COVID-19-associated myocarditis
For COVID-19 frequently asked inpatient questions, click here
For COVID-19 frequently asked outpatient questions, click here
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mounika Reddy Vadiyala, M.B.B.S.[2]
Synonyms and keywords: Novel coronavirus, COVID-19, Wuhan Coronavirus, Coronavirus Disease-19, Coronavirus Disease 2019, SARS-CoV-2, COVID-19, COVID-19, 2019-nCoV, 2019 novel coronavirus, Cardiovascular finding in COVID-19, Myocardial injury in COVID-19, Myocarditis, Myocarditis in COVID-19, COVID-19-associated Myocarditis, SARS-CoV2-associated Myocarditis, Myocardial injury in COVID-19, COVID-19 myocarditis
Overview
Studies have demonstrated that COVID-19 interacts with the cardiovascular system, thereby causing myocardial injury and dysfunction as well as increasing morbidity among patients with underlying cardiovascular conditions.
Historical Perspective
- The novel coronavirus, SARS-CoV-2, is identified as the cause of an outbreak of respiratory illness first detected in Wuhan, China in late December 2019. SARS-CoV-2 has rapidly spread across China and in other countries, raising major global concerns. This novel coronavirus, SARS-CoV-2, was named the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) for it similarity severe acute respiratory syndrome related coronaviruses such as SARS-CoV, which caused acute respiratory distress syndrome (ARDS) in 2002–2003.[1][2][3][4][5]
- On January 30, 2020,the World Health Organization(WHO) declared the outbreak as a Public Health Emergency of International Concern.[6]
- On March 12, 2020, the World Health Organization declared the COVID-19 outbreak a pandemic.[7]
Classification
- There is no established system for the classification of the myocarditis seen in COVID-19.
- For more information regarding general classification, see the myocarditis classification.
Pathophysiology
- Studies have demonstrated that COVID-19 interacts with the cardiovascular system, thereby causing myocardial injury and dysfunction as well as increasing morbidity among patients with underlying cardiovascular conditions.
- Myocarditis is an inflammatory disease of the heart characterized by inflammatory infiltrates and myocardial injury without an ischemic cause.[8]
- The major cause of myocarditis in the United States and other developed countries is viral.[9] [10]
- The mechanism is unknown, though several have been proposed based on the limited data outside of case reports.
- Proposed pathophysiology of SARS-CoV-2 myocarditis
- SARS-CoV-2 infection is caused by binding of the viral surface spike protein (primed by TMPRSS2 - Transmembrane Protease Serine 2) to the human angiotensin-converting enzyme 2 (ACE2) receptor.[11]
- ACE2 is expressed in the lung, principally type II alveolar cells which appears to be the principal portal of entry.[12]
- ACE2 is highly expressed in the heart as well.[13]
- Naive T lymphocytes can be primed for viral antigens via antigen-presenting cells and cardio-tropism by the heart-produced hepatocyte growth factor (HGF) which binds c-Met, an HGF receptor on T lymphocytes.[14]
- The primed CD8+ T lymphocytes migrate to the cardiomyocytes and through cell-mediated cytotoxicity, cause myocardial inflammation.
- In the cytokine storm syndrome, proinflammatory cytokines such as Interleukin-6 (IL-6) are released into the circulation, which further augments T-lymphocyte activation and causes the release of more cytokines.[15]
- Cytokine storms result in increased vascular wall permeability and myocardial edema.[16][17]
- Thus a positive feedback loop of immune activation and myocardial damage is established.[18][8]
- Other proposed mechanism includes damage to myocardial cells resulting from respiratory dysfunction and hypoxemia due to COVID-19.
- Pathological changes in the myocardium
- They could be due to viral replication in the myocardium or immune responses caused by the infection or due to systemic responses to respiratory failure.
- Mononuclear inflammatory infiltration has been observed in the heart tissue in COVID-19 autopsy studies.[19]
Epidemiology and Demographics
- The prevalence of cardiovascular disease among patients with COVID-19 is high, and >7% of patients experience myocardial injury from the infection.[20]
- The overall incidence of acute cardiac injury caused by COVID-19 ranges from 7 to 28% among hospitalized patients.[21][22][23]
- The prevalence of myocarditis among COVID-19 patients has not yet been reported; but a number of cases of myocarditis have been reported in COVID-19 patients.[22][17][24][16][25][26][27][28][29]
- Myocarditis has also been reported as the cause of death in some COVID-19 patients.[30]
Age
- COVID-19-associated myocarditis is more commonly observed among elderly patients.[22][23]
Gender
- There is no data on gender predilection to myocarditis in COVID-19.
Race
- There is no data on racial predilection to myocarditis in COVID-19.
Risk Factors
- Common risk factors in the development of [disease name] are [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].
Natural History, Complications and Prognosis
- The majority of patients with [disease name] remain asymptomatic for [duration/years].
- Early clinical features include [manifestation 1], [manifestation 2], and [manifestation 3].
- If left untreated, [#%] of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
- Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
- Prognosis is generally [excellent/good/poor], and the [1/5/10year mortality/survival rate] of patients with [disease name] is approximately [#%].
Diagnosis
Diagnostic Criteria
- The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met:
- [criterion 1]
- [criterion 2]
- [criterion 3]
- [criterion 4]
Signs and Symptoms
Clinical presentations have varied in the reported COVID-19 cases with myocarditis in the literature with a potential overlap in symptomatology in patients with primary COVID-19 infection and COVID-19 patients with clinically suspected myocarditis. Clinical presentation of SARS-CoV-2 myocarditis varies among cases from mild to severe to fulminant.
- Mild - fatigue and dyspnea,[24][16], chest pain or chest tightness on exertion.[17][25]
- Severe - Many patients deteriorate and show symptoms of tachycardia and acute-onset heart failure with cardiogenic shock.[17][24][16] They may also present with signs of right-sided heart failure, including raised jugular venous pressure, right upper quadrant pain, and peripheral edema.[10]
- Fulminant - Fulminant myocarditis is defined as ventricular dysfunction and heart failure within 2–3 weeks of infection.[8][31][26][32] The early signs resemble those of sepsis: fever, low pulse pressure, cold extremities, and sinus tachycardia.[10][17]
According to a study, ventricular arrhythmias are also seen in the patients of myocarditis.[33]
Physical Examination
- Patients with [disease name] usually appear [general appearance].
- Physical examination may be remarkable for:
- [finding 1]
- [finding 2]
- [finding 3]
- [finding 4]
- [finding 5]
- [finding 6]
Laboratory Findings
Inflammatory biomarkers
- Elevated levels of inflammatory markers including erythrocyte sedimentation rate, C reactive protein, and procalcitonin are usually seen in myocarditis but they are non-specific and do not confirm the diagnosis. Increases levels of Interleukin-6 (IL-6), d-dimer, serum ferritin, prothrombin time were seen in COVID-19 patients.[22][15]
Cardiac biomarkers
- Levels of cardiac enzymes such as cardiac troponins (cardiac troponin I(cTnI), cardiac troponin T (cTnT)) and natriuretic peptides (N-terminal pro-B-type natriuretic peptide (NT-proBNP), and Brain natriuretic peptide (BNP)) usually are elevated in myocarditis due to acute myocardial injury and possible ventricular dilation.
- Elevations of both troponin and NT-proBNP levels were observed in the COVID-19–related myocarditis cases.[17][24][16][25][31][34]
- Elevated NT-pro-BNP level has been associated with worse clinical outcomes in severe COVID-19 patients.[35][36]
- Cardiac troponins and brain natriuretic peptides are sensitive but non-specific in the diagnosis of myocarditis.[37][38][39]
- Although a negative troponin result cannot exclude myocarditis, negative serial high-sensitivity cardiac troponin (hs-cTn) still is helpful in the acute phase and makes the diagnosis of acute myocarditis significantly less likely.[40]
Electrocardiogram
- ECG is usually abnormal in myocarditis but it is neither sensitive nor specific in the diagnosis.[41][9]
- ECG abnormalities ST-elevation and PR depression may be observed in myocarditis in COVID-19 patients.[24][9][31]
- However, these abnormalities are not sensitive in detecting myocarditis in COVID-19. For example, one COVID-19–related myocarditis case showed neither ST-elevation nor PR depression.[17]
- Other ECG abnormalities, including new-onset bundle branch block, premature ventricular complexes, QT prolongation, and bradyarrhythmia with advanced atrioventricular nodal block, can be observed in myocarditis.[16]
The American Heart Association (AHA) recommends further testing with 1 or more cardiac imaging methods such as an echocardiogram or cardiovascular magnetic resonance (CMR) for patients having signs consistent with myocarditis.[10] However, echocardiogram or cardiac imaging can be avoided or delayed until recovery from COVID-19 in the patients with COVID-19 and myocardial injury who are hemodynamically and electrophysiologically stable with mild to moderate elevations of troponin unless the patient clinically deteriorates and develops hemodynamic instability, shock, ventricular arrhythmias, or a severely elevated or rapidly rising troponins.[42]
Echocardiography
- The prominent signs of myocarditis on an echocardiogram are increased wall thickness, chamber dilation, diffuse hypokinesia/dyskinesia, and pericardial effusion in the background of ventricular systolic dysfunction.[43][44][9]
- These findings were noted in COVID-19 related myocarditis cases.[16][24][17]
Cardiac Magnetic Resonance
- Cardiac Magnetic resonance (CMR) has major imaging advantages with highest diagnostic accuracy over echocardiography[45], but it has limitations of availability, the requirement for some breath-holding, the requirement for deep cleaning after use given the high contagious risk of COVID-19 and slower throughput.
- If CMR is performed, revised Lake Louise consensus criteria are used to interpret the results.[46] 1) edema 2) irreversible cell injury 3) hyperemia or capillary leak.
- In all of the SARS-CoV-2–related myocarditis cases for which CMR results were reported, myocardial edema and/or scarring were observed.[24][16][25]
Cardiac Computed Tomography
- Cardiac Computed Tomography scan (CT scan) with contrast enhancement and ECG gating is an effective alternative to CMR in terms of rapid testing and minimal requirement of breath-holding, especially when the patient has to undergo a high-resolution CT scan (HRCT) of the chest for assessment of acute respiratory distress syndrome.
- Myocardial hypertrophy due to edema was observed in COVID -19 related myocarditis.[16]
Endomyocardial biopsy
- Endomyocardial biopsy (EMB) has been recommended as the definitive diagnostic tool for myocarditis by the American Heart Association (AHA) and European Society of Cardiology (ESC).[47] In non–COVID-19 cases, endomyocardial biopsy has traditionally been recommended in fulminant presentations to exclude the rare presentation of eosinophilic, hypersensitive,and giant-cell myocarditis.[48] However, in COVID-19, it may not be feasible because of the instability of the patient, requirement of expertise, false-negative rate and risk of contagiousness, especially if the biopsy results would not change clinical management.[9][10][45]
- EMB samples if obtained should be tested for inflammatory infiltrates and for the presence of viral genomes by DNA/RNA extraction.[9]
- In a COVID-19 case reported, EMB showed diffuse T-lymphocytic inflammatory infiltrates with huge interstitial edema and no replacement fibrosis, suggesting an acute inflammatory process. SARS-CoV-2 genome was absent within the myocardium in molecular analysis.[25]
Treatment
Medical Therapy
- There is no definitive treatment for COVID-19-related-myocarditis; the mainstay of therapy is supportive care.
- As per AHA recommendations, in the patients of fulminant myocarditis, initial management includes the protocol of cardiogenic shock which is the administration of inotropes and/vasopressors and mechanical ventilation[24][26]; and use of extracorporeal membrane oxygenation(ECMO), ventricular assistive devices (VAD) in severe cases.[17][49][31] This protocol has been the mainstay of treatment in COVID-19-related-myocarditis cases as well and proved beneficial in mitigating ventricular systolic dysfunction.
- Though the ESC did not approve the use of intravenous immunoglobulins (IVIG) and corticosteroids in active-infection myocarditis, COVID-19 related myocarditis cases have been reported in which use of immunoglobulins and corticosteroids have been successful.[26][17][24][34]
- Tocilizumab, an anti–IL-6 receptor monoclonal antibody, is being tested in a randomized controlled trial of COVID-19 patients with raised IL-6 levels.[50] This might be beneficial in the setting of cytokine storm syndrome and help reduce myocardial inflammation.[40]
Surgery
- Surgery is the mainstay of therapy for [disease name].
- [Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
- [Surgical procedure] can only be performed for patients with [disease stage] [disease name].
Prevention
- There are no primary preventive measures available for [disease name].
- Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].
- Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].
References
- ↑ https://www.cdc.gov/coronavirus/2019-ncov/about/index.html. Missing or empty
|title=(help) - ↑ Lu, Jian; Cui, Jie; Qian, Zhaohui; Wang, Yirong; Zhang, Hong; Duan, Yuange; Wu, Xinkai; Yao, Xinmin; Song, Yuhe; Li, Xiang; Wu, Changcheng; Tang, Xiaolu (2020). "On the origin and continuing evolution of SARS-CoV-2". National Science Review. doi:10.1093/nsr/nwaa036. ISSN 2095-5138.
- ↑ Huang, Chaolin; Wang, Yeming; Li, Xingwang; Ren, Lili; Zhao, Jianping; Hu, Yi; Zhang, Li; Fan, Guohui; Xu, Jiuyang; Gu, Xiaoying; Cheng, Zhenshun; Yu, Ting; Xia, Jiaan; Wei, Yuan; Wu, Wenjuan; Xie, Xuelei; Yin, Wen; Li, Hui; Liu, Min; Xiao, Yan; Gao, Hong; Guo, Li; Xie, Jungang; Wang, Guangfa; Jiang, Rongmeng; Gao, Zhancheng; Jin, Qi; Wang, Jianwei; Cao, Bin (2020). "Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China". The Lancet. 395 (10223): 497–506. doi:10.1016/S0140-6736(20)30183-5. ISSN 0140-6736.
- ↑ https://www.cdc.gov/coronavirus/2019-ncov/about/transmission.html. Missing or empty
|title=(help) - ↑ "WHO | Novel Coronavirus – China".
- ↑ "Coronavirus (COVID-19) events as they happen".
- ↑ "Coronavirus (COVID-19) events as they happen".
- ↑ 8.0 8.1 8.2 Esfandiarei, Mitra; McManus, Bruce M. (2008). "Molecular Biology and Pathogenesis of Viral Myocarditis". Annual Review of Pathology: Mechanisms of Disease. 3 (1): 127–155. doi:10.1146/annurev.pathmechdis.3.121806.151534. ISSN 1553-4006.
- ↑ 9.0 9.1 9.2 9.3 9.4 9.5 Caforio, A. L. P.; Pankuweit, S.; Arbustini, E.; Basso, C.; Gimeno-Blanes, J.; Felix, S. B.; Fu, M.; Helio, T.; Heymans, S.; Jahns, R.; Klingel, K.; Linhart, A.; Maisch, B.; McKenna, W.; Mogensen, J.; Pinto, Y. M.; Ristic, A.; Schultheiss, H.-P.; Seggewiss, H.; Tavazzi, L.; Thiene, G.; Yilmaz, A.; Charron, P.; Elliott, P. M. (2013). "Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: A position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases". European Heart Journal. 34 (33): 2636–2648. doi:10.1093/eurheartj/eht210. ISSN 0195-668X.
- ↑ 10.0 10.1 10.2 10.3 10.4 Kociol, Robb D.; Cooper, Leslie T.; Fang, James C.; Moslehi, Javid J.; Pang, Peter S.; Sabe, Marwa A.; Shah, Ravi V.; Sims, Daniel B.; Thiene, Gaetano; Vardeny, Orly (2020). "Recognition and Initial Management of Fulminant Myocarditis". Circulation. 141 (6). doi:10.1161/CIR.0000000000000745. ISSN 0009-7322.
- ↑ Hoffmann, Markus; Kleine-Weber, Hannah; Schroeder, Simon; Krüger, Nadine; Herrler, Tanja; Erichsen, Sandra; Schiergens, Tobias S.; Herrler, Georg; Wu, Nai-Huei; Nitsche, Andreas; Müller, Marcel A.; Drosten, Christian; Pöhlmann, Stefan (2020). "SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor". Cell. 181 (2): 271–280.e8. doi:10.1016/j.cell.2020.02.052. ISSN 0092-8674.
- ↑ Zhao, Yu; Zhao, Zixian; Wang, Yujia; Zhou, Yueqing; Ma, Yu; Zuo, Wei (2020). doi:10.1101/2020.01.26.919985. Missing or empty
|title=(help) - ↑ Tikellis, Chris; Thomas, M. C. (2012). "Angiotensin-Converting Enzyme 2 (ACE2) Is a Key Modulator of the Renin Angiotensin System in Health and Disease". International Journal of Peptides. 2012: 1–8. doi:10.1155/2012/256294. ISSN 1687-9767.
- ↑ Komarowska, Izabela; Coe, David; Wang, Guosu; Haas, Robert; Mauro, Claudio; Kishore, Madhav; Cooper, Dianne; Nadkarni, Suchita; Fu, Hongmei; Steinbruchel, Daniel A.; Pitzalis, Costantino; Anderson, Graham; Bucy, Pat; Lombardi, Giovanna; Breckenridge, Ross; Marelli-Berg, Federica M. (2015). "Hepatocyte Growth Factor Receptor c-Met Instructs T Cell Cardiotropism and Promotes T Cell Migration to the Heart via Autocrine Chemokine Release". Immunity. 42 (6): 1087–1099. doi:10.1016/j.immuni.2015.05.014. ISSN 1074-7613.
- ↑ 15.0 15.1 Zhou, Fei; Yu, Ting; Du, Ronghui; Fan, Guohui; Liu, Ying; Liu, Zhibo; Xiang, Jie; Wang, Yeming; Song, Bin; Gu, Xiaoying; Guan, Lulu; Wei, Yuan; Li, Hui; Wu, Xudong; Xu, Jiuyang; Tu, Shengjin; Zhang, Yi; Chen, Hua; Cao, Bin (2020). "Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study". The Lancet. 395 (10229): 1054–1062. doi:10.1016/S0140-6736(20)30566-3. ISSN 0140-6736.
- ↑ 16.0 16.1 16.2 16.3 16.4 16.5 16.6 16.7 16.8 Han, Seongwook; Kim, Hyun Ah; Kim, Jin Young; Kim, In-Cheol (2020). "COVID-19-related myocarditis in a 21-year-old female patient". European Heart Journal. 41 (19): 1859–1859. doi:10.1093/eurheartj/ehaa288. ISSN 0195-668X.
- ↑ 17.0 17.1 17.2 17.3 17.4 17.5 17.6 17.7 17.8 17.9 Zeng, Jia-Hui; Liu, Ying-Xia; Yuan, Jing; Wang, Fu-Xiang; Wu, Wei-Bo; Li, Jin-Xiu; Wang, Li-Fei; Gao, Hong; Wang, Yao; Dong, Chang-Feng; Li, Yi-Jun; Xie, Xiao-Juan; Feng, Cheng; Liu, Lei (2020). "First case of COVID-19 complicated with fulminant myocarditis: a case report and insights". Infection. doi:10.1007/s15010-020-01424-5. ISSN 0300-8126.
- ↑ Iakimov VP (1977). "[F. Engels' theory of the origin of man and modern anthropologic findings]". Arkh Anat Gistol Embriol. 72 (6): 5–11. PMID 409380.
- ↑ Xu, Zhe; Shi, Lei; Wang, Yijin; Zhang, Jiyuan; Huang, Lei; Zhang, Chao; Liu, Shuhong; Zhao, Peng; Liu, Hongxia; Zhu, Li; Tai, Yanhong; Bai, Changqing; Gao, Tingting; Song, Jinwen; Xia, Peng; Dong, Jinghui; Zhao, Jingmin; Wang, Fu-Sheng (2020). "Pathological findings of COVID-19 associated with acute respiratory distress syndrome". The Lancet Respiratory Medicine. 8 (4): 420–422. doi:10.1016/S2213-2600(20)30076-X. ISSN 2213-2600.
- ↑ Clerkin, Kevin J.; Fried, Justin A.; Raikhelkar, Jayant; Sayer, Gabriel; Griffin, Jan M.; Masoumi, Amirali; Jain, Sneha S.; Burkhoff, Daniel; Kumaraiah, Deepa; Rabbani, LeRoy; Schwartz, Allan; Uriel, Nir (2020). "COVID-19 and Cardiovascular Disease". Circulation. 141 (20): 1648–1655. doi:10.1161/CIRCULATIONAHA.120.046941. ISSN 0009-7322.
- ↑ Wang, Dawei; Hu, Bo; Hu, Chang; Zhu, Fangfang; Liu, Xing; Zhang, Jing; Wang, Binbin; Xiang, Hui; Cheng, Zhenshun; Xiong, Yong; Zhao, Yan; Li, Yirong; Wang, Xinghuan; Peng, Zhiyong (2020). "Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China". JAMA. 323 (11): 1061. doi:10.1001/jama.2020.1585. ISSN 0098-7484.
- ↑ 22.0 22.1 22.2 22.3 Shi, Shaobo; Qin, Mu; Shen, Bo; Cai, Yuli; Liu, Tao; Yang, Fan; Gong, Wei; Liu, Xu; Liang, Jinjun; Zhao, Qinyan; Huang, He; Yang, Bo; Huang, Congxin (2020). "Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China". JAMA Cardiology. doi:10.1001/jamacardio.2020.0950. ISSN 2380-6583.
- ↑ 23.0 23.1 Guo, Tao; Fan, Yongzhen; Chen, Ming; Wu, Xiaoyan; Zhang, Lin; He, Tao; Wang, Hairong; Wan, Jing; Wang, Xinghuan; Lu, Zhibing (2020). "Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19)". JAMA Cardiology. doi:10.1001/jamacardio.2020.1017. ISSN 2380-6583.
- ↑ 24.0 24.1 24.2 24.3 24.4 24.5 24.6 24.7 24.8 Inciardi, Riccardo M.; Lupi, Laura; Zaccone, Gregorio; Italia, Leonardo; Raffo, Michela; Tomasoni, Daniela; Cani, Dario S.; Cerini, Manuel; Farina, Davide; Gavazzi, Emanuele; Maroldi, Roberto; Adamo, Marianna; Ammirati, Enrico; Sinagra, Gianfranco; Lombardi, Carlo M.; Metra, Marco (2020). "Cardiac Involvement in a Patient With Coronavirus Disease 2019 (COVID-19)". JAMA Cardiology. doi:10.1001/jamacardio.2020.1096. ISSN 2380-6583.
- ↑ 25.0 25.1 25.2 25.3 25.4 Esposito, Antonio; Godino, Cosmo; Basso, Cristina; Cappelletti, Alberto Maria; Tresoldi, Moreno; De Cobelli, Francesco; Vignale, Davide; Villatore, Andrea; Palmisano, Anna; Gramegna, Mario; Peretto, Giovanni; Sala, Simone (2020). "Acute myocarditis presenting as a reverse Tako-Tsubo syndrome in a patient with SARS-CoV-2 respiratory infection". European Heart Journal. 41 (19): 1861–1862. doi:10.1093/eurheartj/ehaa286. ISSN 0195-668X.
- ↑ 26.0 26.1 26.2 26.3 Fang, Yuan; Wei, Xin; Ma, Fenglian; Hu, Hongde (2020). "Coronavirus fulminant myocarditis treated with glucocorticoid and human immunoglobulin". European Heart Journal. doi:10.1093/eurheartj/ehaa190. ISSN 0195-668X.
- ↑ Tavazzi, Guido; Pellegrini, Carlo; Maurelli, Marco; Belliato, Mirko; Sciutti, Fabio; Bottazzi, Andrea; Sepe, Paola Alessandra; Resasco, Tullia; Camporotondo, Rita; Bruno, Raffaele; Baldanti, Fausto; Paolucci, Stefania; Pelenghi, Stefano; Iotti, Giorgio Antonio; Mojoli, Francesco; Arbustini, Eloisa (2020). "Myocardial localization of coronavirus in COVID‐19 cardiogenic shock". European Journal of Heart Failure. 22 (5): 911–915. doi:10.1002/ejhf.1828. ISSN 1388-9842.
- ↑ Coyle, Justin; Igbinomwanhia, Efehi; Sanchez-Nadales, Alejandro; Danciu, Sorin; Chu, Chae; Shah, Nishit (2020). "A Recovered Case of COVID-19 Myocarditis and ARDS Treated With Corticosteroids, Tocilizumab, and Experimental AT-001". JACC: Case Reports. doi:10.1016/j.jaccas.2020.04.025. ISSN 2666-0849.
- ↑ Luetkens, Julian Alexander; Isaak, Alexander; Zimmer, Sebastian; Nattermann, Jacob; Sprinkart, Alois Martin; Boesecke, Christoph; Rieke, Gereon Jonas; Zachoval, Christian; Heine, Annkristin; Velten, Markus; Duerr, Georg Daniel (2020). "Diffuse Myocardial Inflammation in COVID-19 Associated Myocarditis Detected by Multiparametric Cardiac Magnetic Resonance Imaging". Circulation: Cardiovascular Imaging. 13 (5). doi:10.1161/CIRCIMAGING.120.010897. ISSN 1941-9651.
- ↑ Ruan, Qiurong; Yang, Kun; Wang, Wenxia; Jiang, Lingyu; Song, Jianxin (2020). "Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China". Intensive Care Medicine. 46 (5): 846–848. doi:10.1007/s00134-020-05991-x. ISSN 0342-4642.
- ↑ 31.0 31.1 31.2 31.3 Irabien-Ortiz, Ángela; Carreras-Mora, José; Sionis, Alessandro; Pàmies, Julia; Montiel, José; Tauron, Manel (2020). "Fulminant myocarditis due to COVID-19". Revista Española de Cardiología (English Edition). 73 (6): 503–504. doi:10.1016/j.rec.2020.04.005. ISSN 1885-5857.
- ↑ Wang, Daowen; Li, Sheng; Jiang, Jiangang; Yan, Jiangtao; Zhao, Chunxia; Wang, Yan; Ma, Yexin; Zeng, Hesong; Guo, Xiaomei; Wang, Hong; Tang, Jiarong; Zuo, Houjuan; Lin, Li; Cui, Guanglin (2018). "Chinese society of cardiology expert consensus statement on the diagnosis and treatment of adult fulminant myocarditis". Science China Life Sciences. 62 (2): 187–202. doi:10.1007/s11427-018-9385-3. ISSN 1674-7305.
- ↑ Peretto, Giovanni; Sala, Simone; Rizzo, Stefania; Palmisano, Anna; Esposito, Antonio; De Cobelli, Francesco; Campochiaro, Corrado; De Luca, Giacomo; Foppoli, Luca; Dagna, Lorenzo; Thiene, Gaetano; Basso, Cristina; Della Bella, Paolo (2020). "Ventricular Arrhythmias in Myocarditis". Journal of the American College of Cardiology. 75 (9): 1046–1057. doi:10.1016/j.jacc.2020.01.036. ISSN 0735-1097.
- ↑ 34.0 34.1 Doyen, Denis; Moceri, Pamela; Ducreux, Dorothée; Dellamonica, Jean (2020). "Myocarditis in a patient with COVID-19: a cause of raised troponin and ECG changes". The Lancet. 395 (10235): 1516. doi:10.1016/S0140-6736(20)30912-0. ISSN 0140-6736.
- ↑ Gao, Lei; Jiang, Dan; Wen, Xue-song; Cheng, Xiao-cheng; Sun, Min; He, Bin; You, Lin-na; Lei, Peng; Tan, Xiao-wei; Qin, Shu; Cai, Guo-qiang; Zhang, Dong-ying (2020). "Prognostic value of NT-proBNP in patients with severe COVID-19". Respiratory Research. 21 (1). doi:10.1186/s12931-020-01352-w. ISSN 1465-993X.
- ↑ Han, Huan; Xie, Linlin; Liu, Rui; Yang, Jie; Liu, Fang; Wu, Kailang; Chen, Lang; Hou, Wei; Feng, Yong; Zhu, Chengliang (2020). "Analysis of heart injury laboratory parameters in 273 COVID‐19 patients in one hospital in Wuhan, China". Journal of Medical Virology. 92 (7): 819–823. doi:10.1002/jmv.25809. ISSN 0146-6615.
- ↑ Lauer, Bernward; Niederau, Christoph; Kühl, Uwe; Schannwell, Mira; Pauschinger, Matthias; Strauer, Bodo-Eckhard; Schultheiss, Heinz-Peter (1997). "Cardiac Troponin T in Patients With Clinically Suspected Myocarditis". Journal of the American College of Cardiology. 30 (5): 1354–1359. doi:10.1016/S0735-1097(97)00317-3. ISSN 0735-1097.
- ↑ Heymans, S. (2007). "Myocarditis and heart failure: need for better diagnostic, predictive, and therapeutic tools". European Heart Journal. 28 (11): 1279–1280. doi:10.1093/eurheartj/ehm111. ISSN 0195-668X.
- ↑ Jensen, Juliana; Ma, Li-Ping; Fu, Michael L. X.; Svaninger, David; Lundberg, Per-Arne; Hammarsten, Ola (2010). "Inflammation increases NT-proBNP and the NT-proBNP/BNP ratio". Clinical Research in Cardiology. 99 (7): 445–452. doi:10.1007/s00392-010-0140-z. ISSN 1861-0684.
- ↑ 40.0 40.1 Siripanthong, Bhurint; Nazarian, Saman; Muser, Daniele; Deo, Rajat; Santangeli, Pasquale; Khanji, Mohammed Y.; Cooper, Leslie T.; Chahal, C. Anwar A. (2020). "Recognizing COVID-19–related myocarditis: The possible pathophysiology and proposed guideline for diagnosis and management". Heart Rhythm. doi:10.1016/j.hrthm.2020.05.001. ISSN 1547-5271.
- ↑ Ukena, Christian; Mahfoud, Felix; Kindermann, Ingrid; Kandolf, Reinhard; Kindermann, Michael; Böhm, Michael (2011). "Prognostic electrocardiographic parameters in patients with suspected myocarditis". European Journal of Heart Failure. 13 (4): 398–405. doi:10.1093/eurjhf/hfq229. ISSN 1388-9842.
- ↑ Hendren, Nicholas S.; Drazner, Mark H.; Bozkurt, Biykem; Cooper, Leslie T. (2020). "Description and Proposed Management of the Acute COVID-19 Cardiovascular Syndrome". Circulation. 141 (23): 1903–1914. doi:10.1161/CIRCULATIONAHA.120.047349. ISSN 0009-7322.
- ↑ Pinamonti, Bruno; Alberti, Ezip; Cigalotto, Alessandro; Dreas, Lorella; Salvi, Alessandro; Silvestri, Furio; Camerini, Fulvio (1988). "Echocardiographic findings in myocarditis". The American Journal of Cardiology. 62 (4): 285–291. doi:10.1016/0002-9149(88)90226-3. ISSN 0002-9149.
- ↑ Felker, G.Michael; Boehmer, John P; Hruban, Ralph H; Hutchins, Grover M; Kasper, Edward K; Baughman, Kenneth L; Hare, Joshua M (2000). "Echocardiographic findings in fulminant and acute myocarditis". Journal of the American College of Cardiology. 36 (1): 227–232. doi:10.1016/S0735-1097(00)00690-2. ISSN 0735-1097.
- ↑ 45.0 45.1 Friedrich, Matthias G.; Strohm, Oliver; Schulz-Menger, Jeanette; Marciniak, Heinz; Luft, Friedrich C.; Dietz, Rainer (1998). "Contrast Media–Enhanced Magnetic Resonance Imaging Visualizes Myocardial Changes in the Course of Viral Myocarditis". Circulation. 97 (18): 1802–1809. doi:10.1161/01.CIR.97.18.1802. ISSN 0009-7322.
- ↑ Friedrich, Matthias G.; Sechtem, Udo; Schulz-Menger, Jeanette; Holmvang, Godtfred; Alakija, Pauline; Cooper, Leslie T.; White, James A.; Abdel-Aty, Hassan; Gutberlet, Matthias; Prasad, Sanjay; Aletras, Anthony; Laissy, Jean-Pierre; Paterson, Ian; Filipchuk, Neil G.; Kumar, Andreas; Pauschinger, Matthias; Liu, Peter (2009). "Cardiovascular Magnetic Resonance in Myocarditis: A JACC White Paper". Journal of the American College of Cardiology. 53 (17): 1475–1487. doi:10.1016/j.jacc.2009.02.007. ISSN 0735-1097.
- ↑ Dennert, R.; Crijns, H. J.; Heymans, S. (2008). "Acute viral myocarditis". European Heart Journal. 29 (17): 2073–2082. doi:10.1093/eurheartj/ehn296. ISSN 0195-668X.
- ↑ Cooper, Leslie T.; Baughman, Kenneth L.; Feldman, Arthur M.; Frustaci, Andrea; Jessup, Mariell; Kuhl, Uwe; Levine, Glenn N.; Narula, Jagat; Starling, Randall C.; Towbin, Jeffrey; Virmani, Renu (2007). "The Role of Endomyocardial Biopsy in the Management of Cardiovascular Disease". Circulation. 116 (19): 2216–2233. doi:10.1161/CIRCULATIONAHA.107.186093. ISSN 0009-7322.
- ↑ Rao, Sangeetha; Sasser, William; Diaz, Franco; Sharma, Nirmal; Alten, Jeffrey (2014). "Coronavirus Associated Fulminant Myocarditis Successfully Treated With Intravenous Immunoglobulin and Extracorporeal Membrane Oxygenation". Chest. 146 (4): 336A. doi:10.1378/chest.1992018. ISSN 0012-3692.
- ↑ "Favipiravir Combined With Tocilizumab in the Treatment of Corona Virus Disease 2019 - Full Text View - ClinicalTrials.gov".