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Parameters of the interaction of the left atrium and left ventricle, atrioventricular (AV) coupling, are used in the diagnosis and follow-up of diastolic dysfunction in adults. Pediatric parameters of AV coupling have not been evaluated so far. The aim of this multicenter study was to investigate parameters of AV coupling in a large cohort of healthy infants and children using noninvasive real-time three-dimensional echocardiography. The authors hypothesized that the contribution of the different left atrial (LA) volumes to left ventricular (LV) stroke volume differs over a range of different heart rates.Three-dimensional echocardiographic data sets from 332 subjects (ages 0 days to 18.5 years) were analyzed prospectively. Volume-time curves of the left atrium and left ventricle were generated. Conduit volume was calculated and percentiles were established by the lambda-mu-sigma method of Cole and Green. Contributions of active, passive, and conduit volume to LV filling were measured and related to heart rate by linear regression. LV and LA peak filling rates (PFR) and peak emptying rates (PER) and time to PFR and PER normalized to the R-R interval (PFRConduit volume increased with body surface area. The contribution of LA active emptying to LV filling tended to increase with decreasing heart rate, while the contribution of passive emptying decreased. Conduit volume contributed most to LV filling (median, 57.58 %; interquartile range, 12.85%) with a tendency to increase with decreasing heart rate. Close diastolic AV coupling was demonstrated by virtually identical LV PFRAssessment of conduit volume and AV coupling by three-dimensional echocardiography is feasible in infants and children. The references of this study can serve as a basis to further investigate the role of parameters of AV coupling in pediatric patients with heart diseases concerning diastolic and LA function.

BACKGROUND Genetics of sudden cardiac deaths (SCD) remains frequently undetected. Genetic analysis is recommended in undefined selected cases in the 2021 ERC-guideline. The emergency medical service and physicians (EMS) may play a pivotal role for unraveling SCD by saving biomaterial for later molecular autopsy. Since for high-throughput DNA-sequencing (NGS) high quality genomic DNA is needed. We investigated in a prospective proof-of-concept study the role of the EMS for the identification of genetic forms of SCDs in the young. METHODS We included patients aged 1-50 years with need for cardiopulmonary resuscitation attempts (CPR). Cases with non-natural deaths were excluded. In two German counties with 562,904 residents 39,506 services were analysed. Paired end panel-sequencing was performed, and variants were classified according to guidelines of the American College of Medical Genetics (ACMG). RESULTS 769 CPR-attempts were recorded (1.95% of all EMS-services; CPR-incidence 68/100,000). In 103 cases CPR were performed in patients

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.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 (SVi). Conventional quantitative blood flow measurements were used to quantify and differentiate between low (group A) and high (group B) collateral flow.Group B showed significantly lower SVi IVC in inspiration, end-inspiration, expiration, and SVi ΔIVC compared with group A (23.6±4.8 mL/m2 to 33.4±8.0; P=0.005). PV flow resulted in a lower mean SVi PV (11.6±7.6 mL/m2, vs. 14.0±11.4 mL/m2) as well as a significantly lower peak systolic S-wave velocity (Smax) (P=0.005), S/D-ratio (Smax/peak diastolic wave velocity) (P=0.015), and shorter diastolic deceleration time (DTD; P=0.030; median DTD=134 ms) compared with group A (DTD=202 ms).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.

In children with congenital heart disease (CHD), excessive perioperative bleeding is associated with increased morbidity and mortality, thus making adequate perioperative hemostasis crucial. We investigate the prevalence of acquired von Willebrand syndrome type 2A (aVWS) in CHD and develop a treatment algorithm for patients with aVWS and CHD (TAPAC) to reduce perioperative blood loss.Retrospective cohort study.Single-center study.A total of 627 patients with CHD, undergoing corrective cardiac surgery between January 2008 and May 2017.The evaluation of perioperative bleeding risk was based on the laboratory parameters von Willebrand factor (VWF) antigen, ristocetin cofactor activity, platelet function analyzer (PFA) closure time adenosine diphosphate, and PFA epinephrine. According to the bleeding risk, treatment was performed with desmopressin or VWF.aVWS was confirmed in 63.3 %, with a prevalence of 45.5% in the moderate and 66.3 % in the high-risk group. In addition, prevalence increased with ascending peak velocity above the stenosis (v max ) from 40.0% at less than or equal to 3 m/s to 83.3% at greater than 5 m/s. TAPAC reduced mean blood loss by 36.3% in comparison with a historical control cohort ( plt; 0.001), without increasing the number of thrombotic or thromboembolic events during the hospital stay. With ascending v max , there was an increase in perioperative blood loss in the historical cohort ( plt; 0.001), which was not evident in the TAPAC cohort ( p = 0.230).The prevalence of aVWS in CHD seems to be higher than assumed and leads to significantly higher perioperative blood loss, especially at high v max . Identifying these patients through appropriate laboratory analytics and adequate treatment could reduce blood loss effectively.

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Background Right ventricular outflow tract (RVOT) stenosis after repair of tetralogy of Fallot has been linked with favorable right ventricular remodeling but adverse outcomes. The aim of our study was to assess the hemodynamic impact and prognostic relevance of right ventricular pressure load in this population. Methods and Results A total of 296 patients with repaired tetralogy of Fallot (mean age, 17.8±7.9 years) were included in a prospective cardiovascular magnetic resonance multicenter study. Myocardial strain was quantified by feature tracking technique at study entry. Follow‐up, including the need for pulmonary valve replacement, was assessed. The combined end point consisted of ventricular tachycardia and cardiac death. A higher echocardiographic RVOT peak gradient was significantly associated with smaller right ventricular volumes and less pulmonary regurgitation, but lower biventricular longitudinal strain. During a follow‐up of 10.1 (0.1–12.9) years, the primary end point was reached in 19 of 296 patients (cardiac death, n=6; sustained ventricular tachycardia, n=2; and nonsustained ventricular tachycardia, n=11). A higher RVOT gradient was associated with the combined outcome (hazard ratio [HR], 1.03; 95% CI, 1.00–1.06; P =0.026), and a cutoff gradient of ≥25 mm Hg was predictive for cardiovascular events (HR, 3.69; 95% CI, 1.47–9.27; P =0.005). In patients with pulmonary regurgitation ≥25%, a mild residual RVOT gradient (15–30 mm Hg) was not associated with a lower risk for pulmonary valve replacement. Conclusions Higher RVOT gradients were associated with less pulmonary regurgitation and smaller right ventricular dimensions but were related to reduced biventricular strain and emerged as univariate predictors of adverse events. Mild residual pressure gradients did not protect from pulmonary valve replacement. These results may have implications for the indication for RVOT reintervention in this population.

Mutations in RBM20 encoding the RNA-binding motif protein 20 (RBM20) are associated with an early onset and clinically severe forms of cardiomyopathies. Transcriptome analyses revealed RBM20 as an important regulator of cardiac alternative splicing. RBM20 mutations are especially localized in exons 9 and 11 including the highly conserved arginine and serine-rich domain (RS domain). Here, we investigated in several cardiomyopathy patients, the previously described RBM20-mutation p.Pro638Leu localized within the RS domain. In addition, we identified in a patient the novel mutation p.Val914Ala localized in the (glutamate-rich) Glu-rich domain of RBM20 encoded by exon 11. Its impact on the disease was investigated with a novel TTN- and RYR2-splicing assay based on the patients' cardiac messenger RNA. Furthermore, we showed in cell culture and in human cardiac tissue that mutant RBM20-p.Pro638Leu is not localized in the nuclei but causes an abnormal cytoplasmic localization of the protein. In contrast the splicing deficient RBM20-p.Val914Ala has no influence on the intracellular localization. These results indicate that disease-associated variants in RBM20 lead to aberrant splicing through different pathomechanisms dependent on the localization of the mutation. This might have an impact on the future development of therapeutic strategies for the treatment of RBM20-induced cardiomyopathies.

Purpose Quantitative blood flow measurements in thoracic vessels are dependent on the patient's respiration due to intrathoracic pressure changes. Several registration techniques for tracing the patient's breathing curve exist exploiting various physiological characteristics. In the presented study two registration techniques were investigated to estimate the time-shift between the associated respiration curves and the impact on respiration-dependent hemodynamic measures. Materials and methods Using flow-sensitive real-time magnetic resonance imaging (3.0 T, temporal resolution = 24–26 ms) data were acquired during a 13 s time-interval under normal physiological (no) and forced breathing (fo) in the ascending aorta (AAo) and inferior vena cava (IVC). Breathing curves were obtained by using (1) an abdominal placed respiratory belt (=standard, RB) and (2) by applying a self-developed edge-detection software (ED). Respiration curves were divided into four intervals (end-expiration, inspiration, end-inspiration and expiration) to generate respiration-dependent stroke volumes (SVs) and cardiac indices (CIs). Data were available from 12 healthy controls (16.2 ± 8.8 yrs) and 18 Fontan-patients (18.6 ± 7.1 yrs). Results Respiration curves acquired with RB differs from and are shifted compared to those obtained by ED (controls: average shift = 207 ± 168 ms, Fontan-patients: average shift = 106 ± 235 ms). This time-shift results in statistical significant differences in cardiac indices CIAAo,fo in controls (ΔCIAAo,fo: expiration: +0.16 L/min/m2, p = 0.018), in CIIVC,no in Fontan-patients (ΔCIIVC,no: end-expiration: +0.94 L/min/m2, p = 0.002 and end-inspiration: −1.04 L/min/m2, p = 0.017) and in CIIVC,fo in Fontan-patients (ΔCIIVC,fo: end-expiration: +1.31 L/min/m2, p = 0.009; inspiration: −2.26 L/min/m2, p = 0.008 and end-inspiration: −1.87 L/min/m2, p = 0.029). Conclusions A time-shift between both applied respiratory tracking techniques was observed resulting in significant differences in respiration-dependent CIs, which could influence the clinical decision-making.

Background Percutaneous pulmonary valve implantation (PPVI) numbers are rising but are still minor compared to surgery due to several contraindications. We sought to analyze the impact of PPVI compared to standard surgery in an unselected cohort with dysfunctional right ventricular outflow tract (RVOT). Reasons for PPVI failure and possible contraindications were explored. Methods Between 2010 and 2015 all consecutive patients who underwent surgery or intervention for a dysfunctional RVOT were investigated. Results A total of 382 cases was identified – 246 patients underwent successful valve insertion: 166 surgeries (166/246 = 67.4%) with 55/166 homografts (33.1%), 106 Contegra ® grafts (63.8%), 5 Hancock valves (3.0%). Overall, 70/246 patients presented a priori with an enlarged RVOT > 28 mm (28.5%) not appropriate for PPVI and 14/246 (5.7%) had additional defects necessitating surgery. Some 31/246 patients had surgery for initial repair of congenital defects or were too small ( ® valves (63.7%), 29 Melody valves (36.3%)]. The RVOT was too large for PPVI in 22/246 patients (8.9%). A total 20/246 patients (8.1%) showed coronary compression after balloon interrogation. In 4/246 patients PPVI was not possible due to technical issues (1.4%). Conclusion PPVI could be performed successfully in 80/382 patients (20.9%). An enlarged RVOT, small patient size, and coronary compression were the major obstacles for interventional management. Future developments for larger RVOTs and smaller body weight may expand the indication for PPVI.

Genetics of sudden cardiac deaths (SCD) remains frequently undetected. Genetic analysis is recommended in undefined selected cases in the 2021 ERC-guideline. The emergency medical service and physicians (EMS) may play a pivotal role for unraveling SCD by saving biomaterial for later molecular autopsy. Since for high-throughput DNA-sequencing (NGS) high quality genomic DNA is needed. We investigated in a prospective proof-of-concept study the role of the EMS for the identification of genetic forms of SCDs in the young.We included patients aged 1-50 years with need for cardiopulmonary resuscitation attempts (CPR). Cases with non-natural deaths were excluded. In two German counties with 562,904 residents 39,506 services were analysed. Paired end panel-sequencing was performed, and variants were classified according to guidelines of the American College of Medical Genetics (ACMG).769 CPR-attempts were recorded (1.95% of all EMS-services; CPR-incidence 68/100,000). In 103 cases CPR were performed in patients 50y. 58% died on scene, 26% were discharged from hospital. 24 subjects were included for genotyping. Of these 33% died on scene, 37.5% were discharged from hospital. 25% of the genotyped patients were carriers of (likely) pathogenic (ACMG-4/-5) variants. 67% carried variants with unknown significance (ACMG-3). 2 of them had familial history for arrhythmogenic cardiomyopathy or had to be re-classified as ACMG-4 carriers due to whole exome sequencing.The EMS contributes especially in fatal OHCA-cases to increase the yield of identified genetic conditions by collecting a blood sample on scene. Thus, the EMS can contribute significantly to primary and secondary prophylaxis in affected families.

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 PM, TMS), accuracies (PM, 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).

Background Real-time 3D echocardiography is a promising method for non-invasive assessment of right ventricular performance in children with congenital heart disease. Volume quantification using knowledge-based reconstruction (KBR) enables the calculation of right ventricular dimensions by matching endocardial landmarks with a reference library of right ventricular shapes. However, paediatric reference values for volumes based on KBR are missing. Aim of this study was to establish reference values for right ventricular volumes in a large paediatric population using 3D echocardiography and KBR. Methods In a multicentre prospective-design study, 545 healthy children and adolescents (age range, 1 day to 216 months) underwent 3D echocardiography of the right ventricle using two different vendors (iE33, Philips or Vivid 7, GE). Volume analysis was performed by a semiautomatic quantification software (VMS, Ventripoint Diagnostics Ltd., Washington, US). Reference centiles were computed using Cole's LMS method and the gamlss package in R. For vendor comparison, 3D datasets were recorded subsequently in 20 subjects using both ultrasound devices. Results 3D datasets of 406/545 (74.5%) subjects provided an adequate image quality. Right ventricular volumes had a significant association with age, body size and sex. We created sex-specific percentiles indexed to body surface area (BSA). Intra- and interobserver-variation for all volume calculations were excellent with intraclass correlation coefficients (ICCs) between 0.973-0.998. Agreement of both vendors showed slightly higher end-diastolic and stroke volumes (bias ± standard deviation 2.2%±6.8% respectively 4.5%±8.1%) and smaller end-systolic volumes (-0.9±10.3%) using Philips datasets. Conclusions Calculation of ventricular volumes by KBR allows reliable non-invasive assessment of right ventricular volumes with excellent intra- and interobserver variations. The calculated percentiles based on a large paediatric population serve as a reference and may facilitate the use of real-time 3D echocardiography for the analysis of right ventricular size and function.

Objective This single center study compared the risk of bacterial endocarditis (BE) after surgical and percutaneous pulmonary valve implantation. Methods Between Jan 1st 2010 and Dec 31st 2015 all patients who received a biological pulmonary valve (surgical/interventional) were identified. The clinical follow-up was analyzed with regard to BE applying the modified Duke criteria and echocardiographic findings. Results We identified 246 patients who underwent a biological pulmonary valve implantation. The mean age was 15.9 years, (SD 12.7, Median 13.1). There were 166 surgical patients (67.5%), with 55 homografts (22.4%, mean diameter 27.4 mm), 106 Contegra® grafts (43.1%, mean diameter 17.4) and 5 Hancock® valves (2.0, mean diameter 25.6 mm) and 80 percutaneous pulmonary valve implantations (PPVI) (32.5%) with 51 Edwards Sapien® valves (20.7%, mean diameter 25.2 mm) and 29 Melody® valves (11.8%, mean diameter 21.9 mm). Patients with a bovione jugular conduit as the biologiocal substrate had an increased risk for BE and patients with Melody® valves had the highest risk for BE that was 5–8 times higher as compared to other valves. BE episodes were detected in 5/106 Contegras® (4,7%, 1.5 per 100 person-years), and in 6/29 of the Melody® valves (20.7%, 4.8 per 100 person-years). There were no cases of BE in patients treated with Edwards Sapien®, homografts or Hankock® valves. Conclusion Whereas homografts and Edwards Sapien® valves seem to have a very low risk of BE, this risk is increased in Contegra® conduits and in Melody® valves.

Background Various techniques are described to facilitate stable stent implantation in aortic arch stenosis or coarctation. We describe an alternative technique, which due to its unique appearance during stent implantation, we have named “Dog Bone Technique” (DBT). Technique The stent/balloon assembly is placed across the stenosis, the long sheath is retrieved to uncover the distal 20–50% of the stent. The balloon is inflated with the pressure inflator just to expand slightly the stent. Thereafter the sheath is pulled back and the proximal end is uncovered and partially inflated; therewith the assembly takes the typical “dog bone” shape before complete inflation and final positioning. Repositioning of the stent and control angiography is possible at each time of this procedure. Results Between 1/2010 and 12/2014 we implanted 91 stents in 87 patients (mean age 20.2 years). About 71 patients had native or re-coarctation and 16 patients had transverse aortic arch stenosis. In 38 patients (44%) a pharmacological exercise test with Orciprenaline was performed during implantation resulting in high-cardiac output. In none of the patients reduction of cardiac output by adenosine or a rapid pacing of the right ventricle was required for stable stent implantation. All stents were implanted in the targeted position using this single balloon technique. There were no acute or short-term complications detected. Conclusion DBT is a safe and feasible technique for aortic stent implantation even at high-cardiac output. Other additional techniques for stent placement are not necessary to obtain a stable final position in the target region.

Assessment of left ventricular mass (LVM) is important in the evaluation of patients with congenital heart disease (CHD) and cardiac magnetic resonance imaging (CMR) is the gold standard. Recent software allows LVM calculation by real-time 3-dimensional echocardiography (RT3DE). We investigated the impact of different software analysis tools on LVM determination by CMR or RT3DE in a cohort of patients with heterogeneous left ventricular (LV) disease. 37 subjects (17 patients, mean age 18.7 y; 20 controls, mean age 13.2 y) underwent CMR and RT3DE. CMR LVM and RT3DE calculations were done using two different LV-analysis software packages for each modality: CMR i) customized software “CMR HDZ”, CMR ii) “CMR ISP”; RT3DE i) “Toshiba”, RT3DE ii) “Tomtec”, 4D LV-Analysis Version 3.1 (built 3.1.0.258661). Intra- and interobserver variabilities were calculated. Only RT3DE-derived LVM showed significant software-dependent differences. RT3DE-derived LVM (both softwares) was significantly higher than CMR-derived LVM (both softwares). The two different methods and four evaluation software packages for LVM assessment were well correlated with each other. Intra- and interobserver variability of LVM as assessed by each single modality or software was low. Despite software dependency and overestimation of RT3DE-assessed LVM by 5 to 10%, RT3DE still competes with the gold standard, CMR, even in patients with various forms of LV disease. The use of optimized software, especially for RT3DE, should improve the accuracy of LVM assessment, overcoming LVM overestimation.

Growing interest lies in the assessment of the metabolic status of patients with a univentricular circulation after Fontan operation, especially in changes of amino acid metabolism. Using targeted metabolomic examinations, we investigated amino acid metabolism in a homogeneous adult Fontan-patient group with a dominant left ventricle, seeking biomarker patterns that might permit better understanding of Fontan pathophysiology and early detection of subtle ventricular or circulatory dysfunction. We compared serum amino acid levels (42 analytes; AbsoluteIDQ p180 kit, Biocrates Life Sciences, Innsbruck, Austria) in 20 adult Fontan patients with a dominant left ventricle and those in age- and sex-matched biventricular controls. Serum concentrations of asymmetric dimethylarginine, methionine sulfoxide, glutamic acid, and trans-4-hydroxyproline and the methionine sulfoxide/methionine ratio (Met-SO/Met) were significantly higher and serum concentrations of asparagine, histidine, taurine, and threonine were significantly lower in patients than in controls. Met-SO/Met values exhibited a significant negative correlation with oxygen uptake during exercise. The alterations in amino acid metabolome that we found in Fontan patients suggest links between Fontan pathophysiology, altered cell energy metabolism, oxidative stress, and endothelial dysfunction like those found in biventricular patients with congestive heart failure. Studies of extended amino acid metabolism may allow better understanding of Fontan pathophysiology that will permit early detection of subtle ventricular or circulatory dysfunction in Fontan patients.

New echocardiographic modalities including pulmonary artery acceleration time (PAAT) and right ventricular ejection time (RVET) are evolving to facilitate an early non-invasive diagnosis for pulmonary hypertension (PH) in adults. In children, PAAT depends on age, body surface area (BSA) and heart rate (HR) and is used to predict PH. Normal values of RVET and their role to predict PH in children are still missing. PAAT/RVET-index correlates negatively with PH. We hypothesized that this index is a good predictor for PH in children and adolescents independent of age, BSA and HR and RVET is significantly reduced in PH. PAAT and RVET of 401 healthy children and 30 PH-patients were measured using pulsed-wave-Doppler. PH was diagnosed in PH-group invasively. PAAT/RVET-index for both groups was calculated. Sensitivity and specificity in prediction of PH of PAAT, PAAT z-score and PAAT/RVET-index were compared. We demonstrated normal values of RVET in children. In the healthy group, PAAT and RVET correlated significant positive to age (p

About 50% of patients with arrhythmogenic cardiomyopathy (ACM) carry a pathogenic or likely pathogenic mutation in the desmosomal genes. However, there is a significant number of patients without positive familial anamnesis. Therefore, the molecular reasons for ACM in these patients are frequently unknown and a genetic contribution might be underestimated. Here, we used a next-generation sequencing (NGS) approach and in addition single nucleotide polymor-phism (SNP) arrays for the genetic analysis of two independent index patients without familial medical history. Of note, this genetic strategy revealed a homozygous splice site mutation (DSG2–c.378+1G&gt, T) in the first patient and a nonsense mutation (DSG2–p.L772X) in combination with a large deletion in DSG2 in the second one. In conclusion, a recessive inheritance pattern is likely for both cases, which might contribute to the hidden medical history in both families. This is the first report about these novel loss-of-function mutations in DSG2 that have not been previously identi-fied. Therefore, we suggest performing deep genetic analyses using NGS in combination with SNP arrays also for ACM index patients without obvious familial medical history. In the future, this finding might has relevance for the genetic counseling of similar cases.

Background:Patients with a Fontan circulation have altered cholesterol and lipoprotein values. We analysed small organic molecules in extended phopsholipid and acylcarnitine metabolic pathways (‘metabolomes’) in adult Fontan patients with a dominant left ventricle, seeking differences between profiles in baseline and Fontan circulations.Methods:In an observational matched cross-sectional study, we compared phosphatidylcholine (PC), sphingomyelin (SM), and acylcarnitine metabolomes (105 analytes; AbsoluteIDQ®p180 kit (Biocrates Life Sciences AG, Innsbruck, Austria) in 20 adult Fontan patients having a dominant left ventricle with those in 20 age- and sex-matched healthy controls.Results:Serum levels of total PC ( q-value 0.01), total SM ( q-value 0.0002) were significantly lower, and total acylcarnitines ( q-value 0.02) were significantly higher in patients than in controls. After normalisation of data, serum levels of 12 PC and 1 SM Fontan patients were significantly lower ( q-values Conclusion:Metabolomic profiling can use small specimens to identify biomarker patterns that track derangement in multiple metabolic pathways. The striking alterations in the phospholipid and acylcarnitine metabolome that we found in Fontan patients may reflect altered cell signalling and metabolism as found in heart failure in biventricular patients, chronic low-level inflammation, and alteration of functional or structural properties of lymphatic or blood vessels.Trial registration number:ClinicalTrials.gov Identifier NCT03886935

Background Interventional closure of patent ductus arteriosus (PDA) has become a common and safe procedure in most pediatric cath labs. Interventional treatment of PDAs still remains a challenge in those children with low body weight and a large PDA. The Nit-Occlud PDA-R® device was developed and especially designed for large PDAs. We report our most recent experience in children with a body weight lower than 10 kg. Materials and Methods The PDA-R® device was used in seven children (age 1–10, median 6 months) with a body weight from 4.1 to 9.7 kg (median 5.9 kg): ductal length was 12 mm (median), with a large ampulla (median 9 mm) which exceeded the diameter of the aorta (median 6 mm) and large diameter (median minimal diameter 4 mm). In six cases, the Nit-Occlud PDA-R was selected with an aortic disc of 12 mm and in one case an occluder with an aortic disc of 14 mm. Results Occlusion of the PDA was documented by angiography and/or echocardiography in all cases. At a mean follow-up of 21.4 months, no flow obstruction to the left or right pulmonary artery or new onset coarctation of the aorta was noted. Conclusions The Nit-Occlud PDA-R® device is suitable in children with a body weight below 10 kg when a relative large PDA is present. © 2015 Wiley Periodicals, Inc.

Introduction In the search for a biodegradable device that leaves nothing but the tissue of the patient after complete endotheliazation and absorption, the BioSTAR® device was introduced in 2007 (CE Mark in European community and HPB in Canada) for ASD and PFO closure. It consists of a metal framework covered by a biodegradable membrane generated from a layer of porcine collagen that is broken down and absorbed over time. In a sheep model, the results were promising, showing complete closure of the defect with degradation of approximately 90% of the implanted membrane material after two years. Methods We report a retrospective analysis of implantation failures, early and late complications in a series of 34 patients with 30 implanted BioStar® devices in a single center with a total follow-up of more than 75 patient years. Results We report 12% of implantation failures, 9% of early and 12% of late complications. Implantation failures include one embolized device, which was interventionally retrieved. Early complications were exclusively rhythm disturbances, one patient needed electrical and pharmacological therapy. Four relevant late complications occurred. One device required explantation after 61 days because of recurrent severe fever episodes, severe headache, and malaise that subsequently subsided after device removal. One patient presented with Dressler's syndrome with pericardial effusion 5 month after implantation requiring pericardiocentesis and steroid treatment. One device showed a central residual shunt that was not clearly seen initially. Finally, one device was explanted after hemorrhagic pericardial effusion due to perforation of an arm of the frame through the right atrial roof into the pericardial fold after 19 months. Conclusion We conclude that implantation of the Biostar® device is difficult in patients with deficient aortic rims and early complications are similar to those seen in other devices. Of importance, the late complications seen with the Biostar® device might be attributable to specific material and immunological properties of the partially biodegradable device. Although a biodegradable device might theoretically be more favorable more efforts for optimization of these devices have to be taken. © 2015 Wiley Periodicals, Inc.

Functional assessment of the right ventricle using real-time three-dimensional echocardiography (RT3DE) has fundamental relevance in young patients with congenital heart disease. Reference values for the pediatric population are scarce. This multicenter study was designed to (1) validate new evaluation software for RT3DE and (2) establish pediatric reference values.For validation, right ventricular (RV) end-diastolic volume (EDV) and end-systolic volume (ESV) were determined from real-time three-dimensional echocardiographic data sets of 38 subjects (n = 17 healthy individuals and n = 21 patients with congenital heart disease) using new dedicated evaluation software (RV-Function 2.0) and compared with cardiac magnetic resonance investigations of the same patient cohort. In a prospective multicenter design, 360 real-time three-dimensional echocardiographic data sets of healthy children (172 girls) were analyzed. To create reference centiles, the cohort was subdivided into group I (children7 years of age, n = 136 [female and male]), group II (girls 7-18 years of age, n = 106), and group III (boys 7-18 years of age, n = 118).Using RT3DE, RV volumes were slightly higher than using cardiac magnetic resonance (EDV, 0.8 ± 5.8% [limits of agreement, -10.8% to 12.5%; r = 0.993]; ESV, 2.0 ± 13.1% [limits of agreement, -24.2% to 28.2%; r = 0.989). Reproducibility was promising (intraobserver variability, 3.9 ± 11.4% for EDV and -1.7 ± 13.4% for ESV [intraclass correlation coefficient range, 0.94-0.98]; interobserver variability, 1.9 ± 11.8% for EDV and -0.3 ± 22.8% for ESV [intraclass correlation coefficient range, 0.85-0.96]). Regarding functional parameters, no significant gender differences were found among children in group I. In contrast, children in groups II and III differed in RV volumes, dimensional parameters, and tricuspid annular plane systolic excursion (P .005); the children did not differ in deformation parameters. Feasibility was 90%.RT3DE yields accurate and reproducible RV volumes. The calculated percentile curves may facilitate the clinical use of RT3DE to analyze RV function in children.

Background Right ventricular volume quantification using real-time three-dimensional echocardiographic (RT3DE) imaging is limited by technical shortcomings of acquisition and quantification. In this study, a two-step approach was used to overcome these limitations. First, a modified acquisition technique for RT3DE imaging was applied, and second, a software tool using knowledge-based reconstruction (KBR) was used. The approach was validated against the gold standard, cardiac magnetic resonance (CMR) imaging, using CMR and RT3DE data sets from healthy children and from patients with congenital heart disease. Methods Sixty individuals (20 healthy persons, 40 with congenital heart defects; age range, 2.3–43.9 years; median age, 11.3 years) consecutively underwent investigation by CMR and RT3DE imaging. CMR data sets were first quantified by the method of disks (MOD) as the standard. Then CMR and RT3DE data sets were quantified using KBR software and compared with the MOD. Results CMR was more feasible than echocardiography (100% vs 88%). Compared with the MOD (CMR MOD ), there were trivial volume overestimations of KBR for CMR data (CMR KBR ), of end-diastolic volume (EDV) (−1.3 ± 8.6%, r = 0.984) and end-systolic volume (ESV) (−3.4 ± 13.3%, r = 0.985), resulting in a 0.7 ± 8.7% difference in ejection fraction (EF) ( r = 0.882). Comparing CMR MOD and RT3DE imaging, EDV (1.1 ± 7.4%, r = 0.990) and EF (0.8 ± 9.2%, r = 0.871) were slightly underestimated by RT3DE imaging, with a slight overestimation of ESV (−1.5 ± 13.3%, r = 0.977). Intraobserver variability was excellent for KBR of CMR and RT3DE data, with interclass coefficients of correlation of 0.995 and 0.997 for EDV, 0.995 and 0.994 for ESV, and 0.915 and 0.912 for EF. Interobserver variability provided intraclass correlation coefficients of 0.992 and 0.990 for EDV, 0.997 and 0.992 for ESV, and 0.953 and 0.933 for EF. The KBR analysis required a mean time of 5 min. Conclusions KBR is an accurate, versatile, and time-saving method for right ventricular three-dimensional volumetry; it shows excellent reproducibility for RT3DE and CMR data sets. These results suggest that this tool is clinically valuable.

Aims Blood flow rate quantification using two-dimensional phase-contrast MRI (PC-MRI) results in averaging of flow information due to long acquisition times precluding the examination of short-term effects. The aim of this study was to determine respiration-related flow rate variations by non-electrocardiographic triggered real-time phase-contrast MRI (PC-MRI). Methods and results Real-time PC-MRI was applied to study respiration-driven blood flow fluctuations in the ascending aorta (AAo), superior vena cava (SVC), and inferior vena cava (IVC) under normal and forced breathing in 33 healthy children and 10 Fontan patients. Respiration-dependent flow rates were virtually generated by dividing the respiration curve into four segments: expiration, end-expiration, inspiration, and end-inspiration. Whereas in volunteers aortic flow rate was elevated during end-expiration (5.6 ± 3.0%) and decreased during end-inspiration (−5.8 ± 3.5%) in relation to mean blood flow ( P < 0.05), highest flow was detected during inspiration in SVC (10.5 ± 14.1%) and IVC (22.5 ± 12.1%) and lowest flow during expiration (−11.6 ± 13.5%, −13.2 ± 14.1%, P < 0.05). Differences were increased under forced breathing in AAo (10.4 ± 5.5%, −7.4 ± 6.5%, P < 0.05) and SVC (40.0 ± 30.3%, −30.0 ± 19.2%, P < 0.05), whereas were unchanged in IVC (16.5 ± 23.6%, −13.7 ± 21.6%, P = n.s.). Regarding patients, respiratory-dependent flow rate variability was increased and had to be related to the patient's individual quality of Fontan circulation. Conclusion Real-time PC-MRI allows a physiological assessment of respiratory-related flow rate fluctuations in healthy subjects as well as in Fontan patients. Its capability for detection of short-term effects in clinical routine was demonstrated.

Die Echokardiographie ist das Standardverfahren der nichtinvasiven Bildgebung zur Untersuchung des Herz-Kreislauf-Systems von Feten, Kindern und Jugendlichen. Ziel dieser Qualitatsstandards ist, dem Patienten mit angeborenem Herzfehler eine zielgerichtete und umfassende Diagnostik zu gewahrleisten. Dazu werden Anforderungen an den Untersucher hinsichtlich unterschiedlicher Echokardiographiemodalitaten, Untersuchungsablauf, Dokumentation und Befundung definiert. Speziell wird auf Methoden der Bildakquisition und Auswertung eingegangen, die anhand der verfugbaren Literatur bewertet werden. Zusatzlich zur transthorakalen Echokardiographie wird wegen spezieller Anforderungen an Technik und Untersucher auf die fetale und transosophageale Echokardiographie eingegangen. Die Verfahren Gewebe-Doppler, 2-d-Deformationsanalyse und 3-d-Echokardiographie werden anhand des aktuellen Standes der Forschung mit ihren Vor- und Nachteilen kritisch diskutiert und Empfehlungen zum klinischen Einsatz gegeben.

Stenting of vascular, extracardiac or lately intracardiac stenosis has become an established interventional treatment for a variety of problems in congenital or acquired heart disease. Most stent procedures are completed successfully and the long-term outcome is favorable in the majority of cases. Stent collapse or deformation is a well recognized entity in peripheral stents and can be attributed to insufficient radial force; it can also be attributed to excessive external forces, like deformation of stents in the right ventricular outflow tract, where external compression is combined with continuous movement caused by the beating heart. The protection of the thoracic cage may prove to be insufficient in extraordinary circumstances, such as chest compression in trauma or cardiopulmonary resuscitation (CPR). In this case series, we describe three patients in whom large endovascular stents were placed to treat significant stenosis of the aorta, the aortic arch or the venous system of the inferior vena cava close to the atrium. In all patients, CPR was necessary during their clinical course for various reasons; after adequate CPR, including appropriate chest compression all patients survived the initial resuscitation phase. Clinical, echocardiographic as well as radiologic re-evaluation after resuscitation revealed significant stent distortion, compression, displacement or additional vascular injury. The possibility of mechanical deformation of large endovascular stents needs to be considered and recognized when performing CPR; if CPR is successful, immediate re-evaluation of the implanted stents--if possible by biplane fluoroscopy--seems mandatory.