Anker, Stefan Dietmar

[["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.journal","Clinical Research in Cardiology"],["dc.bibliographiccitation.lastpage","9"],["dc.contributor.author","Mordi, Ify R."],["dc.contributor.author","Santema, Bernadet T."],["dc.contributor.author","Kloosterman, Mariëlle"],["dc.contributor.author","Choy, Anna-Maria"],["dc.contributor.author","Rienstra, Michiel"],["dc.contributor.author","van Gelder, Isabelle"],["dc.contributor.author","Anker, Stefan D."],["dc.contributor.author","Cleland, John G."],["dc.contributor.author","Dickstein, Kenneth"],["dc.contributor.author","Filippatos, Gerasimos"],["dc.contributor.author","van der Harst, Pim"],["dc.contributor.author","Hillege, Hans L."],["dc.contributor.author","Metra, Marco"],["dc.contributor.author","Ng, Leong L."],["dc.contributor.author","Ouwerkerk, Wouter"],["dc.contributor.author","Ponikowski, Piotr"],["dc.contributor.author","Samani, Nilesh J."],["dc.contributor.author","van Veldhuisen, Dirk J."],["dc.contributor.author","Zwinderman, Aeilko H."],["dc.contributor.author","Zannad, Faiez"],["dc.contributor.author","Voors, Adriaan A."],["dc.contributor.author","Lang, Chim C."],["dc.date.accessioned","2019-07-09T11:51:01Z"],["dc.date.available","2019-07-09T11:51:01Z"],["dc.date.issued","2019"],["dc.description.abstract","BACKGROUND: In patients with heart failure with reduced ejection fraction (HFrEF) on sub-optimal doses of beta-blockers, it is conceivable that changes in heart rate following treatment intensification might be important regardless of underlying heart rhythm. We aimed to compare the prognostic significance of both achieved heart rate and change in heart rate following beta-blocker uptitration in patients with HFrEF either in sinus rhythm (SR) or atrial fibrillation (AF). METHODS: We performed a post hoc analysis of the BIOSTAT-CHF study. We evaluated 1548 patients with HFrEF (mean age 67 years, 35% AF). Median follow-up was 21 months. Patients were evaluated at baseline and at 9 months. The combined primary outcome was all-cause mortality and heart failure hospitalisation stratified by heart rhythm and heart rate at baseline. RESULTS: Despite similar changes in heart rate and beta-blocker dose, a decrease in heart rate at 9 months was associated with reduced incidence of the primary outcome in both SR and AF patients [HR per 10 bpm decrease-SR: 0.83 (0.75-0.91), p < 0.001; AF: 0.89 (0.81-0.98), p = 0.018], whereas the relationship was less strong for achieved heart rate in AF [HR per 10 bpm higher-SR: 1.26 (1.10-1.46), p = 0.001; AF: 1.08 (0.94-1.23), p = 0.18]. Achieved heart rate at 9 months was only prognostically significant in AF patients with high baseline heart rates (p for interaction 0.017 vs. low). CONCLUSIONS: Following beta-blocker uptitration, both achieved and change in heart rate were prognostically significant regardless of starting heart rate in SR, however, they were only significant in AF patients with high baseline heart rate."],["dc.identifier.doi","10.1007/s00392-018-1409-x"],["dc.identifier.pmid","30610382"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16029"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59857"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation","info:eu-repo/grantAgreement/EC/FP7/242209/EU//BIOSTAT-CHF"],["dc.relation.issn","1861-0692"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Prognostic significance of changes in heart rate following uptitration of beta-blockers in patients with sub-optimally treated heart failure with reduced ejection fraction in sinus rhythm versus atrial fibrillation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2102"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","European Journal of Heart Failure"],["dc.bibliographiccitation.lastpage","2111"],["dc.bibliographiccitation.volume","22"],["dc.contributor.author","Hoes, Martijn F."],["dc.contributor.author","Tromp, Jasper"],["dc.contributor.author","Ouwerkerk, Wouter"],["dc.contributor.author","Bomer, Nils"],["dc.contributor.author","Oberdorf‐Maass, Silke U."],["dc.contributor.author","Samani, Nilesh J."],["dc.contributor.author","Ng, Leong L."],["dc.contributor.author","Lang, Chim C."],["dc.contributor.author","van der Harst, Pim"],["dc.contributor.author","Hillege, Hans"],["dc.contributor.author","Anker, Stefan D."],["dc.contributor.author","Metra, Marco"],["dc.contributor.author","van Veldhuisen, Dirk J."],["dc.contributor.author","Voors, Adriaan A."],["dc.contributor.author","van der Meer, Peter"],["dc.date.accessioned","2019-12-16T11:32:41Z"],["dc.date.accessioned","2021-10-27T13:21:56Z"],["dc.date.available","2019-12-16T11:32:41Z"],["dc.date.available","2021-10-27T13:21:56Z"],["dc.date.issued","2019"],["dc.description.abstract","AIMS: Cathepsin D is a ubiquitous lysosomal protease that is primarily secreted due to oxidative stress. The role of circulating cathepsin D in heart failure (HF) is unknown. The aim of this study is to determine the association between circulating cathepsin D levels and clinical outcomes in patients with HF and to investigate the biological settings that induce the release of cathepsin D in HF. METHODS AND RESULTS: Cathepsin D levels were studied in 2174 patients with HF from the BIOSTAT-CHF index study. Results were validated in 1700 HF patients from the BIOSTAT-CHF validation cohort. The primary combined outcome was all-cause mortality and/or HF hospitalizations. Human pluripotent stem cell-derived cardiomyocytes were subjected to hypoxic, pro-inflammatory signalling and stretch conditions. Additionally, cathepsin D expression was inhibited by targeted short hairpin RNAs (shRNA). Higher levels of cathepsin D were independently associated with diabetes mellitus, renal failure and higher levels of interleukin-6 and N-terminal pro-B-type natriuretic peptide (P < 0.001 for all). Cathepsin D levels were independently associated with the primary combined outcome [hazard ratio (HR) per standard deviation (SD): 1.12; 95% confidence interval (CI) 1.02-1.23], which was validated in an independent cohort (HR per SD: 1.23, 95% CI 1.09-1.40). In vitro experiments demonstrated that human stem cell-derived cardiomyocytes released cathepsin D and troponin T in response to mechanical stretch. ShRNA-mediated silencing of cathepsin D resulted in increased necrosis, abrogated autophagy, increased stress-induced metabolism, and increased release of troponin T from human stem cell-derived cardiomyocytes under stress. CONCLUSIONS: Circulating cathepsin D levels are associated with HF severity and poorer outcome, and reduced levels of cathepsin D may have detrimental effects with therapeutic potential in"],["dc.identifier.doi","10.1002/ejhf.1674"],["dc.identifier.eissn","1879-0844"],["dc.identifier.issn","1388-9842"],["dc.identifier.pmid","31797504"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16943"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/92055"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.relation.eissn","1879-0844"],["dc.relation.issn","1879-0844"],["dc.relation.issn","1388-9842"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","CC BY-NC 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc/4.0"],["dc.subject.ddc","610"],["dc.title","The role of cathepsin D in the pathophysiology of heart failure and its potentially beneficial properties: a translational approach"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1415"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","European Journal of Heart Failure"],["dc.bibliographiccitation.lastpage","1423"],["dc.bibliographiccitation.volume","22"],["dc.contributor.author","Bomer, Nils"],["dc.contributor.author","Grote Beverborg, Niels"],["dc.contributor.author","Hoes, Martijn F."],["dc.contributor.author","Streng, Koen W."],["dc.contributor.author","Vermeer, Mathilde"],["dc.contributor.author","Dokter, Martin M."],["dc.contributor.author","IJmker, Jan"],["dc.contributor.author","Anker, Stefan D."],["dc.contributor.author","Cleland, John G.F."],["dc.contributor.author","Hillege, Hans L."],["dc.contributor.author","Lang, Chim C."],["dc.contributor.author","Ng, Leong L."],["dc.contributor.author","Samani, Nilesh J."],["dc.contributor.author","Tromp, Jasper"],["dc.contributor.author","Veldhuisen, Dirk J."],["dc.contributor.author","Touw, Daan J."],["dc.contributor.author","Voors, Adriaan A."],["dc.contributor.author","Meer, Peter"],["dc.date.accessioned","2019-12-16T11:28:05Z"],["dc.date.accessioned","2021-10-27T13:21:55Z"],["dc.date.available","2019-12-16T11:28:05Z"],["dc.date.available","2021-10-27T13:21:55Z"],["dc.date.issued","2019"],["dc.description.abstract","AIMS: Severe deficiency of the essential trace element selenium can cause myocardial dysfunction although the mechanism at cellular level is uncertain. Whether, in clinical practice, moderate selenium deficiency is associated with worse symptoms and outcome in patients with heart failure is unknown. METHODS AND RESULTS: BIOSTAT-CHF is a multinational, prospective, observational cohort study that enrolled patients with worsening heart failure. Serum concentrations of selenium were measured by inductively coupled plasma mass spectrometry. Primary endpoint was a composite of all-cause mortality and hospitalization for heart failure; secondary endpoint was all-cause mortality. To investigate potential mechanisms by which selenium deficiency might affect prognosis, human cardiomyocytes were cultured in absence of selenium, and mitochondrial function and oxidative stress were assessed. Serum selenium concentration (deficiency) was <70 μg/L in 485 (20.4%) patients, who were older, more often women, had worse New York Heart Association class, more severe signs and symptoms of heart failure and poorer exercise capacity (6-min walking test) and quality of life (Kansas City Cardiomyopathy Questionnaire). Selenium deficiency was associated with higher rates of the primary endpoint [hazard ratio (HR) 1.23; 95% confidence interval (CI) 1.06-1.42] and all-cause mortality (HR 1.52; 95% CI 1.26-1.86). In cultured human cardiomyocytes, selenium deprivation impaired mitochondrial function and oxidative phosphorylation, and increased intracellular reactive oxygen species levels. CONCLUSIONS: Selenium deficiency in heart failure patients is independently associated with impaired exercise tolerance and a 50% higher mortality rate, and impaired mitochondrial function in vitro, in human cardiomyocytes. Clinical trials are needed to investigate the effect of selenium supplements in patients with heart failure, especially if they have low plasma concentrations of selenium."],["dc.identifier.doi","10.1002/ejhf.1644"],["dc.identifier.eissn","1879-0844"],["dc.identifier.issn","1388-9842"],["dc.identifier.pmid","31808274"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16942"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/92054"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.relation.eissn","1879-0844"],["dc.relation.issn","1879-0844"],["dc.relation.issn","1388-9842"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0"],["dc.subject.ddc","610"],["dc.title","Selenium and outcome in heart failure"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]