Thomas W. Johnson

Benefit of switching dual antiplatelet therapy after acute coronary syndrome: the TOPIC (timing of platelet inhibition after acute coronary syndrome) randomized study.

Aims Newer P2Y12 blockers (prasugrel and ticagrelor) demonstrated significant ischaemic benefit over clopidogrel after acute coronary syndrome (ACS). However, both drugs are associated with an increase in bleeding complications. The objective of the present study was to evaluate the benefit of switching dual antiplatelet therapy (DAPT) from aspirin plus a newer P2Y12 blocker to aspirin plus clopidogrel 1 month after ACS. Methods and results We performed an open-label, monocentric, and randomized trial. From March 2014 to April 2016, patients admitted with ACS requiring coronary intervention, on aspirin and a newer P2Y12 blocker and without adverse event at 1 month, were assigned to switch to aspirin and clopidogrel (switched DAPT) or continuation of their drug regimen (unchanged DAPT). The primary outcome was a composite of cardiovascular death, urgent revascularization, stroke and bleeding as defined by the Bleeding Academic Research Consortium (BARC) classification ≥2 at 1 year post ACS. Six hundred and forty six patients were randomized and 645 analysed, corresponding to 322 patients in the switched DAPT and 323 in the unchanged DAPT group. The primary endpoint occurred in 43 (13.4%) patients in the switched DAPT group and in 85 (26.3%) patients in the unchanged DAPT (HR 95%CI 0.48 (0.34-0.68), P < 0.01). No significant differences were reported on ischaemic endpoints, while BARC ≥ 2 bleeding occurred in 13 (4.0%) patients in the switched DAPT and in 48 (14.9%) in the unchanged DAPT group (HR 95%CI 0.30 (0.18-0.50), P < 0.01). Conclusion A switched DAPT is superior to an unchanged DAPT strategy to prevent bleeding complications without increase in ischaemic events following ACS.

Aging 2.0: health information about dementia on Twitter.

Online social media is widespread, easily accessible and attracts a global audience with a widening demographic. As a large proportion of adults now seek health information online and through social media applications, communication about health has become increasingly interactive and dynamic. Online health information has the potential to significantly impact public health, especially as the population gets older and the prevalence of dementia increases. However, little is known about how information pertaining to age-associated diseases is disseminated on popular social media platforms. To fill this knowledge gap, we examined empirically: (i) who is using social media to share information about dementia, (ii) what sources of information about dementia are promoted, and (iii) which dementia themes dominate the discussion. We data-mined the microblogging platform Twitter for content containing dementia-related keywords for a period of 24 hours and retrieved over 9,200 tweets. A coding guide was developed and content analysis conducted on a random sample (10%), and on a subsample from top users’ tweets to assess impact. We found that a majority of tweets contained a link to a third party site rather than personal information, and these links redirected mainly to news sites and health information sites. As well, a large number of tweets discussed recent research findings related to the prediction and risk management of Alzheimer’s disease. The results highlight the need for the dementia research community to harness the reach of this medium and its potential as a tool for multidirectional engagement.

Stent-Based Delivery of Tissue Inhibitor of Metalloproteinase-3 Adenovirus Inhibits Neointimal Formation in Porcine Coronary Arteries

Background—Stent-based antiproliferative therapy appears to decrease in-stent restenosis. However, alternative approaches might produce equivalent efficacy with better long-term safety. In previous work, an adenovirus capable of expressing the tissue inhibitor of metalloproteinase-3 (RAdTIMP-3) inhibited neointima formation in cell cultures and porcine saphenous vein grafts. RAdTIMP-3 decreased smooth muscle cell migration, stabilized the extracellular matrix, and uniquely promoted apoptosis. The current study developed eluting stent technology to deliver RAdTIMP-3 during stenting of pig coronary arteries. Methods and Results—Binding of virus to and elution from stents and transduction of pig coronary arteries were confirmed using &bgr;-galactosidase as a reporter gene in vitro and in vivo. Deployment of RAdTIMP-3–coated stents increased apoptosis and reduced neointimal cell density, but did not increase inflammation or proliferation compared with &bgr;-galactosidase–expressing adenovirus (RAdlacZ). Neointimal area after 28 days was significantly reduced to 1.27±0.19 mm2 with RAdTIMP-3 versus 2.61±0.31 mm2 with RAdlacZ stents (P<0.001) and 2.12±0.20 mm2 with bare stents (P<0.005). Conclusions—Our results demonstrate for the first time to our knowledge the feasibility of adenovirus-coated stent technology and highlight the potential of TIMP-3 to produce significant inhibition of in-stent neointima formation.

Utilizing Social Media to Study Information-Seeking and Ethical Issues in Gene Therapy

Background The field of gene therapy is rapidly evolving, and while hopes of treating disorders of the central nervous system and ethical concerns have been articulated within the academic community, little is known about views and opinions of different stakeholder groups. Objective To address this gap, we utilized social media to investigate the kind of information public users are seeking about gene therapy and the hopes, concerns, and attitudes they express. Methods We conducted a content analysis of questions containing the keywords “gene therapy” from the Q&A site “Yahoo! Answers” for the 5-year period between 2006 and 2010. From the pool of questions retrieved (N=903), we identified those containing at least one theme related to ethics, environment, economics, law, or society (n=173) and then characterized the content of relevant answers (n=399) through emergent coding. Results The results show that users seek a wide range of information regarding gene therapy, with requests for scientific information and ethical issues at the forefront of enquiry. The question sample reveals high expectations for gene therapy that range from cures for genetic and nongenetic diseases to pre- and postnatal enhancement of physiological attributes. Ethics questions are commonly expressed as fears about the impact of gene therapy on self and society. The answer sample echoes these concerns but further suggests that the acceptability of gene therapy varies depending on the specific application. Conclusions Overall, the findings highlight the powerful role of social media as a rich resource for research into attitudes toward biomedicine and as a platform for knowledge exchange and public engagement for topics relating to health and disease.

Prasugrel and bivalirudin for primary angioplasty: Early results on stent thrombosis and bleeding

Optimal treatment of STEMI relies on early mechanical reperfusion with PPCI [1]. Successful revascularisation requires effective adjunctive pharmacology, ideally with agents that provide rapid and reliable anti-platelet and anti-thrombotic effects. A delicate balance exists between effective inhibition of thrombosis and treatment-related bleeding. Incomplete suppression of platelet and thrombin activity may result in stent thrombosis. Advances in anti-thrombotic pharmacology have facilitated a reduction in bleeding risk. The HORIZONS-AMI randomised controlled trial compared bivalirudin with heparin plus GPIIb/IIIa antagonists. In both groups aspirin and the P2Y12 inhibitor clopidogrel were administered. The trial demonstrated a reduced rate of net clinical events and major bleeding with bivalirudin over the previous gold standard treatment with unfractionated heparin and GPIIb/IIIa antagonists [2]. Additionally bivalirudin demonstrated a reduced 30 day mortality. Despite the overall superiority of bivalirudin, an excess of acute stent thromboses (with the majority of events occurring within 5 h of the PCI) was observed in the bivalirudin (2.6%) compared to the heparin+GPIIb/IIIa group (0.9%). Interestingly, the lack of pre-randomization heparin was one of the independent predictors of acute stent thrombosis [3]. Bivalirudin reversibly binds to thrombin, and has a half-life of 25 min. Upon cessation of the infusion, plasma levels rapidly fall to below that demonstrated to reduce ischemic events in PCI. In a highly prothrombotic setting such as STEMI, it may be important to assure peri-procedural thrombin inhibition with an extended infusion. Variabilityof response to clopidogrel andconcerns regardingspeedof onset of ADP-receptor inhibition has led to the adoption of newer generation P2Y12 inhibitors with faster onset of action, greater consistency of effect and increased platelet inhibition. Prasugrel, an irreversible P2Y12-receptor inhibitor demonstrates improved clinical outcomes compared to clopidogrel [4–6]. It has been speculated that combining prasugrel with bivalirudin may negate the risk of early stent thrombosis observed in HORIZONS-AMI through more rapid and consistent platelet inhibition. However, the trial testing this hypothesis (BRAVE-4 trial, ClinTrial.gov NCT00976092) will not publish results before 2013.

Gray Matter Hypoxia in the Brain of the Experimental Autoimmune Encephalomyelitis Model of Multiple Sclerosis.

Background Multiple sclerosis (MS) has a significant inflammatory component and may have significant gray matter (GM) pathophysiology. Brain oxygenation is a sensitive measurement of the balance between metabolic need and oxygen delivery. There is evidence that inflammation and hypoxia are interdependent. In this paper, we applied novel, implanted PO2 sensors to measure hypoxia in cortical and cerebellar GM, in an inflammation-induced mouse model of MS. Objective Quantify oxygenation in cortical and cerebellar GM in the awake, unrestrained experimental autoimmune encephalomyelitis (EAE) mouse model and to relate the results to symptom level and disease time-course. Methods C57BL/6 mice were implanted with a fiber-optic sensor in the cerebellum (n = 13) and cortex (n = 24). Animals were induced with stimulation of the immune response and sensitization to myelin oligodendrocyte glycoprotein (MOG). Controls did not have MOG. We measured PO2 in awake, unrestrained animals from pre-induction (baseline) up to 36 days post-induction for EAE and controls. Results There were more days with hypoxia than hyperoxia (cerebellum: 34/67 vs. 18/67 days; cortex: 85/112 vs. 22/112) compared to time-matched controls. The average decline in PO2 on days that were significantly lower than time-matched controls was -8.8±6.0 mmHg (mean ± SD) for the cerebellum and -8.0±4.6 for the cortex. Conversely, the average increase in PO2 on days that were significantly hyperoxic was +3.2±2.8 mmHg (mean ± SD) for the cerebellum and +0.8±2.1 for the cortex. Cortical hypoxia related to increased behavioral deficits. Evidence for hypoxia occurred before measurable behavioral deficits. Conclusions A highly inflammatory condition primed to a white matter (WM) autoimmune response correlates with significant hypoxia and increased variation in oxygenation in GM of both cerebellum and cortex in the mouse EAE model of MS.

Clinical use of intracoronary imaging. Part 1: guidance and optimization of coronary interventions. An expert consensus document of the European Association of Percutaneous Cardiovascular Interventions

This Consensus Document is the first of two reports summarizing the views of an expert panel organized by the European Association of Percutaneous Cardiovascular Interventions (EAPCI) on the clinical use of intracoronary imaging including intravascular ultrasound (IVUS) and optical coherence tomography (OCT). The first document appraises the role of intracoronary imaging to guide percutaneous coronary interventions (PCIs) in clinical practice. Current evidence regarding the impact of intracoronary imaging guidance on cardiovascular outcomes is summarized, and patients or lesions most likely to derive clinical benefit from an imaging-guided intervention are identified. The relevance of the use of IVUS or OCT prior to PCI for optimizing stent sizing (stent length and diameter) and planning the procedural strategy is discussed. Regarding post-implantation imaging, the consensus group recommends key parameters that characterize an optimal PCI result and provides cut-offs to guide corrective measures and optimize the stenting result. Moreover, routine performance of intracoronary imaging in patients with stent failure (restenosis or stent thrombosis) is recommended. Finally, strengths and limitations of IVUS and OCT for guiding PCI and assessing stent failures and areas that warrant further research are critically discussed.

A Study of Platelet Inhibition, Using a 'Point of Care' Platelet Function Test, following Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction [PINPOINT-PPCI].

Background Rapid coronary recanalization following ST-elevation myocardial infarction (STEMI) requires effective anti-platelet and anti-thrombotic therapies. This study tested the impact of door to end of procedure (‘door-to-end’) time and baseline platelet activity on platelet inhibition within 24hours post-STEMI. Methods and Findings 108 patients, treated with prasugrel and procedural bivalirudin, underwent Multiplate® platelet function testing at baseline, 0, 1, 2 and 24hours post-procedure. Major adverse cardiac events (MACE), bleeding and stent thrombosis (ST) were recorded. Baseline ADP activity was high (88.3U [71.8–109.0]), procedural time and consequently bivalirudin infusion duration were short (median door-to-end time 55minutes [40–70] and infusion duration 30minutes [20–42]). Baseline ADP was observed to influence all subsequent measurements of ADP activity, whereas door-to-end time only influenced ADP immediately post-procedure. High residual platelet reactivity (HRPR ADP>46.8U) was observed in 75% of patients immediately post-procedure and persisted in 24% of patients at 2hours. Five patients suffered in-hospital MACE (4.6%). Acute ST occurred in 4 patients, all were <120mins post-procedure and had HRPR. No significant bleeding was observed. In a post-hoc analysis, pre-procedural morphine use was associated with significantly higher ADP activity following intervention. Conclusions Baseline platelet function, time to STEMI treatment and opiate use all significantly influence immediate post-procedural platelet activity.

European Society of Cardiology, acute cardiovascular care association, SCAD study group: a position paper on spontaneous coronary artery dissection

Spontaneous coronary artery dissection (SCAD) has long been recognized as a cause of acute coronary syndromes (ACS). Initially considered very rare and associated primarily with pregnancy and the peripartum period, the use of higher sensitivity Troponin assays and early angiography in ACS, coupled with greater awareness of the condition, has led to increased diagnosis, and it is now understood that SCAD represents a significant cause of ACS in predominantly young to middle-aged women, with most cases occurring outside the context of recent pregnancy.1,2 Although there are no randomized controlled trials in SCAD, knowledge has further advanced in the last 5-years as a result of an international research effort primarily focused on building and studying national SCAD registries.3–19 These studies have demonstrated, not only that SCAD is a distinct pathophysiological entity, but that there are key differences in management and outcomes compared to ACS of atherosclerotic aetiology. This position paper aims to set-out current knowledge on SCAD for the benefit of practicing clinicians caring for patients with this condition. It presents the consensus on contemporary management and areas of controversy and uncertainty, which remain a focus of ongoing research. The information is provided to support clinical care providers but is not intended to replace individualized decision-making by clinicians and other health care professionals.

Optical coherence tomography attenuation imaging for lipid core detection: an ex-vivo validation study

Lipid-core atherosclerotic plaques are associated with disease progression, procedural complications, and cardiac events. Coronary plaque lipid can be quantified in optical coherence tomography (OCT) pullbacks by measurement of lipid arcs and lipid lengths; parameters frequently used in clinical research, but labor intensive and subjective to analyse. In this study, we investigated the ability of quantitative attenuation, derived from intravascular OCT, to detect plaque lipid. Lipid cores are associated with a high attenuation coefficient. We compared the index of plaque attenuation (IPA), a local quantitative measure of attenuation, to the manually measured lipid score (arc and length) on OCT images, and to the plaque characterization ex-vivo. We confirmed a correlation between the IPA and lipid scores (r2 > 0.7). Comparison to histology shows that high attenuation is associated with fibroatheroma, but also with macrophage presence. IPA is a robust, reproducible, and user-independent measure that facilitates quantification of coronary lipid, a potential tool in clinical research and in guiding percutaneous coronary intervention.