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Revision as of 01:46, 30 June 2020

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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-Myocarditis, Myocardial injury in COVID-19, COVID-19 myocarditis

Overview

Historical Perspective

[Disease name] was first discovered by [scientist name], a [nationality + occupation], in [year] during/following [event].
In [year], [gene] mutations were first identified in the pathogenesis of [disease name].
In [year], the first [discovery] was developed by [scientist] to treat/diagnose [disease name].

Classification

[Disease name] may be classified according to [classification method] into [number] subtypes/groups:

[group1]
[group2]
[group3]

Other variants of [disease name] include [disease subtype 1], [disease subtype 2], and [disease subtype 3].

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.
Among patients with COVID-19, there is a high prevalence of cardiovascular disease, and >7% of patients experience myocardial injury from the infection.^[1]
Myocarditis is an inflammatory disease of the heart characterized by inflammatory infiltrates and myocardial injury without an ischemic cause.^[2]
- The major cause of myocarditis in the United States and other developed countries is viral.^[3] ^[4]
- A number of cases of myocarditis have been reported in COVID-19 patients.^[5]^[6]^[7]^[8]
- Myocarditis has also been reported as the cause of death in some COVID-19 patients.^[9]
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.^[10]
- ACE2 is expressed in the lung, principally type II alveolar cells which appears to be the principal portal of entry.^[11]
- ACE2 is highly expressed in the heart as well.^[12]
- 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.^[13]
- 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.^[14]
- Cytokine storms result in increased vascular wall permeability and myocardial edema.^[7]^[5]
- Thus a positive feedback loop of immune activation and myocardial damage is established.^[15]^[2]
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.^[16]

Causes

Differentiating [disease name] from other Diseases

[Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as:

[Differential dx1]
[Differential dx2]
[Differential dx3]

Epidemiology and Demographics

The prevalence of [disease name] is approximately [number or range] per 100,000 individuals worldwide.
In [year], the incidence of [disease name] was estimated to be [number or range] cases per 100,000 individuals in [location].

Age

Patients of all age groups may develop [disease name].

[Disease name] is more commonly observed among patients aged [age range] years old.
[Disease name] is more commonly observed among [elderly patients/young patients/children].

Gender

[Disease name] affects men and women equally.

[Gender 1] are more commonly affected with [disease name] than [gender 2].
The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.

Race

There is no racial predilection for [disease name].

[Disease name] usually affects individuals of the [race 1] race.
[Race 2] individuals are less likely to develop [disease name].

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 presentation of SARS-CoV-2 myocarditis varies among cases from mild to severe to fulminant.

Mild - fatigue and dyspnea,^[6]^[7], chest pain or chest tightness on exertion.^[5]^[8]
Severe - Many patients deteriorate and show symptoms of tachycardia and acute-onset heart failure with cardiogenic shock.^[5]^[6]^[7] They may also present with signs of right-sided heart failure, including raised jugular venous pressure, right upper quadrant pain, and peripheral edema.^[4]

Fulminant - Fulminant myocarditis is defined as ventricular dysfunction and heart failure within 2–3 weeks of infection.^[2]^[17]^[18]^[19] The early signs resemble those of sepsis: fever, low pulse pressure, cold extremities, and sinus tachycardia.^[4]^[5]

According to a study, ventricular arrhythmias are also seen in the patients of myocarditis.^[20]

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.^[21]^[14]

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.^[5]^[6]^[7]^[8]^[17]^[22]
Elevated NT-pro-BNP level has been associated with worse clinical outcomes in severe COVID-19 patients.^[23]^[24]
Cardiac troponins and brain natriuretic peptides are sensitive but non-specific in the diagnosis of myocarditis.^[25]^[26]^[27]
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.^[28]

Electrocardiogram

ECG is usually abnormal in myocarditis but it is neither sensitive nor specific in the diagnosis.^[29]^[3]
ECG abnormalities ST-elevation and PR depression may be observed in myocarditis in COVID-19 patients.^[6]^[3]^[17]
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.^[5]
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.^[7]

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.^[4] 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.^[30]

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.^[31]^[32]^[3]
These findings were noted in COVID-19 related myocarditis cases.^[7]^[6]^[5]

Cardiac Magnetic Resonance

Cardiac Magnetic resonance (CMR) has major imaging advantages with highest diagnostic accuracy over echocardiography^[33], 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.^[34] 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.^[6]^[7]^[8]

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.^[7]

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).^[35] 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.^[36] 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.^[3]^[4]^[33]
EMB samples if obtained should be tested for inflammatory infiltrates and for the presence of viral genomes by DNA/RNA extraction.^[3]
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.^[8]

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^[6]^[18]; and use of extracorporeal membrane oxygenation(ECMO), ventricular assistive devices (VAD) in severe cases.^[5]^[37]^[17] 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.^[18]^[5]^[6]^[22]
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.^[38] This might be beneficial in the setting of cytokine storm syndrome and help reduce myocardial inflammation.^[28]

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

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↑ ^3.0 ^3.1 ^3.2 ^3.3 ^3.4 ^3.5 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.
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↑ ^5.00 ^5.01 ^5.02 ^5.03 ^5.04 ^5.05 ^5.06 ^5.07 ^5.08 ^5.09 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.
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↑ 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.
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↑ 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.
↑ ^33.0 ^33.1 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".

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@@ Line 102: / Line 102: @@
 According to a study, [[ventricular arrhythmias]] are also seen in the patients of myocarditis.<ref name="PerettoSala2020">{{cite journal|last1=Peretto|first1=Giovanni|last2=Sala|first2=Simone|last3=Rizzo|first3=Stefania|last4=Palmisano|first4=Anna|last5=Esposito|first5=Antonio|last6=De Cobelli|first6=Francesco|last7=Campochiaro|first7=Corrado|last8=De Luca|first8=Giacomo|last9=Foppoli|first9=Luca|last10=Dagna|first10=Lorenzo|last11=Thiene|first11=Gaetano|last12=Basso|first12=Cristina|last13=Della Bella|first13=Paolo|title=Ventricular Arrhythmias in Myocarditis|journal=Journal of the American College of Cardiology|volume=75|issue=9|year=2020|pages=1046–1057|issn=07351097|doi=10.1016/j.jacc.2020.01.036}}</ref>
 === Physical Examination ===
 *Patients with [disease name] usually appear [general appearance].
@@ Line 114: / Line 113: @@
 === Laboratory Findings ===
-==== Biomarkers ====
+==== Inflammatory biomarkers ====
-*'''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.<ref name="ShiQin2020">{{cite journal|last1=Shi|first1=Shaobo|last2=Qin|first2=Mu|last3=Shen|first3=Bo|last4=Cai|first4=Yuli|last5=Liu|first5=Tao|last6=Yang|first6=Fan|last7=Gong|first7=Wei|last8=Liu|first8=Xu|last9=Liang|first9=Jinjun|last10=Zhao|first10=Qinyan|last11=Huang|first11=He|last12=Yang|first12=Bo|last13=Huang|first13=Congxin|title=Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China|journal=JAMA Cardiology|year=2020|issn=2380-6583|doi=10.1001/jamacardio.2020.0950}}</ref><ref name="ZhouYu2020">{{cite journal|last1=Zhou|first1=Fei|last2=Yu|first2=Ting|last3=Du|first3=Ronghui|last4=Fan|first4=Guohui|last5=Liu|first5=Ying|last6=Liu|first6=Zhibo|last7=Xiang|first7=Jie|last8=Wang|first8=Yeming|last9=Song|first9=Bin|last10=Gu|first10=Xiaoying|last11=Guan|first11=Lulu|last12=Wei|first12=Yuan|last13=Li|first13=Hui|last14=Wu|first14=Xudong|last15=Xu|first15=Jiuyang|last16=Tu|first16=Shengjin|last17=Zhang|first17=Yi|last18=Chen|first18=Hua|last19=Cao|first19=Bin|title=Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study|journal=The Lancet|volume=395|issue=10229|year=2020|pages=1054–1062|issn=01406736|doi=10.1016/S0140-6736(20)30566-3}}</ref>
-**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.<ref name="ShiQin2020">{{cite journal|last1=Shi|first1=Shaobo|last2=Qin|first2=Mu|last3=Shen|first3=Bo|last4=Cai|first4=Yuli|last5=Liu|first5=Tao|last6=Yang|first6=Fan|last7=Gong|first7=Wei|last8=Liu|first8=Xu|last9=Liang|first9=Jinjun|last10=Zhao|first10=Qinyan|last11=Huang|first11=He|last12=Yang|first12=Bo|last13=Huang|first13=Congxin|title=Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China|journal=JAMA Cardiology|year=2020|issn=2380-6583|doi=10.1001/jamacardio.2020.0950}}</ref><ref name="ZhouYu2020">{{cite journal|last1=Zhou|first1=Fei|last2=Yu|first2=Ting|last3=Du|first3=Ronghui|last4=Fan|first4=Guohui|last5=Liu|first5=Ying|last6=Liu|first6=Zhibo|last7=Xiang|first7=Jie|last8=Wang|first8=Yeming|last9=Song|first9=Bin|last10=Gu|first10=Xiaoying|last11=Guan|first11=Lulu|last12=Wei|first12=Yuan|last13=Li|first13=Hui|last14=Wu|first14=Xudong|last15=Xu|first15=Jiuyang|last16=Tu|first16=Shengjin|last17=Zhang|first17=Yi|last18=Chen|first18=Hua|last19=Cao|first19=Bin|title=Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study|journal=The Lancet|volume=395|issue=10229|year=2020|pages=1054–1062|issn=01406736|doi=10.1016/S0140-6736(20)30566-3}}</ref>
+==== Cardiac biomarkers ====
-*'''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.
-**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.<ref name="ZengLiu2020">{{cite journal|last1=Zeng|first1=Jia-Hui|last2=Liu|first2=Ying-Xia|last3=Yuan|first3=Jing|last4=Wang|first4=Fu-Xiang|last5=Wu|first5=Wei-Bo|last6=Li|first6=Jin-Xiu|last7=Wang|first7=Li-Fei|last8=Gao|first8=Hong|last9=Wang|first9=Yao|last10=Dong|first10=Chang-Feng|last11=Li|first11=Yi-Jun|last12=Xie|first12=Xiao-Juan|last13=Feng|first13=Cheng|last14=Liu|first14=Lei|title=First case of COVID-19 complicated with fulminant myocarditis: a case report and insights|journal=Infection|year=2020|issn=0300-8126|doi=10.1007/s15010-020-01424-5}}</ref><ref name="InciardiLupi2020">{{cite journal|last1=Inciardi|first1=Riccardo M.|last2=Lupi|first2=Laura|last3=Zaccone|first3=Gregorio|last4=Italia|first4=Leonardo|last5=Raffo|first5=Michela|last6=Tomasoni|first6=Daniela|last7=Cani|first7=Dario S.|last8=Cerini|first8=Manuel|last9=Farina|first9=Davide|last10=Gavazzi|first10=Emanuele|last11=Maroldi|first11=Roberto|last12=Adamo|first12=Marianna|last13=Ammirati|first13=Enrico|last14=Sinagra|first14=Gianfranco|last15=Lombardi|first15=Carlo M.|last16=Metra|first16=Marco|title=Cardiac Involvement in a Patient With Coronavirus Disease 2019 (COVID-19)|journal=JAMA Cardiology|year=2020|issn=2380-6583|doi=10.1001/jamacardio.2020.1096}}</ref><ref name="HanKim2020">{{cite journal|last1=Han|first1=Seongwook|last2=Kim|first2=Hyun Ah|last3=Kim|first3=Jin Young|last4=Kim|first4=In-Cheol|title=COVID-19-related myocarditis in a 21-year-old female patient|journal=European Heart Journal|volume=41|issue=19|year=2020|pages=1859–1859|issn=0195-668X|doi=10.1093/eurheartj/ehaa288}}</ref><ref name="EspositoGodino2020">{{cite journal|last1=Esposito|first1=Antonio|last2=Godino|first2=Cosmo|last3=Basso|first3=Cristina|last4=Cappelletti|first4=Alberto Maria|last5=Tresoldi|first5=Moreno|last6=De Cobelli|first6=Francesco|last7=Vignale|first7=Davide|last8=Villatore|first8=Andrea|last9=Palmisano|first9=Anna|last10=Gramegna|first10=Mario|last11=Peretto|first11=Giovanni|last12=Sala|first12=Simone|title=Acute myocarditis presenting as a reverse Tako-Tsubo syndrome in a patient with SARS-CoV-2 respiratory infection|journal=European Heart Journal|volume=41|issue=19|year=2020|pages=1861–1862|issn=0195-668X|doi=10.1093/eurheartj/ehaa286}}</ref><ref name="Irabien-OrtizCarreras-Mora2020">{{cite journal|last1=Irabien-Ortiz|first1=Ángela|last2=Carreras-Mora|first2=José|last3=Sionis|first3=Alessandro|last4=Pàmies|first4=Julia|last5=Montiel|first5=José|last6=Tauron|first6=Manel|title=Fulminant myocarditis due to COVID-19|journal=Revista Española de Cardiología (English Edition)|volume=73|issue=6|year=2020|pages=503–504|issn=18855857|doi=10.1016/j.rec.2020.04.005}}</ref><ref name="DoyenMoceri2020">{{cite journal|last1=Doyen|first1=Denis|last2=Moceri|first2=Pamela|last3=Ducreux|first3=Dorothée|last4=Dellamonica|first4=Jean|title=Myocarditis in a patient with COVID-19: a cause of raised troponin and ECG changes|journal=The Lancet|volume=395|issue=10235|year=2020|pages=1516|issn=01406736|doi=10.1016/S0140-6736(20)30912-0}}</ref>
-**Elevations of both [[troponin]] and [[NT-proBNP]] levels were observed in the [[COVID-19–related myocarditis]] cases.<ref name="ZengLiu2020">{{cite journal|last1=Zeng|first1=Jia-Hui|last2=Liu|first2=Ying-Xia|last3=Yuan|first3=Jing|last4=Wang|first4=Fu-Xiang|last5=Wu|first5=Wei-Bo|last6=Li|first6=Jin-Xiu|last7=Wang|first7=Li-Fei|last8=Gao|first8=Hong|last9=Wang|first9=Yao|last10=Dong|first10=Chang-Feng|last11=Li|first11=Yi-Jun|last12=Xie|first12=Xiao-Juan|last13=Feng|first13=Cheng|last14=Liu|first14=Lei|title=First case of COVID-19 complicated with fulminant myocarditis: a case report and insights|journal=Infection|year=2020|issn=0300-8126|doi=10.1007/s15010-020-01424-5}}</ref><ref name="InciardiLupi2020">{{cite journal|last1=Inciardi|first1=Riccardo M.|last2=Lupi|first2=Laura|last3=Zaccone|first3=Gregorio|last4=Italia|first4=Leonardo|last5=Raffo|first5=Michela|last6=Tomasoni|first6=Daniela|last7=Cani|first7=Dario S.|last8=Cerini|first8=Manuel|last9=Farina|first9=Davide|last10=Gavazzi|first10=Emanuele|last11=Maroldi|first11=Roberto|last12=Adamo|first12=Marianna|last13=Ammirati|first13=Enrico|last14=Sinagra|first14=Gianfranco|last15=Lombardi|first15=Carlo M.|last16=Metra|first16=Marco|title=Cardiac Involvement in a Patient With Coronavirus Disease 2019 (COVID-19)|journal=JAMA Cardiology|year=2020|issn=2380-6583|doi=10.1001/jamacardio.2020.1096}}</ref><ref name="HanKim2020">{{cite journal|last1=Han|first1=Seongwook|last2=Kim|first2=Hyun Ah|last3=Kim|first3=Jin Young|last4=Kim|first4=In-Cheol|title=COVID-19-related myocarditis in a 21-year-old female patient|journal=European Heart Journal|volume=41|issue=19|year=2020|pages=1859–1859|issn=0195-668X|doi=10.1093/eurheartj/ehaa288}}</ref><ref name="EspositoGodino2020">{{cite journal|last1=Esposito|first1=Antonio|last2=Godino|first2=Cosmo|last3=Basso|first3=Cristina|last4=Cappelletti|first4=Alberto Maria|last5=Tresoldi|first5=Moreno|last6=De Cobelli|first6=Francesco|last7=Vignale|first7=Davide|last8=Villatore|first8=Andrea|last9=Palmisano|first9=Anna|last10=Gramegna|first10=Mario|last11=Peretto|first11=Giovanni|last12=Sala|first12=Simone|title=Acute myocarditis presenting as a reverse Tako-Tsubo syndrome in a patient with SARS-CoV-2 respiratory infection|journal=European Heart Journal|volume=41|issue=19|year=2020|pages=1861–1862|issn=0195-668X|doi=10.1093/eurheartj/ehaa286}}</ref><ref name="Irabien-OrtizCarreras-Mora2020">{{cite journal|last1=Irabien-Ortiz|first1=Ángela|last2=Carreras-Mora|first2=José|last3=Sionis|first3=Alessandro|last4=Pàmies|first4=Julia|last5=Montiel|first5=José|last6=Tauron|first6=Manel|title=Fulminant myocarditis due to COVID-19|journal=Revista Española de Cardiología (English Edition)|volume=73|issue=6|year=2020|pages=503–504|issn=18855857|doi=10.1016/j.rec.2020.04.005}}</ref><ref name="DoyenMoceri2020">{{cite journal|last1=Doyen|first1=Denis|last2=Moceri|first2=Pamela|last3=Ducreux|first3=Dorothée|last4=Dellamonica|first4=Jean|title=Myocarditis in a patient with COVID-19: a cause of raised troponin and ECG changes|journal=The Lancet|volume=395|issue=10235|year=2020|pages=1516|issn=01406736|doi=10.1016/S0140-6736(20)30912-0}}</ref>
+*Elevated NT-pro-BNP level has been associated with worse clinical outcomes in severe [[COVID-19]] patients.<ref name="GaoJiang2020">{{cite journal|last1=Gao|first1=Lei|last2=Jiang|first2=Dan|last3=Wen|first3=Xue-song|last4=Cheng|first4=Xiao-cheng|last5=Sun|first5=Min|last6=He|first6=Bin|last7=You|first7=Lin-na|last8=Lei|first8=Peng|last9=Tan|first9=Xiao-wei|last10=Qin|first10=Shu|last11=Cai|first11=Guo-qiang|last12=Zhang|first12=Dong-ying|title=Prognostic value of NT-proBNP in patients with severe COVID-19|journal=Respiratory Research|volume=21|issue=1|year=2020|issn=1465-993X|doi=10.1186/s12931-020-01352-w}}</ref><ref name="HanXie2020">{{cite journal|last1=Han|first1=Huan|last2=Xie|first2=Linlin|last3=Liu|first3=Rui|last4=Yang|first4=Jie|last5=Liu|first5=Fang|last6=Wu|first6=Kailang|last7=Chen|first7=Lang|last8=Hou|first8=Wei|last9=Feng|first9=Yong|last10=Zhu|first10=Chengliang|title=Analysis of heart injury laboratory parameters in 273 COVID‐19 patients in one hospital in Wuhan, China|journal=Journal of Medical Virology|volume=92|issue=7|year=2020|pages=819–823|issn=0146-6615|doi=10.1002/jmv.25809}}</ref>
-**Elevated NT-pro-BNP level has been associated with worse clinical outcomes in severe [[COVID-19]] patients.<ref name="GaoJiang2020">{{cite journal|last1=Gao|first1=Lei|last2=Jiang|first2=Dan|last3=Wen|first3=Xue-song|last4=Cheng|first4=Xiao-cheng|last5=Sun|first5=Min|last6=He|first6=Bin|last7=You|first7=Lin-na|last8=Lei|first8=Peng|last9=Tan|first9=Xiao-wei|last10=Qin|first10=Shu|last11=Cai|first11=Guo-qiang|last12=Zhang|first12=Dong-ying|title=Prognostic value of NT-proBNP in patients with severe COVID-19|journal=Respiratory Research|volume=21|issue=1|year=2020|issn=1465-993X|doi=10.1186/s12931-020-01352-w}}</ref><ref name="HanXie2020">{{cite journal|last1=Han|first1=Huan|last2=Xie|first2=Linlin|last3=Liu|first3=Rui|last4=Yang|first4=Jie|last5=Liu|first5=Fang|last6=Wu|first6=Kailang|last7=Chen|first7=Lang|last8=Hou|first8=Wei|last9=Feng|first9=Yong|last10=Zhu|first10=Chengliang|title=Analysis of heart injury laboratory parameters in 273 COVID‐19 patients in one hospital in Wuhan, China|journal=Journal of Medical Virology|volume=92|issue=7|year=2020|pages=819–823|issn=0146-6615|doi=10.1002/jmv.25809}}</ref>
+*Cardiac troponins and brain natriuretic peptides are sensitive but non-specific in the diagnosis of myocarditis.<ref name="LauerNiederau1997">{{cite journal|last1=Lauer|first1=Bernward|last2=Niederau|first2=Christoph|last3=Kühl|first3=Uwe|last4=Schannwell|first4=Mira|last5=Pauschinger|first5=Matthias|last6=Strauer|first6=Bodo-Eckhard|last7=Schultheiss|first7=Heinz-Peter|title=Cardiac Troponin T in Patients With Clinically Suspected Myocarditis|journal=Journal of the American College of Cardiology|volume=30|issue=5|year=1997|pages=1354–1359|issn=07351097|doi=10.1016/S0735-1097(97)00317-3}}</ref><ref name="Heymans2007">{{cite journal|last1=Heymans|first1=S.|title=Myocarditis and heart failure: need for better diagnostic, predictive, and therapeutic tools|journal=European Heart Journal|volume=28|issue=11|year=2007|pages=1279–1280|issn=0195-668X|doi=10.1093/eurheartj/ehm111}}</ref><ref name="JensenMa2010">{{cite journal|last1=Jensen|first1=Juliana|last2=Ma|first2=Li-Ping|last3=Fu|first3=Michael L. X.|last4=Svaninger|first4=David|last5=Lundberg|first5=Per-Arne|last6=Hammarsten|first6=Ola|title=Inflammation increases NT-proBNP and the NT-proBNP/BNP ratio|journal=Clinical Research in Cardiology|volume=99|issue=7|year=2010|pages=445–452|issn=1861-0684|doi=10.1007/s00392-010-0140-z}}</ref>
-** Cardiac troponins and brain natriuretic peptides are sensitive but non-specific in the diagnosis of myocarditis.<ref name="LauerNiederau1997">{{cite journal|last1=Lauer|first1=Bernward|last2=Niederau|first2=Christoph|last3=Kühl|first3=Uwe|last4=Schannwell|first4=Mira|last5=Pauschinger|first5=Matthias|last6=Strauer|first6=Bodo-Eckhard|last7=Schultheiss|first7=Heinz-Peter|title=Cardiac Troponin T in Patients With Clinically Suspected Myocarditis|journal=Journal of the American College of Cardiology|volume=30|issue=5|year=1997|pages=1354–1359|issn=07351097|doi=10.1016/S0735-1097(97)00317-3}}</ref><ref name="Heymans2007">{{cite journal|last1=Heymans|first1=S.|title=Myocarditis and heart failure: need for better diagnostic, predictive, and therapeutic tools|journal=European Heart Journal|volume=28|issue=11|year=2007|pages=1279–1280|issn=0195-668X|doi=10.1093/eurheartj/ehm111}}</ref><ref name="JensenMa2010">{{cite journal|last1=Jensen|first1=Juliana|last2=Ma|first2=Li-Ping|last3=Fu|first3=Michael L. X.|last4=Svaninger|first4=David|last5=Lundberg|first5=Per-Arne|last6=Hammarsten|first6=Ola|title=Inflammation increases NT-proBNP and the NT-proBNP/BNP ratio|journal=Clinical Research in Cardiology|volume=99|issue=7|year=2010|pages=445–452|issn=1861-0684|doi=10.1007/s00392-010-0140-z}}</ref>
+*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.<ref name="SiripanthongNazarian2020">{{cite journal|last1=Siripanthong|first1=Bhurint|last2=Nazarian|first2=Saman|last3=Muser|first3=Daniele|last4=Deo|first4=Rajat|last5=Santangeli|first5=Pasquale|last6=Khanji|first6=Mohammed Y.|last7=Cooper|first7=Leslie T.|last8=Chahal|first8=C. Anwar A.|title=Recognizing COVID-19–related myocarditis: The possible pathophysiology and proposed guideline for diagnosis and management|journal=Heart Rhythm|year=2020|issn=15475271|doi=10.1016/j.hrthm.2020.05.001}}</ref>
-***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.<ref name="SiripanthongNazarian2020">{{cite journal|last1=Siripanthong|first1=Bhurint|last2=Nazarian|first2=Saman|last3=Muser|first3=Daniele|last4=Deo|first4=Rajat|last5=Santangeli|first5=Pasquale|last6=Khanji|first6=Mohammed Y.|last7=Cooper|first7=Leslie T.|last8=Chahal|first8=C. Anwar A.|title=Recognizing COVID-19–related myocarditis: The possible pathophysiology and proposed guideline for diagnosis and management|journal=Heart Rhythm|year=2020|issn=15475271|doi=10.1016/j.hrthm.2020.05.001}}</ref>
 === Electrocardiogram ===
@@ Line 152: / Line 150: @@
 == Treatment ==
 === Medical Therapy ===
-*There is no treatment for [disease name]; the mainstay of therapy is supportive care.
-*The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
-*[Medical therapy 1] acts by [mechanism of action 1].
-*Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].
+*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]]<ref name="InciardiLupi2020">{{cite journal|last1=Inciardi|first1=Riccardo M.|last2=Lupi|first2=Laura|last3=Zaccone|first3=Gregorio|last4=Italia|first4=Leonardo|last5=Raffo|first5=Michela|last6=Tomasoni|first6=Daniela|last7=Cani|first7=Dario S.|last8=Cerini|first8=Manuel|last9=Farina|first9=Davide|last10=Gavazzi|first10=Emanuele|last11=Maroldi|first11=Roberto|last12=Adamo|first12=Marianna|last13=Ammirati|first13=Enrico|last14=Sinagra|first14=Gianfranco|last15=Lombardi|first15=Carlo M.|last16=Metra|first16=Marco|title=Cardiac Involvement in a Patient With Coronavirus Disease 2019 (COVID-19)|journal=JAMA Cardiology|year=2020|issn=2380-6583|doi=10.1001/jamacardio.2020.1096}}</ref><ref name="FangWei2020">{{cite journal|last1=Fang|first1=Yuan|last2=Wei|first2=Xin|last3=Ma|first3=Fenglian|last4=Hu|first4=Hongde|title=Coronavirus fulminant myocarditis treated with glucocorticoid and human immunoglobulin|journal=European Heart Journal|year=2020|issn=0195-668X|doi=10.1093/eurheartj/ehaa190}}</ref>; and use of [[extracorporeal membrane oxygenation]]([[ECMO]]), [[ventricular assistive devices]] ([[VAD]]) in severe cases.<ref name="ZengLiu2020">{{cite journal|last1=Zeng|first1=Jia-Hui|last2=Liu|first2=Ying-Xia|last3=Yuan|first3=Jing|last4=Wang|first4=Fu-Xiang|last5=Wu|first5=Wei-Bo|last6=Li|first6=Jin-Xiu|last7=Wang|first7=Li-Fei|last8=Gao|first8=Hong|last9=Wang|first9=Yao|last10=Dong|first10=Chang-Feng|last11=Li|first11=Yi-Jun|last12=Xie|first12=Xiao-Juan|last13=Feng|first13=Cheng|last14=Liu|first14=Lei|title=First case of COVID-19 complicated with fulminant myocarditis: a case report and insights|journal=Infection|year=2020|issn=0300-8126|doi=10.1007/s15010-020-01424-5}}</ref><ref name="RaoSasser2014">{{cite journal|last1=Rao|first1=Sangeetha|last2=Sasser|first2=William|last3=Diaz|first3=Franco|last4=Sharma|first4=Nirmal|last5=Alten|first5=Jeffrey|title=Coronavirus Associated Fulminant Myocarditis Successfully Treated With Intravenous Immunoglobulin and Extracorporeal Membrane Oxygenation|journal=Chest|volume=146|issue=4|year=2014|pages=336A|issn=00123692|doi=10.1378/chest.1992018}}</ref><ref name="Irabien-OrtizCarreras-Mora2020">{{cite journal|last1=Irabien-Ortiz|first1=Ángela|last2=Carreras-Mora|first2=José|last3=Sionis|first3=Alessandro|last4=Pàmies|first4=Julia|last5=Montiel|first5=José|last6=Tauron|first6=Manel|title=Fulminant myocarditis due to COVID-19|journal=Revista Española de Cardiología (English Edition)|volume=73|issue=6|year=2020|pages=503–504|issn=18855857|doi=10.1016/j.rec.2020.04.005}}</ref> 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.<ref name="FangWei2020">{{cite journal|last1=Fang|first1=Yuan|last2=Wei|first2=Xin|last3=Ma|first3=Fenglian|last4=Hu|first4=Hongde|title=Coronavirus fulminant myocarditis treated with glucocorticoid and human immunoglobulin|journal=European Heart Journal|year=2020|issn=0195-668X|doi=10.1093/eurheartj/ehaa190}}</ref><ref name="ZengLiu2020">{{cite journal|last1=Zeng|first1=Jia-Hui|last2=Liu|first2=Ying-Xia|last3=Yuan|first3=Jing|last4=Wang|first4=Fu-Xiang|last5=Wu|first5=Wei-Bo|last6=Li|first6=Jin-Xiu|last7=Wang|first7=Li-Fei|last8=Gao|first8=Hong|last9=Wang|first9=Yao|last10=Dong|first10=Chang-Feng|last11=Li|first11=Yi-Jun|last12=Xie|first12=Xiao-Juan|last13=Feng|first13=Cheng|last14=Liu|first14=Lei|title=First case of COVID-19 complicated with fulminant myocarditis: a case report and insights|journal=Infection|year=2020|issn=0300-8126|doi=10.1007/s15010-020-01424-5}}</ref><ref name="InciardiLupi2020">{{cite journal|last1=Inciardi|first1=Riccardo M.|last2=Lupi|first2=Laura|last3=Zaccone|first3=Gregorio|last4=Italia|first4=Leonardo|last5=Raffo|first5=Michela|last6=Tomasoni|first6=Daniela|last7=Cani|first7=Dario S.|last8=Cerini|first8=Manuel|last9=Farina|first9=Davide|last10=Gavazzi|first10=Emanuele|last11=Maroldi|first11=Roberto|last12=Adamo|first12=Marianna|last13=Ammirati|first13=Enrico|last14=Sinagra|first14=Gianfranco|last15=Lombardi|first15=Carlo M.|last16=Metra|first16=Marco|title=Cardiac Involvement in a Patient With Coronavirus Disease 2019 (COVID-19)|journal=JAMA Cardiology|year=2020|issn=2380-6583|doi=10.1001/jamacardio.2020.1096}}</ref><ref name="DoyenMoceri2020">{{cite journal|last1=Doyen|first1=Denis|last2=Moceri|first2=Pamela|last3=Ducreux|first3=Dorothée|last4=Dellamonica|first4=Jean|title=Myocarditis in a patient with COVID-19: a cause of raised troponin and ECG changes|journal=The Lancet|volume=395|issue=10235|year=2020|pages=1516|issn=01406736|doi=10.1016/S0140-6736(20)30912-0}}</ref>
+*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.<ref>{{cite web |url=https://clinicaltrials.gov/ct2/show/NCT04310228 |title=Favipiravir Combined With Tocilizumab in the Treatment of Corona Virus Disease 2019 - Full Text View - ClinicalTrials.gov |format= |work= |accessdate=}}</ref> This might be beneficial in the setting of cytokine storm syndrome and help reduce myocardial inflammation.<ref name="SiripanthongNazarian2020">{{cite journal|last1=Siripanthong|first1=Bhurint|last2=Nazarian|first2=Saman|last3=Muser|first3=Daniele|last4=Deo|first4=Rajat|last5=Santangeli|first5=Pasquale|last6=Khanji|first6=Mohammed Y.|last7=Cooper|first7=Leslie T.|last8=Chahal|first8=C. Anwar A.|title=Recognizing COVID-19–related myocarditis: The possible pathophysiology and proposed guideline for diagnosis and management|journal=Heart Rhythm|year=2020|issn=15475271|doi=10.1016/j.hrthm.2020.05.001}}</ref>
 === Surgery ===
 *Surgery is the mainstay of therapy for [disease name].