Idiopathic enlargement of the right atrium masking left atrial aneurysm in a neonate.

An idiopathic enlargement of the right atrium is an extremely rare cardiac malformation. There are no established guidelines for the management of this disease, especially concerning medical versus surgical therapeutic approach and the timing for an operation. We report in this case about a neonate that first was treated conservatively until the age of 5 month and finally got an operative resection of the aneurysm. After surgery, unexpected complications occurred. A second aneurysm in the left atrium was demasked. Furthermore, a progressive dilatation of both atrial chambers after resection required regular follow-up and ongoing evaluation of treatment.

[Life-threatening subcutaneous emphysema after minor blow to the neck]. / Lebensbedrohliches Hautemphysem nach banalem Stoß gegen den Hals.

After a minor blow to the neck from the handlebars of a bike, a 5-year-old boy developed a massive subcutaneous emphysema with respiratory distress. Orotracheal intubation was performed. A computed tomography (CT) scan of the neck and thorax showed a pneumomediastinum and a bilateral pneumothorax. No injury to the large airways was identified. The patient was stabilized by insertion of chest tubes and controlled ventilation. The endoscopic examination of the trachea revealed a tear of the pars membranacea, which was successfully treated conservatively. The specific features of the injury and the airway management are discussed based on a review of the current literature.

Dysregulated autophagy in restrictive cardiomyopathy due to Pro209Leu mutation in BAG3.

Myofibrillary myopathies (MFM) are hereditary myopathies histologically characterized by degeneration of myofibrils and aggregation of proteins in striated muscle. Cardiomyopathy is common in MFM but the pathophysiological mechanisms are not well understood. The BAG3-Pro209Leu mutation is associated with early onset MFM and severe restrictive cardiomyopathy (RCM), often necessitating heart transplantation during childhood. We report on a young male patient with a BAG3-Pro209Leu mutation who underwent heart transplantation at eight years of age. Detailed morphological analyses of the explanted heart tissue showed intracytoplasmic inclusions, aggregation of BAG3 and desmin, disintegration of myofibers and Z-disk alterations. The presence of undegraded autophagosomes, seen by electron microscopy, as well as increased levels of p62, LC3-I and WIPI1, detected by immunohistochemistry and western blot analyses, indicated a dysregulation of autophagy. Parkin and PINK1, proteins involved in mitophagy, were slightly increased whereas mitochondrial OXPHOS activities were not altered. These findings indicate that altered autophagy plays a role in the pathogenesis and rapid progression of RCM in MFM caused by the BAG3-Pro209Leu mutation, which could have implications for future therapeutic strategies.

Preserved heart function after left ventricular pressure overload in adult mice subjected to neonatal cardiac hypoplasia.

Intrauterine growth restriction in animal models reduces heart size and cardiomyocyte number at birth. Such incomplete cardiomyocyte endowment is believed to increase susceptibility toward cardiovascular disease in adulthood, a phenomenon referred to as developmental programming. We have previously described a mouse model of impaired myocardial development leading to a 25% reduction of cardiomyocyte number in neonates. This study investigated the response of these hypoplastic hearts to pressure overload in adulthood, applied by abdominal aortic constriction (AAC). Echocardiography revealed a similar hypertrophic response in hypoplastic hearts compared with controls over the first 2 weeks. Subsequently, control mice develop mild left ventricular (LV) dilation, wall thinning and contractile dysfunction 4 weeks after AAC, whereas hypoplastic hearts fully maintain LV dimensions, wall thickness and contractility. At the cellular level, controls exhibit increased cardiomyocyte cross-sectional area after 4 weeks pressure overload compared with sham operated animals, but this hypertrophic response is markedly attenuated in hypoplastic hearts. AAC mediated induction of fibrosis, apoptosis or cell cycle activity was not different between groups. Expression of fetal genes, indicative of pathological conditions, was similar in hypoplastic and control hearts after AAC. Among various signaling pathways involved in cardiac hypertrophy, pressure overload induces p38 MAP-kinase activity in hypoplastic hearts but not controls compared with the respective sham operated animals. In summary, based on the mouse model used in this study, our data indicates that adult hearts after neonatal cardiac hypoplasia show an altered growth response to pressure overload, eventually resulting in better functional outcome compared with controls.

[Arrhythmogenic right ventricular dysplasia/cardiomyopathy - diagnosis in childhood]. / Arrhythmogene rechtsventrikuläre Dysplasie/Cardiomyopathie. Diagnostik im Kindesalter.

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a rare, but important cause for sudden death in adolescents and young adults. Part of the patients affected show the pattern of autosomal-dominant inheritance. Two pediatric patients with ARVD/C are presented who may reflect the spectrum of clinical presentation of ARVD/C in childhood resulting in difficulties or even delay to establish the correct diagnosis. One patient with a sporadic form of ARVD/C presented with a syncope and spontaneous as well as inducible ventricular tachycardia. On the ECG, an epsilon wave could be identified. An automatic cardioverter defibrillator was implanted. The second patient had a familiar form of ARVD/C with no symptoms. There was a history of frequent sudden deaths in this family. Biopsies of the right ventricular myocardium showed fibrosis with deposition of fatty tissue. There was clear evidence of ARVD/C in the necropsy of the patient's aunt. Therapy with propanolol was started in this patient.

Primary repair of tetralogy of fallot in infancy--the effect on growth of the pulmonary arteries and the risk for late reinterventions.

We sought to analyse the long-term follow-up after primary repair of tetralogy of Fallot in infancy in the first year of life, paying particular attention to growth of the pulmonary arteries and the need for reintervention. We performed a combined retro- and prospective echocardiographic study, including measurements of the pulmonary valve and right and left pulmonary arteries, indexed to the square root of body surface area, in 62 patients prior to primary repair, 18 to 24 months after this event, and at the most recent follow-up, with a mean of 80.4+/-24 months. Of these, 38 patients, with an age at operation of 5.0+/-3.4 months, had presented preoperatively with hypoxic spells or increasing cyanosis. The remaining 24 patients had been asymptomatic, with adequate flow of blood to the lungs. Their age at elective operation was 7.4+/-3.0 months. A transannular patch was needed in 37 patients (63%). There were 3 early postoperative deaths (4.8%). Cross-sectional echocardiography revealed a significantly smaller diameter for the pulmonary valve in patients who had been symptomatic preoperatively compared to the asymptomatic patients (1.09 versus 1.3 cm/BSA0.5; p = 0.019). The diameters of the right and left pulmonary arteries did not differ significantly between the groups. Examination of echocardiographic data obtained 18 to 24 months postoperatively in 43 patients revealed a significant increase in the diameter of the pulmonary arteries; 0.83+/-0.17 cm/BSA0.5 versus 1.1+/-0.26 cm/BSA0.5 for the diameter of the right pulmonary artery, 0.85+/-0.2 cm/BSA0.5 versus 1.0+/-0.25 cm/BSA0.5 for the left pulmonary artery. On comparison between individuals, 18.6% and 25.6% of the patients, respectively, did not show any change in the diameters of their right and left pulmonary arteries, whereas the increase in diameter reached or exceeded the measurements in normal controls in 55.8% and 46.5% of the patients, respectively. On recent follow-up, with a range from 56 to 147 months, no further increase in the indexed diameters of the pulmonaries could be documented in 21 of 33 patients. Of these, 9.1% and 18.2%, respectively, presented with small right and left pulmonary arteries compared with measurements obtained in normal controls. Moderate pulmonary incompetence was found on colour flow mapping in one-third. Of 56 longterm survivors, 8 (14%) had required reinterventions, which were surgical in 6 and achieved by transcatheter techniques in the other 2 patients. Thus, primary correction of tetralogy of Fallot in infancy, with restoration of normal pressures and flows, resulted in sustained increase in the diameters of the right and left pulmonary arteries. It allowed for early normal development of the proximal pulmonary arterial system in most patients regardless of their age and symptomatic status at operation. Patients with persistent subnormal diameter of the pulmonary arteries did not present with significantly elevated right ventricular pressure. Early one-stage repair of tetralogy of Fallot in infancy was associated with a low rate of reinterventions.

Transcatheter closure of various types of defects within the oval fossa using the double umbrella device (CardioSEAL)--feasibility and echocardiographic follow-up.

Data on long-term follow-up for closure of so-called secundum type" atrial septal defects within the oval fossa using recently developed devices are limited, and results focused on presence of residual shunting. The purpose of our study was to report the experience from a single center establishing the effectiveness of transcatheter closure in patients with various types of defect other than those located centrally within the oval fossa. A total of 72 patients was included in this study. On transesophageal echocardiography, the size of the defects varied from 6 to 18 mm, with estimation of the stretched diameter from 11 to 21 mm. The ratio of stretched diameter to the extent of the residual septum ranged from 0.28 to 0.54. Mean follow-up was 30.5+7.4 months, with a range from 13 to 42 months. The rate of closure using devices with diameters from 28 to 40 mm increased from 80% immediately after implantation to 93% in the 57 patients examined 24 months after implantation. For further analysis, we compared the 44 patients with a solitary, centrally located, defect to 28 having morphological variations, including superiorly located defects with deficient superior and aortic rims, multifenestrated and aneurysmal defects, or isolated additional defects. There was no incidence of formation of thrombus, sustained atrial arrhythmia, or infective endocarditis. Residual shunting was not influenced by location or morphology of the defects, but increased with size, stretched diameter, and the ratio of pulmonary to systemic flows. Serial transthoracic echocardiographic findings revealed malposition of one right-sided superior arm of the device in 8 patients, while protrusion of one left-sided arm onto the right atrial aspect was observed in 3 patients. Fluoroscopy showed fatigue fracture of a single arm in 7 patients (9.7%) within the first 6 months after implantation. These results demonstrate that transcatheter closure with the non self-centering double umbrella device was effective and safe on medium-term follow-up, and could be extended to defects within the oval fossa having various morphologies. Residual shunting resolved with time, and was not related to either morphology or the position of the device.

Experimental preseeding of the STARFlex atrial septal occluder device with autologous cells.

Devices used in interventional cardiology are permanent implants. However, most of the devices fulfill only a temporary function. For example, atrial septal defect (ASD) occluders serve as mechanical shields until complete in- and overgrowth of the occluding device by endogenous tissue from the defect edges has occurred. Thereafter, the foreign body material of the devices is no longer needed and bears potential long-term adverse effects. The concept of "biodegradable" occluder devices that act as transient mechanical shields to close the defects and as scaffolds for overgrowth with autologous tissue is, therefore, tempting. Since rapid and complete ingrowth as well as coverage by firm tissue is a prerequisite for any such "biological" occluder devices, the feasibility and short-term in vivo response to STARFlex devices preceeded with autologous cells was studied in an experimental sheep model. The experiments demonstrated that autologous cell preceeding of cardiovascular implants is technically feasible. Cells survived the mechanical stress of device implantation. A precoating of conventional STARFlex occluders led to an increased cellular density after cell seeding of the device, an increased resistance of the precultured cytolayer against mechanical stress, and a significantly higher poststress viability of "implanted" cells. Experimental closure of ASD using autologous-cell preseeded STARFlex devices was uncomplicated. In the sheep model this led to rapid, complete, and firm ingrowth of the device into the adjacent atrial tissue. A thicker layer of young fibrous granulation tissue in organization was found on the preceeded devices compared with the unseeded control group after 4 weeks in vivo. Currently, an increased thrombogenicity limits in vivo application.

[Antegrade flow in the aorta ascendens despite aortic atresia: 2 case reports with retrograde coronary perfusion through coronary fistulas and sinusoids]. / Antegrader Fluss in der Aorta ascendens trotz Aortenatresie: Zwei Fallbeschreibungen mit retrograder Koronarperfusion durch koronare Fisteln und Sinusoide.

In aortic atresia, coronary perfusion normally occurs through retrograde blood flow in the ascending aorta. We report on two patients with antegrade flow in the ascending aorta despite aortic atresia. In one patient with hypoplastic left heart syndrome (aortic atresia, severe mitral stenosis), an intact interatrial septum/premature closure of the foramen ovale was found. While no other way of left atrial or ventricular decompression was found, echocardiography, angiography and the post-mortem examination showed left ventricular to coronary sinusoids as the sole pathway for systemic oxygenation. In a second patient with complex congenital heart disease, including aortic atresia, antegrade flow in the ascending aorta was through a left coronary fistula with shunt flow originating from the pulmonary trunk. This report describes systemic perfusion depending on retrograde coronary flow due to coronary-cameral (sinusoids) and coronary arterio-venous fistulas leading to the phenomenon of antegrade blood flow in the ascending aorta despite aortic atresia.

Suppression of growth plate chondrocyte proliferation by corticosteroids.

Growth depression is a side effect of high-dose glucocorticoid therapy in childhood. It is partially mediated by alterations of the somatotropic hormone axis and partially by direct local effects on growth plate chondrocytes. The mechanisms of interaction of corticosteroids and somatotropic and calciotropic hormones at the cellular level were recently investigated in more detail, using experimental models of primary cultures of growth plate chondrocytes. In proliferative chondrocytes, growth hormone (GH) and the calciotropic hormones parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D [1alpha,25(OH)2D3] increase cell proliferation via stimulation of paracrine insulin-like growth factor-I (IGF-I) secretion. Corticosteroids decreased GH, and PTH or 1alpha,25(OH)2D3 stimulated cell growth in a dose-dependent manner. Corticosteroids in high doses reduced the expression of the GH receptor and type 1 IGF receptor. But the main antiproliferative molecular effect of corticosteroid was the reduction in basal and hormone-stimulated IGF-I secretion. The in vitro results are in accordance with the observation in animal experiments and in children treated with corticosteroids, demonstrating that the growth-depressing effect of corticosteroids can be compensated for by supraphysiological doses of GH or IGF-I.

Dexamethasone impairs growth hormone (GH)-stimulated growth by suppression of local insulin-like growth factor (IGF)-I production and expression of GH- and IGF-I-receptor in cultured rat chondrocytes.

Growth depression as a side effect of glucocorticoid therapy in childhood is partially mediated by alterations of the somatotropic hormone axis. The mechanisms of interaction between glucocorticoids and somatotropic hormones on the cellular and molecular level are poorly understood. In an experimental model of primary cultured rat growth plate chondrocytes, basal as well as GH (40 ng/ml) or insulin-like growth factor (IGF)-I (60 ng/ml)-stimulated growth was suppressed dose dependently (10(-l2)-10(-7)M) by dexamethasone (Dexa). An IGF-I antibody specifically and dose dependently inhibited the GH- but not the basic fibroblast growth factor (bFGF)-stimulated cell proliferation. GH increased the IGF-I concentration in conditioned serum-free culture medium; this was reversed by concomitant Dexa. Dexa time dependently suppressed the transcription of GH receptor (GHR) messenger RNA (mRNA) and down-regulated the basal and GH-stimulated expression of GHR. Whereas no suppressive effect on basal type I IGF-receptor (IGFR) was observed, Dexa blocked the IGF-I induced increase of IGF binding. These results were confirmed by GHR and IGFR immunostaining. We conclude that Dexa impairs the GH-induced stimulation of local secretion and paracrine action of IGF-I and reduces the homologous increase of IGFR and GHR expression. The above experiments give further insight on the interaction between GH and glucocorticoids on the cellular and molecular level of growth plate chondrocytes.