Author + information
- Alicia Prieto-Lobato, MD,
- Raquel Ramos-Martínez, MD,
- Nuria Vallejo-Calcerrada, MD,
- Miguel Corbí-Pascual, MD and
- Juan G. Córdoba-Soriano, MD∗ (, )@JGCorSo
- ↵∗Address for correspondence:
Dr. Juan Gabriel Córdoba Soriano, Cardiology Department, Complejo Hospitalario Universitario de Albacete, C/ Hermanos Falcó 37 02006, Albacete, Spain.
Coronavirus disease-2019 (COVID-19) triggers a hypercoagulable state with a high incidence of thrombotic complications. We have noted a higher than expected incidence of stent thrombosis in these patients. (Level of Difficulty: Intermediate.)
Advances in percutaneous coronary intervention (PCI) techniques, improvement in coronary stent designs, and more effective antithrombotic therapies have made coronary stent thrombosis a rare complication. The incidence at 30 days is <1%, whereas rates of late and very late stent thrombosis are 0.5% to 1% and 0.2% to 2% per year, respectively (1). Coronavirus disease-2019 (COVID-19) has modified the usual presentation of many diseases as we know them. This disease promotes a sustained prothrombotic state, triggered by interactions among proinflammatory cytokines, procoagulant factors, and platelets. We have recently observed an increase in stent thrombosis during the COVID-19 pandemic peak in our center, the Complejo Hospitalario Universitario de Albacete in Albacete, Spain.
• COVID-19 increases both arterial and venous thrombogenicity.
• The SARS-CoV-2 hypercoagulable state may lead to a stent thrombosis trigger in the presence of other mechanical and biological risk factors.
• Recommendations on antithrombotic treatment and PCI for acute coronary syndromes should be maintained during COVID-19 treatment.
A 49-year-old man underwent primary angioplasty for a lateral ST-segment elevation myocardial infarction (STEMI) 6 h after the onset of symptoms (Figures 1A to 1F). Balloon angioplasty in a small ramus intermedius was performed. To decrease hospital length of stay, ad hoc PCI was performed in the circumflex artery with 2 overlapped drug-eluting stents (DES) (Videos 1 and 2). Thirty minutes later, there was new onset of more intense chest pain with marked ST-segment depression in the precordial leads. Acute circumflex artery stent thrombosis was confirmed by repeat angiography (Video 3). Optical coherence tomography demonstrated in-stent mixed thrombus with mild proximal stent underexpansion and a nonsignificant dissection of the distal stent edge. Intracoronary tirofiban was effective in reducing thrombus burden, and proximal overexpansion of the stent was performed (Videos 4 and 5). The patient received acetyl salicylic acid (ASA), ticagrelor, and a 24-h continuous infusion of tirofiban after the procedure. He had dry cough with a chest radiograph compatible with COVID-19 infection, but no tests were performed because we were at the early stage of the pandemic and the threshold of suspicion was high. The patient was discharged at 4 days. Serological testing 23 days later confirmed that immunoglobulin G was positive for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2).
A 71-year-old man was admitted in 2007 for an inferior STEMI that was treated with right coronary artery DES. He presented with a high-risk non-STEMI resulting from very late right coronary artery stent thrombosis. Thrombectomy, tirofiban, and 2 DESs restored flow. The patient reported fever and cough some days before admission; blood testing and chest radiograph showed COVID-19–compatible findings. The patient remained asymptomatic, and no confirmatory tests were performed for the same reason as in the first patient.
An 86-year-old man with history of non-STEMI in 2018 that was treated with left anterior descending (LAD) artery DES underwent primary angioplasty for 6 h of chest pain and an anterior STEMI. Very late LAD artery stent thrombosis was found, and a new DES was implanted. The patient was asymptomatic, but because the COVID-19 pandemic had reached its peak, a pre-admission polymerase chain reaction test was performed, with a positive result. The patient had a favorable course and was discharged 5 days later.
An 85-year old man underwent PCI with ostial LAD artery DES implantation in 2005. He presented at the pandemic peak with chest pain, a left ventricular ejection fraction of 30%, and anterior ST-segment elevation with prior Q waves (Figures 2A to 2D). The result of immunoglobulin M serological testing was positive despite the absence of respiratory symptoms. Angiography demonstrated very late LAD artery stent thrombosis (Video 6), which was treated with balloon angioplasty, thrombectomy, and tirofiban (Video 7). Intravascular ultrasound was performed and showed in-stent thrombus, appropriate stent expansion, and nonsignificant neoatherosclerosis (Video 8). The patient was treated with combined lopinavir and ritonavir, and despite his age, received ASA and prasugrel as antiplatelet therapy. Ten days later, prasugrel was replaced by clopidogrel (after antiviral treatment was completed), and the patient was discharged.
The COVID-19 pandemic has significantly decreased worldwide interventional cardiology activity. In Spain, cardiac catheterization procedures have been reduced by 48%, with a reduction of 40% for primary angioplasty (2). Similar data have been reported in the United States (3). Compared with the immediate period before the pandemic peak (February 1 to 23, 2020), we experienced a 38% decrease in PCIs at our center between March 15, 2020 and April 5, 2020 (31 vs. 50). Moreover, we had an increase in the incidence of stent thrombosis (4 vs. 0; 13% of PCIs performed during this period). In 2019, we performed 899 PCIs, with 11 (1.2%) cases of stent thrombosis. Given the perception of a high rate of stent thrombosis among COVID-19 cases in other centers in Spain, a prospective registry is being conducted.
A greater thrombogenic predisposition, both arterial and venous, during COVID-19 has been established. Pathophysiologically, the cytokine storm that occurs 5 to 7 days after the onset of symptoms promotes the coagulation cascade, as well as platelet activation mediated by interleukin-6 and tissue factor. The latter induces an increase in thrombin and fibrin synthesis, as well as platelet production. Thrombocytosis can occur, as can high levels of D-dimer and fibrinogen, with intravascular disseminated coagulation criteria often fulfilled (4,5). Additionally, endothelial damage, which could be caused by the virus binding to the angiotensin-converting enzyme receptor and the stasis promoted by the permanent inflammation, would complete the Virchow triad criteria (6).
We present 1 case of acute stent thrombosis and 3 very late stent thrombosis cases (Table 1). Despite no initial COVID-19 testing in 2 cases, symptoms and subsequent testing (Figures 3A to 3D) supported that the patients were infected at the time of stent thrombosis (Table 2).
Very late stent thrombosis with a first-generation DES occurs in the presence of a sustained inflammatory response. Other factors such as delayed endothelialization, late malapposition, or neoatherosclerosis plaque rupture can sometimes be implicated (7). Two of our patients had chronic kidney disease, which can induce a permanent inflammatory response, and 1 patient had a first-generation DES. The patient with acute stent thrombosis had mild proximal stent underexpansion detected by optical coherence tomography. All patients were receiving appropriate antiplatelet therapy at the time of stent thrombosis; the patient with acute thrombosis was following an ASA-clopidogrel regimen, whereas the 3 patients with very late stent thrombosis were taking ASA therapy. We think that SARS-CoV-2 infection triggered stent thrombosis in these patients.
Finally, the latest official statements for COVID-19 patients recommend following current PCI guidelines (8). Expert recommendations have been published on antithrombotic therapy management, with special consideration given to possible interactions with the drugs used for COVID-19 (9). This is especially important with drugs metabolized through CYP3A4, such as clopidogrel or ticagrelor, which could interact with antiviral agents such as lopinavir combined with ritonavir or darunavir combined with cobicistat. Therefore, prasugrel could be the drug of choice in patients without contraindications (prior stroke) but who are >75 years of age or have a weight <60 kg if antiviral agents are considered indispensable. Because of the low evidence on the effectiveness of these antiviral agents against SARS-CoV-2, antiplatelet therapy should be prioritized for COVID-19 patients in the setting of acute coronary syndromes.
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Case Reports author instructions page.
- Abbreviations and Acronyms
- acetyl salicylic acid
- coronavirus disease-2019
- drug-eluting stent
- left anterior descending
- percutaneous coronary intervention
- severe acute respiratory syndrome-coronavirus-2
- ST-segment elevation myocardial infarction
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