Browsing by Author "Ewert, Peter"

Abstract Aims The post-approval MELODY Registry aimed to obtain multicentre registry data after transcatheter pulmonary valve implantation (TPVI) with the Melody™ valve (Medtronic plc.) in a large-scale cohort of patients with congenital heart disease (CHD). Methods and results Retrospective analysis of multicentre registry data after TPVI with the Melody™ valve. Eight hundred and forty-five patients (mean age: 21.0 ± 11.1 years) underwent TPVI in 42 centres between December 2006 and September 2013 and were followed-up for a median of 5.9 years (range: 0–11.0 years). The composite endpoint of TPVI-related events during follow-up (i.e. death, reoperation, or reintervention >48 h after TPVI) showed an incidence rate of 4.2% per person per year [95% confidence interval (CI) 3.7–4.9]. Transcatheter pulmonary valve implantation infective endocarditis (I.E.) showed an incidence rate of 2.3% per person per year (95% CI 1.9–2.8) and resulted in significant morbidity and in nine deaths. In multivariable Cox proportional hazard models, the invasively measured residual right ventricle (RV)-to-pulmonary artery (PA) pressure gradient (per 5 mmHg) was associated with the risk of the composite endpoint (adjusted hazard ratio: 1.21, 95% CI 1.12–1.30; P < 0.0001) and the risk of TPVI I.E. (adjusted hazard ratio: 1.19, 95% CI 1.07–1.32; P = 0.002). Major procedural complications (death, surgical, or interventional treatment requirement) occurred in 0.5%, 1.2%, and 2.0%, respectively. Acutely, the RV-to-PA pressure gradient and the percentage of patients with pulmonary regurgitation grade >2 improved significantly from 36 [interquartile range (IQR) 24–47] to 12 (IQR 7–17) mmHg and 47 to 1%, respectively (P < 0.001 for each). Conclusion The post-approval MELODY Registry confirms the efficacy of TPVI with the Melody™ valve in a large-scale cohort of CHD patients. The residual invasively measured RV-to-PA pressure gradient may serve as a target for further improvement in the composite endpoint and TPVI I.E. However, TPVI I.E. remains a significant concern causing significant morbidity and mortality.

The progress in fetal cardiology allows for the early diagnosis of congenital heart defects, but there is still a lack of data on the psychological situation of parents expecting a child with a congenital heart defect. In this cross-sectional study, 77 parents (45 women and 32 men) expecting a child with a heart defect were interviewed with different questionnaires. The standardized Hospital Anxiety and Depression Scale (HADS) questionnaire was used to assess the psychological state of the parents. Various statistical procedures were performed to determine the prevalence, risk factors, and predictors of anxiety and depression. The prevalence for prenatal anxiety was 11.8% and for depressed mood 6.6%, whereas the postnatal prevalence was 25% for anxiety and 16.7% for depressed mood. The mother is influential in protecting against depression as a contact person (p = 0.035). Women were more affected by anxiety and depression than men (p = 0.036). A significant and positive correlation was observed between anxiety and depression before birth (ρ = 0.649, p < 0.001) and after birth (ρ = 0.808, p < 0.001). The level of education correlated negatively with depression (p = 0.016) and anxiety (p = 0.017) before birth. Significantly higher anxiety and depression scores were not observed among health and social workers (p = 0.084), first-time mothers (p = 0.190), and parents whose pregnancies were due to medical assistance (p = 0.051). Close collaboration between maternal-fetal care units, pediatric cardiologists and psychiatric/psychosomatic disciplines is a possible strategy to reduce stress in parents. Therefore, an expert team of professionals, educating with understandable terms and sufficient knowledge about fetal heart disease in parenting counseling, is required. The support of affected parents can positively impact the treatment of the child and should be integrated into the daily routine of the clinic.

Abstract Systemic-to-pulmonary shunt malfunction contributes to morbidity in children with complex congenital heart disease after palliative procedure. Neointimal hyperplasia might play a role in the pathogenesis increasing risk for shunt obstruction. The aim was to evaluate the role of epidermal growth factor receptor (EGFR) and matrix-metalloproteinase 9 (MMP-9) in the formation of neointimal within shunts. Immunohistochemistry was performed with anti-EGFR and anti-MMP-9 on shunts removed at follow-up palliative or corrective procedure. Whole-genome single-nucleotide polymorphisms genotyping was performed on DNA extracted from patients´ blood samples and allele frequencies were compared between the group of patients with shunts displaying severe stenosis (≥ 40% of lumen) and the remaining group. Immunohistochemistry detected EGFR and MMP-9 in 24 of 31 shunts, located mainly in the luminal area. Cross-sectional area of EGFR and MMP-9 measured in median 0.19 mm 2 (IQR 0.1–0.3 mm 2 ) and 0.04 mm 2 (IQR 0.03–0.09 mm 2 ), respectively, and correlated positively with the area of neointimal measured on histology ( r  = 0.729, p  < 0.001 and r  = 0.0479, p  = 0.018, respectively). There was a trend of inverse correlation between the dose of acetylsalicylic acid and the degree of EGFR, but not MMP-9, expression within neointima. Certain alleles in epidermal growth factor (EGF) and tissue inhibitor of metalloproteinases 1 (TIMP-1) were associated with increased stenosis and neointimal hyperplasia within shunts. EGFR and MMP-9 contribute to neointimal proliferation in SP shunts of children with complex cyanotic heart disease. SP shunts from patients carrying certain risk alleles in the genes encoding for EGF and TIMP-1 displayed increased neointima.

We present results of the histopathological work-up of an atrial septal defect occluder that was explanted 15 months after interventional implantation due to a significant residual shunt. Complete endothelialization of the surface and a mild inflammatory reaction was demonstrated.

Abstract OBJECTIVES Neointimal hyperplasia might affect systemic-to-pulmonary shunt failure in infants with complex cyanotic congenital heart disease. The aim of this study was to elucidate histopathologic changes in polytetrafluoroethylene shunts and to determine whether increased neointimal formation is associated with early interventions comprising balloon dilatation, stent implantation and shunt revision. Furthermore, we intended to identify clinical factors associated with increased neointimal proliferation. METHODS Removed shunts were processed for histopathological analysis. Slides were stained with hematoxylin/eosin and Richardson. Immunohistochemistry was performed with anti-alpha-smooth muscle actin and anti-CD68. Non-parametric analysis and univariable regressions were performed to identify clinical factors associated with neointimal hyperplasia and shunt stenosis. RESULTS Fifty-seven shunts (39 modified Blalock–Taussig anastomosis, 8 right ventricle-to-pulmonary artery anastomosis, 10 central shunts) were analysed. Area of neointimal proliferation within the shunt was in median 0.75 mm2 (interquartile range, 0.3–1.57 mm2) and relative shunt stenosis in median 16.7% (interquartile range, 6.7–30.8%). Neointimal hyperplasia and shunt stenosis correlated with each other and were significantly greater in the group that required early interventions and shunt revision. Univariable linear regression identified smaller shunt size and lower acetylsalicylic acid dosage as factors to be associated with greater neointimal proliferation and shunt stenosis. CONCLUSIONS In infants with complex cyanotic congenital heart disease, neointimal hyperplasia in systemic-to-pulmonary shunts is associated with early interventions comprising balloon dilatation, stent implantation and shunt revision. Smaller shunt size and lower aspirin dosage are associated with increased neointimal proliferation.

Abstract Myocarditis represents an important cause for acute heart failure. MYKKE, a prospective multicenter registry of pediatric patients with myocarditis, aims to gain knowledge on courses, diagnostics, and therapy of pediatric myocarditis. The role of mechanical circulatory support (MCS) in children with severe heart failure and myocarditis is unclear. The aim of this study was to determine characteristics and outcome of patients with severe heart failure requiring MCS and/or heart transplantation. The MYKKE cohort between September 2013 and 2016 was analyzed. A total of 195 patients were prospectively enrolled by 17 German hospitals. Twenty‐eight patients (14%) received MCS (median 1.5 years), more frequently in the youngest age group (0‐2 years) than in the older groups ( P  < 0.001; 2‐12 and 13‐18 years). In the MCS group, 50% received a VAD, 36% ECMO, and 14% both, with a survival rate of 79%. The weaning rate was 43% (12/28). Nine (32%) patients were transplanted, one had ongoing support, and six (21%) died. Histology was positive for myocarditis in 63% of the MCS group. Patients within the whole cohort with age <2 years and/or ejection fraction <30% had a significantly worse survival with high risk for MCS, transplantation, and death ( P  < 0.001). Myocarditis represents a life‐threatening disease with an overall mortality of 4.6% in this cohort. The fulminant form more often affected the youngest, leading to significantly higher rate of MCS, transplantation, and mortality. MCS represents an important and life‐saving therapeutic option in children with myocarditis with a weaning rate of 43%.

Background: The surgical creation of an aortopulmonary shunt is an important tool in the therapy of complex congenital heart defects. We report on a transcatheter approach to establish an aortopulmonary shunt in piglets. Material, Methods and Results: In 10 piglets with a median body weight of 10.5 kg (8-12 kg), a central aortopulmonary shunt was created by radiofrequency perforation from the aorta to the pulmonary trunk, followed by stent implantation. The procedures were performed via the femoral vessels through 5F sheaths under biplane fluoroscopy guidance. A total of six bare metal coronary stents and five polytetrafluoroethylene-covered coronary stents of 3-4 mm diameter were deployed. Four animals were sacrificed immediately after intervention; six pigs were reevaluated 4-5 weeks later for stent patency and measurement of shunt volume. The procedure was successful in all pigs. Median shunt volume was Op:Qs = 2.4:1. At re-evaluation median body weight had increased to 18 kg (15.5-27.5 kg) P < 0.028. Four of six stents were completely obstructed due to tissue ingrowth in the bare metal stents (two cases) and thrombus formation in the covered stents (two cases). A third bare metal stent had a residual lumen, and a third covered stent was fully open without any thrombus formation or tissue ingrowth. Conclusions: Transcatheter creation of an aortopulmonary shunt by radiofrequency perforation and stent implantation is feasible. The use of appropriate covered stents and an effective anticoagulatory regimen seem to be crucial to keep the shunts open. (C) 2010 Wiley-Liss, Inc.

Objectives: The aim of this animal study was to establish a shunt connection between superior vena cava (SVC) and right pulmonary artery (RPA) by transvascular intervention solely. Background: After initial shunt creation, the establishment of the upper cavo-pulmonary anastomosis (UCPA) is the second out of three open chest operations young infants with univentricular anatomy are subjected to. To avoid the risks of reoperation with cardiovascular bypass, we sought to replace this surgical step by an interventional technique. Methods: After cannulation of jugular and femoral veins in four piglets (mean body weight of 12.5 kg) an UCPA was created by radiofrequency perforation from the SVC across the right atrium into the RPA and subsequent implantation of covered stents. The perforation was guided by biplane fluoroscopy and the perforation wire premounted with a coaxial catheter was advanced into the distal pulmonary artery and exchanged for a stiffer wire. A long sheath was brought into the RPA and an 80 mm long expanded poly-tetra-fluoro-ethylene (ePTFE)-covered Cheatham Platinum stent was then implanted connecting the SVC with the RPA. Results: Immediate angiography showed antegrade flow from SVC to RPA. Angiographic re-evaluation after a median period of 4 weeks showed partial in-stent stenosis but patent lumina. Additionally, veno-venous collaterals from the SVC to the right atrium had developed. Histology of the explanted stents revealed parietal thrombi and mild to moderate pseudo intima proliferation inside the lumina. Conclusions: The transvascular creation of an upper unidirectional cavo-pulmonary anastomosis in piglets is technically feasible using standard catheterization equipment. (c) 2012 Wiley Periodicals, Inc.