Ulrike Salzer-Muhar

Predictors of Spontaneous Closure of Isolated Secundum Atrial Septal Defect in Children: A Longitudinal Study

OBJECTIVES. The goals were to assess the frequency of spontaneous closure of isolated secundum atrial septal defect in children and to identify predictors of spontaneous atrial septal defect closure. METHODS. A retrospective cohort study was performed in a tertiary care pediatric cardiology center. Consecutive patients (n = 200) diagnosed as having isolated atrial septal defects (no multiple or fenestrated atrial septal defects, no additional congenital heart disease, and no syndromes) were monitored for >6 months with serial 2-dimensional echocardiography, according to a standardized protocol. RESULTS. The median age at diagnosis was 5 months (minimum: 0 months; maximum: 13.9 years). The atrial septal defect diameter at diagnosis was 4 to 5 mm in 40% of cases, 6 to 7 mm in 28% of cases, 8 to 10 mm in 21% of cases, and >10 mm in 11% of cases. The median age at the final follow-up evaluation was 4.5 years (range: 6.8 months to 16.2 years). Thirty-four percent of atrial septal defects showed spontaneous closure, and 28% decreased to a diameter of ≤3 mm. Logistic regression analysis revealed atrial septal defect diameter and age at diagnosis as independent predictors of spontaneous closure or regression to ≤3-mm defect size. Of atrial septal defects with a diameter of 4 to 5 mm at diagnosis, 56% showed spontaneous closure, 30% regressed to a diameter of ≤3 mm, and none required surgical closure. Of atrial septal defects with a diameter of >10 mm at diagnosis, none closed spontaneously, whereas 77% required surgical or device closure. Gender and observation time were not associated with spontaneous atrial septal defect closure or regression to ≤3 mm. CONCLUSIONS. In the present study population of children with atrial septal defects, 62% showed spontaneous closure (34%) or regression to ≤3 mm (28%). Initial atrial septal defect diameter was the main predictor of spontaneous closure.

Incidence and Diagnosis of Thrombosis in Children With Short-Term Central Venous Lines of the Upper Venous System

OBJECTIVES. Deep venous thrombosis in children is frequently related to central venous lines. Study objectives were to determine objectively the incidence of deep venous thrombosis in children with short-term central venous lines and to assess the diagnostic value of venography, venous ultrasonography, and echocardiography, in a prospective cohort study. METHODS. Consecutive children with congenital heart disease requiring short-term central venous lines in the upper venous system were screened systematically for deep venous thrombosis by using venography, venous ultrasonography, and echocardiography, according to standardized protocols. RESULTS. The study population consisted of 90 children (median age: 2.7 years; range: birth to 18 years). Most central venous lines (97%) were located in the jugular veins. The overall incidence of deep venous thrombosis was 25 cases (28%) among 90 children. Venography identified deep venous thrombosis located in the subclavian and central veins but missed most deep venous thrombosis in the jugular veins. Venous ultrasonography had good sensitivity in the jugular veins but did not detect deep venous thrombosis in central veins. Echocardiography detected only 1 case of central deep venous thrombosis. CONCLUSIONS. The incidence of central venous line-related deep venous thrombosis in children with short-term central venous lines is high and comparable to reports for children with long-term central venous lines. Sensitivities of venography, venous ultrasonography, and echocardiography in children vary depending on the affected venous segment. A combination of diagnostic tests is required for sensitive detection of central venous line-related deep venous thrombosis in the upper venous system.

Fetal MRI detects early alterations of brain development in Tetralogy of Fallot

OBJECTIVE Prenatal imaging has identified alterations of brain growth in fetuses with congenital heart disease. However, little is known about the timing of altered brain development and its occurrence in specific congenital heart disease subgroups. This magnetic resonance imaging study aimed to identify early (median, 25 gestational weeks [GW]) changes in fetal total brain (TBV), gray matter (GMV), and subcortical brain (SBV) volumes in Tetralogy of Fallot (TOF) cases in utero. STUDY DESIGN Fetal magnetic resonance imaging (1.5 Tesla) was performed in 24 fetuses who were diagnosed with TOF and 24 normal age-matched control fetuses (20-34 GW). TBV, GMV, SBV, intracranial cavity, cerebellar, ventricular, and external cerebrospinal fluid volumes were quantified by manual segmentation based on coronal T2-weighted sequences. Mixed model analyses of variance and t-tests were conducted to compare cases and control fetuses. RESULTS TBV was significantly lower (P < .001) in early (<25 GW) and late TOF cases. Both GMV (P = .003) and SBV (P = .001) were affected. The GMV-to-SBV ratio declined in fetuses with TOF (P = .026). Compared with normal fetuses, ventricular volume was increased (P = .0048). External cerebrospinal fluid was enlarged in relation to head size (P < .001). Intracranial cavity volume (P = .314) and cerebellar volume (P = .074) were not significantly reduced in fetuses with TOF. CONCLUSION TOF is associated with smaller volumes of gray and white matter and enlarged cerebrospinal fluid spaces. These changes are present at ≤25 GW and indicate altered fetal brain growth in this pathophysiologic entity during early stages of human brain development.

Structural congenital brain disease in congenital heart disease: Results from a fetal MRI program

OBJECTIVE To identify the type and incidence of fetal brain pathology in fetuses with a prenatal diagnosis of congenital heart disease (CHD). PATIENTS AND METHODS 67 pregnant women underwent a fetal MR-examinations between 20 and 38 gestational weeks. MR was done on a 1.5 T superconducting system. The type of cardiac malformation was defined by fetal echocardiography. Fetuses with a chromosomal abnormality or an extracardiac anomaly were excluded. RESULTS Fetal MRI scans in the final study cohort (53 fetuses) yielded normal results in 32 fetuses and a brain abnormality in 21 fetuses. Congenital brain disease (CBD) was found in 39% of the final study cohort of fetuses with CHD. MRI findings were classified into malformations, acquired lesions and widening of the ventricles and/or outer CSF spaces (malformations: 7 fetuses, acquired lesions: 5 fetuses, changes in CSF spaces: 9 fetuses). Asymmetry of the ventricles was the most common finding in the CSF group. CONCLUSIONS Our data suggest that fetal MRI can be used to characterize structural CBD in CHD. Advanced MRI techniques such as diffusion tensor imaging and proton spectroscopy are tools that, in the future, will certainly shed light on the spectrum of structural and functional CBDs that are associated with CHD.

Ventricular interaction in children after repair of tetralogy of Fallot: a longitudinal echocardiographic study

AIMS Progressive right ventricular (RV) dilation due to pulmonary regurgitation (PR) after repair of tetralogy of Fallot (TOF) may impair left ventricular (LV) filling. Our aim was to analyse long-term time courses of M-mode LV and RV measurements and to relate these to the degree of PR. METHODS AND RESULTS Retrospective longitudinal cohort of children (n = 88) after repair of TOF followed by serial echocardiography over 9 years. LV and RV diameters were expressed by z-scores based on normal paediatric reference values. Time courses of LV and RV diameter z-scores, degree of PR, and influence of co-variables were analysed using mixed regression models. LV diameter z-scores were significantly lowered before repair, increased after surgery, but fell again over time; thus, mean LV diameters were significantly lower than normal population means at all times. LV diameter z-scores correlated negatively with RV dilation and degree of PR. Notably, they were significantly higher in patients with previous shunts. After pulmonary valve replacement, LV diameter z-scores recovered to normal, whereas RV diameter z-scores remained abnormal. CONCLUSION Our results confirm progressive adverse RV-LV interaction in the long-term post-operative follow-up of TOF. The use of z-scores facilitated the analysis of time courses of LV and RV diameters.

NT-pro BNP in acute childhood myocarditis

To the Editor: After reading the article by Hill et al and the comment in the Science section of the New York Times, I felt humiliated and unsettled by the revelation that the professional competence of many pediatric cardiologists, at least in a specific area, fell far short of expectation. In this study approximately one-third of presumably well-trained and certified pediatric cardiologists now out in practice failed to correctly interpret abnormal electrocardiogram results obtained from children before participation in active sports. The specifics of some of the abnormal electrocardiogram results would serve as markers for potential sudden death on the athletic field. And then adding insult to injury, approximately 20% of the children whose electrocardiograms were submitted for interpretation would have been misdirected on the basis of electrocardiographic interpretation as to whether they should or should not engage in active sports. These findings are clearly an indictment of our pediatric cardiology training programs and our certification standards and furthermore question the skill and reliability of the practicing pediatric cardiologist for interpreting elecrocardiocardiograms. As a pediatric cardiologist who has worked in an academic setting for >50 years, I have noticed with dismay the diminishing interest in time on the part of our pediatric cardiology trainees in the essentials of electrocardiographic interpretation, physical examination, and auscultation, which are the bedrock of their training and, I might add, of no less importance to the practicing pediatric cardiologist. This unsettling situation has its origins in the focus on ‘‘high tech’’ to the subordination of the development of strong clinical skills. I have observed on multiple occasions a trainee or a staff pediatric cardiologist skim over a physical examination or an electrocardiogram and refer a patient for echocardiography with the implied wisdom that that is where the answers are found. To our discredit, educators and role models have failed to spark enthusiasm in the domain of mastering clinical skills, with special focus on physical examination, auscultation, and electrocardiography. Slighting clinical skills occurs with students and mature pediatric cardiologists alike, and this is reflected in a diminished quality of health care. The public respects and admires our unique expertise, and I don’t think that we are serving them well in light of our clinical shortcomings. In my view, learning the fundamentals and focusing on excellence begins in the pediatric cardiology outpatient clinic. Again to our discredit, in the mind of many trainees and their seniors fulfilling an obligation in the outpatient clinic is tantamount to a necessary evil. The educators themselves often fail to polish their clinical skills and express only a marginal interest in outpatient clinics. No wonder the trainees tend to downplay the learning

Surface LAMP-2 Is an Endocytic Receptor That Diverts Antigen Internalized by Human Dendritic Cells into Highly Immunogenic Exosomes

The lysosome-associated membrane protein (LAMP) family includes the dendritic cell endocytic receptors DC-LAMP and CD68, as well as LAMP-1 and LAMP-2. In this study we identify LAMP-1 (CD107a) and LAMP-2 (CD107b) on the surface of human monocyte-derived dendritic cells (MoDC) and show only LAMP-2 is internalized after ligation by specific Abs, including H4B4, and traffics rapidly but transiently to the MHC class II loading compartment, as does Ag conjugated to H4B4. However, pulsing MoDC with conjugates of primary (keyhole limpet hemocyanin; KLH) and recall (Bet v 1) Ags (H4B4*KLH and H4B4*Bet v 1) induced significantly less CD4 cell proliferation than pulsing with native Ag or Ag conjugated to control mAb (ISO*KLH and ISO*Bet v 1). In H4B4*KLH-pulsed MoDC, the duration of KLH residence in MHC class II loading compartments was significantly reduced, as were surface HLA-DR and DR-bound KLH-derived peptides. Paradoxically, MoDC pulsed with H4B4*KLH, but not the other KLH preparations, induced robust proliferation of CD4 cells separated from them by a transwell membrane, indicating factors in the supernatant were responsible. Furthermore, extracellular vesicles from supernatants of H4B4*KLH-pulsed MoDC contained significantly more HLA-DR and KLH than those purified from control MoDC, and KLH was concentrated specifically in exosomes that were a uniquely effective source of Ag in standard T cell proliferation assays. In summary, we identify LAMP-2 as an endocytic receptor on human MoDC that routes cargo into unusual Ag processing pathways, which reduces surface expression of Ag-derived peptides while selectively enriching Ag within immunogenic exosomes. This novel pathway has implications for the initiation of immune responses both locally and at distant sites.

Fetal cardiac disease and fetal lung volume: an in utero MRI investigation.

Magnetic resonance imaging (MRI) is a powerful, noninvasive tool to study fetal lung volumes after 18 weeks of gestation in vivo. In neonates with congenital heart disease (CHD), proper lung function is essential for postnatal survival. Antenatal detection of abnormal pulmonary development may help to optimize prenatal and perinatal management of at‐risk fetuses. We aimed to investigate lung volumes in fetuses with prenatally diagnosed heart disease.

Special Schooling in Children with Congenital Heart Disease: A Risk Factor for Being Disadvantaged in the World of Employment

The objective of this study was to evaluate type of schooling in children with congenital heart disease (CHD) who were inpatients at a tertiary pediatric cardiology center. This retrospective cohort study included 227 consecutive children with CHD (male, 125; female, 102) who had been inpatients from 1996 to 2005. Data on type of schooling had been documented by the in-hospital teacher at the time of admission. Medical data were obtained by reviewing medical charts. The primary endpoint was the percentage of children requiring special schooling, which was related to the respective percentage in the Austrian pediatric background population. Furthermore, the influence of clinical and demographic covariables was assessed. Fifteen percent (vs. 3.6% in the background population) of the study cohort required special schooling; 86% of them had a history of cardiac surgery. Cardiopulmonary bypass surgery in the first year of life showed a trend for an association with an increased frequency of special schooling. There were no significant associations with the Aristotle Basic Score (a measure for procedure complexity in CHD), gender, or first language. In conclusion, the need for special schooling is increased in children with CHD.

Preterm infants who later require duct ligation show different vital signs and pH in early postnatal life

The study investigated early postnatal vital signs in very low birthweight (VLBW) infants who later developed patent ductus arteriosus (PDA). We hypothesised that the early postnatal course of vital signs and blood gas variables might differ between infants whose PDA closed spontaneously, those who responded to ibuprofen and those who later required PDA ligation.