Effect of comedication with proton pump inhibitors (PPIs) on post-interventional residual platelet aggregation in patients undergoing coronary stenting treated by dual antiplatelet therapy

Introduction

Currently, there is an intense debate about whether comedication with proton pump inhibitors (PPIs) weakens the antiplatelet effect of clopidogrel in patients undergoing coronary stent implantation. Competing mechanisms on the hepatic cytochrome 2C19 level are proposed. The aim of this study was to assess the impact of PPI treatment on clopidogrel response by measuring the ex vivo platelet aggregation in patients with coronary intervention.

Methods

1425 consecutive patients with symptomatic coronary artery disease undergoing percutaneous coronary intervention were enrolled in this single centre study. PPI comedication was defined as PPI intake ≥ 1 week prior to a 600 mg clopidogrel loading dose. PPI treatment was based on physician preference. Residual platelet aggregation (RPA) was measured by optical aggregometry. To correct for potential selection bias, propensity score matching was applied.

Results

RPA was significantly higher in PPI-treated patients compared with non-PPI-users (final aggregation 34.0% vs. 29.8%, p < 0.001). Low responder defined as RPA in the upper tertile were more often found in PPI-users. After adjustment for relevant confounders, PPI treatment was independently associated with higher RPA-levels.

Discussion

We demonstrated that peri-procedural co-administration of PPIs significantly decreases the effect of clopidogrel on RPA. To assess if clopidogrel-PPI interaction results in a higher susceptibility for cardiovascular events remains subject to further investigations.     

Platelet-leukocyte interactions in inflammation and atherothrombosis

Inflammatory processes at the vascular wall result in the development of atherosclerosis. Platelet interactions with leukocytes may play a key role in the initiation of inflammation. They trigger autocrine and paracrine activation processes, leading to leukocyte recruitment (in)to the vascular wall. This article highlights the molecular basis and the inflammatory pathways initiated by platelet-leukocyte interactions.     

Inhibition of foam cell formation using a soluble CD68-Fc fusion protein

The appearance of lipid-rich foam cells is a major feature of vulnerable atherosclerotic plaque formation. The transformation of macrophages into foam cells results from excessive uptake of cholesterol-rich particles by scavenger receptors such as CD68. We cloned a CD68-Fc immunoadhesin, a fusion protein consisting of the extracellular domain of the human CD68 and a human Fc domain, and investigated the function in vitro. Specific binding of CD68-Fc to OxLDL with an affinity of 10 nmol/L was determined by surface plasmon resonance and increased binding to lipid-rich human and ApoE^?/? mice plaque tissue. This was confirmed both by immunohistochemical staining of CD68-Fc-treated paraffin sections from human plaques and by ELISA-based quantification of CD68-Fc binding to human atherosclerotic plaque extracts. In an in vitro model of macrophage/foam cell formation, CD68-Fc reduced foam cell formation significantly. This was caused both by interference of CD68-Fc with OxLDL uptake into macrophages and platelets and by the inhibition of platelet/OxLDL phagocytosis. Finally, expression of metalloproteinases by macrophages/foam cells was inhibited by CD68-Fc. In conclusion, CD68-Fc seems to be a promising new tool for preventing macrophage/foam cell formation. Thus, CD68-Fc might offer a novel therapeutic strategy for patients with acute coronary syndrome by modulating the generation of vulnerable plaques.     

Catheter ablation of ventricular tachycardias in patients with ischemic cardiomyopathy: validation of voltage mapping criteria for substrate modification by myocardial viability assessment using FDG PET

Background  

Catheter ablation is of growing importance in patients with an ischemic cardiomyopathy and recurrent episodes of ventricular tachyarrhythmias. Most ablation strategies in these patients are based on the detection of areas of scar and border zones to normal myocardium. However, the mapping criteria for identifying these areas have not been validated sufficiently so far. Therefore, we have performed a comparison between electroanatomical bipolar voltage maps obtained during substrate-based VT ablation procedures and [18 F]fluoro-2-deoxyglucose PET studies performed prior to these procedures.     

Diffusion-weighted MRI of bone marrow oedema, soft tissue oedema and synovitis in paediatric patients: feasibility and initial experience

ABSTRACT: BACKGROUND: MRI has become the mainstay of diagnostic imaging in paediatric rheumatology for lesion detection, differential diagnosis and therapy surveillance. MR imaging of synovitis, in particular, is indispensable for early diagnosis and follow-up in arthritis patients. We used diffusion-weighted MRI (DWI) as a new imaging modality in comparison to standard MRI sequences to study bone marrow oedema, soft-tissue oedema and synovitis in paediatric patients. METHODS: A total of 52 patients (mean age 11 +/- 5 years) with bone marrow oedema (n = 31), soft-tissue oedema (n = 20) and synovitis (n = 15) were examined with transversal diffusion-weighted single-shot echoplanar imaging in addition to standard MR sequences (T2W TIRM, T1W pre- and post-contrast). Diffusion-weighted images were used for lesion detection and apparent diffusion coefficient (ADC, unit x 10-3 mm2/s) values were measured with ROI technique on ADC maps. RESULTS: In 50 of 52 patients, DWI delineated the lesion of interest corresponding to pathological signal increase on standard sequences. Mean ADC was 1.60 +/- 0.14 (range 1.38 - 1.99) in osseous lesions, 1.72 +/- 0.31 (range 1.43 - 2.56) in soft tissue oedema and 2.82 +/- 0.24 (range 2.47 - 3.18) for joint effusion (ANOVA p < 0.001). No significant difference in mean ADC was seen for inflammatory vs. non-inflammatory lesions. Relative signal intensity of oedema was similar for DWI and T2W TIRM. DWI visualised synovial restricted diffusion with a mean ADC of 2.12 +/- 0.45 in 12 of 15 patients with synovitis. CONCLUSIONS: Diffusion-weighted MRI reliably visualises osseous and soft tissue oedema, as compared to standard sequences. DWI of synovitis is feasible in large joints and presents a novel approach to contrast-free imaging of synovitis. Whole-body DWI for chronic non-bacterial osteomyelitis should be evaluated in future studies.     

Automatic postprocessing for the assessment of quantitative human myocardial perfusion using MRI

Objective  

Quantitative determination of myocardial perfusion currently involves time-consuming postprocessing. This retrospective study presents automatic postprocessing consisting of image registration and image segmentation to obtain regional signal intensity time courses and quantitative perfusion values.     

Platelets in cardiovascular imaging

Coronary artery disease remains a major hazard within the western world despite early revascularisation and advanced medical therapy strategies. One of its major substrates is platelet activation and thrombus formation, triggering acute events such as myocardial infarction and ischemic strokes. There are a variety of non-invasive imaging strategies being translated from bench to bedside into clinical practice that tackle specific aspects of the pathophysiology of thrombus formation. Some of those techniques are able to visualize native contrast differences between thrombus and surrounding tissue, others focus on the use of specific contrast agents targeting thrombotic components such as fibrin or activated platelets. Some of those techniques are still in the pre-clinical stage; others have already entered the clinical arena. The current review article will introduce different techniques and their stage of development on their way from bench to bedside with a specific focus on cardiac magnetic resonance imaging, that has evolved over the last years providing high quality information on anatomy, perfusion and myocardial tissue characteristics such as scarring in clinical practice. Finally, we will give an outlook on how this exciting field might evolve in the future.     

Non-invasive imaging of glycoprotein VI binding to injured arterial lesions

Glycoprotein VI (GPVI) is the major platelet collagen receptor and plays a critical role in the process of thrombosis at sites of atherosclerotic lesions. This study evaluates the feasibility of radiolabeled soluble GPVI to identify injured arterial lesions. Radiolabeling was carried out using the iodogen method and resulted in the radioiodinated GPVI in radiochemical yields between 97-100%. The biodistribution of [(125)I]GPVI was determined in normal mice and demonstrated a blood clearance halftime of approximately 5.5 hours. Vascular lesions were induced in the carotid artery in wild type and ApoE(-/-)mice. Immediately after injury radioiodinated GPVI was injected intravenously. Binding of [(123)I]GPVI to carotid lesions was assessed by szintigraphic in vivo imaging. Carotid arteries were explanted for ex vivo autoradiography and histological characterization of the lesion. In vivo and ex vivo imaging revealed substantial accumulation of radioiodinated GPVI in the injured artery wall, with a ratio of lesion to control vessel of 3:1 and 7:1, respectively. Because GPVI is the critical collagen receptor that mediates platelet adhesion to vascular lesions, soluble radiolabeled GPVI may be an agent for non-invasive imaging of thrombogenic thus, vulnerable atherosclerotic plaques.