Cardioembolic stroke, the most common subtype of stroke in COVID 19: A single center experience from Isfahan, Iran
Marzieh Tajmirriahi1, Maryam Masjedi Esfahani1, Zahra Amouaghaei1, Nahid Mansori1, Pantea Miralaei1, Sahar Sadat Lalehzar1, Peiman Shirani2, Mohammad Saadatnia1
1 Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
2 Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran; Department of Neurosurgery, University of Cincinnati; Department of Neurology, University of Cincinnati, Cincinnati, OH
|Date of Submission||09-Jul-2021|
|Date of Decision||15-Sep-2021|
|Date of Acceptance||09-Dec-2021|
|Date of Web Publication||21-Feb-2023|
Dr. Mohammad Saadatnia
Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences, Isfahan
Source of Support: None, Conflict of Interest: None
Background: Some studies showed the cerebrovascular manifestation in patients with recently pandemic coronavirus 2 named the coronavirus disease 2019 (COVID-19). However, there are rare reports about stroke subtypes in these patients. Here, we reported the stroke subtype in patients with laboratory-confirmed diagnosis of COVID-19 and treated at our hospitals, which are located in Isfahan, Iran. Materials and Methods: This is a retrospective, observational case series. Data were collected from March 01, 2020, to May 20, 2020, at three designated special care centers for COVID-19 of Isfahan University of Medical Sciences. The study included 1188 consecutive hospitalized patients with laboratory-confirmed diagnosis of COVID-19. Results: Of 1188 COVID-19 patients, 7 (0.5%) patients developed stroke. Five (0.4%) had ischemic arterial stroke, 1 (0.08%) hemorrhagic stroke and 1(0.08 %) cerebral venous and sinus thrombosis. Sixty percent of ischemic stroke were cardioembolic stroke (CE) and the rest 2 (40%) were embolic stroke of undetermined source. Three male patients (40%) had stroke as a presenting and admitted symptom of COVID-19. Four patients (57%) had severe COVID-19. Conclusion: Stroke was an uncommon manifestation in COVID-19 patients. CE was a common subtype of stroke in COVID-19 patients in our centers.
Keywords: COVID-19, embolic stroke, infection, stroke
|How to cite this article:|
Tajmirriahi M, Masjedi Esfahani M, Amouaghaei Z, Mansori N, Miralaei P, Lalehzar SS, Shirani P, Saadatnia M. Cardioembolic stroke, the most common subtype of stroke in COVID 19: A single center experience from Isfahan, Iran. J Res Med Sci 2023;28:10
|How to cite this URL:|
Tajmirriahi M, Masjedi Esfahani M, Amouaghaei Z, Mansori N, Miralaei P, Lalehzar SS, Shirani P, Saadatnia M. Cardioembolic stroke, the most common subtype of stroke in COVID 19: A single center experience from Isfahan, Iran. J Res Med Sci [serial online] 2023 [cited 2023 Mar 20];28:10. Available from: https://www.jmsjournal.net/text.asp?2023/28/1/10/370174
| Introduction|| |
Coronavirus disease 2019 (COVID 19) has multiple neurological manifestations including stroke. Acute stroke has been reported to be one of the uncommon presentations in COVID-19 patients with an incidence of 1%–6%.,,,, The consequent imbalance in vasodilation, neuroinflammation, oxidative stress, and thrombogenesis is thought to be the underlying mechanism for stroke pathophysiology during COVID-19. As the data on stroke and COVID-19 are emerging, there is a rare report regarding the subtype of stroke in this population. Here, we report the stroke subtype of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in 1188 patients with laboratory-confirmed diagnosis of COVID-19 and treated at our hospitals, which are located in Isfahan, Iran.
| Methods|| |
Study design and participants
This retrospective, observational study was done at three centers (Khorshid Hospital, Alzahra Hospital, and Kashani hospital) of Isfahan University of Medical Science (IUMS) in Isfahan, Iran. These three centers are designated hospitals assigned by the government to treat patients with COVID-19. We retrospectively analyzed consecutive patients from March 01, 2020, to May 20, 2020, who had been diagnosed as having COVID-19, according to the World Health Organization (WHO) interim guidance.
Assays for COVID-19 were completed in accordance with standards recognized by the WHO. A confirmed case of COVID-19 was defined as a positive result on high amount sequencing or real-time reverse transcription–polymerase chain reaction analysis using a sample obtained through a nasopharyngeal swab.
According to the clinical care needs, radiologic assessments included chest and head computed tomography (CT), and all laboratory testing (a complete blood cell count, blood chemical analysis, coagulation testing, assessment of liver and renal function testing, C-reactive protein, creatine kinase, and lactate dehydrogenase) was performed. One thousand one hundred and eighty-eight hospitalized patients with laboratory confirmation of SARS-CoV-2 were included in the analysis.
Before enrollment, verbal consent was obtained from patients or a relative for patients who could not give consent. The study was performed in accordance with the principles of the Declaration of Helsinki. This study was approved by the Ethics Committee of IUMS on March 01, 2020 (Ethical code: IR.MUI.MED.REC.1399.202).
We used all medical records, nursing records, laboratory findings, and radiologic evaluations for all patients with laboratory-confirmed SARS-CoV-2 infection. All epidemiologic data on age, sex, comorbidities (hypertension, diabetes, smoking, opium addiction, cardiac or cerebrovascular disease, malignancy, and chronic kidney disease), typical symptoms from onset to hospital admission (fever, cough, anorexia, diarrhea, throat pain, and abdominal pain), nervous system symptoms, laboratory findings, and CT scan (chest and head if available) were also included.
Subjective symptoms were afforded by patients who were conscious, cognitively and mentally normal, and linguistically capable to respond to interview. Any missing or uncertain records were clarified through direct communication with involved patients, health-care clinicians, and their families. We defined the degree of severity of COVID-19 (severe vs. nonsevere) at the time of admission using the American Thoracic Society guidelines for community-acquired pneumonia.
All consecutive patients with clinical confirmation of stroke syndrome in neurological consultation during this time frame were included. All stroke diagnoses were reviewed and confirmed by two trained stroke neurologists. Major difference between two reviewers was resolved by consultation with a third reviewer. Stroke subtype and diagnosis were according to the TOAST criteria. Acute ischemic stroke (AIS) patients underwent a standard diagnostic evaluation, including brain CT scan and magnetic resonance imaging (MRI) imaging, intracranial and extracranial vascular imaging, and cardiac evaluation, including electrocardiogram (ECG), continuous cardiac telemetry for at least 24 h, and transthoracic echocardiography. We also included embolic stroke of undetermined source (ESUS) as nonlacunar cryptogenic ischemic strokes in whom embolism was the likely stroke mechanism. Baseline characteristics of stroke patients, type of stroke, Modified Rankin Scale (MRS) at discharge, risk factors for stroke, medications, the National Institutes of Health Stroke Scale/Score, time to presentation – hr, sign and symptom of stroke, vascular territory, imaging for diagnosis of stroke, treatment for stoke, echocardiography findings, ECG findings, cervical and cerebral vessel investigation, and COVID-19 symptoms were recorded. We also followed the patients after 1 month with telephone interview, and the prognosis according to MRS was recorded.
| Results|| |
Among 1188 COVID-19 patients during March 01, 2020, to May 20, 2020, 7 (0.58%) patients developed stroke [Table 1]. Three patients from all COVID-19 (0.25%) had stroke as a presenting symptom of COVID-19. Four from seven stroke patients (57%) had severe COVID-19 manifestation and developed stroke during hospitalization. The average time of onset of stroke after COVID-19 diagnosis was 6.7 days. Of seven patients with acute stroke, five from all COVID-19 (0.42%) and five from seven stroke patients (71.4%) were ischemic arterial stroke, one (0.08%) was hemorrhagic stroke, and one (0.08%) was found to have cerebral venous and sinus thrombosis as the etiology of stroke. The etiology of ischemic stroke was cardioembolic stroke (CE) in three patients from five ischemic stroke patients (60%) and ESUS in two patients (40%). The mortality rate was 40% among stroke patients. [Table 1] shows the clinical characteristics of seven stroke patients with COVID-19.
|Table 1: Clinical characteristic of seven stroke patients with coronavirus disease 2019|
Click here to view
| Discussion|| |
In this study, we showed that the incidence of stroke in COVID patients was not too high and the most frequent type was AIS. Among the AIS patients, the most stroke subtype was CS.
We showed low frequency (0.5%) of cerebrovascular disease in COVID-19 patients. It was in contrary of reports from China that was nearly to 5%. However, recent studies, similar to our study, showed low frequency (1%–2%) of AIS in COVID-19 patients.,,,, Indeed, we included stroke with specific symptom (clinically stroke syndrome), therefore, maybe some stroke patients with nonspecific stroke symptom were overlooked.
Similar to report from other studies,,,,,,, these patients were associated with severe disease and had a higher incidence of risk factors such as hypertension, diabetes, coronary artery disease, and previous cerebrovascular disease. Average time of onset of stroke after COVID 19 diagnosis was lower than Chinese studies. Avula et al study showed stroke can be as a presenting symptom of COVID 19, we showed stroke as a presenting symptom of COVID-19 in near to 50% of patients.
Although Avula et al. revealed that the most plausible mechanism of early cerebrovascular accidents in COVID-19 could be hypercoagulability leading to macro and micro in situ thrombi formation in the vessels, we showed that CE was the most subtype of AIS (60%) and the rest was ESUS (40%). Similar to our study, other recent studies,, showed ESUS and cryptogenic stroke was near to 50% of AIS in COVID-19 patients. Some studies showed that COVID-19 patients are likely to be at risk of arrhythmia due to underlying comorbidities (myocardial injury, myocardial ischemia, hypoxia, shock, and electrolyte disturbances), polypharmacy, and the disease process., All of these mechanisms could be risk factors of CE in COVID-19 patients. As we showed, one patient with new atrial fibrillation, one patient with stress cardiomyopathy (low-ejection fraction), and one patient with myocardial infarction developed embolic stroke.
| Conclusion|| |
Stroke was an uncommon manifestation in COVID-19 patients. CE was a common subtype of stroke in COVID-19 patients in our center, and it can be due to arrhythmia because of underlying comorbidities, polypharmacy, and disease process.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, et al.
Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol 2020;77:683-90.
Jillella DV, Janocko NJ, Nahab F, Benameur K, Greene JG, Wright WL, et al
. Ischemic stroke in COVID-19: An urgent need for early identifcation and management. PLoS One 2020;15:e0239443.
Siegler JE, Cardona P, Arenillas JF, Talavera B, Guillen AN, Chavarría-Miranda A, et al.
Cerebrovascular events and outcomes in hospitalized patients with COVID-19: The SVIN COVID-19 Multinational Registry. Int J Stroke 2021;16:437-47.
Requena M, Olivé-Gadea M, Muchada M, García-Tornel Á, Deck M, Juega J, et al
. COVID-19 and stroke: Incidence and etiological description in a high-volume center. J Stroke Cerebrovasc Dis 2020;29:105225.
Tan YK, Goh C, Leow AS, Tambyah PA, Ang A, Yap ES, et al.
COVID-19 and ischemic stroke: A systematic review and meta-summary of the literature. J Thromb Thrombolysis 2020;50:587-95.
Divani AA, Andalib S, Di Napoli M, Lattanzi S, Hussain MS, Biller J, et al.
Coronavirus disease 2019 and stroke: Clinical manifestations and pathophysiological insights. J Stroke Cerebrovasc Dis 2020;29:104941.
World Health Organization. Clinical Management of Severe Acute Respiratory Infection when Novel Coronavirus (nCoV) Infection is Suspected: Interim Guidance; January 2020. Available from: https://apps.who.int/iris/handle/10665/331446
. [Last accessed on 2020 Feb 05].
Metlay JP, Waterer GW, Long AC, Anzueto A, Brozek J, Crothers K, et al
. Diagnosis and treatment of adults with community-acquired pneumonia: An official clinical practice guideline of the American Thoracic Society and Infectious Disease Society of America. Am J Respir Crit Care Med 2019;200:e45-67.
Adams HP Jr., Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, et al.
Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke 1993;24:35-41.
Hart RG, Diener HC, Coutts SB, Easton JD, Granger CB, O'Donnell MJ, et al
. Embolic strokes of undetermined source: The case for a new clinical construct. Lancet Neurol 2014;13:429-38.
Wilson JL, Hareendran A, Grant M, Baird T, Schulz UG, Muir KW, et al.
Improving the assessment of outcomes in stroke: Use of a structured interview to assign grades on the modified Rankin scale. Stroke. 2002;33:2243-6.
Yaghi S, Ishida K, Torres J, Mac Grory B, Raz E, Humbert K, et al
. SARS2-CoV-2 and stroke in a New York healthcare system. Stroke 2020;51:2002-11.
Avula A, Nalleballe K, Narula N, Sapozhnikov S, Dandu V, Toom S, et al
. COVID-19 presenting as stroke. Brain Behav Immun 2020;87:115-9.
Kochi AN, Tagliari AP, Forleo GB, Fassini GM, Tondo C. Cardiac and arrhythmic complications in patients with COVID-19. J Cardiovasc Electrophysiol 2020;31:1003-8.
Carpenter A, Chambers OJ, El Harchi A, Bond R, Hanington O, Harmer SC, et al.
COVID-19 management and arrhythmia: Risks and challenges for clinicians treating patients affected by SARS-CoV-2. Front Cardiovasc Med 2020;7:85.