-up of at least 5 years (mean follow-up, 9.6 +/- 2.6 years) after Fontan-type procedures were included. All patients had undergone cardiac catheterization either as part of the regular postoperative protocol or because of symptomatic atrial tachycardia or increasing cyanosis. RESULTS Freedom from reoperation for up to 5 years was documented for 82% of patients and decreased to 76% after 8 years. Late reoperations included conversion of an atriopulmonary anastomosis to a total cavopulmonary anastomosis in 2 patients with atrial dysrhythmia and implantation of an extracardiac conduit in 1 patient with left atrial isomerism and intrapulmonary arteriovenous malformations after a Kawashima operation. Decline in sinus node function with symptomatic bradycardia required pacemaker therapy in 10 patients (11%). Transcatheter interventions included fenestration occlusion in 5 of the 11 patients with initial baffle fenestration. In 6 of 17 patients with aortopulmonary collaterals, coil occlusion was indicated to reduce future systemic ventricular volume load. Various systemic venous collaterals were documented in 11 patients and required coil occlusion in 2. One patient with symptomatic protein-losing enteropathy underwent transcatheter fenestration creation without sustained relief of symptoms. Freedom from transcatheter interventions decreased from 94% to 82% after 5 and 10 years, respectively. CONCLUSIONS During long-term follow-up, reoperations are rare and mainly involve Fontan conversion to either a lateral-tunnel or extracardiac-conduit procedure. Detailed angiographic evaluation on a routine basis allows identification of the vascular sites of origin of aortopulmonary collateral vessels and systemic venous collaterals potentially developing during long-term follow-up. Transcatheter interventions including fenestration occlusion and occlusion of venous collaterals and aortopulmonary collaterals were performed to maintain and improve the Fontan circulation in clinically symptomatic and asymptomatic patients. During long-term follow-up after Fontan-type operations, a regular postoperative cardiac catheterization protocol is recommended.

Open heart surgery immediately after birth following prenatal diagnosis of a large right pulmonary artery to left atrium communication.

A 24-year-old gravida II para I was referred at 37 + 4 weeks of pregnancy for prenatal ultrasound because of fetal cardiomegaly. The second trimester scanning was reported as normal. High resolution ultrasound (HDI 5000, ATL, Zipf, Austria, 5 to 7 MHz curved array) confirmed massive cardiomegaly with ventricular hypertrophy (apical wall thickness 11 mm; Figure 1a) and 100◦ left axis deviation. Mild regurgitation of the mitral and tricuspid valve was present. The left atrium showed an anomalous saccular aneurysm of about 12 mm in diameter. Color Doppler sonography demonstrated continuous turbulent flow in this area, directing toward the left atrium (Figure 1b). At atrial level a secundum atrial septal defect with left to right shunting was found. The main pulmonary artery was markedly dilated (21 mm, >95th percentile) and showed regurgitation with oscillating flow (Figure 1c). A right pulmonary artery (RPA) to left atrium (LA) fistula was diagnosed based on visualization of a large vessel (11 mm) originating from the pulmonary artery communicating with the aneurysmatic bulge of the left atrium (Figure 1d). The pulmonary veins appeared to drain normally into the LA. No other malformations were found. Further Doppler examination revealed absent end-diastolic flow in the umbilical artery and an abnormal flow in the ductus venosus but no other hemodynamic impairment signs. Two days later the situation deteriorated, as evidenced by a reverse flow in the ductus, increasing atrioventricular regurgitation and intermittent premature atrial contractions, so that delivery was planned. In view of the expected poor circulatory condition, an emergency cardiac surgical repair was scheduled in continuity with the cesarean section.

Recanalisation of bilateral superior vena cava after total cavopulmonary connection

Systemvenöse Kollateralgefäße werden häufig nach Glenn- oder modifizierter Fontan-Operation beobachtet. Therapie der Wahl zum Verschluss kleinkalibriger Gefäße ist die Embolisation mit Hilfe von replatzierbaren Metallspiralen. Etwas problematischer ist die Situation bei Patienten mit großen Kollateralen wie z. B. einer rekanalisierten bilateralen oberen Hohlvene. Wir berichten über zwei Patienten, bei denen mehrere Jahre nach Fontan-Operation bei zunehmender Zyanose eine rekanalisierte linke bzw. rechte obere Hohlvene diagnostiziert wurde. Bei beiden Patienten gelang der interventionelle Verschluss dieser großlumigen Venen mittels 8 mm Amplatzer®-Muscular-VSD-Occluder, die arteriellen Sauerstoffsättigungen stiegen bei beiden Patienten postinterventionell an. Der Verschluss rekanalisierter oberer Hohlvenen nach Fontan’scher Kreislauftrennung ist mittels Amplatzer®-Muscular-VSD-Occluder technisch ohne Probleme möglich. Um die erneute Formation von venovenösen Kollateralen zu vermeiden muss darauf geachtet werden, dass der Okkluder in die V. cava knapp unterhalb der Mündung der V. azygos/hemiazygos platziert wird. Formation of systemic to pulmonary venous or systemic venous left atrial collaterals frequently occurs in patients after Glenn or Fontan-type operations. Embolization with detachable metal coils is the therapy of choice for the closure of small vessels. These devices however are not appropriate for the occlusion of large collaterals, e. g. recanalised bilateral caval veins. We report two patients who presented late after Fontan-type operations with a gradual decrease in oxygen saturation due to recanalisation of bilateral caval veins. Interventional closure of these large veins was carried out successfully with the use of 8 mm Amplatzer® muscular VSD Occluders, resulting in an increase of arterial oxygen saturations. The closure of recanalised bilateral superior caval veins after Fontan procedures is possible without technical problems by means of the Amplatzer® muscular VSD Occluder. In order to avoid future formation of venous collaterals via the azygos or hemiazgos system, the occluder should be placed in the vena cava below the orifice of the azygos/ hemiazygos vein.

Recanalisation of bilateral superior vena cava after total cavopulmonary connection. Interventional occlusion with the Amplatzer VSD Occluder.

Systemvenöse Kollateralgefäße werden häufig nach Glenn- oder modifizierter Fontan-Operation beobachtet. Therapie der Wahl zum Verschluss kleinkalibriger Gefäße ist die Embolisation mit Hilfe von replatzierbaren Metallspiralen. Etwas problematischer ist die Situation bei Patienten mit großen Kollateralen wie z. B. einer rekanalisierten bilateralen oberen Hohlvene. Wir berichten über zwei Patienten, bei denen mehrere Jahre nach Fontan-Operation bei zunehmender Zyanose eine rekanalisierte linke bzw. rechte obere Hohlvene diagnostiziert wurde. Bei beiden Patienten gelang der interventionelle Verschluss dieser großlumigen Venen mittels 8 mm Amplatzer®-Muscular-VSD-Occluder, die arteriellen Sauerstoffsättigungen stiegen bei beiden Patienten postinterventionell an. Der Verschluss rekanalisierter oberer Hohlvenen nach Fontan’scher Kreislauftrennung ist mittels Amplatzer®-Muscular-VSD-Occluder technisch ohne Probleme möglich. Um die erneute Formation von venovenösen Kollateralen zu vermeiden muss darauf geachtet werden, dass der Okkluder in die V. cava knapp unterhalb der Mündung der V. azygos/hemiazygos platziert wird. Formation of systemic to pulmonary venous or systemic venous left atrial collaterals frequently occurs in patients after Glenn or Fontan-type operations. Embolization with detachable metal coils is the therapy of choice for the closure of small vessels. These devices however are not appropriate for the occlusion of large collaterals, e. g. recanalised bilateral caval veins. We report two patients who presented late after Fontan-type operations with a gradual decrease in oxygen saturation due to recanalisation of bilateral caval veins. Interventional closure of these large veins was carried out successfully with the use of 8 mm Amplatzer® muscular VSD Occluders, resulting in an increase of arterial oxygen saturations. The closure of recanalised bilateral superior caval veins after Fontan procedures is possible without technical problems by means of the Amplatzer® muscular VSD Occluder. In order to avoid future formation of venous collaterals via the azygos or hemiazgos system, the occluder should be placed in the vena cava below the orifice of the azygos/ hemiazygos vein.

Bacterial endocarditis of a recanalized Waterston-Cooley anastomosis - : Interventional transcatheter occlusion with an Amplatzer-ASD occluder

Dr. Claudia Ambrock · Dr. Rita Roller · Dr. Michael Schmelz Department of Internal Medicine Ermstalklinik Bad Urach, Germany Sirs: Prior to the era of primary surgical correction, treatment of patients with tetralogy of Fallot was performed according to a staged approach: Since surgical correction could not be performed in infancy with reasonable mortality, the majority of patients underwent palliative aortopulmonary shunt procedures in order to defer surgical correction into childhood. Following the pioneering work of Alfred Blalock and Helen Taussig in 1944 resulting in the inauguration of the Blalock-Taussig shunt, several different palliative aortopulmonary shunt procedures were introduced in the 1950s and 1960s. They include the Potts shunt connecting the descending aorta with the left pulmonary artery and the WaterstonCooley anastomosis, a central shunt with direct anastomosis between the posterior wall of the ascending aorta and the right pulmonary artery [1]. The Waterston-Cooley shunt was abandoned in the 1970s and 1980s because of its considerable disadvantages: Frequently excessive pulmonary blood flow from a large anastomosis resulted in congestive heart failure and pulmonary hypertension with consecutive development of pulmonary vascular disease. Furthermore in a considerable number of patients the Waterston-Cooley anastomosis was associated with distortion and obstruction of the right pulmonary artery at the site of anastomosis [2–6]. At the time of surgical correction aorto-pulmonary shunts are either ligated or transsected. Similar to surgical ligation of patent arterial ducts, which is associated with a risk of residual shunting of up to 18% [7] if the duct is not transsected, recanalization of an aortopulmonary shunt may occur in cases of surgical ligation. Recanalization of a Waterston-Cooley anastomosis results in an increased risk of bacterial endocarditis. In the underlying case report we report diagnosis and treatment of a patient following surgical correction of tetralogy of Fallot who developed bacterial endocarditis due to a clinically unrecognized recanalization of a Waterston-Cooley anastomosis.

Asymptomatisches Cor triatriatum bei einer 2¼ Jahre alten Patientin

We report on an asymptomatic 2 1/4 year old girl. Echocardiography revealed cor triatriatum with a membrane separating the left atrium. Transesophageal echocardiography demonstrated 3 large perforations of the intraatrial membrane. Using Doppler sonography, no pressure gradients across these orifices were identified. Obstruction of the intraatrial membrane and pulmonary hypertension were excluded by cardiac catheterization. We therefore decided against surgical resection of the membrane and to follow the patient noninvasively by echocardiography. Follow-up over 18 months revealed no development of an obstruction across the intraatrial membrane. Our case shows that immediate surgical correction is not necessary in all patients with cor triatriatum. Conservative management of these patients requires full evaluation of the hemodynamics and careful follow-up examinations by echocardiography. Wir berichten über ein 2¼ Jahre altes asymptomatisches Mädchen mit bislang unauffälliger Entwicklung. Echokardiographisch fand sich als Zufallsbefund ein Cor triatriatum. In der transösophagealen Echokardiographie zeigten sich 3 größere Perforationen in der linksatrialen Membran. Durch Herzkatheteruntersuchung wurde eine Obstruktion der linksatrialen Membran und eine pulmonale Hypertension ausgeschlossen. Wir sahen deshalb keine Indikation zu einer operativen Korrektur. Echokardiographische Verlaufskontrollen erbrachten über 18 Monate keinen Hinweis für eine Obstruktion der linksatrialen Membran durch Verkleinerung der Perforationen. Unser Fall zeigt, dass eine sofortige operative Intervention nicht bei allen Patienten mit Cor triatriatum notwendig ist. Voraussetzung sind eine sorgfältige Evaluation der Hämodynamik und engmaschige echokardiographische Verlaufskontrollen.

Severe Pulmonary Valve Incompetence Late After Debanding: Repair by Bicuspidization

We report a simple valve repair for severe pulmonary incompetence in a 25-year-old patient. The patient had been operated on twice before for ventricular septal defect and coarctation of the aorta. The first operation consisted of pulmonary artery banding and coarctectomy and end-to-end anastomosis at 4 months, followed by debanding and transinfundibular ventricular septal defect closure at 6 years of age. Massive pulmonary incompetence was due to destruction of one valve cusp with the right ventricular outflow tract and pulmonary artery dilated secondarily. Repair consisted of pulmonary valve bicuspidization and right ventricular remodelling.

Fallot Tetralogie mit Abgang der rechten Pulmonalarterie aus der Aorta aszendens: Nichtinvasive Diagnostik und operative Korrektur bei einem 7 Wochen alten Säugling

Anomalous origin of one pulmonary artery from the ascending aorta is a rare anomaly which is almost always associated with hypertension in the contralateral pulmonary artery originating from the right ventricle. We report echocardiographic evaluation of an infant with tetralogy of Fallot and aortic origin of the right pulmonary artery. Since all relevant information regarding anatomy and hemodynamics could be obtained by echocardiography, cardiac catheterization and angiography were unnecessary. Surgical correction including transatrial patch closure of the ventricular septal defect, resection of the infundibular stenosis and direct reimplantation of the right pulmonary artery was performed successfully at the age of 7 weeks. The postoperative course was uneventful and persistent pulmonary hypertension was excluded by echocardiography. Our case shows that complete echocardiographic evaluation is possible in infants with this complex cardiac malformation. We recommend reserving cardiac catheterization for those patients with echocardiographic evidence of significant elevation of pulmonary vascular resistance. In order to avoid irreversible pulmonary vascular changes early surgical correction within the first 3 months of life should be performed in all children with aortic origin of a pulmonary artery including those with associated tetralogy of Fallot. Der Abgang einer Pulmonalarterie aus der Aorta aszendens ist eine seltene Anomalie, die meist auch mit einer pulmonalen Hypertension der regulär mit dem rechten Ventrikel konnektierten Pulmonalarterie einhergeht. Wir berichten über die echokardiographische Evaluation der Anatomie und Hämodynamik bei einem Kind mit Fallot Tetralogie und Abgang der rechten Pulmonalarterie aus der Aorta aszendens. Eine invasive Diagnostik durch Herzkatheteruntersuchung und Angiokardiographie wurde nicht notwendig. Die operative Korrektur mit transatrialem Patchverschluss des Ventrikelseptumdefektes, Resektion der subvalvulären Pulmonalstenose und direkter Reimplantation der rechten Pulmonalarterie erfolgte im Alter von 7 Wochen. Der postoperative Verlauf war komplikationslos, echokardiographisch konnte eine persistierende pulmonale Hypertension ausgeschlossen werden. Unser Fall zeigt, dass auch bei Kindern mit dieser komplexen kardialen Anomalie eine invasive Diagnostik nicht prinzipiell erforderlich ist. Eine Herzkatheteruntersuchung kann den Fällen vorbehalten bleiben, in denen sich echokardiographisch Hinweise für eine signifikante pulmonale Widerstandserhöhung ergeben. Um irreversible pulmonale Gefäßveränderungen zu vermeiden, sollte auch bei Kindern mit Fallot Tetralogie und Fehlabgang einer Pulmonalarterie aus der Aorta die operative Korrektur vor dem Alter von 3 Monaten erfolgen.

[Asymptomatic cor triatriatum in a 2 1/4 year old patient].

We report on an asymptomatic 2 1/4 year old girl. Echocardiography revealed cor triatriatum with a membrane separating the left atrium. Transesophageal echocardiography demonstrated 3 large perforations of the intraatrial membrane. Using Doppler sonography, no pressure gradients across these orifices were identified. Obstruction of the intraatrial membrane and pulmonary hypertension were excluded by cardiac catheterization. We therefore decided against surgical resection of the membrane and to follow the patient noninvasively by echocardiography. Follow-up over 18 months revealed no development of an obstruction across the intraatrial membrane. Our case shows that immediate surgical correction is not necessary in all patients with cor triatriatum. Conservative management of these patients requires full evaluation of the hemodynamics and careful follow-up examinations by echocardiography. Wir berichten über ein 2¼ Jahre altes asymptomatisches Mädchen mit bislang unauffälliger Entwicklung. Echokardiographisch fand sich als Zufallsbefund ein Cor triatriatum. In der transösophagealen Echokardiographie zeigten sich 3 größere Perforationen in der linksatrialen Membran. Durch Herzkatheteruntersuchung wurde eine Obstruktion der linksatrialen Membran und eine pulmonale Hypertension ausgeschlossen. Wir sahen deshalb keine Indikation zu einer operativen Korrektur. Echokardiographische Verlaufskontrollen erbrachten über 18 Monate keinen Hinweis für eine Obstruktion der linksatrialen Membran durch Verkleinerung der Perforationen. Unser Fall zeigt, dass eine sofortige operative Intervention nicht bei allen Patienten mit Cor triatriatum notwendig ist. Voraussetzung sind eine sorgfältige Evaluation der Hämodynamik und engmaschige echokardiographische Verlaufskontrollen.