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COVID-19 is the first major pandemic the modern world has faced since the Spanish influenza pandemic of 1918 and has had a profound impact on all aspects of society.1 Governments worldwide have established emergency plans to help tackle and reduce the rapid spread of the infection, with social isolation being implemented by most to varying degrees. Healthcare systems are facing unprecedented challenges and real-time restructuring and, as expected, this has resulted in an excess mortality worldwide.1 The first fatality with COVID-19 in the UK was reported on 2 March 2020, with subsequent nationwide lockdown on 23 March 2020. Public health concerns have focused on the increases in mortality directly attributable to COVID-19 and the indirect consequences of the pandemic on the healthcare system’s ability to manage non-COVID-19 related life-threatening illnesses due to diversion of established healthcare resources and capacity. This is a complex situation and there is also some overlap in direct and indirect causes of mortality. For example, as with other viral and respiratory illnesses, there is the potential for COVID-19 to trigger other fatal events that may not have otherwise happened. For example, it is well described that there is a 44% increase in myocardial infarction in the weeks after respiratory tract infections.2 There is also the concern that patients themselves may be reluctant to seek attention because of concerns regarding contracting COVID-19 in the hospital or burdening an overstretched healthcare system that is trying to cope with seriously ill patients with COVID-19. In the current issue of Heart, Wu and colleagues have assessed the impact of COVID-19 on both the population incidence and location of acute cardiovascular mortality that sheds light on some of these potential causes of excess cardiovascular mortality.3
The first question is whether all the excess deaths are caused directly by COVID-19. Death from COVID-19 is usually directly attributable to respiratory failure.1 However, there has been concern about the short-term and long-term cardiovascular consequences and the impact on acute cardiovascular mortality. The analysis by Wu and colleagues clearly shows an excess cardiovascular mortality during the first wave of the pandemic in England and Wales.3 They report that following the first COVID-19-related death on 2 March 2020, there were 28 969 acute cardiovascular deaths and an excess acute cardiovascular mortality of 2085 (a proportional increase of 8%) compared with the expected historical average in the same time period of the year. According to the coding and registrations, these excess deaths were seen in both those with or without COVID-19, suggesting that mortality was increased by both the direct and indirect consequences of the COVID-19 pandemic.
The second question is whether COVID-19 has triggered cardiovascular events and mortality. Our understanding of the clinical manifestations of COVID-19 has grown substantially since the beginning of the pandemic, and we know that increasing age, certain ethnic groups and a comorbid state, such as diabetes mellitus and hypertension, have a negative impact on an individual’s susceptibility to, and prognosis following, infection. Myocardial injury is associated with a much worse outcome and a marked increase in mortality in patients with COVID-19, with a number of mechanisms being postulated.4 Direct myocardial infiltration of the viral pathogen causing myocarditis resulting in myocyte injury or death and heart failure has been described but accounts for only a minority of cases.5 This alone cannot account for the excess in cardiovascular deaths. Indirect mechanisms include myocardial injury due to systemic inflammatory response, increased thrombogenicity leading to systemic and atherothrombotic events, and increased cardiac strain and type II myocardial infarction due to myocardial oxygen supply and demand imbalance.5 The excess of cardiovascular mortality was predominantly seen in pulmonary embolism and atherothrombotic events and was not observed in other cardiovascular conditions such as aortic dissection and endocarditis. This is likely accounted for by the prothrombotic, endothelial and inflammatory effects of COVID-19. Thus, there is a clear link of COVID-19 causing excess cardiovascular disease and events.
The third and perhaps most interesting question is whether there was an increase of cardiovascular death across all areas of society, suggesting a generalised increase in cardiovascular mortality or whether there was evidence of avoidance of using healthcare services where mortality rates would differ across society. This is a key question and was, in part, addressed by the analysis of Wu and colleagues.3 Throughout Europe, we have seen a marked decline in acute unscheduled hospital admissions with acute coronary syndrome, heart failure, cardiac arrhythmias and stroke during the early stages of the pandemic, with a similar pattern seen in the UK.6 7 This has raised questions of whether the reduction in admission is the result of people not presenting due to concerns of contracting COVID-19 in the hospital, wanting to avoid burdening the NHS during the pandemic or reduced referrals from primary to tertiary services. Whatever the reason, this has led to concern that patients are presenting too late or not presenting at all, with recent studies demonstrating an increase in out-of-hospital cardiac arrests.8 However, to date, there has been no assessment of the effect of COVID-19 on cardiovascular death. Wu and colleagues demonstrate that absolute cardiovascular mortality decreased in the hospital but increased in the community, suggesting that patients were avoiding calling healthcare services or admission to the hospital. Consistent with this, the most frequent cause of excess acute cardiovascular death in people’s homes was acute coronary syndrome, with the greatest increase seen in cardiac arrest. Conversely, in the hospital, the most common cause was pulmonary embolism, with the greatest increase seen in cardiogenic shock, ventricular tachycardia and ventricular fibrillation. This would suggest either sicker patients with more marked symptoms continued to present or to be referred to the hospital, or those who did present, presented later in their illness where the opportunity to intervene and to improve outcomes was less. This is perhaps the most troubling part of these findings from the pandemic because we have effective treatments for these conditions which are life-saving, and much of the excess cardiovascular deaths might have been avoided.
Limitations of the data do need to be, and have been, acknowledged. The proportions of deaths attributed to COVID-19 have a number of problems and likely represent the lack of community testing: many patients will have had unrecognised and undiagnosed COVID-19. It is also impossible to know whether COVID-19 is the direct cause of acute cardiovascular death or whether patients who were confirmed or suspected of having COVID-19 also had other risk factors for the cause of cardiovascular death. Moreover, many such events could have occurred during any viral pandemic, such as with influenza,2 and this is particularly pertinent to care homes and hospices. Indeed, one could argue that this cohort is prone to these conditions with and without superimposed COVID-19 infection, and it will be important to consider whether a so-called ‘harvesting effect’ may be seen as the pandemic lifts. Has COVID-19 brought forward deaths that would otherwise have happened in the next 6–12 months? Hopefully, Wu and colleagues will revisit their analysis in years to come.
Overall, the authors have provided an important and thought-provoking insight into the relationship between COVID-19 and acute cardiovascular death during the pandemic and more importantly have highlighted the shift in pattern of mortality towards increased community deaths. Whether the effects of COVID-19 on acute cardiovascular death are direct or indirect, it has had a significant impact on mortality worldwide. However, the evidence presented by Wu and colleagues provides us with an important message to our patients and society: it is important to seek emergency medical attention for symptoms indicative of serious life-threatening cardiovascular disease even during the height of the pandemic. Here, the risk of fatal stroke and myocardial infarction outweighs the COVID-19 risk to the patient, and the healthcare system had capacity within acute specialities outside of the intensive care and dedicated COVID-19 units to provide life-saving treatments. This ultimately begs the question: is the fear of disease worse than the disease itself?
Contributors TS and DEN drafted and wrote the paper.
Funding TS and DEN are supported by the British Heart Foundation (CH/09/002, RG/16/10/32375, RE/18/5/34216). TS is supported by MRC (MR/T029153/1). DEN is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA).
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research.
Patient consent for publication Not required.
Provenance and peer review Commissioned; internally peer reviewed.
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