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BackgroundDespite the use of high-sensitive cardiac troponin there remains a group of high-sensitive cardiac troponin negative patients with unstable angina with a non-neglectable risk for future adverse cardiovascular events, emphasising the need for additional risk stratification. Plasma extracellular vesicles are small bilayer membrane vesicles known for their potential role as biomarker source. Their role in unstable angina remains unexplored. We investigate if extracellular vesicle proteins are associated with unstable angina in patients with chest pain and low high-sensitive cardiac troponin.MethodsThe MINERVA study included patients presenting with acute chest pain but no acute coronary syndrome. We performed an exploratory retrospective case-control analysis among 269 patients. Cases were defined as patients with low high-sensitive cardiac troponin and proven ischemia. Patients without ischemia were selected as controls. Blood samples were fractionated to analyse the EV proteins in three plasma-subfractions: TEX, HDL and LDL. Protein levels were quantified using electrochemiluminescence immunoassay.ResultsLower levels of (adjusted) EV cystatin c in the TEX subfraction were associated with having unstable angina (OR 0.93 95% CI 0.88-0.99).ConclusionIn patients with acute chest pain but low high-sensitive cardiac troponin, lower levels of plasma extracellular vesicle cystatin c are associated with having unstable angina. This finding is hypothesis generating only considering the small sample size and needs to be confirmed in larger cohort studies, but still identifies extracellular vesicle proteins as source for additional risk stratification.

BackgroundIn selected patients with an acute myocardial infarction (AMI) complicated by Cardiogenic shock (CS), mechanical circulatory support with Impella may be beneficial, although conclusive evidence is still lacking. Nevertheless, it has been suggested that Impella initiation prior to primary PCI might improve survival.ObjectiveTo investigate the effect pre-PCI versus immediate post-PCI Impella initiation on short term mortality.MethodsA prospective, single center, observational study, was performed including all patients with STEMI complicated by CS, treated with primary PCI and Impella. Thirty day mortality was compared between patients with Impella initiation pre-PCI and immediately post-PCI.ResultsA total of 88 patients were included. In the pre-PCI group (n = 21), admission heart rate was lower (84 versus 94 bpm, p = 0.04) and no IABP was implanted before Impella initiation, versus 17.9% in post-PCI group (n = 67), p = 0.04. Total 30-day all-cause mortality was 58%, and was lower in pre-PCI group, 47.6% versus 61.2% in the post-PCI group, however not statistically significant (HR 0.7, 95% CI 0.3-1.3, p = 0.21). Thirty-day cardiac mortality was significantly lower in the pre-PCI group, 19% versus 44.7% in the post-PCI group (HR 0.3, 95% CI 0.09-0.96, p = 0.042).ConclusionPre-PCI Impella initiation in AMICS patients was not associated with a statistically significant difference in 30-day all-cause mortality, compared to post-PCI Impella initiation.

Since high-density lipoprotein (HDL) has pro-endothelial and anti-thrombotic effects, a HDL recruiting stent may prevent restenosis. In the present study we address the functional characteristics of an apolipoprotein A-I (ApoA-I) antibody coating in vitro. Subsequently, we tested its biological performance applied on stents in vivo in rabbits.The impact of anti ApoA-I- versus apoB-antibody coated stainless steel discs were evaluated in vitro for endothelial cell adhesion, thrombin generation and platelet adhesion. In vivo, response to injury in the iliac artery of New Zealand white rabbits was used as read out comparing apoA-I-coated versus bare metal stents.ApoA-I antibody coated metal discs showed increased endothelial cell adhesion and proliferation and decreased thrombin generation and platelet adhesion, compared to control discs. In vivo, no difference was observed between ApoA-I and BMS stents in lumen stenosis (23.3±13.8% versus 23.3±11.3%, p=0.77) or intima surface area (0.81±0.62 mm2 vs 0.84±0.55 mm2, p=0.85). Immunohistochemistry also revealed no differences in cell proliferation, fibrin deposition, inflammation and endothelialization.ApoA-I antibody coating has potent pro-endothelial and anti-thrombotic effects in vitro, but failed to enhance stent performance in a balloon injury rabbit model in vivo.

The introduction of drug-eluting stents (DES) has dramatically reduced restenosis rates compared with bare metal stents, but in-stent thrombosis remains a safety concern, necessitating prolonged dual anti-platelet therapy. The drug 6-Mercaptopurine (6-MP) has been shown to have beneficial effects in a cell-specific fashion on smooth muscle cells (SMC), endothelial cells and macrophages. We generated and analyzed a novel bioresorbable polymer coated DES, releasing 6-MP into the vessel wall, to reduce restenosis by inhibiting SMC proliferation and decreasing inflammation, without negatively affecting endothelialization of the stent surface.Stents spray-coated with a bioresorbable polymer containing 0, 30 or 300 μg 6-MP were implanted in the iliac arteries of 17 male New Zealand White rabbits. Animals were euthanized for stent harvest 1 week after implantation for evaluation of cellular stent coverage and after 4 weeks for morphometric analyses of the lesions.Four weeks after implantation, the high dose of 6-MP attenuated restenosis with 16% compared to controls. Reduced neointima formation could at least partly be explained by an almost 2-fold induction of the cell cycle inhibiting kinase p27Kip1. Additionally, inflammation score, the quantification of RAM11-positive cells in the vessel wall, was significantly reduced in the high dose group with 23% compared to the control group. Evaluation with scanning electron microscopy showed 6-MP did not inhibit strut coverage 1 week after implantation.We demonstrate that novel stents coated with a bioresorbable polymer coating eluting 6-MP inhibit restenosis and attenuate inflammation, while stimulating endothelial coverage. The 6-MP-eluting stents demonstrate that inhibition of restenosis without leaving uncovered metal is feasible, bringing stents without risk of late thrombosis one step closer to the patient.

BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) activity is a biomarker predicting cardiovascular diseases in a real-world. However, the prognostic value in patients undergoing primary percutaneous coronary intervention (pPCI) for ST-segment elevation myocardial infarction (STEMI) on long-term clinical outcomes is unknown. METHODS: Lp-PLA2 activity was measured in samples obtained prior to pPCI from consecutive STEMI patients in a high-volume intervention center from 2005 until 2007. Five years all-cause mortality was estimated with the Kaplan-Meier method and compared among tertiles of Lp-PLA2 activity during complete follow-up and with a landmark at 30 days. In a subpopulation clinical endpoints were assessed at three years. The prognostic value of Lp-PLA2, in addition to the Thrombolysis In Myocardial Infarction or multimarker risk score, was assessed in multivariable Cox regression. RESULTS: The cohort (n = 987) was divided into tertiles (low 179 nmol/min/mL). Among the tertiles differences in baseline characteristics associated with long-term mortality were observed. However, no significant differences in five years mortality in association with Lp-PLA2 activity levels were found; intermediate versus low Lp-PLA2 (HR 0.97; CI 95% 0.68-1.40; p = 0.88) or high versus low Lp-PLA2 (HR 0.75; CI 95% 0.51-1.11; p = 0.15). Both in a landmark analysis and after adjustments for the established risk scores and selection of cases with biomarkers obtained, non-significant differences among the tertiles were observed. In the subpopulation no significant differences in clinical endpoints were observed among the tertiles. CONCLUSION: Lp-PLA2 activity levels at admission prior to pPCI in STEMI patients are not associated with the incidence of short and/or long-term clinical endpoints. Lp-PLA2 as an independent and clinically useful biomarker in the risk stratification of STEMI patients still remains to be proven.

BACKGROUND: Plaque disruption with superimposed thrombus is the predominant mechanism responsible for the onset of acute coronary syndromes. Studies have shown that plaque disruption and thrombotic occlusion are frequently separated in time. We established the histopathological characteristics of material aspirated during primary percutaneous coronary intervention (PCI) in a large consecutive ST-elevation myocardial infarction (STEMI) population. METHODOLOGY/PRINCIPAL FINDINGS: Thrombus aspiration during primary PCI was performed in 1,362 STEMI patients. Thrombus age was classified as fresh (5 day). Further, the presence of plaque was documented. The histopathological findings were related to the clinical, angiographic, and procedural characteristics. Material could be aspirated in 1,009 patients (74%). Components of plaque were found in 395 of these patients (39%). Fresh thrombus was found in 577 of 959 patients (60%) compared to 382 patients (40%) with lytic or organized thrombi. Distal embolization was present in 21% of patients with lytic thrombus compared to 12% and 15% of patients with fresh or organized thrombus. CONCLUSIONS/SIGNIFICANCE: Material could be obtained in 74% of STEMI patients treated with thrombus aspiration during primary PCI. In 40% of patients thrombus age is older than 24 h, indicating that plaque disruption and thrombus formation occur significantly earlier than the onset of symptoms in many patients.