Altered Serum Proteins Suggest Inflammation, Fibrogenesis and Angiogenesis in Adult Patients with a Fontan Circulation.

Previous omics research in patients with complex congenital heart disease and single-ventricle circulation (irrespective of the stage of palliative repair) revealed alterations in cardiac and systemic metabolism, inter alia abnormalities in energy metabolism, and inflammation, oxidative stress or endothelial dysfunction. We employed an affinity-proteomics approach focused on cell surface markers, cytokines, and chemokines in the serum of 20 adult Fontan patients with a good functioning systemic left ventricle, and we 20 matched controls to reveal any specific processes on a cellular level. Analysis of 349 proteins revealed 4 altered protein levels related to chronic inflammation, with elevated levels of syndecan-1 and glycophorin-A, as well as decreased levels of leukemia inhibitory factor and nerve growth factor-ß in Fontan patients compared to controls. All in all, this means that Fontan circulation carries specific physiological and metabolic instabilities, including chronic inflammation, oxidative stress imbalance, and consequently, possible damage to cell structure and alterations in translational pathways. A combination of proteomics-based biomarkers and the traditional biomarkers (uric acid, γGT, and cholesterol) performed best in classification (patient vs. control). A metabolism- and signaling-based approach may be helpful for a better understanding of Fontan (patho-)physiology. Syndecan-1, glycophorin-A, leukemia inhibitory factor, and nerve growth factor-ß, especially in combination with uric acid, γGT, and cholesterol, might be interesting candidate parameters to complement traditional diagnostic imaging tools and the determination of traditional biomarkers, yielding a better understanding of the development of comorbidities in Fontan patients, and they may play a future role in the identification of targets to mitigate inflammation and comorbidities in Fontan patients.

The Manchester Triage System in a Pediatric Emergency Department of an Austrian University Hospital: A Retrospective Analysis of Urgency Levels.

OBJECTIVES: The Manchester Triage System (MTS) has entered widespread international use in emergency departments (EDs). This retrospective study analyzes urgency of patient visits (PV) at the ED of the Clinic for Pediatrics at the Medical University of Innsbruck. METHODS: We collected demographic and outcome information, including PV urgency levels (UL) according to the MTS, for 3 years (2015-2018), separating PV during regular office hours (ROH; 8:00 am to 5:00 pm) from PV during afternoon and night hours (5:00 pm to 8:00 am), and PV on weekdays from PV on weekends and bank holidays (WE). RESULTS: A total of 56,088 PV were registered with a UL. Most (68.4%) PV were classified as nonurgent. During ROH, more PV per hour (PV/h) were recorded than during afternoon and night hours (3.0 PV/h vs 1.6 PV/h), with a higher proportion of less urgent cases during ROH. On WE, the amount of PV/h was higher than on weekdays (3.6 PV/h vs 2.8 PV/h), with a higher proportion of nonurgent cases (74.6% vs 68.6%). Likelihoods of inpatient admission and hospital stay lengths increased in step with UL. CONCLUSIONS: The MTS proved useful for delineating UL distributions. The MTS analyses may be of value in managing EDs. Prompted by the results of our study, a general practice pediatric care unit was established to support the ED during WE.

Subdural Hygroma in an Infant with Marfan's Syndrome.

Based on a patient encounter in which genetically confirmed Marfan's syndrome (MFS) underlay a spontaneously resolving subdural hygroma (SDHy) diagnosed in infancy, we review the literature of MFS clinically manifest in early life (early-onset MFS [EOMFS]) and of differential diagnoses of SDHy and subdural hemorrhage (SDHe) at this age. We found that rare instances of SDHy in the infant are associated with EOMFS. The most likely triggers are minimal trauma in daily life or spontaneous intracranial hypotension. The differential diagnosis of etiologies of SDHy include abusive and nonabusive head trauma, followed by perinatal events and infections. Incidental SDHy and benign enlargement of the subarachnoid spaces must further be kept in mind. SDHy exceptionally also may accompany orphan diseases. Thus, in the infant, EOMFS should be considered as a cause of SDHe and/or SDHy. Even in the absence of congestive heart failure, the combination of respiratory distress syndrome, muscular hypotonia, and joint hyperflexibility signals EOMFS. If EOMFS is suspected, monitoring is indicated for development of SDHe and SDHy with or without macrocephaly. Close follow-up is mandatory.

Method comparison of HPLC-ninhydrin-photometry and UHPLC-PITC-tandem mass spectrometry for serum amino acid analyses in patients with complex congenital heart disease and controls.

INTRODUCTION: Metabolomics studies are not routine when quantifying amino acids (AA) in congenital heart disease (CHD). OBJECTIVES: Comparative analysis of 24 AA in serum by traditional high-performance liquid chromatography (HPLC) based on ion exchange and ninhydrin derivatisation followed by photometry (PM) with ultra-high-performance liquid chromatography and phenylisothiocyanate derivatisation followed by tandem mass spectrometry (TMS); interpretation of findings in CHD patients and controls. METHODS: PM: Sample analysis as above (total run time, ~ 119 min). TMS: Sample analysis by AbsoluteIDQ® p180 kit assay (BIOCRATES Life Sciences AG, Innsbruck, Austria), which employs PITC derivatisation; separation of analytes on a Waters Acquity UHPLC BEH18 C18 reversed-phase column, using water and acetonitrile with 0.1% formic acid as the mobile phases; and quantification on a Triple-Stage Quadrupole tandem mass spectrometer (Thermo Fisher Scientific, Waltham, MA) with electrospray ionisation in the presence of internal standards (total run time, ~ 8 min). Calculation of coefficients of variation (CV) (for precision), intra- and interday accuracies, limits of detection (LOD), limits of quantification (LOQ), and mean concentrations. RESULTS: Both methods yielded acceptable results with regard to precision (CV < 10% PM, < 20% TMS), accuracies (< 10% PM, < 34% TMS), LOD, and LOQ. For both Fontan patients and controls AA concentrations differed significantly between methods, but patterns yielded overall were parallel. CONCLUSION: Serum AA concentrations differ with analytical methods but both methods are suitable for AA pattern recognition. TMS is a time-saving alternative to traditional PM under physiological conditions as well as in patients with CHD. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier NCT03886935, date of registration March 27th, 2019 (retrospectively registered).

National Survey on Training in Pediatric Cardiology by the "Junges Forum" of the DGPK.

BACKGROUND: This is the first national survey of residents and fellows in pediatric cardiology in Germany evaluating training, research activity, and the general working environment. METHODS: An online questionnaire including 62 questions (SurveyMonkey) was developed by the "Junges Forum" of the German Society of Pediatric Cardiology. Fellows and residents during training and up to 3 years after completing their pediatric cardiology fellowship were invited to participate. RESULTS: A total of 102 pediatric cardiology fellows and residents completed the questionnaire. Many participants complained about their training as being unstructured (47%) and non-transparent (37%). The numbers of technical and catheter interventions required by the national medical board in Germany cannot be achieved, especially regarding invasive procedures. Sixty per cent work more than contractually agreed, usually in Germany it is 40 hours daytime work plus on calls, while 90% of all participants prefer less than 50 weekly working hours; 50% of the participants are engaged in research that is usually done during their spare time. More than 90% are satisfied with their professional relationships with colleagues and coworkers. Seventy-eight per cent describe their career perspectives as promising, and 84% would start a fellowship in pediatric cardiology again. CONCLUSION: The majority of pediatric cardiology fellows and residents are satisfied with their working environment and with their choice of a career in pediatric cardiology. Besides the heavy work load, we identified the urgent desire for better structured transparent clinical training concept including the teaching of manual skills, i.e., invasive procedures and catheterization.

Presumed prenatal closure of foramen ovale and persistent pulmonary hypertension of the newborn.

Prenatal closure of foramen ovale without CHD is a rarely reported entity. Therefore, clinical and echocardiographic findings are poorly defined in these patients. We report a patient with prenatal closure of foramen ovale that presented with severe pulmonary hypertension of the newborn and left ventricular failure. Judicious management strategies were utilised to successfully treat both life-threatening conditions.

Standardized training for AVT pacing in paediatric patients with postoperative junctional ectopic tachycardia.

BACKGROUND: Junctional ectopic tachycardia is a serious complication of surgery for paediatric congenital heart disease. R-wave synchronized atrial (AVT) pacing, an innovative temporary pacing technique, restores atrioventricular synchrony in these patients. The method is highly effective but technically complex. A standardized training model exists for doctors but not for paediatric intensive care nurses. AIMS: This study seeks to evaluate whether a standardized programme involving simulation and vignettes increases knowledge of AVT pacing and accuracy of its documentation, as well as recognition and management of specific complications. STUDY DESIGN: This study was an experimental simulation test with before and after descriptive evaluation. METHODS: A custom-made simulation model was used in combination with standardized training. Before and after training, 10 paediatric nurse specialists were asked to document pacing, to identify complications and to intervene as necessary. Four clinical scenarios were presented: effective AVT pacing, ineffective AVT pacing, pacing with narrow interval between atrial pacing and ventricular sensing and pacemaker-induced tachycardia. Identification and management of complications were evaluated using a 3-point scale. RESULTS: Training improved the quality of documentation and complication management. At outset, documentation by 1 of 10 participants was completely correct, and after training, documentation by 8 of 10 participants was completely correct. Before training, 30% of interpretations of the four presented clinical scenarios were correct (12/40) versus 83% (33/40) after training. The decision to notify a doctor of a complication was correct in 83% (33/40) before versus 95% (38/40) after the training. CONCLUSION: Standardized simulation training improves quality and safety in AVT pacing, with more accurate documentation of the pacing mode and better recognition and management of specific complications during pacing. RELEVANCE TO CLINICAL PRACTICE: AVT pacing should be performed in conjunction with standardized simulation training in paediatric cardiac intensive care units.

R-wave synchronised atrial pacing in pediatric patients with postoperative junctional ectopic tachycardia: the atrioventricular interval investigated by computational analysis and clinical evaluation.

BACKGROUND: R-wave synchronised atrial pacing is an effective temporary pacing therapy in infants with postoperative junctional ectopic tachycardia. In the technique currently used, adverse short or long intervals between atrial pacing and ventricular sensing (AP-VS) may be observed during routine clinical practice. OBJECTIVES: The aim of the study was to analyse outcomes of R-wave synchronised atrial pacing and the relationship between maximum tracking rates and AP-VS intervals. METHODS: Calculated AP-VS intervals were compared with those predicted by experienced pediatric cardiologist. RESULTS: A maximum tracking rate (MTR) set 10 bpm higher than the heart rate (HR) may result in undesirable short AP-VS intervals (minimum 83 ms). A MTR set 20 bpm above the HR is the hemodynamically better choice (minimum 96 ms). Effects of either setting on the AP-VS interval could not be predicted by experienced observers. In our newly proposed technique the AP-VS interval approaches 95 ms for HR > 210 bpm and 130 ms for HR < 130 bpm. The progression is linear and decreases strictly (- 0.4 ms/bpm) between the two extreme levels. CONCLUSIONS: Adjusting the AP-VS interval in the currently used technique is complex and may imply unfavorable pacemaker settings. A new pacemaker design is advisable to allow direct control of the AP-VS interval.

Management of postoperative junctional ectopic tachycardia in pediatric patients: a survey of 30 centers in Germany, Austria, and Switzerland.

Postoperative junctional ectopic tachycardia (JET) is a frequent complication after pediatric cardiac surgery. Current recommendations on how and when to treat JET are inconsistent. We evaluated the management strategies of postoperative JET in German-speaking countries. We sent an online survey to 30 centers of pediatric cardiology that perform surgery for congenital heart defects in Germany (24), Austria (4), and Switzerland (2). The survey asked 18 questions about how and in what treatment sequence postoperative JET was managed. All 30 centers completed the survey (100% return rate). There was general agreement that the management of JET is based on administration of antiarrhythmic drugs, body surface cooling, and temporary pacing. Many centers presented treatment algorithms based on published literature, all centers named amiodarone as the first drug of choice. Significant disagreement was found concerning the timing and sequential order of additional therapeutic measures and particularly about the dosing of amiodarone and the role of R-wave synchronized atrial pacing. CONCLUSION: This survey reveals that from center to center, the treatment of postoperative JET may vary substantially. Future work should focus on those treatment modalities where a high rate of variation is found. Such studies may be of value to achieve commonly adopted treatment recommendations. What is known: • Treatment of postoperative junctional ectopic tachycardia is predominantly based on administration of antiarrhythmic drugs, therapeutic cooling, and temporary pacing. • Amiodarone is the antiarrhythmic drug of choice in this context. What is new: • Dosing and duration of administration of amiodarone differ relevantly from center to center. • The sequential order of drug administration, therapeutic cooling, and pacing is not consistent.

Breast milk feeding in infants with inherited metabolic disorders other than phenylketonuria - a 10-year single-center experience.

BACKGROUND: Published data on breast milk feeding in infants suffering from inherited metabolic disorders (IMDs) other than phenylketonuria (PKU) are limited and described outcome is variable. OBJECTIVE: We aimed to evaluate retrospectively whether breastfeeding and/or breast milk feeding are feasible in infants with IMDs including organic acidemias, fatty acid oxidation disorders, urea cycle disorders, aminoacidopathies or disorders of galactose metabolism. METHODS: Data on breastfeeding and breast milk feeding as well as monitoring and neurological outcome were collected retrospectively from our database of patients with the mentioned IMD, who were followed in our metabolic center within the last 10 years. RESULTS: Twenty patients were included in the study, who were either breast fed on demand or received expressed breast milk. All the infants were evaluated clinically and biochemically at 2-4-week intervals, with weight gain as the leading parameter to determine metabolic control. Good metabolic control and adequate neurological development were achieved in all patients but one, who experienced the only metabolic crisis observed within the study period. CONCLUSION: Breast milk feeding with close clinical and biochemical monitoring is feasible in most IMD and should be considered as it offers nutritional and immunological benefits.

Impact of Different Diagnostic Criteria on the Reported Prevalence of Junctional Ectopic Tachycardia After Pediatric Cardiac Surgery.

OBJECTIVES: Junctional ectopic tachycardia is a frequent complication after pediatric cardiac surgery. A uniform definition of postoperative junctional ectopic tachycardia has yet to be established in the literature. The objective of this study is to analyze differences in the general and age-related prevalence of postoperative junctional ectopic tachycardia according to different diagnostic definitions. DESIGN: Data files and electrocardiograms of 743 patients (age, 1 d to 17.6 yr) who underwent surgery for congenital heart disease during a 3-year period were reviewed. The prevalence of postoperative junctional ectopic tachycardia in this cohort was determined according to six different definitions identified in the literature and one definition introduced for analytical purposes. Agreement between the definitions was analyzed according to Cohen κ coefficients. A receiver operating characteristic analysis was performed to determine the ability of different definitions to discriminate between patients with increased postoperative morbidity and without. SETTING: A university-affiliated tertiary pediatric cardiac PICU. PATIENTS: Infants and children who underwent heart surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The prevalence of postoperative junctional ectopic tachycardia ranged from 2.0% to 8.3% according to the seven different definitions. Even among definitions for which the general prevalence was almost equal, the distribution according to age varied. Most definitions used a frequency criterion to define postoperative junctional ectopic tachycardia. Definitions based on a fixed frequency criterion did not identify cases of postoperative junctional ectopic tachycardia in patients older than 12 months. The grade of agreement was moderate or poor between definitions using a fixed or dynamic frequency criterion and those not based on a critical heart rate (κ = 0.37-0.66). In the receiver operating characteristic analysis, the definition with a fixed frequency criterion of 180 beats/min or an age-related frequency criterion according to the 95th percentile showed the optimal cut-off value to determine increased postoperative morbidity. CONCLUSIONS: Different definitions of junctional ectopic tachycardia after pediatric cardiac surgery lead to relevant differences in the reported prevalence and age distribution pattern. A uniform definition of postoperative junctional ectopic tachycardia is needed to provide comparable study results and to improve the diagnosis of junctional ectopic tachycardia in pediatric patients.

Decline of Systolic and Diastolic 2D Strain Rate During Follow-Up of HLHS Patients After Fontan Palliation.

Accurate assessment of ventricular function is particularly important in children with hypoplastic left heart syndrome (HLHS) after completion of the total cavopulmonary connection (TCPC). For this purpose, two-dimensional speckle tracking (2DST) is a promising technique as it does not depend on the angle of insonation or the geometry of the ventricle. The objective of this study was to assess changes in systolic and diastolic right ventricular (RV) function within a 5-year follow-up period of HLHS patients after TCPC using conventional and 2DST echocardiography. RV fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE), E/A, E/e' and 2DST parameters [global longitudinal peak systolic strain (GS) and strain rate (GSRs), global strain rate in early (GSRe) and late (GSRa) diastole] of 40 HLHS patients were compared at 1.6 and at 5.1 years after TCPC. RVFAC, E/A, E/e' and GS did not change, whereas TAPSE (13.7 ± 3.2 vs. 10.5 ± 2.4 mm/m(2), p < 0.001), GSRs (-1.56 ± 0.28 vs. -1.35 ± 0.31 1/s, p < 0.001), GSRe (2.22 ± 0.49 vs. 1.96 ± 0.44 1/s, p = 0.004) and GSRa (1.19 ± 0.39 vs. 0.92 ± 0.39 1/s, p < 0.001) decreased significantly. Systolic and diastolic RV function parameters of HLHS patients decreased from 1.6 to 5.1 years after TCPC in our patients. Changes in global strain rate parameters may be signaling early RV dysfunction that is not detectable by traditional echocardiography. Further study is needed to verify this and to determine whether these changes are clinically relevant.

Potential Drug-Nutrient Interactions of 45 Vitamins, Minerals, Trace Elements, and Associated Dietary Compounds with Acetylsalicylic Acid and Warfarin-A Review of the Literature.

In cardiology, acetylsalicylic acid (ASA) and warfarin are among the most commonly used prophylactic therapies against thromboembolic events. Drug-drug interactions are generally well-known. Less known are the drug-nutrient interactions (DNIs), impeding drug absorption and altering micronutritional status. ASA and warfarin might influence the micronutritional status of patients through different mechanisms such as binding or modification of binding properties of ligands, absorption, transport, cellular use or concentration, or excretion. Our article reviews the drug-nutrient interactions that alter micronutritional status. Some of these mechanisms could be investigated with the aim to potentiate the drug effects. DNIs are seen occasionally in ASA and warfarin and could be managed through simple strategies such as risk stratification of DNIs on an individual patient basis; micronutritional status assessment as part of the medical history; extensive use of the drug-interaction probability scale to reference little-known interactions, and application of a personal, predictive, and preventive medical model using omics.

Comparative Metabolomics in Single Ventricle Patients after Fontan Palliation: A Strong Case for a Targeted Metabolic Therapy.

Most studies on single ventricle (SV) circulation take a physiological or anatomical approach. Although there is a tight coupling between cardiac contractility and metabolism, the metabolic perspective on this patient population is very recent. Early findings point to major metabolic disturbances, with both impaired glucose and fatty acid oxidation in the cardiomyocytes. Additionally, Fontan patients have systemic metabolic derangements such as abnormal glucose metabolism and hypocholesterolemia. Our literature review compares the metabolism of patients with a SV circulation after Fontan palliation with that of patients with a healthy biventricular (BV) heart, or different subtypes of a failing BV heart, by Pubmed review of the literature on cardiac metabolism, Fontan failure, heart failure (HF), ketosis, metabolism published in English from 1939 to 2023. Early evidence demonstrates that SV circulation is not only a hemodynamic burden requiring staged palliation, but also a metabolic issue with alterations similar to what is known for HF in a BV circulation. Alterations of fatty acid and glucose oxidation were found, resulting in metabolic instability and impaired energy production. As reported for patients with BV HF, stimulating ketone oxidation may be an effective treatment strategy for HF in these patients. Few but promising clinical trials have been conducted thus far to evaluate therapeutic ketosis with HF using a variety of instruments, including ketogenic diet, ketone esters, and sodium-glucose co-transporter-2 (SGLT2) inhibitors. An initial trial on a small cohort demonstrated favorable outcomes for Fontan patients treated with SGLT2 inhibitors. Therapeutic ketosis is worth considering in the treatment of Fontan patients, as ketones positively affect not only the myocardial energy metabolism, but also the global Fontan physiopathology. Induced ketosis seems promising as a concerted therapeutic strategy.

Influence of Respiration on Collateral Flow in the Fontan Population Using Real-time Phase-contrast Cardiovascular Magnetic Resonance: Collateral Flow Does Not Protect the Ventricle From Volume Deficiency and Diastolic Dysfunction.

PURPOSE: The clinical significance of collateral flow for the ventricular function of patients with univentricular hearts is often debated. This study evaluates the impact of collateral flow on respiration-dependent preload modification and diastolic function in Fontan patients assessed by systemic and pulmonary vein (PV) flow patterns. MATERIALS AND METHODS: Real-time phase-contrast cardiovascular magnetic resonance was performed in the right upper PV, ascending aorta, superior, and inferior vena cava (IVC) in 21 Fontan patients and 11 healthy individuals. The patients' respiratory cycle was divided into 4 periods to generate respiratory-dependent stroke volumes (SV i ). Conventional quantitative blood flow measurements were used to quantify and differentiate between low (group A) and high (group B) collateral flow. RESULTS: Group B showed significantly lower SV i IVC in inspiration, end-inspiration, expiration, and SV i ΔIVC compared with group A (23.6±4.8 mL/m 2 to 33.4±8.0; P =0.005). PV flow resulted in a lower mean SV i PV (11.6±7.6 mL/m 2 , vs. 14.0±11.4 mL/m 2 ) as well as a significantly lower peak systolic S-wave velocity (S max ) ( P =0.005), S/D-ratio (S max /peak diastolic wave velocity) ( P =0.015), and shorter diastolic deceleration time (DT D ; P =0.030; median DT D =134 ms) compared with group A (DT D =202 ms). CONCLUSIONS: This study demonstrates the incapability of Fontan patients to properly increase preload by inspiration in the presence of significant collateral flow. The results further show that collateral flow is associated with a volume-deprived ventricle and impaired diastolic function.

Fetal myocardial peak systolic strain before and after intrauterine red blood cell transfusion--a tissue Doppler imaging study.

OBJECTIVES: The purpose of this study is to evaluate the cardiac function in anemic fetuses by tissue Doppler imaging (TDI) measuring the myocardial peak systolic strain (PS) in fetuses before and after intrauterine transfusion (IUT) of red blood cells. METHODS: In our prospective clinical study in anemic fetuses, high-frame-rate TDI data files from a four-chamber view of fetal hearts pre- and post-IUT were analyzed. The biventricular PS parameters of the mid-segment of the ventricular walls [region of interest (ROI) 1 right ventricle, ROI 2 left ventricle] and the basal segment of the ventricular walls (ROI 3 tricuspid annulus, ROI 4 mitral annulus) were compared with the PS data of the normal controls. RESULTS: We analyzed the pre-/post-data sets from the 15 hearts of anemic fetuses and from the 17 controls. The threshold of statistical significance was set to P≤0.05. Compared with the controls, in anemic fetuses the left ventricular longitudinal myocardial PS (ROI 2, P=0.001) and PS in the basal segment of the right ventricle (ROI 3 P=0.009) was significantly increased (absolute amount). Compared with pre-IUT, post-IUT PS decreased significantly in both ventricles (ROI 1 P=0.025, ROI 2 P=0.02). Compared with the controls, post-IUT left ventricular PS was still higher (absolute amount) (ROI 2, P=0.026; ROI 4, P=0.009). CONCLUSIONS: The increase in myocardial PS due to severe fetal anemia is partially normalized by IUT. In anemic fetuses, assessment of TDI fetal myocardial PS is feasible.

Postnatal recurrence and transesophageal inducibility of prenatally treated fetal supraventricular tachycardia.

BACKGROUND: Antiarrhythmic treatment of fetal supraventricular tachycardia (SVT) is used to prevent morbidity and mortality. The postnatal management of survivors is often arbitrary and varied. OBJECTIVE: The purpose of this study was to examine the utility of a risk-based postnatal management strategy. METHODS: Sixty-six prenatally treated newborns with fetal long or short ventriculoatrial tachycardia were reviewed. Postnatal diagnoses included atrioventricular reentrant tachycardia, atrial ectopic tachycardia, and permanent junctional reciprocating tachycardia. Unless SVT persisted to birth, early neonatal observation without treatment was recommended. For newborns without spontaneous arrhythmia after ≥2 days of observation, inducibility was tested by transesophageal pacing study (TEPS). Postnatal therapy was advised for spontaneous or inducible SVT. Characteristics associated with these outcomes were analyzed. RESULTS: Twenty-eight patients (42%) experienced SVT at or early after birth, which was associated with fetal long ventriculoatrial tachycardia (odds ratio [OR] 6.8; 95% confidence interval [CI] 1.88-24.57; P = .0029); delayed in utero cardioversion with treatment (median 11 days vs 5.5 days; P < .0001); prenatal treatment with multiple antiarrhythmics (OR 4.42; 95% CI 1.56-12.55; P = .0059); and postnatal atrial ectopic tachycardia/permanent junctional reciprocating (OR 18.0; 95% CI 2.11-153.9; P = .0013). Of the 38 neonates undergoing TEPS, 19 (50%) had inducible tachyarrhythmias. Recurrence of SVT during infancy or childhood was documented in 4 of 6 patients with SVT at birth (66%), 8 of 22 patients with early neonatal SVT (36%), 4 of 19 patients with inducible SVT (21%), and 0 of 19 untreated patients without inducible SVT (0%) (P = .0032). CONCLUSION: The postnatal risk of SVT is related to the arrhythmia mechanism and prenatal treatment response. In newborns without spontaneous SVT, TEPS may be useful to guide the need for postnatal treatment on the basis of SVT inducibility.

Metabolomics and random forests in patients with complex congenital heart disease.

Introduction: It is increasingly common to simultaneously determine a large number of metabolites in order to assess the metabolic state of, or clarify biochemical pathways in, an organism ("metabolomics"). This approach is increasingly used in the investigation of the development of heart failure. Recently, the first reports with respect to a metabolomic approach for the assessment of patients with complex congenital heart disease have been published. Classical statistical analysis of such data is challenging. Objective: This study aims to present an alternative to classical statistics with respect to identifying relevant metabolites in a classification task and numerically estimating their relative impact. Methods: Data from two metabolomic studies on 20 patients with complex congenital heart disease and Fontan circulation and 20 controls were reanalysed using random forest (RF) methodology. Results were compared to those of classical statistics. Results: RF analysis required no elaborate data pre-processing. The ranking of the variables with respect to classification impact (subject diseased, or not) was remarkably similar irrespective of the evaluation method used, leading to identical clinical interpretation. Conclusion: In metabolomic classification in adult patients with complex congenital heart disease, RF analysis as a one-step method delivers the most adequate results with minimum effort. RF may serve as an adjunct to traditional statistics also in this small but crucial-to-monitor patient group.

Supportive methods for childhood acute lymphoblastic leukemia then and now: A compilation for clinical practice.

Survival of childhood acute lymphoblastic leukemia has significantly improved over the past decades. In the early years of chemotherapeutic development, improvement in survival rates could be attained only by increasing the cytostatic dose, also by modulation of the frequency and combination of chemotherapeutic agents associated with severe short- and long-time side-effects and toxicity in a developing child's organism. Years later, new treatment options have yielded promising results through targeted immune and molecular drugs, especially in relapsed and refractory leukemia, and are continuously added to conventional therapy or even replace first-line treatment. Compared to conventional strategies, these new therapies have different side-effects, requiring special supportive measures. Supportive treatment includes the prevention of serious acute and sometimes life-threatening events as well as managing therapy-related long-term side-effects and preemptive treatment of complications and is thus mandatory for successful oncological therapy. Inadequate supportive therapy is still one of the main causes of treatment failure, mortality, poor quality of life, and unsatisfactory long-term outcome in children with acute lymphoblastic leukemia. But nowadays it is a challenge to find a way through the flood of supportive recommendations and guidelines that are available in the literature. Furthermore, the development of new therapies for childhood leukemia has changed the range of supportive methods and must be observed in addition to conventional recommendations. This review aims to provide a clear and recent compilation of the most important supportive methods in the field of childhood leukemia, based on conventional regimes as well as the most promising new therapeutic approaches to date.