Reperfusion of ST-Segment-Elevation Myocardial Infarction in the COVID-19 Era: Business as Usual?

We are in the midst of a generation-defining global pandemic, the scope, scale, and pace of which is unprecedented. Coronavirus 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 virus), occurs in addition to existing challenges to emergency services, like ST-elevation myocardial infarction (STEMI). Both conditions may coexist, initial presentations can overlap, and true and reliable point-of-care testing does not exist. Furthermore, symptoms alone are unhelpful, as most screened for COVID-19 test negative (30% can be false negative) and ≈80% of COVID-19 infections are asymptomatic. Experts dealing with the COVID-19 epidemic in China recommend fibrinolytic therapy (FT) over primary percutaneous coronary intervention (PPCI) for STEMI. In this perspective, we analyze the arguments for a FT-based strategy in patients presenting with STEMI in the COVID-19 era. Collectively, we feel that this is a reasonable consideration, because fibrinolysis may be the best compromise of prompt reperfusion for the patient with the least resource implications for the institution, buying time for a complete clinical picture to be made. In caring for our patients, we must recognize that optimal care strategies, established outside the challenges of a pandemic, may be potentially suboptimal during one.

Safety and Efficacy of Fibrinolytic Therapy

FT was the first effective reperfusion treatment to be systematically implemented for STEMI. Subsequently, PPCI was proven superior to FT, becoming the standard of STEMI care across the Western world. Yet, geographically isolated areas with low population density retain fibrinolytic-focused reperfusion strategies (≈2% to 13% of STEMIs in contemporary US practice),[1] as do most developing countries. STREAM (Strategic Reperfusion Early After Myocardial Infarction) was a contemporary fibrinolytic trial, recruiting STEMI patients ≤3 hours of symptom onset, who were unable to access PPCI ≤1 hour of first medical contact. Patients were randomized to FT, with PCI after 6 to 24 hours, or PPCI (median difference between fibrinolytic administration and PCI ≥78 minutes). Outcomes of FT versus PPCI were similar for the composite of death, shock, heart failure, or reinfarction. Need for emergent angiography in the fibrinolytic arm was 36%; mortality was <5% in both groups. Intracranial hemorrhage was higher with FT (1.0% vs 0.5%, P=0.02).[2] Bottom line: When delays in PPCI are unavoidable, a pharmacoinvasive approach is not worse than PPCI in the P2Y12 inhibitor era.

System Delays in PPCI

Timely PPCI relies heavily on systems of care, not just individual operators. PPCI treatment delays in the COVID-19 era arise, even among COVID-19 negative patients, through the steps and time in the emergency room required to establish contact history, symptomatology, chest x-ray, etc, before transfer to the cardiac catheterization laboratory (CCL). CCL staff require time to don personal protective equipment and may perform their usual roles more slowly.[3] In this setting, immediate fibrinolytic administration in the emergency department may mitigate systems-based delays. A door-to-needle time of 30 minutes may be more achievable than a door-to-balloon time of 90 minutes. The mortality benefit associated with primary PCI may be lost if door-to-balloon time is delayed by >1 hour compared with FT door-to-needle time.[4] Early reperfusion may be more important than the mode of reperfusion.

Infection Risk to CCL Personnel

COVID-19 is highly contagious, with proximity-dependent spread and viability in aerosols for hours, or on surfaces for days.[5] Infection of healthcare workers is a major concern; in Italy and Spain, 8% to 12% of those infected are healthcare workers. The use of personal protective equipment minimizes risk but does not remove it. Guidance on appropriate personal protective equipment has also changed during the pandemic. Nonfatal infections, with resultant quarantines, may decimate clinical care teams. In the context of the long incubation period of the virus and anticipated duration of the pandemic, absence of a significant proportion of interventional cardiologists and CCL personnel may have wider consequences for healthcare systems.

Resources

Hospitals at the heart of the pandemic find themselves in an unfamiliar resource-limited environment typical of outbreak medicine, such as scarcity of personal protective equipment, extensive staff absences, competing needs for equipment, and lack of beds. The resource implications for PPCI and thrombolysis are different. Single-bolus FT is easy to administer, overcoming the inescapable delays and resource-intensive requirements of PPCI during the COVID-19 era. Additionally, for patients with both STEMI and COVID-19, the shorter length of stay promised by PPCI is negated by the time required to treat hospitalized COVID-19 infections. Patients initially treated with FT could complete their pharmacoinvasive management during convalescence (or, for persons under investigation, after COVID-19 is ruled out) when resource implications and infection risk to CCL personnel reduce. Lytic therapy is less resource-intensive for the system overall.

Are some patients more appropriate for FT than others (Figure)? Patients without extensive infarcts who present early (<3 hours) may be well-suited for FT, but careful monitoring and consideration for rescue PCI in case of failed reperfusion after 1 hour of FT administration is essential. Poor candidates for FT include delayed presentations, large infarcts, hemodynamic or electrical instability, or FT contraindications who should be considered for PPCI where feasible. A major challenge are the myocarditis-like syndromes, with COVID-19 mimicking STEMI, which may not have the same benign consequences as routine invasive angiography when given FT. Ultimately, fulminant respiratory failure may render any reperfusion strategy futile. We acknowledge that many cardiologists are unfamiliar with the logistics of FT or have negative opinions about their use. Adopting FT will require most staff to familiarize with this practice and explore ways to leverage electronic health records (eg, dedicated order sets).

Proposed STEMI reperfusion algorithm for coronavirus 2019 (COVID-19)–positive/presumed positive patients. Contraindications to fibrinolytic therapy as listed in 2013 American Heart Association/American College of Cardiology STEMI guidelines. ACE indicates angiotensin converting enzyme; CCL, cardiac catheterization laboratory; CV, cardiovascular; IRA, infarct related artery; PCI, percutaneous coronary intervention; PI, pharmacoinvasive strategy; PUI, person under investigation; STE, ST-elevation; and STEMI, ST-elevation myocardial infarction.

In conclusion, a blanket policy of PPCI for all STEMI patients may be hard to both justify and operationally deliver in the current environment when resources to protect the workforce are limiting and systems delays may shift the balance in favor of fibrinolytic strategies. Furthermore, centers experiencing acute staff shortages may need to adopt FT if they are unable to provide PPCI safely and sustainably. When transfer to the CCL is considered, it should be done cognizant of the overall implications, not simply based on patient risk–benefit or operator preference. These are challenging and unprecedented times, and we should not pretend that we can provide business as usual.

Acknowledgements

The authors thank Dr Hayley B. Gershengorn for her assistance in developing the proposed algorithm.

Disclosures

Dr Cohen reports consultancies with Medtronic, Abiomed, Terumo Medical, Merit Medical, and AstraZeneca; and ownership of Accumed Radial Systems. The other authors report no conflicts.