Search

Background Fluid overload is a serious complication in the treatment of infants with extracorporeal membrane oxygenation (ECMO). Volume overload leads to prolonged ECMO therapy if left untreated. The renal replacement therapy of choice in pediatric patients is peritoneal dialysis or conventional dialysis using a “large” hemofiltration machine via a Shaldon catheter or directly connected to the ECMO system. This study describes the implementation of a novel minimized hemodiafiltration (HDF) system in pediatric patients on ECMO. Methods This retrospective analysis included 13 infants up to 5 kg who underwent 15 veno-arterial (V-A) ECMO runs with HDF. A minimized HDF system is integrated into an existing ECMO system (18 mL priming volume), connected post-oxygenation to the venous line, before the ECMO pump. Two infusion pumps are attached to the inlet and outlet of the hemofilter to control the HDF system.In addition to retention values (creatine and urea) at six defined time points, flow rates, dialysis parameters, and volume withdrawal were examined, as well as the number of HDF system changes. Results With a mean ECMO runtime of 156 hours, the HDF system was utilized for 131 hours. The mean blood flow through the hemofilter was 192 mL/min. The mean dialysate flow was 170 mL/h, with a mean volume deprivation of 39 mL/h. The HDF system was changed once in seven cases and twice in three cases. Conclusion There were no complications with the minimized HDF system in all 15 applications. It allows safe patient volume management when treating infants with ECMO, with effective elimination of urinary substances.

Pulmonary function is reduced in children after preterm birth. The variety of subgroups ranges from early to late preterm births. Limitations in pulmonary function can be observed even after late preterm birth without signs of bronchopulmonary dysplasia and/or history of mechanical ventilation. Whether this reduction in lung function is reflected in the cardiopulmonary capacity of these children is unclear. This study aims to investigate the impact of moderate to late premature birth on cardiopulmonary function. Cardiopulmonary exercise testing on a treadmill was performed by 33 former preterm infants between 8 and 10 years of age who were born between 32 + 0 and 36 + 6 weeks of gestation and compared with a control group of 19 children born in term of comparable age and sex. The former preterm children achieved comparable results to the term-born controls with respect to most of the cardiopulmonary exercise parameters $$(\dot{V}O_2peak 43.9\pm6.6\frac{\frac{ml}{kg}}{min}\min vs.41.9\pm8.8\frac{ml}{kg}/\min)$$ ( V ˙ O 2 p e a k 43.9 ± 6.6 ml kg min min v s . 41.9 ± 8.8 ml kg / min ) . The only differences were in a slightly higher oxygen uptake efficiency slope $$(OUES\;of\;1.6\;\pm0.4\;vs\;1.4\;\pm\;0.4)$$ ( O U E S o f 1.6 ± 0.4 v s 1.4 ± 0.4 ) and higher peak minute ventilation $$\dot VEpeak\;of\;55.2\pm 11.3 ml/min\;vs.\;49.1\;ml\;\pm\;8.8/min)$$ V ˙ E p e a k o f 55.2 ± 11.3 m l / m i n v s . 49.1 m l ± 8.8 / m i n ) in the group of children born preterm. With respect to heart rate recovery $$(-35.3\;\pm\;13.8\;bpm\;vs.\;-37.2\;bpm\;\pm\;14.0\;after\;1\;min)$$ ( - 35.3 ± 13.8 b p m v s . - 37.2 b p m ± 14.0 a f t e r 1 m i n ) and breathing efficiency $$\dot{(V}E/\dot VCO_2\;of\;35.9\;\pm\;4.1\;vs\;34.0\;\pm4.6)$$ ( V ˙ E / V ˙ C O 2 o f 35.9 ± 4.1 v s 34.0 ± 4.6 ) , there were no significant differences.Conclusion: Children born preterm did not show limitations in cardiopulmonary function in comparison with matched controls. What is Known:• Preterm birth is associated with reduced pulmonary function in later life, this is also true for former late preterms.• As a consequence of being born premature, the lungs have not finished their important embryological development. Cardiopulmonary fitness is an important parameter for overall mortality and morbidity in children and adults and a good pulmonary function is therefore paramount. What is New:• Children born prematurely were comparable to an age- and sex-matched control group with regards to almost all cardiopulmonary exercise variables.• A significantly higher OUES, a surrogate parameter for VO2peak was found for the group of former preterm children, most likely reflecting on more physical exercise in this group. Importantly, there were no signs of impaired cardiopulmonary function in the group of former preterm children.

Background The aim of this study was to evaluate the long-term outcome and freedom from pulmonary valve replacement (PVR) after initial repair of tetralogy of Fallot (TOF). Patients and Methods The cohort of 306 patients treated between 1980 and 2017 was divided into anatomical subgroups according to the diagnosis of TOF-pulmonary stenosis, TOF-pulmonary atresia and TOF-double outlet right ventricle. Patients were treated with transannular patch (TAP), valve sparing repair (VSR), or conduits from the right ventricle to the pulmonary arteries (RVPA conduits). Results There were 21 deaths (6.9%), 14 being hospital deaths (4.6%) after primary correction and four deaths (1.3%) occurred after PVR. One patient died after a non-cardiac operation (0.3%). There were two late deaths (0.7%). During the past 12 years no early mortality has been observed. Ninety-one patients (30.4%) received PVR after a median of 12.1 ± 7.0 years with an early mortality of 4.4% (n = 4) and no late mortality. A significant difference in freedom from reoperation after TAP, VSR, and RVPA-conduits could be identified. Multivariate analysis displayed transannular repair (p = 0.016), primary palliation (p Conclusion TOF repair has a beneficial long-term prognosis with low morbidity and mortality. Pulmonary valve Z-scores

Purpose Cardiopulmonary exercise testing (CPET) in preschoolers (4–6 years) represents a challenge. Most studies investigating CPET have been limited to older children (> 8 year). However, knowledge of the performance of small children is essential for evaluating their cardiorespiratory fitness. This study strives to compare a modified Bruce protocol with a new age-appropriate incremental CPET during natural movement running outdoors, using a mobile device. Methods A group of 22 4–6-year-old healthy children was tested indoor on a treadmill (TM) using the modified Bruce protocol. The results were compared with a self-paced incremental running test, using a mobile CPET device in an outdoor park. The speeds were described as (1) slow walking, (2) slow running, (3) regular running, and (4) running with full speed as long as possible. Results Mean exercise time outdoors (6,57 min) was significantly shorter than on the treadmill (11,20 min), $$\dot{V}{O}_{2peak}$$ V ˙ O 2 p e a k (51.1 ml/min/kg vs. 40.1 ml/min/kg), RER (1.1 vs. 0.98) and important CPET parameters such as $$\dot{V}E$$ V ˙ E max, O2pulse, heart rate and breath rate were significantly higher outdoors. The submaximal parameter OUES was comparable between both the tests. Conclusions Testing very young children with a mobile device is a new alternative to treadmill testing. With a significantly shorter test duration, significantly higher values for almost all cardiopulmonary variables can be achieved without losing the ability to determine VT1 and VT2. It avoids common treadmill problems and allows for individualized exercise testing. The aim is to standardize exercise times with individual protocols instead of standardizing protocols with individual exercise times, allowing for better comparability.

Background A growing number of patients with a single ventricle anatomy, who had a Fontan palliation as a child, are now reaching adulthood. Many need an epimyocardial pacemaker system with an optional telemonitoring (TM) unit, which evaluates the collected data and sends it via Internet to the patient's physician. There are no data on the reliability and clinical relevance of these systems in this patient group. Methods We analyzed data in 48 consecutive patients (mean age 18 years, standard deviation 9 years) with a Fontan or Fontan-like palliation who received a cardiac implantable electronic device with a TM unit from Biotronik (Home Monitoring) or Medtronic (CareLink) between 2005 and 2020 with regard to the reliability and clinical relevance of the downloaded data. Results The observation period was from 4 months to 14 years (mean 7 years, standard deviation 3.9 years). A total of 2.9 event messages (EMs)/patient/month and 1.3 intracardiac electrogram recordings/patient/month were received. Two patients died during follow-up. The combination of regularly arriving statistical data and 313 clinically relevant EMs led to the modification of antiarrhythmic or diuretic medication, hospitalization with cardioversion or ablation, and cortisone therapy to avoid exit block in 21 (44%) patients. Conclusion TM is an instrument to receive functional and physiologic parameters of our Fontan patients. It provides the ability to respond early for signs of system failure, or arrhythmia, even if the patient is not experiencing any problems. It is a useful tool to manage this difficult patient population without frequent hospital visits.

Due to the Corona-lockdowns the closure of sports facilities and schools has led to a decline in physical activity (PA) for months. PA is essential for maintaining cardiopulmonary function assessed by peak oxygen uptake. Since peak oxygen uptake represents the best predictor for mortality and morbidity in children with congenital heart disease the impact of lockdowns on this parameter is vital.We evaluated retrospectively cardiopulmonary exercise data from our patient collective from before lockdown with twin-paired data from during lockdown. The twin-pairing was achieved by matching patients with similar heart disease, age, sex, and test method. Cardiopulmonary exercise testing was achieved on either the treadmill or the bicycle.We were able to twin-pair 90 cases (26 twins with heart disease and 19 healthy twins). There was a significant decrease of cardiopulmonary function (V̇OWe observed a significant decline of peak oxygen uptake during lockdown in the group of congenital heart disease (CHD) patients. This involved a loss of cardiac function as well as pulmonary function. This could be explained by limited access to sports facilities and restriction of regular daily movement due to school closure and overprotection. Healthy children improved their pulmonary function. This might be an indication of an improvement of exercise during confinement.Aufgrund des Corona-Lockdowns hat die Schließung von Sportanlagen und Schulen über Monate zu einem Rückgang der körperlichen Aktivität geführt. Körperliche Aktivität ist für die Aufrechterhaltung der kardiopulmonalen Funktion, bewertet durch die maximale Sauerstoffaufnahme, unerlässlich. Da die maximale Sauerstoffaufnahme der beste Prädiktor für Mortalität und Morbidität bei Kindern mit angeborenen Herzerkrankungen ist, sind die Auswirkungen des Lockdowns auf diesen Parameter von entscheidender Bedeutung. Spiroergometriedaten unseres Patientenkollektivs aus der Zeit vor dem Lockdown wurde mit Daten von statistischen Zwillingen aus dem gleichen Kollektiv während des Lockdowns verglichen. Die Zwillingspaarung wurde erreicht, indem Patienten mit ähnlichen Herzerkrankungen, Alter, Geschlecht und Testmodalitäten verglichen wurden. Die Spiroergometrie wurde entweder auf dem Laufband oder auf dem Fahrrad durchgeführt. Insgesamt wurden 90 Datensätze verbunden (26 Zwillinge mit Herzkrankheit und 19 gesunde Zwillinge). In der Kohorte der Herzerkrankten konnte eine signifikante Verschlechterung der kardiopulmonalen Funktion (V̇OAufgrund des Corona-Lockdowns hat die Schließung von Sportanlagen und Schulen über Monate zu einem Rückgang der körperlichen Aktivität geführt. Körperliche Aktivität ist für die Aufrechterhaltung der kardiopulmonalen Funktion, bewertet durch die maximale Sauerstoffaufnahme, unerlässlich. Da die maximale Sauerstoffaufnahme der beste Prädiktor für Mortalität und Morbidität bei Kindern mit angeborenen Herzerkrankungen ist, sind die Auswirkungen des Lockdowns auf diesen Parameter von entscheidender Bedeutung. Spiroergometriedaten unseres Patientenkollektivs aus der Zeit vor dem Lockdown wurde mit Daten von statistischen Zwillingen aus dem gleichen Kollektiv während des Lockdowns verglichen. Die Zwillingspaarung wurde erreicht, indem Patienten mit ähnlichen Herzerkrankungen, Alter, Geschlecht und Testmodalitäten verglichen wurden. Die Spiroergometrie wurde entweder auf dem Laufband oder auf dem Fahrrad durchgeführt. Insgesamt wurden 90 Datensätze verbunden (26 Zwillinge mit Herzkrankheit und 19 gesunde Zwillinge). In der Kohorte der Herzerkrankten konnte eine signifikante Verschlechterung der kardiopulmonalen Funktion (V̇O

There is extensive knowledge about uphill running on a treadmill, although paucity regarding the influence of uphill trail running on exercise capacity in runners. The purpose of this study was to compare an uphill field test with a treadmill test with 1% inclination especially considering cardiopulmonary exercise variables. The difference in those tests between a group of trail runners and a group of road runners was tested for establishing a test specifically for trail runners. Ten male endurance road runners and ten male trail runners performed one maximal incremental treadmill test with 1% inclination and a maximal incremental field test on a hill at 16% inclination which they were instructed to run up four times for three minutes, each time with a higher pace. A mobile cardiopulmonary exercise testing unit was used to measure ventilation. There were no significant differences between trail runners and road runners. The equivalence factor was comparable between both groups. V˙O2peak was comparable for both test protocols. However, there was a significant difference between the two test protocols regarding lactate concentration, the respiratory exchange ratio, running cost, heart rate, Breathing reserve, and O2pulse. The greater lactate concentration and running cost recorded uphill indicate a higher energy demand during trail running than level road running.

Background Cardiac pacing can be challenging after a Fontan operation, and limited data exist regarding strategies to plan these epimyocardial systems while minimizing the number of surgical procedures. Methods A retrospective review of all our 47 patients (mean age 18 years, standard deviation 9 years) with a Fontan palliation who received an epimyocardial cardiac implantable electronic device (CIED) between 2002 and 2020 with regard to the stability of the epimyocardial lead parameters and the incidence of system revisions. Results Over the last 18 years, 84 implantations or revisions of the epimyocardial CIED in 47 Fontan patients were performed. Mean age at time of the first implantation was 9.4 (range 0.28-29.3) years. Follow-up period ranges from 0.11 to 18.2 (mean 7.7, standard deviation 4.2) years. A total of 123 pacing leads were implanted of which 99 are still active. From 2010 triple lead cardiac resynchronization devices were used in 17 patients to better cope with lead problems. The initial pacing threshold of the leads inactivated during this study period proved significantly higher (mean 1.66 V) than in the "all leads" group (mean 1.27 V, p = .0005) or the group of the still active leads (mean 1.17 V, p = .00004). Conclusions When implanted with a low pacing threshold, the bipolar epimyocardial electrodes show stable and good long-term results in young patients with a Fontan circulation. Resynchronization pacing systems and the prospective implantation of reserve leads may help to reduce the rate of resternotomies and provide a flexible concept to deal with lead failure.

Background Protein-losing enteropathy (PLE) is a severe complication of the Fontan circulation. There is increasing discussion about whether lymphatic dysregulation is involved as pathomechanism of PLE. This investigation focuses on the interplay between alteration of lymphatic cells and immunologic pathway alterations.Methods Micro-ribonucleic acid (miRNA) expression profiling was performed in 49 patients (n = 10 Fontan patients with PLE, n = 30 Fontan patients without PLE, and n = 9 patients with dextro-transposition of the great arteries (dTGA). miRNA pathway analysis was performed to identify significantly enriched pathways. To determine lymphocyte populations and subtypes multiparameter flow cytometry was used.Results miRNAs pathway analysis of Fontan patients with PLE revealed 20 significantly changed networks of which four of the ten largest were associated with immunologic processes. This finding is supported by significant T cell deficiency with decreased CD4+ count (p = 0.0002), altered CD4 +/CD8+ ratio, and significantly modified CD4+ (p Conclusion PLE in Fontan patients is associated with severe lymphopenia, T cell deficiency, significant alterations of T cell differentiation, and increased Treg frequency reflecting an immune status of chronic inflammation and shortened protection against pathogens and autoimmunity. These cellular alterations seemed to be dysregulated by several miRNA controlled immunological pathways.

Introduction Sudden cardiac death in a young athlete is the leading cause of mortality in athletes during sport. Specific knowledge about cardiac adaptations are necessary for a better understanding of the underlying causes of such events. Methods A retrospective analysis of the electrocardiogram and echocardiographic data obtained during the yearly medical examination of the entire German junior national climbing team was undertaken. First, data from 1 examination were used. In a second step, data from 2 examinations spaced 2 y apart were analyzed for a selected subgroup to gain more knowledge about adaptations to climbing. The data from the subgroup were compared to an age- and sex-matched control group of Nordic skiers from the German junior national Nordic skiing team. Results Forty-seven young climbers (20 girls, 27 boys) were examined once. There were no pathological findings in the electrocardiogram or echocardiography. The left ventricular (LV) measurements fell between those for athletes and nonathletes. Eight boys and 6 girls from this group were tested twice over a timeframe of 27.5 mo. All LV measurements increased over time. After 2 y, the measurements from the climbers were comparable to those of the Nordic skiers. Conclusions Hypertrophic cardiomyopathy (hypertrophy of the LV) is the leading cause of sudden cardiac death in athletes. An increase in LV dimensions was observed in the young climbers in this study. LV dimensions being comparable to high-level Nordic skiers after 2 y in the national team imply structural changes over time in this cohort.

OBJECTIVES Left superior vena cava (LSVC)-related obstruction of mitral inflow is a rare finding in patients with complex cardiac anomalies like hypoplastic left heart complex. We report our experience by establishing a left superior to right superior caval vein continuity (innominate vein creation by direct LSVC–right superior vena cava end-to-side-anastomosis), and coronary sinus unroofing if indicated for LSVC-related mitral inflow obstruction. METHODS Nineteen patients (median age: 1.0 ± 0.3 years; range: 7 days–4.8 years) underwent anatomical correction of LSVC without the use of foreign material in conjunction with repair or palliation of congenital anomalies in a single centre between April 2015 and November 2019. Indications for the procedure were LSVC-related obstruction of left ventricular inflow due to a dilated coronary sinus. Additional procedures included mitral (n = 7) or atrioventricular (n = 3) valve surgery, right ventricular to pulmonary artery conduit (n = 3), first stage palliation (n = 3) or biventricular repair (n = 5) of hypoplastic left heart complex. Three patients needed secondary mitral valve replacement (n = 3). RESULTS All LSVC or coronary sinus-related obstructions were effectively relieved. No patient died early, 2 patients died late after the procedure. One patient needed stenting of the superior vena cava below the unobstructed cephalad vein anastomosis at the former right superior vena cava-cannulation-site. Follow-up was complete and demonstrated an 89.5% survival after 2.5 ± 0.4 years. Innominate vein patency was 100% documented by echocardiography (n = 19), cardiac catheterization (n = 6) or both. Mean mitral valve z-scores before the operation were −1.7 ± 0.2 (range −3.8 to 0.3) and increased to 0.7 ± 0.2 (range −0.7 to 1.9) after LSVC repair. CONCLUSIONS Anatomical correction by surgical creation of an innominate vein is an effective method to relieve LSVC-related obstructions and promotes mitral valvar growth. Mitral ring sizes were at least normalized after surgery at the time of discharge. Further prospective follow-up studies to evaluate the growth potential of left-sided heart structures by reporting cardiac z-scores are needed to evaluate the true impact of coronary sinus unroofing.

Fontan patients with protein‐losing enteropathy (PLE) represent poor candidates for cardiac transplantation due to end‐organ injury and severely impaired clinical condition. Ventricular assist device (VAD) therapy has evolved as a promising bridge to transplant strategy improving quality of life and survival on the waiting list. However, VAD therapy for the Fontan circulation remains challenging. For Fontan patients with preserved ventricular function implantation of a right ventricular assist device (RVAD) has been described by Prêtre et al as bridge to transplant. We present the second case of RVAD support in a Fontan patient with PLE.

Background Brain injury and subsequent neurodevelopmental disorders are major determinants for later-life outcomes in neonates with transposition of the great arteries (TGA). Purpose To quantitatively assess cerebral perfusion in neonates with TGA undergoing arterial switch operation (ASO) using transfontanellar contrast-enhanced US (T-CEUS). Materials and Methods In a prospective single-center cross-sectional diagnostic study, neonates with TGA scheduled for ASO were recruited from February 2018 to February 2020. Measurements were performed at five time points before, during, and after surgery (T

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.

Background For an optimal interplay based on the data-secure exchange of diagnostic data between patients, ambulatory care, and hospital care, we implemented the first tele-medical network for pediatric cardiology in Germany, the Congenital Cardiology Cloud. This study focuses on its feasibility, technical characteristics, and implementation in routine clinical work. Methods Tele-medical traffic comprised numbers of incoming/outgoing data, related file types, treatment options for tele-medically processed patients, and patient classification with respect to the severity of disease. Proof of feasibility was related to the number of successful tele-medical transmissions of discharge documents at the end of the observation period (02/2020–10/2020). Results Analysis of Congenital Cardiology Cloud's data communication showed a number of 1178 files for a total of 349 patients, favoring transmissions towards the clinic. Incoming traffic was predominantly characterized by diagnostic data regarding tele-consultations (76.6%), consisting of a multitude of file types, whereas 93.4% of the dispatched data corresponded to discharge letters. The number of tele-consultations counted up to 61, with a necessary subsequent treatment or diagnostic procedure in 90.2% of the presented cases. Tele-medically processed patients generally showed to be more complex (severe chronic heart disease 42.4% vs. 23.7%). At the end of the observation period, 97.6% of the discharge documents were transmitted via telemedicine. Discussion The implementation of the first tele-medical network for pediatric cardiology in Germany proves recent technological developments to successfully enable innovative patient care, connecting the ambulatory and hospital sector for a joint patient advice, predominantly in more complex cases. Possible governmentally guided refinancing concepts will show its long-term feasibility.

Perfusion : the leading journal in the field of extra-corporeal circulation (2022). doi:10.1177/02676591221127926, Published by Sage, London [u.a.]

Introduction Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) are emerging biomarkers for systemic inflammation and have been shown to predict morbidity and mortality for several diseases. However, lack of pediatric reference intervals (RIs) prevents their comprehensive use in patient care and medical research. Material and methods We calculated reference intervals and corresponding confidence intervals for NLR, PLR, and LMR from birth to 18 years using a data-mining approach: We analyzed 232 746 blood counts from 60 685 patients performed during patient care and excluded patients with elevated C-reactive protein and procalcitonin. Test results were separated according to age and sex, and the distribution of physiological ratios was estimated using an indirect approach (refineR). Additionally, we investigated the ratios' diagnostic benefit for different inflammatory diseases (acute appendicitis, asthma, Bell's palsy, Henoch-Schonlein purpura, and cystic fibrosis) using the newly obtained reference intervals. Results We estimated age- and sex-specific reference intervals from birth to adulthood for NLR, PLR, and LMR. Analyses in pediatric inflammatory diseases showed that PLR and LMR were poor markers to detect the examined inflammatory diseases, while NLR was significantly increased in patients with appendicitis and asthma. Conclusion We provide pediatric reference intervals for NLR, PLR, and LMR to improve the interpretation of these biomarkers in children.

The birth prevalence of laterality defects is about 1.1/10,000 comprising different phenotypes ranging from situs inversus totalis to heterotaxy, mostly associated with complex congenital heart defects (CHD) and situs abnormalities such as intestinal malrotation, biliary atresia, asplenia, or polysplenia. A proportion of laterality defects arise in the context of primary ciliary dyskinesia (PCD) accompanied by respiratory symptoms or infertility. In this study, exome sequencing (ES) was performed in 14 case-parent trios/quattros with clinical exclusion of PCD prior to analysis. Moreover, all cases and parents underwent detailed clinical phenotyping including physical examination, echocardiography by a skilled paediatric cardiologist and abdominal ultrasound examinations not to miss mildly affected individuals. Subsequent survey of the exome data comprised filtering for monoallelic de novo, rare biallelic, and X-linked recessive variants. In two families, rare variants of uncertain significance (VUS) in PKD1L1 and ZIC3 were identified. Both genes have been associated with laterality defects. In two of the remaining families, biallelic variants in LMBRD1 and DNAH17, respectively, were prioritized. In another family, an ultra-rare de novo variant in WDR47 was found. Extensive exome survey of 2,109 single exomes of individuals with situs inversus totalis, heterotaxy, or isolated CHD identified two individuals with novel monoallelic variants in WDR47, but no further individuals with biallelic variants in DNAH17 or LMBRD1. Overall, ES of 14 case-parent trios/quattros with cardiovascular laterality defects identified rare VUS in two families in known disease-associated genes PKD1L1 and ZIC3 and suggests DNAH17, LMBRD1, and WDR47 as potential genes involved in laterality defects.

OBJECTIVES Complications after Fontan surgery have been associated with arise and classification of abnormal thoracic lymphatic perfusion pattern. This study compiles abnormal abdominal lymphatic perfusion patterns and investigates their impact on serum protein readings. METHODS We performed a retrospective analysis of patients who underwent magnetic resonance imaging with T2-weighted lymphatic imaging and serum protein measurements 6 months after having Fontan surgery. The abdominal lymphatic images were classified according to the anatomical lymphatic drainage patterns into 2 categories: (1) para-aortic (types 1–4); (2) portal-venous (types 1–3). Thoracic lymphatic images were classified (types 1–4) as described earlier. RESULTS A total of 71 patients were included in the study. Para-aortic lymphatic perfusion patterns were classified as type 1 in 4, type 2 in 13, type 3 in 37 and type 4 in16 out of 71 patients. Portal-venous lymphatic perfusion patterns were classified as type 1 in 20, type 2 in 10 and type 3 in 41 patients. Thoracic lymphatic perfusion patterns were classified as type 1 in 8, type 2 in 11, type 3 in 39 and type 4 in 13 patients. The serum protein level was 66 (interquartile range: 7.5) g/l (< standard value in 37%). Higher-grade para-aortic (p = 0.0062), portal-venous (p = 0.022) and thoracic (p = 0.011) lymphatic abnormalities were correlated with lower total serum protein levels. Higher ratings of para-aortic lymphatic abnormalities were significantly associated with higher ratings of portal-venous abnormalities (p < 0.0001). Ratings of para-aortic and portal-venous classifications were correlated with the thoracic classification (p < 0.001). CONCLUSIONS Abnormal abdominal lymphatic perfusion patterns can be classified according to anatomical structures with increasing severity. Higher grade abdominal and thoracic lymphatic perfusion patterns are associated with lower serum protein values.

OBJECTIVES We evaluated 4384 procedures performed between 1957 and 2018, collected in the National Register for Congenital Heart Defects, conducted on 997 patients with 1823 pulmonary valve replacements (PVRs), including 226 implanted via catheter [transcatheter valve (TCV)]. Main study targets are as follows: TCV benefit, valve type durability, decade-wise treatment changes and procedure frequencies over the lifetime of a PVR patient. METHODS We studied TCV impact on surgical valve replacement (via Kaplan–Meier); pulmonary valve type-specific performance (Kaplan–Meier and Cox regressions with age group as stratification or ordinary variable); procedure interval changes over the decades (Kaplan–Meier); procedure load, i.e. frequency of any procedure/surgical PVR/interventional or surgical PVR by patient age (multistate analyses). RESULTS TCV performance was equivalent to surgical PVRs and extended durability significantly. Homografts were most durable; Contegras lasted comparably less in older; and Hancock devices lasted less in younger patients. Matrix P-valves showed poorer performance. Age group stratification improves the precision of valve-specific explantation hazard estimations. The current median interval between procedures is 2.6 years; it became significantly shorter in most age groups below 40 years. At 30 years, 80% of patients had undergone ≥3 procedures, 20% ≥3 surgical PVRs and 42% ≥3 surgical or interventional PVRs. CONCLUSIONS TCVs doubled freedom from explantation of conventional valves. Homografts’ age group-specific explantation hazard ratio was lowest; Matrix P’s hazard ratio was highest. Age-stratified Cox regressions improve the precision of prosthesis durability evaluations. The median time between procedures for PVR patients shortened significantly to 2.6 years. At 30 years, 42% had ≥3 PVRs.

Aufgrund von kinderkardiologischen und -herzchirurgischen Behandlungserfolgen erreichen heutzutage mehr als 90 % der Patienten mit angeborenem Herzfehler das Erwachsenenalter. Die sehr heterogene Gruppe von schatzungsweise ca. 250.000–350.000 Patienten in Deutschland ubersteigt mittlerweile die Zahl der padiatrischen Patienten mit angeborenem Herzfehler (ca. 120.000). In der stetig wachsenden Gruppe der Erwachsenen mit angeborenem Herzfehler (EMAH) ist die grundlegende Unterscheidung anhand des zugrunde liegenden Herzfehlers und der individuellen Krankengeschichte empfehlenswert. Mithilfe einer systematischen Kategorisierung konnen der Behandlungs- und Betreuungsaufwand sowie das individuelle Risiko des Patienten relativ gut eingeschatzt werden. Nichtkorrigierte Herzfehler, Residualprobleme nach Korrekturen oder Palliationen und eine klinisch relevante Herzinsuffizienz sind die wichtigsten chirurgischen Behandlungsindikationen fur erwachsene Patienten mit angeborenen Herzfehlern.

PURPOSE: Rare genetic variants in KDR, encoding the vascular endothelial growth factor receptor 2 (VEGFR2), have been reported in patients with tetralogy of Fallot (TOF). However, their role in disease causality and pathogenesis remains unclear. METHODS: We conducted exome sequencing in a familial case of TOF and large-scale genetic studies, including burden testing, in >1,500 patients with TOF. We studied gene-targeted mice and conducted cell-based assays to explore the role of KDR genetic variation in the etiology of TOF. RESULTS: Exome sequencing in a family with two siblings affected by TOF revealed biallelic missense variants in KDR. Studies in knock-in mice and in HEK 293T cells identified embryonic lethality for one variant when occurring in the homozygous state, and a significantly reduced VEGFR2 phosphorylation for both variants. Rare variant burden analysis conducted in a set of 1,569 patients of European descent with TOF identified a 46-fold enrichment of protein-truncating variants (PTVs) in TOF cases compared to controls (P = 7 × 10-11). CONCLUSION: Rare KDR variants, in particular PTVs, strongly associate with TOF, likely in the setting of different inheritance patterns. Supported by genetic and in vivo and in vitro functional analysis, we propose loss-of-function of VEGFR2 as one of the mechanisms involved in the pathogenesis of TOF. ispartof: GENETICS IN MEDICINE vol:23 issue:10 pages:1952-1960 ispartof: location:United States status: published

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.

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., Graphical abstract, Highlights • First comprehensive transcriptomic study of human RVH via RNA expression and network analysis • First human RVH study using exclusively freshly isolated myocardium • Known hypertrophy genes are regulated the strongest by competing endogenous RNA networks in RVH • Epigenetic mRNA regulation in RVH by ncRNAs is dependent on sex and age, Molecular Biology; Omics