Regina Bökenkamp

Development of the cardiac coronary vascular endothelium, studied with antiendothelial antibodies, in chicken-quail chimeras.

The endothelium of the coronary vascular system has been described in the literature as originating from different sources, varying from aortic endothelium for the main coronary stems, endocardium for the intramyocardial network, and sinus venosus lining for the venous part of the coronary system. Using an antibody against quail endothelial cells (alpha-MB1), we investigated the development of the coronary vascular system in the quail (Hamburger and Hamilton stages 15 to 35) and in a series of 36 quail-chicken chimeras. In the chimeras, pieces of quail epicardial primordium and/or liver tissue were transplanted into the pericardial cavity of a chicken host. The results showed that the coronary vascular endothelial distribution closely followed the formation of the epicardial covering of the heart. However, pure epicardial primordium transplants did not lead to endothelial cell formation, whereas a liver graft with or without an epicardial contribution did have this capacity. The first endothelial cells were seen to reach the heart at the sinus venosus region, subsequently spreading through the inner curvature to the atrioventricular sulcus and the outflow tract and, last of all, over the ventricular surfaces. At these sites, the precursor cells and small vessels were seen to invade the sinus venosus wall, the ventricular and atrial myocardium, and the mesenchymal border of the aortic orifice. Connections with the endocardium of the heart tube were only observed in the right ventricular outflow region. Initially, the connections with the aortic endothelium were multiple, but later in development only two of these connections persisted to form the proximal part of the two main coronary arteries. Connections to the pulmonary orifice were never observed. Our transplantation data showed that the entire coronary endothelial vasculature originated from an extracardiac source. Moreover, using the developing subepicardial layer as a matrix, we showed that the endothelial cells reached the heart from the liver region. Ingrowth into the various cardiac segments was also observed. Implications for the relation to specific congenital cardiac malformations are discussed.

Congenital heart disease in twin-to-twin transfusion syndrome treated with fetoscopic laser surgery.

OBJECTIVEnTo determine the incidence of congenital heart disease (CHD) and right ventricular outflow tract obstruction (RVOTO) in twin-to-twin transfusion syndrome (TTTS) treated with fetoscopic laser surgery and evaluate the role of increased afterload by determining the difference in blood pressure and endothelin-1 at birth between donor and recipient twins.nnnDESIGNnProspective study.nnnSETTINGnTertiary medical center, serving as the national referral center for fetoscopic laser surgery for TTTS in The Netherlands.nnnPATIENTSnAll consecutive cases of monochorionic twins with TTTS treated with laser (n = 46 twin pairs) and monochorionic twins without TTTS (n = 55 twin pairs) delivered at our center between June 2002 and June 2005 were included in the study.nnnINTERVENTIONSnEchocardiography was performed within 1 week after delivery. At birth, blood pressure was measured in all survivors and endothelin-1 was determined in umbilical cord blood. Data on RVOTO in TTTS treated with laser surgery at our center but delivered elsewhere were reviewed retrospectively from medical records.nnnRESULTSnThe incidence of CHD in the TTTS group and non-TTTS group was 5.4% (4/74) and 2.3% (2/87) (P = .42), respectively. RVOTO was diagnosed in 1 recipient twin delivered at our center and 2 recipient twins delivered elsewhere. The incidence of RVOTO in recipients was 4% (3/75). Mean systolic blood pressure at birth was similar in donor and recipient twins, respectively, 53 mm Hg vs. 56 mm Hg (P = .42). Mean endothelin-1 level at birth was also similar between donors and recipients, respectively, 14.3 ng/L and 13.2 ng/L (P = .64).nnnCONCLUSIONnThe incidence of CHD in TTTS treated with fetoscopic laser surgery is higher than in the general population (5.4% vs. 0.5%). We found no difference in afterload parameters between donors and recipients after laser treatment.

Insights into the pathogenesis and genetic background of patency of the ductus arteriosus.

The unique differentiation program of the ductus arteriosus (DA) is essential for its specific task during fetal life and for the adapting circulation after birth. Phenotypic changes occur in the DA during the normal maturation and definitive closure. Morphological abnormalities of the vessel wall characterize the persistent DA (PDA) in older children. Here, we give an overview of the animal models of DA regulation and remodeling. Genetic research has identified the cause of syndromic forms of PDA, such as the TFAP2B mutations in Char syndrome. Genes that interfere with the remodeling of vascular smooth muscle cells (VSMCs) of the ductal media are affected in virtually all of these anomalies. Therefore, the pivotal regulatory role of VSMCs is emphasized. A better understanding of the genetic background of this developmental process may help develop new strategies to manipulate the DA in premature infants, neonates with duct-dependent anomalies, and patients with syndromic and non-syndromic PDA.

Resynchronization therapy after congenital heart surgery to improve left ventricular function.

This report describes the mid‐term beneficial hemodynamic effect of biventricular pacing in an infant with congestive heart failure after congenital heart surgery, due to resynchronization of the left and right ventricle, optimization of the AV delay, and (partial) correction of the LV dyssynchrony. (PACE 2003; 26:2042–2044)

Persistent ductus arteriosus in the brown-norway inbred rat strain

Persistent ductus arteriosus (PDA) is a common cardiovascular anomaly in children caused by the pathologic persistence of the left sixth pharyngeal arch artery. The inbred Brown-Norway (BN) rat presents with increased vascular fragility due to an aortic elastin deficit resulting from decreased elastin synthesis. The strikingly high prevalence of PDA in BN rats in a pilot study led us to investigate this vascular anomaly in 12 adolescent BN rats. In all BN rats, a PDA was observed macroscopically, whereas a ligamentum arteriosum was found in adult controls. The macroscopic appearance of the PDA was tubular (n = 2), stenotic (n = 8), or diverticular (n = 2). The PDA had the structure of a muscular artery with intimal thickening. In the normal closing ductus of the neonatal controls, the media consisted of layers of smooth muscle cells (SMCs) intermingled with layers of elastin. The intima was thin and poor in elastin. By contrast, the media of PDA in BN rats elastin lamellae were absent and the intima contained many elastic fibers. The abnormal distribution of elastin in the PDA of BN rats suggests that impaired elastin metabolism is related to the persistence of the ductus and implicates a genetically determined factor that may link the PDA with aortic fragility.

Low-energy radiofrequency catheter ablation as therapy for supraventricular tachycardia in a premature neonate

A premature neonate with hydrops was born at 32 weeks of gestation after successful direct fetal amiodarone therapy via cordocentesis for incessant supraventricular tachycardia. After birth the tachycardia could not be controlled despite high doses of amiodarone and flecainide and the patient developed severe respiratory and circulatory failure. After 3 weeks, weighing 2xa0kg, he underwent successful and uncomplicated catheter ablation of a left free-wall accessory pathway using low-energy radiofrequency. Conclusion:radiofrequency catheter ablation is rarely used in neonates, but when used with caution may provide the optimal treatment.

Pulmonary hypertension in two severe combined immunodeficiency disease patients posthaematopoietic stem cell transplantation

Pulmonary hypertension (PH) is an uncommon, potentially life-threatening disorder of the lung vasculature. The aetiology of PH is not fully clarified; however, it has been associated with various conditions such as heart disease, infection, collagen vascular disease, veno-occlusive disease (VOD), drugs and toxins (Widlitz & Barst, 2003). PH has very rarely been associated with haematopoietic stem cell transplantation (HSCT) and was mostly associated with vasculopathy or VOD (Hackman et al, 1989; Bruckmann et al, 1991; Seguchi et al, 2000). Recently, Steward et al (2003) described patients with malignant infantile osteopetrosis who developed PH posttransplantation. To illustrate that not only osteopetrosis patients are susceptible to PH in the post-HSCT period, we report two cases with severe immunodeficiency syndrome (SCID) that developed this complication.

Accessory Atrioventricular Myocardial Pathways in Mouse Heart Development: Substrate for Supraventricular Tachycardias

Atrioventricular reentry tachycardia (AVRT) requiring an accessory atrioventricular pathway (AP) is the most common type of arrhythmia in the perinatal period. The etiology of these arrhythmias is not fully understood as well as their capability to dissipate spontaneously in the first year of life. Temporary presence of APs during annulus fibrosus development might cause this specific type of arrhythmias. To study the presence of APs, electrophysiological recordings of ventricular activation patterns and immunohistochemical analyses with antibodies specifically against atrial myosin light chain 2 (MLC-2a), Periostin, Nkx2.5, and Connexin-43 were performed in embryonic mouse hearts ranging from 11.5 to 18.5 days post-conception (dpc). The electrophysiological recordings revealed the presence of functional APs in early (13.5–15.5 dpc) and late (16.5–18.5 dpc) postseptated stages of mouse heart development. These APs stained positive for MLC-2a and Nkx2.5 and negative for Periostin and Connexin-43. Longitudinal analyses showed that APs gradually decreased in number (p = 0.003) and size (p = 0.035) at subsequent developmental stages (13.5–18.5 dpc). Expression of periostin was observed in the developing annulus fibrosus, adjacent to APs and other locations where formation of fibrous tissue is essential. We conclude that functional APs are present during normal mouse heart development. These APs can serve as transient substrate for AVRTs in the perinatal period of development.

Surgical Correction of Supravalvar Aortic Stenosis: 52 Years’ Experience

Objectives: Supravalvar aortic stenosis (SVAS) is a rare congenital anomaly. The “single-patch technique,” “‘two sinus augmentation with an inverted Y-patch” (both nonsymmetrical corrections), “three-patch technique,” and the “slide aortoplasty” (both symmetrical corrections) are the techniques implemented by the majority of surgeons for the correction of SVAS. In the few studies that compared these techniques, no technique was shown to be superior over another. The aim of the present study is to review the 52-year experience with the surgical correction of SVAS in two of four congenital cardiothoracic surgical centers in the Netherlands. Methods: We retrospectively reviewed all patient files of those who underwent an operation to correct their SVAS, between 1962 and 2014 in our centers. Patients were divided according to their operating technique. These groups were compared using the end points freedom from reoperation and mortality. Results: A total of 49 patients were included, 23 (46.9%) patients in the nonsymmetrical group and 26 (53.1%) patients in the symmetrical group. Survival after 20 years in the nonsymmetrical group was 80% (standard error [SE]: 0.091) and in the symmetrical group was 85% (SE: 0.085; P = .163). Freedom from reoperation after 20 years in the nonsymmetrical group was 88% (SE: 0.079) and in the symmetrical group was 71% (SE: 0.107; P = 0.313). Conclusion: In this patient group, there is no significant difference in survival and freedom from reoperation between the different surgical techniques for SVAS repair. Compared to the survival in the general population, the survival of SVAS patients is remarkably low. Apparently, SVAS is not a benign disease and probably patients should be followed more closely for the rest of their lives.

Left atrial isomerism: biventricular repair.

OBJECTIVEnBiventricular repair of hearts with left atrial isomerism often necessitates complex atrial and ventricular baffle procedures. We analysed our experience with an accent on baffle techniques.nnnMETHODSnFrom 1997 until 2008, 12 patients (four male) with left atrial isomerism received biventricular repair. Their median age at surgery was 9 (range: 1-24) months. Four patients had dextrocardia. Nine patients presented with left superior vena cava, three with absent right superior vena cava, five with unroofed coronary sinus and nine others with inferior vena cava interruption with (hemi)azygos continuation. Anomalous pulmonary venous drainage was present in three patients. Eight had a monoatrium. Atrioventricular septal defect (AVSD) occurred in six (complete AVSD in two), One patient with complete AVSD had right pulmonary agenesia with long segment tracheal stenosis. Multiple VSDs presented in one whereas three patients had double-outlet right ventricle (DORV) (one with borderline LV hypoplasia). Two had previous pulmonary artery banding. Complex intra-atrial baffle constructions were performed in seven patients. Complete AVSDs were corrected using two patches and all other AVSDs had one patch repair. Multiple VSDs were closed directly. DORV patients had intraventricular tunnel repair.nnnRESULTSnNo early mortality occurred. Median follow-up was 54 (range: 2-134) months. One patient with complete AVSD and pulmonary agenesia died late after tracheal repair. Four patients needed five re-operations (closure of residual ASD (one), relief of left (two) or right (two) ventricular outflow obstruction, pulmonary artery branch plasty (one)). There was no atrial baffle stenosis. Four received a pacemaker. All survivors are in NYHA class I.nnnCONCLUSIONSnSurvival and functional status of left isomerism patients after biventricular repair is good. Complex repairs with atrial or ventricular baffles are frequent. Arrhythmias were common and pose a concern late after repair.