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BACKGROUND There is overlap in genetic causes and cardiac features in noncompaction cardiomyopathy (NCCM), hypertrophic cardiomyopathy (HCM), and dilated cardiomyopathy (DCM).OBJECTIVES The goal of this study was to predict phenotype and outcome in relatives according to the clinical features and genotype of NCCM index cases.METHODS Retrospective DNA and cardiac screening of relatives of 113 families from 143 index patients were used to classify NCCM cases according to the cardiac phenotype. These cases were classified as isolated NCCM, NCCM with left ventricular (LV) dilation (DCM), and NCCM with LV hypertrophy (HCM).RESULTS In 58 (51%) families, screening identified 73 relatives with NCCM and 34 with DCM or HCM without NCCM. The yield of family screening was higher in families with a mutation (p CONCLUSIONS The phenotype of relatives may be predicted according to the NCCM phenotype and the mutation of index patients. NCCM phenotypes were related to outcome. In this way, clinical and genetic features of index patients may help prediction of outcome in relatives. (C) 2019 by the American College of Cardiology Foundation.

Supplemental Digital Content is available in the text., Background: Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease. While ≈50% of patients with HCM carry a sarcomere gene mutation (sarcomere mutation-positive, HCMSMP), the genetic background is unknown in the other half of the patients (sarcomere mutation-negative, HCMSMN). Genotype-specific differences have been reported in cardiac function. Moreover, HCMSMN patients have later disease onset and a better prognosis than HCMSMP patients. To define if genotype-specific derailments at the protein level may explain the heterogeneity in disease development, we performed a proteomic analysis in cardiac tissue from a clinically well-phenotyped HCM patient group. Methods: A proteomics screen was performed in cardiac tissue from 39 HCMSMP patients, 11HCMSMN patients, and 8 nonfailing controls. Patients with HCM had obstructive cardiomyopathy with left ventricular outflow tract obstruction and diastolic dysfunction. A novel MYBPC32373insG mouse model was used to confirm functional relevance of our proteomic findings. Results: In all HCM patient samples, we found lower levels of metabolic pathway proteins and higher levels of extracellular matrix proteins. Levels of total and detyrosinated α-tubulin were markedly higher in HCMSMP than in HCMSMN and controls. Higher tubulin detyrosination was also found in 2 unrelated MYBPC3 mouse models and its inhibition with parthenolide normalized contraction and relaxation time of isolated cardiomyocytes. Conclusions: Our findings indicate that microtubules and especially its detyrosination contribute to the pathomechanism of patients with HCMSMP. This is of clinical importance since it represents a potential treatment target to improve cardiac function in patients with HCMSMP, whereas a beneficial effect may be limited in patients with HCMSMN.

Contains fulltext : 170591.pdf (Publisher’s version ) (Open Access) Cardiopulmonary exercise testing is an important tool to predict prognosis in children and adults with heart failure. A much less sophisticated exercise test is the 6 min walk test, which has been shown an independent predictor for morbidity and mortality in adults with heart failure. Therefore, we hypothesized that the 6 min walk test could be predictive for outcome in children with dilated cardiomyopathy. We prospectively included 49 children with dilated cardiomyopathy >/=6 years who performed a 6 min walk test. Median age was 11.9 years (interquartile range [IQR] 7.4-15.1), median time after diagnosis was 3.6 years (IQR 0.6-7.4). The 6 min walk distance was transformed to a percentage of predicted, using age- and gender-specific norm values (6MWD%). For all patients, mean 6MWD% was 70 +/- 21%. Median follow-up was 33 months (IQR 14-50). Ten patients reached the combined endpoint of death or heart transplantation. Using univariable Cox regression, a higher 6MWD% resulted in a lower risk of death or transplantation (hazard ratio 0.95 per percentage increase, p = 0.006). A receiver operating characteristic curve was generated to define the optimal threshold to identify patients at highest risk for an endpoint. Patients with a 6MWD% < 63% had a 2 year transplant-free survival of 73%, in contrast to a transplant-free survival of 92% in patients with a 6MWD% >/= 63% (p = 0.003). In children with dilated cardiomyopathy, the 6 min walk test is a simple and feasible tool to identify children with a higher risk of death or heart transplantation.

Background: This study aimed to evaluate the changes in heart transplantation (HTx) waiting list mortality following the introduction of the Berlin Heart EXCOR (BH EXCOR) in the Netherlands, as well as the occurrence of adverse events in these children. Methods: A retrospective, single-center study was conducted including all pediatric patients (≤18 years) awaiting HTx. Patients were grouped in two eras based on availability of the BH EXCOR in our center, era I (1998-2006; not available) and era II (2007 to July 31, 2018; available). Results: In total, 87 patients were included, 15 in era I and 72 in era II. Extracorporeal membrane oxygenator support was required in 1 (7%) patient in era I and in 13 (18%) patients in era II. Overall mortality (7/15 in era I vs 16/72 in era II; 47% vs 22%, P = .06) and transplantation rates (8/15 in era I vs 47/72 in era II; 53% vs 65%, P = .39) did not differ significantly. Eleven (39%) patients of the pediatric ventricular assist device (VAD) population died, with the predominant cause being cerebrovascular accidents (CVAs) in eight (29%) patients. Furthermore, 14 (50%) of the pediatric VAD patients survived to transplantation. Adverse events most frequently occurring in VAD patients included CVA in 14 (50%), mostly (68%) within 30 days after VAD implantation, and bleeding requiring rethoracotomy in 14 (50%), all within 30 days after VAD implantation. Conclusions: The introduction of the BH EXCOR has positively impacted the survival of pediatric patients with end-stage heart failure in our center. The predominant cause of death changed from end-stage heart failure in era I to CVA in era II. We emphasize the need for large prospective registry–based studies.

Contains fulltext : 219837.pdf (Publisher’s version ) (Open Access) A single 6-min walk test (6MWT) can be used to identify children with dilated cardiomyopathy (DCM) with a high risk of death or heart transplantation. To determine if repeated 6MWT has added value in addition to a single 6MWT in predicting death or heart transplantation in children with DCM. Prospective multicenter cohort study including ambulatory DCM patients >/= 6 years. A 6MWT was performed 1 to 4 times per year. The distance walked was expressed as percentage of predicted (6MWD%). We compared the temporal evolution of 6MWD% in patients with and without the study endpoint (SE: all-cause death or heart transplantation), using a linear mixed effects model. In 57 patients, we obtained a median of 4 (IQR 2-6) 6MWTs per patient during a median of 3.0 years of observation (IQR 1.5-5.1). Fourteen patients reached a SE (3 deaths, 11 heart transplantations). At any time during follow-up, the average estimate of 6MWD% was significantly lower in patients with a SE compared to patients without a SE. In both patients groups, 6MWD% remained constant over time. An absolute 1% lower 6MWD% was associated with an 11% higher risk (hazard) of the SE (HR 0.90, 95% CI 0.86-0.95 p < 0.001). Children with DCM who died or underwent heart transplantation had systematically reduced 6MWD%. The performance of all patients was stable over time, so repeated measurement of 6MWT within this time frame had little added value over a single test. 01 februari 2020

Contains fulltext : 220641.pdf (Publisher’s version ) (Closed access) While the role of plasma renin activity (PRA) in heart failure has been widely studied in adults, comprehensive data on pediatric heart failure remain lacking. This drawback is increasingly being addressed by academic research. Nevertheless, such pediatric investigations are commonly conducted only once due to ethical constraints. Therefore, the quality of bioanalytical data must be ensured to acquire meaningful insights into maturing humoral parameters. However, appropriate post-validation assessment of bioanalytical runs is currently underrepresented by regulatory guidance. Thus, for applications in an academic environment, an easy-to-handle six-step bioanalytical quality control system was designed based on regulatory guidelines (e.g. U.S. Food and Drug Administration) combined with international recommendations (e.g. Clinical and Laboratory Standards Institute) and current scientific discussion. Its applicability to an enzyme-linked immunosorbent assay for determination of PRA was investigated within three pediatric trials of the EU-funded "Labeling of Enalapril in Neonates up to Adolescents" project. This quality control system identified 15 % bioanalytical runs as non-compliant to the predefined specifications and ensured the reliable quantification of 940 pharmacodynamic samples. The inter-run assessment of quality controls was able to demonstrate the comparability of the study results. Furthermore, 86 % of incurred sample reanalysis pairs complied with regulatory requirements (>67 %), thus underlining the long-term reproducibility of the utilized ligand-binding assay. Successful participation in interlaboratory testing confirmed the accuracy of the applied method throughout the entire study period. Further investigations showed no notable differences between the five applied lots of the PRA assay. The applicability of this quality control system was proven in an academic environment and ensured reliable results for PRA over the entire 24-month study period.

Background: Dilated cardiomyopathy (DCM) in children is an important cause of severe heart failure and carries a poor prognosis. Adults with heart failure are at increased risk of anxiety and depression and such symptoms predict adverse clinical outcomes such as mortality. In children with DCM, studies examining these associations are scarce. Aims: We studied whether in children with DCM: (1) the level of emotional and behavioral problems was increased as compared to normative data, and (2) depressive and anxiety problems were associated with the combined risk of death or cardiac transplantation. Methods: To assess emotional and behavioral problems in children with DCM, parents of 68 children, aged 1.5–18 years (6.9±5.7 years), completed the Child Behavior Checklist. Results: Compared to normative data, more young children (1.5–5 years) with DCM had somatic complaints (24.3% vs. 8.0%; p < .001), but fewer had externalizing problems (5.4% vs. 17.0%; p = .049). Overall internalizing problems did not reach significance. Compared to normative data, more older children (6–18 years) showed internalizing problems (38.7% vs. 17.0%; p = .001), including depressive (29.0% vs. 8.0%; p < .001) and anxiety problems (19.4% vs. 8.0%; p = .023), and somatic complaints (29.0% vs. 8.0%; p < .001). Anxiety and depressive problems, corrected for heart failure severity, did not predict the risk of death or cardiac transplantation. Conclusion: Children of 6 years and older showed more depressive and anxiety problems than the normative population. Moreover, in both age groups, somatic problems were common. No association with outcome could be demonstrated.

Objectives: This study aimed to evaluate the predicting value of quantitative and qualitative dyssynchrony parameters as assessed by two-dimensional speckle tracking echocardiography (STE) on outcome in children with dilated cardiomyopathy (DCM). Furthermore, the reproducibility of these parameters was investigated.Background: In previous studies in adults with heart failure, several dyssynchrony parameters have been shown to be a valuable predictor of clinical outcome.Methods: This multicenter, prospective study included 75 children with DCM and 75 healthy age-matched controls. Using STE, quantitative (time to global peak strain and parameters describing intraventricular time differences) and qualitative dyssynchrony parameters (pattern analysis) of the apical four-chamber, three-chamber, two-chamber views, and the short axis of the left ventricle were assessed. Cox regression was used to identify risk factors for the primary endpoints of death or heart transplantation. Inter-observer and intra-observer variability were described.Results: During a median of 21 months follow-up, 10 patients (13%) reached an endpoint. Although quantitative dyssynchrony measures were higher in patients as compared to controls, the inter-observer and intra-observer variability were high. Pattern analysis showed mainly reduced strain, instead of dyssynchronous patterns.Conclusions: In this study, quantitative dyssynchrony parameters were not reproducible, precluding their use in children. Qualitative pattern analysis showed predominantly reduced strain, suggesting that in children with DCM dyssynchrony may be a minor problem.

BackgroundDilated cardiomyopathy in children causes heart failure and has a poor prognosis. Health-related quality of life in this patient group is unknown. Moreover, results may provide detailed information of parents’ sense of their child’s functioning. We hypothesised that health-related quality of life, as rated by parents, and the paediatric heart failure score, as assessed by physicians, have both predictive value on outcome.Methods and resultsIn this prospective study, health-related quality of life was assessed by parent reports: the Infant Toddler Quality of Life questionnaire (0–4 years) or Child Health Questionnaire-Parent Form 50 (4–18 years) at 3–6-month intervals. We included 90 children (median age 3.8 years, interquartile range (IQR) 0.9–12.3) whose parents completed 515 questionnaires. At the same visit, physicians completed the New York University Pediatric Heart Failure Index. Compared with Dutch normative data, quality of life was severely impaired at diagnosis (0–4 years: 7/10 subscales and 4–18 years: 8/11 subscales) and ⩾1 year after diagnosis (3/10 and 6/11 subscales). Older children were more impaired (pConclusionPhysical impairment rated by parents and heart failure severity assessed by physicians independently predicted the risk of death or heart transplantation in children with dilated cardiomyopathy.

SummaryVentricular assist devices (VADs) are widely accepted as therapy to bridge children to heart transplantation. We provide a systematic review of the current state of clinical outcomes in children after paediatric VAD support by the Berlin Heart EXCOR (BH EXCOR) device. A systematic literature search was performed in April 2018. Studies reporting clinical outcomes in at least 15 children supported by a BH EXCOR VAD were included. Additionally, we focused on outcomes in small children and compared outcomes of children supported by a left ventricular assist device (LVAD) versus children supported by a biventricular assist device (BiVAD). Eighteen publications fulfilled the inclusion criteria and were included in this systematic review. Mortality rates ranged from 6.3% [confidence interval (CI) 0.0–18.1%] to 38.9% (2.8–75.0%) while transplantation rates ranged from 37.0% (CI 18.8–55.2%) to 72.5% (CI 63.9–81.2%) and successful weaning rates from 0.0% to 20.7% (CI 6.0–35.5%). In children under 1 year of age, mortality rates ranged from 20.0% to 55.5% and transplantation rates ranged from 0.0% to 62.5%. BiVAD support seemed to result in worse clinical outcomes than LVAD support. Incidence of stroke ranged from 5.0% to 47.0% in all children supported with the BH EXCOR. Although a high incidence of adverse events such as stroke and pump thrombosis is reported, VAD support should be considered in children with end-stage heart failure awaiting heart transplantation. Further research is warranted, especially on optimal timing of device implantation and anticoagulation regimens.

Familial hypertrophic cardiomyopathy (HCM) is usually caused by autosomal dominant pathogenic mutations in genes encoding sarcomeric or sarcomere-associated cardiac muscle proteins. The disease mainly affects adults, although young children with severe HCM have also been reported. We describe four unrelated neonates with lethal cardiomyopathy, and performed molecular studies to identify the genetic defect. We also present a literature overview of reported patients with compound heterozygous or homozygous pathogenic MYBPC3 mutations and describe their clinical characteristics. All four children presented with feeding difficulties, failure to thrive, and dyspnea. They died from cardiac failure before age 13 weeks. Features of left ventricular noncompaction were diagnosed in three patients. In the fourth, hypertrabeculation was not a clear feature, but could not be excluded. All of them had septal defects. Two patients were compound heterozygotes for the pathogenic c.2373dup p.(Trp792fs) and c.2827C > T p.(Arg943*) mutations, and two were homozygous for the c.2373dup and c.2827C > T mutations. All patients with biallelic truncating pathogenic mutations in MYBPC3 reported so far (n=21) were diagnosed with severe cardiomyopathy and/or died within the first few months of life. In 62% (13/21), septal defects or a patent ductus arteriosus accompanied cardiomyopathy. In contrast to heterozygous pathogenic mutations, homozygous or compound heterozygous truncating pathogenic MYBPC3 mutations cause severe neonatal cardiomyopathy with features of left ventricular noncompaction and septal defects in approximately 60% of patients.

BACKGROUND: The policy for listing and transplant for children with dilated cardiomyopathy (DCM) in The Netherlands has been conservative because of low donor availability. The effects of this policy on outcome are reported.METHODS: This was a multicenter, nationwide study performed in 148 children with DCM. The primary outcome was death or heart transplant.RESULTS: Overall, 43 patients (29%) died or were transplanted. Within 1 year of diagnosis, 21 patients died, and only 4 underwent transplantation (3 on mechanical circulatory support). The I-year survival was 85% (95% confidence interval [CI] = 79-91), and 5-year survival was 84% (95% CI = 78-90). Transplantation-free survival at 1 year was 82% (95% CI = 75-88) and at 5 years was 72% (95% CI = 64-80). Within 1 year of diagnosis, with death as the main end-point (21 of 25, 84%), intensive care unit admission (hazard ratio = 2.6, p = 0.05) and mechanical circulatory support (hazard ratio = 3.2, p = 0.03) were risk factors (multivariable Cox analysis); inotropic support was longer in patients reaching an end-point. At >1 year after diagnosis, with transplantation as the main end-point (15 of 18, 83%), age >6 years (hazard ratio = 6.1, p = 0.02) was a risk factor. There were 56 (38%) children who recovered, 50% within 1 year of diagnosis. Recovery was associated with younger age; was similar in patients with myocarditis (43%) and idiopathic disease (41%); and was similar in patients initially admitted to the intensive care unit, admitted to the ward, or treated as outpatients.CONCLUSIONS: The transplantation rate in our cohort in the first year was low, with 1-year and 5-year survival rates similar to other cohorts. Our results suggest that a conservative approach to list children for transplantation early after presentation may be justifiable except for patients with prolonged intensive care unit or mechanical circulatory support. (C) 2015 International Society for Heart and Lung Transplantation. All rights reserved.

BackgroundDilated cardiomyopathy is a rare but serious disorder in children. No effective diagnostic or treatment tools are readily available. This study aimed to evaluate the efficacy of intravenous immunoglobulins in children with new onset dilated cardiomyopathy.Methods and resultsIn this retrospective cohort study, 94 children with new onset dilated cardiomyopathy were followed during a median period of 33 months. All patients with secondary dilated cardiomyopathy – for example, genetic, auto-immune or structural defects – had been excluded. Viral tests were performed in all patients and 18 (19%) children met the criteria for the diagnosis “probable or definite viral myocarditis”. Intravenous immunoglobulins were administered to 21 (22%) patients. Overall transplant-free survival was 75% in 5 years and did not differ between treatment groups. The treatment was associated with a higher recovery rate within 5 years, compared with non-treated children (70 versus 43%, log rank=0.045). After correction for possible confounders the hazard ratio for recovery with intravenous immunoglobulins was not significant (hazard ratio: 2.1; 95% CI: 1.0–4.6; p=0.056). Administration of intravenous immunoglobulins resulted in a greater improvement in the shortening fraction of the left ventricle.ConclusionIn our population of children with new onset dilated cardiomyopathy, of either viral or idiopathic origin, intravenous immunoglobulins were administered to a minority of the patients and did not influence transplant-free survival, but were associated with better improvement of systolic left ventricular function and with better recovery. Our results support the concept that children with new onset dilated cardiomyopathy might benefit from intravenous immunoglobulins.

BACKGROUND The clinical outcomes of noncompaction cardiomyopathy (NCCM) range from asymptomatic to heart failure, arrhythmias, and sudden cardiac death. Genetics play an important role in NCCM.OBJECTIVES This study investigated the correlations among genetics, clinical features, and outcomes in adults and children diagnosed with NCCM.METHODS A retrospective multicenter study from 4 cardiogenetic centers in the Netherlands classified 327 unrelated NCCM patients into 3 categories: 1) genetic, with a mutation in 32% (81 adults; 23 children) of patients; 2) probably genetic, familial cardiomyopathy without a mutation in 16% (45 adults; 8 children) of patients; or 3) sporadic, no family history, without mutation in 52% (149 adults; 21 children) of patients. Clinical features and major adverse cardiac events (MACE) during follow-up were compared across the children and adults.RESULTS MYH7, MYBPC3, and TTN mutations were the most common mutations (71%) found in genetic NCCM. The risk of having reduced left ventricular (LV) systolic dysfunction was higher for genetic patients compared with the probably genetic and sporadic cases (p = 0.024), with the highest risk in patients with multiple mutations and TTN mutations. Mutations were more frequent in children (p = 0.04) and were associated with MACE (p = 0.025). Adults were more likely to have sporadic NCCM. High risk for cardiac events in children and adults was related to LV systolic dysfunction in mutation carriers, but not in sporadic cases. Patients with MYH7 mutations had low risk for MACE (p = 0.03).CONCLUSIONS NCCM is a heterogeneous condition, and genetic stratification has a role in clinical care. Distinguishing genetic from nongenetic NCCM complements prediction of outcome and may lead to management and follow-up tailored to genetic status. (c) 2018 by the American College of Cardiology Foundation.

Endocarditis of congenital coronary fistulas in the cardiac chambers is rare, especially in the paediatric age group. We describe the case of a 9-year-old boy with a fistula from the dilated right coronary artery to the junction of the superior caval vein to the right atrium, complicated by endocarditis. Treatment consisted of 6 weeks of antibiotics and interventional closure of the fistula 3 months later with an Amplatzer vascular plug.

Objectives Immunocompromised patients can suffer prolonged norovirus symptoms and virus shedding for many years. Little is known about the prevalence of chronic norovirus infection among solid organ transplant (SOT) recipients. In this study, 2182 SOT recipients were retrospectively tested for chronic norovirus infection. Methods The first and last norovirus positive faecal samples of SOT recipients were sequenced to distinguish between persisting infection and re-infection. Patient charts were reviewed to obtain data on health status and treatments. Results In all, 101 of 2182 (4.6%) recipients were norovirus infected and 23 (22.8%) of these developed chronic norovirus infection. Chronic norovirus infection was found among allogeneic heart, kidney and lung transplant recipients. The median shedding period at the end of the study period was 218 days (range 32–1164 days). Conclusions This study shows that chronic norovirus infection is not a rare phenomenon among SOT recipients in a tertiary-care hospital. Further research is needed to study the risk of norovirus transmission to other immunocompromised patients in the hospital and to the general population.

Contains fulltext : 171290.pdf (Publisher’s version ) (Open Access) In adults with heart failure, central sleep apnea (CSA), often manifested as Cheyne-Stokes respiration, is common, and has been associated with adverse outcome. Heart failure in children is commonly caused by dilated cardiomyopathy (DCM). It is unknown whether children with heart failure secondary to DCM have CSA, and whether CSA is related to the severity of heart failure. In this prospective observational study, 37 patients (/=1) was found in 19 % of the patients. AHI ranged from 1.2 to 4.5/h. The occurrence of CSA was not related to the severity of heart failure. Three older patients showed a breathing pattern mimicking Cheyne-Stokes respiration, two of whom required heart transplantation. CSA was found in 19 % of the children with heart failure secondary to DCM. No relation was found with the severity of heart failure. In a small subset of children with severe DCM, a pattern mimicking Cheyne-Stokes respiration was registered.

Aims Primary pulmonary vein stenosis (PVS) is a rare cardiac abnormality that exhibits a high morbidity and mortality rate. The disease is characterized by obstruction of the pulmonary venous blood flow owing to congenital hypoplasia of individual extra-pulmonary veins. We describe a consanguineous Turkish family with four affected siblings with primary PVS in association with prenatal lymphatic abnormalities. We aimed to map the first gene for primary PVS. Methods and results Patients had extensive cardiological examinations including electrocardiograms, echocardiograms, ventilation–perfusion scans, and cardiac catheterizations. All patients died before the age of 16 months because of severe progressive primary PVS. Chromosomal analysis revealed normal karyotypes. We performed a genome-wide linkage analysis using 250 K single nucleotide polymorphism arrays and found the first locus for primary PVS on chromosome 2q35-2q36.1 [multipoint logarithms (base 10) of odds (LOD) scores 3.6]. By fine-mapping with microsatellite markers, we confirmed the homozygous region that extended 6.6 Mb (D2S164–D2S133). Sequencing 12 (188 exons) of the 88 genes from the region revealed no disease-causing sequence variations. Conclusion Our findings open perspectives for the identification of the genetic cause(s) leading to PVS, which might contribute to elucidate the pathological mechanisms involved in this disorder.

Background: An increasing number of children are requiring circulatory suport. Hospitals offering pediatric Ventricular Assist Device (VAD) should have devices of different sizes available to cover the full range of patient sizes incurring considerable expense. As in adults, post-operative bleeding often complicates VAD implantation. The use of a Levitronix Centrimag centrifugal pump, connected to Berlin Heart Excor cannulae, seems an attractive and logic combination, both in terms of patient safety and of hospital economics. Methods: We describe 3 children with therapy resistant cardiac failure who underwent extracorporeal membrane oxygenation (ECMO) as a rescue before proceeding to placement of the Berlin Heart Excor paracorporeal assist device. The Levitronix Centrimag pump was used as an intermediate device to allow the patients to be stabilised. Therefore, only Berlin Heart cannulae of different sizes have to be readily available; if successful stabilization can be achieved, the Berlin Heart Excor ventricles and the drive unit can then be ordered to replace the Levitronix pump. Results: Two patients were successfully stabilised with the Levitronix pump and were switched to the definitive Berlin Heart Excor ventricles after 6 days of support. The third child succumbed due to intractable pulmonary hemorrhage in severely damaged lungs. No device related complications, especially no thrombo-embolic events, occurred during Levitronix support. Conclusion: The Levitronix Centrimag pump was easy to handle and gave effective circulatory support, the patients were only switched to the Berlin Heart Excor system after stabilization. In patients with a high risk of failure, it is a relatively cheap but safe and effective support system.

Contains fulltext : 69461.pdf (Publisher’s version ) (Closed access) After Fontan operation, patients are limited in increasing cardiac output and in exercise capacity. This has been related to impaired preload or other factors leading to decreased global ventricular performance with stress. To study these factors, the stress responses of functionally univentricular hearts were assessed at rest and during low-dose dobutamine stress using cardiovascular magnetic resonance imaging. Thirty-two patients after Fontan completion at young age were included (27 with total cavopulmonary connection, 5 with atriopulmonary connection; mean age 13.3 years, range 7.5 to 22.2; 23 male patients; median follow-up after Fontan operation 8.1 years, range 5.2 to 17.8). A multiphase short-axis stack of 10 to 12 contiguous slices of the systemic ventricle was obtained at rest and during low-dose dobutamine stress cardiovascular magnetic resonance imaging (maximum 7.5 microg/kg/min). With stress-testing, heart rate, ejection fraction, and cardiac index increased adequately (p

Item does not contain fulltext N-terminal pro-B-type natriuretic peptide (NT-proBNP) is an important predictor of outcome in adults with heart failure. In children with heart failure secondary to dilated cardiomyopathy (DC) markers that reliably predict disease progression and outcome during follow-up are scarce. We investigated whether serial NT-proBNP measurements were predictive for outcome in children with DC. All available NT-proBNP measurements in children with DC were analyzed. Linear mixed-effect models and Cox regression were used to analyze the predictive value of NT-proBNP on the end point of cardiac death (death, heart transplantation, or mechanical circulatory support). During 7 years, 115 patients were included. At diagnosis, median NT-proBNP was high and not predictive for outcome. At any time during follow-up, a twofold higher NT-proBNP resulted in a 2.9 times higher risk in the first year (p 30 days HR 2.9; >1 year HR 6.4). In patients with idiopathic DC (IDC) at 30 days after diagnosis, NT-proBNP >/=7,990 pg/ml showed a 1- and 2-year event-free survival of 79% and 71% and >1 year after diagnosis NT-proBNP >/=924 pg/ml showed a 2- and 5-year event-free survival of 50% and 40%, whereas below both thresholds event-free survival was 100%. In non-IDC, these thresholds were not predictive for outcome. In conclusion, NT-proBNP at any time during follow-up and its change over time were significantly predictive for the risk of cardiac death in children with DC. In children with IDC >1 year after diagnosis, NT-proBNP >924 pg/ml identified a subgroup with a poor outcome.

Right and left ventricular function after chronic pulmonary artery banding in rats assessed with biventricular pressure-volume loops. Am J Physiol Heart Circ Physiol 291: H1580-H1586, 2006. First published May 5, 2006; doi:10.1152/ajpheart.00286.2006.-In many patients with congenital heart disease, the right ventricle (RV) is subjected to abnormal loading conditions. To better understand the state of compensated RV hypertrophy, which could eventually progress to decompensation, we studied the effects of RV pressure overload in rats. In the present study, we report the biventricular adaptation to 6 wk of pulmonary artery banding (PAB). PAB resulted in an RV pressure overload to similar to 60% of systemic level and a twofold increase in RV mass (P

Objectives Mechanical circulatory support (MCS) with a ventricular assist device (VAD) as a bridge to heart transplantation (HTx) or recovery may improve outcome in children with terminal heart failure. We report our experience with MCS in children eligible for HTx and its effect on waiting list mortality. Methods Retrospective single-centre cohort study, National Paediatric HTx Programme including all children eligible for HTx, since the introduction of MCS-VAD in 2006. Results A total of 43 patients were eligible for HTx, median age 11.7 years [Inter Quartile Range (IQR) 3.0-14.7]. In 18 patients, (42%) a VAD was implanted, 11 (61%) survived to HTx (n = 9) or recovery (n = 2). Techniques and devices used were left ventricular assist device (n = 16, 89%), in 4 cases preceded by extracorporeal membrane oxygenation (ECMO), and biventricular assist device (n = 2, 11%), both preceded by ECMO. In the VAD group, median time to death (n = 7) was 18 days (IQR 7-75), median time to HTx (n = 9) 66 days (IQR 33-223) and 2 patients recovered after 30 and 308 days. The main cause of death on MCS was neurological injury in 4 patients (22%) and systemic thrombo-embolic events in 2 (11%). The most common serious adverse events included confirmed thrombus requiring pump replacement (in 11 patients, 61%) and pericardial effusion leading to rethoracotomy (in 5 patients, 28%). Compared with the era before MCS (1998-2006), waiting list mortality decreased from 44 to 21%, and is now mainly related to complications of VAD support. Conclusions Since the introduction of MCS-VAD, waiting list mortality halved and more children with end-stage heart failure survived to heart transplantation, thus improving outcome. Although there is substantial mortality and morbidity, overall mortality decreases, making MCS-VAD an essential therapeutic tool. The need for donor organs remains critically urgent.

Kawasaki disease (KD) is a pediatric vasculitis. Its main complication is the development of coronary artery aneurysms (CAA), with giant CAA at the end of the spectrum. We evaluated regression and event-free rates in a non-Asian cohort of patients with giant CAA using the current z-scores adjusted for body surface area instead of absolute diameters. KD patients with giant CAA (z-score ≥10) visiting our outpatient clinic between January 1999 and September 2015 were included. Patient characteristics and clinical details were extracted from medical records. Regression was defined as all coronary arteries having a z-score of ≤3. A major adverse event was defined as cardiac death, myocardial infarction, cardiogenic shock, or any coronary intervention. Regression-free and event-free rates were calculated using the Kaplan–Meier method. We included 52 patients with giant CAA of which 45 had been monitored since the acute phase. The 1-, 2-, and 5-year regression-free rates were 0.86, 0.78, and 0.65, respectively. The 5-year, 10-year, and 15-year event-free rates were 0.79, 0.75, and 0.65, respectively. Four children, whose CAA would not have been classified as ‘giant’ based on absolute diameters instead of z-scores, had experienced an event during follow-up. Conclusion: We found a high percentage of children in whom the lumen of giant CAA completely normalized. Four children not classified as ‘giant’ based on absolute diameters with z-scores of ≥10 experienced a cardiac event. Hence, the use of z-scores seems to be justified. Electronic supplementary material The online version of this article (doi:10.1007/s00246-017-1590-0) contains supplementary material, which is available to authorized users.

ObjectivesTo evaluate the results of balloon dilatation of stenotic homografts in children, adolescents, and young adults and to identify factors that might influence or predict the effect of the dilatation.BackgroundHomografts are widely used in congenital cardiac surgery; however, the longevity remains a problem mostly because of stenosis in the homograft. The effect of treatment by balloon dilatation is unclear.MethodsIn a retrospective study, the effect of balloon dilatation was determined by the percentage of reduction of the peak systolic pressure gradient over the homograft during catheterisation and the postponement of re-intervention or replacement of the homograft in months. Successful dilatations – defined in this study as a reduction of more than 33% and postponement of more than 18 months – were compared with unsuccessful dilatations in search of factors influencing or predicting the results.ResultsThe mean reduction of the peak systolic pressure gradient was 30% in 40 procedures. Re-intervention or replacement of the homograft was postponed by a mean of 19 months. In all, 14 balloon dilatations (35%) were successful; the mean reduction was 49% and the mean postponement was 34 months. The time since homograft implantation, the presence of calcification, the homograft/balloon ratio, and the pressure applied during dilatation all tended to correlate with outcome, but were not statistically significant.ConclusionsBalloon dilatation is able to reduce the peak systolic pressure gradient over homografts in a subgroup of patients and can be of clinical significance to postpone re-intervention or pulmonary valve replacement.

In the spring and summer of 2008 two seriously ill male infants were admitted to a paediatric intensive care unit. Initially, both had a fever, were drinking less and were pale complexioned. Physical examination revealed tachycardia, slow capillary filling and liver enlargement. Within a few hours, both infants developed circulatory and respiratory failure. A chest radiograph showed that the heart was enlarged and echocardiography revealed that the pump function of both ventricles was severely diminished. Myocarditis caused by Coxsackie virus B3 was diagnosed when the virus was demonstrated in serum and faeces. At the last follow-up, one infant still had severe pump function disorders, and the other one died. Coxsackie virus B3 is a non-polio enterovirus that usually causes mild clinical syndromes but is also associated with myocarditis and overwhelming, systemic neonatal infections. In neonates with mild symptoms one should be alert to progression to circulatory insufficiency, especially if the mother experiences a flu-like illness in the perinatal period. Early recognition of heart failure and adequate diagnostic testing for cardiotropic viruses is important as morbidity and mortality is considerable.

In many forms of congenital heart disease, the right ventricle (RV) is subject to abnormal loading conditions resulting in RV hypertrophy and remodeling. We determined the alterations in RV cytoplasmic proteomic phenotype that occur during prolonged periods of RV pressure overload. We performed a differential proteomic profiling study on RV hypertrophy using an animal model of various durations of pulmonary artery banding (PAB) in parallel with hemodynamic characterization. This hemodynamic evaluation showed that after 6, 12 and 20 weeks of PAB, the RV is in a compensated state of hypertrophy. Overall, the majority of protein changes were metabolism related indicating a shift towards the glycolytic pathway at the expense of beta-oxidation in the RV of the PAB animals. The changes in proteins related to the glycolytic pathway, exemplified by enolase and creatine kinase B-chain, tended to precede changes in beta-oxidation. In parallel, increases in stress chaperones, exemplified by several phosphorylated HSP-27 species, are present from the 6 week time point, whereas increases in antioxidant proteins, exemplified by peroxiredoxin 2 and 6, appear to be restricted to the 12 week time point. The p38 MAPK signal transduction pathway appears not to be activated. Observed protein changes are likely part of a protective mechanism against the development of RV failure.

Right ventricular (RV) hypertrophy is an important problem in congenital heart disease. We determined the alterations in phenotype that occur in the initial phase of RV hypertrophy and their possible correlations with the degree of hypertrophy. Therefore, we performed a differential proteomic profiling study on RV hypertrophy using an animal model of pulmonary artery banding (PAB) in parallel with hemodynamic characterization. The RV homogenates were subfractionated in myofilament and cytoplasmic proteins, which subsequently were separated by two-dimensional gel electrophoresis (2-DE), excised, and analyzed by mass spectrometry (MS). The cytoplasmic fraction showed expression changes in metabolic proteins, indicative of a shift from fatty acid to glucose as a substrate for energy supply. Up-regulation of three HSP-27s (1.9-, 1.7-, and 3.5-fold) indicated an altered stress response in RV hypertrophy. Detailed analysis by immunoblotting and MS showed that two of these HSP-27s were at least phosphorylated on Ser15. The myofilament fraction showed up-regulation of desmin and alpha-B-crystallin (1.4-and 1.3-fold, respectively). This alteration in desmin was confirmed by 1-DE immunoblots. Certain differentially expressed proteins, such as HSP-27, showed a significant correlation with the RV weight to the body weight ratio in the PAB rats, suggesting an association with the degree of hypertrophy.