High thrombus burden despite thrombolytic therapy in ST-elevation myocardial infarction in a patient with COVID-19

Consideration of thrombolysis as first-line reperfusion therapy in patients with COVID-19 and STEMI is rec-ommended by ACC/SCAI guidelines. We describe a patient with COVID-19, who presented with ST-elevation myocardial infarction and was treated with thrombolysis and anticoagulation. He was later found to have a significant persistent thrombus burden requiring thrombec-tomy and stent placement. Invasive hemodynamics on multiple high-dose pressers revealed a high cardiac output state with low systemic vascular resistance, consistent with distributive rather than cardiogenic shock. Our case illustrates that thrombolytic therapy alone may not be adequate in patients with STEMI and COVID-19, as well as the importance of early invasive hemodynamics in management of shock in patient with STEMI and COVID-19 infection.


Case report
A 59-year-old man with a history of diabetes, hypertension, and hyperlipidemia presented to the emergency department with substernal chest pain. He also reported a two-week history of cough, pleuritic chest discomfort, and night sweats.
On the night prior to admission, about 14-16 hours prior to arrival in the ED, he developed intermittent substernal chest pain, which spontaneously resolved. Chest pain recurred 90 minutes prior to presentation and remained constant and severe, prompting his family to call paramedics. On arrival, he was afebrile, normotensive, bradycardic to 46 beats per minute, tachypneic to 35 breaths per minute, and hypoxemic saturating 75% on 15 L of oxygen via non-rebreather. Patient was illappearing and emergently intubated for worsening respiratory distress and hypoxemia.
Q waves were evident in the inferior leads, and initial troponin was elevated to 25 ng/mL, suggesting a delayed presentation. Other laboratory tests (Table 1) showed leukocytosis to 12,760 cells/µL with a left shift and no lymphopenia, increased creatinine level of 1.90 mg/dL, and elevated inflammatory markers including ferritin (2,634 ng/dL), Creactive protein (259 mg/L), D-dimer (3.52 ng/mL FEU), and interleukin-6 (26 pg/mL). Chest x-ray showed patchy bilateral infiltrates concerning for COVID-19 pneumonia. Chest CT angiography excluded pulmonary embolus and aortic dissection, confirmed bilateral infiltrates. Transthoracic echocardiography showed severely reduced left ventricular ejection fraction of 25% with marked inferolateral wall motion abnormality, mildly depressed right ventricular systolic function, no significant valvular dysfunction, and no pericardial effusion.
Patient received loading doses of aspirin and ticagelor with heparin bolus and drip with a plan for emergent percutaneous coronary intervention (PCI). However, due to a concurrent hemodynamically unstable STEMI occupying the catheterization lab and an anticipated delay of greater than 120 minutes to invasive management, chemical thrombolysis was ultimately  The patient was hypotensive and transferred to the intensive care unit on dopamine, norepinephrine, and vasopressin.
Given the EKG improvement after the administration of thrombolysis and significant bilateral consolidations on CT chest, shock was attributed toward most likely mixed cardiogenic and distributive shock from his underlying pulmonary infection.
Cardiac catheterization was performed 48 hours after thrombolysis due to persistent mixed shock. Coronary angiography revealed subacute appearing thrombosis in two coronary territories, left circumflex (LCX) and right coronary artery (RCA). A large thrombus was identified in the proximal-to-mid LCX, resulting in 90% obstruction with TIMI-3 flow (Fig. 2).
A clear atherosclerotic lesion could not be identified. The RCA was an ectatic, large, dominant vessel with thrombic occlusion in the distal vessel just after the take-off of the posterior descending artery, which remained patent but was a small (1 mm) vessel with TIMI-2 flow (Fig. 3). There did not appear to be any collateral flow to the distal RCA territory. Mild non-obstructive coronary artery disease was seen in the left anterior descending artery and ramus intermedius. Extensive clot was extracted from the LCX by aspiration thrombectomy. However, due to incomplete removal and persistent occlusion, a single drug-eluting stent was placed with 0% residual stenosis and maintenance of TIMI-3 blood flow (Fig. 4). The RCA was not intervened upon as the territory was thought to be non-viable due to inferior Q waves noted on EKG.
Prior to PCI, on positive pressure ventilation (5 cmH 2 0) and vasopressor support, right heart catheterization (RHC) identified the following intracardiac pressures: mean right atrial 9 mmHg, right ventricle 42/5 mmHg, pulmonary artery 42/18 (26) mmHg, and mean pulmonary artery capillary wedge 17 mmHg. Per thermodilution, the mean cardiac output was 8.2 L/minute and mean cardiac index was 3.97 L/min/m2, with a systemic vascular resistance (SVR) of 721 dynes, suggesting a high cardiac output state and low SVR on background vasopressor support more consistent with a predominance of distributive versus cardiogenic shock as a primary mechanism for his hypotension.   Oxygen requirements improved, and he was extubated on day 13. The patient was discharged on hospital day 19 on apixaban and ticagrelor and, on follow-up phone conversations, continues to improve symptomatically.

Discussion
Currently, pathophysiology of the COVID-19 virus is incompletely understood thus creating clinical management challenges. Hypercoagulability and increased rate of arterial thrombosis in multiple vascular beds, including coronary thrombosis causing STEMI, has been observed in patients with COVID-19 (Tan et al., 2020;Tang et al., 2020;Zhang et al., 2020). Proposed mechanisms of hypercoagulability and arterial thrombosis include development of antiphospholipid an-tibodies, complement-mediated endothelial injury, and plaque destabilization due to systemic inflammation (Campbell and Kahwash, 2020;Xiong et al., 2020;Zhang et al., 2020). Consideration of thrombolysis for first-line treatment of STEMI in order to decrease catheterization lab exposure has been suggested for COVID-19 positive patients in ACC/SCAI guidelines (Welt et al., 2020). A case series of STEMI in COVID-19 patients by Bangalore et al. (2020) observed inferior outcomes and a 100% prevalence of elevated D-dimer relative to STEMI patients with COVID-19 (Bangalore et al., 2020). Importantly, most of the patients in this series were managed with emergent cardiac catheterization and not thrombolysis, but notably still with poor outcomes. Bangalore et al. (2020) also found that 10 out of their 18 COVID-19-positive patients with ST elevations on EKG ultimately had noncoronary myocardial injury, There is a nonobstructive lesion in the mid left circumflex coronary artery that was significantly reduced in size but could not be completely obliterated following PCI (Star). PCI: percutaneous coronary intervention.
which is an important consideration to make when deciding whether to give thrombolytics to someone and exposing them to a higher risk of bleeding (Bangalore et al., 2020). It should be noted that, at the time of presentation, it was not known that the patient had a COVID-19 infection. At the time, due to the typical chest pain pattern and the EKG pattern, the pretest probability of coronary obstruction was high enough for this patient to proceed with thrombolysis. While our patient had risk factors for coronary artery disease, we believe that his presentation of heavy thrombus burden in two coronary distributions despite lytic therapy and anticoagulation may be out of proportion to his risk. We believe his coronary occlusions were due to simultaneous thrombotic occlusions triggered by the hy-

Ethics approval and consent to participate
As this is a case report intended for medical and educational purposes, it does not meet regulation criteria necessitating IRB approval, and therefore no IRB approval was obtained. Consent for publication was obtained by the patient and the patient's family.