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1.
Artigo em Inglês | MEDLINE | ID: mdl-32222407

RESUMO

BACKGROUND: If the transfemoral access is not feasible, a transapical access or surgical aortic valve replacement (SAVR) are alternatives for patients with aortic valve stenosis. OBJECTIVES: To identify patient groups who benefit from SAVR or transapical transcatheter aortic valve replacement (TA-TAVR), we compared in-hospital outcomes of patients in a nationwide dataset. METHODS: We identified 19,016 isolated SAVR and 6432 TA-TAVR performed in Germany from 2014 to 2016. We adjusted for risk factors using a covariate- and propensity-adjusted analysis. RESULTS: Patients undergoing TA-TAVR were older, had more comorbidities, and accordingly greater estimated operative risk (logistic European System for Cardiac Operative Risk Evaluation 5.3 vs 17.0, P < .001). However, adjusted risk for in-hospital complications such as stroke, acute kidney injury, relevant bleeding, and prolonged mechanical ventilation >48 hours was lower in patients undergoing TA-TAVR (all P < .001). When we compared in-hospital mortality of all patients undergoing either TA-TAVR or SAVR, neither treatment strategy had a clear advantage (covariate-adjusted odds ratio [caOR], 1.13, P = .251; propensity-adjusted OR [paOR], 1.12, P = .309). Two patient subgroups seem to benefit more from SAVR than TA-TAVR: patients <75 years (caOR, 1.29, P = .237; paOR, 2.12, P = .001) and those with European System for Cardiac Operative Risk Evaluation 4-9 (caOR, 1.32, P = .114; paOR, 1.43, P = .041). Female patients had a tendency toward lower risk for in-hospital mortality when undergoing SAVR (caOR, 1.42, P = .030). In patients with chronic renal failure, TA-TAVR was superior (caOR, 0.56, P = .039, P = .040). CONCLUSIONS: Patients <75 years and those at low operative risk who underwent SAVR had lower in-hospital mortality than those undergoing TA-TAVR. Patients with chronic renal failure who underwent TA-TAVR had lower in hospital mortality than those that underwent SAVR.

3.
PLoS One ; 15(2): e0227345, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32023258

RESUMO

AIMS: Patients with postoperative delirium (POD) after transcatheter aortic valve replacement (TAVR) are ventilated and hospitalized longer and suffer increased in-hospital mortality. This study hypothesized that a minimalistic approach with conscious sedation during transfemoral aortic valve replacement (TF-AVR) protects against delirium, time of mechanical ventilation, and increased length of stay in intensive care unit (ICU) compared to intubation anaesthesia. METHODS AND RESULTS: 308 patients which underwent TF-AVR in our centre between 01/2013 and 08/2017 were retrospectively evaluated regarding postoperative delirium, time of mechanical ventilation, and days in ICU. TF-AVR was performed with intubation anaesthesia in 245 patients and with conscious sedation in 63. The operative risk estimated by the logEUROScore was similar in both groups (intubation: 13.28 +/-9.06%, conscious sedation: 12.24 +/-6.77%, p = 0.395). In the conscious sedation group procedure duration was shorter (0.61 +/-0.91h vs. 1.75 +/-0.96h, p<0.001). The risk for intraprocedural complications was not influenced by the anaesthesia method (OR conscious sedation instead of intubation 1.66, p = 0.117), but days on ICU (-2.21 days, p<0.0001) and minutes of mechanical ventilation (-531.2 min, p < 0.0001) were reduced. Furthermore, the risk of POD was decreased when TF-AVR was performed under conscious sedation (6.35% vs. 18.18%, OR 0.29, p = 0.021). CONCLUSIONS: Time of mechanical ventilation, risk of POD, and days on ICU were substantially reduced in patients who underwent TF-AVR under conscious sedation. Our data suggest that TF-AVR with conscious sedation is safe with a beneficial postoperative course in clinical practice, and should be considered the favoured approach.

4.
Sci Rep ; 10(1): 2241, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32042042

RESUMO

Endothelial cells take pivotal roles in the heart and the vascular system and their differentiation, subspecification and function is determined by gene expression. A stable, in vitro cardiac endothelial cell line could provide high cell numbers as needed for many epigenetic analyses and facilitate the understanding of molecular mechanisms involved in endothelial cell biology. To test their suitability for transcriptomic or epigenetic studies, we compared the transcriptome of cultured immortalized mouse cardiac endothelial cells (MCEC) to primary cardiac endothelial cells (pEC). Whole transcriptome comparison of MCEC and pEC showed a correlation of 0.75-0.77. Interestingly, correlation of gene expression declined in endothelial cell-typical genes. In MCEC, we found a broad downregulation of genes that are highly expressed in pEC, including well-described markers of endothelial cell differentiation. Accordingly, systematic analysis revealed a downregulation of genes associated with typical endothelial cell functions in MCEC, while genes related to mitotic cell cycle were upregulated when compared to pEC. In conclusion, the findings from this study suggest that primary cardiac endothelial cells should preferably be used for genome-wide transcriptome or epigenome studies. The suitability of in vitro cell lines for experiments investigating single genes or signaling pathways should be carefully validated before use.

5.
Heart ; 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32071092

RESUMO

OBJECTIVE: Transcatheter aortic valve implantation (TAVI) is the most common aortic valve replacement in Germany. Since 2015, to ensure high-quality procedures, hospitals in Germany and other countries that meet the minimum requirement of 50 interventions per centre are being certified to perform TAVI. This study analyses the impact of these requirements on case number and in-hospital outcomes. METHODS: All isolated TAVI procedures and in-hospital outcomes between 2008 and 2016 were identified by International Classification of Diseases (ICD) and the German Operation and Procedure Classification codes. RESULTS: 73 467 isolated transfemoral and transapical TAVI procedures were performed in Germany between 2008 and 2016. During this period, the number of TAVI procedures per year rose steeply, whereas the overall rates of hospital mortality and complications declined. In 2008, the majority of procedures were performed in hospitals with fewer than 50 cases per year (54.63%). Until 2014, the share of patients treated in low-volume centres constantly decreased to 5.35%. After the revision of recommendations, it further declined to 1.99%. In the 2 years after the introduction of the minimum requirements on case numbers, patients were at decreased risk for in-hospital mortality when treated in a high-volume centre (risk-adjusted OR 0.62, p=0.012). The risk for other in-hospital outcomes (stroke, permanent pacemaker implantation and bleeding events) did not differ after risk adjustment (p=0.346, p=0.142 and p=0.633). CONCLUSION: A minimum volume of 50 procedures per centre and year appears suitable to allow for sufficient routine and thus better in-hospital outcomes, while ensuring nationwide coverage of TAVI procedures.

7.
Clin Res Cardiol ; 109(3): 315-323, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31325043

RESUMO

BACKGROUND: Inflammation drives atherosclerosis and its complications. Anti-inflammatory therapy with interleukin 1 beta (IL-1ß) antibody reduces cardiovascular events in patients with elevated high-sensitive C-reactive protein (hsCRP). This study aims to identify the share of patients with coronary heart disease (CHD) and residual inflammation who may benefit from anti-inflammatory therapy. METHODS: hsCRP and low-density lipoprotein (LDL) levels were determined in 2741 all-comers admitted to the cardiological ward of our tertiary referral hospital between June 2016 and June 2018. Patients without CHD, with acute coronary syndrome, chronic or recurrent systemic infection, use of immunosuppressant or anti-inflammatory agents, chronic inflammatory diseases, chemotherapy, terminal organ failure, traumatic injury and pregnancy were excluded. RESULTS: 856 patients with stable CHD were included. 42.7% of those had elevated hsCRP ≥ 2 mg/l. Within the group of patients with LDL-cholesterol < 70 mg/dl, 30.9% shared increased hsCRP indicating residual inflammation. After multivariate adjusted backward selection elevated Lipoprotein (a) (OR 1.61, p = 0.048), elevated proBNP (OR 2.57, p < 0.0001), smoking (OR 1.70, p = 0.022), and obesity (OR 2.28, p = 0.007) were associated with elevated hsCRP. In contrast, the use of ezetimibe was associated with normal hsCRP (OR 0.51, p = 0.014). In the subgroup of patients with on-target LDL-cholesterol < 70 mg/dl, backward selection identified elevated proBNP (OR 3.49, p = 0.007) as independent predictor of elevated hsCRP in patients with LDL-cholesterol < 70 mg/dl. CONCLUSION: One-third of all-comers patients with CHD showed increased levels of hsCRP despite a LDL-cholesterol < 70 mg/dl potentially qualifying for an anti-inflammatory therapy. Elevated proBNP is an independent risk factor for hsCRP elevation.

8.
Clin Res Cardiol ; 109(3): 385-392, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31300835

RESUMO

AIM: Cardiac arrest is the most serious complication in acute coronary syndromes. Glycoprotein IIb/IIIa inhibitors (GPI) are used in selected acute coronary syndrome patients. If the use of GPI leads to an increase in bleeding events and influences survival in patients after cardiac arrest is unknown. METHODS: We report retrospective data of a single center registry of patients after successful intra- and out-of-hospital cardiac arrest between 2002 and 2013. Inclusion criteria were survival for at least 6 h and successful percutaneous coronary intervention (PCI) within the first 24 h. Patients treated with other fibrinolytic agents or being supported by an extracorporeal life support system were excluded from the analysis. RESULTS: 310 patients were included in our study. 204 received GPI (GPI+), 106 did not (GPI-). Patients in the GPI+ group were significantly younger (62.8 vs. 68.0 years, p < 0.001) and had larger myocardial infarction sizes (maximum creatine kinase 3407 vs. 1450 U/l, p < 0.001). CPR duration, SOFA score and first lactate did not differ between the groups. Any bleeding occurred significantly more often in the GPI+ group (83.3% vs. 67.0%, p = 0.001). Decline of hemoglobin within the first 24 h was higher in the GPI+ group (-1.59 ± 1.71 mg/dl vs. -0.88 ± 1.95 mg/dl, p = 0.004), number of transfused packed red blood cells in the first 4 days, however, were similar (1.18 ± 0.40 vs. 0.90 ± 0.41 packs, p = 0.378). Survival at ICU discharge was significantly higher in the GPI+ group (77.5% vs. 63.2%, p = 0.008). The use of GPI was an independent predictor of hospital survival (OR 3.07, CI 1.31-7.20, p = 0.010). The positive effect for GPI persisted after nearest neighbor propensity score matching including 144 patients (OR 3.27, 95% CI 1.48-7.21, p = 0.003). CONCLUSION: After cardiac arrest, bleeding incidence was significantly higher in patients treated with GPI. Incidence of bleedings requiring transfusion, however, was similar. In this retrospective analysis, the use of GPI was an independent predictor of hospital survival. We suggest that GPI may not be withheld from cardiac arrest survivors due to potential risk of bleeding.

9.
Resuscitation ; 146: 149-154, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31811881

RESUMO

INTRODUCTION: Initiation of venoarterial extracorporeal membrane oxygenation (ECMO) under ongoing cardiopulmonary resuscitation (eCPR) in patients with refractory cardiac arrest may improve otherwise deleterious outcome. In general, the duration of mechanical resuscitation from collapse to ECMO ranges from 40 to 70 min. CPR-related injuries are reported frequently in non-eCPR patients. We wanted to quantify CPR-related injuries in eCPR patients. METHODS: All eCPR patients cannulated at a tertiary referral medical center between October 2010 and October 2017 were included in a retrospective registry study. A full-body CT scan was performed within the first 24 h after eCPR. RESULTS: A total of 103 patients (mean age 58.8 ±â€¯16.7 years, CPR duration 61.7 ±â€¯31.9 min, and hospital survival 13.6 %) underwent eCPR and immediate full-body computed tomography (CT). Full-body CT detected the cause for collapse in 16.5% of patients. Average number of pathologies detected per CT scan was 6.5 ±â€¯3.3 findings per patient, of which 2.6 ±â€¯1.5 findings were retrospectively considered of clinical relevance for subsequent treatment. Most frequent findings were multiple rib or sternal fractures (65.5%), pneumo- or hemothorax (32.3%) and pulmonary infiltrates (91.3%). Intracranial bleedings and cerebral edema were frequent (10.7% and 26.2%). A total of 20 patients (19.4%) had findings in whole-body CT that were considered to be so severe that further treatment was considered futile and therapy was subsequently discontinued. Most findings were associated with poor outcome with the exception of rib fractures, bleedings and abdominal trauma, which might have been caused by vigorous resuscitation efforts and were associated with favorable outcome. CONCLUSION: A full-body CT scan performed after eCPR revealed substantial clinically significant findings. Therefore, it might be reasonable to routinely perform a full-body CT in all eCPR patients.

10.
J Card Fail ; 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31790816

RESUMO

BACKGROUND: In patients with chronic heart failure (CHF), volume overload is usually described as an expansion of plasma volume. Additional red cell volume (RCV) expansion is less commonly recognized. So far, little is known about quantitative differences in blood volume status and its different components in patients with stable CHF compared to healthy controls. METHODS: This study aimed to quantify blood volume and its constituents, RCV and plasma volume, by using an abbreviated carbon monoxide rebreathing method with particular focus on its primary measure total hemoglobin mass in 47 patients (10 women) with systolic CHF and a left ventricular ejection fraction of 29.0 ± 9.4%. These were compared to an age-matched control group of 84 healthy subjects (44 women) using the same method. RESULTS: In both absolute and body-surface-area-corrected analysis, hemoglobin mass (446 ± 81 vs 353 ± 64 g/m2) as well as RCV (1293 ± 231 vs 1033 ± 176 mL/m2) were significantly increased in CHF. In addition, significant plasma volume expansion was observed in CHF (2069 ± 400 vs 1750 ± 231 mL/m2) and, in conjunction with RCV, constituted a significantly increased blood volume (3361 ± 574 vs 2783 ± 369 mL/m2). In 66% of patients with compensated CHF, RCV was excessive compared to 14% in the control group. CONCLUSIONS: An increased RCV is a relevant contributing factor to hypervolemia in stable CHF. This is associated with an increased oxygen-carrying capacity, so it may be regarded as a possible compensatory mechanism for a reduced ejection fraction.

12.
Sci Rep ; 9(1): 17937, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31784656

RESUMO

Diabetes worsens atherosclerosis progression and leads to a defect in repair of arteries after cholesterol reduction, a process termed regression. Empagliflozin reduces blood glucose levels via inhibition of the sodium glucose cotransporter 2 (SGLT-2) in the kidney and has been shown to lead to a marked reduction in cardiovascular events in humans. To determine whether glucose lowering by empagliflozin accelerates atherosclerosis regression in a mouse model, male C57BL/6J mice were treated intraperitoneally with LDLR- and SRB1- antisense oligonucleotides and fed a high cholesterol diet for 16 weeks to induce severe hypercholesterolemia and atherosclerosis progression. At week 14 all mice were rendered diabetic by streptozotocin (STZ) injections. At week 16 a baseline group was sacrificed and displayed substantial atherosclerosis of the aortic root. In the remaining mice, plasma cholesterol was lowered by switching to chow diet and treatment with LDLR sense oligonucleotides to induce atherosclerosis regression. These mice then received either empagliflozin or vehicle for three weeks. Atherosclerotic plaques in the empagliflozin treated mice were significantly smaller, showed decreased lipid and CD68+ macrophage content, as well as greater collagen content. Proliferation of plaque resident macrophages and leukocyte adhesion to the vascular wall were significantly decreased in empagliflozin-treated mice. In summary, plasma glucose lowering by empagliflozin improves plaque regression in diabetic mice.

13.
Cochrane Database Syst Rev ; 12: CD013252, 2019 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-31858590

RESUMO

BACKGROUND: Clinicians must balance the risks of bleeding and thrombosis after percutaneous coronary intervention (PCI) in people with an indication for anticoagulation. The potential of non-vitamin K antagonists (NOACs) to prevent bleeding complications is promising, but evidence remains limited. OBJECTIVES: To review the evidence from randomised controlled trials assessing the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) compared to vitamin K antagonists post-percutaneous coronary intervention (PCI) in people with an indication for anticoagulation. SEARCH METHODS: We identified studies by searching CENTRAL, MEDLINE, Embase, the Conference Proceedings Citation Index - Science and two clinical trials registers in February 2019. We checked bibliographies of identified studies and applied no language restrictions. SELECTION CRITERIA: We searched for randomised controlled trials (RCT) that compared NOACs and vitamin K antagonists for people with an indication for anticoagulation who underwent PCI. DATA COLLECTION AND ANALYSIS: Two review authors independently checked the results of searches to identify relevant studies, assessed each included study, and extracted study data. We conducted random-effects, pairwise analyses using Review Manager 5 and network meta-analyses (NMA) using the R package 'netmeta'. We ranked competing treatments by P scores, which are derived from the P values of all pairwise comparisons, and allow ranking of treatments on a continuous 0 to 1 scale. MAIN RESULTS: We identified nine RCTs that met the inclusion criteria, but four were ongoing trials, and were not included in this analysis. We included five RCTs, with 8373 participants, in the NMA (two RCTs compared apixaban to a vitamin K antagonist, two RCTs compared rivaroxaban to a vitamin K antagonist, and one RCT compared dabigatran to a vitamin K antagonist). Very low- to moderate-certainty evidence suggests little or no difference between NOACs and vitamin K antagonists in death from cardiovascular causes (not reported in the dabigatran trial), myocardial infarction, stroke, death from any cause, and stent thrombosis. Apixaban (RR 0.85, 95% CI 0.77 to 0.95), high dose rivaroxaban (RR 0.86, 95% CI 0.74 to 1.00), and low dose rivaroxaban (RR 0.80, 95% CI 0.68 to 0.92) probably reduce the risk of recurrent hospitalisation compared with vitamin K antagonists. No studies looked at health-related quality of life. Very low- to moderate-certainty evidence suggests that NOACs may be safer than vitamin K antagonists in terms of bleeding. Both high dose dabigatran (RR 0.53, 95% CI 0.29 to 0.97), and low dose dabigatran (RR 0.38, 95% CI 0.21 to 0.70) may reduce major bleeding more than vitamin K antagonists. High dose dabigatran (RR 0.83, 95% CI 0.72 to 0.96), low dose dabigatran (RR 0.66, 95% CI 0.58 to 0.75), apixaban (RR 0,67 , 95% Cl 0.51 to 0.88), high dose rivaroxaban (RR 0.66, 95% CI 0.52 to 0.83), and low dose rivaroxaban (RR 0.71, 95% CI 0.57 to 0.88) probably reduce non-major bleeding more than vitamin K antagonists. The results from the NMA were inconclusive between the different NOACs for all primary and secondary outcomes. AUTHORS' CONCLUSIONS: Very low- to moderate-certainty evidence suggests no meaningful difference in efficacy outcomes between non-vitamin K antagonist oral anticoagulants (NOAC) and vitamin K antagonists following percutaneous coronary interventions (PCI) in people with non-valvular atrial fibrillation. NOACs probably reduce the risk of recurrent hospitalisation for adverse events compared with vitamin K antagonists. Low- to moderate-certainty evidence suggests that dabigatran may reduce the rates of major and non-major bleeding, and apixaban and rivaroxaban probably reduce the rates of non-major bleeding compared with vitamin K antagonists. Our network meta-analysis did not show superiority of one NOAC over another for any of the outcomes. Head to head trials, directly comparing NOACs against each other, are required to provide more certain evidence.

14.
Int J Mol Sci ; 20(21)2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31683713

RESUMO

The serine protease high-temperature-required protein A2 (HtrA2) has been identified as a key intracellular molecule promoting apoptosis in cells during ischemia reperfusion (IR) injury. IR injury in ST-segment elevation myocardial infarction (STEMI) contributes to overall myocardial damage. HtrA2 has further been shown to be significantly increased in the serum of patients with STEMI. In the present pilot study, we use human umbilical vein endothelial cells (HUVECs) to investigate whether extracellular HtrA2 induces apoptosis using Annexin V staining. Furthermore, we examine whether HtrA2 is released extracellularly after staurosporine-induced apoptosis using ELISA. We find that HtrA2 is released upon induction of apoptosis by staurosporine into the cell culture medium. Furthermore, treatment of HUVECs with extracellular HtrA2-induces apoptosis, while the addition of anti-HtrA2 antibodies reduces both HtrA2- and staurosporine-induced endothelial cell apoptosis. In conclusion, we show here that extracellular HtrA2 induces apoptosis in human endothelial cells, although the exact molecular mechanisms have to be investigated in future.

15.
Circ Cardiovasc Interv ; 12(11): e008160, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31707805

RESUMO

BACKGROUND: Among stented patients with atrial fibrillation, double therapy with a novel oral anticoagulant plus single antiplatelet therapy (SAPT) reduces bleeding or cardiovascular rehospitalizations compared with a vitamin K antagonist (VKA) based triple therapy regimen. A recent study demonstrated that apixaban based double therapy reduced bleeding compared with VKA based double therapy. However, it remains unknown whether rivaroxaban based double therapy is superior to a VKA based double therapy. METHODS: Patient with stented atrial fibrillation (n=2124) were randomized to 3 groups: rivaroxaban 15 mg od plus a P2Y12 inhibitor (Group 1, n=709); rivaroxaban 2.5 mg bid plus dual antiplatelet therapy (DAPT; Group 2, n=709); and warfarin plus DAPT (Group 3, n=706). Before randomization, subjects were stratified according to a prespecified duration of DAPT (1, 6, or 12 months). After the prespecified DAPT duration, subjects in Group 2 were switched to rivaroxaban 15 mg plus low dose aspirin, and those in Group 3 were switched to VKA plus low dose aspirin. The Wei, Lin, and Weissfeld time to multiple events method was used to compare the occurrence of all bleeding and cardiovascular rehospitalizations among subjects on a novel oral anticoagulant versus VKA based double therapy. RESULTS: A total of 906 subjects were prespecified to a 1 or 6 months DAPT duration and received at least one dose of study drug. Twenty subjects (3.3%) assigned to novel oral anticoagulant+SAPT, and 15 (5.1%) subjects assigned to VKA+SAPT experienced multiple rehospitalizations. In total, 124 (20.3%) events occurred among subjects on novel oral anticoagulant+SAPT compared with 87 (29.6%) among subjects on VKA+SAPT (hazard ratio=0.65 [95% CI, 0.45-0.93], P=0.008). CONCLUSIONS: Among stented patients with atrial fibrillation, rivaroxaban plus SAPT was superior to warfarin plus SAPT in lowering total bleeding and cardiovascular rehospitalization. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01830543.

16.
Am Heart J ; 218: 100-109, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31715433

RESUMO

For 4 decades, antithrombotic therapy with aspirin has been a cornerstone of secondary prevention for patients with chronic atherosclerotic cardiovascular disease (ASCVD). Unfortunately, despite the use of evidence-based therapies, patients with ASCVD continue to have recurrent major adverse cardiovascular events including death, myocardial infarction, and stroke-at a rate of approximately 2%-4% per year. To combat this continuing risk, several recent trials have evaluated the efficacy and safety of more intensive antithrombotic strategies through prolonged dual antiplatelet therapy (DAPT), combining a P2Y12 receptor antagonists and low-dose aspirin, or alternatively applying a dual pathway inhibition approach, combining low-dose non-vitamin K antagonist anticoagulant and low-dose aspirin. Both combination strategies have been shown to reduce recurrent ischemic events but at the cost of increased bleeding events. The clinical application of these antithrombotic strategies requires clinicians to assess and balance the risk of recurrent ischemic and bleeding events in an individual patient. Furthermore, clinicians may also need to adapt their antithrombotic strategies to achieve best patient outcomes, as ASCVD is a progressive disease and the risks of cardiovascular ischemic and bleeding events may shift over time. This state-of-the-art article reviews evidence from the trials and provides a practical approach to the application of DAPT and dual pathway antithrombotic therapy in the long-term management of patients with chronic ASCVD.

18.
PLoS One ; 14(10): e0224181, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31644579

RESUMO

BACKGROUND: Platelets are key components in atherogenesis and determine the course of its clinical sequelae acute coronary syndrome (ACS). Components of the innate immune system-the superfamily of TLR receptors-are present in platelets and represent a link between atherothrombosis and inflammation. We hypothesize that alteration in platelet TLR mRNA expression is a result of inflammation driving coronary atherosclerosis and may represent an alternative platelet activation pathway in ACS. TLR2-, TLR4- and TLR9- mRNA-expression was determined in ACS patients and compared to patients with invasive exclusion of atherosclerotic lesions of coronary arteries. METHODS: A total of fifty-four patients were enrolled in this clinical retrospective cohort single centre study. Total RNA from sepharose-filtered highly purified platelets was isolated using acid guanidinium thiocyanate-phenol-chloroform extraction and transcribed to cDNA using a first strand cDNA synthesis kit. To determine absolute copy numbers of TLR2, TLR4 and TLR9 we used plasmid based quantitative PCR with normalisation to an internal control. RESULTS: We found that mRNA expression levels of TLR2 but not TLR 4 and 9 are up-regulated in platelets of patients with ACS when compared to patients without coronary atherosclerosis. CONCLUSION: Our results suggest elevated TLR2 mRNA expression in platelets as a biomarker reflecting the underlying inflammation in ACS and possibly severity of coronary atherosclerosis. Platelet TLR2 may represent a link between inflammation and atherothrombosis in ACS.

19.
Artigo em Inglês | MEDLINE | ID: mdl-31620937

RESUMO

In the context of interventional cardiology, platelet function testing may identify patients treated with P2Y12-inhibitors at an increased risk of mortality, thrombosis and bleeding. Several whole blood point-of-care platelet function analyzers are available; however, inter-device differences have not been examined systematically. To compare three platelet function tests under standardized in vitro conditions. Healthy volunteer (n = 10) blood samples were spiked with increasing concentrations of ticagrelor (0-7500 ng/mL) and/or ASA (0-3280 ng/mL), measured on three platelet function analyzers (TEG®6s, Multiplate®, and VerifyNow®) and respective Effective Concentration (EC) levels EC10, EC50 and EC90 were calculated. Repeatability was assessed in a separate group of pooled blood samples (n = 10) spiked with ticagrelor at EC10, EC50 and EC90. ASA had no impact on ADP-activated channels for all three devices. TEG®6s was able to distinguish (p ≤ 0.05) between all ticagrelor EC zones; VerifyNow® and Multiplate® were able to distinguish between three and two zones, respectively. Multiplate® showed the largest window between EC10 and EC90 (19-9153 ng/mL), followed by TEG®6s (144-2589 ng/mL), and VerifyNow® (191-1100 ng/mL). Drug effect models distribution of disagreements were identified for TEG®6s (5.0%), VerifyNow® (8.3%), and Multiplate® (13.3%). TEG®6s showed the smallest average coefficient of variation between EC conditions (5.1%), followed by Multiplate® (14.1%), and VerifyNow® (17.7%). Linear models could be generated between TEG®6s and Multiplate®, but not VerifyNow®. Significant differences were found between whole blood point-of-care platelet function analyzers and the clinical impact of these differences needs to be further investigated.

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