Targeted gene delivery to vascular smooth muscle cells (VSMCs) could prevent or improve a variety of diseases affecting the vasculature and particularly the aorta. Thus, we aimed to develop a delivery vector that efficiently targets VSMCs. We selected engineered adeno-associated virus (AAV) capsids from a random AAV capsid library and tested the top enriched motifs in parallel screening through individual barcoding.
View Article and Find Full Text PDFImmune rejection remains the major obstacle to long-term survival of allogeneic lung transplants. The expression of major histocompatibility complex molecules and minor histocompatibility antigens triggers allogeneic immune responses that can lead to allograft rejection. Transplant outcomes therefore depend on long-term immunosuppression, which is associated with severe side effects.
View Article and Find Full Text PDFOne of the most important medical interventions for individuals with heart valvular disease is heart valve replacement, which is not without substantial challenges, particularly for pediatric patients. Due to their biological properties and biocompatibility, natural tissue-originated scaffolds derived from human or animal sources are one type of scaffold that is widely used in tissue engineering. However, they are known for their high potential for immunogenicity.
View Article and Find Full Text PDFIn recent years, SGLT2 inhibitors have become an integral part of heart failure therapy, and several mechanisms contributing to cardiorenal protection have been identified. In this study, we place special emphasis on the atria and investigate acute electrophysiological effects of dapagliflozin to assess the antiarrhythmic potential of SGLT2 inhibitors. Direct electrophysiological effects of dapagliflozin were investigated in patch clamp experiments on isolated atrial cardiomyocytes.
View Article and Find Full Text PDFTo reduce adhesions after left ventricular assist device (LVAD) implantation, pericardial closure using an expanded polytetrafluoroethylene (ePTFE) patch has been suggested. However, as foreign material, ePTFE patches could increase the risk of infectious complications. In this single-center retrospective study, we investigated outcomes of pericardial closure using an ePTFE patch in LVAD implantation.
View Article and Find Full Text PDFIntroduction: Following heart transplantation, a cascade of immunological responses is initiated influencing the clinical outcome and long-term survival of the transplanted patients. The anti-inflammatory cytokine interleukin-10 (IL-10) was shown to be elevated in the blood of heart transplant recipients directly after transplantation but the releasing cell populations and the composition of lymphocyte subsets following transplantation have not been thoroughly studied.
Methods: We identified immune cells by immunophenotyping and analyzed intracellular IL-10 production in peripheral blood mononuclear cells (PBMC) of heart transplanted patients (n= 17) before, directly after and 24h post heart transplantation.
Mechanical circulatory support has proven effective in managing postcardiotomy cardiogenic shock by stabilizing patients' hemodynamics and ensuring adequate organ perfusion. Among the available device modalities, the combination of extracorporeal life support and a microaxial flow pump for left ventricular unloading has emerged as a valuable tool in the surgical armamentarium. In this publication, we provide recommendations for the application and weaning of temporary mechanical circulatory support in cardiogenic shock patients, derived from a consensus among leading cardiac centers in German-speaking countries.
View Article and Find Full Text PDFObjectives: Patients with ischemic cardiomyopathy undergoing coronary artery bypass grafting (CABG) surgery may develop postcardiotomy cardiogenic shock. In these cases, implantation of an Impella 5.0 or 5.
View Article and Find Full Text PDFRationale: The neurokinin-III receptor was recently shown to regulate atrial cardiomyocyte excitability by inhibiting atrial background potassium currents. TASK-1 (hK3.1) two-pore-domain potassium channels, which are expressed atrial-specifically in the human heart, contribute significantly to atrial background potassium currents.
View Article and Find Full Text PDFExtending selection criteria to face donor organ shortage in heart transplantation (HTx) may increase the risk of mortality. normothermic perfusion (EVP) limits ischemic time allowing assessment of graft function. We investigated the outcome of HTx in 80 high-risk recipients transplanted with marginal donor and EVP-preserved grafts, from 2016 to 2021.
View Article and Find Full Text PDFAims: Patients after heart transplantation (HTX) often require oral anticoagulants (OACs) due to atrial arrhythmias or thromboembolic events but little is known about the post-transplant use of direct oral anticoagulants (DOACs). We investigated the frequency, indications, and complications of DOACs and vitamin K antagonists (VKAs) after HTX.
Methods: We screened all adult patients for the use of post-transplant OACs who underwent HTX at Heidelberg Heart Center between 2000 and 2021.
Background: Bilateral lung transplantation (LuTx) remains the only established treatment for children with end-stage pulmonary arterial hypertension (PAH). Although PAH is the second most common indication for LuTx, little is known about optimal perioperative management and midterm clinical outcomes.
Methods: Prospective observational study on consecutive children with PAH who underwent LuTx with scheduled postoperative VA-ECMO support at Hannover Medical School from December 2013 to June 2020.
Pretransplant allosensitization to human leukocyte antigens (HLA) increases the recipient's waiting list time and mortality in lung transplantation. Rather than waiting for crossmatch-negative donors, since 2013, recipients with preformed donor-specific antiHLA antibodies (pfDSA) have been managed with repeated IgA- and IgM-enriched intravenous immunoglobulin (IgGAM) infusions, usually in combination with plasmapheresis before IgGAM and a single dose of antiCD20 antibody. This retrospective study presents our 9-year experience with patients transplanted with pfDSA.
View Article and Find Full Text PDFObjectives: Total ischaemic time (IT) is considered a limiting factor in lung transplantation. In this retrospective study, we investigate effects of IT and disease burden on outcomes after bilateral lung transplantation.
Methods: A total of 1298 patients undergoing bilateral lung transplantation between January 2010 and May 2022 (follow-up 100%, median 54 months) were included.
Donor shortages have led transplant centers to extend their criteria for lung donors. Accepting lung donors ≥70 years of age has previously shown good short-term outcomes; however, no mid- and long-term outcome data on these extended criteria donors has been published to date. In this study, all patients who underwent lung transplantation between 06/2010 and 12/2019 were included in the analysis, and the outcomes were compared between patients receiving organs from donors <70 years of age and patients transplanted with lungs from donors ≥70 years of age.
View Article and Find Full Text PDFEarly kinetics of lymphocyte subsets involved in tolerance and rejection following heart transplantation (HTx) are barely defined. Here, we aimed to delineate the early alloimmune response immediately after HTx. Therefore, blood samples from 23 heart-transplanted patients were collected before (pre-), immediately (T0), 24 hours (T24), and 3 weeks (3 wks) after HTx.
View Article and Find Full Text PDFUnlabelled: Tricuspid valve regurgitation (TVR) is often observed after orthotopic heart transplantation. However, there is a scarcity of data regarding long-term outcomes of patients with TVR.
Methods: Between January 2008 and December 2015, 169 patients underwent orthotopic heart transplantation at our center and were included in this study.
Objectives: In recent years, an increase in severe and even fatal outcomes related to oesophageal or airway button battery (BB) ingestion by infants and small children has been reported. Extensive tissue necrosis caused by lodged BB can lead to major complications, including tracheoesophageal fistula (TEF). In these instances, best treatment remains controversial.
View Article and Find Full Text PDFBackground: When advanced heart failure occurs in cardiac amyloidosis, prognosis is poor. In this setting heart transplantation (HTX) is a treatment option for selected patients. We here present the results of post-transplantation outcomes in cardiac amyloidosis within the Eurotransplant area, investigating possible predictors of survival.
View Article and Find Full Text PDFPurpose: The goal of this study was to show possible effects of performing the actual procedure of mitral valve repair (MVR) on personalized silicone models 1 day before operation.
Description: Based on preoperative 3-dimensional echocardiography recordings, flexible 3-dimensional replicas of the depicted pathologic mitral valves could be produced and used for a simulation of reconstructive techniques analogous to the upcoming MVR procedure. We integrated this step of personalized surgical planning into the clinical routine of 6 MVR cases with 3 different surgeons.
The use of ventricular assist devices as a bridge to transplant or as destination therapy has increased. Wound complications increase morbidity in this cohort. Cold atmospheric plasma is a source of reactive oxygen and nitrogen species and can reduce the microbial load in skin wounds without negative effects on the surrounding tissue.
View Article and Find Full Text PDFThe Berlin Heart EXCOR is a paracorporeal, pulsatile ventricular assist device used in patients of all age groups. However, adolescent and adult patients on EXCOR support are scarcely explored. Herein, we present a detailed description of infectious complications in this patient cohort.
View Article and Find Full Text PDFAims: Atrial flutter (AFL) is a common late-onset complication after heart transplantation (HTX) and is associated with worse clinical outcomes. Methods: This study investigated the frequency, risk factors, and outcomes of late-onset post-transplant AFL. We analyzed 639 adult patients undergoing HTX at the Heidelberg Heart Center between 1989 and 2019.
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