Handling new challenges in acute coronary syndrome from the pandemic.
Case: A 45-year-old male with past medical history of hyperlipidemia and hypertension presents to the emergency department via EMS complaining of severe substernal chest pain and shortness of breath. His ECG on arrival shows significant ST elevations (STE) in several anterior and lateral leads, concerning for an occlusive myocardial infarction (MI). However, he also reports several days of cough and fever and tested positive for COVID-19 six days ago. When consulted, the on-call interventional cardiologist requests that you administer fibrinolytics in light of his COVID-19 status.
The COVID-19 pandemic has created a plethora of new problems within healthcare systems worldwide. Among these issues lies the diagnosis and treatment of suspected acute MI. Existing paradigms for acute coronary syndrome must now account for the variable clinical presentations of COVID-19, delays in EMS transportation and difficulties in mobilizing the resources for emergent percutaneous coronary intervention (PCI).
The true toll of the pandemic will likely take years to uncover and define, but analysis of spring and summer of 2020 has already demonstrated a significant decrease in the volume of patients presenting to hospitals for any reason, including MI.
Comparing incidence rates of hospitalization for acute MI (STEMI and NSTEMI) between spring of 2019 and 2020 within the large Kaiser Permanente system in Northern California has revealed a decrease of up to 48% during the COVID-19 period. Of note, the demographic characteristics of patients presenting for MI was not significantly different between the two time periods. This significant decrease in presentations was also documented in other settings during the pandemic such as Northern Italy, Madrid and Hong Kong.[2-5]
In terms of STEMI, the pandemic has caused significant difficulty in reaching the traditional “gold standard” of care in terms of availability of PCI and the timing PCI. Analysis of both systems in Bergamo and Madrid highlighted the difficulty in preparing the staff and resources for PCI with appropriate PPE.[2,4] In Bergamo, patients were not taken for PCI if they required non-invasive positive pressure ventilation for suspected COVID-19.  This additional stress on the healthcare systems pushed for a reorganization of existing regional hospital networks.
The pandemic has created new challenges in the emergency department approach to STEMI diagnosis and management. Case reports and series have demonstrated an increased risk of the development of myocardial infarction, acute heart failure, cardiac dysrhythmias and myocarditis in patients with confirmed COVID-19.
Back in the pre-COVID era, a good history and STE were enough impetus for transfer to the cardiac catheterization laboratory to rule out obstructive coronary artery disease. In the current COVID-19 pandemic, one must consider the myriad of cardiovascular presentations and complications for which catheterization plays little to no role, but also be cognizant of the potentially unnecessary risk of exposure to consultants and staff.
In a recent correspondence piece, a small case series of 18 COVID-19 patients with STE on electrocardiogram (ECG) highlighted these challenges. Of the 18 patients, 10 had STE on presentation while eight developed it during hospitalization, with a median time of six days.
Most patients had underlying risk factors, including hypertension (65%), hypercholesterolemia (65%), diabetes (35%), and/or history of coronary artery disease (18%). The most common signs and symptoms were respiratory (83%) and/or fever (72%). Only 33% had chest pain.
In terms of the relationship between ECG findings, echocardiography, and presence of obstructive disease, 14 patients (78%) had focal elevations with eight (57%) of those having a low ejection fraction (EF) on echocardiography. Nine patients in total underwent coronary angiography, six of whom had obstructive disease. Five of these patients had an intervention performed, one post-fibrinolysis.
As the case series highlights, while “false positive” transfers to the catheterization laboratory are to be expected, in the pandemic they may be more scrutinized and less tolerated as we expose additional medical staff to contagion. Furthermore, it highlights the difficulty in differentiating STE due to coronary occlusion compared with myocarditis. Conversely, there are also cases of delayed care when patients with concerning symptoms and ECGs with STE have been delayed from definitive therapy due to an attribution of their symptoms to solely COVID-19.
Significant hypercoagulability is another feared complication of COVID-19 that recent research has brought to light, having been demonstrated both through laboratory analysis and through clinical presentations. This may manifest in significantly higher risk of ischemic stroke or VTE in patients with COVID-19, even when compared to other viral infections such as influenza.
Additionally, some interventional cardiologists have documented a higher thrombus burden in patients with COVID-19 taken for emergent PCI. The clinical significance of this thrombus burden remains under investigation, but may lead to more difficulty and complications with PCI.[10, 11]
Due to the structural and clinical barriers to achieving previous standards of care for acute MI, some have proposed a shift towards the use of fibrinolytics for myocardial infarction, such as alteplase or tenectaplase. In health systems where PCI is not readily available, fibrinolytics may offer a timely alternative for suspected occlusive MI.
It’s important to note that the use of fibrinolytics for MI is not a novel approach in many health systems. In high-income countries, only 25-50% of patients with STEMI transferred for PCI reach the catheterization lab within 120 minutes of first-contact, as recommended by the ACC/AHA guidelines.
However, PCI may still play a significant role in patients who receive fibrinolytics for suspected occlusive MI. A “pharmacoinvasive” strategy for STEMI involves the administration of fibrinolytics in the pre-hospital setting or at a non-PCI-capable hospital, followed by transfer to a PCI-capable hospital for delayed invasive intervention within two- to 24-hours.
Such an approach would allow patients with suspected MI to be transported to the nearest hospital with fibrinolytic capacity, rather than risk significant delay to any definitive treatment. It would also allow time for the patient’s COVID-19 status to be investigated. A proposed algorithm from China called for a pharmacoinvasive strategy for all STEMI patients unless there was a clear contraindication to fibrinolysis. 
For the emergency physician, there are no straightforward solutions to these problems, but it is important to know the various approaches to these cases. If administering fibrinolytics for STEMI, one must monitor for evidence of primary failure of fibrinolysis, which has been reported as 40-45% of cases.  Signs of failure include continued chest pain, hemodynamic instability, continued electrical dysrhythmias.
ECG markers of failed reperfusion include less than 50% resolution of STE on anterior leads and less than 70% resolution of STE in inferior leads. These patients should be referred for immediate PCI if possible. Ideal patients for a pharmacoinvasive strategy include those presenting to a non-PCI hospital within three hours of symptom onset, with significant PCI-related delay preventing the patient from reaching the catheterization lab within 120 minutes.
Patients presenting with cardiogenic shock or high-risk MIs (defined as TIMI score > 5) should ideally be referred for PCI. ED providers should also consider the presence of any contraindications to fibrinolytics. Lastly, if there is significant doubt in diagnosis of MI, referral for PCI may be preferred to minimize the risk of unnecessary iatrogenic complications from fibrinolytic therapy.
A recent statement published by the American College of Emergency Physicians, American College of Cardiology, Society for Cardiovascular Angiography and Interventions (SCAI) recommends primary PCI as the standard of care “when it can be provided in a timely manner, with an expert team outfitted with PPE in a dedicated CCL room.” 
The statement allows for a fibrinolytic strategy at non-PCI capable hospitals or in situations where primary PCI cannot be executed. As COVID-19 numbers surge in various parts of the United States, traditional strategies prioritizing primary PCI may not be feasible in all cases. As emergency physicians, we should be aware of our hospitals’ guidelines and strategies for suspected STEMI. As it stands, the evidence offers a variety of choices within this clinically unclear environment.
- Solomon MD, McNulty EJ, Rana JS, et al. The Covid-19 Pandemic and the Incidence of Acute Myocardial Infarction. N Engl J Med. 2020;383(7):691-693. DOI: 10.1056/NEJMc2015630
- De Filippo O, D’Ascenzo F, Angelini F, et al. Reduced Rate of Hospital Admissions for ACS during Covid-19 Outbreak in Northern Italy. N Engl J Med. 2020;383(1):88-89.DOI: 10.1056/NEJMc2009166
- Dauerman HL. The Unbearable Thrombus of COVID-19: Primary PCI, Thrombus, and COVID-19. J Am Coll Cardiol. 2020;76(10):1177-1180. DOI: 10.1016/j.jacc.2020.07.027
- Rodriguez-Leor O, Cid-Álvarez B, Pérez de Prado A, et al. Impact of COVID-19 on ST-segment elevation myocardial infarction care. The Spanish experience [published online ahead of print, 2020 Sep 8]. Rev Esp Cardiol (Engl Ed). 2020;S1885-5857(20)30362-5. DOI: 10.1016/j.rec.2020.08.002
- Wood S. The mystery of the missing STEMIs during the COVID-19 pandemic. tctMD. April 2, 2020. https://www.tctmd.com/news/mystery-missing-stemis-during-covid-19-pandemic. Accessed Sept 28, 2020.
- Madjid M, Safavi-Naeini P, Solomon SD, Vardeny O. Potential Effects of Coronaviruses on the Cardiovascular System: A Review. JAMA Cardiol. 2020;5(7):831-840. DOI: 10.1001/jamacardio.2020.1286
- Bangalore S, Sharma A, Slotwiner A, et al. ST-Segment Elevation in Patients with Covid-19 – A Case Series. N Engl J Med. 2020;382(25):2478-2480. DOI: 10.1056/NEJMc2009020
- Panigada M, Bottino N, Tagliabue P, et al. Hypercoagulability of COVID-19 patients in intensive care unit: A report of thromboelastography findings and other parameters of hemostasis. J Thromb Haemost. 2020;18(7):1738-1742. DOI: 10.1111/jth.14850
- Merkler AE, Parikh NS, Mir S, et al. Risk of Ischemic Stroke in Patients With Coronavirus Disease 2019 (COVID-19) vs Patients With Influenza [published online ahead of print, 2020 Jul 2]. JAMA Neurol. 2020;e202730. DOI: 10.1001/jamaneurol.2020.2730
- Dauerman HL. The Unbearable Thrombus of COVID-19: Primary PCI, Thrombus, and COVID-19. J Am Coll Cardiol. 2020;76(10):1177-1180.DOI: 10.1016/j.jacc.2020.07.027
- Choudry FA, Hamshere SM, Rathod KS, et al. High Thrombus Burden in Patients With COVID-19 Presenting With ST-Segment Elevation Myocardial Infarction. J Am Coll Cardiol. 2020;76(10):1168-1176.DOI: 10.1016/j.jacc.2020.07.022
- Vora AN, Holmes DN, Rokos I, et al. Fibrinolysis use among patients requiring interhospital transfer for ST-segment elevation myocardial infarction care: a report from the US National Cardiovascular Data Registry. JAMA Intern Med. 2015;175(2):207-215. DOI: 10.1001/jamainternmed.2014.6573
- Engel Gonzalez P, Omar W, Patel KV, et al. Fibrinolytic Strategy for ST-Segment-Elevation Myocardial Infarction: A Contemporary Review in Context of the COVID-19 Pandemic. Circ Cardiovasc Interv. 2020;13(9):e009622. DOI: 10.1161/CIRCINTERVENTIONS.120.009622
- Zeng J, Huang J, Pan L. How to balance acute myocardial infarction and COVID-19: the protocols from Sichuan Provincial People’s Hospital. Intensive Care Med. 2020;46(6):1111-1113. DOI: 10.1007/s00134-020-05993-9
- Cannon CP, Gibson CM, McCabe CH, et al. TNK-tissue plasminogen activator compared with front-loaded alteplase in acute myocardial infarction: results of the TIMI 10B trial. Thrombolysis in Myocardial Infarction (TIMI) 10B Investigators. Circulation. 1998;98(25):2805-2814. DOI: 10.1161/01.cir.98.25.2805
- de Lemos JA, Braunwald E. ST segment resolution as a tool for assessing the efficacy of reperfusion therapy. J Am Coll Cardiol. 2001;38(5):1283-1294. DOI: 10.1016/s0735-1097(01)01550-9
- Mahmud E, Dauerman HL, Welt FGP, et al. Management of acute myocardial infarction during the COVID-19 pandemic: A Consensus Statement from the Society for Cardiovascular Angiography and Interventions (SCAI), the American College of Cardiology (ACC), and the American College of Emergency Physicians (ACEP). Catheter Cardiovasc Interv. 2020;96(2):336-345. DOI: 10.1002/ccd.28946