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STEMI Mimics, Safety Fears During COVID-19 Pandemic Spark Debate Over Fibrinolytic Use

Anecdotal evidence observing COVID-19 patients presenting STEMI without obstructed arteries brings fibrinolytic therapy to forefront of discussion

Case-reports and anecdotal evidence are highlighting the rise of COVID-19 positive patients who present STEMI symptoms without arterial occlusion, sparking debate over whether to use the alternative therapy for coronary reperfusion.

During the COVID-19 pandemic, reports have shown that COVID-19 patients had elevated troponin levels that indicate myocardial damage but no obstructive disease.

Correspondence published in the New England Journal of Medicine on April 17 identified 18 COVID-19 patients at six New York-based hospitals with ST-segment elevation that indicated potential acute myocardial infarction. 1

Coronary angiography was performed on nine of the 18 patients. Of the nine, obstructive disease was observed only in six patients, leading the researchers to conclude that "there was variability in presentation, a high prevalence of nonobstructive disease, and a poor prognosis.."

Another report from the research team led by Professor Giulio Stefanini from the Humanitas Clinical and Research Hospital IRCCS in Rozzano-Milan, Italy also observed frequent cases of non-ischemic causes of ST elevation among 28 COVID-19 patients treated at a cath lab in Lombardy, Italy – one of the most affected regions worldwide. 2

According to the retrospective case series, about 40 percent of STEMI patients who tested positive for COVID-19 did not have an identifiable culprit lesion via a coronary angiography. A coronary angiography confirming arterial occlusion showed that only 17 patients (60.7 percent) of the studied patients had major lesions requiring reperfusion. The remaining 11 patients (39 percent) had no arterial occlusion. The entire patient population underwent urgent angiography and none received fibrinolytic therapy.

However, the research team noted that it was difficult to confirm the reason behind the STEMI mimics, pointing towards the possibility of a type 2 myocardial infarction, myocarditis caused by SARS-CoV-2 infection, endothelial dysfunction association with SARS-CoV-2, or a cytokine storm.

To PCI or not to PCI? Dilemma of COVID-19 pandemic

STEMI patients require coronary reperfusion therapy with primary percutaneous coronary intervention (PCI). Fibrinolytic therapy is an alternative when PCI is not feasible. However, these case-reports are currently complicating the argument for or against fibrinolytic therapy since applying fibrinolytics to COVID-19 infected patients with unobstructed arteries can worsen clinical outcomes by causing bleeding.

The evidence stacked against fibrinolytic therapy as compared to primary PCI set the grounds for a dilemma wherein cardiologists have to weigh the risk of infection versus clinical outcomes during the COVID-19 pandemic.

Although primary PCI has proved to be more suitable for STEMI patients, carrying out the procedure puts medical staff and patients at risk for COVID-19 infection. PCI may also not be feasible when hospitals are flooded with COVID-19 patients. In this particular time, hospitals may have to allocate cardiovascular disease experts to treating and managing infected patients.

Accordingly, Professor Matthew J. Daniels from the University of Manchester, U.K. suggested fibrinolytic therapy may be considered as a primary treatment over primary PCI for STEMI patients who have symptoms within three hours and have no high-risk clinical findings in a Circulation paper on April 13. 3

The argument is that the COVID-19 crisis increases the total time to treatment, leading to delayed reperfusion since more time is consumed during the process of confirming a patient¡¯s medical history in the emergency room, tracing contacts, and carrying out additional tests to rule out COVID-19 patients, among others.

In this case, Daniels noted that fibrinolytics may alleviate this problem by shortening the door-to-needle time while also protecting essential health care staff, including the cardiac intervention team.

On the other hand, Stefanini who observed STEMI mimics on the ground made the opposing argument against fibrinolytic therapy.

"Our findings show that STEMI may represent the first clinical manifestation of COVID-19," the research team wrote, warning that "in approximately 40 percent of COVID-19 patients with STEMI, a culprit lesion is not identifiable by coronary angiography.¡¯

"Our findings also show that a strategy relying on systematic fibrinolysis is not justified, since reperfusion appears not to be required in a significant proportion of COVID-19 patients with STEMI," they added. "A dedicated diagnostic pathway should be delineated for COVID-19 patients with STEMI, aimed at minimizing the patient¡¯s procedural risks and healthcare providers¡¯ risk of infection."

ACC/SCAI/ACEP recommendations delineate "no fibrinolytic benefit" for STEMI mimics

As the controversy continues, a joint recommendation from the American College of Cardiology (ACC), Society for Cardiovascular Angiography and Interventions (SCAI), and the American College of Emergency Physicians (ACEP) published in the Journal of American College of Cardiology (JACC) on April 20 pointed towards no fibrinolytic benefit for STEMI mimics. 4

The recommendation indicated that administrating fibrinolytic therapy to patients with STEMI mimics could cause bleeding while not resolving the problem of ST-segment elevation, ultimately leading to an invasive diagnostic test.

Accordingly, the societies called upon PCI-centered medical centers to monitor whether they can proceed with timely primary PCI based on medical staff allocations and available personal protective equipment (PPE). Fibrinolytic therapy was recommended only when there was a lack of medical support.

Experience from field stresses COVID-19 screening first, PCI second

Professor Yan Li of Tangu Hospital in Xi¡¯an, China also outlined a treatment strategy for COVID-19 patients with suspected STEMI after treating patients during the most critical outbreak period in China on May 14 during a Live Webinar titled "China-Asia Pacific Interventional Cardiologists Facing COVID-19 as One." 5

According to Li, the cardiology department at Tangdu Hospital adhered to the "Chinese consensus," published in Circulation, to treat a total of 163 patients admitted with ACS and severe CVD disease. The Chinese consensus outlined the importance of triaging cardiovascular patients.

Tangdu Hospital categorized patients into STEMI, hemodynamically stable STEMI without fibrinolytic therapy, and NSTEMI to apply a treatment strategy for each patient group.

STEMI patients were first transported to a treatment facility and fibrinolytic therapy was performed under safety protection. After screening for COVID-19, patients were then transported to a PCI hospital.

Hemodynamically stable STEMI patients were first screened for COVID-19, and PCI was performed if the patient tested negative for COVID-19.

NSTEMI patients were also first screened for COVID-19 while medical professionals utilized level III PPE as needed. Unstable NSTEMI patients were treated according to STEMI patient protocol.

"Assessing the benefits of COVID-19 treatment versus cardiovascular disease treatment was a key question for cardiologists at Tangdu Hospital when making treatment decisions," Li said. "AMI patients were common but they were difficult to treat during the COVID-19 epidemic."

In light of all these findings, experts are highlighting the difficulties of executing PCI and staying within the appropriate door-to-balloon time frame during the pandemic, citing issues of hospital staff shortage, epidemiological investigations, and personal protective gear, among others. Because the decision to PCI is complicated by the fact that patients are presenting STEMI without obstructed arteries, experts are calling for a better strategy that improves upon the traditional treatment process.


  1. https://www.nejm.org/doi/full/10.1056/NEJMc2009020
  2. https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.120.047525
  3. https://www.acc.org/latest-in-cardiology/ten-points-to-remember/2020/04/20/15/48/reperfusion-of-stemi-in-the-covid
  4. https://www.onlinejacc.org/content/accj/early/2020/04/23/j.jacc.2020.04.039.full.pdf
  5. http://arkadin1.gensee.com/webcast/site/vod/play-a88e82a16e3a4bcab71509b7504393c4

Edited by

Pil Hyung Lee
Pil Hyung Lee, MD

Asan Medical Center, Korea (Republic of)

Written by

YoonJee Marian Chu
YoonJee Marian Chu, Medical Journalist
Read Biography

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