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Figure.  Images of the Patient’s Coronary Arteries
Images of the Patient’s Coronary Arteries

A, Coronary angiography demonstrates occlusion of the proximal left anterior descending coronary artery (arrowheads). B-E, Optical coherence tomography images showing a large mixed thrombus (B and C; yellow asterisks) overlying a segment with uncovered struts (D; white arrowheads), with malapposition at the proximal segment of the stent (E; yellow arrowheads). The black asterisk denotes the wire artifact.

1.
Shi  S, Qin  M, Shen  B,  et al.  Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China.   JAMA Cardiol. Published online March 25, 2020. doi:10.1001/jamacardio.2020.0950PubMedGoogle Scholar
2.
Driggin  E, Madhavan  MV, Bikdeli  B,  et al.  Cardiovascular considerations for patients, health care workers, and health systems during the COVID-19 pandemic.   J Am Coll Cardiol. 2020;75(18):2352-2371. doi:10.1016/j.jacc.2020.03.031PubMedGoogle ScholarCrossref
3.
Wang  J, Hajizadeh  N, Moore  EE,  et al.  Tissue plasminogen activator (tPA) treatment for COVID-19 associated acute respiratory distress syndrome (ARDS): a case series.   J Thromb Haemost. Published online April 10, 2020. doi:10.1111/jth.14828PubMedGoogle Scholar
4.
Alfonso  F.  The “vulnerable” stent why so dreadful?   J Am Coll Cardiol. 2008;51(25):2403-2406. doi:10.1016/j.jacc.2008.03.029PubMedGoogle ScholarCrossref
Research Letter
July 8, 2020

Late Coronary Stent Thrombosis in a Patient With Coronavirus Disease 2019

Author Affiliations
  • 1Hospital Universitario de La Princesa, Madrid, Spain
  • 2Instituto de Investigación Sanitaria de La Princesa, Centro de Investigación Biomédica en Red–Enfermedades Cardiovasculares, Hospital Universitario de La Princesa, Department of Cardiology, Universidad Autónoma de Madrid, Madrid, Spain
JAMA Cardiol. 2020;5(10):1195-1198. doi:10.1001/jamacardio.2020.2459

The excessive inflammatory response and hypercoaguable state associated with coronavirus disease 2019 (COVID-19) might trigger acute coronary events or stent thrombosis. However, cases of stent thrombosis directly associated with COVID-19 have not been reported.

Methods

We describe a patient with COVID-19 developing late drug-eluting stent thrombosis. Academic ethics committee approval was waived because this was a single-case report; written informed consent was obtained from the patient.

Results

An 81-year-old man with hypertension, coronary artery disease, and recent COVID-19 infection presented in April 2020 with an anterior ST-segment elevation myocardial infarction. Five years prior to admission, following a myocardial infarction, drug-eluting stents were implanted in his left main to left anterior descending coronary artery (LAD), circumflex coronary artery, and right coronary artery. Three months prior to admission, an exercise test with a positive result led to the implantation of a durable-polymer ridaforolimus drug-eluting stent (3 × 15 mm) in a de novo lesion in the proximal left anterior descending coronary artery, overlapping with the stent coming from the left main coronary artery. He was compliant with a dual antiplatelet regimen of aspirin and clopidogrel. Ten days prior to admission, he was admitted to another hospital for dyspnea and fever, with a final diagnosis of COVID-19 with bilateral pneumonia. A marked increase in inflammatory markers was observed, including elevated levels of D-dimer (63 μg/mL [to convert to nanomoles per liter, multiply by 5.476]), fibrinogen (850 mg/dL [to convert to grams per liter, multiply by 0.01]), lactate dehydrogenase (423 U/L [to convert microkatals per liter, multiply by 0.0167]), C-reactive protein (5.5 mg/dL [to convert to milligrams per liter, multiply by 10]), and interleukin 6 (95 pg/mL). Treatment included hydroxychloroquine, azithromycin, and oxygen, with clinical improvement. On transfer to our institution, urgent coronary angiography revealed thrombotic occlusion of the left anterior descending coronary artery stent (Figure, A). Mechanical thromboaspiration failed to retrieve any macroscopic thrombus but restored coronary flow. Optical coherence tomography revealed a large occlusive mixed thrombus (Figure, B and C) overlying a segment with uncovered struts (Figure, D). Malapposition was demonstrated at the proximal segment of the stent (Figure, E). The minimal stent area was 4.6 mm2, with a stent expansion (compared with mean reference lumen areas) of 72%. Balloon angioplasty (with a 3.0-mm, noncompliant balloon at 22 atmospheres) obtained an excellent angiographic result. Repeated optical coherence tomography revealed some residual thrombus but improved expansion and malapposition.

A real-time reverse transcriptase–polymerase chain reaction test had a positive result for severe acute respiratory syndrome coronavirus 2. The patient was treated with tirofiban, aspirin, and ticagrelor with a favorable clinical course and discharged 2 days later.

Discussion

Severe acute respiratory syndrome coronavirus 2 is currently causing a pandemic, with an exponential increase in cases worldwide. Only 15% of patients with COVID-19 require hospitalization, typically for pneumonia, but 5% require intensive care.1,2 Severe cases show elevation in cardiac troponins and clinical evidence of myocardial injury, with some reported cases of myocarditis.1,2 Coronavirus disease 2019 activates the angiotensin-converting enzyme 2 receptor, which is largely expressed in vascular tissues, and may induce endothelial dysfunction.1,2 It has been speculated that coronary plaque destabilization might occur in patients with excessive inflammatory response characterized by a cytokine storm, which may be further aggravated in a scenario of severe hypoxia. The hallmark of severe COVID-19 is coagulopathy, with some patients meeting criteria for disseminated intravascular coagulation.3 This is a predominantly prothrombotic phenomenon, with high venous thromboembolism rates, microvascular thrombosis, elevated D-dimer and fibrinogen levels, and low antithrombin levels.1-3 Ritonavir, which is frequently prescribed to patients with severe COVID-19 disease,1-3 decreases the levels of clopidogrel active metabolite and was not given to this patient.

To our knowledge, this is the first description of stent thrombosis in a patient with COVID-19. The cause of this complication appears to be multifaceted. First, optical coherence tomography unraveled several potential underlying mechanical factors (stent underexpansion, uncovered struts, and malapposition) that may predispose the patient to stent thrombosis.4 The relative importance of each of these factors in this patient is difficult to establish, but most of the thrombus was associated with uncovered rather than malapposed struts. Second, the intense inflammatory and prothrombotic milieu, which is characteristic of COVID-19 infection,1,2 may constitute the trigger event eliciting late stent thrombosis.

Nevertheless, because this is a single-case report, we are unable to establish that the episode of stent thrombosis was actually caused by COVID-19 disease. This also precludes generalizability of our findings to other patients with COVID-19. However, these findings suggest that special care should be paid to optimize antithrombotic therapy in patients with COVID-19 with previous coronary artery disease.

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Article Information

Accepted for Publication: May 18, 2020.

Corresponding Author: Fernando Alfonso, MD, PhD, Instituto de Investigación Sanitaria de La Princesa, Centro de Investigación Biomédica en Red–Enfermedades Cardiovasculares, Hospital Universitario de La Princesa, Department of Cardiology, Universidad Autónoma de Madrid, c/Diego de León 62, Madrid 28006, Spain(falf@hotmail.com).

Published Online: July 8, 2020. doi:10.1001/jamacardio.2020.2459

Author Contributions: Drs Antuña and Alfonso had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Alfonso, Antuña, Cuesta, Rivero.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Alfonso, Antuña, Rivero.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Antuña.

Obtained funding: Antuña.

Administrative, technical, or material support: Antuña, Del Val.

Supervision: Alfonso, Antuña, Cuesta, Rivero.

Other: Antuña.

Conflict of Interest Disclosures: None reported.

References
1.
Shi  S, Qin  M, Shen  B,  et al.  Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China.   JAMA Cardiol. Published online March 25, 2020. doi:10.1001/jamacardio.2020.0950PubMedGoogle Scholar
2.
Driggin  E, Madhavan  MV, Bikdeli  B,  et al.  Cardiovascular considerations for patients, health care workers, and health systems during the COVID-19 pandemic.   J Am Coll Cardiol. 2020;75(18):2352-2371. doi:10.1016/j.jacc.2020.03.031PubMedGoogle ScholarCrossref
3.
Wang  J, Hajizadeh  N, Moore  EE,  et al.  Tissue plasminogen activator (tPA) treatment for COVID-19 associated acute respiratory distress syndrome (ARDS): a case series.   J Thromb Haemost. Published online April 10, 2020. doi:10.1111/jth.14828PubMedGoogle Scholar
4.
Alfonso  F.  The “vulnerable” stent why so dreadful?   J Am Coll Cardiol. 2008;51(25):2403-2406. doi:10.1016/j.jacc.2008.03.029PubMedGoogle ScholarCrossref
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