Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): FWF Background and aims Proprotein convertase subtilisin/kexin type-9 (PCSK9) is an enzyme promoting the degradation of low-density lipoprotein receptors (LDL-R) in hepatocytes. Inhibition of PCSK9 has emerged as a novel target for lipid-lowering therapy. Monocytes are crucially involved in the pathogenesis of atherosclerosis and can be divided into three subsets. The aim of this study was to examine whether circulating levels of PCSK9 are associated with monocyte subsets. Methods We included 69 patients with stable coronary artery disease. PCSK9 levels were measured and monocyte subsets were assessed by flow cytometry and divided into classical monocytes (CD14++CD16-; CM), intermediate monocytes (CD14++CD16+; IM) and non-classical monocytes (CD14 + CD16++; NCM). Results Mean age was 64 years and 80% of patients were male. Patients on statin treatment (n = 55) showed higher PCSK9-levels (245.4 (206.0-305.5) ng/mL) as opposed to those without statin treatment (186.1 (162.3-275.4) ng/mL; p = 0.05). In patients on statin treatment, CM correlated with circulating PCSK9 levels (R = 0.29; p = 0.04), while NCM showed an inverse correlation with PCSK9 levels (R=-0.33; p = 0.02). Patients with PCSK9 levels above the median showed a significantly higher proportion of CM as compared to patients with PCSK-9 below the median (83.5 IQR 79.2-86.7 vs. 80.4, IQR 76.5-85.2%; p = 0.05). Conversely, PCSK9 levels >median were associated with a significantly lower proportion of NCM as compared to those with PCSK9 <median (10.2, IQR 7.3-14.6 vs. 14.3, IQR 10.9-18.7%; p = 0.02). In contrast, IM showed no association with PCSK-9 levels. Conclusions We hereby provide a novel link between PCSK9 regulation, innate immunity and atherosclerotic disease in statin-treated patients.
Funding Acknowledgements Type of funding sources: None. Background Recent guidelines on acute coronary syndromes (ACS) recommend initiating lipid-lowering therapy (LLT) as soon as possible in order to obtain >50% LDL-cholesterol reduction with a low-density-lipoprotein-cholesterol (LDL-c) <1.4 mmol/L. Aim To define the current LLT policy in Europe after an ACS and to assess whether in hospital initiation of combination therapy of high potency (HP) statin with or without ezetimibe improves the adherence rate to target LDL-c levels as compared to a step-by-step LLT approach. Methods and results Data on LLT and lipid levels during and up to one year after hospitalisation were gathered retrospectively for 286 ACS patients who were admitted in 28 hospitals (70% academic) across 16 European countries between the years 2021 and 2022. Patients (median age 61 years, 75.9% men) were mostly admitted in dedicated cardiology departments/intensive cardiac care units (96.8%). A total 59% had ST-elevation myocardial infarction and 88% were treated with percutaneous coronary intervention. At baseline 69.9% of the patients had dyslipidaemia, 35 (14.6%) were on HP statin, 5 (3.9%) were on ezetimibe, and 6 (2.2%) were on HP statin/ezetimibe combination therapy. The median LDL-c on admission was 3.27 [interquartile range (IQR): 2.4-4.1] mmol/L. HP statin only was the predominant LLT during hospitalisation (62%) and was primarily initiated within 24h from admission (figure). During hospitalization, HP statin/ezetimibe combination therapy was administered in 24.0% of the cases. Combination therapy in hospital was given more frequently in high income countries (n=8) as compared to middle income countries (34.0% vs 10.8%, p<0.001). After one year, LLT up titration to combination therapy with ezetimibe or with PCSK9 inhibition was observed among 40 patients (14%, to a total of 37.4%) and 3 patients (1.6%), respectively. At follow-up, median LDL-c level was 1.6 (IQR 1.3-2.0) mmol/L and the median relative LDL-c reduction was 45.4% (IQR 27.2-64.0). Adherence to target LDL-c with > 50% reduction was achieved in 17.8% of the total population, in 22.4% of the high-income countries and in 12.3% of the middle-income countries (p=0.04). Patients treated with combination therapy at discharge had a higher relative LDL-c reduction than those with HP statin therapy only at discharge (median 52.5% vs 43.8%, p=0.007) and had a numerically higher target lipid status (23.9% vs 17.2%, p=0.24) Conclusions Despite high rates of high intensity LLT during hospitalisation, target LDL-c with > 50% LDL reduction was achieved only in 17.8%. Greater, yet insufficient, LDL-c reduction was observed when combination therapy of high dose statin with ezetimibe was initiated during the index hospitalisation.
Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): -) Association for the Promotion of Research on Arteriosclerosis, Thrombosis and Vascular Biology (ATVB) -) Ludwig Boltzmann Cluster for Cardiovascular Research BACKGROUND Critically ill patients admitted to an intensive care unit (ICU) exhibit a high mortality rate irrespective of the initial cause of hospitalization. Neprilysin is a neutral endopeptidase degrading an array of vasoactive peptides, including bradykinin, adrenomedullin and natriuretic peptides and became a drug target within the treatment of heart failure with reduced ejection fraction. The aim of this study was to analyze whether circulating levels of neprilysin at ICU admission are associated with 30-day mortality, due to its physiologic effects. METHODS In this single-center prospective observational study, 222 consecutive patients admitted to a tertiary ICU at a university hospital were included. Blood was drawn at admission and soluble neprilysin levels were measured using ELISA. RESULTS Median simplified acute physiology score was 44 and 30-day mortality was 35.1% in medical patients (n = 151) and 7.1% in patients after surgery and heart valve interventions (n = 71). Neprilysin levels did not differ according to survival status after 30 days and admission type. When assessing neprilysin and survival according to admission type, no association was found in medical patients, while in patients after surgery or heart valve intervention, 30-day survivors exhibited significantly lower neprilysin levels as compared to those that died within 30 days (660.2, IQR: 156.4 – 2512.5 pg/ml versus 6532.6, IQR: 1840.1 – 10000.0 pg/ml; p = 0.02). Neprilysin predicted mortality independently from age, gender, NT-proBNP, and SAPS II score (OR per 1-SD increase of neprilysin: 2.52, 95%CI 1.01–6.32; p = 0.049). Additionally, neprilysin was markedly elevated in patients with sepsis and septic shock (p < 0.05). CONCLUSION At the time of ICU-admission, circulating levels of neprilysin independently predicted 30-day mortality in patients following cardiac surgery or heart valve intervention, but not in critically ill medical patients.
Funding Acknowledgements Type of funding sources: None. Background Despite the increase of extracorporeal membrane oxygenation (ECMO) employment around the globe over the last decades, studies describing the emergency use of venoarterial (VA)-ECMO in the cardiac catheterization laboratory (CCL) are scarce. Purpose The aim of this study was to describe the patient population that received ECMO in the CCL of a tertiary care center and the associated complications and outcomes. Methods In this single-center retrospective study we reviewed the baseline clinical and laboratory characteristics, indications and outcomes of adult patients, who received VA-ECMO between 2011 and 2019. Results In the given time period, ECMO use in the CCL increased drastically. Mean age of the 83 patients was 58.3 ± 12.5 years, 78.3% were male. From 2011 to 2018 ECMO-use in the CCL increased drastically. The most common indication for ECMO implantation was cardiac arrest (66%), followed by cardiogenic shock (12%), high-risk PCI (11%), and procedure-related complications (10%). While 30-day mortality in the total study population was 69%, it varied greatly depending on the underlying indication for ECMO therapy (cardiac arrest 78%, cardiogenic shock 20%, high-risk PCI 44%, procedure-related complications 88%). The most commonly occurring complications were acute kidney injury (20%) and cannula site bleeding (20%), followed by extremity complications (19%), sepsis (18%), major bleeding (10%) and stroke (8%). Of interest, patients receiving ECMO therapy after in-hospital cardiac arrest showed greater survival rates (28.2%) as compared to patients after out of hospital cardiac arrest (18.2%; p=0.045). High serum lactate levels (p=0.018) and low baseline pH values (p=0.001) at baseline were associated with a significantly increased 30-day mortality after ECMO implantation. Conclusion The emergency use of VA-ECMO in the CCL increased over the last years and was associated with a high 30-day mortality in our study population. Still, a >20% survival rate in the group of patients with refractory cardiac arrest, an otherwise futile situation, suggests that VA-ECMO implantation is reasonable in selected patients. As high admission serum lactate levels and the baseline pH are strong predictors of outcome, such parameters may be used to guide decision making.
Background Inflammation is regarded as an important trigger for disease progression in heart failure (HF) and activation of the inflammatory system was implicated in the pathophysiology of acute heart failure (AHF). Toll-like receptors (TLRs) play an important role in acute inflammatory processes in critically ill patients by binding to pathogen associated molecular patterns (PAMP) and danger associated molecular patterns (DAMP). However, it is not known whether the expression patterns of TLRs on neutrophils and monocytes are associated with outcome in patients with severe AHF requiring intensive care unit (ICU) admission. The aim of this prospective, observational study was to analyze whether TLR-expression on monocytes or neutrophils is associated with 30-day survival in patients with severe AHF. Methods We included 84 patients with severe AHF admitted to a cardiac ICU. Blood was taken at admission and mean fluorescence activity (MFI) of TLR-2, TLR-4 and TLR-9 on monocytes and neutrophils was analyzed by flow cytometry. Results Median age was 64 (IQR 48–74) years and 76.2% of patients were male. Median NT-proBNP was 4941 (IQR 1298–12273) pg/mL and 30-day mortality was 33.3%. TLR-4 expression on monocytes in survivors (740 IQR 694–854) was significantly lower than in non-survivors (871 IQR 723–979; p<0.05). TLR-2 and TLR-9 expression on monocytes and TLR expression on neutrophils was not associated with survival. TLR-4 expression on monocytes was significantly associated with survival independent of age, sex, creatinine and NT-proBNP levels. Conclusion Monocyte TLR-4 expression predicts mortality in patients admitted to a cardiac ICU for severe acute heart failure. This suggests that activation of the innate immune system by TLR-binding of DAMPS may play a significant role in critically ill acute heart failure patients.
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