Discussion
The global COVID-19 pandemic has resulted in significant disruption to healthcare systems. In particular, there is a growing body of evidence worldwide demonstrating a significant decrease of up to 40% in the volume of patients presenting through PPCI services during the pandemic.5 18–20 Our data support these findings with heart attack services in London experiencing a 21% decrease in cases compared with the same period in 2019. There could be a number of explanations for this observation. First, patients experiencing chest pain may have been reluctant to seek medical attention either in fear of viral transmission or not wishing to burden the already stretched healthcare system. Second, patients with no cardiac history may have attributed their myocardial infarction symptoms to COVID-19 infection and, as per government advice at the time, did not seek immediate help. Finally, those patients who did seek help may not have been prioritised by the ambulance service who were under immense pressure at the time and a proportion of these patients may have deteriorated and died before receiving medical attention. In addition to the fall in acute presentations, survey data suggest a corresponding increase in the incidence of cardiac related complications associated with untreated STEMI21; however, the long-term implications remain unclear.
The key to an effective PPCI service is minimisation of total ischaemic time.4 Critical to this pathway is prompt identification of STEMI, rapid transfer to a PPCI centre and immediate revascularisation on arrival. Delays at any stage during this pathway may increase myocardial ischaemia time resulting in reduced myocardial salvage, larger infarct size and subsequent long term morbidity.22 23 COVID-19 resulted in multiple potential delays to this pathway. Our analysis comparing the 2020 study population to the 2019 control population in a busy metropolitan city importantly revealed comparable door to balloon times between the two groups, contrary to previous reports24 with comparable in-hospital mortality rates. This suggests that modifications to the existing in-hospital PPCI pathways, such as routine use of PPE and redeployment of staff to other clinical areas, neither delayed the time taken to achieve coronary revascularisation (door to balloon time) or resulted in worse outcomes. However, the median ischaemic time was 36 min longer in 2020 than 2019, driven predominantly by an increase in the median time from first call for help to arrival at a PPCI centre. The likely explanation for this is the impact of a high volume of COVID-19-illness related calls overwhelming paramedic emergency services leading to a delayed response time, although additional time for paramedics to don PPE may also have contributed. The increased door to balloon time and subsequent increased ischaemic time for COVID-19 positive patients compared with COVID-19 negative patients in 2020 likely reflects the increased procedural complexity of these cases rather than system-related delays as all centres mandated full PPE for all PPCI cases given the unknown COVID-19 status at time of procedure. While systemic thrombolysis has been suggested as an alternative strategy to managing patients with STEMI during the pandemic,3 our data suggest that even at the peak of COVID-19 related admissions to hospital, it was possible to maintain effective PPCI services.
Current literature suggest that patients with COVID-19 presenting with STEMI have higher rates of in-hospital mortality, compared with those without concurrent COVID-19.25 Our data support this finding with more than doubling in the rate of in-hospital mortality for these patients. Furthermore, the increased frequency of ICU admission and longer length of stay have significant implications on hospital resources. Importantly, there was no significant difference in the baseline characteristics between COVID-19 positive and COVID-19 negative patients. The cause of this excess mortality is not clear but it is likely that a number of factors may be contributory. First, COVID-19 itself is associated with high in-hospital mortality and the infarct in addition to systemic illness results in poor prognosis particularly in those with significant comorbidity.5 Second, delays in presentation result in longer ischaemic which is known to be associated with larger infarct size and therefore these patients are more likely to develop fatal post-MI complications.26 Third, patients with COVID-19 appear to be highly prothrombotic compared with COVID-19 negative patients, with studies demonstrating high incidence of pulmonary thromboembolic disease as well as thrombi in other organs such at the kidneys.8 High coronary thrombus burden at presentation is independently associated with increased rates of major adverse cardiovascular events and mortality.27 28 Furthermore, intraprocedural distal embolisation of thrombus may disrupt microvascular function resulting in angiographic no reflow and increase infarct size.29 Thrombus burden determination is highly subjective and as such we employed thrombus aspiration usage and reduced TIMI flow at the end of the procedure as surrogates. Reduced TIMI flow is frequently seen with distal embolisation of thrombotic material.30 This study demonstrates an increased use of thrombus aspiration and glycoprotein IIb/IIIa inhibitors within the COVID-19 cohort, with higher rates of reduced TIMI flow, suggesting a higher thrombotic burden when compared with non-COVID-19 patients with STEMI. Glycoprotein IIb/IIIa inhibitors have a class IIa indication for adjunctive therapy with PCI with evidence of high thrombotic burden4 and may be of benefit in patients with COVID-19 although with increased risk of bleeding. A targeted antithrombotic approach may be of benefit in these patients to decrease rates of distal embolisation of thrombus and subsequently decrease infarct size in order to improve long-term outcomes but further prospective studies are required.
Choudry et al6 have recently published a single centre experience demonstrating a signal of increased thrombus burden in COVID-19 patients with STEMI (n=39) with higher use of aspiration thrombectomy and glycoprotein IIb/IIIa inhibitors, as well as higher postintervention TIMI thrombus grade and lower resultant myocardial blush score. Importantly, our multicentre study includes the largest cohort of COVID-19 positive patients with STEMI (n=46) compared with COVID-19 negative patients with similar presentation during the same time period, and in addition to confirming these findings also demonstrates a significant increase in mortality in the COVID-19 positive group and delays in door to balloon time. Our additional control group of patients with STEMI from 2019 provides key insights into the effects of modifications to existing PPCI pathways. Mafham et al20 have highlighted a substantial reduction in acute coronary syndrome presentations in England during the COVID-19 pandemic period compared with 2019. Our study provides further analysis based on the presence or absence of concurrent COVID-19 infection and validates their findings by providing details of both the heart attack pathways and procedural characteristics.
Limitations of the current study include its retrospective design in the first instance and therefore the potential introduction of information bias. Additionally, we only included patients receiving PCI for STEMI and data on those subjects with STEMI who did not undergo PCI (including those receiving systemic thrombolysis only and those managed medically in the first instance) were not included in our analysis. Moreover, patients who underwent coronary angiography that revealed no culprit lesion were excluded from the analysis. It has been reported that in COVID-19 positive patients presenting with STEMI between 33% and 39% of cases demonstrate no culprit lesion on angiography.5 25 This represents a large proportion of admissions through the PPCI pathway and the effects of pathway modifications on this cohort within our study are not assessed. While this is a large study of PPCI services in a metropolitan city, the COVID-19 positive group was relatively small making up less than 5% of the cohort and therefore findings within this group should be interpreted with caution. Moreover, data are limited to in-hospital outcomes. Long-term prospective follow-up will be required to determine the true association between COVID-19 and excess mortality following STEMI. Furthermore, the threshold used by emergency service to initiate the PPCI pathway, during the pandemic, may have been influenced by factors relating to infection control and resource management. This may have contributed to the reduction seen in PPCI activations worldwide in 2020. Finally, the outcome of those patients who did not present to the PPCI service is unknown. They may have significantly worse late outcomes, with heart failure, arrhythmia and death as yet unmeasured in the community.