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Background: Intima proliferation and in-stent restenosis is a challenging situation in interventional treatment of small vessel obstruction. Al/Al 2 O 3 nanowires have been shown to accelerate vascular endothelial cell proliferation and migration in vitro, while suppressing vascular smooth muscle cell growth. Moreover, surface modification of Al/Al 2 O 3 nanowires with poly[bis(2,2,2-trifluoromethoxy)phosphazene (PTFEP) coating enables further advantages such as reduced platelet adhesion. Therefore, the study's goal was to compare the biocompatibility of novel Al/Al 2 O 3  + PTFEP coated nanowire bare-metal stents to uncoated control stents in vivo using optical coherence tomography (OCT), quantitative angiography and histomorphometric assessment., Methods: 15 Al/Al 2 O 3  + PTFEP coated and 19 control stents were implanted in the cervical arteries of 9 Aachen minipigs. After 90 days, in-stent stenosis, thrombogenicity, and inflammatory response were assessed. Scanning electron microscopy was used to analyse the stent surface., Results: OCT analysis revealed that neointimal proliferation in Al/Al 2 O 3  + PTFEP coated stents was significantly reduced compared to control stents. The neointimal area was 1.16 ± 0.77 mm 2 in Al/Al 2 O 3  + PTFEP coated stents vs. 1.98 ± 1.04 mm 2 in control stents (p = 0.004), and the neointimal thickness was 0.28 ± 0.20 vs. 0.47 ± 0.10 (p = 0.003). Quantitative angiography showed a tendency to less neointimal growth in coated stents. Histomorphometry showed no significant difference between the two groups and revealed an apparent inflammatory reaction surrounding the stent struts., Conclusions: At long-term follow-up, Al/Al 2 O 3  + PTFEP coated stents placed in peripheral arteries demonstrated good tolerance with no treatment-associated vascular obstruction and reduced in-stent restenosis in OCT. These preliminary in vivo findings indicate that Al/Al 2 O 3  + PTFEP coated nanowire stents may have translational potential to be used for the prevention of in-stent restenosis., Competing Interests: Declaration of competing interest The following co-authors hold a patent which is related to the contents of the manuscript: Ayman Haidar, Michael Veith, Cenk Aktas, Hashim Abdul-Khaliq, Ali Awadelkareem. Patent title: Beschichtung oder mit einer Beschichtung versehener Körper sowie Verfahren zu deren Herstellung. DAKZ 10 2017 113 7580. 2018; Deutsches Patent- und Markenamt. https://register.dpma.de/DPMAregister/pat/register?AKZ=1020171137580. In addition to this we declare that we have no conflicts of interest to disclose regarding this publication. If any conflicts of interest arise during the course of the publication, we will promptly disclose them to the editor of the publication or to the appropriate parties., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Ventricular assist devices (VAD) are increasingly used in patients with end-stage heart failure due to acquired heart disease. Limited data exists on the use and outcome of this technology in children., Methods: All children (<18 years of age) with VAD support included in the German National Register for Congenital Heart Defects were identified and data on demographics, underlying cardiac defect, previous surgery, associated conditions, type of procedure, complications and outcome were collected., Results: Overall, 64 patients (median age 2.1 years; 45.3% female) receiving a VAD between 1999 and 2015 at 8 German centres were included in the analysis. The underlying diagnosis was congenital heart disease (CHD) in 25 and cardiomyopathy in 39 children. The number of reported VAD implantations increased from 13 in the time period 2000-2004 to 27 implantations in the time period 2010-2014. During a median duration of VAD support of 54 days, 28.1% of patients experienced bleeding complications (6.3% intracerebral bleeding), 14.1% thrombotic (10.9% VAD thrombosis) and 23.4% thromboembolic complications (including cerebral infarction in 18.8% of patients). Children with cardiomyopathy were more likely to receive a cardiac transplantation (79.5% vs. 28.0%) compared to CHD patients. Survival of cardiomyopathy patients was significantly better compared to the CHD cohort (p < 0.0001). Multivariate Cox-proportional analysis revealed a diagnosis of CHD (hazard ratio [HR] 4.04, p = 0.001), age at VAD implantation (HR 1.09/year, p = 0.04) and the need for pre-VAD extracorporeal membrane oxygenation (ECMO) support (HR 3.23, p = 0.03) as independent predictors of mortality., Conclusions: The uptake of VAD therapy in children is increasing. Morbidity and mortality remain high, especially in patients with congenital heart disease and those requiring ECMO before VAD implantation., (Copyright © 2021. Published by Elsevier B.V.)

Background: Patients with simple shunt lesions, such as atrial septal defect (ASD), ventricular septal defect (VSD) and persistent arterial duct (PDA) remain at risk of developing pulmonary hypertension (PH) even after correction of their cardiac defect. We aimed to assess the contemporary prevalence of PH in a well characterized nationwide group of patients based on the German National Register for Congenital Heart Defects., Methods and Results: We included all patients >16 years of age with an isolated diagnosis of ASD, VSD or PDA. Only patients with previous surgical or interventional closure of the defect were included. Patients with genetic syndromes were excluded. Out of 49,597 CHD patients in the register we identified 825 patients with closed, isolated simple defects (52% ASD, 41% VSD, 7% PDA). Of these, 25 (3%) developed PH after a median follow-up of 16 years from defect closure. The risk of PH increased significantly with age at follow-up (p < 0.0001) and age at repair (p < 0.0001) on logistic regression analysis Patients with PH were significantly more likely to be symptomatic (59% vs. 9% in NYHA class ≥2, p < 0.0001) and had significantly higher mortality (hazard ratio 13.4, p < 0.0001) compared to the remaining patients., Conclusions: Based on data from the German National Register CHD Register we report a PH prevalence of 3.0% in patients with corrected, simple lesions. Patients with PH were more symptomatic and had significantly increased mortality risk. Life-long surveillance and low threshold for workup is recommended to ascertain diagnosis of PH, which has important prognostic and clinical implications., Competing Interests: Declaration of competing interest The authors and the institutions involved have received support by Actelion, Pfizer and GlaxoSmithKline Group of Companies (GSK)., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Survival rates of children with congenital heart disease (CHD) have increased significantly in the decade. There is now increased interest in the long-term outcome and quality of life of these children., Aims: To assess the educational achievement of patients with CHD in Germany., Study Design: Cross-sectional study using an online survey. The recruitment of study participants was carried out via the database of the German National Register for Congenital Heart Defects (NRCHD)., Subjects: Patients born between 1992 and 2011 were enrolled in the study. For 2609 study participants (female = 1870 (71.7%); 1072 (41.1%) patients; 1537 (58.9%) parents), who participated in the survey, detailed information regarding the underlying CHD diagnosis and clinical data was available., Outcome Measures: Age at enrollment, secondary school form, school year repetition, school degree., Results: The large majority of study participants were enrolled at a conventional elementary school (83.4%) and started school at the age of 6 years or below (73.3%). In total 45.7% of graduated study participants graduated with the qualification necessary to study at any university. In terms of analysis of the different CHD severity subgroups 57.3% of patients with a mild CHD, 47.5% with a moderate CHD and only 35.1% suffering from a severe CHD attained a high school diploma., Conclusions: In our study, the majority of participating CHD patients had a standard school career. These initial results are of great importance to affected families and treating physicians as they show that, in general, a normal school career is possible for all CHD patients., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Cardiac resynchronization therapy (CRT) is an established option for patients with heart failure. Limited data exists on indications and outcome of CRT in contemporary congenital heart disease (CHD) patients., Methods and Results: All patients with CRT registered in the German National Register for Congenital Heart Defects were systematically identified. We analysed data on demographics, type of congenital defect as well as repair, associated conditions, indication for CRT, heart failure medication, combination with a defibrillator or pacemaker and outcome. Overall, 65 patients with CRT were identified. The most common congenital diagnoses were Tetralogy of Fallot (n = 11), congenitally corrected transposition of the great arteries (ccTGA) (n = 9) and double outlet right ventricle (n = 6). The majority of patients (n = 48, 87%) had conventional antibradycardia pacing or ICD indications. Of these, the majority (n = 44) underwent an upgrade to a CRT system to avoid the detrimental consequences of longstanding conventional ventricular single-site pacing, whereas four patients required an ICD due to heart failure and a history of malignant ventricular tachycardia. During a median follow-up of 6.9 years 19 patients developed complications: 16 patients experienced pacemaker lead dysfunction and 3 patients pacemaker infection., Conclusions: The current study based on a large national register for CHD shows that CRT is feasible and can be used as an adjunct in the heart failure treatment of selected CHD patients. Uptake of this therapy proved to be low in this nationwide study and CRT implantation was largely used in patients with a pre-existing pacing indication or those requiring an ICD., (Copyright © 2018. Published by Elsevier B.V.)

Background: Due to the great advances in the care of patients with congenital heart disease (CHD), mortality has decreased significantly over the last decades. Nonetheless, mortality for adults with congenital heart disease (ACHD) is still higher than for the general population. An analysis regarding causes of death in a nationwide contemporary cohort of ACHD is lacking., Methods: A well-characterized cohort of the German National Register for Congenital Heart Defects was screened for patients over the age of 18 years who died between January 2001 and January 2015. Data relating to the cardiac diagnosis, symptoms, operations, interventions, comorbidities, and causes of death were analyzed., Results: During a median follow-up of 3.67 years (IQR 1.32-9.41), 239 (9.2%) out of 2596 patients died during the study period (110 female (46%), mean age at death 39.8 ± 17.8 years). The majority of these deaths was CHD-related (171 patients (71.5%)). Leading causes of death were heart failure (n=66, 27.6%), and sudden cardiac death (n=55, 23.0%). Deceased patients had a more complex CHD and more extracardiac comorbidities compared with living patients., Conclusions: Causes of death of ACHD patients in a large contemporary cohort from a national register are in the majority still CHD-related, with heart failure being the leading cause of death. Additionally, extracardiac comorbidities gain increasing importance., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Patients, their relatives, as well as medical specialists from the fields of paediatric cardiology, cardiology and cardiac surgery were surveyed to investigate the current research needs in the field of congenital heart disease (CHD) focussing specifically on the needs of those affected., Material and Methods: An online survey including four groups of patients with CHD (Fontan circulation, transposition of the great arteries [TGA] after atrial switch [AS] and after arterial switch operation [ASO], tetralogy of Fallot [TOF]) was performed. Each questionnaire comprised twelve topics. Persons affected (patients and relatives) were surveyed by means of CHD group specific questionnaires. Participants were recruited through the German National Register for Congenital Heart Defects., Results: N=596 affected persons (Fontan circulation: n=189; TGA after AS: n=64; TGA after ASO: n=90; TOF: n=253) and 75 physicians (57.3% paediatric cardiologists, 28.0% cardiologists, 10.7% cardiac surgeons, 4.0% other) participated. In general, those affected assume a greater need for research than physicians. Regarding the CHD related topics to be the focus of future research, those affected largely agreed with the participating physicians, although with a different ranking of research topics., Conclusions: Based on the results of our study the challenges immanent in routine care for the CHD patient groups investigated can be identified. Accordingly, these topics should be prioritized in the research of the coming years., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Glass coatings are of great interest for biomedical implant application due to their excellent properties. Nowadays they are used in different fields including drug delivery, for bone tissue regeneration or as implant. Nevertheless they can only be applied using high temperatures. Therefore their usage in the field of cardiovascular implant application is still restricted. Accordingly new developments in this field have been carried out to overcome this problem and to coat cardiovascular implants. Here, novel glass-like coatings have been developed and applied using sol-gel technique at moderate temperatures. The biocompatibility and selectivity have been analyzed using human endothelial cells. The obtained results clarify that the developed compositions can either promote or suppress endothelial cell growth only by altering the sintering atmosphere. A later application as thin layer on cardiovascular implants like stents is conceivable.

Background: The Ross procedure is an established option for aortic valve replacement in young patients. It does, however, involve implantation of a valved conduit in the pulmonary position and dissection in the right ventricular (RV) myocardium with the possibility of RV impairment. Aortic valve reconstruction (AVr) may avoid the drawbacks of this method., Methods: To assess ventricular performance, 2-dimensional (2D) echocardiography and longitudinal strain analysis were performed in 19 patients after a Ross procedure and 19 patients after AVr and compared with 19 age-matched healthy controls., Results: Left ventricular (LV) volumes were significantly increased in both patient groups compared with controls (p < 0.05). Right ventricular (RV) volumes were significantly elevated in the Ross group compared with the AVr group (p < 0.05) and controls (p < 0.01). Peak longitudinal LV strain was significantly reduced in the Ross group (-14.8% ± 4.7%) compared with the AVr group (-18.8% ± 2.5%; p = 0.003) and healthy controls (-20.2% ± 3.9%; p = 0.001). Peak longitudinal RV strain was also significantly reduced in the Ross group (-21.8% ± 4.8%) compared with the AVr group (-25.1% ± 2.5%; p = 0.02) and healthy controls (-26.5% ± 3.2%; p = 0.003). Reduced RV strain was associated with increased pressure gradients of the pulmonary substitute (r = 0.48; p = 0.04) but not with follow-up time, RV volumes, or RV ejection fraction (EF)., Conclusions: Elevation of LV volumes can still be noticed in patients years after the Ross operation or AVr. Increased RV volumes and a reduced RV longitudinal strain are found after the Ross operation, indicating persistent systolic RV dysfunction even in patients with mild RV pressure overload., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: Assessment of cardiac function by speckle-tracking (2D-S) echocardiography in the transitional period from fetal to neonatal life in a healthy population., Methods: Ultrasound assessment of cardiac function of 30 healthy fetuses at the gestational age of 28 weeks, and follow-up after birth using 2-D strain derived novel parameters such as longitudinal strain (S), strain rate (SR), tissue velocities, MPI- and E/E'-index, E/A- and E'/A'-rate of both right (RV) and left ventricles (LV) and interventricular septum (IVS) and comparison to conventionally measured cardiac stroke volume (SV), cardiac output (CO) and ejection fraction (EF)., Results: Ultrasound 2D-S performance and analysis were technically feasible and reproducible in all 30 fetuses and in the neonatal period. In fetuses, tissue velocities and SR measurements were homogenous for all regions of interest in both ventricles, and strain increased from apex to base and was significantly higher in the RV compared to LV. All calculated indices were almost identical for RV and LV. After birth, strain and strain rate exhibited significantly lower values, and systolic tissue velocities were higher in comparison to fetal values in both chambers and in all regions of interest., Conclusion: Speckle-tracking echocardiography is a feasible and reproducible technique in analyzing both fetal and newborn cardiac functions. Therefore, it might be useful in clinical routine examinations and give new insights in transitional physiology., (© 2013. Published by Elsevier Ireland Ltd. All rights reserved.)

Cell-material surface interaction plays a critical role in osseointegration of prosthetic implants used in orthopedic surgeries and dentistry. Different technical approaches exist to improve surface properties of such implants either by coating or by modification of their topography. Femtosecond laser treatment was used in this study to generate microspotted lines separated by 75, 125, or 175μm wide nanostructured interlines on stainless steel (316L) plates. The hydrophobicity and carbon content of the metallic surface were improved simultaneously through this method. In vitro testing of the laser treated plates revealed a significant improvement in adhesion of human endothelial cells and human bone marrow mesenchymal stem cells (hBM MSCs), the cells involved in microvessel and bone formation, respectively, and a significant decrease in fibroblast adhesion, which is implicated in osteolysis and aseptic loosening of prostheses. The hBM MSCs showed an increased bone formation rate on the laser treated plates under osteogenic conditions; the highest mineral deposition was obtained on the surface with 125μm interline distance (292±18mg/cm(2) vs. 228±43mg/cm(2) on untreated surface). Further in vivo testing of these laser treated surfaces in the native prosthetic implant niche would give a real insight into their effectiveness in improving osseointegration and their potential use in clinical applications., (Copyright © 2013 Elsevier B.V. All rights reserved.)

In-stent restenosis is a common complication after stent surgery which leads to a dangerous wall narrowing of a blood vessel. Laser assisted patterning is one of the effective methods to modify the stent surface to control cell-surface interactions which play a major role in the restenosis. In this current study, 316 LS stainless steel substrates are structured by focusing a femtosecond laser beam down to a spot size of 50 μm. By altering the laser induced spot density three distinct surfaces (low density (LD), medium density (MD) and high density (HD)) were prepared. While such surfaces are composed of primary microstructures, due to fast melting and re-solidification by ultra-short laser pulses, nanofeatures are also observed as secondary structures. Following a detailed surface characterization (chemical and physical properties of the surface), we used a well-established co-culture assay of human microvascular endothelial cells and human fibroblasts to check the cell compatibility of the prepared surfaces. The surfaces were analyzed in terms of cell adherence, proliferation, cell morphology and the differentiation of the fibroblast into the myofibroblast, which is a process indicating a general fibrotic shift within a certain tissue. It is observed that myofibroblast proliferation decreases significantly on laser treated samples in comparison to non-treated ones. On the other hand endothelial cell proliferation is not affected by the surface topography which is composed of micro- and nanostructures. Such surfaces may be used to modify stent surfaces for prevention or at least reduction of restenosis., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Unicuspid anatomy of the aortic valve is infrequent but may require intervention by age 40 for severe regurgitation. We propose a new repair technique for the regurgitant unicuspid valve by converting it into a bicuspid aortic valve., Methods: Between November 2003 and September 2007, 20 patients underwent regurgitant unicuspid aortic valve repair: 13 had aortic regurgitation (AR) and 7 had combined regurgitation and stenosis. Four patients had previously undergone balloon valvuloplasty for critical aortic stenosis. The aim of the repair was to construct a bicuspid valve with two normal commissures and unrestricted cusp motion. The fused cusp tissue was divided anteriorly and a new commissure of normal height was created. Noncoronary and right coronary cusps were extended with autologous pericardium. Concomitant operations included ascending aortic replacement in 7 and resection of subaortic stenosis in 1., Results: No early or late deaths occurred. Intraoperative echocardiography revealed minimal or no AR in 19 patients. Follow-up was 4 to 47 months. One patient underwent valve re-repair for recurrent and progressive aortic regurgitation 3 years postoperatively. All other valves remained stable throughout the follow-up period. Freedom from relevant aortic insufficiency (> or = II) at 4 years was 77%; freedom from reoperation was 67%; and freedom from valve replacement was 100%., Conclusions: The regurgitant unicuspid aortic valve can be repaired successfully and reproducibly by converting it into bicuspid anatomy. The functional results are comparable with those obtained in reconstructed bicuspid aortic valves. With this approach, replacement can be avoided in most patients with regurgitant unicuspid aortic valves.

Background: Cardiac allograft vasculopathy (CAV) in patients who have undergone heart transplantation leads to graft dysfunction and is still the major concern for long-term survival. Evaluation of coronary flow velocity reserve (CFR) has been established for diagnosis of CAV. Systemic application of adenosine vs intracoronary testing for CFR has been validated in adults; however, its accuracy in pediatric patients has not yet been proven., Methods: CFR was prospectively measured in 33 clinically asymptomatic pediatric heart transplant recipients. CFR measurements were made in the left anterior descending (LAD) artery using a 0.014-inch Doppler FloWire (Cardiometrics). CFR was defined as the ratio of hyperemic (after adenosine injection) to basal (before adenosine) average peak velocity (APV). Adenosine (Adrekar) was administered by intracoronary (15 or 30 mug bolus) and systemic (0.1 mg/kg) injection in each patient. Epicardial CAV was evaluated in coronary angiograms (Stanford criteria) and microvasculopathy was diagnosed in endomyocardial biopsies (evidence of luminal stenosis) blinded to clinical data., Results: Thirty-three patients were included in this study. Their median age (range) was 11.9 (1.4 to 17) years and median post-transplant time 4.3 (1 to 11.7) years. Seventeen of the 33 patients had epicardial CAV (mainly peripheral obliterations or B1 and B2 lesions) and microvascular CAV. Epicardial CAV only was found in 4 patients and microvasculopathy only was present in only 1 patient. CFR was significantly reduced in patients with epicardial CAV and microvasculopathy when compared with patients without any signs of CAV: 206 +/- 53 vs 276 +/- 39 (p < 0.001) for the systemic application and 213 +/- 50 vs 271 +/- 45 (p = 0.004) for the intracoronary application., Conclusions: CFR and coronary vasoreactivity to adenosine are decreased in pediatric patients with CAV and correlate with histopathologic and angiographic evidence of microvascular disease. Measurement of CFR with intracoronary and systemic application of adenosine is comparable, while systemic application is necessary for non-invasive measurement of CFR in pediatric patients.

Background: Post-transplant lymphoproliferative disease (PTLD) is a severe complication in transplant recipients. Detection of increased Epstein-Barr viral (EBV) load in the peripheral blood acts as a surrogate marker for increased risk of PTLD development. We prospectively monitored EBV load, immunosuppression and PTLD in pediatric heart transplant (HTx) patients to determine risk factors for an increased EBV load and risk of PTLD., Methods: Forty-one pediatric heart transplant recipients were included and underwent prospective monitoring of their immunosuppression and ethylene-diamine tetraacetic acid (EDTA) blood sampling for EBV load (copies/microg DNA) measurement using quantitative real-time polymerase chain reaction (PCR; TaqMan) during January 2001 to December 2006., Results: EBV load was measurable in 70% and was significantly increased (>2,000 copies/microg DNA) in 35% of the patients, with a median EBV load of 5,100 (range 0 to 50,665 copies/microg DNA). Increased EBV load was detected in patients receiving CsA-azathioprine or more than two doses of anti-thymocyte globulin (ATG) and in those <10 years of age, without any significant differences in CsA blood levels. Lowest or negative EBV load was measured in patients receiving CsA-mycophenolate mofetil (MMF) or CsA only. CsA blood levels were not predictable for increased EBV load or PTLD. Six patients developed a EBV-associated B-cell lymphoma (PTLD), among whom 4 (67%) were receiving CsA-azathioprine., Conclusions: Frequent EBV load monitoring identifies patients at high risk for PTLD development. Azathioprine and ATG are major risk factors for increased EBV load and PTLD and patients may benefit from a change of immunosuppression in addition to pre-emptive anti-viral or anti-tumor strategies.

Brain protection is essential during neonatal and pediatric cardiac surgery. Deep hypothermia is still the most important method for achieving neuroprotection during cardiopulmonary bypass. Previously, we could demonstrate that deep hypothermia induces substantial cytotoxicity in brain cells as well as increased release of the pro-inflammatory cytokine interleukin-6 (IL-6), which plays an important role in neuroprotection and neuroregeneration. Deep hypothermia is also associated with increased levels of the astrocytic protein S100B in the serum and cerebrospinal fluid of patients. Since S100B may modulate pro-inflammatory cytokines and may stimulate neurite outgrowth, we have tested the hypothesis that nanomolar concentrations of S100B may increase IL-6 release from brain cells and support axonal outgrowth from organotypic brain slices under hypothermic conditions. S100B administration substantially reduced neuronal and glial cytotoxicity under hypothermic conditions. In the presence of S100B hypothermia-induced IL-6 release in primary astrocytes was significantly increased but reduced in BV-2 microglial cells and primary neurons. Surprisingly, deep hypothermia increased axonal outgrowth from brain slices and--in contrast to our hypothesis--this hypothermia-induced neurite outgrowth was inhibited by S100B. These data suggest that S100B differentially influences cytokine release and cytotoxicity from distinct brain cells and may inhibit neuroregeneration by suppressing hypothermia-induced axonal outgrowth.

An aneurysm of a 14-mm Contegra bovine conduit 5 years after a total repair of tetralogy of Fallot was confirmed by echocardiography, angiography, and magnetic resonance tomography. The conduit was replaced. Histologic examination of the explanted conduit revealed an acellular homogenous material with occasional elastic fibers, fragile, diffuse and complex collagenization throughout the conduit and mild foreign body reaction. Pannus formed over the top of all commissures and on the conduit wall, with extensive mineralization. Close follow-up is seen as mandatory for early detection of the bovine vein conduit aneurysm, particularly in patients in whom small-sized conduits are implanted.