Disease- and sex-specific differences in patients with heart valve disease: a proteome study

Pressure overload in patients with aortic valve stenosis and volume overload in mitral valve regurgitation trigger specific forms of cardiac remodeling; however, little is known about similarities and differences in myocardial proteome regulation. We performed proteome profiling of 75 human left ventricular myocardial biopsies (aortic stenosis = 41, mitral regurgitation = 17, and controls = 17) using high-resolution tandem mass spectrometry next to clinical and hemodynamic parameter acquisition. In patients of both disease groups, proteins related to ECM and cytoskeleton were more abundant, whereas those related to energy metabolism and proteostasis were less abundant compared with controls. In addition, disease group-specific and sex-specific differences have been observed. Male patients with aortic stenosis showed more proteins related to fibrosis and less to energy metabolism, whereas female patients showed strong reduction in proteostasis-related proteins. Clinical imaging was in line with proteomic findings, showing elevation of fibrosis in both patient groups and sex differences. Disease- and sex-specific proteomic profiles provide insight into cardiac remodeling in patients with heart valve disease and might help improve the understanding of molecular mechanisms and the development of individualized treatment strategies

Heart re-transplantation in Eurotransplant

Internationally 3% of the donor hearts are distributed to re-transplant patients. In Eurotransplant, only patients with a primary graft dysfunction (PGD) within 1 week after heart transplantation (HTX) are indicated for high urgency listing. The aim of this study is to provide evidence for the discussion on whether these patients should still be allocated with priority. All consecutive HTX performed in the period 1981-2015 were included. Multivariate Cox' model was built including: donor and recipient age and gender, ischaemia time, recipient diagnose, urgency status and era. The study population included 18 490 HTX, of these 463 (2.6%) were repeat transplants. The major indications for re-HTX were cardiac allograft vasculopathy (CAV) (50%), PGD (26%) and acute rejection (21%). In a multivariate model, compared with first HTX hazards ratio and 95% confidence interval for repeat HTX were 2.27 (1.83-2.82) for PGD, 2.24 (1.76-2.85) for acute rejection and 1.22 (1.00-1.48) for CAV (P < 0.0001). Outcome after cardiac re-HTX strongly depends on the indication for re-HTX with acceptable outcomes for CAV. In contrast, just 47.5% of all hearts transplanted in patients who were re-transplanted for PGD still functioned at 1-month post-transplant. Alternative options like VA-ECMO should be first offered before opting for acute re-transplantation

The DZHK research platform: maximisation of scientific value by enabling access to health data and biological samples collected in cardiovascular clinical studies

The German Centre for Cardiovascular Research (DZHK) is one of the German Centres for Health Research and aims to conduct early and guideline-relevant studies to develop new therapies and diagnostics that impact the lives of people with cardiovascular disease. Therefore, DZHK members designed a collaboratively organised and integrated research platform connecting all sites and partners. The overarching objectives of the research platform are the standardisation of prospective data and biological sample collections among all studies and the development of a sustainable centrally standardised storage in compliance with general legal regulations and the FAIR principles. The main elements of the DZHK infrastructure are web-based and central units for data management, LIMS, IDMS, and transfer office, embedded in a framework consisting of the DZHK Use and Access Policy, and the Ethics and Data Protection Concept. This framework is characterised by a modular design allowing a high standardisation across all studies. For studies that require even tighter criteria additional quality levels are defined. In addition, the Public Open Data strategy is an important focus of DZHK. The DZHK operates as one legal entity holding all rights of data and biological sample usage, according to the DZHK Use and Access Policy. All DZHK studies collect a basic set of data and biosamples, accompanied by specific clinical and imaging data and biobanking. The DZHK infrastructure was constructed by scientists with the focus on the needs of scientists conducting clinical studies. Through this, the DZHK enables the interdisciplinary and multiple use of data and biological samples by scientists inside and outside the DZHK. So far, 27 DZHK studies recruited well over 11,200 participants suffering from major cardiovascular disorders such as myocardial infarction or heart failure. Currently, data and samples of five DZHK studies of the DZHK Heart Bank can be applied for

Mechanical unloading by miniature axial flow pumps in late cardiac allograft failure due to acute rejection

Allograft failure secondary to rejection commonly requires a multimodal treatment, ultimately including mechanical circulatory support. A few case reports have demonstrated the use of Impella-devices due to its assumed favorable safety profile in this fragile cohort. However, this treatment option does not play a role in choice of anti-rejective therapy in clinical routine up to date. We summarize our institutional experiences and literature mini-review on Impella-based treatment strategies in allograft rejection after heart transplantation. In all seven cases, three from our institution and four reported in the literature, Impella-based therapies led to hemodynamic stabilization in allograft failure secondary to rejection. Adverse events included hemolysis, non-fatal bleeding and in one patient a relevant aortic valve insufficiency occurred. All patients showed an improvement of allograft function. Two patients died in context of severe immunosuppression or late secondary organ failure. Based on the limited available data, we propose that Impella-mediated mechanical unloading represents a valuable option for hemodynamic stabilization in severe allograft failure due to rejection, enabling an initiation of causal therapy and thereby potentially representing an opportunity to prevent mortality. Furthermore, we hypothesize it might add to the traditional therapeutic approaches by facilitating recovery by decompressing the myocardium in allograft rejection

Non-specific removal of antibodies in patients with idiopathic dilated cardiomyopathy: implications for xenotransplantation

We assessed the efficiency of non-specific extracorporeal immunoadsorption (EIA), using polyclonal anti-human immunoglobulin antibodies, in depleting the serum of anti-galactose{alpha}1,3galactose (Gal) antibody and in decreasing serum cytotoxicity in 5 patients with idiopathic dilated cardiomyopathy. The mean concentrations of anti-Gal immunoglobulin (Ig)M and IgG before EIA were 74 μg/ml and 159 μg/ml, respectively. After EIA, these concentrations decreased by 86% and 88%, respectively. Both anti-Gal IgM and IgG returned to pre-EIA concentrations within 1 month, without rebound to greater than baseline concentrations. After EIA, mean serum cytotoxicity also decreased from 90% to 17%, with recovery by 1 month. Extracorporeal immunoadsorption proved safe in patients with heart failure and was effective in depleting anti-Gal antibody and in decreasing serum cytotoxicity to pig cells