Coronary artery disease and schizophrenia: the interplay of heart and mind

This editorial refers to ‘The effect of schizophrenia on major adverse cardiac events, length of hospital stay, and prevalence of somatic comorbidities following acute coronary syndrome’, by R. Attar et al., doi:10.1093/ehjqcco/qcy055

Relationship between lipoproteins, thrombosis and atrial fibrillation

The prothrombotic state in atrial fibrillation (AF) occurs as a result of multifaceted interactions, known as Virchow’s triad of hypercoagulability, structural abnormalities, and blood stasis. More recently, there is emerging evidence that lipoproteins are implicated in this process, beyond their traditional role in atherosclerosis. In this review, we provide an overview of the various lipoproteins and explore the association between lipoproteins and AF, the effects of lipoproteins on haemostasis, and the potential contribution of lipoproteins to thrombogenesis in AF. There are several types of lipoproteins based on size, lipid composition, and apolipoprotein category, namely: chylomicrons, very low-density lipoprotein, low-density lipoprotein (LDL), intermediate-density lipoprotein, and high-density lipoprotein. Each of these lipoproteins may contain numerous lipid species and proteins with a variety of different functions. Furthermore, the lipoprotein particles may be oxidized causing an alteration in their structure and content. Of note, there is a paradoxical inverse relationship between total cholesterol and LDL cholesterol (LDL-C) levels, and incident AF. The mechanism by which this occurs may be related to the stabilizing effect of cholesterol on myocardial membranes, along with its role in inflammation. Overall, specific lipoproteins may interact with haemostatic pathways to promote excess platelet activation and thrombin generation, as well as inhibiting fibrinolysis. In this regard, LDL-C has been shown to be an independent risk factor for thromboembolic events in AF. The complex relationship between lipoproteins, thrombosis and AF warrants further research with an aim to improve our knowledge base and contribute to our overall understanding of lipoprotein-mediated thrombosis

Case series of iatrogenic coronary stent avulsion: a rare complication with varied management strategies

Background Coronary stent avulsion is a rare, infrequently reported complication of percutaneous coronary intervention (PCI) with no consensus on management options. Case summary This case series presents three descriptions of iatrogenic coronary stent avulsions, and three different bailout management strategies. All patients presented with acute coronary syndrome and required PCI. In the first case, a freshly implanted stent was entrapped in a coronary guidewire and avulsed upon withdrawal of the wire into the aortic sinus. In the second case, a staged procedure to implant a new stent was complicated by stent dislodgement and entanglement with a recently implanted stent leading to avulsion of both stents into the aortic sinus and resultant dissection to the coronary arteries. In the third case, following a successful stent implantation, the tip of the coronary guidewire was bound to the proximal edge of the stent resulting in avulsion of the newly implanted stent into the ascending aorta upon retraction of the wire at the end of the procedure. The first two patients were managed percutaneously, and the third surgically. All patients have had acceptable technical and clinical outcomes. Discussion In the absence of a consensus on best bailout management strategy, we discuss the mechanisms of and the potential management options for this rare, but serious, complication

The role of procoagulant phospholipids on the surface of circulating blood cells in thrombosis and haemostasis

Phospholipids (PLs) are found in all cell types and are required for structural support and cell activation signalling pathways. In resting cells, PLs are asymmetrically distributed throughout the plasma membrane with native procoagulant aminophospholipids (aPLs) being actively maintained in the inner leaflet of the membrane. Upon platelet activation, aPLs rapidly externalize to the outer leaflet and are essential for supporting the coagulation cascade by providing binding sites for factors in the cell-based model. More recent work has uncovered a role for enzymatically oxidized PLs (eoxPLs) in facilitating coagulation, working in concert with native aPLs. Despite this, the role of aPLs and eoxPLs in thrombo-inflammatory conditions, such as arterial and venous thrombosis, has not been fully elucidated. In this review, we describe the biochemical structures, distribution and regulation of aPL externalization and summarize the literature on eoxPL generation in circulating blood cells. We focus on the currently understood role of these lipids in mediating coagulation reactions in vitro, in vivo and in human thrombotic disease. Finally, we highlight gaps in our understanding in how these lipids vary in health and disease, which may place them as future therapeutic targets for the management of thrombo-inflammatory conditions

Case series of iatrogenic coronary stent avulsion: a rare complication with varied management strategies

Background Coronary stent avulsion is a rare, infrequently reported complication of percutaneous coronary intervention (PCI) with no consensus on management options. Case summary This case series presents three descriptions of iatrogenic coronary stent avulsions, and three different bailout management strategies. All patients presented with acute coronary syndrome and required PCI. In the first case, a freshly implanted stent was entrapped in a coronary guidewire and avulsed upon withdrawal of the wire into the aortic sinus. In the second case, a staged procedure to implant a new stent was complicated by stent dislodgement and entanglement with a recently implanted stent leading to avulsion of both stents into the aortic sinus and resultant dissection to the coronary arteries. In the third case, following a successful stent implantation, the tip of the coronary guidewire was bound to the proximal edge of the stent resulting in avulsion of the newly implanted stent into the ascending aorta upon retraction of the wire at the end of the procedure. The first two patients were managed percutaneously, and the third surgically. All patients have had acceptable technical and clinical outcomes. Discussion In the absence of a consensus on best bailout management strategy, we discuss the mechanisms of and the potential management options for this rare, but serious, complication

Severe symptomatic aortic stenosis: medical therapy and transcatheter aortic valve implantation (TAVI)—a real-world retrospective cohort analysis of outcomes and cost-effectiveness using national data

Objectives: Determine the real-world difference between 2 groups of patients with severe aortic stenosis and similar baseline comorbidities: surgical turn down (STD) patients, who were managed medically prior to the availability of transcatheter aortic valve implantation (TAVI) following formal surgical outpatient assessment, and patients managed with a TAVI implant. Design: Retrospective cohort study from real-world data. Setting: Electronic patient letters were searched for patients with a diagnosis of severe aortic stenosis and a formal outpatient STD prior to the availability of TAVI (1999–2009). The second group comprised the first 90 cases of TAVI in South Wales (2009 onwards). 2 years prior to and 5 years following TAVI/STD were assessed. Patient data were pseudoanonymised, using the Secure Anonymized Information Linkage (SAIL) databank, and extracted from Office National Statistics (ONS), PatientEpisode Database for Wales (PEDW) and general practitioner databases. Population: 90 patients who had undergone TAVI in South Wales, and 65 STD patients who were medically managed. Main outcome measures: Survival, hospital admission frequency and length of stay, primary care visits, and cost-effectiveness. Results: TAVI patients were significantly older (81.8 vs 79.2), more likely to be male (59.1% vs 49.3%), baseline comorbidities were balanced. Mortality in TAVI versus STD was 28% vs 70% at 1000 days follow-up. There were significantly more hospital admissions per year in the TAVI group prior to TAVI/STD (1.5 (IQR 1.0– 2.4) vs 1.0 IQR (0.5–1.5)). Post TAVI/STD, the TAVI group had significantly lower hospital admissions (0.3 (IQR 0.0–1.0) vs 1.2 (IQR 0.7–3.0)) and lengths of stay (0.4 (IQR 0.0–13.8) vs 11.0 (IQR 2.5–28.5), p<0.05). The incremental cost-effectiveness ratio (ICER) for TAVI was £10 533 per quality-adjusted life year (QALY). Conclusions: TAVI patients were more likely to survive and avoid hospital admissions compared with the medically managed STD group. The ICER for TAVI was £10 533 per QALY, making it a cost-effective procedure

The impact of coronary perforation in percutaneous interventions involving the left main stem coronary artery in the United Kingdom 2007-2014: Insights from the British Cardiovascular Intervention Society database

Background Percutaneous coronary intervention (PCI) is increasingly utilized for treatment of coronary disease involving the unprotected left main stem (ULMS). However, no studies to date have examined the outcomes of such interventions when complicated by coronary perforation (CP). Methods Using the British Cardiovascular Intervention society (BCIS) database, data were analyzed on all ULMS‐PCI procedures complicated by CP in England and Wales between 2007 and 2014. Multivariate logistic regressions were used to identify predictors of ULMS CP and to evaluate the association between this complication and outcomes. Results During 10,373 ULMS‐PCI procedures, CP occurred more frequently than in non‐ULMS‐PCI (0.9 vs. 0.4%, p < .001) with a stable annual incidence. Covariates associated with CP included number of stents used, female gender, use of rotational atherectomy and chronic total occlusion (CTO) intervention. Adjusted odds of adverse outcomes for ULMS‐PCI complicated by CP were higher for peri‐procedural complications including cardiogenic shock, tamponade, side‐branch loss, DC cardioversion, in‐hospital major bleeding, transfusion requirement, and peri‐procedural myocardial infarction. There were also significantly increased odds for in‐hospital major adverse cardiac events (MACCE, OR 8.961, 95% CI [4.902–16.383]) and 30‐day mortality (OR 5.301, 95% CI [2.741–10.251]). Conclusions CP is an infrequent event during ULMS‐PCI and is predicted by female gender, rotational atherectomy, CTO interventions or number of stents used. CP was associated with significantly higher odds of mortality and morbidity, but at rates similar to previously published all‐comer PCI complicated by CP

The impact of intracoronary imaging on PCI outcomes in cases utilising rotational atherectomy: an analysis of 8,417 rotational atherectomy cases from the British Cardiovascular Intervention Society Database

Introduction. There is increasing evidence supporting the use of intracoronary imaging to optimize the outcomes of percutaneous coronary intervention (PCI). However, there are no studies examining the impact of imaging on PCI outcomes in cases utilising rotational atherectomy (RA-PCI). Our study examines the determinants and outcomes of using intracoronary imaging in RA-PCI cases including 12-month mortality. Methods. Using the British Cardiac Intervention Society database, data were analysed on all RA-PCI procedures in the UK between 2007 and 2014. Descriptive statistics and multivariate logistic regressions were used to examine baseline, procedural, and outcome associations with intravascular imaging. Results. Intracoronary imaging was used in 1,279 out of 8,417 RA-PCI cases (15.2%). Baseline covariates associated with significantly more imaging use were number of stents used, smoking history, previous CABG, pressure wire use, proximal LAD disease, laser use, glycoprotein inhibitor use, cutting balloons, number of restenosis attempted, off-site surgery, and unprotected left main stem (uLMS) PCI. Adjusted rates of in-hospital major adverse cardiac/cerebrovascular events (IH-MACCE), its individual components (death, peri-procedural MI, stroke, and major bleed), or 12-month mortality were not significantly altered by the use of imaging in RA-PCI. However, subgroup analysis demonstrated a signal towards reduction in 12-month mortality in uLMS RA-PCI cases utilising intracoronary imaging (OR 0.67, 95% CI 0.44–1.03). Conclusions. Intracoronary imaging use during RA-PCI is associated with higher risk of baseline and procedural characteristics. There were no differences observed in IH-MACCE or 12-month mortality with intracoronary imaging in RA-PCI

Differential Roles of the PKC Novel Isoforms, PKCδ and PKCε, in Mouse and Human Platelets

Background Increasing evidence suggests that individual isoforms of protein kinase C (PKC) play distinct roles in regulating platelet activation. Methodology/Principal Findings In this study, we focus on the role of two novel PKC isoforms, PKCδ and PKCε, in both mouse and human platelets. PKCδ is robustly expressed in human platelets and undergoes transient tyrosine phosphorylation upon stimulation by thrombin or the collagen receptor, GPVI, which becomes sustained in the presence of the pan-PKC inhibitor, Ro 31-8220. In mouse platelets, however, PKCδ undergoes sustained tyrosine phosphorylation upon activation. In contrast the related isoform, PKCε, is expressed at high levels in mouse but not human platelets. There is a marked inhibition in aggregation and dense granule secretion to low concentrations of GPVI agonists in mouse platelets lacking PKCε in contrast to a minor inhibition in response to G protein-coupled receptor agonists. This reduction is mediated by inhibition of tyrosine phosphorylation of the FcRγ-chain and downstream proteins, an effect also observed in wild-type mouse platelets in the presence of a PKC inhibitor. Conclusions These results demonstrate a reciprocal relationship in levels of the novel PKC isoforms δ and ε in human and mouse platelets and a selective role for PKCε in signalling through GPVI

Phospholipid membranes drive abdominal aortic aneurysm development through stimulating coagulation factor activity

Abdominal aortic aneurysm (AAA) is an inflammatory vascular disease with high mortality and limited treatment options. How blood lipids regulate AAA development is unknown. Here lipidomics and genetic models demonstrate a central role for procoagulant enzymatically oxidized phospholipids (eoxPL) in regulating AAA. Specifically, through activating coagulation, eoxPL either promoted or inhibited AAA depending on tissue localization. Ang II administration to ApoE−/− mice increased intravascular coagulation during AAA development. Lipidomics revealed large numbers of eoxPL formed within mouse and human AAA lesions. Deletion of eoxPL-generating enzymes (Alox12 or Alox15) or administration of the factor Xa inhibitor rivaroxaban significantly reduced AAA. Alox-deficient mice displayed constitutively dysregulated hemostasis, including a consumptive coagulopathy, characterized by compensatory increase in prothrombotic aminophospholipids (aPL) in circulating cell membranes. Intravenously administered procoagulant PL caused clotting factor activation and depletion, induced a bleeding defect, and significantly reduced AAA development. These data suggest that Alox deletion reduces AAA through diverting coagulation away from the vessel wall due to eoxPL deficiency, instead activating clotting factor consumption and depletion in the circulation. In mouse whole blood, ∼44 eoxPL molecular species formed within minutes of clot initiation. These were significantly elevated with ApoE−/− deletion, and many were absent in Alox−/− mice, identifying specific eoxPL that modulate AAA. Correlation networks demonstrated eoxPL belonged to subfamilies defined by oxylipin composition. Thus, procoagulant PL regulate AAA development through complex interactions with clotting factors. Modulation of the delicate balance between bleeding and thrombosis within either the vessel wall or circulation was revealed that can either drive or prevent disease development