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-__NOTOC__
-{{COVID-19}}
-To go to the COVID-19 project topics list, click '''[[COVID-19 Project Topics|here]]'''.
-{{CMG}} {{AE}} {{mitra}}{{MC}}{{TAM}}{{AyeshaFJ}}{{MRV}}{{SaraH}}
-==Overview==
-==Complications==
-===Myocardial injury===
-*COVID-19 patients with cardiovascular comorbidities have higher mortality.
-*Hospitalized patients with COVID-19 and Cardiovascular disease seem to be more prevalent in both the USA and China. <ref name="pmid32354800">{{cite journal| author=Kang Y, Chen T, Mui D, Ferrari V, Jagasia D, Scherrer-Crosbie M | display-authors=etal| title=Cardiovascular manifestations and treatment considerations in covid-19. | journal=Heart | year= 2020 | volume=  | issue=  | pages=  | pmid=32354800 | doi=10.1136/heartjnl-2020-317056 | pmc=7211105 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32354800  }} </ref>
-*In a case series with 187 patients who had confirmed COVID-19, 27.8% of patients had a myocardial injury, which caused cardiac dysfunction and arrhythmias. The result was significantly higher mortality among patients with myocardial injury.
-* It seems to be advisable to triage patients with COVID-19 based on their underlying CVD for a more aggressive treatment plan.
-*The mortality during hospitalization was shown to be 7.62% for patients without underlying CVD and normal TnT levels, 13.33% for those with underlying CVD and normal TnT levels, 37.50% for those without underlying CVD but elevated TnT levels, and 69.44% for those with underlying CVD and elevated TnTs.<ref name="pmid32219356">{{cite journal| author=Guo T, Fan Y, Chen M, Wu X, Zhang L, He T | display-authors=etal| title=Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19). | journal=JAMA Cardiol | year= 2020 | volume=  | issue=  | pages=  | pmid=32219356 | doi=10.1001/jamacardio.2020.1017 | pmc=7101506 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32219356  }} </ref>
-===Acute Coronary Syndromes===
-====Pathophysiology====
-The mechanism of COVID-19 cardiovascular injury has not been fully understood and is likely multifactorial.
-*SARS-CoV-2 virus attaches to ACE 2 protein for ligand binding before entering the cell via receptor-mediated endocytosis.
-**Based on single-cell RNA sequencing more than 7.5% of myocardial cells have positive ACE2 expression. This protein can mediate the entry of SARS-CoV-2 and result in direct cardiotoxicity.
-*The cytokine release caused by the virus may lead to vascular inflammation, plaque instability, myocardial inflammation, a hypercoagulable state, or direct myocardial suppression.
-Pathological changes:
-*In the level of cardiac tissue: minimal change to interstitial inflammatory infiltration and myocyte necrosis
-*In the level of vasculature: micro-thrombosis and vascular inflammation<ref name="pmid32354800">{{cite journal| author=Kang Y, Chen T, Mui D, Ferrari V, Jagasia D, Scherrer-Crosbie M | display-authors=etal| title=Cardiovascular manifestations and treatment considerations in covid-19. | journal=Heart | year= 2020 | volume=  | issue=  | pages=  | pmid=32354800 | doi=10.1136/heartjnl-2020-317056 | pmc=7211105 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32354800  }} </ref>
-====Signs and Symptoms====
-The signs and symptoms of acute coronary syndrome include:<ref name="pmid16267320">{{cite journal| author=Abidov A, Rozanski A, Hachamovitch R, Hayes SW, Aboul-Enein F, Cohen I et al.| title=Prognostic significance of dyspnea in patients referred for cardiac stress testing. | journal=N Engl J Med | year= 2005 | volume= 353 | issue= 18 | pages= 1889-98 | pmid=16267320 | doi=10.1056/NEJMoa042741 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16267320  }}  [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17213112 Review in: Evid Based Med. 2006 Jun;11(3):91] </ref>
-*[[Chest pain]]
-:*[[Chest pain|Substernal chest pain]]
-:*Occurs at rest or [[exertion]]
-:*Radiation to neck, jaw, left shoulder and left arm
-:*Aggravated by physical activity and emotional stress
-:*Relieved by rest, [[nitroglycerin]] or both
-*Chest discomfort described crushing, squeezing, burning, choking, tightness or aching
-*[[Dyspnea]]
-*[[Diaphoresis]]
-*[[Nausea]] and [[vomiting]]
-*[[Fatigue]]
-*[[Syncope]]
-====Treatment====
-In patients with ACS, and COVID-19, treatment should follow the guidelines of the updated Society for Cardiovascular Angiography and Interventions.<ref name="pmid32354800">{{cite journal| author=Kang Y, Chen T, Mui D, Ferrari V, Jagasia D, Scherrer-Crosbie M | display-authors=etal| title=Cardiovascular manifestations and treatment considerations in covid-19. | journal=Heart | year= 2020 | volume=  | issue=  | pages=  | pmid=32354800 | doi=10.1136/heartjnl-2020-317056 | pmc=7211105 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32354800  }} </ref> <ref name="pmid32212409">{{cite journal| author=Szerlip M, Anwaruddin S, Aronow HD, Cohen MG, Daniels MJ, Dehghani P | display-authors=etal| title=Considerations for cardiac catheterization laboratory procedures during the COVID-19 pandemic perspectives from the Society for Cardiovascular Angiography and Interventions Emerging Leader Mentorship (SCAI ELM) Members and Graduates. | journal=Catheter Cardiovasc Interv | year= 2020 | volume=  | issue=  | pages=  | pmid=32212409 | doi=10.1002/ccd.28887 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32212409  }} </ref>
-===ST-Elevation Myocardial Infarction (STEMI)===
-A US model from 9 major centers showed a 38% drop in total STEMI activations during the COVID-19 pandemic. There is a 40% reduction noted in Spain as well. there was also a delay between the first presentation to a medical encounter up to 318 min. This is important since COVID-19 can potentially be a cause of STEMI through microthrombi, cytokine storm, coronary spasm, or direct endothelial injury.<ref name="pmid32550258">{{cite journal| author=Ullah W, Sattar Y, Saeed R, Ahmad A, Boigon MI, Haas DC | display-authors=etal| title=As the COVID-19 pandemic drags on, where have all the STEMIs gone? | journal=Int J Cardiol Heart Vasc | year= 2020 | volume= 29 | issue=  | pages= 100550 | pmid=32550258 | doi=10.1016/j.ijcha.2020.100550 | pmc=7261452 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32550258  }} </ref>
-*Potential etiologies for the reduction in STEMI PPCI activations:
-**avoidance of medical care due to social distancing or concerns of contracting COVID-19 in the hospital
-**STEMI misdiagnosis
-**increased use of pharmacological reperfusion due to COVID-19
-It is very important to realize if patients' anxiety is the reason behind decreasing the presentation of STEMI to U.S. hospitals.<ref name="pmid32283124">{{cite journal| author=Garcia S, Albaghdadi MS, Meraj PM, Schmidt C, Garberich R, Jaffer FA | display-authors=etal| title=Reduction in ST-Segment Elevation Cardiac Catheterization Laboratory Activations in the United States During COVID-19 Pandemic. | journal=J Am Coll Cardiol | year= 2020 | volume= 75 | issue= 22 | pages= 2871-2872 | pmid=32283124 | doi=10.1016/j.jacc.2020.04.011 | pmc=7151384 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32283124  }} </ref>
-*Treatment of STEMI & COVID-19: The specific protocols for the treatment have been evolving. Early recommendations showed intravenous thrombolysis as first-line therapy for STEMI patients with confirmed COVID-19 since most hospitals do not have protected cardiac catheterization labs.<ref name="pmid32550258">{{cite journal| author=Ullah W, Sattar Y, Saeed R, Ahmad A, Boigon MI, Haas DC | display-authors=etal| title=As the COVID-19 pandemic drags on, where have all the STEMIs gone? | journal=Int J Cardiol Heart Vasc | year= 2020 | volume= 29 | issue=  | pages= 100550 | pmid=32550258 | doi=10.1016/j.ijcha.2020.100550 | pmc=7261452 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32550258  }} </ref>
-===Heart Failure===
-====Pathophysiology====
-*Patients with chronic heart failure (HF) may be at higher risk of developing severe COVID-19 infection due to the advanced age and the presence of multiple comorbidities.
-*Both de novo acute heart failure and acute decompensation of chronic heart failure can occur in patients with COVID-19.
-*Presumed pathophysiologic mechanisms for the development of new or worsening heart failure in patients with COVID-19 include:<ref name="pmid32219357">{{Cite pmid|32219357}}</ref> <ref name="pmid32360242">{{Cite pmid|32360242}}</ref> <ref name="pmid32186331">{{Cite pmid|32186331}}</ref> <ref name="pmid30625066">{{Cite pmid|30625066}}</ref> <ref name="pmid32140732">{{Cite pmid|32140732}}</ref>
-**Acute exacerbation of chronic heart failure
-**Acute myocardial injury (which in turn can be caused by several mechanisms)
-**Stress cardiomyopathy (i.e., Takotsubo cardiomyopathy)
-**Impaired myocardial relaxation resulting in diastolic dysfunction [i.e., Heart failure with preserved ejection fraction (HFpEF)]
-**Right-sided heart failure, secondary to pulmonary hypertension caused by hypoxia and acute respiratory distress syndrome (ARDS)
-====Symptoms and signs====
-*[[Dyspnea]]: may overlap with dyspnea due to concomitant respiratory involvement and ARDS due to COVID-19 infection
-*Lower limb edema
-*[[Orthopnea]]
-*Paroxysmal nocturnal dyspnea
-*Confusion and altered mentation
-*Cool extremities
-*Cyanosis
-*Syncope
-*Fatigue
-*Hemoptysis
-*Palpitations
-*Weakness
-*Wheezing or cardiac asthma
-*Distended jugular veins
-*Crackles on auscultation
-====Electrocardiography (ECG)====
-*There is no specific electrocardiographic sign for acute heart failure in COVID-19 patients.
-*The ECG may help in identifying preexisting cardiac abnormalities and precipitating factors such as ischemia, myocarditis, and arrhythmias.
-*These ECG findings may include:
-**Low QRS Voltage
-**Left ventricular hypertrophy
-**Left atrial enlargement
-**Left bundle branch block
-**Poor R progression
-**ST-T changes
-====Chest x-ray (CXR)====
-*The Chest x-ray may show evidence of:
-**Cardiomegaly
-**Pulmonary congestion
-**Increased pulmonary vascular markings.
-*Signs of pulmonary edema may be obscured by underlying respiratory involvement and ARDS due to COVID-19.
-====Echocardiography====
-*A complete standard transthoracic (TTE) has not been recommended in COVID-19 patients considering the limited personal protective equipment (PPE) and the risk of exposure of additional health care personnel.<ref name="pmid32391912">{{Cite pmid|32391912}}</ref>
-*To deal with limited resources (both personal protective equipment and personnel) and reducing the exposure time of personnel, a focused TTE to find gross abnormalities in cardiac structure/function seems satisfactory.
-*In addition, bedside options, which may be performed by the trained personnel who might already be in the room with these patients, might also be considered. These include:
-**Cardiac point-of-care ultrasound (POCUS)
-**Focused cardiac ultrasound study (FoCUS)
-**Critical care echocardiography
-*Cardiac ultrasound can help in assessing the following parameters:
-**Left ventricular systolic function (ejection fraction) to distinguish systolic dysfunction with a reduced ejection fraction (<40%) from diastolic dysfunction with a preserved ejection fraction.
-**Left ventricular diastolic function
-**Left ventricular structural abnormalities, including LV size and LV wall thickness
-**Left atrial size
-**Right ventricular size and function
-**Detection and quantification of valvular abnormalities
-**Measurement of systolic pulmonary artery pressure
-**Detection and quantification of pericardial effusion
-**Detection of regional wall motion abnormalities/reduced strain that would suggest an underlying ischemia
-====Cardiac biomarkers====
-*Cardiac Troponins:
-**Elevated cardiac troponin levels suggest the presence of myocardial cell injury or death.
-**Cardiac troponin levels may increase in patients with chronic or acute decompensated HF.<ref name="pmid20863950">{{Cite pmid|20863950}}</ref>
-*Natriuretic Peptides:
-**Natriuretic peptides (BNP/NT-proBNP) are released from the heart in response to increased myocardial stress and are quantitative markers of increased intracardiac filling pressure.<ref name="pmid28062628">{{Cite pmid|28062628}}</ref>
-**Elevated BNP and NT-proBNP are of both diagnostic and prognostic significance in patients with heart failure.
-**Increased BNP or NT-proBNP levels have been demonstrated in COVID-19 patients.
-**Increased NT-proBNP level was associated with worse clinical outcomes in patients with severe COVID-19.<ref name="pmid32293449">{{Cite pmid|32293449}}</ref> <ref name="pmid32232979">{{Cite pmid|32232979}}</ref>
-**However, increased natriuretic peptide levels are frequently seen among patients with severe inflammatory or respiratory diseases.<ref name="pmid18298480">{{Cite pmid|18298480}}</ref> <ref name="pmid16442916">{{Cite pmid|16442916}}</ref> <ref name="pmid28322314">{{Cite pmid|28322314}}</ref> <ref name="pmid23837838">{{Cite pmid|23837838}}</ref> <ref name="pmid21478812">{{Cite pmid|21478812}}</ref>
-**Therefore, routine measurement of BNP/NT-proBNP has not been recommended in COVID-19 patients, unless there is a high suspicion of HF based on clinical grounds.
-====Treatment====
-*Patients with chronic heart failure are recommended to continue their previous guideline-directed medical therapy, including beta-blockers, ACEI or ARB, and mineralocorticoid receptor antagonists. <ref name="pmid31129923">{{Cite pmid|31129923}}</ref>
-*Acute heart failure in the setting of COVID-19 is generally treated similarly to acute heart failure in other settings. These may include:
-**Fluid restriction
-**Diuretic therapy
-**Vasopressors and/or inotropes
-**Ventricular assisted devices and extracorporeal membrane oxygenation (ECMO)
-*Beta-blockers should not be initiated during the acute stage due to their negative inotropic effects.<ref name="pmid24251454">{{Cite pmid|24251454}}</ref>
-*Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) should be used with caution in patients with acute heart failure due to their effect on fluid and sodium retention.<ref name="pmid12656651">{{Cite pmid|12656651}}</ref>
-===Cardiogenic Shock===
-===Myocarditis===
-====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]].<ref name="ClerkinFried2020">{{cite journal|last1=Clerkin|first1=Kevin J.|last2=Fried|first2=Justin A.|last3=Raikhelkar|first3=Jayant|last4=Sayer|first4=Gabriel|last5=Griffin|first5=Jan M.|last6=Masoumi|first6=Amirali|last7=Jain|first7=Sneha S.|last8=Burkhoff|first8=Daniel|last9=Kumaraiah|first9=Deepa|last10=Rabbani|first10=LeRoy|last11=Schwartz|first11=Allan|last12=Uriel|first12=Nir|title=COVID-19 and Cardiovascular Disease|journal=Circulation|volume=141|issue=20|year=2020|pages=1648–1655|issn=0009-7322|doi=10.1161/CIRCULATIONAHA.120.046941}}</ref>
-*[[Myocarditis]] is an [[inflammatory]] disease of the heart characterized by [[inflammatory]] infiltrates and [[myocardial]] injury without an [[Ischemia|ischemic]] cause.<ref name="EsfandiareiMcManus2008">{{cite journal|last1=Esfandiarei|first1=Mitra|last2=McManus|first2=Bruce M.|title=Molecular Biology and Pathogenesis of Viral Myocarditis|journal=Annual Review of Pathology: Mechanisms of Disease|volume=3|issue=1|year=2008|pages=127–155|issn=1553-4006|doi=10.1146/annurev.pathmechdis.3.121806.151534}}</ref>
-**The major cause of [[myocarditis]] in the United States and other developed countries is viral.<ref name="CaforioPankuweit2013">{{cite journal|last1=Caforio|first1=A. L. P.|last2=Pankuweit|first2=S.|last3=Arbustini|first3=E.|last4=Basso|first4=C.|last5=Gimeno-Blanes|first5=J.|last6=Felix|first6=S. B.|last7=Fu|first7=M.|last8=Helio|first8=T.|last9=Heymans|first9=S.|last10=Jahns|first10=R.|last11=Klingel|first11=K.|last12=Linhart|first12=A.|last13=Maisch|first13=B.|last14=McKenna|first14=W.|last15=Mogensen|first15=J.|last16=Pinto|first16=Y. M.|last17=Ristic|first17=A.|last18=Schultheiss|first18=H.-P.|last19=Seggewiss|first19=H.|last20=Tavazzi|first20=L.|last21=Thiene|first21=G.|last22=Yilmaz|first22=A.|last23=Charron|first23=P.|last24=Elliott|first24=P. M.|title=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|journal=European Heart Journal|volume=34|issue=33|year=2013|pages=2636–2648|issn=0195-668X|doi=10.1093/eurheartj/eht210}}</ref> <ref name="KociolCooper2020">{{cite journal|last1=Kociol|first1=Robb D.|last2=Cooper|first2=Leslie T.|last3=Fang|first3=James C.|last4=Moslehi|first4=Javid J.|last5=Pang|first5=Peter S.|last6=Sabe|first6=Marwa A.|last7=Shah|first7=Ravi V.|last8=Sims|first8=Daniel B.|last9=Thiene|first9=Gaetano|last10=Vardeny|first10=Orly|title=Recognition and Initial Management of Fulminant Myocarditis|journal=Circulation|volume=141|issue=6|year=2020|issn=0009-7322|doi=10.1161/CIR.0000000000000745}}</ref>
-**A number of cases of [[myocarditis]] have been reported in [[COVID-19]] patients.<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>
-**[[Myocarditis]] has also been reported as the cause of death in some [[COVID-19]] patients.<ref name="RuanYang2020">{{cite journal|last1=Ruan|first1=Qiurong|last2=Yang|first2=Kun|last3=Wang|first3=Wenxia|last4=Jiang|first4=Lingyu|last5=Song|first5=Jianxin|title=Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China|journal=Intensive Care Medicine|volume=46|issue=5|year=2020|pages=846–848|issn=0342-4642|doi=10.1007/s00134-020-05991-x}}</ref>
-*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.<ref name="HoffmannKleine-Weber2020">{{cite journal|last1=Hoffmann|first1=Markus|last2=Kleine-Weber|first2=Hannah|last3=Schroeder|first3=Simon|last4=Krüger|first4=Nadine|last5=Herrler|first5=Tanja|last6=Erichsen|first6=Sandra|last7=Schiergens|first7=Tobias S.|last8=Herrler|first8=Georg|last9=Wu|first9=Nai-Huei|last10=Nitsche|first10=Andreas|last11=Müller|first11=Marcel A.|last12=Drosten|first12=Christian|last13=Pöhlmann|first13=Stefan|title=SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor|journal=Cell|volume=181|issue=2|year=2020|pages=271–280.e8|issn=00928674|doi=10.1016/j.cell.2020.02.052}}</ref>
-**ACE2 is expressed in the [[lung]], principally type II [[alveolar]] cells which appears to be the principal portal of entry.<ref name="ZhaoZhao2020">{{cite journal|last1=Zhao|first1=Yu|last2=Zhao|first2=Zixian|last3=Wang|first3=Yujia|last4=Zhou|first4=Yueqing|last5=Ma|first5=Yu|last6=Zuo|first6=Wei|year=2020|doi=10.1101/2020.01.26.919985}}</ref>
-**[[ACE2]] is highly expressed in the [[heart]] as well.<ref name="TikellisThomas2012">{{cite journal|last1=Tikellis|first1=Chris|last2=Thomas|first2=M. C.|title=Angiotensin-Converting Enzyme 2 (ACE2) Is a Key Modulator of the Renin Angiotensin System in Health and Disease|journal=International Journal of Peptides|volume=2012|year=2012|pages=1–8|issn=1687-9767|doi=10.1155/2012/256294}}</ref>
-**[[Naive T cell|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.<ref name="KomarowskaCoe2015">{{cite journal|last1=Komarowska|first1=Izabela|last2=Coe|first2=David|last3=Wang|first3=Guosu|last4=Haas|first4=Robert|last5=Mauro|first5=Claudio|last6=Kishore|first6=Madhav|last7=Cooper|first7=Dianne|last8=Nadkarni|first8=Suchita|last9=Fu|first9=Hongmei|last10=Steinbruchel|first10=Daniel A.|last11=Pitzalis|first11=Costantino|last12=Anderson|first12=Graham|last13=Bucy|first13=Pat|last14=Lombardi|first14=Giovanna|last15=Breckenridge|first15=Ross|last16=Marelli-Berg|first16=Federica M.|title=Hepatocyte Growth Factor Receptor c-Met Instructs T Cell Cardiotropism and Promotes T Cell Migration to the Heart via Autocrine Chemokine Release|journal=Immunity|volume=42|issue=6|year=2015|pages=1087–1099|issn=10747613|doi=10.1016/j.immuni.2015.05.014}}</ref>
-**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-lymphocytes|T-lymphocyte]] activation and causes the release of more [[Cytokine|cytokines]].<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>
-**[[Cytokine storm|Cytokine storms]] result in increased vascular wall permeability and [[Myocardium|myocardial]] [[edema]].<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="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>
-**Thus a positive feedback loop of [[immune]] activation and [[myocardial]] damage is established.<ref name="pmid409380">{{cite journal| author=Iakimov VP| title=[F. Engels' theory of the origin of man and modern anthropologic findings]. | journal=Arkh Anat Gistol Embriol | year= 1977 | volume= 72 | issue= 6 | pages= 5-11 | pmid=409380 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=409380  }} </ref><ref name="EsfandiareiMcManus2008">{{cite journal|last1=Esfandiarei|first1=Mitra|last2=McManus|first2=Bruce M.|title=Molecular Biology and Pathogenesis of Viral Myocarditis|journal=Annual Review of Pathology: Mechanisms of Disease|volume=3|issue=1|year=2008|pages=127–155|issn=1553-4006|doi=10.1146/annurev.pathmechdis.3.121806.151534}}</ref>
-*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.<ref name="XuShi2020">{{cite journal|last1=Xu|first1=Zhe|last2=Shi|first2=Lei|last3=Wang|first3=Yijin|last4=Zhang|first4=Jiyuan|last5=Huang|first5=Lei|last6=Zhang|first6=Chao|last7=Liu|first7=Shuhong|last8=Zhao|first8=Peng|last9=Liu|first9=Hongxia|last10=Zhu|first10=Li|last11=Tai|first11=Yanhong|last12=Bai|first12=Changqing|last13=Gao|first13=Tingting|last14=Song|first14=Jinwen|last15=Xia|first15=Peng|last16=Dong|first16=Jinghui|last17=Zhao|first17=Jingmin|last18=Wang|first18=Fu-Sheng|title=Pathological findings of COVID-19 associated with acute respiratory distress syndrome|journal=The Lancet Respiratory Medicine|volume=8|issue=4|year=2020|pages=420–422|issn=22132600|doi=10.1016/S2213-2600(20)30076-X}}</ref>
-====Signs and symptoms====
-Clinical presentation of [[SARS-CoV-2]] [[myocarditis]] varies among cases from mild to severe to fulminant.
-*Mild - fatigue and [[dyspnea]],<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>, [[chest pain]] or chest tightness on exertion.<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="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>
-*Severe - Many patients deteriorate and show symptoms of [[tachycardia]] and [[heart failure|acute-onset heart failure]] with [[cardiogenic shock]].<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> They may also present with signs of [[heart failure|right-sided heart failure]], including raised [[jugular venous pressure]], right upper quadrant pain, and [[peripheral edema]].<ref name="KociolCooper2020">{{cite journal|last1=Kociol|first1=Robb D.|last2=Cooper|first2=Leslie T.|last3=Fang|first3=James C.|last4=Moslehi|first4=Javid J.|last5=Pang|first5=Peter S.|last6=Sabe|first6=Marwa A.|last7=Shah|first7=Ravi V.|last8=Sims|first8=Daniel B.|last9=Thiene|first9=Gaetano|last10=Vardeny|first10=Orly|title=Recognition and Initial Management of Fulminant Myocarditis|journal=Circulation|volume=141|issue=6|year=2020|issn=0009-7322|doi=10.1161/CIR.0000000000000745}}</ref>
-*Fulminant - [[Fulminant myocarditis]] is defined as [[ventricular dysfunction]] and [[heart failure]] within 2–3 weeks of infection.<ref name="EsfandiareiMcManus2008">{{cite journal|last1=Esfandiarei|first1=Mitra|last2=McManus|first2=Bruce M.|title=Molecular Biology and Pathogenesis of Viral Myocarditis|journal=Annual Review of Pathology: Mechanisms of Disease|volume=3|issue=1|year=2008|pages=127–155|issn=1553-4006|doi=10.1146/annurev.pathmechdis.3.121806.151534}}</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="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="WangLi2018">{{cite journal|last1=Wang|first1=Daowen|last2=Li|first2=Sheng|last3=Jiang|first3=Jiangang|last4=Yan|first4=Jiangtao|last5=Zhao|first5=Chunxia|last6=Wang|first6=Yan|last7=Ma|first7=Yexin|last8=Zeng|first8=Hesong|last9=Guo|first9=Xiaomei|last10=Wang|first10=Hong|last11=Tang|first11=Jiarong|last12=Zuo|first12=Houjuan|last13=Lin|first13=Li|last14=Cui|first14=Guanglin|title=Chinese society of cardiology expert consensus statement on the diagnosis and treatment of adult fulminant myocarditis|journal=Science China Life Sciences|volume=62|issue=2|year=2018|pages=187–202|issn=1674-7305|doi=10.1007/s11427-018-9385-3}}</ref> The early signs resemble those of [[sepsis]]: fever, low [[pulse pressure]], cold extremities, and [[sinus tachycardia]].<ref name="KociolCooper2020">{{cite journal|last1=Kociol|first1=Robb D.|last2=Cooper|first2=Leslie T.|last3=Fang|first3=James C.|last4=Moslehi|first4=Javid J.|last5=Pang|first5=Peter S.|last6=Sabe|first6=Marwa A.|last7=Shah|first7=Ravi V.|last8=Sims|first8=Daniel B.|last9=Thiene|first9=Gaetano|last10=Vardeny|first10=Orly|title=Recognition and Initial Management of Fulminant Myocarditis|journal=Circulation|volume=141|issue=6|year=2020|issn=0009-7322|doi=10.1161/CIR.0000000000000745}}</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>
-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>
-====Diagnostic testing====
-*'''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>
-**'''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.<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>
-*** 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>
-*'''Electrocardiogram'''
-**[[Electrocardiogram|ECG]] is usually abnormal in myocarditis but it is neither sensitive nor specific in the diagnosis.<ref name="UkenaMahfoud2011">{{cite journal|last1=Ukena|first1=Christian|last2=Mahfoud|first2=Felix|last3=Kindermann|first3=Ingrid|last4=Kandolf|first4=Reinhard|last5=Kindermann|first5=Michael|last6=Böhm|first6=Michael|title=Prognostic electrocardiographic parameters in patients with suspected myocarditis|journal=European Journal of Heart Failure|volume=13|issue=4|year=2011|pages=398–405|issn=13889842|doi=10.1093/eurjhf/hfq229}}</ref><ref name="CaforioPankuweit2013">{{cite journal|last1=Caforio|first1=A. L. P.|last2=Pankuweit|first2=S.|last3=Arbustini|first3=E.|last4=Basso|first4=C.|last5=Gimeno-Blanes|first5=J.|last6=Felix|first6=S. B.|last7=Fu|first7=M.|last8=Helio|first8=T.|last9=Heymans|first9=S.|last10=Jahns|first10=R.|last11=Klingel|first11=K.|last12=Linhart|first12=A.|last13=Maisch|first13=B.|last14=McKenna|first14=W.|last15=Mogensen|first15=J.|last16=Pinto|first16=Y. M.|last17=Ristic|first17=A.|last18=Schultheiss|first18=H.-P.|last19=Seggewiss|first19=H.|last20=Tavazzi|first20=L.|last21=Thiene|first21=G.|last22=Yilmaz|first22=A.|last23=Charron|first23=P.|last24=Elliott|first24=P. M.|title=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|journal=European Heart Journal|volume=34|issue=33|year=2013|pages=2636–2648|issn=0195-668X|doi=10.1093/eurheartj/eht210}}</ref>
-**[[Electrocardiogram|ECG]] abnormalities [[ST-elevation]] and [[PR depression]] may be observed in [[myocarditis]] in COVID-19 patients.<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="CaforioPankuweit2013">{{cite journal|last1=Caforio|first1=A. L. P.|last2=Pankuweit|first2=S.|last3=Arbustini|first3=E.|last4=Basso|first4=C.|last5=Gimeno-Blanes|first5=J.|last6=Felix|first6=S. B.|last7=Fu|first7=M.|last8=Helio|first8=T.|last9=Heymans|first9=S.|last10=Jahns|first10=R.|last11=Klingel|first11=K.|last12=Linhart|first12=A.|last13=Maisch|first13=B.|last14=McKenna|first14=W.|last15=Mogensen|first15=J.|last16=Pinto|first16=Y. M.|last17=Ristic|first17=A.|last18=Schultheiss|first18=H.-P.|last19=Seggewiss|first19=H.|last20=Tavazzi|first20=L.|last21=Thiene|first21=G.|last22=Yilmaz|first22=A.|last23=Charron|first23=P.|last24=Elliott|first24=P. M.|title=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|journal=European Heart Journal|volume=34|issue=33|year=2013|pages=2636–2648|issn=0195-668X|doi=10.1093/eurheartj/eht210}}</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>
-**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.<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>
-**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.<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>
-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.<ref name="KociolCooper2020">{{cite journal|last1=Kociol|first1=Robb D.|last2=Cooper|first2=Leslie T.|last3=Fang|first3=James C.|last4=Moslehi|first4=Javid J.|last5=Pang|first5=Peter S.|last6=Sabe|first6=Marwa A.|last7=Shah|first7=Ravi V.|last8=Sims|first8=Daniel B.|last9=Thiene|first9=Gaetano|last10=Vardeny|first10=Orly|title=Recognition and Initial Management of Fulminant Myocarditis|journal=Circulation|volume=141|issue=6|year=2020|issn=0009-7322|doi=10.1161/CIR.0000000000000745}}</ref> 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.<ref name="HendrenDrazner2020">{{cite journal|last1=Hendren|first1=Nicholas S.|last2=Drazner|first2=Mark H.|last3=Bozkurt|first3=Biykem|last4=Cooper|first4=Leslie T.|title=Description and Proposed Management of the Acute COVID-19 Cardiovascular Syndrome|journal=Circulation|volume=141|issue=23|year=2020|pages=1903–1914|issn=0009-7322|doi=10.1161/CIRCULATIONAHA.120.047349}}</ref>
-*'''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]].<ref name="PinamontiAlberti1988">{{cite journal|last1=Pinamonti|first1=Bruno|last2=Alberti|first2=Ezip|last3=Cigalotto|first3=Alessandro|last4=Dreas|first4=Lorella|last5=Salvi|first5=Alessandro|last6=Silvestri|first6=Furio|last7=Camerini|first7=Fulvio|title=Echocardiographic findings in myocarditis|journal=The American Journal of Cardiology|volume=62|issue=4|year=1988|pages=285–291|issn=00029149|doi=10.1016/0002-9149(88)90226-3}}</ref><ref name="FelkerBoehmer2000">{{cite journal|last1=Felker|first1=G.Michael|last2=Boehmer|first2=John P|last3=Hruban|first3=Ralph H|last4=Hutchins|first4=Grover M|last5=Kasper|first5=Edward K|last6=Baughman|first6=Kenneth L|last7=Hare|first7=Joshua M|title=Echocardiographic findings in fulminant and acute myocarditis|journal=Journal of the American College of Cardiology|volume=36|issue=1|year=2000|pages=227–232|issn=07351097|doi=10.1016/S0735-1097(00)00690-2}}</ref><ref name="CaforioPankuweit2013">{{cite journal|last1=Caforio|first1=A. L. P.|last2=Pankuweit|first2=S.|last3=Arbustini|first3=E.|last4=Basso|first4=C.|last5=Gimeno-Blanes|first5=J.|last6=Felix|first6=S. B.|last7=Fu|first7=M.|last8=Helio|first8=T.|last9=Heymans|first9=S.|last10=Jahns|first10=R.|last11=Klingel|first11=K.|last12=Linhart|first12=A.|last13=Maisch|first13=B.|last14=McKenna|first14=W.|last15=Mogensen|first15=J.|last16=Pinto|first16=Y. M.|last17=Ristic|first17=A.|last18=Schultheiss|first18=H.-P.|last19=Seggewiss|first19=H.|last20=Tavazzi|first20=L.|last21=Thiene|first21=G.|last22=Yilmaz|first22=A.|last23=Charron|first23=P.|last24=Elliott|first24=P. M.|title=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|journal=European Heart Journal|volume=34|issue=33|year=2013|pages=2636–2648|issn=0195-668X|doi=10.1093/eurheartj/eht210}}</ref>
-**These findings were noted in COVID-19 related myocarditis cases.<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="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="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>
-*'''[[Cardiac Magnetic Resonance]]''':
-**Cardiac Magnetic resonance (CMR) has major imaging advantages with highest diagnostic accuracy over [[echocardiography]]<ref name="FriedrichStrohm1998">{{cite journal|last1=Friedrich|first1=Matthias G.|last2=Strohm|first2=Oliver|last3=Schulz-Menger|first3=Jeanette|last4=Marciniak|first4=Heinz|last5=Luft|first5=Friedrich C.|last6=Dietz|first6=Rainer|title=Contrast Media–Enhanced Magnetic Resonance Imaging Visualizes Myocardial Changes in the Course of Viral Myocarditis|journal=Circulation|volume=97|issue=18|year=1998|pages=1802–1809|issn=0009-7322|doi=10.1161/01.CIR.97.18.1802}}</ref>, 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.<ref name="FriedrichSechtem2009">{{cite journal|last1=Friedrich|first1=Matthias G.|last2=Sechtem|first2=Udo|last3=Schulz-Menger|first3=Jeanette|last4=Holmvang|first4=Godtfred|last5=Alakija|first5=Pauline|last6=Cooper|first6=Leslie T.|last7=White|first7=James A.|last8=Abdel-Aty|first8=Hassan|last9=Gutberlet|first9=Matthias|last10=Prasad|first10=Sanjay|last11=Aletras|first11=Anthony|last12=Laissy|first12=Jean-Pierre|last13=Paterson|first13=Ian|last14=Filipchuk|first14=Neil G.|last15=Kumar|first15=Andreas|last16=Pauschinger|first16=Matthias|last17=Liu|first17=Peter|title=Cardiovascular Magnetic Resonance in Myocarditis: A JACC White Paper|journal=Journal of the American College of Cardiology|volume=53|issue=17|year=2009|pages=1475–1487|issn=07351097|doi=10.1016/j.jacc.2009.02.007}}</ref> 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.<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>
-*'''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.<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>
-*'''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).<ref name="DennertCrijns2008">{{cite journal|last1=Dennert|first1=R.|last2=Crijns|first2=H. J.|last3=Heymans|first3=S.|title=Acute viral myocarditis|journal=European Heart Journal|volume=29|issue=17|year=2008|pages=2073–2082|issn=0195-668X|doi=10.1093/eurheartj/ehn296}}</ref> 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.<ref name="CooperBaughman2007">{{cite journal|last1=Cooper|first1=Leslie T.|last2=Baughman|first2=Kenneth L.|last3=Feldman|first3=Arthur M.|last4=Frustaci|first4=Andrea|last5=Jessup|first5=Mariell|last6=Kuhl|first6=Uwe|last7=Levine|first7=Glenn N.|last8=Narula|first8=Jagat|last9=Starling|first9=Randall C.|last10=Towbin|first10=Jeffrey|last11=Virmani|first11=Renu|title=The Role of Endomyocardial Biopsy in the Management of Cardiovascular Disease|journal=Circulation|volume=116|issue=19|year=2007|pages=2216–2233|issn=0009-7322|doi=10.1161/CIRCULATIONAHA.107.186093}}</ref> 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.<ref name="CaforioPankuweit2013">{{cite journal|last1=Caforio|first1=A. L. P.|last2=Pankuweit|first2=S.|last3=Arbustini|first3=E.|last4=Basso|first4=C.|last5=Gimeno-Blanes|first5=J.|last6=Felix|first6=S. B.|last7=Fu|first7=M.|last8=Helio|first8=T.|last9=Heymans|first9=S.|last10=Jahns|first10=R.|last11=Klingel|first11=K.|last12=Linhart|first12=A.|last13=Maisch|first13=B.|last14=McKenna|first14=W.|last15=Mogensen|first15=J.|last16=Pinto|first16=Y. M.|last17=Ristic|first17=A.|last18=Schultheiss|first18=H.-P.|last19=Seggewiss|first19=H.|last20=Tavazzi|first20=L.|last21=Thiene|first21=G.|last22=Yilmaz|first22=A.|last23=Charron|first23=P.|last24=Elliott|first24=P. M.|title=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|journal=European Heart Journal|volume=34|issue=33|year=2013|pages=2636–2648|issn=0195-668X|doi=10.1093/eurheartj/eht210}}</ref><ref name="KociolCooper2020">{{cite journal|last1=Kociol|first1=Robb D.|last2=Cooper|first2=Leslie T.|last3=Fang|first3=James C.|last4=Moslehi|first4=Javid J.|last5=Pang|first5=Peter S.|last6=Sabe|first6=Marwa A.|last7=Shah|first7=Ravi V.|last8=Sims|first8=Daniel B.|last9=Thiene|first9=Gaetano|last10=Vardeny|first10=Orly|title=Recognition and Initial Management of Fulminant Myocarditis|journal=Circulation|volume=141|issue=6|year=2020|issn=0009-7322|doi=10.1161/CIR.0000000000000745}}</ref><ref name="FriedrichStrohm1998">{{cite journal|last1=Friedrich|first1=Matthias G.|last2=Strohm|first2=Oliver|last3=Schulz-Menger|first3=Jeanette|last4=Marciniak|first4=Heinz|last5=Luft|first5=Friedrich C.|last6=Dietz|first6=Rainer|title=Contrast Media–Enhanced Magnetic Resonance Imaging Visualizes Myocardial Changes in the Course of Viral Myocarditis|journal=Circulation|volume=97|issue=18|year=1998|pages=1802–1809|issn=0009-7322|doi=10.1161/01.CIR.97.18.1802}}</ref>
-**EMB samples if obtained should be tested for inflammatory infiltrates and for the presence of viral genomes by DNA/RNA extraction.<ref name="CaforioPankuweit2013">{{cite journal|last1=Caforio|first1=A. L. P.|last2=Pankuweit|first2=S.|last3=Arbustini|first3=E.|last4=Basso|first4=C.|last5=Gimeno-Blanes|first5=J.|last6=Felix|first6=S. B.|last7=Fu|first7=M.|last8=Helio|first8=T.|last9=Heymans|first9=S.|last10=Jahns|first10=R.|last11=Klingel|first11=K.|last12=Linhart|first12=A.|last13=Maisch|first13=B.|last14=McKenna|first14=W.|last15=Mogensen|first15=J.|last16=Pinto|first16=Y. M.|last17=Ristic|first17=A.|last18=Schultheiss|first18=H.-P.|last19=Seggewiss|first19=H.|last20=Tavazzi|first20=L.|last21=Thiene|first21=G.|last22=Yilmaz|first22=A.|last23=Charron|first23=P.|last24=Elliott|first24=P. M.|title=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|journal=European Heart Journal|volume=34|issue=33|year=2013|pages=2636–2648|issn=0195-668X|doi=10.1093/eurheartj/eht210}}</ref>
-**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.<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>
-====Treatment====
-*There is no definitive treatment for COVID-19-related-myocarditis.
-*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>
-===Pericarditis===
-[[Pericarditis]] is a rare manifestation of [[COVID-19]]. There are very few case reports of pericarditis in COVID-19 patients.<ref name="DabbaghAurora2020">{{cite journal|last1=Dabbagh|first1=Mohammed F.|last2=Aurora|first2=Lindsey|last3=D’Souza|first3=Penny|last4=Weinmann|first4=Allison J.|last5=Bhargava|first5=Pallavi|last6=Basir|first6=Mir B.|title=Cardiac Tamponade Secondary to COVID-19|journal=JACC: Case Reports|year=2020|issn=26660849|doi=10.1016/j.jaccas.2020.04.009}}</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="MaceiraLopez-Lereu2020">{{cite journal|last1=Maceira|first1=Alicia M|last2=Lopez-Lereu|first2=Maria P|last3=Higueras Ortega|first3=Laura|last4=García-Gonzalez|first4=Pilar|last5=Broseta Torres|first5=Ricardo|last6=Solsona Caravaca|first6=Javier|last7=Ventura Perez|first7=Bruno|last8=Andres Soler|first8=Jorge|last9=Dominguez Mafe|first9=Eloy|last10=Monmeneu|first10=Jose V|last11=Voges|first11=Inga|title=Subacute perimyocarditis in a young patient with COVID-19 infection|journal=European Heart Journal - Case Reports|year=2020|issn=2514-2119|doi=10.1093/ehjcr/ytaa157}}</ref><ref name="ByrneSado2020">{{cite journal|last1=Byrne|first1=Jonathan|last2=Sado|first2=Daniel|last3=O’Gallagher|first3=Kevin|last4=Hua|first4=Alina|title=Life-threatening cardiac tamponade complicating myo-pericarditis in COVID-19|journal=European Heart Journal|volume=41|issue=22|year=2020|pages=2130–2130|issn=0195-668X|doi=10.1093/eurheartj/ehaa253}}</ref>
-===='''Pathophysiology'''====
-*[[Viral]] infections are a common cause of [[pericarditis]]. It is hypothesized that viruses cause pericardial [[inflammation]] via direct cytotoxic effects or via immune-mediated mechanisms.<ref name="TomkowskiSwedberg2015">{{cite journal|last1=Tomkowski|first1=Witold|last2=Swedberg|first2=Karl|last3=Seferovic|first3=Petar|last4=Sabaté Tenas|first4=Manel|last5=Ristić|first5=Arsen D|last6=Pavie|first6=Alain|last7=Mayosi|first7=Bongani|last8=Maisch|first8=Bernhard|last9=Lionis|first9=Christos|last10=Klingel|first10=Karin|last11=Gueret|first11=Pascal|last12=Brucato|first12=Antonio|last13=Bogaert|first13=Jan|last14=Barón-Esquivias|first14=Gonzalo|last15=Badano|first15=Luigi|last16=Imazio|first16=Massimo|last17=Charron|first17=Philippe|last18=Adler|first18=Yehuda|last19=Achenbach|first19=Stephan|last20=Agewall|first20=Stefan|last21=Al-Attar|first21=Nawwar|last22=Angel Ferrer|first22=Juan|last23=Arad|first23=Michael|last24=Asteggiano|first24=Riccardo|last25=Bueno|first25=Héctor|last26=Caforio|first26=Alida L P|last27=Carerj|first27=Scipione|last28=Ceconi|first28=Claudio|last29=Evangelista|first29=Arturo|last30=Flachskampf|first30=Frank|last31=Giannakoulas|first31=George|last32=Gielen|first32=Stephan|last33=Habib|first33=Gilbert|last34=Kolh|first34=Philippe|last35=Lambrinou|first35=Ekaterini|last36=Lancellotti|first36=Patrizio|last37=Lazaros|first37=George|last38=Linhart|first38=Ales|last39=Meurin|first39=Philippe|last40=Nieman|first40=Koen|last41=Piepoli|first41=Massimo F|last42=Price|first42=Susanna|last43=Roos-Hesselink|first43=Jolien|last44=Roubille|first44=François|last45=Ruschitzka|first45=Frank|last46=Sagristà Sauleda|first46=Jaume|last47=Sousa-Uva|first47=Miguel|last48=Uwe Voigt|first48=Jens|last49=Luis Zamorano|first49=Jose|last50=Zamorano|first50=Jose Luis|last51=Aboyans|first51=Victor|last52=Achenbach|first52=Stephan|last53=Agewall|first53=Stefan|last54=Badimon|first54=Lina|last55=Barón-Esquivias|first55=Gonzalo|last56=Baumgartner|first56=Helmut|last57=Bax|first57=Jeroen J|last58=Bueno|first58=Héctor|last59=Carerj|first59=Scipione|last60=Dean|first60=Veronica|last61=Erol|first61=Çetin|last62=Fitzimons|first62=Donna|last63=Gaemperli|first63=Oliver|last64=Kirchhof|first64=Paulus|last65=Kolh|first65=Philippe|last66=Lancellotti|first66=Patrizio|last67=Lip|first67=Gregory YH|last68=Nihoyannopoulos|first68=Petros|last69=Piepoli|first69=Massimo F|last70=Ponikowski|first70=Piotr|last71=Roffi|first71=Marco|last72=Torbicki|first72=Adam|last73=Vaz Carneiro|first73=Antonio|last74=Windecker|first74=Stephan|last75=Shuka|first75=Naltin|last76=Sisakian|first76=Hamayak|last77=Mascherbauer|first77=Julia|last78=Isayev|first78=Elnur|last79=Shumavets|first79=Vadim|last80=Van Camp|first80=Guy|last81=Gatzov|first81=Plamen|last82=Hanzevacki|first82=Jadranka Separovic|last83=Moustra|first83=Hera Heracleous|last84=Linhart|first84=Ales|last85=Møller|first85=Jacob Eifer|last86=Aboleineen|first86=Mohamed Wafaie|last87=Põder|first87=Pentti|last88=Lehtonen|first88=Jukka|last89=Antov|first89=Slobodan|last90=Damy|first90=Thibaud|last91=Schieffer|first91=Bernhard|last92=Dimitriadis|first92=Kyriakos|last93=Kiss|first93=Robert Gabor|last94=Rafnsson|first94=Arnar|last95=Arad|first95=Michael|last96=Novo|first96=Salvatore|last97=Mirrakhimov|first97=Erkin|last98=Stradinš|first98=Peteris|last99=Kavoliuniene|first99=Ausra|last100=Codreanu|first100=Andrei|last101=Dingli |first101=Philip|last102=Vataman|first102=Eleonora|last103=El Hattaoui|first103=Mustapaha|last104=Samstad|first104=Stein Olav|last105=Hoffman|first105=Piotr|last106=Lopes|first106=Luís Rocha|last107=Dimulescu|first107=Doina Ruxandra|last108=Arutyunov|first108=Grigory P|last109=Pavlovic|first109=Milan|last110=Dúbrava|first110=Juraj|last111=Sauleda|first111=Jaume Sagristà|last112=Andersson|first112=Bert|last113=Müller|first113=Hajo|last114=Bouma|first114=Berto J|last115=Abaci|first115=Adnan|last116=Archbold|first116=Andrew|last117=Nesukay|first117=Elena|title=2015 ESC Guidelines for the diagnosis and management of pericardial diseases|journal=European Heart Journal|volume=36|issue=42|year=2015|pages=2921–2964|issn=0195-668X|doi=10.1093/eurheartj/ehv318}}</ref>
-*COVID-19 has been reported to trigger an exaggerated inflammatory response in patients which might be leading to pericarditis and subsequent [[pericardial effusion]] in certain patients; however, the exact mechanism is unclear.
-===='''Signs and Symptoms'''====
-*Fever
-*Chest pain
-*[[Dyspnea]]
-===='''Diagnostic testing'''====
-*[[Electrocardiogram]]: [[ST-elevation]] and [[PR depression]] are seen in [[pericarditis]] but it is not specific in COVID-19-related pericarditis.
-*Imaging: On imaging by [[echocardiography]] and [[CT chest]], the reported cases showed [[pericardial effusion]]. In two of the reported cases, late gadolinium sequences of [[CMR]] done to rule out [[myocarditis]] also showed extensive enhancement of the walls of the heart and the [[pericardium]].<ref name="MaceiraLopez-Lereu2020">{{cite journal|last1=Maceira|first1=Alicia M|last2=Lopez-Lereu|first2=Maria P|last3=Higueras Ortega|first3=Laura|last4=García-Gonzalez|first4=Pilar|last5=Broseta Torres|first5=Ricardo|last6=Solsona Caravaca|first6=Javier|last7=Ventura Perez|first7=Bruno|last8=Andres Soler|first8=Jorge|last9=Dominguez Mafe|first9=Eloy|last10=Monmeneu|first10=Jose V|last11=Voges|first11=Inga|title=Subacute perimyocarditis in a young patient with COVID-19 infection|journal=European Heart Journal - Case Reports|year=2020|issn=2514-2119|doi=10.1093/ehjcr/ytaa157}}</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>
-===='''Treatment'''====
-===Arrhythmias                              ===
-==== Pathophysiology:                                                                                                                                                                                                                                                 ====
-* Respiratory disease is the chief target of Coronavirus disease 2019 (COVID-19).
-* One-third of patients with severe disease also reported other symptoms including [[Cardiac arrhythmia|arrhythmia]]. According to a study done in Wuhan, China, 16.7% of hospitalized and 44.4% of ICU patients with COVID-19 had arrhythmias.
-* Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes S-spike to bind to angiotensin-converting enzyme 2 (ACE2) receptors to enter the cells.
-* Type 1 and type 2 [[pneumocytes]] exhibit ACE 2 receptors in the lung. Studies report that coronary [[endothelial cells]] in the heart and intrarenal endothelial cells and renal tubular epithelial cells in the kidney exhibit ACE2. ACE2 is an inverse regulator of the [[renin-angiotensin system]].
-* The interaction between SARS-CoV2 and ACE2 can bring about changes in ACE2 pathways prompting intense injury to the lung, heart, and [[Endothelium|endothelial cells]]. [[Hypoxemia|Hypoxia]] and [[Electrolyte disturbance|electrolyte abnormalities]] that are common in the acute phase of severe [[COVID-19]] can potentiate [[Cardiac arrhythmia|cardiac arrhythmias]].
-* Binding of SARS-CoV-2 to ACE2 receptors can result into [[hypokalemia]] which causes various types of [[Cardiac arrhythmia|arrhythmia]].
-* Elevated levels of [[Cytokine|cytokines]] as a result of the [[Systemic inflammatory response syndrome|systemic inflammatory response]] of the severe [[COVID-19|Coronavirus disease 2019]] (COVID-19) can cause injury to multiple organs, including [[Cardiac muscle|cardiac myocytes]].
-* According to the data based on studies on previous [[Severe acute respiratory syndrome]] ([[Severe acute respiratory syndrome|SARS]]) and the [[Middle East respiratory syndrome coronavirus infection|Middle East respiratory syndrome]] ([[Middle East respiratory syndrome coronavirus infection|MERS]]) epidemic and the ongoing [[COVID-19]] outbreak, multiple mechanisms have been suggested for cardiac damage.<ref name="WangHu2020">{{cite journal|last1=Wang|first1=Dawei|last2=Hu|first2=Bo|last3=Hu|first3=Chang|last4=Zhu|first4=Fangfang|last5=Liu|first5=Xing|last6=Zhang|first6=Jing|last7=Wang|first7=Binbin|last8=Xiang|first8=Hui|last9=Cheng|first9=Zhenshun|last10=Xiong|first10=Yong|last11=Zhao|first11=Yan|last12=Li|first12=Yirong|last13=Wang|first13=Xinghuan|last14=Peng|first14=Zhiyong|title=Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China|journal=JAMA|volume=323|issue=11|year=2020|pages=1061|issn=0098-7484|doi=10.1001/jama.2020.1585}}</ref><ref name="XuShi2020">{{cite journal|last1=Xu|first1=Zhe|last2=Shi|first2=Lei|last3=Wang|first3=Yijin|last4=Zhang|first4=Jiyuan|last5=Huang|first5=Lei|last6=Zhang|first6=Chao|last7=Liu|first7=Shuhong|last8=Zhao|first8=Peng|last9=Liu|first9=Hongxia|last10=Zhu|first10=Li|last11=Tai|first11=Yanhong|last12=Bai|first12=Changqing|last13=Gao|first13=Tingting|last14=Song|first14=Jinwen|last15=Xia|first15=Peng|last16=Dong|first16=Jinghui|last17=Zhao|first17=Jingmin|last18=Wang|first18=Fu-Sheng|title=Pathological findings of COVID-19 associated with acute respiratory distress syndrome|journal=The Lancet Respiratory Medicine|volume=8|issue=4|year=2020|pages=420–422|issn=22132600|doi=10.1016/S2213-2600(20)30076-X}}</ref><ref name="ChenPrendergast2020">{{cite journal|last1=Chen|first1=Mao|last2=Prendergast|first2=Bernard|last3=Redwood|first3=Simon|last4=Xiong|first4=Tian-Yuan|title=Coronaviruses and the cardiovascular system: acute and long-term implications|journal=European Heart Journal|volume=41|issue=19|year=2020|pages=1798–1800|issn=0195-668X|doi=10.1093/eurheartj/ehaa231}}</ref><ref name="ClerkinFried2020">{{cite journal|last1=Clerkin|first1=Kevin J.|last2=Fried|first2=Justin A.|last3=Raikhelkar|first3=Jayant|last4=Sayer|first4=Gabriel|last5=Griffin|first5=Jan M.|last6=Masoumi|first6=Amirali|last7=Jain|first7=Sneha S.|last8=Burkhoff|first8=Daniel|last9=Kumaraiah|first9=Deepa|last10=Rabbani|first10=LeRoy|last11=Schwartz|first11=Allan|last12=Uriel|first12=Nir|title=COVID-19 and Cardiovascular Disease|journal=Circulation|volume=141|issue=20|year=2020|pages=1648–1655|issn=0009-7322|doi=10.1161/CIRCULATIONAHA.120.046941}}</ref>
-==== Signs and Symptoms: ====
-Arrhythmia or conduction system disease is the nonspecific clinical presentation of COVID-19. Patients may be tachycardic (with or without palpitations) in the setting of other COVID-19-related symptoms (eg, fever, shortness of breath, pain, etc).
-*'''Palpitations:''' According to a study done in Hubei province,[[Palpitation|palpitations]] were reported as a presenting symptom by 7.3 percent of patients.<ref name="pmid32044814">{{cite journal| author=Liu K, Fang YY, Deng Y, Liu W, Wang MF, Ma JP | display-authors=etal| title=Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province. | journal=Chin Med J (Engl) | year= 2020 | volume= 133 | issue= 9 | pages= 1025-1031 | pmid=32044814 | doi=10.1097/CM9.0000000000000744 | pmc=7147277 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32044814  }} </ref><ref name="pmid32201335">{{cite journal| author=Driggin E, Madhavan MV, Bikdeli B, Chuich T, Laracy J, Biondi-Zoccai G | display-authors=etal| title=Cardiovascular Considerations for Patients, Health Care Workers, and Health Systems During the COVID-19 Pandemic. | journal=J Am Coll Cardiol | year= 2020 | volume= 75 | issue= 18 | pages= 2352-2371 | pmid=32201335 | doi=10.1016/j.jacc.2020.03.031 | pmc=7198856 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32201335  }} </ref>
-*'''Prolong QT Interval:''' According to a multicenter study done in New York that involved 4250 COVID-19 patients, 260 patients (6.1 percent) had [[QT interval|corrected QT interval]] (QTc) >500 milliseconds at the time of admittance. However, in another study that involved 84 patients who got [[hydroxychloroquine]] and [[azithromycin]], the baseline QTc interval was 435 milliseconds before receiving these medications.<ref name="pmid32320003">{{cite journal| author=Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW | display-authors=etal| title=Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. | journal=JAMA | year= 2020 | volume=  | issue=  | pages=  | pmid=32320003 | doi=10.1001/jama.2020.6775 | pmc=7177629 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32320003  }} </ref><ref name="GiudicessiNoseworthy2020">{{cite journal|last1=Giudicessi|first1=John R.|last2=Noseworthy|first2=Peter A.|last3=Friedman|first3=Paul A.|last4=Ackerman|first4=Michael J.|title=Urgent Guidance for Navigating and Circumventing the QTc-Prolonging and Torsadogenic Potential of Possible Pharmacotherapies for Coronavirus Disease 19 (COVID-19)|journal=Mayo Clinic Proceedings|volume=95|issue=6|year=2020|pages=1213–1221|issn=00256196|doi=10.1016/j.mayocp.2020.03.024}}</ref>
-*'''Atrial Arrhythmia:''' According to a study, among 393 patients with COVID-19, [[Cardiac arrhythmia|atrial arrhythmias]] were more common among patients requiring invasive [[mechanical ventilation]] than noninvasive [[mechanical ventilation]] (17.7 versus 1.9 percent).<ref name="GoyalChoi2020">{{cite journal|last1=Goyal|first1=Parag|last2=Choi|first2=Justin J.|last3=Pinheiro|first3=Laura C.|last4=Schenck|first4=Edward J.|last5=Chen|first5=Ruijun|last6=Jabri|first6=Assem|last7=Satlin|first7=Michael J.|last8=Campion|first8=Thomas R.|last9=Nahid|first9=Musarrat|last10=Ringel|first10=Joanna B.|last11=Hoffman|first11=Katherine L.|last12=Alshak|first12=Mark N.|last13=Li|first13=Han A.|last14=Wehmeyer|first14=Graham T.|last15=Rajan|first15=Mangala|last16=Reshetnyak|first16=Evgeniya|last17=Hupert|first17=Nathaniel|last18=Horn|first18=Evelyn M.|last19=Martinez|first19=Fernando J.|last20=Gulick|first20=Roy M.|last21=Safford|first21=Monika M.|title=Clinical Characteristics of Covid-19 in New York City|journal=New England Journal of Medicine|volume=382|issue=24|year=2020|pages=2372–2374|issn=0028-4793|doi=10.1056/NEJMc2010419}}</ref>
-*'''Ventricular Arrhythmia:''' According to a study done in Wuhan, China. among 187 hospitalized patients with [[COVID-19]], 11 patients (5.9 percent) developed [[Ventricular arrhythmias|ventricular tachyarrhythmias]].<ref name="pmid32219356">{{cite journal| author=Guo T, Fan Y, Chen M, Wu X, Zhang L, He T | display-authors=etal| title=Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19). | journal=JAMA Cardiol | year= 2020 | volume=  | issue=  | pages=  | pmid=32219356 | doi=10.1001/jamacardio.2020.1017 | pmc=7101506 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32219356  }} </ref>
-*'''Cardiac Arrest:''' According to a Lombardia Cardiac Arrest Registry (Lombardia CARe) of the region Lombardia in Italy. Out of 9806 cases of [[COVID-19]], 362 cases of out-of-hospital [[cardiac arrest]] were reported during the study time frame in 2020. During a similar period in 2019, 229 cases of out-of-hospital [[cardiac arrest]] were reported, which means an increment of 58% was observed in 2020 among [[COVID-19]] patients. According to the records from a tertiary care hospital in Wuhan. Out of 761 patients with severe [[COVID-19]], 151 patients developed in-hospital [[cardiac arrest]]. 136 patients received resuscitation. Out of 136 patients, 119 patients had a respiratory cause. 10 patients had a cardiac cause. 7 patients had other causes. Ventricular fibrillation or pulseless ventricular tachycardia was observed in 8 patients (5.9%), [[Pulseless electrical activity]] in 6 patients (4.4%), and [[asystole]] in 122 [[COVID-19]] patients (89.7%).<ref name="BaldiSechi2020">{{cite journal|last1=Baldi|first1=Enrico|last2=Sechi|first2=Giuseppe M.|last3=Mare|first3=Claudio|last4=Canevari|first4=Fabrizio|last5=Brancaglione|first5=Antonella|last6=Primi|first6=Roberto|last7=Klersy|first7=Catherine|last8=Palo|first8=Alessandra|last9=Contri|first9=Enrico|last10=Ronchi|first10=Vincenza|last11=Beretta|first11=Giorgio|last12=Reali|first12=Francesca|last13=Parogni|first13=Pierpaolo|last14=Facchin|first14=Fabio|last15=Bua|first15=Davide|last16=Rizzi|first16=Ugo|last17=Bussi|first17=Daniele|last18=Ruggeri|first18=Simone|last19=Oltrona Visconti|first19=Luigi|last20=Savastano|first20=Simone|title=Out-of-Hospital Cardiac Arrest during the Covid-19 Outbreak in Italy|journal=New England Journal of Medicine|year=2020|issn=0028-4793|doi=10.1056/NEJMc2010418}}</ref><ref name="ShaoXu2020">{{cite journal|last1=Shao|first1=Fei|last2=Xu|first2=Shuang|last3=Ma|first3=Xuedi|last4=Xu|first4=Zhouming|last5=Lyu|first5=Jiayou|last6=Ng|first6=Michael|last7=Cui|first7=Hao|last8=Yu|first8=Changxiao|last9=Zhang|first9=Qing|last10=Sun|first10=Peng|last11=Tang|first11=Ziren|title=In-hospital cardiac arrest outcomes among patients with COVID-19 pneumonia in Wuhan, China|journal=Resuscitation|volume=151|year=2020|pages=18–23|issn=03009572|doi=10.1016/j.resuscitation.2020.04.005}}</ref>
-==== Diagnostic Testing: ====
-*'''ECG:''' Most patients with the severe [[COVID-19]], and especially patients who receive [[QT-prolonging medications]], should have a baseline [[electrocardiogram]] (ECG) performed at the time of admission to the hospital.The best technique to get the [[QT interval]] is with a 12-lead electrocardiogram (ECG). However, to scale back exposure to hospital workers, this could not perpetually be possible. A single-lead [[ECG]] might underestimate the QT interval, and there ought to be an effort to use a multiple-lead telemetry system to observe the QT interval.<ref name="GandhiSolomon2020">{{cite journal|last1=Gandhi|first1=Rajesh T.|last2=Solomon|first2=Caren G.|last3=Lynch|first3=John B.|last4=del Rio|first4=Carlos|title=Mild or Moderate Covid-19|journal=New England Journal of Medicine|year=2020|issn=0028-4793|doi=10.1056/NEJMcp2009249}}</ref><ref name="ChangSaleh2020">{{cite journal|last1=Chang|first1=David|last2=Saleh|first2=Moussa|last3=Gabriels|first3=James|last4=Ismail|first4=Haisam|last5=Goldner|first5=Bruce|last6=Willner|first6=Jonathan|last7=Beldner|first7=Stuart|last8=Mitra|first8=Raman|last9=John|first9=Roy|last10=Epstein|first10=Laurence M.|title=Inpatient Use of Ambulatory Telemetry Monitors for COVID-19 Patients Treated With Hydroxychloroquine and/or Azithromycin|journal=Journal of the American College of Cardiology|volume=75|issue=23|year=2020|pages=2992–2993|issn=07351097|doi=10.1016/j.jacc.2020.04.032}}</ref>
-*'''Transthoracic echocardiography:''' [[Transthoracic echocardiography]] is recommended for an inpatient with [[heart failure]], [[arrhythmia]], ECG changes, or newly diagnosed [[cardiomegaly]] on chest [[x-ray]] or [[CT]]-chest.<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>
-==== Treatment:====
-*'''Polymorphic Ventricular Tachycardia (torsades de pointes):''' All patients with [[torsades de pointes]] (TdP) should be determined if they are hemodynamically stable or unstable through immediate evaluation of the symptoms, vital signs, and level of consciousness.<ref name="PanchalBerg2018">{{cite journal|last1=Panchal|first1=Ashish R.|last2=Berg|first2=Katherine M.|last3=Kudenchuk|first3=Peter J.|last4=Del Rios|first4=Marina|last5=Hirsch|first5=Karen G.|last6=Link|first6=Mark S.|last7=Kurz|first7=Michael C.|last8=Chan|first8=Paul S.|last9=Cabañas|first9=José G.|last10=Morley|first10=Peter T.|last11=Hazinski|first11=Mary Fran|last12=Donnino|first12=Michael W.|title=2018 American Heart Association Focused Update on Advanced Cardiovascular Life Support Use of Antiarrhythmic Drugs During and Immediately After Cardiac Arrest: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care|journal=Circulation|volume=138|issue=23|year=2018|issn=0009-7322|doi=10.1161/CIR.0000000000000613}}</ref>
-**'''Unstable patients:''' Patients with [[COVID-19]] with sustained [[torsades de pointes]] (TdP) usually become hemodynamically unstable, severely symptomatic because of perfusion failure, or pulseless and should be treated according to [[standard resuscitation algorithms]], including [[cardioversion/defibrillation]]. Initial treatment with antiarrhythmic medications is not indicated for hemodynamically unstable or pulseless patients except intravenous (IV) magnesium.
-**'''Stable patients:''' In a patient with a single episode of TdP, treatment with IV magnesium along with correction of metabolic/electrolyte disturbances or removal of any inciting medications may be sufficient. The patient should be kept under observation until the [[electrolytes]], and the [[QT interval]] nearly normalizes. An IV bolus of 2-gram magnesium sulfate is the standard therapy for an adult. This is equivalent to a dose of 8.12 mmol of magnesium. The clinical situation of a patient determines the rate of magnesium infusion. Infusion occurs over one to two minutes in patients with pulseless [[cardiac arrest]]. The infusion should occur over 15 minutes in patients without [[cardiac arrest]] as a rapid IV bolus of magnesium can result in [[hypotension]] and [[asystole]]. Some patients are given a continuous bolus of IV magnesium at a rate of 3 to 20 mg/min until the QT interval is below 0.50 seconds.<ref name="TzivoniBanai1988">{{cite journal|last1=Tzivoni|first1=D|last2=Banai|first2=S|last3=Schuger|first3=C|last4=Benhorin|first4=J|last5=Keren|first5=A|last6=Gottlieb|first6=S|last7=Stern|first7=S|title=Treatment of torsade de pointes with magnesium sulfate.|journal=Circulation|volume=77|issue=2|year=1988|pages=392–397|issn=0009-7322|doi=10.1161/01.CIR.77.2.392}}</ref><ref name="NeumarOtto2010">{{cite journal|last1=Neumar|first1=R. W.|last2=Otto|first2=C. W.|last3=Link|first3=M. S.|last4=Kronick|first4=S. L.|last5=Shuster|first5=M.|last6=Callaway|first6=C. W.|last7=Kudenchuk|first7=P. J.|last8=Ornato|first8=J. P.|last9=McNally|first9=B.|last10=Silvers|first10=S. M.|last11=Passman|first11=R. S.|last12=White|first12=R. D.|last13=Hess|first13=E. P.|last14=Tang|first14=W.|last15=Davis|first15=D.|last16=Sinz|first16=E.|last17=Morrison|first17=L. J.|title=Part 8: Adult Advanced Cardiovascular Life Support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care|journal=Circulation|volume=122|issue=18_suppl_3|year=2010|pages=S729–S767|issn=0009-7322|doi=10.1161/CIRCULATIONAHA.110.970988}}</ref>
-*'''Other Cardiac arrhythmia:''' The treatment for other [[arrhythmias]] in [[COVID-19]] patients is the same as in patients with arrhythmias without COVID-19 infection.
-===Out-of-hospital cardiac arrest and Sudden Cardiac Death===
-====Pathophysiology====
-*'''Drug induced:'''
-Since the [[COVID-19]] [[pandemic]], several [[pharmacological]] [[therapies]] have been proposed, one of them is of two [[anti-malarial]] and [[antirheumatic]] drugs called [[Chloroquine]] or [[Hydroxychloroquine]]. Due to their cost-effectiveness and easy availability, there is a surge in the use of [[Chloroquine]] and [[Hydroxychloroquine]], with or without [[Azithromycin]]. The [[clinical trials]] in order to estimate their [[efficacy]] are still in the preliminary stage, however, a notable concern is of their [[cardiac]] [[adverse effects]]. This includes [[QT prolongation]] and [[Torsade de pointes]] (TdP) leading to [[sudden cardiac death]]. The risk is there when these drugs are prescribed separately, however it increases several folds when these drugs are administered together, especially in patients with underlying [[hepatic]] [[disease]] or [[renal failure]].
-*'''Genetic susceptibility:'''
-[[Epidemiological]] studies have shown that [[African Americans]] have higher [[COVID-19]] associated [[morbidity]] and [[mortality]] as compared to people from other ethnic groups. Recent studies show that this ethnic predilection is due to the genetics factors which contribute to a common ion channel variant p.Ser1103Tyr-SCN5A which confer an increased risk of drug-induced long QT syndrome (DI-LQTS) and drug-induced sudden cardiac death (DI-SCD). p.Ser1103Tyr-SCN5A generates late or persistent sodium current which is further aggravated by [[hypoxia]] or [[respiratory acidosis]] secondary to [[lungs]] involvement in [[COVID-19]]. This has and has been linked to an increased risk of ventricular arrhythmia (VA) such as torsade de pointes  and sudden cardiac death (SCD) in African Americans
-===Spontaneous Coronary Artery Dissection===
-====Pathophysiology====
-* In patients with an inflammatory overload, a localized inflammation of the coronary adventitia and periadventitial fat can occur. This could lead to the development of sudden coronary artery dissection in a susceptible patient.
-====Signs and symptoms====
-====Treatment====
-==References==
-{{reflist|2}}
-<references />

Cardiovascular Disorders and COVID-19: Difference between revisions

Latest revision as of 20:53, 11 July 2020

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