A trial emulation comparing thromboprophylaxis versus no thromboprophylaxis among ward-based patients with covid-19

209 Figure 1Kaplan-Meier curves displaying cumulative all-cause mortality[Figure omitted. See PDF]Conflict of InterestNo conflicts of interest

The Direct and Indirect Effects of COVID-19 on Acute Coronary Syndromes.

The novel SARS-CoV-2 has directly and indirectly impacted patients with acute coronary syndrome (ACS). The onset of the COVID-19 pandemic correlated with an abrupt decline in hospitalizations with ACS and increased out-of-hospital deaths. Worse outcomes in ACS patients with concomitant COVID-19 have been reported, and acute myocardial injury secondary to SARS-CoV-2 infection is recognized. A rapid adaptation of existing ACS pathways has been required such that overburdened health care systems may manage both a novel contagion and existing illness. As SARS-CoV-2 is now endemic, future research is required to better define the complex interplay of COVID-19 infection and cardiovascular disease.

Modified Thromboelastography for Peri-interventional Assessment of Platelet Function in Cardiology Patients: A Narrative Review.

Viscoelastic testing (VET), such as thromboelastography, can measure whole blood coagulation dynamics in real time and is used across a range of clinical settings, including cardiac surgery, liver transplant, and trauma. The use of modified thromboelastography with platelet function assessment (TEG(R) PlateletMapping(R) Assay) can provide an analysis of platelet contribution to hemostasis, including the contribution of the P2Y12 receptor and thromboxane pathway to platelet function. The TEG PlateletMapping Assay has shown high correlation with the current gold standard test of platelet function, light transmission aggregometry, to measure arachidonic acid and adenosine diphosphate agonist-induced platelet activation. Studies have also shown comparable results with other whole blood platelet function tests. In this review, we explore the clinical applications of modified thromboelastography with platelet function assessment. This includes guiding dual antiplatelet therapy in relation to cardiac procedures, such as percutaneous coronary interventions, transcatheter aortic valve replacement, and left atrial appendage closure. We also explore the developing use of thromboelastography in the emergency care setting of coronavirus disease 2019, which is commonly associated with a hypercoagulable and hypofibrinolytic state. Despite a general lack of high-quality, grade 1 evidence regarding the use of modified thromboelastography with platelet function assessment in these disease areas, the ability of the TEG PlateletMapping Assay to measure global hemostasis and platelet reactivity rapidly and to view and evaluate results at the point of care makes it a promising area for further study for managing patient treatment and optimizing hemostatic therapy.

The Direct and Indirect Effects of COVID-19 on Acute Coronary Syndromes.

The novel SARS-CoV-2 has directly and indirectly impacted patients with acute coronary syndrome (ACS). The onset of the COVID-19 pandemic correlated with an abrupt decline in hospitalizations with ACS and increased out-of-hospital deaths. Worse outcomes in ACS patients with concomitant COVID-19 have been reported, and acute myocardial injury secondary to SARS-CoV-2 infection is recognized. A rapid adaptation of existing ACS pathways has been required such that overburdened health care systems may manage both a novel contagion and existing illness. As SARS-CoV-2 is now endemic, future research is required to better define the complex interplay of COVID-19 infection and cardiovascular disease.

Very early invasive angiography versus standard of care in higher-risk non-ST elevation myocardial infarction: study protocol for the prospective multicentre randomised controlled RAPID N-STEMI trial.

BACKGROUND: There are a paucity of randomised data on the optimal timing of invasive coronary angiography (ICA) in higher-risk patients with non-ST elevation myocardial infarction (N-STEMI). International guideline recommendations for early ICA are primarily based on retrospective subgroup analyses of neutral trials. AIMS: The RAPID N-STEMI trial aims to determine whether very early percutaneous revascularisation improves clinical outcomes as compared with a standard of care strategy in higher-risk N-STEMI patients. METHODS AND ANALYSIS: RAPID N-STEMI is a prospective, multicentre, open-label, randomised-controlled, pragmatic strategy trial. Higher-risk N-STEMI patients, as defined by Global Registry of Acute Coronary Events 2.0 score ≥118, or >90 with at least one additional high-risk feature, were randomised to either: very early ICA±revascularisation or standard of care timing of ICA±revascularisation. The primary outcome is the proportion of participants with at least one of the following events (all-cause mortality, non-fatal myocardial infarction and hospital admission for heart failure) at 12 months. Key secondary outcomes include major bleeding and stroke. A hypothesis generating cardiac magnetic resonance (CMR) substudy will provide mechanistic data on infarct size, myocardial salvage and residual ischaemia post percutaneous coronary intervention. On 7 April 2021, the sponsor discontinued enrolment due to the impact of the COVID-19 pandemic and lower than expected event rates. 425 patients were enrolled, and 61 patients underwent CMR. ETHICS AND DISSEMINATION: The trial has been reviewed and approved by the East of England Cambridge East Research Ethics Committee (18/EE/0222). The study results will be submitted for publication within 6 months of completion. TRIAL REGISTRATION NUMBER: NCT03707314; Pre-results.

Indirect Impact of the COVID-19 Pandemic on Activity and Outcomes of Transcatheter and Surgical Treatment of Aortic Stenosis in England.

[Figure: see text].

International Prospective Registry of Acute Coronary Syndromes in Patients With COVID-19.

BACKGROUND: Published data suggest worse outcomes in acute coronary syndrome (ACS) patients and concurrent coronavirus disease 2019 (COVID-19) infection. Mechanisms remain unclear. OBJECTIVES: The purpose of this study was to report the demographics, angiographic findings, and in-hospital outcomes of COVID-19 ACS patients and compare these with pre-COVID-19 cohorts. METHODS: From March 1, 2020 to July 31, 2020, data from 55 international centers were entered into a prospective, COVID-ACS Registry. Patients were COVID-19 positive (or had a high index of clinical suspicion) and underwent invasive coronary angiography for suspected ACS. Outcomes were in-hospital major cardiovascular events (all-cause mortality, re-myocardial infarction, heart failure, stroke, unplanned revascularization, or stent thrombosis). Results were compared with national pre-COVID-19 databases (MINAP [Myocardial Ischaemia National Audit Project] 2019 and BCIS [British Cardiovascular Intervention Society] 2018 to 2019). RESULTS: In 144 ST-segment elevation myocardial infarction (STEMI) and 121 non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients, symptom-to-admission times were significantly prolonged (COVID-STEMI vs. BCIS: median 339.0 min vs. 173.0 min; p < 0.001; COVID NSTE-ACS vs. MINAP: 417.0 min vs. 295.0 min; p = 0.012). Mortality in COVID-ACS patients was significantly higher than BCIS/MINAP control subjects in both subgroups (COVID-STEMI: 22.9% vs. 5.7%; p < 0.001; COVID NSTE-ACS: 6.6% vs. 1.2%; p < 0.001), which remained following multivariate propensity analysis adjusting for comorbidities (STEMI subgroup odds ratio: 3.33 [95% confidence interval: 2.04 to 5.42]). Cardiogenic shock occurred in 20.1% of COVID-STEMI patients versus 8.7% of BCIS patients (p < 0.001). CONCLUSIONS: In this multicenter international registry, COVID-19-positive ACS patients presented later and had increased in-hospital mortality compared with a pre-COVID-19 ACS population. Excessive rates of and mortality from cardiogenic shock were major contributors to the worse outcomes in COVID-19 positive STEMI patients.

Outcomes following PCI in CABG candidates during the COVID-19 pandemic: The prospective multicentre UK-ReVasc registry.

OBJECTIVES: To describe outcomes following percutaneous coronary intervention (PCI) in patients who would usually have undergone coronary artery bypass grafting (CABG). BACKGROUND: In the United Kingdom, cardiac surgery for coronary artery disease (CAD) was dramatically reduced during the first wave of the COVID-19 pandemic. Many patients with "surgical disease" instead underwent PCI. METHODS: Between 1 March 2020 and 31 July 2020, 215 patients with recognized "surgical" CAD who underwent PCI were enrolled in the prospective UK-ReVasc Registry (ReVR). 30-day major cardiovascular event outcomes were collected. Findings in ReVR patients were directly compared to reference PCI and isolated CABG pre-COVID-19 data from British Cardiovascular Intervention Society (BCIS) and National Cardiac Audit Programme (NCAP) databases. RESULTS: ReVR patients had higher incidence of diabetes (34.4% vs 26.4%, P = .008), multi-vessel disease with left main stem disease (51.4% vs 3.0%, P < .001) and left anterior descending artery involvement (94.8% vs 67.2%, P < .001) compared to BCIS data. SYNTAX Score in ReVR was high (mean 28.0). Increased use of transradial access (93.3% vs 88.6%, P = .03), intracoronary imaging (43.6% vs 14.4%, P < .001) and calcium modification (23.6% vs 3.5%, P < .001) was observed. No difference in in-hospital mortality was demonstrated compared to PCI and CABG data (ReVR 1.4% vs BCIS 0.7%, P = .19; vs NCAP 1.0%, P = .48). Inpatient stay was half compared to CABG (3.0 vs 6.0 days). Low-event rates in ReVR were maintained to 30-day follow-up. CONCLUSIONS: PCI undertaken using contemporary techniques produces excellent short-term results in patients who would be otherwise CABG candidates. Longer-term follow-up is essential to determine whether these outcomes are maintained over time.

'Valve for Life': tackling the deficit in transcatheter treatment of heart valve disease in the UK.

Transcatheter aortic valve implantation (TAVI) is a proven treatment for life-threatening aortic valve disease, predominantly severe aortic stenosis. However, even among developed nations, access to TAVI is not uniform. The Valve for Life initiative was launched by the European Association of Percutaneous Cardiovascular Interventions in 2015 with the objective of improving access to transcatheter valve interventions across Europe. The UK has been identified as a country with low penetration of these procedures and has been selected as the fourth nation to be included in the initiative. Specifically, the number of TAVI procedures carried out in the UK is significantly lower than almost all other European nations. Furthermore, there is substantial geographical inequity in access to TAVI within the UK. As a consequence of this underprovision, waiting times for TAVI are long, and mortality among those waiting intervention is significant. This article reviews these issues, reports new data on access to TAVI in the UK and presents the proposals of the UK Valve for Life team to address the current problems in association with the British Cardiovascular Intervention Society.

Revascularisation strategies in patients with significant left main coronary disease during the COVID-19 pandemic.

BACKGROUND: There are limited data on the impact of the COVID-19 pandemic on left main (LM) coronary revascularisation activity, choice of revascularisation strategy, and post-procedural outcomes. METHODS: All patients with LM disease (≥50% stenosis) undergoing coronary revascularisation in England between January 1, 2017 and August 19, 2020 were included (n = 22,235), stratified by time-period (pre-COVID: 01/01/2017-29/2/2020; COVID: 1/3/2020-19/8/2020) and revascularisation strategy (percutaneous coronary intervention (PCI) vs. coronary artery bypass grafting (CABG). Logistic regression models were performed to examine odds ratio (OR) of 1) receipt of CABG (vs. PCI) and 2) in-hospital and 30-day postprocedural mortality, in the COVID-19 period (vs. pre-COVID). RESULTS: There was a decline of 1,354 LM revascularisation procedures between March 1, 2020 and July 31, 2020 compared with previous years' (2017-2019) averages (-48.8%). An increased utilization of PCI over CABG was observed in the COVID period (receipt of CABG vs. PCI: OR 0.46 [0.39, 0.53] compared with 2017), consistent across all age groups. No difference in adjusted in-hospital or 30-day mortality was observed between pre-COVID and COVID periods for both PCI (odds ratio (OR): 0.72 [0.51. 1.02] and 0.83 [0.62, 1.11], respectively) and CABG (OR 0.98 [0.45, 2.14] and 1.51 [0.77, 2.98], respectively) groups. CONCLUSION: LM revascularisation activity has significantly declined during the COVID period, with a shift towards PCI as the preferred strategy. Postprocedural mortality within each revascularisation group was similar in the pre-COVID and COVID periods, reflecting maintenance in quality of outcomes during the pandemic. Future measures are required to safely restore LM revascularisation activity to pre-COVID levels.

Racial differences in management and outcomes of acute myocardial infarction during COVID-19 pandemic.

OBJECTIVE: There are concerns that healthcare and outcomes of black, Asian and minority ethnic (BAME) communities are disproportionately impacted by the COVID-19 pandemic. We investigated admission rates, treatment and mortality of BAME with acute myocardial infarction (AMI) during COVID-19. METHODS: Using multisource national healthcare records, patients hospitalised with AMI in England during 1 February-27 May 2020 were included in the COVID-19 group, whereas patients admitted during the same period in the previous three consecutive years were included in a pre-COVID-19 group. Multilevel hierarchical regression analyses were used to quantify the changes in-hospital and 7-day mortality in BAME compared with whites. RESULTS: Of 73 746 patients, higher proportions of BAME patients (16.7% vs 10.1%) were hospitalised with AMI during the COVID-19 period compared with pre-COVID-19. BAME patients admitted during the COVID-19 period were younger, male and likely to present with ST-elevation acute myocardial infarction. COVID-19 BAME group admitted with non-ST-elevation acute myocardial infarction less frequently received coronary angiography (86.1% vs 90.0%, p<0.001) and had a longer median delay to reperfusion (4.1 hours vs 3.7 hours, p<0.001) compared with whites. BAME had higher in-hospital (OR 1.68, 95% CI 1.27 to 2.28) and 7-day mortality (OR 1.81 95% CI 1.31 to 2.19) during COVID-19 compared with pre-COVID-19 period. CONCLUSION: In this multisource linked cohort study, compared with whites, BAME patients had proportionally higher hospitalisation rates with AMI, less frequently received guidelines indicated care and had higher early mortality during COVID-19 period compared with pre-COVID-19 period. There is a need to develop clinical pathways to achieve equity in the management of these vulnerable populations.

Is the true clinical value of high-sensitivity troponins as a biomarker of risk? The concept that detection of high-sensitivity troponin 'never means nothing'.

INTRODUCTION: High-sensitivity troponin (hs-cTn) assays are central to the diagnosis of myocardial infarction (MI). Their increased sensitivity has facilitated rapid pathways for the exclusion of MI. However, hs-cTn is now more readily detectable in patients without symptoms typical of MI, in whom a degree of myocardial injury is assumed. Recently, the practice of using the 99th centile of hs-cTn as a working 'upper reference limit' has been challenged. There is increasing evidence that hs-cTn may provide useful prognostic information, regardless of any suspicion of MI, and as such these assays may have potential as a general biomarker for mortality. This raises the concept that detection of hs-cTn 'never means nothing.' AREAS COVERED: In this review, we will evaluate the evidence for the use of hs-cTn assays outside their common clinical indication to rule out or diagnose acute MI. EXPERT OPINION: The data presented suggest that hs-cTn testing may in the future have a generalized role as a biomarker of mortality risk and may be used less as a test for ruling in acute MI, but will remain a frontline test to exclude that diagnosis in ED. Further, the data suggest that the detection of hs-cTn 'never means nothing.'

Outcomes of COVID-19-positive acute coronary syndrome patients: A multisource electronic healthcare records study from England.

BACKGROUND: Patients with underlying cardiovascular disease and coronavirus disease 2019 (COVID-19) infection are at increased risk of morbidity and mortality. OBJECTIVES: This study was designed to characterize the presenting profile and outcomes of patients hospitalized with acute coronary syndrome (ACS) and COVID-19 infection. METHODS: This observational cohort study was conducted using multisource data from all acute NHS hospitals in England. All consecutive patients hospitalized with diagnosis of ACS with or without COVID-19 infection between 1 March and 31 May 2020 were included. The primary outcome was in-hospital and 30-day mortality. RESULTS: A total of 12 958 patients were hospitalized with ACS during the study period, of which 517 (4.0%) were COVID-19-positive and were more likely to present with non-ST-elevation acute myocardial infarction. The COVID-19 ACS group were generally older, Black Asian and Minority ethnicity, more comorbid and had unfavourable presenting clinical characteristics such as elevated cardiac troponin, pulmonary oedema, cardiogenic shock and poor left ventricular systolic function compared with the non-COVID-19 ACS group. They were less likely to receive an invasive coronary angiography (67.7% vs 81.0%), percutaneous coronary intervention (PCI) (30.2% vs 53.9%) and dual antiplatelet medication (76.3% vs 88.0%). After adjusting for all the baseline differences, patients with COVID-19 ACS had higher in-hospital (adjusted odds ratio (aOR): 3.27; 95% confidence interval (CI): 2.41-4.42) and 30-day mortality (aOR: 6.53; 95% CI: 5.1-8.36) compared to patients with the non-COVID-19 ACS. CONCLUSION: COVID-19 infection was present in 4% of patients hospitalized with an ACS in England and is associated with lower rates of guideline-recommended treatment and significant mortality hazard.

In-Hospital and 30-Day Mortality After Percutaneous Coronary Intervention in England in the Pre-COVID and COVID Eras.

BACKGROUND: Public reporting of percutaneous coronary intervention (PCI) outcomes is a performance metric and a requirement in many healthcare systems. There are inconsistent data on the causes of death after PCI, and the proportion of these deaths that are attributable to cardiac causes. METHODS: All patients undergoing PCI in England between January 1, 2017 and May 10, 2020 (n = 273,141) were retrospectively analyzed according to their outcome from the date of PCI: no death, in-hospital death, postdischarge death, and total 30-day death. The present study examined short-term primary causes of death after PCI in a national cohort before and during COVID-19. RESULTS: The overall rates of in-hospital and 30-day death were 1.9% and 2.8%, respectively. The rate of 30-day death declined between 2017 (2.9%) and February 2020 (2.5%), mainly due to lower in-hospital death (2.1% vs 1.5%), before rising again from March 1, 2020 (3.2%) due to higher rates of postdischarge mortality. Only 59.6% of 30-day deaths were due to cardiac causes, with the most common causes being acute coronary syndrome, cardiogenic shock, and heart failure, and this persisted throughout the study period. In the 30-day death group, 10.4% after March 1, 2020 were due to confirmed COVID-19. CONCLUSIONS: In this nationwide study, we show that 40% of 30-day deaths are due to non-cardiac causes. Non-cardiac deaths have increased even more from the start of the COVID-19 pandemic, with 1 in 10 deaths from March 2020 being COVID-19 related. These findings raise a question of whether public reporting of PCI outcomes should be cause specific.

Impact of the COVID-19 Pandemic on Percutaneous Coronary Intervention in England: Insights From the British Cardiovascular Intervention Society PCI Database Cohort.

BACKGROUND: The objective of the study was to evaluate changes in percutaneous coronary intervention (PCI) practice in England by analyzing procedural numbers, changes in the clinical presentation, and characteristics of patients and their clinical outcomes during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: We conducted a retrospective cohort study of all patients who underwent PCI in England between January 2017 and April 2020 in the British Cardiovascular Intervention Society database. RESULTS: Forty-four hospitals reported PCI procedures for 126 491 patients. There were ≈700 procedures performed each week before the lockdown. After the March 23, 2020 lockdown (11th/12th week in 2020), there was a 49% fall in the number of PCI procedures after the 12th week in 2020. The decrease was greatest in PCI procedures performed for stable angina (66%), followed by non-ST-segment-elevation myocardial infarction (45%), and ST-segment-elevation myocardial infarction (33%). Patients after the lockdown were younger (64.5 versus 65.5 years, P<0.001) and less likely to have diabetes (20.4% versus 24.6%, P<0.001), hypertension (52.0% versus 56.8%, P=0.001), previous myocardial infarction (23.5% versus 26.7%, P=0.008), previous PCI (24.3% versus 28.3%, P=0.001), or previous coronary artery bypass graft (4.6% versus 7.2%, P<0.001) compared with before the lockdown. CONCLUSIONS: The lockdown in England has resulted in a significant decline in PCI procedures. Fewer patients underwent PCI for stable angina. This enabled greater capacity for urgent and emergency cases, and a reduced length of stay was seen for such patients. Significant changes in the characteristics of patients towards a lower risk phenotype were observed, particularly for non-ST-segment-elevation myocardial infarction, reflecting a more conservative approach to this cohort.

Impact of COVID-19 on cardiac procedure activity in England and associated 30-day mortality.

AIMS: Limited data exist on the impact of COVID-19 on national changes in cardiac procedure activity, including patient characteristics and clinical outcomes before and during the COVID-19 pandemic. METHODS AND RESULTS: All major cardiac procedures (n = 374 899) performed between 1 January and 31 May for the years 2018, 2019, and 2020 were analysed, stratified by procedure type and time-period (pre-COVID: January-May 2018 and 2019 and January-February 2020 and COVID: March-May 2020). Multivariable logistic regression was performed to examine the odds ratio (OR) of 30-day mortality for procedures performed in the COVID period. Overall, there was a deficit of 45 501 procedures during the COVID period compared to the monthly averages (March-May) in 2018-2019. Cardiac catheterization and device implantations were the most affected in terms of numbers (n = 19 637 and n = 10 453), whereas surgical procedures such as mitral valve replacement, other valve replacement/repair, atrioseptal defect/ventriculoseptal defect repair, and coronary artery bypass grafting were the most affected as a relative percentage difference (Δ) to previous years' averages. Transcatheter aortic valve replacement was the least affected (Δ -10.6%). No difference in 30-day mortality was observed between pre-COVID and COVID time-periods for all cardiac procedures except cardiac catheterization [OR 1.25 95% confidence interval (CI) 1.07-1.47, P = 0.006] and cardiac device implantation (OR 1.35 95% CI 1.15-1.58, P < 0.001). CONCLUSION: Cardiac procedural activity has significantly declined across England during the COVID-19 pandemic, with a deficit in excess of 45 000 procedures, without an increase in risk of mortality for most cardiac procedures performed during the pandemic. Major restructuring of cardiac services is necessary to deal with this deficit, which would inevitably impact long-term morbidity and mortality.

Impact of COVID-19 on percutaneous coronary intervention for ST-elevation myocardial infarction.

BACKGROUND: The objective of the study was to identify any changes in primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) in England by analysing procedural numbers, clinical characteristics and patient outcomes during the COVID-19 pandemic. METHODS: We conducted a retrospective cohort study of patients who underwent PCI in England between January 2017 and April 2020 in the British Cardiovascular Intervention Society-National Institute of Cardiovascular Outcomes Research database. Analysis was restricted to 44 hospitals that reported contemporaneous activity on PCI. Only patients with primary PCI for STEMI were included in the analysis. RESULTS: A total of 34 127 patients with STEMI (primary PCI 33 938, facilitated PCI 108, rescue PCI 81) were included in the study. There was a decline in the number of procedures by 43% (n=497) in April 2020 compared with the average monthly procedures between 2017 and 2019 (n=865). For all patients, the median time from symptom to hospital showed increased after the lockdown (150 (99-270) vs 135 (89-250) min, p=0.004) and a longer door-to-balloon time after the lockdown (48 (21-112) vs 37 (16-94) min, p<0.001). The in-hospital mortality rate was 4.8% before the lockdown and 3.5% after the lockdown (p=0.12). Following adjustment for baseline characteristics, no differences were observed for in-hospital death (OR 0.87, 95% CI 0.45 to 1.68, p=0.67) and major adverse cardiovascular events (OR 0.71, 95% CI 0.39 to 1.32, p=0.28). CONCLUSIONS: Following the lockdown in England, we observed a decline in primary PCI procedures for STEMI and increases in overall symptom-to-hospital and door-to-balloon time for patients with STEMI. Restructuring health services during COVID-19 has not adversely influenced in-hospital outcomes.