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287 result(s) for "Westermann, Dirk"
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Inflammation and fibrosis in murine models of heart failure
Heart failure is a consequence of various cardiovascular diseases and associated with poor prognosis. Despite progress in the treatment of heart failure in the past decades, prevalence and hospitalisation rates are still increasing. Heart failure is typically associated with cardiac remodelling. Here, inflammation and fibrosis are thought to play crucial roles. During cardiac inflammation, immune cells invade the cardiac tissue and modulate tissue-damaging responses. Cardiac fibrosis, however, is characterised by an increased amount and a disrupted composition of extracellular matrix proteins. As evidence exists that cardiac inflammation and fibrosis are potentially reversible in experimental and clinical set ups, they are interesting targets for innovative heart failure treatments. In this context, animal models are important as they mimic clinical conditions of heart failure patients. The advantages of mice in this respect are short generation times and genetic modifications. As numerous murine models of heart failure exist, the selection of a proper disease model for a distinct research question is demanding. To facilitate this selection, this review aims to provide an overview about the current understanding of the pathogenesis of cardiac inflammation and fibrosis in six frequently used murine models of heart failure. Hence, it compares the models of myocardial infarction with or without reperfusion, transverse aortic constriction, chronic subjection to angiotensin II or deoxycorticosterone acetate, and coxsackievirus B3-induced viral myocarditis in this context. It furthermore provides information about the clinical relevance and the limitations of each model, and, if applicable, about the recent advancements in their methodological proceedings.
Matrix metalloproteinases in coronary artery disease and myocardial infarction
Cardiovascular diseases (CVDs) remain the leading cause of death worldwide. Most cardiovascular deaths are caused by ischaemic heart diseases such as myocardial infarction (MI). Hereby atherosclerosis in the coronary arteries often precedes disease manifestation. Since tissue remodelling plays an important role in the development and progression of atherosclerosis as well as in outcome after MI, regulation of matrix metalloproteinases (MMPs) as the major ECM-degrading enzymes with diverse other functions is crucial. Here, we provide an overview of the expression profiles of MMPs in coronary artery and left ventricular tissue using publicly available data from whole tissue to single-cell resolution. To approach an association between MMP expression and the development and outcome of CVDs, we further review studies investigating polymorphisms in MMP genes since polymorphisms are known to have an impact on gene expression. This review therefore aims to shed light on the role of MMPs in atherosclerosis and MI by summarizing current knowledge from publically available datasets, human studies, and analyses of polymorphisms up to preclinical and clinical trials of pharmacological MMP inhibition.
Oxidative stress in ischemia and reperfusion: current concepts, novel ideas and future perspectives
Oxidative stress remains a major contributor to myocardial injury after ischemia followed by reperfusion (I/R) as the reperfusion of the myocardial infarction (MI) area inevitably leads to a cascade of I/R injury. This review focused on concepts of the antioxidative defense system and elucidates recent research using antioxidants like vitamin C, E and β-carotene or essential trace elements to activate compounds of antioxidative pathways in the circulation. In this context, important defense mechanisms like superoxide dismutase and glutathione peroxidase will be described. Furthermore, the different mechanisms through which myocardial protection can be addressed, like ischemic postconditioning in myocardial infarction or adjunctive measures like targeted temperature management as well as new theories, including the role of iron in I/R injury, will be discussed.
Diagnostic Evaluation of a High-Sensitivity Troponin I Point-of-Care Assay
Increasing numbers of patients are presenting worldwide to emergency departments with suspected myocardial infarction. The use of point-of-care troponin assays might enable faster decision-making in this high-risk population and reduce the burden on emergency facilities. Here, we evaluate the diagnostic performance of a point-of-care high-sensitivity troponin I assay. We conducted a prospective cohort study including patients presenting to the emergency department with suspected myocardial infarction from July 2013 to July 2016. A diagnostic algorithm for a high-sensitivity troponin I point-of-care assay was developed in a derivation data set with 669 patients and validated in an additional 610 patients. The derived 0/1 h algorithm for the point-of-care assay consisted of an admission troponin I <4 ng/L and a δ from 0 h to 1 h <3 ng/L for rule out and an admission troponin I ≥90 ng/L or a δ from 0 h to 1 h ≥20 ng/L for rule in of non-ST-elevation myocardial infarction. Application to the validation cohort showed a negative predictive value of 99.7% (95% CI, 98.1%-100.0%) and 48.0% of patients ruled out, whereas 14.6% were ruled in with a positive predictive value of 86.5% (95% CI, 77.6%-92.8%). The diagnostic performance of the point-of-care high-sensitivity assay was highly comparable to guideline-recommended use of a laboratory-based high-sensitivity troponin assay. The clinical application of a 0/1 h diagnostic algorithm based on a high-sensitivity troponin I point-of-care assay is safe, and diagnostic performance is comparable to a laboratory-based high-sensitivity troponin I assay.
miRNA-197 and miRNA-223 Predict Cardiovascular Death in a Cohort of Patients with Symptomatic Coronary Artery Disease
Circulating microRNAs (miRNAs) have been described as potential diagnostic biomarkers in cardiovascular disease and in particular, coronary artery disease (CAD). Few studies were undertaken to perform analyses with regard to risk stratification of future cardiovascular events. miR-126, miR-197 and miR-223 are involved in endovascular inflammation and platelet activation and have been described as biomarkers in the diagnosis of CAD. They were identified in a prospective study in relation to future myocardial infarction. The aim of our study was to further evaluate the prognostic value of these miRNAs in a large prospective cohort of patients with documented CAD. Levels of miR-126, miR-197 and miR-223 were evaluated in serum samples of 873 CAD patients with respect to the endpoint cardiovascular death. miRNA quantification was performed using real time polymerase chain reaction (RT-qPCR). The median follow-up period was 4 years (IQR 2.78-5.04). The median age of all patients was 64 years (IQR 57-69) with 80.2% males. 38.9% of the patients presented with acute coronary syndrome (ACS), 61.1% were diagnosed with stable angina pectoris (SAP). Elevated levels of miRNA-197 and miRNA-223 reliably predicted future cardiovascular death in the overall group (miRNA-197: hazard ratio (HR) 1.77 per one standard deviation (SD) increase (95% confidence interval (CI) 1.20; 2.60), p = 0.004, C-index 0.78; miRNA-223: HR 2.23 per one SD increase (1.20; 4.14), p = 0.011, C-index 0.80). In ACS patients the prognostic power of both miRNAs was even higher (miRNA-197: HR 2.24 per one SD increase (1.25; 4.01), p = 0.006, C-index 0.89); miRA-223: HR 4.94 per one SD increase (1.42; 17.20), p = 0.012, C-index 0.89). Serum-derived circulating miRNA-197 and miRNA-223 were identified as predictors for cardiovascular death in a large patient cohort with CAD. These results reinforce the assumption that circulating miRNAs are promising biomarkers with prognostic value with respect to future cardiovascular events.
Levelized Cost of Electricity for Electric Vehicle Charging in Off-Grid Solar-Powered Microgrid: A Practical Case Study
The number of electric vehicles is constantly increasing in Europe and around the world. Providing a reliable charging infrastructure for the se vehicles is a major challenge for distribution grid operators. Off-grid microgrids have become a promising solution to this challenge, using renewable energy sources such as solar power to meet the demand in a sustainable way. This paper presents a practical study of a solar-powered microgrid operating at a university campus in Ilmenau, Germany, aimed at supporting electric vehicle (EV) charging at public workplaces. The system includes eight charging stations and utilizes renewable energy to reduce grid dependency. Statistical methods, including distribution functions, medians, and mean values, were applied to classify and evaluate the dataset to analyze energy generation and variable load patterns, as well as system performance. The results show that the Ilmenau microgrid can meet EV charging demand during the warm season but underperform during the cold season. An economic analysis determined costs of EUR 0.58/kWh based on pre-2020 component prices and EUR 0.46/kWh based on 2025 market prices. The calculated annual cost per employee is EUR 308.29 over a 20-year period. Increasing energy storage was found to be neither cost-effective nor operationally beneficial. The scalability of the microgrid to larger workplaces is investigated, and recommendations for system improvements are provided.
Procedural volume and outcomes in patients undergoing VA-ECMO support
Background Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used in patients with critical cardiopulmonary failure. To investigate the association between hospital VA-ECMO procedure volume and outcomes in a large, nationwide registry. Methods By using administrative data from the German Federal Health Monitoring System, we analyzed all VA-ECMO procedures performed in Germany from 2013 to 2016 regarding the association of procedural volumes with outcomes and complications. Results During the study period, 10,207 VA-ECMO procedures were performed; mean age was 61 years, 43.4% had prior CPR, and 71.2% were male patients. Acute coronary syndrome was the primary diagnosis for VA-ECMO implantation ( n  = 6202, 60.8%). The majority of implantations ( n  = 5421) were performed at hospitals in the lowest volume category (≤ 50 implantations per year). There was a significant association between annualized volume of VA-ECMO procedures and 30-day in-hospital mortality for centers with lower vs. higher volume per year. Multivariable logistic regression showed an increased 30-day in-hospital mortality at hospitals with the lowest volume category (adjusted odds ratio 1.13, 95% confidence interval [CI] 1.01–1.27, p  = 0.034). Similarly, higher likelihood for complications was observed at hospitals with lower vs. higher annual VA-ECMO volume (adjusted odds ratio 1.46, 95% CI 1.29–1.66, p  = 0.001). Conclusions In this analysis of more than 10,000 VA-ECMO procedures for cardiogenic shock, the majority of implantations were performed at hospitals with the lowest annual volume. Thirty-day in-hospital mortality and likelihood for complications were higher at hospitals with the lowest annual VA-ECMO volume.
Radiation exposure reduction in peripheral interventions using digital variance angiography versus conventional angiography
Digital variance angiography (DVA) exhibits promising prospects with respect to radiation exposure in digital subtraction angiography (DSA). This study aimed to determine the reduction of radiation dose in endovascular peripheral interventions (EPI) using DVA. The DVA imaging tool v6.0 (Kinepict Medical Imaging Tool, version 6.0.4, Kinepict Health Ltd., Budapest, Hungary) was utilized for patients undergoing EPI using digital angiography. EPI normal dose (EPI-ND) protocols were adapted from 1.20 to 0.81 µGy/frame to EPI low dose (EPI-LD) protocols using DVA-LD acquisitions with 0.36 µGy/frame and occasionally 0.24 µGy/frame based on specific examination requirements. The dose area product (DAP) was evaluated and contrast-to-noise ratio (CNR) was measured for each DSA acquisition. Evaluation included 370 EPI-ND and 62 EPI-LD using DVA-LD of three lower extremity regions (mean age: 73 ± 11 years, 67% male). LD protocols decreased median DAP of ND protocols significantly by 62.0% in pelvic, 53.8% in femoral and popliteal, and 59.4% in cruro-pedal regions, respectively ( p  < .005). DVA-LD increased median CNR significantly compared to DSA-LD ( p  < .001), and was equal to DSA-ND ( p  > .15). Image quality was enhanced by CNR DVA−LD /CNR DSA−ND ratio of 1.9 in pelvic, 2.4 in femoral and popliteal and in cruro-pedal regions. DVA reveals significant radiation dose reduction in lower extremity EPIs and enhances image contrast while decreasing noise.
Venting during venoarterial extracorporeal membrane oxygenation
Cardiogenic shock and cardiac arrest contribute pre-dominantly to mortality in acute cardiovascular care. Here, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has emerged as an established therapeutic option for patients suffering from these life-threatening entities. VA-ECMO provides temporary circulatory support until causative treatments are effective and enables recovery or serves as a bridging strategy to surgical ventricular assist devices, heart transplantation or decision-making. However, in-hospital mortality rate in this treatment population is still around 60%. In the recently published ARREST trial, VA-ECMO treatment lowered mortality rate in patients with ongoing cardiac arrest due to therapy refractory ventricular fibrillation compared to standard advanced cardiac life support in selected patients. Whether VA-ECMO can reduce mortality compared to standard of care in cardiogenic shock has to be evaluated in the ongoing prospective randomized studies EURO-SHOCK (NCT03813134) and ECLS-SHOCK (NCT03637205). As an innate drawback of VA-ECMO treatment, the retrograde aortic flow could lead to an elevation of left ventricular (LV) afterload, increase in LV filling pressure, mitral regurgitation, and elevated left atrial pressure. This may compromise myocardial function and recovery, pulmonary hemodynamics—possibly with concomitant pulmonary congestion and even lung failure—and contribute to poor outcomes in a relevant proportion of treated patients. To overcome these detrimental effects, a multitude of venting strategies are currently engaged for both preventive and emergent unloading. This review aims to provide a comprehensive and structured synopsis of existing venting modalities and their specific hemodynamic characteristics. We discuss in detail the available data on outcome categories and complication rates related to the respective venting option.
Temporal trends in incidence, causes, use of mechanical circulatory support and mortality in cardiogenic shock
Aim The management of cardiogenic shock remains a clinical challenge even in well‐developed healthcare systems, best illustrated by its high mortality despite numerous innovative proposals for management. The aim of this study was to describe temporal trends in incidence, causes, use of mechanical circulatory support, and mortality in cardiogenic shock in Germany. Methods and results Data on all cardiogenic shock patients treated in German hospitals between 2005 and 2017 were obtained from the Federal Bureau of Statistics. The data set comprised 441 696 patients with cardiogenic shock, mean age 71 (±13.8) years, 171 383 (39%) female patients. Incidence rates increased from 33.1/100 000 population in 2005 (27 246 cases) to 51.7/100 000 population in 2017 (42 779 cases). Acute myocardial infarction was the most common cause of cardiogenic shock in 2005–07 (43 422 of 82 037 cases, 52.9%), but the proportion of cases caused by it decreased until 2014–17 (73 274 of 165 873 cases, 44.2%). Over time, intra‐aortic balloon pump (2005: 5104; 2017: 973 cases) was used less frequently, whereas use of extracorporeal‐membrane‐oxygenation (2007: 35; 2017: 2414 cases) and percutaneous left ventricular assist devices (2005: 27; 2017: 1323 cases) increased. Mortality remained high at around 60% without relevant temporal trends in patients without acute myocardial infarction and slightly decreased in patients with acute myocardial infarction. Conclusions In this large, nation‐wide study, annual incidence of cardiogenic shock was growing, its causes were changing, and mortality was high despite a shift towards use of novel mechanical circulatory support devices. This highlights the need to address the evidence gap in this field, in particular for cardiogenic shock caused by diseases other than acute myocardial infarction.