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Background: The objective of this IRB-approved retrospective monocentric study was to identify risk factors for mortality after surgery for congenital heart defects (CHDs) in pediatric patients using machine learning (ML). CHD belongs to the most common congenital malformations, and remains the leading mortality cause from birth defects. Methods: The most recent available hospital encounter for each patient with an age n = 73 events]). All models were then applied to predict the outcome in an independent holdout test dataset (40% of the cohort). Results: RSF and XGB achieved average C-indices of 0.85 (±0.01) and 0.79 (±0.03), respectively. Feature importance was assessed with ‘SHapley Additive exPlanations’ (SHAP) and ‘Time-dependent explanations of machine learning survival models’ (SurvSHAP(t)), both of which revealed high importance of the maximum values of serum creatinine observed within 72 h post-surgery for both ML methods. Conclusions: ML methods, along with model explainability tools, can reveal interesting insights into mortality risk after surgery for CHD. The proposed analytical workflow can serve as a blueprint for translating the analysis into a federated setting that builds upon the infrastructure of the German Medical Informatics Initiative.

BackgroundMyocarditis represents one of the most common causes of Sudden Cardiac Death in children. Myocardial involvement during a viral infection is believed to be higher as a consequence of intensive exertion. Recommendations for return to sports are based on cohort and case studies only. This study aims to investigate the relationship between physical activity and myocarditis in the young.PatientEvery patient in the MYKKE registry fulfilling criteria for suspicion of myocarditis was sent a questionnaire regarding the physical activity before, during and after the onset of myocarditis.MethodThis study is a subproject within the MYKKE registry, a multicenter registry for children and adolescents with suspected myocarditis. The observation period for this analysis was 93 months (September 2013–June 2021). Anamnestic, cardiac magnetic resonance images, echocardiography, biopsy and laboratory records from every patient were retrieved from the MYKKE registry database.Results58 patients (mean age 14.6 years) were enrolled from 10 centers. Most patients participated in curricular physical activity and 36% in competitive sports before the onset of myocarditis. There was no significant difference of heart function at admission between the physically active and inactive subjects (ejection fraction of 51.8 ± 8.6% for the active group vs. 54.4 ± 7.7% for the inactive group). The recommendations regarding the return to sports varied widely and followed current guidelines in 45%. Most patients did not receive an exercise test before returning to sports.ConclusionSports before the onset of myocarditis was not associated with a more severe outcome. There is still a discrepancy between current literature and actual recommendations given by health care providers. The fact that most participants did not receive an exercise test before being cleared for sports represents a serious omission.

BackgroundDue to rapid medical and technological progress, more and more pediatric patients with terminal cardiac insufficiency are being implanted with a ventricular assist device as a bridge to transplant without legal approval for hospital discharge. EXCOR® Active is a recently developed mobile driving unit for the EXCOR® ventricular assist device (EXCOR® VAD) with a long-lasting battery life that can manage small blood pumps, offering improved mobility for pediatric patients. This study strives to elaborate the requirements necessary for a safe home healthcare environment (HHE) for pediatric patients on EXCOR® VAD powered by the EXCOR® Active driving unit.Materials and methodsPatient- and device-related preconditions (medical, ethical, psychological, technical, structural, organizational) were analyzed with regard to feasibility and safety in three individual patient cases. Included were pediatric patients with terminal cardiac insufficiency in a stable medical condition receiving in-hospital treatment with a univentricular or biventricular EXCOR® VAD powered by EXCOR® Active. Analysis was single-center, data was obtained 05/2020–02/2022.ResultsA total of three patients on EXCOR® VAD were identified for HHE treatment with the EXCOR® Active driving unit. Switch was performed safely and increased mobility led to improved psychomotor development and improved quality of life. No complications directly related to HHE-treatment occurred. One patient recently underwent an orthotopic heart transplant, one patient remains in HHE, and one patient died due to a complication not related to the HHE. Ethical approval for off-label use was obtained and patients and parents were given the required technical training and psychological support. Caregivers and medical professionals involved in the patients’ care at home were briefed intensely. Remote consultations were implemented and interdisciplinary in-hospital checks reduced to a long-term 4-week-scheme.ConclusionWhile it is challenging to discharge pediatric patients being treated with a paracorporeal ventricular assist device (EXCOR® VAD) from hospital, it is feasible and can be managed safely with the novel driving unit EXCOR® Active. A HHE may help to improve patients’ psychomotor development, offer normalized social contacts and strengthen both patients’ and parents’ physical and mental resources. Legal approval and another study with a larger sample size are warranted.

BackgroundIn Fontans, exercise tolerance is poorer compared to their healthy peers. Higher V˙O2peak represents a strong predictor for mortality and morbidity in these patients. Cardiac rehabilitation programs have been shown to improve cardiopulmonary function in Fontans. More habitual physical activity should therefore lead to a better exercise tolerance.MethodsWe performed cardiopulmonary exercise testing in 24 Fontan patients who had engaged in physical activity for a minimum of 3 h per week over their lifetime. As a control we performed cardiopulmonary exercise testing in 20 Fontan patients who had undertaken no physical activity or

(1) Purpose: to compare right ventricular (RV) functional parameters in children with surgically repaired congenital heart disease (CHD) using single/double breath hold (BH) and free-breathing (FB) real-time compressed sensing (CS) cine cardiac magnetic resonance (cMRI) with standard retrospective segmented multi breath hold (RMB) cine cMRI. (2) Methods: Twenty patients with CHD underwent BH and FB, as well as RMB cine cMRI, at 3T to obtain a stack of continuous axial images of the RV. Two radiologists independently performed qualitative analysis of the image quality (rated on a 5-point scale; 1 = non-diagnostic to 5 = excellent) and quantitative analysis of the RV volume measurements. (3) Results: The best image quality was provided by RMB (4.5; range 2–5) compared to BH (3.9; range 3–5; p = 0.04) and FB (3.6; range 3–5; p < 0.01). The RV functional parameters were comparable among BH, FB, and RMB with a difference of less than 5%. The scan times for BH (44 ± 38 s, p < 0.01) and FB (24 ± 7 s, p < 0.01) were significantly reduced compared to for RMB (261 ± 68 s). (4) Conclusions: CS-FB and CS-BH real-time cine cMRI in children with CHD provides diagnostic image quality with excellent accuracy for measuring RV function with a significantly reduced scan time compared to RMB.

Introduction: All the research investigating the cardiopulmonary capacity in climbers is focused on predictors for climbing performance. The effects of climbing on the cardiovascular system in adolescents climbing at an elite level (national team) have not been evaluated.Material and methods: Retrospective analysis of the cardiopulmonary exercise test (CPET) performed on a cycle ergometer during the annual medical examination of the entire German Junior National climbing team on one occasion and for a selected subgroup on two occasions spaced two years apart. The data from the subgroup was compared to an age- and gender-matched control of Nordic skiers from the German Junior National Nordic skiing team. Results: 47 climbers (20 girls, 27 boys) were examined once. The VO2peak achieved by the athletes was 41.3 mL kg−1 min−1 (boys) and 39.8 mL kg−1 min−1 (girls). 8 boys and 6 girls were tested twice over a period of 27.5 months. The parameters of the exercise test measured on both occasions were significantly lower than those of the 8 male and 6 female Nordic skiers. There was no change with respect to any variables (e.g. VO2peak, peak work load, peak heart rate, peak lactate or O2 pulse) over the examined period. Conclusions: The elite climbers investigated in this study showed comparable VO2peak values to athletes from team and combat sports. The Nordic skiers to which they were compared showed significantly higher values consistant with the fact that this is an endurance sport. Even though the cardiopulmonary measurements of the Nordic skiers still improved after two years of training, no adaptations could be observed in the elite climbers.

Background: Reliable laboratory parameters identifying complications after Fontan surgery including the lymphatic abnormalities and the development of protein-losing enteropathy (PLE) are rare. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocte ratio (PLR) are inflammatory markers and have been studied to predict outcome and prognosis in various diseases. The aim of this study was to investigate NLR and PLR from birth to follow-up after Fontan and evaluate their use as prognostic parameters for single ventricle patients regarding the development of lymphatic malformations during follow-up.Materials and Methods: Sixty-six univentricular patients who underwent Fontan surgery and had 6-month follow-up magnetic resonance imaging (MRI) with T2 weighted lymphatic imaging after total cavopulmonary connection (TCPC) surgery were included in the study. NLR and PLR were determined at specific time points, from neonatal age to follow-up after Fontan operation and correlated to data from the MRI 6 months after Fontan.Results: NLR and PLR increase significantly over time from the first surgery during infancy to the follow-up after Fontan (both p < 0.0001), with a significant increase after the Glenn surgery for both ratios (each p < 0.0001). Higher NLR (p = 0.002) and higher PLR (p = 0.004) correlated with higher-grade classification of lymphatic abnormalities in T2-weighted imaging 6 months after Fontan surgery and higher NLR correlated with higher transpulmonary gradient prior to Fontan surgery (p = 0.035) Both ratios showed a significant correlation to total protein at follow-up (NLR p = 0.0038; PLR

[This corrects the article DOI: 10.1371/journal.pgen.1009679.].

Abstract Background X-linked Duchenne muscular dystrophy (DMD), the most frequent human hereditary skeletal muscle myopathy, inevitably leads to progressive dilated cardiomyopathy. We assessed the effect and safety of a combined treatment with the ACE-inhibitor enalapril and the β-blocker metoprolol in a German cohort of infantile and juvenile DMD patients with preserved left ventricular function. Methods Trial design Sixteen weeks single-arm open run-in therapy with enalapril and metoprolol followed by a two-arm 1:1 randomized double-blind placebo-controlled treatment in a multicenter setting. Inclusion criteria: DMD boys aged 10–14 years with left ventricular fractional shortening [LV-FS] ≥ 30% in echocardiography. Primary endpoint: time from randomization to first occurrence of LV-FS

Abstract Background Postoperative fluid management in critically ill neonates and infants with capillary leak syndrome (CLS) and extensive volume overload after cardiac surgery on cardiopulmonary bypass is challenging. CLS is often resistant to conventional diuretic therapy, aggravating the course of weaning from invasive ventilation, increasing length of stay on ICU and morbidity and mortality. Methods Tolvaptan (TLV, vasopressin type 2 receptor antagonist) was used as an additive diuretic in neonates and infants with CLS after cardiac surgery. Retrospective analysis of 25 patients with CLS including preoperative and postoperative parameters was performed. Multivariate regression analysis was performed to identify predictors for TLV response. Results Multivariate analysis identified urinary output during 24 h after TLV administration and mean blood pressure (BP) on day 2 of TLV treatment as predictors for TLV response (AUC = 0.956). Responder showed greater weight reduction (p

Numerous genetic studies have established a role for rare genomic variants in Congenital Heart Disease (CHD) at the copy number variation (CNV) and de novo variant (DNV) level. To identify novel haploinsufficient CHD disease genes, we performed an integrative analysis of CNVs and DNVs identified in probands with CHD including cases with sporadic thoracic aortic aneurysm. We assembled CNV data from 7,958 cases and 14,082 controls and performed a gene-wise analysis of the burden of rare genomic deletions in cases versus controls. In addition, we performed variation rate testing for DNVs identified in 2,489 parent-offspring trios. Our analysis revealed 21 genes which were significantly affected by rare CNVs and/or DNVs in probands. Fourteen of these genes have previously been associated with CHD while the remaining genes (FEZ1, MYO16, ARID1B, NALCN, WAC, KDM5B and WHSC1) have only been associated in small cases series or show new associations with CHD. In addition, a systems level analysis revealed affected protein-protein interaction networks involved in Notch signaling pathway, heart morphogenesis, DNA repair and cilia/centrosome function. Taken together, this approach highlights the importance of re-analyzing existing datasets to strengthen disease association and identify novel disease genes and pathways.

Primary surgical repair remains the traditional treatment for patients with critical duct-dependent coarctation of the aorta (CoA). Initial surgical repair might not be possible or associated with higher risks if additional comorbidities arise in small infants and neonates. Balloon angioplasty (BA) has been described as a rescue strategy for these children. We describe the feasibility of a palliative BA and rescue stent implantation via an alternative antegrade right-axillary artery approach in an initially inoperable infant with pneumonia and respiratory failure and severe CoA, where the stenosis was not passable by traditional retrograde femoral access. This case adds new aspects to the therapy of critical CoA: Stent implantation provides a bridge to surgery in critically ill infants and does not preclude successful surgical repair. Further, if the classic retrograde approach is not possible, the right axillary artery access should be considered as an alternative to pass the stenosis.

Background: Protein-losing enteropathy (PLE) is a severe complication of the univentricular Fontan circulation and associated with disturbances in salt and water homeostasis. Fontan patients with PLE have a poor prognosis, with increased morbidity and mortality. Due to limited therapeutic strategies, patients are often treated only symptomatically. Methods: We report our first experience of Tolvaptan (TLV) treatment in a Fontan patient with PLE, severe volume retention and hyponatraemia, refractory to conventional diuretic therapy. In addition to clinical parameters, we monitored drug effects including tissue sodium and volume status via serial 23 Na-magnetic resonance imaging ( 23 Na-MRI) and bioimpedance spectroscopy compared with age-matched controls. Results: 23 Na-MRI identified elevated tissue sodium, which decreased under TLV treatment, as well as volume status, while serum sodium increased and the patient’s symptoms improved. During long-term treatment, we were able to differentiate between sodium and volume status in our patient, suggesting that TLV uncoupled body sodium from water. Conclusion: TLV in addition to loop diuretics improved clinical symptoms of PLE and lowered tissue sodium overload. Long-term effects should be further evaluated in Fontan patients.

Summary: Right ventricular hypertrophy (RVH) occurs in high pressure afterload, e.g., tetralogy of Fallot/pulmonary stenosis (TOF/PS). Such RVH is associated with alterations in energy metabolism, neurohormonal and epigenetic dysregulation (e.g., microRNA), and fetal gene reprogramming in animal models. However, comprehensive expression profiling of competing endogenous RNA in human RVH has not been performed. Here, we unravel several previously unknown circular, long non-coding, and microRNAs, predicted to regulate expression of genes specific to human RVH in the non-failing heart (TOF/PS). These genes are significantly overrepresented in pathways related to regulation of glucose and lipid metabolism (SIK1, FABP4), cell surface interactions (THBS2, FN1), apoptosis (PIK3IP1, SIK1), extracellular matrix composition (CTGF, IGF1), and other biological events. This is the first unbiased RNA sequencing study of human compensated RVH encompassing coding and non-coding RNA expression and predicted sponging of miRNAs by non-coding RNAs. These findings advance our understanding of adaptive RVH and highlight future therapeutic targets.

Cinematic rendering (CR) is based on a new algorithm that creates a photo-realistic three-dimensional (3D) picture from cross-sectional images. Previous studies have shown its positive impact on preoperative planning. To date, CR presentation has only been possible on 2D screens which limited natural 3D perception. To depict CR-hearts spatially, we used mixed-reality technology and mapped corresponding hearts as holograms in 3D space. Our aim was to assess the benefits of CR-holograms in the preoperative planning of cardiac surgery. Including 3D prints allowed a direct comparison of two spatially resolved display methods. Twenty-six patients were recruited between February and September 2019. CT or MRI was used to visualize the patient's heart preoperatively. The surgeon was shown the anatomy in cross-sections on a 2D screen, followed by spatial representations as a 3D print and as a high-resolution hologram. The holographic representation was carried out using mixed-reality glasses (HoloLens®). To create the 3D prints, corresponding structures were segmented to create STL files which were printed out of resin. In 22 questions, divided in 5 categories (3D-imaging effect, representation of pathology, structure resolution, cost/benefit ratio, influence on surgery), the surgeons compared each spatial representation with the 2D method, using a five-level Likert scale. The surgical preparation time was assessed by comparing retrospectively matched patient pairs, using a paired t-test. CR-holograms surpassed 2D-monitor imaging in all categories. CR-holograms were superior to 3D prints in all categories (mean Likert scale 4.4 ± 1.0 vs. 3.7 ± 1.3, P < 0.05). Compared to 3D prints it especially improved the depth perception (4.7 ± 0.7 vs. 3.7 ± 1.2) and the representation of the pathology (4.4 ± 0.9 vs. 3.6 ± 1.2). 3D imaging reduced the intraoperative preparation time (n = 24, 59 ± 23 min vs. 73 ± 43 min, P < 0.05). In conclusion, the combination of an extremely photo-realistic presentation via cinematic rendering and the spatial presentation in 3D space via mixed-reality technology allows a previously unattained level of comprehension of anatomy and pathology in preoperative planning.

Chronic heart failure (HF) in adults causes remodeling of the cardiomyocyte transverse tubular system (t-system), which contributes to disease progression by impairing excitation-contraction (EC) coupling. However, it is unknown if t-system remodeling occurs in pediatric heart failure. This study investigated the t-system in pediatric viral myocarditis. The t-system and integrity of EC coupling junctions (co-localization of L-type Ca2+ channels with ryanodine receptors and junctophilin-2) were analyzed by 3D confocal microscopy in left-ventricular (LV) samples from 5 children with myocarditis (age 14 ± 3 months), undergoing ventricular assist device (VAD) implantation, and 5 children with atrioventricular septum defect (AVSD, age 17 ± 3 months), undergoing corrective surgery. LV ejection fraction (EF) was 58.4 ± 2.3% in AVSD and 12.2 ± 2.4% in acute myocarditis. Cardiomyocytes from myocarditis samples showed increased t-tubule distance (1.27 ± 0.05 μm, n = 34 cells) and dilation of t-tubules (volume-length ratio: 0.64 ± 0.02 μm2) when compared with AVSD (0.90 ± 0.02 μm, p < 0.001; 0.52 ± 0.02 μm2, n = 61, p < 0.01). Intriguingly, 4 out of 5 myocarditis samples exhibited sheet-like t-tubules (t-sheets), a characteristic feature of adult chronic heart failure. The fraction of extracellular matrix was slightly higher in myocarditis (26.6 ± 1.4%) than in AVSD samples (24.4 ± 0.8%, p < 0.05). In one case of myocarditis, a second biopsy was taken and analyzed at VAD explantation after extensive cardiac recovery (EF from 7 to 56%) and clinical remission. When compared with pre-VAD, t-tubule distance and density were unchanged, as well as volume-length ratio (0.67 ± 0.04 μm2 vs. 0.72 ± 0.05 μm2, p = 0.5), reflecting extant t-sheets. However, junctophilin-2 cluster density was considerably higher (0.12 ± 0.02 μm−3 vs. 0.05 ± 0.01 μm−3, n = 9/10, p < 0.001), approaching values of AVSD (0.13 ± 0.05 μm−3, n = 56), and the measure of intact EC coupling junctions showed a distinct increase (20.2 ± 5.0% vs. 6.8 ± 2.2%, p < 0.001). Severe t-system loss and remodeling to t-sheets can occur in acute HF in young children, resembling the structural changes of chronically failing adult hearts. T-system remodeling might contribute to cardiac dysfunction in viral myocarditis. Although t-system recovery remains elusive, recovery of EC coupling junctions may be possible and deserves further investigation.

Lymphatic congestion in single-ventricle patients has been associated with increased morbidity and poor outcomes. Little is known about the dynamics of lymphatic abnormalities over time, on their association with clinical presentation or response to catheter interventions. This retrospective, single-center study describes Fontan patients who underwent at least two magnetic resonance imaging (MRI) studies. T2-weighted lymphatic imaging was used to classify thoracic and abdominal (para-aortic and portal-venous) lymphatic abnormalities. The relationship between lymphatic congestion and hemodynamic changes after cardiac catheter interventions, clinical presentation and MRI data was analyzed. A total of 33 Fontan patients underwent at least two cardiac MRI studies. Twenty-two patients had two, eight had three and three had four lymphatic imaging studies (total of 80 MRIs studies). No significant changes in lymphatic classification between MRI 1 and 2 were observed for thoracic (p = 0.400), para-aortic (0.670) and portal-venous (p = 0.822) abnormalities. No significant correlation between lymphatic classification and hemodynamic changes after intervention or MRI parameters was found. This study illustrates thoracic and abdominal lymphatic abnormalities in serial T2-weighted imaging after Fontan. Fontan patients did not demonstrate significant changes in their lymphatic perfusion, despite clinical or hemodynamic changes. We assume that lymphatic congestion might develop after total cavopulmonary connection (TCPC) and remain relatively stable, despite further intervention targeting hemodynamic parameters.

Ventricular assist devices (VADs) are used to provide mechanical circulatory support to patients with end-stage heart failure. The driveline connecting the external power source to the pump(s) of the intra-corporal VAD breaches the protective skin barrier and provides a track for microbes to invade the interior of the patient’s body. Driveline infection constitutes a major and potentially fatal vulnerability of VAD therapy. Driveline infection cannot traditionally be salvaged and requires the extraction of the entire VAD system. We report here the successful eradication of a VAD driveline infection with a taurolidine-containing antimicrobial solution used for preventing the infection of cardiac implantable electronic devices. If replicated in more cases, the novel treatment concept described here may provide a valuable alternative management strategy of salvage rather than explantation for VAD driveline infection.

In this paper, we are investigating the interaction between different passive material models and the mechano-electrical feedback (MEF) in cardiac modeling. Various types of passive mechanical laws (nearly incompressible/compressible, polynomial/exponential-type, transversally isotropic/orthotropic material models) are integrated in a fully coupled electromechanical model in order to study their specific influence on the overall MEF behavior. Our computational model is based on a three-dimensional (3D) geometry of a healthy rat left ventricle reconstructed from magnetic resonance imaging (MRI). The electromechanically coupled problem is solved using a fully implicit finite element-based approach. The effects of different passive material models on the MEF are studied with the help of numerical examples. It turns out that there is a significant difference between the behavior of the MEF for compressible and incompressible material models. Numerical results for the incompressible models exhibit that a change in the electrophysiology can be observed such that the transmembrane potential (TP) is unable to reach the resting state in the repolarization phase, and this leads to non-zero relaxation deformations. The most significant and strongest effects of the MEF on the rat cardiac muscle response are observed for the exponential passive material law.

For therapeutic decisions regarding uni- or biventricular surgical repair in congenital heart disease (CHD), left ventricular mass (LVM) is an important factor. The aim of this retrospective study was to determine the LVM of infants with CHD in thoracic computed tomography angiographies (CTAs) and to evaluate its usefulness as a prognostic parameter, with special attention paid to hypoplastic left heart (HLH) patients. Manual segmentation of the left ventricular endo- and epicardial volumes was performed in CTAs of 132 infants. LVMs were determined from these volumes and normalized to body surface area. LVMs of patients with different types of CHD were compared to each other using analyses of variances (ANOVA). An LVM cutoff for discrimination between uni- and biventricular repair was determined using receiver operating characteristics. Survival rates were calculated using Kaplan–Meier statistics. Patients with a clinical diagnosis of an HLH had significantly lower mean LVM (21.88 g/m2) compared to patients without applicable disease (50.22 g/m2; p < 0.0001) and compared to other CHDs, including persistent truncus arteriosus, left ventricular outflow tract obstruction, transposition of the great arteries, pulmonary artery stenosis or atresia, and double-outlet right ventricle (all, p < 0.05). The LVM cutoff for uni- vs. biventricular surgery was 33.9 g/m2 (sensitivity: 82.3%; specificity: 73.7%; PPV: 94.9%). In a subanalysis of HLH patients, a sensitivity of 50.0%, specificity of 100%, PPV of 100%, and NPV of 83.3% was determined. Patient survival was not significantly different between the surgical approaches or between patients with LVM above or below the cutoff. LVM can be measured in chest CTA of newborns with CHD and can be used as a prognostic factor.

OBJECTIVES:Coagulation factor XIII (FXIII) plays a key role in fibrin clot stabilization-an essential process for wound healing following cardiothoracic surgery. However, FXIII deficiency as a risk for post-operative bleeding in pediatric cardiac surgery involving cardiopulmonary bypass (CPB) for congenital heart disease (CHD) is controversially discussed. Thus, as primary outcome measures, we analyzed the association of pre-operative FXIII activity and post-operative chest tube drainage (CTD) loss with transfusion requirements post-operatively. Secondary outcomes included the influence of cyanosis and sex on transfusion. METHODS:Our retrospective analysis (2009-2010) encompassed a single center series of 76 cardio-surgical cases with CPB (0-17 years, mean age 5.61 years) that were post-operatively admitted to our pediatric intensive care unit (PICU). The observational period was 48 hours after cardiac surgery. Blood cell counts and coagulation status, including FXIII activity were routinely performed pre- and post-operatively. The administered amount of blood products and volume expanders was recorded electronically, along with the amount of CTD loss. Uni- and multivariate logistic regression analysis was performed to calculate the associations (odds ratios) of variables with post-operative transfusion needs. RESULTS:FXIII activities remained stable following CPB surgery. There was no association of pre- and post-operative FXIII activities and transfusion of blood products or volume expanders in the first 48 hours after surgery. Similarly, FXIII showed no association with CTD loss. Cyanosis and female sex were associated with transfusion rates. CONCLUSIONS:Although essentially involved in wound healing and clotting after surgery, FXIII activity does not serve as a valid predictor of post-operative transfusion need.

BACKGROUND:Coarctation of the aorta (CoA) accounts for 5-8% of all congenital heart defects. CoA can be detected in up to 20% of patients with Ullrich-Turner syndrome (UTS), in which a part or all of one of the X chromosomes is absent. The etiology of non-syndromic CoA is poorly understood. In the present work, we test the hypothesis that rare copy number variation (CNV) especially on the gonosomes, contribute to the etiology of non-syndromic CoA. METHODS:We performed high-resolution genome-wide CNV analysis using the Affymetrix SNP 6.0 microarray platform for 70 individuals with sporadic CoA, 3 families with inherited CoA (n=13) and 605 controls. Our analysis comprised genome wide association, CNV burden and linkage. CNV was validated by multiplex ligation-dependent probe amplification. RESULTS:We identified a significant abundance of large (>100 kb) CNVs on the X chromosome in males with CoA (p=0.005). 11 out of 51 (~ 22%) male cases had these large CNVs. Association analysis in the sporadic cohort revealed 14 novel loci for CoA. The locus on 21q22.3 in the sporadic CoA cohort overlapped with a gene locus identified in all familial cases of CoA (candidate gene TRPM2). We identified one CNV locus within a locus with high multipoint LOD score from a linkage analysis of the familial cases (SEPT9); another locus overlapped with a region implicated in Kabuki syndrome. In the familial cases, we identified a total of 7 CNV loci that were exclusively present in cases but not in unaffected family members. CONCLUSION:Of all candidate loci identified, the TRPM2 locus was the most frequently implicated autosomal locus in sporadic and familial cases. However, the abundance of large CNVs on the X chromosome of affected males suggests that gonosomal aberrations are not only responsible for syndromic CoA but also involved in the development of sporadic and non-syndromic CoA and their male dominance.

QUESTIONS UNDER STUDY: To evaluate the diagnostic value of serum Cystatin C and urine neutrophil gelatinase-associated lipocalin (NGAL) for the detection of acute kidney injury in patients undergoing congenital heart surgery. METHODS: Serial samples of serum Cystatin C and urine NGAL were collected from 139 consecutive patients with congenital heart defects aged 3 days to 30 years after admission to the intensive care unit, 2 and 6 hours after the end of cardiopulmonary bypass. Biomarker levels were compared to perioperative data retrospectively. Acute kidney injury was defined according to the paediatric-modified RIFLE classification. RESULTS: According to the paediatric-modified RIFLE criteria 53% of patients developed evidence of acute kidney injury. Serum Cystatin C concentrations were strongly correlated with severity of acute kidney injury. Optimal sensitivity of 80% and specificity of 66% for the prediction of acute kidney injury occurred at a cut-off value of 0.995 mg/l, 2 hours after the end of cardiopulmonary bypass. The 2 hour urine NGAL concentration was significantly correlated to the duration of cardiopulmonary bypass, time of aortic cross clamping, and serum lactate concentration. Moreover a significant correlation was found between urine NGAL and both length of hospital stay and mechanical ventilation. CONCLUSIONS: In patients after congenital heart surgery, urine NGAL indicates the damaging force of cardiopulmonary bypass and serum Cystatin C is a valuable predictive biomarker for resulting acute kidney injury.