key: cord-0790830-nii0agzq authors: Ranard, Lauren S; Engel, David J; Kirtane, Ajay J; Masoumi, Amirali title: Coronary and cerebral thrombosis in a young patient after mild COVID-19 illness: a case report date: 2020-10-01 journal: Eur Heart J Case Rep DOI: 10.1093/ehjcr/ytaa270 sha: 47c087f5137c0dac3e1bec16d73ff8483481a013 doc_id: 790830 cord_uid: nii0agzq BACKGROUND: COVID-19 has spread worldwide and has caused significant morbidity and mortality. Myocardial injury and thrombo-embolism are known complications for those with severe forms of disease. The incidence and risk factors for these complications for those patients who are asymptomatic or with mild forms of COVID-19 is unknown. CASE SUMMARY: In this report we describe the case of a 35-year-old man with no past cardiac history who presented with chest pain and a high-sensitivity troponin level of 386 ng/L in the context of an unspecified mild viral illness 1 month previously. Diagnostic evaluation revealed a new cardiomyopathy, left ventricular thrombus, and mid right coronary artery thrombosis. The coronary thrombosis was treated with thrombectomy. SARS-CoV-2 antibodies returned positive. He initially did well post-procedure; however, prior to discharge, he developed a second arterial thrombo-embolism event, a middle cerebral artery stroke. He was treated with thrombectomy and remains hospitalized. DISCUSSION: Recognition that mild COVID-19 can be complicated by subsequent cardiac injury and/or coagulopathy is important. As more people recover from this viral illness and return to normal activity levels, discussion among cardiac experts has begun regarding screening for occult myocardial injury in those who plan to resume competitive athletic activity. This case highlights the need for investigation regarding (i) the duration of thrombophilia after recovery from illness; (ii) the population that should receive thromboprophylaxis; and (iii) the duration of thromboprophylaxis therapy for COVID-19. Coronarvirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in significant morbidity and mortality. 1 Cardiovascular complications, specifically myocardial injury, heart failure, and thrombo-embolic complications, have been well described in patients with severe manifestations of COVID-19. 2 In the hospitalized COVID-19 population, the estimated incidence of developing at least one thromboembolism event is described to be between 8% and 17%, and the specific incidence of arterial thrombosis is estimated to be 3.5-3.7%. 3, 4 Most reported arterial thrombosis events involve peripheral arterial embolism and cerebrovascular infarction. 5 Multivessel in situ coronary thrombosis in the setting of severe COVID-19 illness requiring hospitalization has been described in one case report. 6 To our knowledge, there are no reports describing myocardial injury and thrombosis in patients with mild forms of COVID-19. A 35-year-old man with mild intermittent asthma, class I obesity, and no additional personal/familial cardiovascular risk factors presented to the emergency department (ED) complaining of 1 day of intermittent chest discomfort with associated left-sided jaw pain and nausea. The symptoms began while at rest on the morning prior to admission, subsided through the day, and returned with increased severity in the evening, leading to ED presentation. The patient was in a usual state of health until 1 month previously; at that time, he developed symptoms of cough, non-specific chest pain, dyspnoea, and intermittent fevers (T max 38.78 C). His albuterol inhaler provided only mild relief of symptoms. A chest radiograph (CXR) performed at an urgent care centre was reportedly unremarkable. He was presumed to have COVID-19 as well as an asthma exacerbation; however, he did not receive COVID-19 testing. He was prescribed a 5-day course of azithromycin and a combination inhaler (ipratropium bromide and albuterol). His symptoms resolved within 1 week, and he felt well until the day prior to index presentation. In the ED, temperature was 37.6 C, heart rate 66 b.p.m., respiratory rate 18 breaths/min, and oxygen saturation was 99% on ambient air. Blood pressure was 123/81 mmHg (left arm) and 126/80 mmHg (right arm). The physical exam was unremarkable. The initial work-up in the ED consisted of a 12-lead electrocardiogram (ECG), laboratory testing ( Table 1) , and CXR. The ECG demonstrated sinus rhythm with inferior T-wave inversions, and nonspecific lateral ST depression ( Figure 1 ). Initial laboratory tests were remarkable for a high-sensitivity troponin T (hs-cTnT) of 386 ng/L (normal: < _22 ng/L). The CXR showed a normal cardiac silhouette and clear lung fields. Given the elevated hs-cTnT, the patient received 325 mg aspirin and 80 mg enoxaparin. Subsequent hs-cTnT increased to 502 ng/L, and then to 768 ng/L. A nasopharyngeal swab for SARS-CoV-2 RNA was negative. Transthoracic echocardiogram (TTE) demonstrated a mildly dilated left ventricle [left ventricular (LV) end-diastolic diameter 5.9 cm] and global hypokinesis [ejection fraction (EF) 20-25%] but akinetic inferior and inferolateral walls. A 2.0 cm  0.7 cm mobile thrombus was visualized in the LV apex ( Figure 2 ; Supplementary material online, Video S1). The patient underwent urgent left heart catheterization. Coronary angiography revealed a mid right coronary artery (RCA) thrombus causing 100% occlusion with TIMI 0 flow (Supplementary material online, Video S2). The left coronary anatomy had no coronary disease and demonstrated no retrograde filling of the RCA. After discussion regarding pros and cons of intervention in this setting, reperfusion was elected given the ongoing symptoms. Intravenous cangrelor bolus was administered (2550 lg). Mechanical aspiration thrombectomy and subsequent mechanical-power aspiration thrombectomy were performed utilizing the Indigo System with CAT RX Coronary Aspiration Catheter (Penumbra). Postthrombectomy, a large amount of residual thrombus burden remained, causing 70% residual stenosis and TIMI 2 flow (Supplementary material online, Video S3). At this time, the cangrelor bolus was complete and the patient was administered a loading dose of 180 mg ticagrelor, and started on a tirofiban infusion (loading dose of 2125 lg followed by 12.75 lg/min for 18 h). On admission to the cardiac care unit, he was haemodynamically stable. Subsequently, SARS-CoV-2 antibody testing (Elecsys anti-SARS-CoV-2 test, electrochemiluminescence immunoassay) returned positive. Cardiac magnetic resonance imaging with late gadolinium enhancement tissue characterization demonstrated LVEF of 39%, and near transmural myocardial infarction of the basal-mid 29 inferoseptum and inferior segments with a subendocardial nonenhancing central area suggestive of microvascular obstruction ( Figure 3) . There was no evidence of remote myocardial inflammation on T2-weighted or late gadolinium enhancement imaging. The patient remained chest pain free post-coronary intervention, completed the 18-h tirofiban infusion, and was moved to the cardiology wards. Serial ECGs performed throughout the admission demonstrated non-dynamic ST and T wave changes, unchanged from that shown in Figure 1 . This is a 35-year-old man who presented with newly reduced EF, LV thrombus, and acute coronary thrombosis in the setting of a prior viral illness during the peak of the COVID-19 pandemic. His SARS-CoV-2 antibodies returned positive. suggesting that his recent viral illness was COVID-19. Those with severe COVID-19 are likely to have a predisposition to thrombosis related to excessive inflammation, hypoxia, immobilization, and diffuse intravascular coagulation. Endotheliopathy appears to contribute to the pathophysiology of microcirculatory changes in SARS-CoV-2 infections as the receptor for viral adhesion is an angiotensin-converting enzyme 2 receptor present on endothelial cells. 7 Viral replication can cause inflammatory cell infiltration and endothelial cell apoptosis, leading to microvascular prothrombotic effects and microcirculatory dysfunction and thrombo-embolism. 8 However, the role of this process in those with mild illness or who have recently recovered from COVID-19 infection is unknown. This patient's reduced EF probably pre-dates this acute coronary syndrome (ACS) presentation and accounts for the formation of the large apical thrombus. The normal D-dimer additionally suggests chronicity to his presentation. Although there were no signs of inflammatory myocarditis on cardiac magnetic resonance imaging with non-elevated inflammatory biomarkers, an incomplete recovery of EF after myocarditis remains possible. An endomyocardial biopsy was not performed for further evaluation given the risks associated with performing such a procedure on therapeutic anticoagulation. Possible sequences of events leading up to this patient's presentation include (i) embolization of LV thrombus to the RCA causing ACS; or (ii) an independent thrombotic phenomenon in both the left ventricle and RCA. Recognition that COVID-19 associated with mild symptoms can be complicated by subsequent cardiac injury and/or coagulopathy is important. As more people recover from this viral illness and return to normal activity levels, discussion among cardiac experts has begun regarding screening for occult myocardial injury in those who plan to resume intense and competitive athletic activity. For example, the ACC Sports and Exercise Cardiology Council has put forward a return-to-play guideline algorithm for competitive athletes and highly active people who contracted COVID-19 with mild or severe disease that includes hs-cTnT, TTE, and ECG testing prior to returning to play. 9 This patient's presentation provides support for this conservative approach. Lastly, this case highlights the need for investigation regarding (i) the duration of thrombotic derangements after recovery from illness; (ii) the population that should receive thromboprophylaxis; and (iii) the duration of thromboprophylaxis therapy in COVID-19. Patients with mild forms of COVID-19 remain at risk for COVID-19associated cardiac injury and coagulopathy. More studies are needed to identify those at risk for COVID-19-associated coagulopathy and occult myocardial injury. Supplementary material is available at European Heart Journal -Case Reports online. An interactive web-based dashboard to track COVID-19 in real time Approach to acute cardiovascular complications in COVID-19 infection Incidence of thrombotic complications in critically ill ICU patients with COVID-19 Humanitas COVID-19 Task Force. Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: an updated analysis Multivessel coronary thrombosis in a patient with COVID-19 pneumonia Endothelial cell infection and endotheliitis in COVID-19 COVID-19 and its implications for thrombosis and anticoagulation A game plan for the resumption of sport and exercise after coronavirus disease 2019 (COVID-19) infection Coronary and cerebral thrombosis in a young patient after mild COVID-19 illness The authors would like to thank Shmuel Chen MD PhD, Kevin Clerkin MD MSc, Jonathan Kochav MD, Nitasha Dhiman MD MPH, Jay S. Leb MD, and Dimitrios Karmpaliotis MD PhD for their contributions to this manuscript.Slide sets: A fully edited slide set detailing this case and suitable for local presentation is available online as Supplementary data. The authors confirm that written consent for submission and publication of this case report including images and associated text has been obtained from the patient in line with COPE guidance.Conflict of interest: A.J.K. reports institutional funding to Columbia University and/or the Cardiovascular Research Foundation from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, CSI, CathWorks, Siemens, Philips, and ReCor Medical. In addition to research grants, institutional funding includes fees paid to Columbia University and/or the Cardiovascular Research Foundation for speaking engagements and/or consulting; no speaking/consulting fees were personally received. Personal: travel expenses/meals from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, CSI, CathWorks, Siemens, Philips, ReCor Medical, Chiesi, OpSens, Zoll, and Regeneron. The remaining authors have nothing to disclose.