Circulating miRNA Fingerprint and Endothelial Function in Myocardial Infarction : Comparison at Acute Event and One-Year Follow-Up

MicroRNAs (miRNA) are major regulators of intercellular communication and key players in the pathophysiology of cardiovascular disease. This study aimed to determine the miRNA fingerprint in a cohort of 53 patients with acute myocardial infarction (AMI) with non-ST-segment elevation (NSTEMI) relative to miRNA expression in healthy controls (n = 51). miRNA expression was initially profiled by miRNA array in the serum of patients undergoing cardiac catheterization during NSTEMI (n = 8) and 1 year past the event (follow-up, n = 8) and validated in the entire cohort. In total, 58 miRNAs were differentially expressed during AMI (p < 0.05), while 36 were modified at follow-up (Fisher's exact test: p = 0.0138). Enrichment analyses revealed differential regulation of biological processes by miRNA at each specific time point (AMI vs. follow-up). During AMI, the miRNA profile was associated mainly with processes involved in vascular development. However, 1 year after AMI, changes in miRNA expression were partially related to the regulation of cardiac tissue morphogenesis. Linear correlation analysis of miRNA with serum levels of cytokines and chemokines revealed that let-7g-5p, let-7e-5p, and miR-26a-5p expression was inversely associated with serum levels of pro-inflammatory cytokines TNF- , and the chemokines MCP-3 and MDC. Transient transfection of human endothelial cells (HUVEC) with let-7e-5p inhibitor or mimic demonstrated a key role for this miRNA in endothelial function regulation in terms of cell adhesion and angiogenesis capacity. HUVEC transfected with let-7e-5p mimic showed a 20% increase in adhesion capacity, whereas transfection with let-7e-5p inhibitor increased the number of tube-like structures. This study pinpoints circulating miRNA expression fingerprint in NSTEMI patients, specific to the acute event and changes at 1-year follow-up. Additionally, given its involvement in modulating endothelial cell function and vascularization, altered let-7e-5p expression may constitute a therapeutic biomarker and target for ischemic heart disease

Disparate miRNA expression in serum and plasma of patients with acute myocardial infarction: a systematic and paired comparative analysis

Despite the promising value of miRNAs in the diagnostic and prognostic of cardiovascular disease (CVD), recent meta-analyses did not support their potential. Methodological variances in studies may interfere with miRNA profle and afect their results. This study determines if the blood starting material is a source of variance in miRNA profle by performing a paired comparison in plasma and serum of the expression of primary miRNAs associated with CVD. Circulating miRNA yield was similar in both plasma and serum, although a signifcant increase was observed in patients with Non-ST-elevation myocardial infarction (NSTEMI) compared to control volunteers. When normalized by the expression of miR-484, diferent patterns of miRNA expression between serum and plasma. Although NSTEMI modifed the expression of miR-1 and miR-208 in both serum and plasma, plasma displayed a higher variance than serum (Levene's test p<0.01). For miR-133a and miR-26a, diferences were only detected in serum (p=0.0240), and conversely, miR-499a showed diferences only in plasma of NSTEMI (p=0.001). Interestingly, miR-21 showed an opposite pattern of expression, being increased in serum (2−ΔΔCt:5.7, p=0.0221) and decreased in plasma (2−ΔΔCt: 0.5, p=0.0107). Plasma and serum exhibit diferent patterns of circulating miRNA expression in NSTEMI and suggest that results from studies with diferent starting material could not be comparable

Frequency and predictors of thrombus inside the guiding catheter during interventional procedures: an optical coherence tomography study

Optical coherence tomography (OCT) is able to identify thrombus. We detect the frequency of thrombus inside the guiding catheter by OCT and its relationship with clinical and procedural factors. We screened 77 patients who underwent OCT pullbacks. Only patients with visible guiding catheter were finally included (35) and divided into thrombus (21) or no-thrombus group (14). Patients within thrombus group were mostly males (100 vs. 71 %, p = 0.05), with acute coronary syndrome (76 vs. 36 %, p = 0.02) and received more frequently percutaneous coronary intervention (86 vs. 43 %, p = 0.01) as compared to other group. A second dose of heparin was more frequently administered in thrombus than in other group (86 vs. 50 %, p = 0.01). Time between first heparin administration and OCT pullback (41[28–57] vs. 20 min [10–32], p = 0.001), time elapsed from second heparin administration and OCT pullback (29 [19–48] vs. 16 min [12–22], p = 0.002) and total procedural time (47 [36–69] vs. 31 min [26–39], p = 0.005) were longer in thrombus compared to other group. At multivariate analysis, total procedural time and time between first heparin administration and OCT pullback were only predictors of intra-catheter thrombus (HR 0.6 [0.3–0.9], p = 0.03 and HR 1.9 [1.1–3.2], p = 0.02, respectively). Thrombus inside guiding catheter may be a frequent finding in long interventional procedure. Future studies are warranted to determine its clinical impact

Effects of cobalt-chromium everolimus eluting stents or bare metal stent on fatal and non-fatal cardiovascular events: Patient level meta-analysis

Objectives: To examine the safety and effectiveness of cobalt-chromium everolimus eluting stents compared with bare metal stents.Design: Individual patient data meta-analysis of randomised controlled trials. Cox proportional regression models stratified by trial, containing random effects, were used to assess the impact of stent type on outcomes. Hazard ratios with 95% confidence interval for outcomes were reported.Data sources and study selection: Medline, Embase, the Cochrane Central Register of Controlled Trials. Randomised controlled trials that compared cobalt-chromium everolimus eluting stents with bare metal stents were selected. The principal investigators whose trials met the inclusion criteria provided data for individual patients.Primary outcomes: The primary outcome was cardiac mortality. Secondary endpoints were myocardial infarction, definite stent thrombosis, definite or probable stent thrombosis, target vessel revascularisation, and all cause death.Results: The search yielded five randomised controlled trials, comprising 4896 participants. Compared with patients receiving bare metal stents, participants receiving cobalt-chromium everolimus eluting stents had a significant reduction of cardiac mortality (hazard ratio 0.67, 95% confidence interval 0.49 to 0.91; P=0.01), myocardial infarction (0.71, 0.55 to 0.92; P=0.01), definite stent thrombosis (0.41, 0.22 to 0.76; P=0.005), definite or probable stent thrombosis (0.48, 0.31 to 0.73; P<0.001), and target vessel revascularisation (0.29, 0.20 to 0.41; P<0.001) at a median follow-up of 720 days. There was no significant difference in all cause death between groups (0.83, 0.65 to 1.06; P=0.14). Findings remained unchanged at multivariable regression after adjustment for the acuity of clinical syndrome (for instance, acute coronary syndrome v stable coro

Reproducibility of qualitative assessment of stent struts coverage by optical coherence tomography

Assessment of stent strut coverage by optical coherence tomography (OCT) is not standardized. The methodology most commonly used is based on a visual binary qualitative assessment (strut covered or not). However, the influence of magnification (zoom setting) to the inter- and intra-observer agreements has not yet been evaluated. Aim of our study was therefore to evaluate the agreements of this approach, taking into account various zoom settings. 126 struts from 10 selec

Cost-effectiveness of percutaneous coronary intervention with cobalt-chromium everolimus eluting stents versus bare metal stents: Results from a patient level meta-analysis of randomized trials

Background: Second-generation drug eluting stents (DES) may reduce costs and improve clinical outcomes compared to first-generation DES with improved cost-effectiveness when compared to bare metal stents (BMS). We aimed to conduct an economic evaluation of a cobalt-chromium everolimus eluting stent (Co-Cr EES) compared with BMS in percutaneous coronary intervention (PCI). Objective: To conduct a cost-effectiveness analysis (CEA) of a cobalt-chromium everolimus eluting stent (Co-Cr EES) versus BMS in PCI. Methods: A Markov state transition model with a 2-year time horizon was applied from a US Medicare setting with patients undergoing PCI with Co-Cr EES or BMS. Baseline characteristics, treatment effects, and safety measures were taken from a patient level meta-analysis of 5 RCTs (n=4,896). The base-case analysis evaluated stent-related outcomes; a secondary analysis considered the broader set of outcomes reported in the meta-analysis. Results: The base-case and secondary analyses reported an additional 0.018 and 0.013 quality-adjusted life years (QALYs) and cost savings of $236 and$288, respectively with Co-Cr EES versus BMS. Results were robust to sensitivity analyses and were most sensitive to the price of clopidogrel. In the probabilistic sensitivity analysis, Co-Cr EES was associated with a greater than 99% chance of being cost savin

Data standards for transcatheter aortic valve implantation: the European Unified Registries for Heart Care Evaluation and Randomised Trials (EuroHeart)

Funding: European Society of Cardiology.publishersversionepub_ahead_of_prin

Amphilimus- vs. zotarolimus-eluting stents in patients with diabetes mellitus and coronary artery disease: the SUGAR trial

Aim: Patients with diabetes mellitus are at high risk of adverse events after percutaneous revascularization, with no differences in outcomes between most contemporary drug-eluting stents. The Cre8 EVO stent releases a formulation of sirolimus with an amphiphilic carrier from laser-dug wells, and has shown clinical benefits in diabetes. We aimed to compare Cre8 EVO stents to Resolute Onyx stents (a contemporary polymer-based zotarolimus-eluting stent) in patients with diabetes. Methods and results: We did an investigator-initiated, randomized, controlled, assessor-blinded trial at 23 sites in Spain. Eligible patients had diabetes and required percutaneous coronary intervention. A total of 1175 patients were randomly assigned (1:1) to receive Cre8 EVO or Resolute Onyx stents. The primary endpoint was target-lesion failure, defined as a composite of cardiac death, target-vessel myocardial infarction, and clinically indicated target-lesion revascularization at 1-year follow-up. The trial had a non-inferiority design with a 4% margin for the primary endpoint. A superiority analysis was planned if non-inferiority was confirmed. There were 106 primary events, 42 (7.2%) in the Cre8 EVO group and 64 (10.9%) in the Resolute Onyx group [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.44 to 0.96; pnon-inferiority <0.001; psuperiority = 0.030]. Among the secondary endpoints, Cre8 EVO stents had significantly lower rate than Resolute Onyx stents of target-vessel failure (7.5% vs 11.1%, HR 0.67, 95% CI 0.46 to 0.99; p = 0.042). Probable or definite stent thrombosis and all-cause death were not significantly different between groups. Conclusions: In patients with diabetes, Cre8 EVO stents were non-inferior to Resolute Onyx stents with regard to target-lesion failure composite outcome. An exploratory analysis for superiority at 1 year suggests that the Cre8 EVO stents might be superior to Resolute Onyx stents with regard to the same outcome