ST-Elevation Myocardial Infarction due to Acute Thrombosis in an Adolescent With COVID-19

A previously healthy 49-kg 15-year-old girl presented to the emergency department with a 1-day history of acute-onset, severe chest pain with left shoulder radiation, nausea, and vomiting. She was in her usual state of health until 1 week before presentation, when she developed dyspnea. She developed anosmia 4 days before presentation. The patient’s sister had a positive SARS-CoV-2 polymerase chain reaction result on the day before the patient’s presentation and another close contact had an upper respiratory infection the week before the patient’s symptom onset but did not have SARS-CoV-2 testing. The patient had no significant past medical history, did not smoke, and took no medications.

On initial presentation, the patient was afebrile but ill-appearing with mild tachypnea, normal heart rate, blood pressure, and oxygen saturation in room air. Physical examination revealed no dyspnea, murmur, gallop, conjunctivitis, rash, or calf tenderness. A radiograph of the chest was normal.

Electrocardiography revealed ST elevation in anterolateral leads (V3–V6, I, and aVL), ST depression in leads V1 and V2, and T-wave inversion in lead III (Fig 1). She was given 325 mg of aspirin.

Her initial laboratory evaluation was notable for elevated troponin (0.579 ng/mL; upper limit of normal [ULN] 0.119 ng/mL) and D-dimer (0.92 mg/L; ULN 0.5 mg/L). Results for SARS-CoV-2 polymerase chain reaction on nasopharyngeal swab were positive. There was neutrophilic leukocytosis (15 000/μL) with lymphopenia (absolute lymphocyte count 790/μL). C-reactive protein, procalcitonin, erythrocyte sedimentation rate, platelet count, and ferritin were all normal. A urine pregnancy test result was negative.

Given the concern for cardiac chest pain, with the differential diagnosis including STEMI, myocarditis, and MIS-C, the patient was transferred to a pediatric quaternary care center for further evaluation and management. Repeat laboratory evaluation after arrival at the pediatric referral center (4 hours after initial presentation) revealed rising troponin (13.7 ng/mL) and D-dimer (1.23 mg/L) and elevated serum N-terminal-pro hormone B-type natriuretic peptide (676 pg/mL; ULN 125 pg/mL). She received 1 dose of intravenous immunoglobulin (IVIg) at 2 g/kg given concern for myocarditis and/or MIS-C. Transthoracic echocardiogram revealed akinesis of the left ventricular (LV) apex with normal function of the basal and midwall segments and a resultant ejection fraction of 54% (Supplemental Videos 1 and 2). Right ventricular function was normal and coronary arteries were normal in origin and size. For the diagnosis of STEMI, she was taken emergently to the cardiac catheterization laboratory for coronary angiography under general anesthesia.

In the catherization laboratory, LV end diastolic pressure was elevated (11 mm Hg). Coronary angiography revealed a thrombus in the distal ramus branch of the left coronary artery with abrupt cessation of flow in the distal left anterior descending coronary artery, consistent with complete occlusion near the LV apex (Fig 2, Supplemental Video 3). The right coronary arteries were patent. Given the time to catheterization, distal nature of the thrombosis, and small coronary artery size, percutaneous coronary intervention (PCI) and/or thrombectomy were not performed. A bolus of unfractionated heparin (100 U/kg) was given, followed by a continuous infusion (goal anti–factor Xa level 0.5–0.7 U/mL). For antiplatelet therapy, 2 boluses and 24-hour continuous infusion of eptifibatide (glycoprotein IIb/IIIa inhibitor) were administered, followed by dual antiplatelet therapy (DAPT) with clopidogrel and aspirin.

She was admitted to the pediatric cardiac ICU and treated for acute COVID-19 with a 5-day course of remdesivir. Corticosteroids were not prescribed given the lack of hypoxemia. No additional IVIg nor other immunomodulatory medications were prescribed because her clinical picture was not consistent with MIS-C.

Ultrasonography revealed no deep vein thromboses. Agitated saline echocardiography revealed no patent foramen ovale. She had no personal history of thrombosis. The family history revealed miscarriages in the patient’s mother and sister but no family history of atherosclerosis or MI at a young age. Standard coagulation tests were normal. Targeted thrombophilia testing revealed normal protein C, protein S, and antithrombin III levels, with negative results for prothrombin mutation and lupus anticoagulant. The results for β-2 glycoprotein and anticardiolipin antibodies were negative, aside from an elevated anticardiolipin immunoglobulin G of 56.4 CU (ULN < 20.0 CU). A lipid profile revealed a low high-density lipoprotein at 27.7 mg/dL.

After a peak to 20 ng/dL, serum troponin declined after initiation of antithrombotic therapy. D-dimer declined at 24 hours. At discharge, DAPT, apixaban, atorvastatin, and metoprolol succinate were prescribed.

After discharge, the patient established coordinated care with an adult cardiologist in her hometown and a pediatric cardiologist at the pediatric hospital from which she was discharged. She developed small LV thrombi in the setting of apical akinesis and anticoagulation noncompliance. The patient’s medications were resumed and close outpatient follow-up with her cardiologist was planned.

We present the first reported case of an adolescent with STEMI in the setting of acute SARS-CoV-2 infection. Hypercoagulability⁶  and thrombotic disease⁷  in COVID-19 is thought to be related to microcirculatory inflammation and platelet activation resulting in vascular thromboses.⁵  Inflammatory platelet activation is thought to play a role in MI due to COVID-19 in adults^5,6  and STEMI may be the first presenting clinical manifestation¹  as it was in this pediatric case. Additionally, with the COVID-19 pandemic, MIS-C has emerged.²  Coronary artery ectasia in MIS-C is common, and coronary pathology similar to that seen in Kawasaki disease is associated with myocardial ischemia and infarction.^3,8,9  The association between MI and COVID-19 in children has been anticipated but not yet reported.

There is risk of thromboembolic events in patients with COVID-19. The pathogenesis, although incompletely understood, is likely related to the triad of Virchow of endothelial injury, hypercoagulable state, and blood flow stasis.¹⁰  Endothelial dysfunction is thought to be caused by direct invasion of the endothelial cells by SARS-CoV-2.¹¹  COVID-19 has been associated with a hypercoagulable state induced by increased prothrombotic factors.^5,12  Interestingly, our patient exhibited no elevated inflammatory markers. Although preexisting prothrombotic conditions and family history of thrombosis may pose additional thrombosis risk associated with SARS-CoV-2 infection, the evidence for thrombophilia testing in adults varies widely. Some literature surmises that COVID-19 disease itself suffices as a primary cause of thrombosis and recommends no additional testing, although others suggest extensive testing.^13,14  It is unknown how to apply this range of recommendations to a child with MI. In this case, the patient’s only finding on thrombophilia testing was elevated anticardiolipin IgG. The patient may have developed antiphospholipid syndrome as a result of COVID-19; however, follow-up testing at 12 weeks will be needed to confirm this diagnosis.^15,16  Finally, the patient was not overweight, and her lipid panel revealed merely a low high-density lipoprotein; this was not thought to be a strong risk factor in a healthy 15-year-old patient. Nevertheless, the patient was prescribed atorvastatin for post-MI management for the hypothesized beneficial pleotropic effects, including decreased inflammation, inhibition of platelet aggregation, improved endothelial function, stimulation of endothelial progenitor cells, and increased plaque stability.^17,18 

LV dysfunction by echocardiography should prompt consideration of COVID-19–associated myocarditis. In this case, an empirical dose of IVIg was given for the potential of myocarditis and MIS-C. When ST-segment elevation is noted in a child presenting with COVID-19, myopericarditis should also be considered. In addition, the differential diagnosis of ST elevation is broad and can be divided into ischemic and nonischemic etiologies. Nonischemic etiologies include pericarditis, early repolarization, bundle-branch blocks, and LV hypertrophy with strain.¹⁷  Although the majority of adults who present with acute chest pain, ST elevation, and ischemia have had atherosclerotic plaque rupture, it is important to consider alternative causes of ischemia, particularly in young people.^18,19 

The standard of care for adults is door-to-PCI time within 90 minutes.^16,20  This standard has been reinforced during the COVID-19 pandemic.²¹  Additionally, if PCI is not feasible, transfer to a primary PCI center with intervention within 120 minutes is recommended.^17,20 

Treatment strategies for adolescents with STEMI will need to be extrapolated from the adult recommendations.^17,20  Primary stenting, balloon angioplasty, and manual aspiration thrombectomy were considered in this patient. However, intervention was not attempted because of the small vessel size, evidence of flow around the thrombus, and risk of dissection. Rather, systemic antithrombotic therapies were employed. Alternatively, intracoronary or systemic fibrinolytic therapy, both described in coronary thrombosis due to Kawasaki disease, might be considered in COVID-19–associated STEMI in children.⁸ 

This case presents an adolescent requiring emergent PCI for COVID-19–associated STEMI. Centers without pediatric interventional cardiology expertise should consider whether the age and/or weight threshold should be lowered to include the care of a child requiring PCI for STEMI. The unusual presentation of STEMI in an adolescent, as well as the potential reluctance of adult centers to care for a child requiring PCI, contributed to the delay in this patient’s evaluation. Systemic fibrinolytic therapy might be considered if a delay to PCI is projected.^17,20  Transfer from an adult PCI center to a pediatric center poses challenges. Most pediatric centers are not staffed for emergent PCI. Adult STEMI evaluations can often be done without general anesthesia; however, this may not be feasible in a child. SARS-CoV-2 infection posed an additional issue in this patient who received general anesthesia with endotracheal intubation.

This case describes a 15-year-old patient with acute coronary artery thrombosis–induced STEMI secondary to COVID-19. Coronary artery thrombosis was not a consequence of MIS-C. This patient was treated with systemic anticoagulation and DAPT. Although pediatric MI is exceedingly rare, the hyperinflammatory and hypercoagulable state caused by COVID-19 may be a novel cause of pediatric MI. In addition to myopericarditis, the potential for acute coronary artery thrombosis must be considered in children with COVID-19 presenting with chest pain. PCI centers should reconsider age and weight thresholds for intervention in children. Pediatric centers should consider the need for emergent PCI in a child presenting with MI. Nevertheless, further study of this disease entity is needed, and its distinction from MIS-C must be made.

We thank Drs Aken Desai, James Gaensbauer, Nicholas Houska, Katja Gist, and Michele Loi for their contributions to the care of this patient, participation in reviewing this article, and for the care they provide for children with heart disease, COVID-19, and thrombosis.

COVID-19

coronavirus disease 2019

DAPT

dual antiplatelet therapy

IVIg

intravenous immunoglobulin

LV

left ventricular

MI

myocardial infarction

MIS-C

multisystem inflammatory syndrome in children

PCI

percutaneous coronary intervention

SARS-CoV-2

severe acute respiratory syndrome coronavirus 2

STEMI

ST-elevation myocardial infarction