Out-of-hours primary percutaneous coronary intervention for ST-elevation myocardial infarction is not associated with excess mortality: a study of 3347 patients treated in an integrated cardiac network

OBJECTIVES: Timely delivery of primary percutaneous coronary intervention (PPCI) is the treatment of choice for ST-segment elevation myocardial infarction (STEMI). Optimum delivery of PPCI requires an integrated network of hospitals, following a multidisciplinary, consultant-led, protocol-driven approach. We investigated whether such a strategy was effective in providing equally effective in-hospital and long-term outcomes for STEMI patients treated by PPCI within normal working hours compared with those treated out-of-hours (OOHs). DESIGN: Observational study. SETTING: Large PPCI centre in London. PARTICIPANTS: 3347 STEMI patients were treated with PPCI between 2004 and 2012. The follow-up median was 3.3 years (IQR: 1.2–4.6 years). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint was long-term major adverse cardiac events (MACE) with all-cause mortality a secondary endpoint. RESULTS: Of the 3347 STEMI patients, 1299 patients (38.8%) underwent PPCI during a weekday between 08:00 and 18:00 (routine-hours group) and 2048 (61.2%) underwent PPCI on a weekday between 18:00 and 08:00 or a weekend (OOHs group). There were no differences in baseline characteristics between the two groups with comparable door-to-balloon times (in-hours (IHs) 67.8 min vs OOHs 69.6 min, p=0.709), call-to-balloon times (IHs 116.63 vs OOHs 127.15 min, p=0.60) and procedural success. In hospital mortality rates were comparable between the two groups (IHs 3.6% vs OOHs 3.2%) with timing of presentation not predictive of outcome (HR 1.25 (95% CI 0.74 to 2.11). Over the follow-up period there were no significant differences in rates of mortality (IHs 7.4% vs OFHs 7.2%, p=0.442) or MACE (IHs 15.4% vs OFHs 14.1%, p=0.192) between the two groups. After adjustment for confounding variables using multivariate analysis, timing of presentation was not an independent predictor of mortality (HR 1.04 95% CI 0.78 to 1.39). CONCLUSIONS: This large registry study demonstrates that the delivery of PPCI with a multidisciplinary, consultant-led, protocol-driven approach provides safe and effective treatment for patients regardless of the time of presentation

Randomised, double-blind, placebo-controlled study investigating the effects of inorganic nitrate on vascular function, platelet reactivity and restenosis in stable angina: protocol of the NITRATE-OCT study

KSR and this work are funded by an NIHR Doctoral Fellowship (DRF-2014-07-008

Platelet-Rich Plasma Promotes the Proliferation of Human Muscle Derived Progenitor Cells and Maintains Their Stemness

Human muscle-derived progenitor cells (hMDPCs) offer great promise for muscle cell-based regenerative medicine; however, prolonged ex-vivo expansion using animal sera is necessary to acquire sufficient cells for transplantation. Due to the risks associated with the use of animal sera, the development of a strategy for the ex vivo expansion of hMDPCs is required. The purpose of this study was to investigate the efficacy of using platelet-rich plasma (PRP) for the ex-vivo expansion of hMDPCs. Pre-plated MDPCs, myoendothelial cells, and pericytes are three populations of hMDPCs that we isolated by the modified pre-plate technique and Fluorescence Activated Cell Sorting (FACS), respectively. Pooled allogeneic human PRP was obtained from a local blood bank, and the effect that thrombin-activated PRP-releasate supplemented media had on the ex-vivo expansion of the hMDPCs was tested against FBS supplemented media, both in vitro and in vivo. PRP significantly enhanced short and long-term cell proliferation, with or without FBS supplementation. Antibody-neutralization of PDGF significantly blocked the mitogenic/proliferative effects that PRP had on the hMDPCs. A more stable and sustained expression of markers associated with stemness, and a decreased expression of lineage specific markers was observed in the PRP-expanded cells when compared with the FBS-expanded cells. The in vitro osteogenic, chondrogenic, and myogenic differentiation capacities of the hMDPCs were not altered when expanded in media supplemented with PRP. All populations of hMDPCs that were expanded in PRP supplemented media retained their ability to regenerate myofibers in vivo. Our data demonstrated that PRP promoted the proliferation and maintained the multi-differentiation capacities of the hMDPCs during ex-vivo expansion by maintaining the cells in an undifferentiated state. Moreover, PDGF appears to be a key contributing factor to the beneficial effect that PRP has on the proliferation of hMDPCs. © 2013 Li et al

Randomised, double-blind, placebo-controlled clinical trial investigating the effects of inorganic nitrate in hypertension-induced target organ damage: protocol of the NITRATE-TOD study in the UK

© 2020 Author(s). Introduction: Arterial stiffness and left ventricular (LV) hypertrophy are the key markers of hypertensive target organ damage (TOD) associated with increased cardiovascular morbidity and mortality. We have previously shown that dietary inorganic nitrate supplementation lowers blood pressure (BP) in hypertension, however, whether this approach might also improve markers of hypertensive TOD is unknown. In this study, we will investigate whether daily dietary inorganic nitrate administration reduces LV mass and improves measures of arterial stiffness. Methods and design: NITRATE-TOD is a double-blind, randomised, single-centre, placebo-controlled phase II trial aiming to enrol 160 patients with suboptimal BP control on one or more antihypertensives. Patients will be randomised to receive 4 months once daily dose of either nitrate-rich beetroot juice or nitrate-deplete beetroot juice (placebo). The primary outcomes are reduction in LV mass and reduction in pulse wave velocity (PWV) and central BP. The study has a power of 95% for detecting a 9 g LV mass change by cardiovascular MRI (∼6% change for a mildly hypertrophied heart of 150 g). For PWV, we have a power of >95% for detecting a 0.6 m/s absolute change. For central systolic BP, we have a>90% power to detect a 5.8 mm Hg difference in central systolic BP. Secondary end points include change in ultrasound flow-mediated dilation, change in plasma nitrate and nitrite concentration and change in BP. Ethics and dissemination: The study was approved by the London - City and East Research Ethics Committee (10/H0703/98). Trial results will be published according to the Consolidated Standards of Reporting Trials statement and will be presented at conferences and reported in peer-reviewed journals

An Observational Study Assessing Immediate Complete Versus Delayed Complete Revascularisation in Patients with Multi-Vessel Disease Undergoing Primary Percutaneous Coronary Intervention.

Background: More than half of the patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) have multi-vessel coronary artery disease. This is associated with worse outcomes compared with single vessel disease. Whilst evidence now exists to support complete revascularisation for bystander disease the optimal timing is still debated. This study aimed to compare clinical outcomes in patients with STEMI and multi-vessel disease who underwent complete revascularisation as inpatients in comparison to patients who had staged PCI as early outpatients. Methods and results: We conducted an observational cohort study consisting of 1522 patients who underwent primary PCI with multi-vessel disease from 2012 to 2019. Exclusions included patients with cardiogenic shock and previous CABG. Patients were split into 2 groups depending on whether they had complete revascularisation performed as inpatients or as staged PCI at later outpatient dates. The primary outcome of this study was major adverse cardiac events (consisting of myocardial infarction, target vessel revascularisation and all-cause mortality).834 (54.8%) patients underwent complete inpatient revascularisation and 688 patients (45.2%) had outpatient PCI (median 43 days post discharge). Of the inpatient group, 652 patients (78.2%) underwent complete revascularisation during the index procedure whilst 182 (21.8%) patients underwent inpatient bystander PCI in a second procedure. Overall, there were no significant differences between the groups with regards to their baseline or procedural characteristics. Over the follow-up period there was no significant difference in MACE between the cohorts (P = .62), which persisted after multivariate adjustment (HR 1.21 [95% CI 0.72-1.96]). Furthermore, in propensity-matched analysis there was no significant difference in outcome between the groups (HR: 0.86 95% CI: 0.75-1.25). Conclusions: Our study demonstrated that the timing of bystander PCI after STEMI did not appear to have an effect on cardiovascular outcomes. We suggest that patients with multi-vessel disease can potentially be discharged promptly and undergo early outpatient bystander PCI. This could significantly reduce length of stay in hospital

Molecular psychiatry of zebrafish

Due to their well-characterized neural development and high genetic homology to mammals, zebrafish (Danio rerio) have emerged as a powerful model organism in the field of biological psychiatry. Here, we discuss the molecular psychiatry of zebrafish, and its implications for translational neuroscience research and modeling central nervous system (CNS) disorders. In particular, we outline recent genetic and technological developments allowing for in vivo examinations, high-throughput screening and whole-brain analyses in larval and adult zebrafish. We also summarize the application of these molecular techniques to the understanding of neuropsychiatric disease, outlining the potential of zebrafish for modeling complex brain disorders, including attention-deficit/hyperactivity disorder (ADHD), aggression, post-traumatic stress and substance abuse. Critically evaluating the advantages and limitations of larval and adult fish tests, we suggest that zebrafish models become a rapidly emerging new field in modern molecular psychiatry research

The Use of Novel Oral Anti-Coagulant's (NOAC) compared to Vitamin K Antagonists (Warfarin) in patients with Left Ventricular thrombus after Acute Myocardial Infarction (AMI).

This is a pre-copyedited, author-produced version of an article accepted for publication in European Heart Journal - Cardiovascular Pharmacotherapy following peer review. The version of record: Daniel A Jones, Paul Wright, Momin A Alizadeh, Sadeer Fhadil, Krishnaraj S Rathod, Oliver Guttmann, Charles Knight, Adam Timmis, Andreas Baumbach, Andrew Wragg, Anthony Mathur, Sotiris Antoniou, The Use of Novel Oral Anti-Coagulant’s (NOAC) compared to Vitamin K Antagonists (Warfarin) in patients with Left Ventricular thrombus after Acute Myocardial Infarction (AMI), European Heart Journal - Cardiovascular Pharmacotherapy, pvaa096, https://doi.org/10.1093/ehjcvp/pvaa096AIM: Current guidelines recommend the use of Vitamin K Antagonist (VKA) for up to 3 - 6 months for treatment of LV thrombus post-acute myocardial infarction (AMI). However, based on evidence supporting non-inferiority of Novel Oral Anti-Coagulant's (NOAC) compared to VKA for other indications such as DVT, PE and thrombo-embolic prevention in atrial fibrillation, NOACs are being increasingly used off licence for the treatment of LV thrombus post AMI. In this study we investigated the safety and effect of NOACs compared to VKA on LV thrombus resolution in patients presenting with AMI. METHODS AND RESULTS: This was an observational study of 2,328 consecutive patients undergoing Coronary Angiography +/- Percutaneous Coronary Intervention (PCI) for AMI between May 2015- December 2018, at a UK cardiac centre. Patients' details were collected from the hospital electronic database. The primary end-point was rate of LV thrombus resolution with bleeding rates a secondary outcome.Left ventricular (LV) thrombus was diagnosed in 101 (4.3%) patients. Sixty patients (59.4%) were started on VKA and 41 patients (40.6%) on NOAC therapy (rivaroxaban: 58.5%, apixaban, 36.5% and edoxaban: 5.0%). Both groups were well matched in terms of baseline characteristics including age, previous cardiac history (Previous MI, PCI, CABG), and cardiovascular risk factors (Hypertension, Diabetes, Hypercholesterolaemia).Over the follow up period (median 2.2 years), overall rates of LV thrombus resolution were 86.1%. There was greater and earlier LV thrombus resolution in the NOAC group compared to patients treated with warfarin (82% vs 64.4%, p = 0.0018, at 1 year), which persisted after adjusting for baseline variables (OR 1.8 95% CI 1.2-2.9). Major bleeding events during the f/u period were lower in the NOAC group, compared with VKA group (0% vs 6.7%, p = 0.030) with no difference in rates of systemic thromboembolism (5% vs 2.4%, p = 0.388). CONCLUSION: This data suggests improved thrombus resolution in post ACS LV thrombosis in patients treated with NOACs compared to vitamin K antagonists. This improvement in thrombus resolution was accompanied with a better safety profile for NOAC patients' vs VKA treated patients. Thus, provides data to support a randomised trial to answer this question

Regulation of inflammation in Japanese encephalitis

Uncontrolled inflammatory response of the central nervous system is a hallmark of severe Japanese encephalitis (JE). Although inflammation is necessary to mount an efficient immune response against virus infections, exacerbated inflammatory response is often detrimental. In this context, cells of the monocytic lineage appear to be important forces driving JE pathogenesis

COVID-19 and changes in activity and treatment of ST elevation MI from a UK cardiac centre.

Background: The international healthcare response to COVID-19 has been driven by epidemiological data related to case numbers and case fatality rate. Second order effects have been less well studied. This study aimed to characterise the changes in emergency activity of a high-volume cardiac catheterisation centre and to cautiously model any excess indirect morbidity and mortality. Method: Retrospective cohort study of patients admitted with acute coronary syndrome fulfilling criteria for the heart attack centre (HAC) pathway at St. Bartholomew's hospital, UK. Electronic data were collected for the study period March 16th - May 16th 2020 inclusive and stored on a dedicated research server. Standard governance procedures were observed in line with the British Cardiovascular Intervention Society audit. Results: There was a 28% fall in the number of primary percutaneous coronary interventions (PCIs) for ST elevation myocardial infarction (STEMI) during the study period (111 vs. 154) and 36% fewer activations of the HAC pathway (312 vs. 485), compared to the same time period averaged across three preceding years. In the context of 'missing STEMIs', the excess harm attributable to COVID-19 could result in an absolute increase of 1.3% in mortality, 1.9% in nonfatal MI and 4.5% in recurrent ischemia. Conclusions: The emergency activity of a high-volume PCI centre was significantly reduced for STEMI during the peak of the first wave of COVID-19. Our data can be used as an exemplar to help future modelling within cardiovascular workstreams to refine aggregate estimates of the impact of COVID-19 and inform targeted policy action