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

Characterising the role of inflammatory procoagulant phospholipids in arterial thrombosis

Arterial thrombosis is an inflammatory response triggered by atherosclerotic plaque rupture causing acute coronary syndromes (ACS), strokes and death. Clotting reactions require interactions of coagulation proteins with aminophospholipids (aPL) and enzymatically oxidized phospholipids (eoxPL) on the surface of blood cells. This thesis investigates the role of aPL and eoxPL in arterial thrombosis. Using liquid chromatography with tandem mass spectrometry (LC-MS/MS), I quantified eoxPL generated in thrombin-activated platelets from a healthy cohort and demonstrated a large degree of inter- and intra-individual variation. Aspirin supplementation in-vivo reduced the amount of COX-1 derived eoxPL, but increased diacyl 12 hydroxyeicosatetraenoic acid (12-HETE) containing eoxPL (12-HETE-PL) generation without affecting the levels of free 12-HETE. This suggests that aspirin interferes with re-esterification pathways of 12-HETE to acyl lysophospholipids. Lipidomic analysis of arterial thrombi extracted from patients undergoing clot retrieval procedures demonstrated the presence of HETE-PL, with a predominance of platelet-derived 12-HETE-PL. Using a clinical cohort, I demonstrated elevated thrombin generation on the surface of isolated EV and leukocytes, but not platelets, from patients with ACS versus healthy controls (HC). Lipidomic analysis demonstrated no differences between groups in HETE-PL amounts from resting platelets, leukocytes and EV. Nevertheless, as seen with the healthy cohort, thrombin-activated platelets from patients supplemented with aspirin had higher diacyl 12-HETE-PL generation. Finally, there were no differences in the fraction (%) externalized phosphatidylethanolamine (%PE) on the surface of platelets and leukocytes across the groups. However, EV samples had lower %PE in ACS versus HC which, unlike platelets and leukocytes, correlated inversely with thrombin generation. In summary, eoxPL were detected within arterial thrombi and their synthesis is increased with aspirin. Thrombin generation is higher on the surface of EV from ACS patients, which may be explained by differences in the aPL lipidome between groups. Further studies examining therapeutic agents targeting procoagulant lipids are needed

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

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