key: cord-332944-yqhuh3gc
authors: Wu, Jianhua; Mamas, Mamas; Rashid, Muhammad; Weston, Clive; Hains, Julian; Luescher, Tom; de Belder, Mark A; Deanfield, John E; Gale, Chris P
title: Patient response, treatments and mortality for acute myocardial infarction during the COVID-19 pandemic
date: 2020-07-30
journal: Eur Heart J Qual Care Clin Outcomes
DOI: 10.1093/ehjqcco/qcaa062
sha: 
doc_id: 332944
cord_uid: yqhuh3gc

AIM: COVID-19 might have affected the care and outcomes of hospitalised acute myocardial infarction (AMI). We aimed to determine whether the COVID-19 pandemic changed patient response, hospital treatment and mortality from AMI. METHODS AND RESULTS: Admission were classified as non ST-elevation myocardial infarction (NSTEMI) or STEMI at 99 hospitals in England through live feeding from the Myocardial Ischaemia National Audit Project between 1(st) January, 2019 and 22(nd) May, 2020. Time series plots were estimated using a 7-day simple moving average, adjusted for seasonality. From 23(rd) March, 2020 (UK lockdown) median daily hospitalisations decreased more for NSTEMI (69 to 35; IRR 0.51, 95% CI 0.47-0.54) than STEMI (35 to 25; IRR 0.74, 95% CI 0.69-0.80) to a nadir on 19th April, 2020. During lockdown, patients were younger (mean age 68.7 years vs. 66.9 years), less frequently diabetic (24.6% vs. 28.1%) or had cerebrovascular disease (7.0% vs. 8.6%). STEMI more frequently received primary PCI (81.8% vs 78.8%%), thrombolysis was negligible (0.5% vs. 0.3%), median admission-to-coronary angiography duration for NSTEMI decreased (26.2 vs. 64.0 hours), median duration of hospitalisation decreased (4 to 2 days), secondary prevention pharmacotherapy prescription remained unchanged (each >94.7%). Mortality at 30 days increased for NSTEMI (from 5.4% to 7.5%; OR 1.41, 95% CI 1.08-1.80), but decreased for STEMI (from 10.2% to 7.7%; OR 0.73, 95% CI 0.54-0.97). CONCLUSIONS: During COVID-19, there was a substantial decline in admissions with AMI. Those who presented to hospital were younger, less co-morbid and, for NSTEMI, had higher 30-day mortality.

To reduce the spread of COVID-19, many countries have imposed social containment mandates (so called 'lockdown'), which have resulted in a dramatic decline in local population movement, including emergency attendances at hospital. 1, 2 A number of studies have described a decline in patients with AMI presenting to hospital during this period, and some have suggested that people with symptoms of AMI may be delaying, or not, seeking help from the emergency medical services. [3] [4] [5] [6] [7] [8] Equally, in preparation for, and in response to, the large numbers of patients admitted with probable COVID-19, hospitals have undertaken major reorganisation of their emergency care facilities, including cardiac catheterisation laboratories.

The Chinese Society of Cardiology (CSC) expert consensus statement recommended medical management for the majority of patients presenting with non-ST-elevation myocardial infarction (NSTEMI), and thrombolysis in those presenting with STEMI during the COVID-19 pandemic 9 . In contrast, in North America and Canada it has been proposed that thrombolysis may be used as an alternative to primary percutaneous coronary intervention (PCI) for patients with STEMI where restriction in regular services exist, and in the United Kingdom (UK) that primary PCI should remain the preferred reperfusion strategy. [10] [11] [12] To date, evidence concerning the presentation, care and outcomes from AMI during the COVID-19 pandemic is limited. Information has been derived from single centres or small groups of hospitals or, in studies involving routine health system data, have limited information about prognostic characteristics of patients including details of the baseline risk, co-morbidities, call-for-help times, investigations and guideline-indicated treatments and clinical outcomes, particularly from a national perspective. 13, 14 An understanding of how COVID-19 lockdown may have influenced the health seeking behaviour of patients with AMI as well as the delivery of care by specialist services is important if widespread unintended consequences of the pandemic are to be minimised and preparations made for a potential second wave. To that end, the Chief Scientific Advisor to the Government of the United Kingdom commissioned the National Institute for Cardiovascular Outcomes Research to produce a report to support the response of the Department of Health to the COVID-19 pandemic in the UK. This investigation details the first national insights around the patient and healthcare response to AMI during and in the recovery phase of the COVID-9 pandemic. It will also provide updated time series summary data [When published this word will have a hyperlink to cardiovascularcovid.leeds.ac.uk] to monitor the progress of AMI patient characteristics, care and outcomes during the current COVID19 pandemic in England. within 30 days of their previous admission were excluded, as these were considered potential complications / adverse outcomes of the index event.

Time of symptom onset was defined as the time within 10 minutes of when symptoms began, and if there was a prodrome of intermittent pain, the time of onset of those symptoms that led the patient to call for help. For the derivation of symptom to call-for-help duration, only patients who presented to hospital by ambulance were included. Where admission followed an out of hospital cardiac arrest, with no better information available, the time of the arrest was used for the onset of symptoms. The time of hospital admission was defined as the time of arrival of the ambulance at the hospital, or the accident and emergency department registration time for patients who self-presented to the department.

Baseline characteristics were described using numbers and percentages (with 95% confidence interval (CI) of the percentages) for categorical data and means and standard deviations (SD) or medians and interquartile ranges (IQR) for normal and non-normally distributed continuous variables. For NSTEMI, the probability of in-patient all-cause mortality was calculated using the GRACE risk score, 19 to the nadir in admissions (on 19 th April, 2020), and a recovery phase from 20 th April 2020 to 22 nd May 2020)) using χ 2 -squared and t-tests as appropriate to the distributions of the data.

Visual comparison were also made across other dates including first suspect case (31 st December 2019), China lockdown (23 rd January 2020), World Health Organisation declaration of a public health emergency (30 th January 2020), and Italy lockdown (2 nd March 2020). Counts of daily cases were represented as numbers and unadjusted incidence risk ratios (IRR) with accompanying 95% CIs.

For time series plots, a 7-day simple moving average (indicating the mean number of daily admissions for that day and the preceding 6 days), adjusted for seasonality, was estimated.

To provide an estimate of the impact of the COVID-19 pandemic on admissions and the provision of services, an interrupted times series using a generalized linear model for a Poisson distribution, was fitted and adjusted for seasonality with a harmonic term. A scaling adjustment was made after checking for overdispersion, and autocorrelation examined through partial autocorrelation function.

Patient data were deterministically linked to Civil Registration Deaths Data received up to 21 st June 2020 (final follow-up). 7-day and 30-day unadjusted all-cause mortality were reported with accompanying 95% CIs.

Given the NHS reorganisation aimed at managing COVID-19, 20 there may have been a reduction in clinical coding and data submission to NICOR, which could mimic a reduction in AMI admissions during the period of study. This was mitigated and investigated through a number of steps. Regular notifications were actioned by the British Cardiovascular Society and British Cardiovascular Intervention Society to its members, and from NICOR to each hospitals' MINAP audit clerk emphasising the importance of inputting and submitting contemporary data to NICOR. A survey of each acute NHS hospitals' MINAP data coding as well as tracking of submission status was undertaken, and from this, 99 'rapid-reporting' hospitals who provided weekly uploads of MINAP data were identified and used as primary analysis.

All tests were two-sided, and statistical significance was considered as P<0.05.

Statistical analyses were performed in R version 3.6.3. 

The analytical cohort was drawn from 117,327 patients hospitalised with AMI in Patients hospitalised with AMI during the decline phase were younger (66.87 vs 68.69 years), more frequently male (69.6% vs 67.9%, Table 1 ) and less frequently had diabetes (24.5% vs 28.1%) and cerebrovascular disease (7.1% vs 8.6%, Figure 2 ). They had a lower median creatinine concentrations, less frequently self-presented to hospital without making use of the Emergency Ambulance Service (11.4% vs 20.6%) and less frequently had pulmonary oedema (2.5% vs 4.4%, Table 2, Figure 3 ). The median duration in symptom onset to call-for-help and median duration in call-for-help to hospital arrival times for those arriving by ambulance remained stable (Table 2 ). The proportion of patients followed-up by a cardiologist, receiving in-patient echocardiography and, referred for cardiac rehabilitation remained very high, as did the prescription of secondary prevention pharmacotherapies at the time of discharge from hospital ( Figure 3 ). The median length of hospital stay decreased from 4 to 2 days (Table 2) , and all-cause mortality at 30 days remained stable (Figure 4 ).

During the recovery phase (20 th April to 22 nd May 2020), the patient characteristics of admission with AMI were similar to those of patients in the decline phase (Table 1, Figure 2 ).

However, there was a partial return to pre-lockdown rates for self-presentations with AMI to hospitals (16.7% vs 20.6%) and those with pulmonary oedema (3.7% vs 4.4%, Table 2 ). Whilst the median duration in symptom onset to call-for-help was no different from previous phases, the median duration in call-for-help to hospital arrival times for those arriving by ambulance was shorter by 4 minutes ( Table 2 ). The proportion of patients seen by a cardiologist, receiving in-patient echocardiography, referred for cardiac rehabilitation, and use of secondary prevention therapies each remained very high (Table 2, Figure 3 ). The median length of hospital stay increased to 3 days (Figure 3) , and all-cause mortality at 30 days remained stable ( Figure 4) .

There was a 28.6% decrease to a nadir on 19th April in the number of hospitalisations with STEMI representing a decline in the median daily number of admission from 35 to 25 (IRR 0.74, 95% CI 0.69 to 0.80), and remain stable in recovery phase.

The profiles care and outcomes of patients hospitalised with STEMI were not different from STEMI admitted before lockdown (Supplementary Table 1, Figure 3 ). There was however, a 50% reduction in people self-presenting to hospital in the decline phase (8.2% vs 4.0%), which increased following the nadir in admissions (5.8%). During the recovery phase, the median duration in call-for-help to hospital arrival times decreased by 3 minutes compared with pre-lockdown, and there was an increase in the median in-hospital time to reperfusion by 4 minutes. The use of primary PCI was very high throughout the study period and a small number of STEMI received thrombolysis (0.3%). Over the three time periods, the median length of hospital stay changed from 3 to 2 to 3 days, and crude all-cause mortality at 30 days decreased from 10.2% pre lockdown to 7.7% in the decline phase and increased to 8.3% in the recovery phase (Supplement table 1, Figure 4) . Table 2 ). In the decline phase there was a 3% reduction in the proportion of NSTEMI who received an invasive coronary strategy, and less inter-hospital transfers for such an approach. However, for those who received an invasive strategy, the median time to invasive coronary angiography was reduced from 64 to 26 to 38 hours over the three sequential phases (Supplement Table 2 ). Delays to receipt of an invasive coronary strategy for NSTEMI were less likely to be due to catheter laboratory issues and more likely due to patient co-morbidities. During the recovery phase, the median call to hospital admission duration decreased by 5 minutes. Following lockdown, the proportion seen by a cardiologist, the prescription of secondary prevention medications and referral for cardiac rehabilitation were maintained at high levels, but the use of in-patient echocardiography was lower in the decline phase. Over the three time periods, the median length of hospital stay changed from 5 to 2 to 3 days. All-cause mortality at 30 days increased from 5.4% pre lockdown to 7.5% in the decline phase and decreased to 5.0% in the recovery phase (Figure 4 ).

The onset of social containmenta state of lockdownto reduce the spread of COVID19 infection has been associated with almost 50% decline in hospitalisations with AMI and a significantly higher early mortality for NSTEMI until the nadir of admissions, despite high levels of in-hospital care. Although there was an initial recovery in numbers of admission, this plateaued and until the end of the study period remained at two thirds of the pre-lockdown rate. Given the numbers of AMI not attending hospital (and delays to presentation among those admitted), there is likely to be an increase in AMI-related mortality in the community and increased heart failure admissions in the near future. Whilst the decline in admissions support findings from other data sources, [3] [4] [5] [6] [7] [8] 14 this investigation identifies the nadir and, of concern, a cessation in the recovery trajectory of admissions. It is therefore important that there is ongoing public messaging about seeking urgent medical assistance for AMI.

There was a greater decline in admissions with NSTEMI. It is probable that patients with NSTEMI did not seek medical help because they felt that their symptoms, which are less likely to be chest pain or chest discomfort, 21 did not warrant the risk of potential exposure to the COVID19 infection in hospital. Although we elected to stratify the analyses by date of the UK lockdown, it is apparent that the decline in admissions started earlier in 2020, and international media coverage of death, overwhelmed hospitals, country-specific lockdowns as well as a declaration by the World Health Organisation of a public health emergency led many patients with AMI not to go to hospital for fear of catching the COVID19 infection, being isolated on a ward without visitors, and through wanting to protect hospitals. In addition, the association between increasing age or pre-existing health conditions with poorer outcomes following COVID19 infection was well publicised at the start of the pandemic and many patients with NSTEMI would have looked upon themselves as being at significant risk by virtue of their age and co-morbidity.

Early mortality increased for NSTEMI, but not STEMI. In the UK, the management of STEMI is institutionally operationalised 22 , as was evidenced by maintenance of very high levels of care. The safeguarding of the UK nationwide primary PCI service is in contrast to other international recommendations drawn from preliminary information about over-burdened services due to the additional workload arising from COVID-19 patients and hospital measures imposed to reduce the spread of the infection. 8 For NSTEMI, mortality rates increased in the decline phase, when fewer patients were attending hospital. It is possible that other factors were at play, including a higher co-morbidity burden, more myocardial ischemia and potentially the influence of the COVID19 infection. Moreover, there was a decline in NSTEMI with pulmonary oedema, which suggests that cases with large areas of myocardial ischemia may have died in the community. Although, in-hospital care standards were maintained at a high level, we observed a slightly lower use of an invasive coronary strategy and lower inter-hospital transfer rates for this strategy during the decline phase, suggesting that perhaps more patients were managed medically, who otherwise would have receive an invasive management.

In contrast to other countries, where recommendations about the management of patients with AMI were modified, the UK upheld its processes of care for AMI. This was evidenced in all three phases of the period of this study, where the use of evidence-based care were very high, and increased slightly for antiplatelet pharmacotherapies. What is more, the COVID-19 pandemic has enabled a natural experiment of the NHS AMI services in England indicating that for NSTEMI the duration of time to receive an invasive coronary strategy may be dramatically reduced when the ratio of staff and facilities to patients is increased.

Interrogation of these live data from a national registry of AMI offers the opportunity to prepare for future major health crises. First, it is apparent that, prior to Government directives about social distancing, the public appeared to react to the international crisis as it unfolded through the media. Second, whilst social isolation was recommended for higher risk patients, such patients are also at higher risk of AMI. It is important that the public be reminded during the recovery phase that they should attend hospital in the event of a medical emergencya message delivered by both Government and health representatives early during the UK lockdown. Third, although this investigation was unable to quantify all of the adverse consequences associated with the decline and change in presentation of AMI, there is good evidence from the literature of higher rates of death, stroke and heart failure when patients with AMI do not receive treatment or present late. 23 Finally, a latent excess of AMI-related mortality and morbidity should be expected and health services prepared in advance. 23 Although the strengths of this linked registry are apparent, we acknowledge the study limitations. MINAP does not collect data for all cases of AMI in England 24 and for some hospitals, there is a lag in data uploading. This may have over-estimated the decline in rates of admissions. Nonetheless, we surveyed all acute hospitals in England and encouraged rapid reporting. Linkage to the national death registry enabled accurate censorship dates, but given the short-follow-up time it is possible that the full impact of the COVID19 pandemic on the prognosis of patients admitted with AMI is not apparent.

Nationwide data from England linked to death registration, show that following the UK lockdown due to the COVID19 pandemic there was a halving of admissions with AMI to a nadir at about one month suggesting many patients delayed seeking help from the emergency services. Despite evidence for enduring high levels of specialist hospital care and there was an increase in early deaths for NSTEMI. Given that AMI is common, and that delayed or no treatment for AMI is associated with major cardiovascular and cerebrovascular events, Governments and health systems across the globe should prepare for an excess of AMI-related mortality and morbidity in the near future. The funding organizations for this study had no involvement in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication.

Data availability: The authors do not have authorisation to share the data, but the data can be accessed through NHS Digital upon approval.

Updates of all Figures are available at cardiovascularcovid.leeds.ac.uk All cells represent numbers of cases (%, 95% CI) unless otherwise stated.

Data from 99 National Health Service acute hospitals in England. 

Population flow drives spatio-temporal distribution of COVID-19 in China

COVID-19 pandemic and admission rates for and management of acute coronary syndromes in England

Decline of acute coronary syndrome admissions in Austria since the outbreak of COVID-19: the pandemic response causes cardiac collateral damage

Reduced Rate of Hospital Admissions for ACS during Covid-19 Outbreak in Northern Italy

Reduction in ST-Segment Elevation Cardiac Catheterization Laboratory Activations in the United States

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Impact of Coronavirus Disease 2019 (COVID-19) Outbreak on ST-Segment-Elevation Myocardial Infarction Care in Hong Kong

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Get With The Guidelines-Coronary Artery Disease Advisory Work G, Mission Lifeline P, The American Heart Association's Council On Clinical C, The American Heart Association's Council On Clinical Cardiology's Committee On Acute Cardiac C, General Cardiology C, The American Heart Association's Council On Clinical Cardiology's Committee Interventional Cardiovascular Care C

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Circulation 2020. 13

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Completeness and diagnostic validity of recording acute myocardial infarction events in primary care, hospital care, disease registry, and national mortality records: cohort study

Hyperlipidaemia 12935 (30.9%, 30.5-31.3) 453 (30.5%

all cells represent numbers of cases (%, 95% CI) unless otherwise stated; AMI: acute myocardial infarction

IQR: interquartile range; sd: standard deviation; CABG: coronary artery bypass graft; COPD: chronic obstructive pulmonary disease; PCI: percutaneous coronary intervention

Table Heart rate, beats per min, median

If pre-hospital cardiac arrest: no ROSC or return but died in-hospital 532

Clopidogrel/prasugrel/ticagrelor 34280 (97.5%, 97.4-97.7) 1321 (99.2%

all cells represent numbers of cases (%, 95% CI) unless otherwise stated; AMI: acute myocardial infarction

ROSC: return of spontaneous circulation

ACEi/ARB: angiotensin converting enzyme inhibitor/angiotensin receptor blocker