key: cord-314660-ftcrf6c2 authors: Altamimi, H.; Alahmad, Y.; Khazal, F.; Elhassan, M.; AlBinali, H.; Arabi, A.; AlQahtani, A.; Asaad, N.; Al-Hijji, M.; Hamid, T.; Rafie, I.; Omrani, A. S.; AlKaabi, S.; Alkhal, A.; AlMalslmani, M.; Ali, M.; Alkhani, M.; AlNesf, M.; Abu Jalala, S.; Arafa, S.; ElSousy, R.; AlTamimi, O.; Soaly, E.; Abi khalil, C.; Al Suwaidi, J. title: The Outcome of COVID-19 Patients with Acute Myocardial Infarction date: 2020-07-27 journal: nan DOI: 10.1101/2020.07.21.20156349 sha: doc_id: 314660 cord_uid: ftcrf6c2 Background Coronavirus Disease 2019 (COVID-19) is a rapidly expanding global pandemic resulting in significant morbidity and mortality. COVID-19 patients may present with acute myocardial infarction (AMI). The aim of this study is to conduct detailed analysis on patients with AMI and COVID-19. Methods We included all patients admitted with AMI and actively known or found to be COVID-19 positive by PCR between the 4th February 2020 and the 11th June 2020 in the State of Qatar. Patients were divided into ST-elevation myocardial infarction (STEMI) and Non-STE (NSTEMI). Results There were 68 patients (67 men and 1 woman) admitted between the 4th of February 2020 and the 11th of June 2020 with AMI and COVID-19. The mean age was 49.1, 46 patients had STEMI and 22 had NSTEMI. 38% had diabetes mellitus, 31% had hypertension, 16% were smokers, 13% had dyslipidemia, and 14.7% had prior cardiovascular disease. Chest pain and dyspnea were the presenting symptoms in 90% and 12% of patients respectively. Fever (15%) and cough (15%) were the most common COVID-19 symptoms, while the majority had no viral symptoms. Thirty-nine (33 STEMI and 6 NSTEMI) patients underwent coronary angiography, 38 of them had significant coronary disease. Overall in-hospital MACE was low; 1 patient developed stroke and 2 died. Conclusion Contrary to previous small reports, overall in-hospital adverse events were low in this largest cohort of COVID-19 patients presenting with AMI. We hypothesize patient profile including younger age contributed to these findings. Further studies are required to confirm this observation. Beginning December 2019, a sudden outbreak of SARS-CoV-2 (COVID-19) epidemic started in China and spread to many countries around the world. The WHO declared a public health emergency of international concern on the 30 th Jan 2020, and to date COVID-19 has become a global pandemic infecting >12 million individuals. The pandemic has led to more than 548,000 fatalities so far (1). COVID-19 mainly affects the respiratory tract, and its clinical manifestations are mostly fever, dry cough, fatigue, and dyspnea. In some cases, the virus can develop into severe pneumonia, acute respiratory distress syndrome (ARDS) and multiple organ dysfunctions (2) . Substantial minorities of patients hospitalized with COVID-19 may develop cardiovascular complications. Acute COVID-19 myocardial injury may occur secondary to acute myocardial infarction (AMI) or myocarditis and can lead to cardiomyopathy, ventricular arrhythmias, hemodynamic instability, and death (3) . Furthermore, acute myocardial injury as assessed by troponin release alone appears to be prevalent and is independently associated with worse clinical outcomes among hospitalized COVID-19 patients (2, (4) (5) (6) (7) (8) (9) . The mechanism of acute myocardial injury in COVID-19 patients is unresolved. Several cases of myocarditis have been reported (10) (11) (12) (13) , while myocardial infarction due to acute plaque rupture in the coronary artery or increased myocardial demand in acute infection phase is the other proposed mechanism (14) . AMI among COVID-19 patients may result from severe increase in myocardial demand triggered by infection (type II myocardial infarction) or coagulopathy (15, 16) . Direct myocardial injury may also occur as a result of alteration of angiotensin converting enzyme 2 (ACE2) signaling pathways as it binds to ACE2 receptors of the myocardium and the lung after entry into the human body (17) . Finally, circulating cytokines release during a systemic inflammatory stress may also lead to . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 27, 2020. . https://doi.org/10.1101/2020.07.21.20156349 doi: medRxiv preprint atherosclerotic plaque rupture (14) . Detailed data about AMI among COVID-19 patients are limited to three preliminary studies (18) (19) (20) that included small number of patients and case reports (21) (22) (23) (24) (25) (26) (27) (28) . They provide incomplete and conflicting findings some of which suggesting high prevalence of nonobstructive coronary artery disease and dismal in-hospital outcome. We aim to evaluate the clinical presentation, demographics, risk factors, angiographic findings and clinical outcomes of AMI in COVID-19 patients in Qatar and review the published literature. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 27, 2020. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 27, 2020. . https://doi.org/10.1101/2020.07.21.20156349 doi: medRxiv preprint Primary outcome was in-hospital mortality. Secondary outcomes were major adverse cardiovascular events (MACE), including, recurrent myocardial infarction, stroke, decompensated heart failure, sustained ventricular arrhythmia, atrioventricular heart block, and hemodialysis initiation for acute renal failure. In-hospital outcomes were reported for the entire stay at the Heart Hospital and other COVID-19 facility hospitals in Qatar. Data were presented in the form of frequency and percentages for categorical variables and mean ± standard deviation (SD) or Standard Error (SE). Due to the small sample size, only descriptive analysis was performed. Between the 4 th February 2020 and the 11 th June 2020, 68 patients (67 men and 1 woman) were admitted with COVID-19 and AMI. The mean age of patients was 49.1±9 years, 65 patients were South Asians, 2 Arabs and one was African. Forty-six patients had STEMI (28 anterior and 18 inferior) and 22 patients had NSTEMI (Table 1) . Out of the total 68 patients; 4 patients were known to be COVID-19 positive and were under treatment in a COVID-19 facility when they developed STEMI; the remaining patients were diagnosed with COVID-19 at the time of presentation with AMI. Risk factors analysis (Table 1 ) showed 14.7% had prior cardiovascular disease, 38% of patients had diabetes mellitus, 31% had hypertension, 16% were smokers, and 13% had dyslipidemia. Chest pain and dyspnea were the presenting symptoms in 90% and 12% of patients, respectively. Fever (15%) and cough (16%) were the most prevalent COVID-19 symptoms, while the majority of patients had no viral . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted July 27, 2020. . https://doi.org/10.1101/2020.07.21.20156349 doi: medRxiv preprint symptoms. Most patients had normal white blood cell count and no evidence of lymphopenia on admission ( Table 2) . Most patients received evidence-base therapy. Of the 46 STEMI patients; 38 (82.6%) patients underwent reperfusion therapy (32 PPCI and 7 fibrinolytic therapy), while 8 patients did not undergo reperfusion therapy due to late presentation. One patient underwent successful rescue PCI after failed reperfusion by fibrinolytic therapy. Most of the NSTEMI patients (n=16) were managed initially conservatively with medical therapy alone, while 6 patients underwent coronary angiogram due to hemodynamic instability or persistent chest pain. Those 6 patients underwent subsequent revascularization by PCI (n=3) or CABG (n=3). In total, 39 (57.3%) AMI patients (STEMI & NSTEMI) underwent coronary angiography showing obstructive coronary artery disease (CAD) with at least one culprit lesion in all with the exception of one STEMI patient who had mild non-obstructive CAD (Table 3) . Overall in-hospital MACE were low. In-hospital adverse events were reported in 9 patients only (Table 4 ); 4 patients developed decompensated heart failure, 1 had cardiogenic shock, 1 patient had stroke, 1 patient had stent thrombosis and 2 patients died. Of the two mortalities, one was a 57-year old Asian man with diabetes and hypertension who presented with late inferior myocardial infarction, cough, and fever. The patient was managed conservatively including therapeutic doses of low molecular weight heparin and dual antiplatelet therapy. Three days later he deteriorated developing cardiogenic shock and acute renal failure. The patient expired on day 7 of hospitalization. The second patient was also 57-year old Asian man who presented with inferior STEMI, complete heart block and severe COVID-19 pneumonia. Temporary pacemaker was placed, and coronary angiography was performed showing severe 3-. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 27, 2020. . vessel disease including significant left main coronary artery disease. The patient underwent balloon angioplasty of the culprit artery (RCA). Cardiovascular surgery deemed the patient not candidate for surgery and unfortunately, he progressively developed multi-organ failure and expired on hospitalization day 14. The patient who developed stroke was 44-year old man who underwent PPCI for anterior STEMI and COVID-19 pneumonia. Coronary angiography at that time demonstrated extensive thrombus in the LAD. His procedure was complicated by migration of thrombus into the left circumflex artery after ballooning. The patient was further managed with aspiration thrombectomy, and intravenous infusion of heparin and glycoprotein IIb/IIIa inhibitors. His post-intervention LVEF was 32% without evidence of LV thrombus. The patient stabilized and was transferred to COVID-19 facility to complete his therapy, however on day 8 after STEMI he developed right leg weakness. CT Head and CT Cerebral angiogram were performed without evidence of hemorrhagic or ischemic defects. The patient subsequently recovered completely and discharged home. Four of the 68 patients in the study developed STEMI (all anterior) with symptoms while been treated in a COVID-19 facility for a variable duration of time 8-11 days (ages; 28, 43, 54 and 55 years old). All of them were subsequently transferred to the Heart Hospital and underwent coronary angiography with successful PCI to the LAD. Interestingly the youngest patient (28-year old patient) had highly elevated platelet count 914,000 on the day of presentation and gradually resolved to baseline. The patient had no other parameters to suggest inherited coagulopathy. All four patients were discharged home after successful revascularization. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 27, 2020. . Three COVID-19 patients presented with AMI due to stent thrombosis; Two patients presented with NSTEMI and were found to have very-late stent thrombosis, COVID-19 was diagnosed at the time of presentation; a 45-year old Asian man who presented with obtuse marginal coronary artery stent thrombosis, the other patient was a 58-year old Asian man who presented with thrombosis of LAD stent placed 4 years earlier. The third patient with stent thrombosis initially presented with inferior STEMI and underwent PPCI of the RCA, after stabilization he transferred to a COVID facility, unfortunately antiplatelet therapy was prematurely discontinued and he was transferred back to the Heart Hospital with stent thrombosis 14 days later requiring repeat intervention. All three patients were discharged home after completion of the treatment. The current study provides detailed analysis of the largest cohort of patients with COVID-19 presenting with AMI to-date. Our patients were younger with lower cardiovascular risk profile when compared to previously published small reports (18) (19) (20) . In contrast to most of previous reports (18, 19) which suggested high prevalence of non-obstructive coronary artery disease among AMI COVID-19 patients and worse outcome, significant obstructive coronary angiography was highly prevalent in our cohort, moreover, in-hospital adverse events were very low with only 1 stroke and 2 deaths reported. The COVID-19 pandemic had affected cardiovascular diseases and their management in multiple ways. First, the escalation of this health crisis has led to cancellation of elective cardiovascular procedures and outpatient visits, due to the concern of disease transmission among healthcare providers and other patients, as well as to optimize resource allocation. Second, several investigators reported significant decline in AMI rates during the pandemic. De . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 27, 2020. To date there are only three studies one from Lombardy (Italy) (18) , the other from New York city (19) and more recently from the UK (20) that provided detailed information of AMI among COVID-19 patients, in addition to a number of case reports from around the world (Table 6 ). Stefanini et al in a retrospective analysis reported 29 patients who underwent coronary angiography for STEMI in Lombardy, Italy between February 2020 and March 2020, most had unknown COVID status at the time of presentation. The mean age of patients was 68±11 years, 8 patients (28.6%) were women and 3 (10.7%) had a prior myocardial infarction. The majority presented with typical chest pain with or without dyspnea (78.6%), 6 patients (21.4%) had dyspnea without chest pain (ours was 11%). In contrast to ours, all Lombardy patients underwent urgent coronary angiography, and none were treated with fibrinolysis. 39.3% did not have obstructive coronary artery disease. The mortality rate of their cohort was high 11 (39.3%) . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 27, 2020. . patients were more likely to be diabetic and have hypertension. There was evidence of higher thrombogenicity in the COVID-19 group with significantly higher rates of multi-vessel thrombosis and stent thrombosis and in contrast to the other two reports the majority underwent PCI suggesting the presence of significant obstructive CAD. COVID-19 patients had higher incidence of cardiac arrest and a trend of higher in-hospital mortality rate (17.9% vs 6.5% in Non-COVID-19 patients, p=0.10). This in-hospital mortality was much lower than previous reports (18, 19) . Our patients' populations are almost 10 years younger than these three reports (18) (19) (20) , which may explain the improved survival to discharge when compared to their cohorts. Moreover, most of our patients had no COVID-19 symptoms, severe respiratory distress, or other evidence of coagulopathy at the time of presentation. Contrary to both Stefanini (18) and Banglore (19) reports that suggested high prevalence of non-obstructive coronary artery disease . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 27, 2020. . which has been adopted by our institution. Our study is constrained by the limitations inherent in all studies of observational design. We also acknowledge that this is an early report on a relatively small number of patients, however, to the best of our knowledge this is the largest reported cohort to date. Another limitation of the study is the lack of standard definition of COVID-19 associated myocardial infarction which has not been defined to date. Fourth, 35% of our AMI patients did not undergo coronary angiography because their treated physicians regarded them as low-risk cases and is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 27, 2020. Conclusion: Contrary to previous small reports, the majority of COVID-19 patients presenting with AMI have significant obstructive coronary artery disease and overall excellent in-hospital outcome. We hypothesize patient's profile including younger age contributed to these findings. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 27, 2020. . https://doi.org/10.1101/2020.07.21.20156349 doi: medRxiv preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 27, 2020. . is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 27, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 27, 2020. Medications at admission and on discharge. In-hospital Outcome. Reported studies of AMI COVID-19 patients. . It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 27, 2020. . It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 27, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 27, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 27, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted July 27, 2020. . 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