key: cord-0748803-nj91twyb
authors: Ghasemzadeh, Nima; Kim, Nathan; Amlani, Shy; Madan, Mina; Shavadia, Jay S.; Chong, Aun-Yeong; Bagherli, Alireza; Bagai, Akshay; Saw, Jacqueline; Singh, Jyotpal; Dehghani, Payam
title: A Review of ST-elevation Myocardial Infarction in Patients with COVID-19
date: 2022-03-29
journal: Cardiol Clin
DOI: 10.1016/j.ccl.2022.03.007
sha: f64b8213042c8d4f4cb88a973ad3087eb1aaa2e7
doc_id: 748803
cord_uid: nj91twyb

nan

The Coronavirus disease 2019 (COVID- 19) pandemic has led to a significant increase in worldwide morbidity and mortality. Patients with COVID-19 are at risk for developing a variety of cardiovascular conditions including acute coronary syndromes,, stress induced cardiomyopathy, and myocarditis. Patients with COVID-19 who develop ST-elevation myocardial infarction (STEMI) are at a higher risk of morbidity and mortality when compared to their age-and sex-matched STEMI patients without COVID-19. 1 We review current knowledge on the pathophysiology of STEMI in patients with COVID-19, clinical presentation, outcomes, and the effect of the COVID-19 pandemic on overall STEMI care.

Initial reports suggested a drop in the number of patients presenting with STEMI to hospitals in the few months following February-March 2020. [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] However, some centers later witnessed a U-shaped phenomenon in STEMI incidence during the pandemic. 12, 13 This U-shaped phenomenon indicated a decline in STEMI incidence during the first few weeks of the pandemic followed by a rebound in the following weeks.

Pathophysiology COVID-19 is caused by SARS-CoV-2 and has been shown to predispose patients to a pro-thrombotic state, involving both the venous and arterial circulations as well as both J o u r n a l P r e -p r o o f microvascular and macrovascular systems. 14, 15 This prothrombotic state has been shown to be associated with poor prognosis in patients with COVID-19 pneumonia. 16 Several mechanisms are believed to play a role in this process including inflammation, endothelial dysfunction, and platelet activation (Figure-1 ). 17 SARS-CoV-2 infects epithelial respiratory cells by binding to the angiotensin converting enzyme-2 receptor, viral shedding follows, which stimulates an inflammatory response leading in some cases to a cytokine storm mediated by pro-inflammatory cytokines such as interleukin 1β (iL-1 β), iL-2, iL-6, tumor necrosis factor (TNF), and granulocyte macrophage colony stimulating factor (GM-CSF). This cascade then leads to an overexpression of procoagulant factors such as tissue factor, factor VIII, p-selectin, Von Willebrand factor (vWF), fibrinogen and down regulation of anticoagulants which leads to thrombus formation. 18 A pathological analysis of 40 hearts from hospitalized patients in Italy who succumbed to COVID-19 showed that 35% of these patients had evidence of myocardial necrosis. The most common reason for myocardial necrosis was the presence of microthrombi, which were distinctly different in composition from thrombus aspirates from epicardial coronary arteries containing more fibrin and terminal complement. 21

The majority of patients with COVID-19 who presented with STEMI were male in both the Israeli and North American cohorts (Table 1 ). 1, 22 Their age ranged from 56-75 years. 1 Patients with COVID-19 who presented with STEMI had a significantly lower risk factor burden compared to those who were admitted with STEMI before the COVID-19

pandemic. 22 The majority of those patients belonged to racial minorities (23% Hispanics, J o u r n a l P r e -p r o o f 24% Blacks, 6% Asians). The most common presenting symptom was dyspnea and 46% of patients had presence of pulmonary infiltrate on chest x ray. 1 An Italian cohort in Lombardy showed that 85.7% of patients with STEMI experienced myocardial infarction as the first manifestation of COVID-19 and a quarter of those patients reported dyspnea as the initial complaint. 23 Cardiogenic shock is more frequent in patients with COVID-19. 1, 9, 24 

In the North American experience, about a quarter of patients with COVID-19 or suspected of having COVID-19 who presented with STEMI did not undergo emergent coronary angiography. 1 Door to balloon (D2B) time was reported in several studies to be significantly longer in patients with COVID-19 compared to historical controls. In a recent meta-analysis of 19 studies mainly across Asia, Europe, and Canada, the mean D2B time was reported to be 8.1 minutes longer in patients with COVID-19 compared to controls. 25 This difference was more noticeable in the North American centers with a mean difference of 12 minutes. 1 Patients with COVID-19 presenting with STEMI were more likely to receive medical therapy alone compared to controls (20% vs. 2%) and less likely to undergo primary PCI (71% vs. 93%). These patients were more likely to have no identifiable culprit lesion on coronary angiography as compared to the control group (23% vs. 1%). 1 In a meta-analysis of several studies, post-PCI Thrombolysis-in-Myocardial-Infarction (TIMI) flow grade was 60% more likely to be suboptimal with TIMI flow < 3 than control group of patients from the pre-pandemic era. 25 Even though left ventricular ejection fraction (LVEF) following primary PCI was reported to be similar in the North J o u r n a l P r e -p r o o f American experience, several other studies have shown a significantly lower LVEF (-4.2%) following primary PCI in patients with COVID-19 compared to their counterparts (Table-2 ). 25

STEMI patients who underwent PCI during the pandemic had an overall longer duration of hospital stay as shown in several studies. In the North American experience, the average length of hospital stay was 4 days longer in patients with COVID-19 compared to patients without COVID-19. 1 Other studies have shown an increased length of ICU stay in STEMI patients who were admitted during the pandemic era as compared to those admitted prior to the pandemic onset. 25

In the North American experience, the primary composite endpoint of in-hospital death, stroke, recurrent MI, or repeat revascularization was significantly higher in patients with COVID-19 compared to patients without COVID-19 (36% vs. 5%, p<0.001). 1 This was primarily due to markedly higher risk of in-hospital death in patients with COVID-19 as compared to controls (33% vs. 4%, p<0.001). The incidence of stroke was also statistically higher in patients with COVID-19 (3% vs. 0%, P=0.017). In a meta-analysis conducted by Chew et al. the overall mortality of STEMI patients was 27% higher during the pandemic as compared to pre-pandemic controls. 25 Similarly, the Israeli experience reported overall higher composite endpoint of malignant arrhythmia, congestive heart failure, or in-hospital mortality in those admitted with STEMI in the pandemic era as J o u r n a l P r e -p r o o f compared to pre-pandemic controls (12% vs. 8.6%, P=0.04), Table 3 . 22 In a large recent retrospective analysis of both out-of-hospital and in-hospital STEMI patients with COVID-19, the mortality rate was significantly higher when compared to their COVID-19 negative propensity matched counterparts (15.2% vs. 11.2%). In this study, Saad et al.

also compared the outcomes between in-hospital STEMI patients with concomitant COVID-19 to in-hospital STEMI patients without COVID-19 from prior years and reported a dramatically higher mortality rate of 76% as compared to 44% in those without 

Several studies have shown higher cardiovascular disease-related deaths in the COVID-19 era in racial and ethnic minorities including African Americans, Asians, and Hispanics compared to Whites. 27, 28 In a retrospective study of 73,746 patients admitted with AMI in the pandemic and pre-pandemic eras in the United Kingdom, there was a significantly higher odds ratio of AMI in ethnic minority groups as compared to Whites. 28 These patients however, were more likely to be younger, male, with lower body mass index, and a higher prevalence of comorbidities. They were also more likely to present with out of hospital cardiac arrest (7.6% vs. 6.2%, P=0.04) and cardiogenic shock (3.5% vs. 2.4%, p<0.001) as compared to Whites. There was a longer delay in reperfusion therapy in the minority group as compared to Whites with an absolute increase of 30 minutes in the D2B time. 28 The ethnic minorities were significantly less likely to be discharged on dual antiplatelet therapy compared to Whites (70% vs. 73%, p=0.03). Risk of in-hospital and 7-day mortality was significantly higher in the ethnic subgroup compared to Whites. 28 

Even though primary PCI has been the first line reperfusion strategy for STEMI patients in the United States, the rate of fibrinolysis-focused reperfusion strategy remains about 2%-13% nationally. 29 During the COVID-19 pandemic, longer delays were reported to reperfusion. Tim et al. reported longer delays of symptom onset to first medical contact (318 vs. 82.5 minutes), D2B time (110 vs. 84.5 minutes), and catheterization laboratory to balloon time (33 vs. 20.5 minutes) compared to the pre-pandemic era. 30 Delayed presentation, lack of adequate COVID-19 testing early on, potential hazard to staff members, longer assessment times in emergency departments resulting in longer D2B times and therefore, potentially loss of primary PCI benefit, led to suggestions for fibrinolytic-first approach in a selected STEMI patients. 31 However, given the higher rate of no culprit including micro thrombi with slow flow, stress induced cardiomyopathy, COVID-19 induced myocarditis, or pericarditis, fibrinolysis may not only provide no benefit, but confer additional bleeding risk. With the adoption of enhanced safety measures in cardiac catheterization laboratories, greater access to rapid testing, and wider availability of personal protective equipment for staff, a joint recommendation from the ACC, SCAI, and American College of Emergency Physicians (ACEP) later recommended primary PCI for all patients with definite STEMI regardless of COVID-19 diagnosis. 33 Thrombolysis was instead recommended for STEMI patients with severe COVID-19 pneumonia or those for whom transfer to PCI-capable hospital is not possible within 120 minutes from first medical contact. 3233

The COVID-19 pandemic has impacted the delivery of healthcare in all its aspects around the globe. STEMI systems of care which require a synchronized network of referring hospitals, emergency departments, and PCI-capable cardiac catheterization laboratories has similarly been affected. During the initial phase of the pandemic, some studies suggested up to 31% reduction in cardiac catheterization laboratory activations with an estimated 18-20% reduction in primary PCI volume. 11 During the same period, a study by Garcia et al. showed an increase of 20% in D2B times as compared to before the pandemic. 11 Several factors were reported to contribute to the increase in time to reperfusion during the pandemic including overwhelmed emergency rooms, COVID-19 testing requirement in the ED prior to transfer to catheterization laboratory, use of strict infection control measures, and increased use of imaging to triage these patients. 34 Early in the pandemic, it was observed that the time from onset of symptoms to assessment in ED was significantly longer compared to pre-pandemic times. 25 Fear of exposure to COVID-19 in hospitals and concern for overburdening hospital systems were contributing factors. 35, 36 Furthermore, other key challenges in caring for these patients has been shortage of ICU beds and medical equipment such as ventilators, mechanical circulatory support devices, and lack of sufficient health human resources to care for these patients. With adoption of protocols endorsed by cardiovascular societies and with wider access to COVID-19 testing, some of these challenges have been overcome.

Furthermore, triage of low-risk STEMI patients to non-ICU settings has been proposed to mitigate the challenge with the ICU bed shortages. Risk scores such as CADILLAC and

Zwolle have been validated in the non-COVID-19 setting to be useful in triage of lowrisk STEMI patients and theoretically were even more needed during the pandemic. 37 J o u r n a l P r e -p r o o f

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