INTRODUCTION:The BE-ALIVE score is an additive scoring system for estimating 30-day mortality in patients presenting with an acute coronary syndrome (ACS) [1]. However, it had only previously been tested on an internal validation cohort. The aim was to assess the scoring system on an external validation cohort. METHODS:The scoring system comprises six domains: (1) Base Excess (1 point for < -2 mmols/L), (2) Age (<65 years: 0 points, 65-74: 1 point, 75-84: 2 points, ≥ 85: 3 points), (3) Lactate (<2 mmols/L: 0 points, 2-4.9: 1 point, 5-9.9: 3 points, ≥ 10: 6 points), (4) Intubated & Ventilated (2 points), (5) Left Ventricular function (normal or mildly impaired: -1 point, moderately impaired: 1 point, severely impaired: 3 points) and (6) External / out of hospital cardiac arrest (1 point). We applied the BE-ALIVE score was applied to 205 consecutive patients at a different institution. RESULTS:Calibration was strong, with an observed to expected ratio of 1.01, a calibration slope of 1.26 and calibration in the large of -0.03. The Spiegelhalter's Z-statistic was -0.95 (p = 0.34). The AUC was 0.95 (0.92-0.98) in the external validation cohort versus 0.90 (0.85-0.95) during internal validation. Overall performance was excellent with a Brier score of 0.07 versus 0.06 during internal validation. The negative predictive value for 30-day mortality of a BE-ALIVE score < 4 was 98 %, with a positive predicted value of a score ≥ 10 of 95 %. CONCLUSIONS:The BE-ALIVE score remains a robust predictor of 30-day mortality in an external validation cohort.

Introduction Hospital-acquired thrombosis (HAT) is defined as any venous thromboembolism (VTE)-related event during a hospital admission or occurring up to 90 days post discharge, and is associated with significant morbidity, mortality and healthcare-associated costs. Although surgery is an established risk factor for VTE, operations with a short hospital stay (<48 hours) and that permit early ambulation are associated with a low risk of VTE. Many patients undergoing short-stay surgical procedures and who are at low risk of VTE are treated with graduated compression stockings (GCS). However, evidence for the use of GCS in VTE prevention for this cohort is poor.Methods and analysis A multicentre, cluster randomised controlled trial which aims to determine whether GCS are superior in comparison to no GCS in the prevention of VTE for surgical patients undergoing short-stay procedures assessed to be at low risk of VTE. A total of 50 sites (21 472 participants) will be randomised to either intervention (GCS) or control (no GCS). Adult participants (18–59 years) who undergo short-stay surgical procedures and are assessed as low risk of VTE will be included in the study. Participants will provide consent to be contacted for follow-up at 7-days and 90-days postsurgical procedure. The primary outcome is the rate of symptomatic VTE, that is, deep vein thrombosis or pulmonary embolism during admission or within 90 days. Secondary outcomes include healthcare costs and changes in quality of life. The main analysis will be according to the intention-to-treat principle and will compare the rates of VTE at 90 days, measured at an individual level, using hierarchical (multilevel) logistic regression.Ethics and dissemination Ethical approval was granted by the Camden and Kings Cross Research Ethics Committee (22/LO/0390). Findings will be published in a peer-reviewed journal and presented at national and international conferences.Trial registration number ISRCTN13908683.

Hnin, Thet; Mandal, Amit K.J.; Smith, Elliot; Iyengar, Srikanth; Missouris, Constantinos G.; Baker, Christopher Author Information

The COVID-19 pandemic has altered our approach to inpatient echocardiography delivery. There is now a greater focus to address key clinical questions likely to make an immediate impact in management, particularly during the period of widespread infection. Handheld echocardiography (HHE) can be used as a first-line assessment tool, limiting scanning time and exposure to high viral load. This article describes a potential role for HHE during a pandemic. We propose a protocol with a reporting template for a focused core dataset necessary in delivering an acute echocardiography service in the setting of a highly contagious disease, minimising risk to the operator. We cover the scenarios typically encountered in the acute cardiology setting and how an expert trained echocardiography team can identify such pathologies using a limited imaging format and include cardiac presentations encountered in those patients acutely unwell with COVID-19.

Ciraparantag, an anticoagulant reversal agent, is a small molecule specifically designed to bind noncovalently by charge-charge interaction to unfractionated heparin and low-molecular-weight heparin. It shows binding characteristics that are similar to those of direct oral anticoagulants (DOACs). A dynamic light-scattering methodology was used to demonstrate ciraparantag’s binding to the heparins and DOACs and its lack of binding to a variety of proteins including coagulation factors and commonly used drugs. Ciraparantag reaches maximum concentration within minutes after IV administration with a half-life of 12 to 19 minutes. It is primarily hydrolyzed by serum peptidases into 2 metabolites, neither of which has substantial activity. Ciraparantag and its metabolites are recovered almost entirely in the urine. In animal models of bleeding (rat tail transection and liver laceration), a single IV dose of ciraparantag given at peak concentrations of the anticoagulant, but before the bleeding injury, significantly reduced the blood loss. Ciraparantag, given after the bleeding injury, also significantly reduced blood loss. It appears to have substantial ability to reduce blood loss in animal models in which a variety of anticoagulants are used and has potential as a useful DOAC reversal agent.

BACKGROUND:Patients admitted to hospital for surgery are at an increased risk of venous thromboembolism. Pharmaco-thromboprophylaxis and mechanical prophylaxis (usually graduated compression stockings or intermittent pneumatic compression) have been shown to reduce the incidence of venous thromboembolism. The evidence base supporting the National Institute for Health and Care Excellence's recommendation for the use of graduated compression stockings for venous thromboembolism prevention in the UK has recently been challenged. It is unclear if the risks and costs associated with graduated compression stockings are justified for deep-vein thrombosis prevention in moderate- and high-risk elective surgical inpatients receiving low-dose low-molecular-weight heparin pharmaco-thromboprophylaxis. OBJECTIVES:The primary objective was to compare the venous thromboembolism rate in elective surgical inpatients at moderate or high risk of venous thromboembolism who were receiving either graduated compression stockings and low-dose low-molecular-weight heparin (standard care) or low-dose low-molecular-weight heparin alone (intervention). DESIGN:This was a pragmatic, multicentre, prospective, non-inferiority, randomised controlled trial. SETTING:This took place in secondary care NHS hospitals in the UK. PARTICIPANTS:Patients aged ≥ 18 years who were assessed to be at moderate or high risk of venous thromboembolism according to the NHS England venous thromboembolism risk assessment tool (or the trust equivalent based on this form) and who were not contraindicated to low-molecular-weight heparin or graduated compression stockings were deemed eligible to take part. INTERVENTIONS:Participants were randomised 1 : 1 to either low-molecular-weight heparin or low-molecular-weight heparin and graduated compression stockings. MAIN OUTCOME MEASURES:The primary outcome measure was venous thromboembolism up to 90 days after surgery. A combined end point of duplex ultrasound-proven new lower-limb deep-vein thrombosis (symptomatic or asymptomatic) plus imaging-confirmed symptomatic pulmonary embolism. Secondary outcomes included quality of life, compliance with graduated compression stockings and low-molecular-weight heparin during admission, and all-cause mortality. RESULTS:A total of 1905 participants were randomised and 1858 were included in the intention-to-treat analysis. A primary outcome event occurred in 16 out of 937 (1.7%) patients in the low-molecular-weight heparin-alone arm compared with 13 out of 921 (1.4%) patients in the low-molecular-weight heparin plus graduated compression stockings arm. The risk difference between low-molecular-weight heparin and low-molecular-weight heparin plus graduated compression stockings was 0.30% (95% confidence interval -0.65% to 1.26%). As the 95% confidence interval did not cross the non-inferiority margin of 3.5% (p < 0.001 for non-inferiority), the results indicate that non-inferiority of low-molecular-weight heparin alone was shown. LIMITATIONS:In total, 13% of patients did not receive a duplex ultrasound scan that could have detected further asymptomatic deep-vein thrombosis. However, missing scans were balanced between both trial arms. The subpopulation of those aged ≥ 65 years assessed as being at a moderate risk of venous thromboembolism was under-represented in the study; however, this reflects that this group is under-represented in the general population. CONCLUSIONS:For elective surgical patients at moderate or high risk of venous thromboembolism, administration of pharmaco-thromboprophylaxis alone is non-inferior to a combination of pharmaco-thromboprophylaxis and graduated compression stockings. These findings indicate that graduated compression stockings may be unnecessary for most elective surgical patients. FUTURE WORK:Further studies are required to evaluate whether or not adjuvant graduated compression stockings have a role in patients receiving extended thromboprophylaxis, beyond the period of hospital admission, following elective surgery or in patients undergoing emergency surgical procedures. TRIAL REGISTRATION:Current Controlled Trials ISRCTN13911492. FUNDING:This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 69. See the NIHR Journals Library website for further project information.

Background: Coronavirus disease-2019 (COVID-19) poses a risk for health care workers necessitating modifications to existing medical pathways In particular, managing patients with suspected COVID-19 represents a risk to the delivery of a primary percutaneous coronary intervention (PPCI) pathway where time-dependent revascularization is key Methods: We sought to evaluate the effect of the COVID-19 pandemic on an established ambulance-triggered PPCI program involving 2 high-volume heart attack centers in London, United Kingdom A systematic analysis was performed in patients with ST-segment elevation myocardial infarction undergoing PPCI comparing the COVID-19 pandemic period March 1, 2020, to April 30, 2020, with a control group from the previous year Results: During the study period, admissions through the PPCI pathway decreased by 34% The time from symptoms onset to first call for help (2020: 11 min vs 2019: 12 min;p = 0 90) and from symptom onset to arrival at PPCI center (2020: 183 min vs 2019: 178 min;p = 0 99) were comparable;however, the time from arrival at PPCI center to revascularization decreased (2020: 44 min vs 2019: 53 min;p = 0 0004) In-hospital mortality during the study period was significantly lower (5% vs 15%;p = 0 04) COVID-19–positive patients (n = 8) had higher rates of cardiogenic shock (25%), intensive care unit admission (50%), and inpatient mortality (38%) [Formula presented] Conclusion: Our data show that the modifications to the existing PPCI pathway were not associated with treatment delay or adverse outcome The reduction in ST-segment elevation myocardial infarction presentations raises concern that patients may not be seeking appropriate medical attention for chest pain Importantly, we demonstrate that PPCI can be delivered safely and efficiently during the COVID-19 pandemic Categories: OTHER: COVID-19

AbstractObjectivesTo investigate whether the use of graduated compression stockings (GCS) offers any adjuvant benefit when pharmaco-thromboprophylaxis is used for venous thromboembolism prophylaxis in patients undergoing elective surgery.DesignOpen, multicentre, randomised, controlled, non-inferiority trial.SettingSeven National Health Service tertiary hospitals in the United Kingdom.Participants1905 elective surgical inpatients (≥18 years) assessed as being at moderate or high risk of venous thromboembolism were eligible and consented to participate.InterventionParticipants were randomly assigned (1:1) to receive low molecular weight heparin (LMWH) pharmaco-thromboprophylaxis alone or LMWH pharmaco-thromboprophylaxis and GCS.Outcome measuresThe primary outcome was imaging confirmed lower limb deep vein thrombosis with or without symptoms, or pulmonary embolism with symptoms within 90 days of surgery. Secondary outcome measures were quality of life, compliance with stockings and LMWH, lower limb complications related to GCS, bleeding complications, adverse reactions to LMWH, and all cause mortality.ResultsBetween May 2016 and January 2019, 1905 participants were randomised. 1858 were included in the intention to treat analysis (17 were identified as ineligible after randomisation and 30 did not undergo surgery). A primary outcome event occurred in 16 of 937 (1.7%) patients in the LMWH alone group compared with 13 of 921 (1.4%) in the LMWH and GCS group. The risk difference between the two groups was 0.30% (95% confidence interval −0.65% to 1.26%). Because the 95% confidence interval did not cross the non-inferiority margin of 3.5% (P<0.001 for non-inferiority), LMWH alone was confirmed to be non-inferior.ConclusionsFor patients who have elective surgery and are at moderate or high risk of venous thromboembolism, administration of pharmaco-thromboprophylaxis alone is non-inferior to a combination of pharmaco-thromboprophylaxis and GCS. These findings indicate that GCS might be unnecessary in most patients undergoing elective surgery.Trial registrationISRCTN13911492.

Background: There are no data on how fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are associated with the placebo-controlled efficacy of percutaneous coronary intervention (PCI) in stable single-vessel coronary artery disease. Methods: We report the association between prerandomization invasive physiology within ORBITA (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina), a placebo-controlled trial of patients who have stable angina with angiographically severe single-vessel coronary disease clinically eligible for PCI. Patients underwent prerandomization research FFR and iFR assessment. The operator was blinded to these values. Assessment of response variables, treadmill exercise time, stress echocardiography score, symptom frequency, and angina severity were performed at prerandomization and blinded follow-up. Effects were calculated by analysis of covariance. The ability of FFR and iFR to predict placebo-controlled changes in response variables was tested by using regression modeling. Results: Invasive physiology data were available in 196 patients (103 PCI and 93 placebo). At prerandomization, the majority had Canadian Cardiovascular Society class II or III symptoms (150/196, 76.5%). Mean FFR and iFR were 0.69±0.16 and 0.76±0.22, respectively; 97% had ≥1 positive ischemia tests. The estimated effect of PCI on between-arm prerandomization-adjusted total exercise time was 20.7 s (95% confidence interval [CI], –4.0 to 45.5; P =0.100) with no interaction of FFR ( P interaction =0.318) or iFR ( P interaction =0.523). PCI improved stress echocardiography score more than placebo (1.07 segment units; 95% CI, 0.70–1.44; P <0.00001). The placebo-controlled effect of PCI on stress echocardiography score increased progressively with decreasing FFR ( P interaction <0.00001) and decreasing iFR ( P interaction <0.00001). PCI did not improve angina frequency score significantly more than placebo (odds ratio, 1.64; 95% CI, 0.96–2.80; P =0.072) with no detectable evidence of interaction with FFR ( P interaction =0.849) or iFR ( P interaction =0.783). However, PCI resulted in more patient-reported freedom from angina than placebo (49.5% versus 31.5%; odds ratio, 2.47; 95% CI, 1.30–4.72; P =0.006) but neither FFR ( P interaction =0.693) nor iFR ( P interaction =0.761) modified this effect. Conclusions: In patients with stable angina and severe single-vessel disease, the blinded effect of PCI was more clearly seen by stress echocardiography score and freedom from angina than change in treadmill exercise time. Moreover, the lower the FFR or iFR, the greater the magnitude of stress echocardiographic improvement caused by PCI. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02062593.

Background Symptomatic relief is the primary goal of percutaneous coronary intervention (PCI) in stable angina and is commonly observed clinically. However, there is no evidence from blinded, placebo-controlled randomised trials to show its efficacy. Methods ORBITA is a blinded, multicentre randomised trial of PCI versus a placebo procedure for angina relief that was done at five study sites in the UK. We enrolled patients with severe (>= 70%) single-vessel stenoses. After enrolment, patients received 6 weeks of medication optimisation. Patients then had pre-randomisation assessments with cardiopulmonary exercise testing, symptom questionnaires, and dobutamine stress echocardiography. Patients were randomised 1: 1 to undergo PCI or a placebo procedure by use of an automated online randomisation tool. After 6 weeks of follow-up, the assessments done before randomisation were repeated at the final assessment. The primary endpoint was difference in exercise time increment between groups. All analyses were based on the intention-to-treat principle and the study population contained all participants who underwent randomisation. Findings ORBITA enrolled 230 patients with ischaemic symptoms. After the medication optimisation phase and between Jan 6, 2014, and Aug 11, 2017, 200 patients underwent randomisation, with 105 patients assigned PCI and 95 assigned the placebo procedure. Lesions had mean area stenosis of 84.4% (SD 10.2), fractional flow reserve of 0.69 (0.16), and instantaneous wave-free ratio of 0.76 (0.22). There was no significant difference in the primary endpoint of exercise time increment between groups (PCI minus placebo 16.6 s, 95% CI -8.9 to 42.0, p= 0.200). There were no deaths. Serious adverse events included four pressure-wire related complications in the placebo group, which required PCI, and five major bleeding events, including two in the PCI group and three in the placebo group. Interpretation In patients with medically treated angina and severe coronary stenosis, PCI did not increase exercise time by more than the effect of a placebo procedure. The efficacy of invasive procedures can be assessed with a placebo control, as is standard for pharmacotherapy.

Introduction: Significant obesity is an increasing co-morbidity in pulmonary hypertension (PH). We note many patients with echo features of pre-capillary PH (PrePH) who were being classified as post-capillary PH (PostPH), due to elevated pulmonary wedge pressure (PWP). We wished to assess the impact of intrathoracic pressure (ITP) measurements on haemodynamics during artificial alterations of ITP in obese patients and on classification. Methods: Obese individuals underwent invasive cardiac cath and intra-oesophageal pressure (IOP) measurements. Haemodynamics were measured during end-expiration, Valsalva and external compression of the abdomen. Fluid challenge was administered in selected patients. Results: 17 patients underwent investigation between Jan ‘13 and Dec ’16. There was a direct 1:1 linear relationship between ITP, as assessed by IOP, and wedge pressure (PWP) (Fig 1A). There was a tight relationship between IOB and PWP during manoeuvres (Valsalva, 1B; external compression, 1C). Following fluid, PWP rose by 4 mmHg. 14/17 patients were classified as PostPH, but following correction for expected ITP (4mmHg), only 3/17 were classified as PostPH (1D). Conclusions: ITP has a 1:1 relationship on PWP. We show that this may frequently result in misclassification of patients as PostPH who have echo features of PrePH and whose PWP does not change significant with fluid challenge.

Aortic valve stenosis occurs 10-20 years earlier in patients on dialysis compared with the general population. This is likely related to the exposure of the valve to a milieu that predisposes to calcification as well as increased shear stress across the valve. Objective assessment of stenosis severity is largely made using echocardiography though accurate interpretation requires an understanding of the potential pitfalls of the technique and the influence of cardiac output upon the gradient measured across the valve. Timing of valve replacement in severe aortic stenosis is predominantly guided by exercise-induced symptoms (breathlessness, chest pain and [pre] syncope), which are often difficult to assess in the dialysis population who may have limited exercise capacity and symptoms due to renal failure and other comorbidities. Finally, treatment of aortic stenosis remains a constantly evolving area with advances in both conventional surgery and percutaneous techniques.

Coronary guidewire fracture or entrapment is a recognized complication of percutaneous coronary intervention that can result in abrupt vessel closure, thrombosis, or stent deformation. Developments in pressure-wire (PW) design have enabled their use for coronary intervention. We describe two cases where the pressure sensor became trapped against stent struts during PW removal.

Background Patients with ST-elevation myocardial infarction commonly have multi-vessel disease. After treating the culprit, the optimal strategy for residual disease is unknown. Large observational studies suggest deferring treatment of residual disease, but smaller randomised controlled trials (RCTs) suggest multi-vessel primary percutaneous coronary intervention (MV-PPCI) is safe. We examine if allocation bias of high-risk patients could explain conflicting results between observational studies and RCTs. Methods A meta-analysis of registries comparing culprit-only PPCI to MV-PPCI was performed. A meta-regression was performed to determine if allocation bias of high-risk patients could explain differences in outcomes between therapies. Results 47,717 patients (19 studies) were eligible. MV-PPCI had higher mortality than culprit-only PPCI (OR 1.59, 95% CI 1.12 to 2.24, p = 0.03). Higher risk patients were more likely to be allocated to MV-PPCI (OR 1.45, 95% CI 1.18 to 1.78, p = 0.0005). When this was accounted for, there was no difference in mortality (OR 0.99, 95% CI 0.69 to 1.41, p = 0.94). Discussion Clinicians preferentially allocate higher-risk patients to MV-PPCI at the time of STEMI. When this is accounted for, these large observational studies in ‘real world’ patients support the conclusion of the smaller RCTs in the field: MV-PPCI has equivalent mortality to a culprit-only approach.

Background Thrombus aspiration is a mechanistically logical adjunct in primary angioplasty for acute myocardial infarction. Individual randomised controlled trials (RCTs) have not shown a consensus of mortality reduction and there are concerns about stroke. We perform a meta-analysis of all available RCT data on thrombus aspiration, including the large, recently published TOTAL trial. Method and results A meta-analysis of RCTs of thrombus aspiration, including the recent TOTAL data was performed. At 30 days (11 trials; 20,192 patients) there was a marginally non-significant reduction in all cause-mortality with thrombus aspiration (OR 0.844, 95% CI 0.710–1.003, p = 0.05). The longer-term follow-up data (13 trials; 20,142 patients) was similarly non-significant (OR 0.89, 95% CI 0.78–1.01, p = 0.08). At both 30 days and longer-term follow-up, there was a statistically significant increase in stroke with thrombus aspiration (OR 1.56, 95% CI 1.05 to 2.32, p = 0.03, and OR 1.94, 95% CI 1.24 to 3.04, p = 0.04 respectively). Conclusions The point estimates in the meta-analyses suggest that thrombus aspiration may prevent four deaths per thousand at the cost of two strokes per thousand. Although this may initially sound favourable for the procedure, the confidence interval for mortality is still wide enough to encompass no effect, while that of stroke is not. With mortality now so low in STEMI trials, very large numbers of patients are required to reliably identify a clinically important improvement. The task requires massive multi-centre trials or strategies that minimise per-patient costs by using established outcome-reporting infrastructure to focus on mortality, and perhaps introduce “retrospective consent”.

Objectives To i) demonstrate compliance with the Commissioning for Quality and Innovation for venous thromboembolism risk assessment ii) to undertake root cause analysis of Hospital Acquired Thrombosis and to investigate its impact on quality of care. Design Prospective monitoring of all admissions. Setting Imperial College Healthcare Hospitals, London. Participants All Hospital Provider Spells as defined on the NHS Data Model and Dictionary. Main outcome measures i) Percentage of patients undergoing Venous Thromboembolism Risk Assessment (VTE-RA) at and 24-hours after admission ii) root cause analysis of Hospital Acquired Thrombosis up to 90 days following discharge. Results Over a 48-month cycle 83% were overall VTE-RA assessed with 36% in the first 12 months but with significant improvement to ≥95% between April 2013 and April 2015, achieving compliance target since April 2012 involving a massive 633, 850 Spells over the 4 year period. We undertook root cause analysis of all VTE episodes from April 2013 to March 2014, to ascertain Hospital Acquired Thrombosis (HAT), we analysed 433, 174 inpatient days and found a HAT rate of 1 per 1000 with 23% and 24% for DVTs and PEs potentially avoidable respectively. We further analysed VTE risk stratification (n = 1000) and found 37.0% at high risk, 44.4% at medium risk and 18.6 % at low risk, indicating the need of thromboprophylaxis in 81.4% (high and medium) of whom 33.6% were excluded. Conclusions We achieved 95% RA compliance which has favourably impacted on our daily practice and improved the quality of the clinical care.