Myocarditis overview: Difference between revisions

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==Overview==
==Overview==
'''Myocarditis''' is [[inflammation]] of the [[myocardium]]. It may present with [[chest pain]], [[ST segment elevation]], elevated biomarkers of [[myonecrosis]], [[heart failure]], and / or [[sudden death]].
'''Myocarditis''' is [[inflammation]] of the [[myocardium]], the muscular part of the [[heart]]. It may present with [[chest pain]], rapid signs of [[heart failure]], or [[sudden death]].


==Pathophysiology==
==Pathophysiology==
During either an infection or a [[hypersensitivity reaction]], the inflammatory response may cause [[myonecrosis]] either directly or indirectly as part of an [[autoimmune]] reaction.  Myocarditis is a continuum of three phases of the disease processes with each one evolving into the next<ref name="pmid11524405">{{cite journal| author=Liu PP, Mason JW| title=Advances in the understanding of myocarditis. | journal=Circulation | year= 2001 | volume= 104 | issue= 9 | pages= 1076-82 | pmid=11524405 | doi= | pmc= | url= }} </ref>:
During an infection or hypersensitive reaction, the immune system produces inflammatory cells that release chemicals to fight the infection. These inflammatory cells enter the myocardium (heart muscle) where the infection resides. However, the chemicals produced by an immune response can damage the heart muscle ([[myocardium]]). As a result, the heart can become damaged, enlarged, and weak. This damage to the [[myocardium]] leads to symptoms of [[heart failure]].
===Phase I: Viral Infection and Replication===
Viruses such as [[coxsackie virus|coxsackie]] and [[enterovirus]], get internalized in peripheral tissues and activate the immune system. A few of these viral genomes attach to the immunologic cells which circulate throughout the body and lodge in other organs such as the heart where they further replicate and cause localized tissue destruction.
 
===Phase II: Autoimmune Injury===
After the host immune system eliminates the viral genomes from the body, the immune system may remains activated in patients who develop myocarditis.  This leads to the development of an [[autoimmune reaction]] where [[T-cells]] and [[cytokines]] target the host tissue such as the [[myocardium]] which causes further [[myocyte]] damage.
 
===Phase III: Dilated Cardiomyopathy===
[[Cytokines]], which are produced in reaction to infection and [[cell death]], are a leading cause of [[dilated cardiomyopathy]]. Matrix [[metalloproteinase]]s, such as [[gelatinase]], [[collagenase]]s, and [[elastase]]s may also be activated by [[cytokines]] during the [[autoimmune]] phase<ref name="pmid9679721">{{cite journal| author=Ono K, Matsumori A, Shioi T, Furukawa Y, Sasayama S| title=Cytokine gene expression after myocardial infarction in rat hearts: possible implication in left ventricular remodeling. | journal=Circulation | year= 1998 | volume= 98 | issue= 2 | pages= 149-56 | pmid=9679721 | doi= | pmc= | url= }} </ref><ref name="pmid9846575">{{cite journal| author=Lee JK, Zaidi SH, Liu P, Dawood F, Cheah AY, Wen WH et al.| title=A serine elastase inhibitor reduces inflammation and fibrosis and preserves cardiac function after experimentally-induced murine myocarditis. | journal=Nat Med | year= 1998 | volume= 4 | issue= 12 | pages= 1383-91 | pmid=9846575 | doi=10.1038/3973 | pmc= | url= }} </ref>. [[Protease]] produced by [[coxsackie virus]] can also modify the [[sarcoglycan complex]] in [[myocytes]]<ref name="pmid10086389">{{cite journal| author=Badorff C, Lee GH, Lamphear BJ, Martone ME, Campbell KP, Rhoads RE et al.| title=Enteroviral protease 2A cleaves dystrophin: evidence of cytoskeletal disruption in an acquired cardiomyopathy. | journal=Nat Med | year= 1999 | volume= 5 | issue= 3 | pages= 320-6 | pmid=10086389 | doi=10.1038/6543 | pmc= | url= }} </ref> leading to [[ventricular dilation]].
 
[[Eosinophilic]] and [[hypersensitive]] myocarditis may occur secondary to [[parasitic infection]]s, drug [[hypersensitivity]] or [[hypereosinophilic syndrome]]. [[Eosinophilic]] infiltration in [[myocardium]] lead to release of [[eosinophilic]] proteins which increase cellular membrane permeability which in turn leads to [[cell death]]<ref name="pmid17386864">{{cite journal| author=Ginsberg F, Parrillo JE| title=Eosinophilic myocarditis. | journal=Heart Fail Clin | year= 2005 | volume= 1 | issue= 3 | pages= 419-29 | pmid=17386864 | doi=10.1016/j.hfc.2005.06.013 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17386864  }} </ref><ref name="pmid20181108">{{cite journal| author=Amini R, Nielsen C| title=Eosinophilic myocarditis mimicking acute coronary syndrome secondary to idiopathic hypereosinophilic syndrome: a case report. | journal=J Med Case Reports | year= 2010 | volume= 4 | issue=  | pages= 40 | pmid=20181108 | doi=10.1186/1752-1947-4-40 | pmc=PMC2830978 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20181108  }} </ref>.


==Epidemiology and Demographics==
==Epidemiology and Demographics==
In developed countries, myocarditis is generally due to [[viral infections]] such as [[coxsackie B]], [[enterovirus]],[[adenovirus]], [[parvovirus B19]], [[hepatitis C]], and [[herpes virus]] 6. In developing countries, myocarditis is generally due to [[HIV]] and [[rheumatic heart disease]].  In routine [[autopsy|autopsies]], 1-9% of all patients had evidence of myocardial inflammation. In young adults, up to 20% of all cases of [[sudden death]] are due to myocarditis. There is a male predominance.
In developed countries, myocarditis is generally due to [[viral infections]] such as [[coxsackie B]], [[enterovirus]],[[adenovirus]], [[parvovirus B19]], [[hepatitis C]], and [[herpes virus]] 6. In developing countries, myocarditis is generally due to [[HIV]] and [[rheumatic heart disease]].


==Natural History, Complications & Prognosis==
==Natural History, Complications & Prognosis==
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==Clinicopathological classification<ref name="pmid1960305">{{cite journal| author=Lieberman EB, Hutchins GM, Herskowitz A, Rose NR, Baughman KL| title=Clinicopathologic description of myocarditis. | journal=J Am Coll Cardiol | year= 1991 | volume= 18 | issue= 7 | pages= 1617-26 | pmid=1960305 | doi= | pmc= | url= }} </ref>==
==Clinicopathological classification<ref name="pmid1960305">{{cite journal| author=Lieberman EB, Hutchins GM, Herskowitz A, Rose NR, Baughman KL| title=Clinicopathologic description of myocarditis. | journal=J Am Coll Cardiol | year= 1991 | volume= 18 | issue= 7 | pages= 1617-26 | pmid=1960305 | doi= | pmc= | url= }} </ref>==


*'''Fulminant myocarditis''' - Fulminant myocarditis occurs following a viral prodrome.  Fulminant myocarditis presents as acute severe cardiovascular compromise with ventricular dysfunction. The prognosis is good if the patient survives the acute illness<ref name="pmid10706898">{{cite journal| author=McCarthy RE, Boehmer JP, Hruban RH, Hutchins GM, Kasper EK, Hare JM et al.| title=Long-term outcome of fulminant myocarditis as compared with acute (nonfulminant) myocarditis. | journal=N Engl J Med | year= 2000 | volume= 342 | issue= 10 | pages= 690-5 | pmid=10706898 | doi=10.1056/NEJM200003093421003 | pmc= | url= }} </ref>.  On [[endomyocardial biopsy]], there are multiple focci of inflammation.  Fulminant myocarditis is associated with a non-dilated [[hypocontractile left ventricle]] with thick [[interventricular septum]] while acute myocarditis (see below) is associated with a dilated [[hypocontractile left ventricle]] with normal [[interventricular septum]]<ref name="pmid10898439">{{cite journal| author=Felker GM, Boehmer JP, Hruban RH, Hutchins GM, Kasper EK, Baughman KL et al.| title=Echocardiographic findings in fulminant and acute myocarditis. | journal=J Am Coll Cardiol | year= 2000 | volume= 36 | issue= 1 | pages= 227-32 | pmid=10898439 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10898439  }} </ref>.
*'''Fulminant myocarditis''' - Fulminant myocarditis occurs following a viral prodrome.  Fulminant myocarditis presents as acute severe cardiovascular compromise with ventricular dysfunction. The prognosis is good if the patient survives the acute illness<ref name="pmid10706898">{{cite journal| author=McCarthy RE, Boehmer JP, Hruban RH, Hutchins GM, Kasper EK, Hare JM et al.| title=Long-term outcome of fulminant myocarditis as compared with acute (nonfulminant) myocarditis. | journal=N Engl J Med | year= 2000 | volume= 342 | issue= 10 | pages= 690-5 | pmid=10706898 | doi=10.1056/NEJM200003093421003 | pmc= | url= }} </ref>.  On [[endomyocardial biopsy]], there are multiple focci of inflammation.


*'''Acute myocarditis''' - Acute myocarditis presents with a less distinct onset of the illness.  When the patient does present, there is already a decline in left ventricular dysfunction. Acute myocarditis may progress to [[dilated cardiomyopathy]].
*'''Acute myocarditis''' - Acute myocarditis presents with a less distinct onset of the illness.  When the patient does present, there is already a decline in left ventricular dysfunction. Acute myocarditis may progress to [[dilated cardiomyopathy]].
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*'''Chronic persistent myocarditis''' - Chronic persistent myocarditis has a less distinct onset ff the illness. Histologically it is characterized by persistent infiltration and myocyte necrosis.  Despite the presence of symptoms, ventricular dysfunction is absent.
*'''Chronic persistent myocarditis''' - Chronic persistent myocarditis has a less distinct onset ff the illness. Histologically it is characterized by persistent infiltration and myocyte necrosis.  Despite the presence of symptoms, ventricular dysfunction is absent.


==Differential Diagnosis of the Underlying Causes of Myocarditis==
==Symptoms==
(By organ system)
 
{|style="width:70%; height:100px" border="1"
|style="height:100px"; style="width:25%" border="1" bgcolor="LightSteelBlue" | '''Cardiovascular'''
|style="height:100px"; style="width:75%" border="1" bgcolor="Beige" | Acute [[rheumatic fever]], [[Dressler syndrome]]
|-
|-bgcolor="LightSteelBlue"
| '''Chemical / poisoning'''
|bgcolor="Beige"| [[Arsenic]], [[Carbon monoxide]], [[Lead]]
|-
|-bgcolor="LightSteelBlue"
| '''Dermatologic'''
|bgcolor="Beige"| [[Scleroderma]], [[Systemic lupus erythematosus]]
|-
|-bgcolor="LightSteelBlue"
| '''Drug Side Effect'''
|bgcolor="Beige"| Drugs are known to cause hypersensitive myocarditis<ref name="pmid19189924">{{cite journal| author=Pursnani A, Yee H, Slater W, Sarswat N| title=Hypersensitivity myocarditis associated with azithromycin exposure. | journal=Ann Intern Med | year= 2009 | volume= 150 | issue= 3 | pages= 225-6 | pmid=19189924 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19189924  }} </ref><ref name="pmid4010343">{{cite journal| author=Taliercio CP, Olney BA, Lie JT| title=Myocarditis related to drug hypersensitivity. | journal=Mayo Clin Proc | year= 1985 | volume= 60 | issue= 7 | pages= 463-8 | pmid=4010343 | doi= | pmc= | url= }} </ref><ref name="pmid19440116">{{cite journal| author=Ben m'rad M, Leclerc-Mercier S, Blanche P, Franck N, Rozenberg F, Fulla Y et al.| title=Drug-induced hypersensitivity syndrome: clinical and biologic disease patterns in 24 patients. | journal=Medicine (Baltimore) | year= 2009 | volume= 88 | issue= 3 | pages= 131-40 | pmid=19440116 | doi=10.1097/MD.0b013e3181a4d1a1 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19440116  }} </ref>. Peripheral eosinophilia and eosinophilic myocardial infiltrates may be seen on myocardial biopsy. Some of the common drugs are: [[Amphetamines]], [[Benzodiazepines]], [[Carbamazepine]], [[Chloramphenicol]], [[Clozapine]]<ref name="pmid17194170">{{cite journal| author=Haas SJ, Hill R, Krum H, Liew D, Tonkin A, Demos L et al.| title=Clozapine-associated myocarditis: a review of 116 cases of suspected myocarditis associated with the use of clozapine in Australia during 1993-2003. | journal=Drug Saf |year= 2007 | volume= 30 | issue= 1 | pages= 47-57 | pmid=17194170 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17194170  }} </ref>, [[Cocaine]], [[Cyclophosphamide]], [[Dobutamine]]<ref name="pmid7578186">{{cite journal| author=Spear GS|title=Eosinophilic explant carditis with eosinophilia: ?Hypersensitivity to dobutamine infusion. | journal=J Heart Lung Transplant | year= 1995 | volume= 14 | issue= 4 | pages= 755-60 | pmid=7578186 | doi= | pmc= | url= }} </ref><ref name="pmid15090985">{{cite journal| author=Johnson MR| title=Eosinophilic myocarditis in the explanted hearts of cardiac transplant recipients: Interesting pathologic finding or pathophysiologic entity of clinical significance? | journal=Crit Care Med | year= 2004 | volume= 32 | issue= 3 | pages= 888-90 | pmid=15090985 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15090985  }} </ref>, [[Methyldopa]], [[Penicillin]], [[Phenytoin]], [[Spironolactone]], [[Streptomycin]], [[Sulfonamides]], [[Tricyclic antidepressants]].
 
|-
|-bgcolor="LightSteelBlue"
| '''Ear Nose Throat'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Endocrine'''
|bgcolor="Beige"| [[Thyrotoxicosis]]
|-
|-bgcolor="LightSteelBlue"
| '''Environmental'''
|bgcolor="Beige"|  [[Heatstroke]], Scorpion stings, snake bites, bites from black widow spider, wasp venom, tick paralysis
|-
|-bgcolor="LightSteelBlue"
| '''Gastroenterologic'''
|bgcolor="Beige"| [[Celiac disease]]<ref name="pmid12045166">{{cite journal| author=Frustaci A, Cuoco L, Chimenti C, Pieroni M, Fioravanti G, Gentiloni N et al.| title=Celiac disease associated with autoimmune myocarditis. | journal=Circulation | year= 2002 | volume= 105 | issue= 22 | pages= 2611-8 | pmid=12045166 | doi= | pmc= | url= }} </ref>, [[Crohn disease]], [[Ulcerative colitis]]
|-
|-bgcolor="LightSteelBlue"
| '''Genetic'''
|bgcolor="Beige"| [[Haemochromatosis]], [[Friedreich ataxia]]
|-
|-bgcolor="LightSteelBlue"
| '''Hematologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Iatrogenic'''
|bgcolor="Beige"| Inflammatory myocarditis may be seen in post transplant rejection.
|-
|-bgcolor="LightSteelBlue"
| '''Infectious Disease'''
|bgcolor="Beige"|
 
'''Viral:''' The idiopathic myocarditis is the most common  type of myocarditis and is often suspected to be secondary to viral infection<ref name="pmid15699250">{{cite journal| author=Kühl U, Pauschinger M, Noutsias M, Seeberg B, Bock T, Lassner D et al.| title=High prevalence of viral genomes and multiple viral infections in the myocardium of adults with "idiopathic" left ventricular dysfunction. | journal=Circulation | year= 2005 | volume= 111 | issue= 7 | pages= 887-93 | pmid=15699250 | doi=10.1161/01.CIR.0000155616.07901.35 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15699250  }} </ref>. Common virus associated with myocarditis are- [[Adenovirus]]<ref name="pmid12906974">{{cite journal| author=Bowles NE, Ni J, Kearney DL, Pauschinger M, Schultheiss HP, McCarthy R et al.| title=Detection of viruses in myocardial tissues by polymerase chain reaction. evidence of adenovirus as a common cause of myocarditis in children and adults. | journal=J Am Coll Cardiol | year= 2003 | volume= 42 | issue= 3 | pages= 466-72 | pmid=12906974 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12906974  }} </ref><ref name="pmid16172268">{{cite journal| author=Kühl U, Pauschinger M, Seeberg B, Lassner D, Noutsias M, Poller W et al.| title=Viral persistence in the myocardium is associated with progressive cardiac dysfunction. | journal=Circulation | year= 2005 | volume= 112 | issue= 13 | pages= 1965-70 | pmid=16172268 | doi=10.1161/CIRCULATIONAHA.105.548156 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16172268  }} </ref>, [[Arbovirus]], [[Coxsackie B]]<ref name="pmid1558005">{{cite journal|author=Rose NR, Neumann DA, Herskowitz A| title=Coxsackievirus myocarditis. | journal=Adv Intern Med | year= 1992 | volume= 37 | issue=  | pages= 411-29 | pmid=1558005 | doi= | pmc=| url= }} </ref><ref name="pmid4887187">{{cite journal| author=Grist NR, Bell EJ| title=Coxsackie viruses and the heart. | journal=Am Heart J | year= 1969 | volume= 77 | issue= 3 |pages= 295-300 | pmid=4887187 | doi= | pmc= | url= }} </ref>, [[Cytomegalovirus]]<ref name="pmid12906974">{{cite journal| author=Bowles NE, Ni J, Kearney DL, Pauschinger M, Schultheiss HP, McCarthy R et al.| title=Detection of viruses in myocardial tissues by polymerase chain reaction. evidence of adenovirus as a common cause of myocarditis in children and adults. | journal=J Am Coll Cardiol | year= 2003 | volume= 42 | issue= 3 | pages= 466-72 | pmid=12906974 | doi= | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12906974  }} </ref><ref name="pmid2983175">{{cite journal|author=Cohen JI, Corey GR| title=Cytomegalovirus infection in the normal host. | journal=Medicine (Baltimore) | year= 1985 | volume= 64 | issue= 2 | pages= 100-14 | pmid=2983175 |doi= | pmc= | url= }} </ref>, [[Echovirus]], [[Enterovirus]], [[Epstein-Barr virus]]<ref name="pmid12906974">{{cite journal| author=Bowles NE, Ni J, Kearney DL, Pauschinger M, Schultheiss HP, McCarthy R et al.|title=Detection of viruses in myocardial tissues by polymerase chain reaction. evidence of adenovirus as a common cause of myocarditis in children and adults. | journal=J Am Coll Cardiol | year= 2003 | volume= 42 | issue= 3 | pages= 466-72 | pmid=12906974 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12906974  }} </ref><ref name="pmid15557377">{{cite journal| author=Chimenti C, Russo A, Pieroni M, Calabrese F, Verardo R, Thiene G et al.| title=Intramyocyte detection of Epstein-Barr virus genome by laser capture microdissection in patients with inflammatory cardiomyopathy. |journal=Circulation | year= 2004 | volume= 110 | issue= 23 | pages= 3534-9 | pmid=15557377 | doi=10.1161/01.CIR.0000148823.08092.0E | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15557377  }} </ref>, [[Herpes simplex virus]], [[Hepatitis B]], [[Hepatitis C]]<ref name="pmid10908160">{{cite journal| author=Matsumori A, Yutani C, Ikeda Y, Kawai S, Sasayama S| title=Hepatitis C virus from the hearts of patients with myocarditis and cardiomyopathy. | journal=Lab Invest | year= 2000 | volume= 80 | issue= 7 | pages= 1137-42 | pmid=10908160 | doi= | pmc= | url= }} </ref>, [[HIV-1]], [[Influenza]]<ref name="pmid12906974">{{cite journal| author=Bowles NE, Ni J, Kearney DL, Pauschinger M, Schultheiss HP, McCarthy R et al.| title=Detection of viruses in myocardial tissues by polymerase chain reaction. evidence of adenovirus as a common cause of myocarditis in children and adults. | journal=J Am Coll Cardiol | year= 2003 | volume= 42 | issue= 3 | pages= 466-72 | pmid=12906974 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12906974  }} </ref>, [[Mumps]], [[Parvovirus B19]]<ref name="pmid12906974">{{cite journal|author=Bowles NE, Ni J, Kearney DL, Pauschinger M, Schultheiss HP, McCarthy R et al.| title=Detection of viruses in myocardial tissues by polymerase chain reaction. evidence of adenovirus as a common cause of myocarditis in children and adults. | journal=J Am Coll Cardiol | year= 2003 | volume= 42 | issue= 3 | pages= 466-72 | pmid=12906974 | doi= | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12906974  }} </ref><ref name="pmid20456978">{{cite journal|author=Breinholt JP, Moulik M, Dreyer WJ, Denfield SW, Kim JJ, Jefferies JL et al.| title=Viral epidemiologic shift in inflammatory heart disease: the increasing involvement of parvovirus B19 in the myocardium of pediatric cardiac transplant patients. | journal=J Heart Lung Transplant | year= 2010 | volume= 29 | issue= 7 | pages= 739-46 | pmid=20456978 |doi=10.1016/j.healun.2010.03.003 | pmc=PMC2902647 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20456978 }} </ref><ref name="pmid12792925">{{cite journal| author=Pankuweit S, Moll R, Baandrup U, Portig I, Hufnagel G, Maisch B| title=Prevalence of the parvovirus B19 genome in endomyocardial biopsy specimens. | journal=Hum Pathol | year= 2003 | volume= 34 | issue= 5 | pages= 497-503 | pmid=12792925 | doi= | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12792925  }} </ref>, [[Poliomyelitis]], [[Rabies]], [[Respiratory syncytial virus]], [[Rubeola]], [[Varicella]], [[Variola]]/vaccinia<ref name="pmid15120802">{{cite journal| author=Cassimatis DC, Atwood JE, Engler RM, Linz PE, Grabenstein JD, Vernalis MN|title=Smallpox vaccination and myopericarditis: a clinical review. | journal=J Am Coll Cardiol | year= 2004 | volume= 43 | issue= 9 | pages= 1503-10 | pmid=15120802 |doi=10.1016/j.jacc.2003.11.053 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15120802  }} </ref>, [[Viral hepatitis]], [[Yellow fever virus]]
 
'''Bacterial:'''  [[Borrelia burgdorferi]], [[Brucellosis]], [[Clostridia]], [[Diphtheria]], [[Melioidosis]], [[Meningococci]], [[Mycoplasma pneumoniae]], [[Psittacosis]], [[Salmonella typhi]], [[Staphylococci]], [[Streptococci]], [[Tuberculosis]]
 
'''Fungal:'''  [[Actinomycosis]], [[Aspergillosis]], [[Blastomycosis]], [[Candidiasis]], [[Coccidioidomycosis]], [[Cryptococcosis]], [[Histoplasmosis]], [[Mucormycosis]]
 
'''Parasitic:'''  [[Balantidiasis]], [[Chagas disease]], [[Cysticercosis]], [[Echinococcosis]], [[Filariasis]], Heterophyiasis, [[Leishmaniasis]], [[Malaria]], Sarcosporidiosis, [[Schistosomiasis]], [[Toxoplasmosis]], [[Trichinosis]], [[Trypanosomiasis]], [[Visceral larva migrans]]
 
'''Rickettsial:'''  [[Q fever]], [[Rocky mountain spotted fever]], [[Scrub typhus]], [[Typhus fever]]
 
'''Spirochetal:'''  [[leptospirosis]]/Weil disease, [[Lyme disease]], [[relapsing fever]]/[[Borrelia]], [[Syphilis]]
|-
|-bgcolor="LightSteelBlue"
| '''Musculoskeletal / Ortho'''
|bgcolor="Beige"| [[Rheumatoid arthritis]]
|-
|-bgcolor="LightSteelBlue"
| '''Neurologic'''
|bgcolor="Beige"| [[Friedreich ataxia]]
|-
|-bgcolor="LightSteelBlue"
| '''Nutritional / Metabolic'''
|bgcolor="Beige"| [[Amyloidosis]], [[Haemochromatosis]]
|-
|-bgcolor="LightSteelBlue"
| '''Obstetric/Gynecologic'''
|bgcolor="Beige"| [[Peripartum cardiomyopathy]]
|-
|-bgcolor="LightSteelBlue"
| '''Oncologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Opthalmologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Overdose / Toxicity'''
|bgcolor="Beige"| [[Doxorubicin]], Radiation exposure
|-
|-bgcolor="LightSteelBlue"
| '''Psychiatric'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Pulmonary'''
|bgcolor="Beige"| [[Aspergillosis]], [[Sarcoidosis]]
|-
|-bgcolor="LightSteelBlue"
| '''Renal / Electrolyte'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Rheum / Immune / Allergy'''
|bgcolor="Beige"|  [[Crohn disease]], [[Dressler syndrome]], [[Giant cell myocarditis]]<ref name="pmid19026310">{{cite journal| author=Cooper LT, Hare JM, Tazelaar HD, Edwards WD, Starling RC, Deng MC et al.| title=Usefulness of immunosuppression for giant cell myocarditis. | journal=Am J Cardiol | year= 2008 | volume= 102 | issue= 11 | pages= 1535-9 | pmid=19026310 | doi=10.1016/j.amjcard.2008.07.041 | pmc=PMC2613862 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19026310  }} </ref>, [[Kawasaki disease]], [[Rheumatoid arthritis]], [[Sarcoidosis]], [[Scleroderma]], [[Systemic lupus erythematosus]], [[Thyrotoxicosis]], [[Ulcerative colitis]], [[Wegener granulomatosis]]
|-
|-bgcolor="LightSteelBlue"
| '''Sexual'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Trauma'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Urologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Miscellaneous'''
|bgcolor="Beige"|  [[Amyloidosis]], [[Heatstroke]], [[Hyperthermia]], Radiation exposure
|-
|}
 
==Diagnosis==
 
===Symptoms===
The symptoms and the intensity of symptoms associated with myocarditis are variable.  Myocarditis may be associated with no symptoms. If symptoms are present,they may be similar to the flu.  Patients may present with [[chest pain]] as a result of the inflammatory process involving the myocardium or with symptoms of [[congestive heart failure]].  Patients may complain of [[palpitations]], a [[racing heart]] or [[syncope]]. In fulminant myocarditis, patients present with the abrupt onset of [[flu]]-like symptoms and the abrupt onset of [[heart failure]] symptoms. In chronic and acute myocarditis, the onset of symptoms may be more insidious. Symptoms may include:
The symptoms and the intensity of symptoms associated with myocarditis are variable.  Myocarditis may be associated with no symptoms. If symptoms are present,they may be similar to the flu.  Patients may present with [[chest pain]] as a result of the inflammatory process involving the myocardium or with symptoms of [[congestive heart failure]].  Patients may complain of [[palpitations]], a [[racing heart]] or [[syncope]]. In fulminant myocarditis, patients present with the abrupt onset of [[flu]]-like symptoms and the abrupt onset of [[heart failure]] symptoms. In chronic and acute myocarditis, the onset of symptoms may be more insidious. Symptoms may include:
*[[Palpitations]]
*[[Palpitations]]
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*[[Low urine output]]
*[[Low urine output]]


==Diagnosis==
===Physical examination===
===Physical examination===


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===Electrocardiographic Findings===
===Electrocardiographic Findings===
The ECG findings in myocarditis are similar to those in [[pericarditis]] and [[myocardial infarction]]<ref name="pmid3354405">{{cite journal| author=Miklozek CL, Crumpacker CS, Royal HD, Come PC, Sullivan JL, Abelmann WH| title=Myocarditis presenting as acute myocardial infarction. | journal=Am Heart J | year= 1988 | volume= 115 | issue= 4 | pages= 768-76 | pmid=3354405 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3354405  }} </ref><ref name="pmid14645641">{{cite journal| author=Wang K, Asinger RW, Marriott HJ| title=ST-segment elevation in conditions other than acute myocardial infarction. | journal=N Engl J Med | year= 2003 | volume= 349 | issue= 22 | pages= 2128-35 | pmid=14645641 | doi=10.1056/NEJMra022580 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14645641  }} </ref>. Myocarditis should be suspected in patients who are at low risk for [[ischemic heart disease]] and [[MI]] and in those patients with normal coronary arteries on [[coronary angiography]].
The [[electrocardiogram|ECG]] findings most commonly seen in myocarditis are<ref name="pmid11070105">{{cite journal| author=Feldman AM, McNamara D|title=Myocarditis. | journal=N Engl J Med | year= 2000 | volume= 343 | issue= 19 | pages= 1388-98 | pmid=11070105 |doi=10.1056/NEJM200011093431908 | pmc= | url= }} </ref>:
*[[Sinus tachycardia]]
*Diffuse [[T wave]] inversions
*[[ST segment elevation]] without reciprocal depression. This helps in differentiating [[myocarditis]] from [[MI|infarction]] particularly when EKG changes are diffuse.
*Low voltage of the [[QRS]] complexes may be observed.
*[[Arrhythmias]] such as atrial and ventricular ectopic beats, atrial and ventricular [[tachycardia]]s and [[atrial fibrillation]] may also be present and are common in [[Chagas]] heart disease.
*[[Heart block]] is frequently observed in [[giant cell myocarditis]] and cardiac [[sarcoidosis]].


These EKG changes may persist for several months before they resolve spontaneously.
Common [[electrocardiogram|ECG]] findings in myocarditis include<ref name="pmid11070105">{{cite journal| author=Feldman AM, McNamara D| title=Myocarditis. | journal=N Engl J Med | year= 2000 | volume= 343 | issue= 19 | pages= 1388-98 | pmid=11070105 | doi=10.1056/NEJM200011093431908 | pmc= | url= }} </ref>:
* [[Sinus tachycardia]]
* Diffuse [[T wave]] inversions
* [[ST segment]] elevation may also be present


The presence of [[ST segment elevation]] in patients with [[myocarditis]] can mimic [[pericarditis]] and [[myocardial infarction]]. [[Arrhythmias]] and [[heart block]]s may also be observed in myocarditis patients.  Myocarditis can be distinguished from [[pericarditis]] by the presence of [[PR]] depression in the patient with [[pericarditis]].
[[ST segment elevation]] may also be seen in [[pericarditis]]. [[PR]] depression is also present, however, in patients with [[pericarditis]].


===Echocardiography===
===Echocardiography===
[[Echocardiography]] in patients with [[myocarditis]] allows for serial assessment of left ventricular dysfunction<ref name="pmid10898439">{{cite journal| author=Felker GM, Boehmer JP, Hruban RH, Hutchins GM, Kasper EK, Baughman KL et al.| title=Echocardiographic findings in fulminant and acute myocarditis. | journal=J Am Coll Cardiol | year= 2000 | volume= 36 | issue= 1 | pages= 227-32 | pmid=10898439 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10898439 ; }} </ref>, and can be used to distinguish fulminant (non-dilated [[hypocontractile left ventricle]] with thick [[interventricular septum]]) from acute myocarditis (dilated [[hypocontractile left ventricle]] with normal [[interventricular septum]])<ref name="pmid10898439">{{cite journal| author=Felker GM, Boehmer JP, Hruban RH, Hutchins GM, Kasper EK, Baughman KL et al.| title=Echocardiographic findings in fulminant and acute myocarditis. | journal=J Am Coll Cardiol | year= 2000 | volume= 36 | issue= 1 | pages= 227-32 | pmid=10898439 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10898439  }} </ref>.
[[Echocardiography]] in patients with [[myocarditis]] allows for serial assessment of left ventricular dysfunction. <ref name="pmid10898439">{{cite journal| author=Felker GM, Boehmer JP, Hruban RH, Hutchins GM, Kasper EK, Baughman KL et al.| title=Echocardiographic findings in fulminant and acute myocarditis. | journal=J Am Coll Cardiol | year= 2000 | volume= 36 | issue= 1 | pages= 227-32 | pmid=10898439 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10898439  }} </ref>.
 
Echocardiographic findings in myocardits include:
*Wall motion abnormalities<ref name="pmid3400607">{{cite journal| author=Pinamonti B, Alberti E, Cigalotto A, Dreas L, Salvi A, Silvestri F et al.| title=Echocardiographic findings in myocarditis. | journal=Am J Cardiol | year= 1988 | volume= 62 | issue= 4 | pages= 285-91 | pmid=3400607 | doi= | pmc= | url= }} </ref>.
*[[Systolic dysfunction]]<ref name="pmid3400607">{{cite journal| author=Pinamonti B, Alberti E, Cigalotto A, Dreas L, Salvi A, Silvestri F et al.| title=Echocardiographic findings in myocarditis. | journal=Am J Cardiol | year= 1988 | volume= 62 | issue= 4 | pages= 285-91 | pmid=3400607 | doi= | pmc= | url= }} </ref><ref name="pmid6711435">{{cite journal| author=Nieminen MS, Heikkilä J, Karjalainen J| title=Echocardiography in acute infectious myocarditis: relation to clinical and electrocardiographic findings. | journal=Am J Cardiol | year= 1984 | volume= 53 | issue= 9 | pages= 1331-7 | pmid=6711435 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6711435  }} </ref>.
*[[Diastolic dysfunction]]<ref name="pmid8296760">{{cite journal| author=James KB, Lee K, Thomas JD, Hobbs RE, Rincon G, Bott-Silverman C et al.| title=Left ventricular diastolic dysfunction in lymphocytic myocarditis as assessed by Doppler echocardiography. | journal=Am J Cardiol | year= 1994 | volume= 73 | issue= 4 | pages= 282-5 | pmid=8296760 | doi= | pmc= | url= }} </ref>.
*Changes in image texture on echocardiogram, i.e. increase in brightness, heterogeneity, and contrast<ref name="pmid8682119">{{cite journal| author=Lieback E, Hardouin I, Meyer R, Bellach J, Hetzer R| title=Clinical value of echocardiographic tissue characterization in the diagnosis of myocarditis. | journal=Eur Heart J | year= 1996 | volume= 17 | issue= 1 | pages= 135-42 | pmid=8682119 | doi= | pmc= | url= }} </ref>.
*[[Pericardial effusion]]
*Functional regurgitation through the AV valves may be noted due to [[ventricular dilation]].
 
In general, [[left ventricular function]] improves in fulminant myocarditis over a course of approximately 6 months<ref name="pmid10898439">{{cite journal| author=Felker GM, Boehmer JP, Hruban RH, Hutchins GM, Kasper EK, Baughman KL et al.| title=Echocardiographic findings in fulminant and acute myocarditis. | journal=J Am Coll Cardiol | year= 2000 | volume= 36 | issue= 1 | pages= 227-32 | pmid=10898439 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10898439  }} </ref>.


===Endomyocardial Biopsy===
===Endomyocardial Biopsy===
[[Endomyocardial biopsy]] remains the gold standard test to evaluate for the presence of and to subclassify the type of myocarditis.  A small tissue sample of the [[endocardium]] and [[myocardium]] is obtained via right sided cardiac catheterization. The sample is then evaluated by a pathologist using [[immunochemistry]] and special staining techniques as necessary.  Histopathological features include abundant [[edema]] in the myocardial [[interstitium]] and an inflammatory infiltrate which is rich in [[lymphocyte]]s and [[macrophage]]s.  Focal destruction of [[myocytes]] as a result of the inflammatory process results in [[left ventricular dysfunction]].<ref name="pmid11070105">{{cite journal| author=Feldman AM, McNamara D| title=Myocarditis. | journal=N Engl J Med | year= 2000 | volume= 343 | issue= 19 | pages= 1388-98 | pmid=11070105 | doi=10.1056/NEJM200011093431908 | pmc= | url= }} </ref>  [[Endomyocardial biopsy]] is recommended when the results would identify an underlying disease that is amenable to therapy.  Routine performance of [[endomyocardial biopsy]] is not recommended in all patients with myocarditis.
==2009 ACC / AHA Guidelines for Endomyocardial Biopsy<ref name="pmid19324966">{{cite journal| author=Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG et al.| title=2009 focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. | journal=Circulation | year= 2009 | volume= 119 | issue= 14 | pages= e391-479 | pmid=19324966 | doi=10.1161/CIRCULATIONAHA.109.192065 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19324966  }} </ref>==
{{cquote|
'''Class IIa'''
*Endomyocardial biopsy can be useful in patients presenting with [[heart failure]] when a specific diagnosis is suspected that would influence therapy.<ref name="pmid17959655">{{cite journal| author=Cooper LT, Baughman KL, Feldman AM, Frustaci A, Jessup M, Kuhl U et al.| title=The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. | journal=Circulation | year= 2007 | volume= 116 | issue= 19 | pages= 2216-33 | pmid=17959655 | doi=10.1161/CIRCULATIONAHA.107.186093 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17959655  }} </ref> ''(Level of Evidence: C)''


'''Class III'''
Endomyocardial [[biopsy]] remains the gold standard test to evaluate for the presence of and to subclassify the type of myocarditis.  A small tissue sample of the [[endocardium]] and [[myocardium]] is obtained via right sided cardiac catheterization. The sample is then evaluated by a pathologist and if necessary using [[immunochemistry]] and special staining techniques. Histopathological features include abundant [[edema]] in the myocardial [[interstitium]] and an inflammatory infiltrate which is rich in [[lymphocyte]]s and [[macrophage]]s. Focal destruction of [[myocytes]] as a result of the inflammatory process explains the myocardial [[pump failure]].<ref name="pmid11070105">{{cite journal| author=Feldman AM, McNamara D| title=Myocarditis. | journal=N Engl J Med | year= 2000 | volume= 343 | issue= 19 | pages= 1388-98 | pmid=11070105 | doi=10.1056/NEJM200011093431908 | pmc= | url= }} </ref>
*Endomyocardial biopsy should not be performed in the routine evaluation of patients with [[heart failure]].<ref name="pmid17959655">{{cite journal| author=Cooper LT, Baughman KL, Feldman AM, Frustaci A, Jessup M, Kuhl U et al.| title=The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. | journal=Circulation | year= 2007 | volume= 116 | issue= 19 | pages= 2216-33 | pmid=17959655 | doi=10.1161/CIRCULATIONAHA.107.186093 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17959655 }} </ref> ''(Level of Evidence: C)''
}}
 
==The AHA/ACCF/ESC Scientific Statement: The role of Endomyocardial Biopsy in fourteen clinical scenarios<ref name="pmid17959655">{{cite journal| author=Cooper LT, Baughman KL, Feldman AM, Frustaci A, Jessup M, Kuhl U et al.| title=The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. | journal=Circulation | year= 2007 | volume= 116 | issue= 19 | pages= 2216-33 | pmid=17959655 | doi=10.1161/CIRCULATIONAHA.107.186093 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17959655  }} </ref>==
{{cquote|
'''Class I'''
 
1. New-onset [[heart failure]] of <2 weeks’ duration associated with a normal-sized or [[dilated left ventricle]] and hemodynamic compromise. ''(Level of Evidence: B)''
 
2. New-onset [[heart failure]] of 2 weeks’ to 3 months’ duration associated with a dilated left ventricle and new ventricular [[arrhythmias]], second- or third-degree [[heart block]], or failure to respond to usual care within 1 to 2 weeks. ''(Level of Evidence: B)''
 
'''Class IIa'''
 
1. [[Heart failure]] of >3 months’ duration associated with a [[dilated left ventricle]] and new ventricular [[arrhythmias]], second- or third-degree [[heart block]], or failure to respond to usual care within 1 to 2 weeks. ''(Level of Evidence: C)''
 
2. [[Heart failure]] associated with a DCM of any duration associated with suspected allergic reaction and/or [[eosinophilia]]. ''(Level of Evidence: C)''
 
3. [[Heart failure]] associated with suspected [[anthracycline]] [[cardiomyopathy]]. ''(Level of Evidence: C)''
 
4. Heart failure associated with unexplained [[restrictive cardiomyopathy]]. ''(Level of Evidence: C)''
 
5. Suspected [[cardiac tumor]]s. ''(Level of Evidence: C)''
 
6. Unexplained [[cardiomyopathy]] in children. ''(Level of Evidence: C)''
 
'''Class IIb'''
 
1. New-onset heart failure of 2 weeks’ to 3 months’ duration associated with a dilated left ventricle, without new ventricular arrhythmias or second- or third-degree heart block, that responds to usual care within 1 to 2 weeks. ''(Level of Evidence: B)''
 
2. Heart failure of >3 months’ duration associated with a dilated left ventricle, without new ventricular arrhythmias or second- or third-degree heart block, that responds to usual care within 1 to 2 weeks. ''(Level of Evidence: C)''
 
3. Heart failure associated with unexplained HCM. ''(Level of Evidence: C)''
 
4. Suspected ARVD/C. ''(Level of Evidence: C)''
 
5. Unexplained ventricular arrhythmias. ''(Level of Evidence: C)''
 
'''Class III'''
 
1. Unexplained [[atrial fibrillation]]. ''(Level of Evidence: C)''
}}
 
==Complications of Endomyocardial Biopsy<ref name="pmid17959655">{{cite journal| author=Cooper LT, Baughman KL, Feldman AM, Frustaci A, Jessup M, Kuhl U et al.| title=The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. | journal=Circulation | year= 2007 | volume= 116 | issue= 19 | pages= 2216-33 | pmid=17959655 | doi=10.1161/CIRCULATIONAHA.107.186093 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17959655  }} </ref><ref name="pmid20713901">{{cite journal| author=Yilmaz A, Kindermann I, Kindermann M, Mahfoud F, Ukena C, Athanasiadis A et al.| title=Comparative evaluation of left and right ventricular endomyocardial biopsy: differences in complication rate and diagnostic performance. | journal=Circulation | year= 2010 | volume= 122 | issue= 9 | pages= 900-9 | pmid=20713901 | doi=10.1161/CIRCULATIONAHA.109.924167 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20713901  }} </ref>==
Complications may be as high as 6% as observed in a series where 546 patients with cardiomyopathy underwent right ventricular endomyocardial biopsy<ref name="pmid1729344">{{cite journal| author=Deckers JW, Hare JM, Baughman KL| title=Complications of transvenous right ventricular endomyocardial biopsy in adult patients with cardiomyopathy: a seven-year survey of 546 consecutive diagnostic procedures in a tertiary referral center. | journal=J Am Coll Cardiol | year= 1992 | volume= 19 | issue= 1 | pages= 43-7 | pmid=1729344 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1729344  }} </ref>. Several other studies reported the incidence of complications to be 0.5 to 1.5%<ref name="pmid20713901">{{cite journal| author=Yilmaz A, Kindermann I, Kindermann M, Mahfoud F, Ukena C, Athanasiadis A et al.| title=Comparative evaluation of left and right ventricular endomyocardial biopsy: differences in complication rate and diagnostic performance. | journal=Circulation | year= 2010 | volume= 122 | issue= 9 | pages= 900-9 | pmid=20713901 | doi=10.1161/CIRCULATIONAHA.109.924167 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20713901  }} </ref><ref name="pmid18838566">{{cite journal| author=Holzmann M, Nicko A, Kühl U, Noutsias M, Poller W, Hoffmann W et al.| title=Complication rate of right ventricular endomyocardial biopsy via the femoral approach: a retrospective and prospective study analyzing 3048 diagnostic procedures over an 11-year period. | journal=Circulation | year= 2008 | volume= 118 | issue= 17 | pages= 1722-8 | pmid=18838566 | doi=10.1161/CIRCULATIONAHA.107.743427 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18838566  }} </ref>.
 
*Myocardial perforation leading to [[pericardial tamponade]]
*[[Heart block]]
*[[Pulmonary embolization]]
*[[Pneumothorax]]
*[[Nerve injury]]
*[[Hematoma]]
*[[Tricuspid valve]] damage
*[[Arteriovenous fistula]]
*[[Deep venous thrombosis]]
*[[Bleeding]] at the puncture site (venous/arterial due to accidental arterial puncture)
*[[Arrhythmias]] ([[supraventricular tachycardia]]/[[ventricular tachycardia]]/[[complete heart block]])
*[[Tricuspid valve]] damage
*[[Coronary artery]] to [[right ventricle]] [[fistula]]


===Coronary Angiography===
===Coronary Angiography===
Line 279: Line 63:


===Cardiac Magnetic Resonance Imaging===
===Cardiac Magnetic Resonance Imaging===
[[Cardiac MRI]] findings associated with [[myocarditis]] include [[myocardial inflammation]], [[myocardial edema]], [[capillary leak]], and [[reduced left ventricular function]].  While the [[cMRI]] pattern of [[gadolinium]] hyperenhancement in [[ST segment elevation myocardial infarction]] is transmural and extends from the endocardium to the epicardium, the patchy, non-segmental hyperenhancement pattern in [[myocarditis]] in contrast involves the [[epicardium]] and spares the [[subendocardium]]<ref>{{cite journal |author=Skouri HN, Dec GW, Friedrich MG, Cooper LT |title=Noninvasive imaging in myocarditis |journal=J. Am. Coll. Cardiol. |volume=48 |issue=10 |pages=2085-93 |year=2006 |pmid=17112998 |doi=10.1016/j.jacc.2006.08.017}}</ref><ref name="pmid19389557">{{cite journal| author=Friedrich MG, Sechtem U, Schulz-Menger J, Holmvang G, Alakija P, Cooper LT et al.| title=Cardiovascular magnetic resonance in myocarditis: A JACC White Paper. | journal=J Am Coll Cardiol | year= 2009 | volume= 53 | issue= 17 | pages= 1475-87 | pmid=19389557 | doi=10.1016/j.jacc.2009.02.007 | pmc=PMC2743893 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19389557  }}</ref>.
Myocardial inflammation associated with myocarditis appears as a high intensity signal with delayed gadolinium hyperenhancement on cardiac MRI (cMRI). <ref name="pmid15936612">{{cite journal| author=Abdel-Aty H, Boyé P, Zagrosek A, Wassmuth R, Kumar A, Messroghli D et al.| title=Diagnostic performance of cardiovascular magnetic resonance in patients with suspected acute myocarditis: comparison of different approaches. | journal=J Am Coll Cardiol | year= 2005 | volume= 45 | issue= 11 | pages= 1815-22 | pmid=15936612 | doi=10.1016/j.jacc.2004.11.069 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15936612  }} </ref>.  While the cMRI pattern of [[gadolinium]] hyperenhancement in [[ST segment elevation myocardial infarction]] is transmural and extends from the endocardium to the epicardium, the patchy, non-segmental hyperenhancement pattern in [[myocarditis]] in contrast involves the epicardium and spares the subendocardium<ref>{{cite journal |author=Skouri HN, Dec GW, Friedrich MG, Cooper LT |title=Noninvasive imaging in myocarditis |journal=J. Am. Coll. Cardiol. |volume=48 |issue=10 |pages=2085-93 |year=2006 |pmid=17112998 |doi=10.1016/j.jacc.2006.08.017}}</ref>.


===Laboratory Findings===
===Laboratory Findings===
Line 309: Line 93:


====Echocardiography====
====Echocardiography====
In patients with myocarditis there will be a focal wall motion abnormalities, while these will be absent in the patient with pericarditis.
In patients with myocarditis there will be a focal wall motion abnormalities, while these will be absent in the patient with pericarditis.  There may be a [[pericardial effusion]] in the patient with [[pericarditis]], while myocarditis is not associated with a [[pericardial effusion]].


==Treatment==
==Treatment==
[[Bacterial infection]]s are treated with [[antibiotic]]s, dependent on the nature of the pathogen and its sensitivity to antibiotics. As most viral infections cannot be treated with directed therapy, symptomatic treatment is the only form of therapy for those forms of [[myocarditis]], e.g. [[diuretic]]s and/or [[inotrope]]s for ventricular failure. [[ACE inhibitor]] therapy may aid in left ventricular remodeling after the inflammation has begun to resolve.
Insofar as most viral infections cannot be treated with directed therapy, symptomatic treatment is the mainstay of therapy for patients with viral [[myocarditis]]. Supportive therapy includes [[diuretic]]s and [[inotrope]]s for [[left ventricular failure]]. [[ACE inhibitor]] therapy may aid in left ventricular remodeling after the inflammation has begun to resolve.  in patients with fulminant myocarditis, placement of an [[intra-aortic balloon pump]] or a [[left ventricular assist device]] may be necessary as bridge to recovery.
 
According to 2010 HFSA guidelines<ref name="pmid20610207">{{cite journal| author=Heart Failure Society of America. Lindenfeld J, Albert NM, Boehmer JP, Collins SP, Ezekowitz JA et al.| title=HFSA 2010 Comprehensive Heart Failure Practice Guideline. | journal=J Card Fail | year= 2010 | volume= 16 | issue= 6 | pages= e1-194 | pmid=20610207 | doi=10.1016/j.cardfail.2010.04.004 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20610207  }} </ref>, routine use of immunosuppressive therapies in management of myocarditis is not recommended ''(Strength of Evidence A)''. Immunotherapy is beneficial in [[giant cell myocarditis]]. Finally, [[cardiac transplantation]] can be performed in patients with severe myocarditis who fail to recover.


According to 2010 HFSA guidelines<ref name="pmid20610207">{{cite journal| author=Heart Failure Society of America. Lindenfeld J, Albert NM, Boehmer JP, Collins SP, Ezekowitz JA et al.| title=HFSA 2010 Comprehensive Heart Failure Practice Guideline. | journal=J Card Fail | year= 2010 | volume= 16 | issue= 6 | pages= e1-194 | pmid=20610207 | doi=10.1016/j.cardfail.2010.04.004 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20610207  }} </ref>, routine use of immunosuppressive therapies in management of myocarditis is not recommended ''(Strength of Evidence A)''. Immunotherapy is beneficial in [[giant cell myocarditis]]. Other alternative therapy in severe myocarditis is transplantation.
[[Bacterial infection]]s are treated with [[antibiotic]]s the selection of which is based upon the nature of the pathogen and its sensitivity to antibiotics.


==References==
==References==

Revision as of 22:13, 11 September 2011

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Varun Kumar, M.B.B.S.

Overview

Myocarditis is inflammation of the myocardium, the muscular part of the heart. It may present with chest pain, rapid signs of heart failure, or sudden death.

Pathophysiology

During an infection or hypersensitive reaction, the immune system produces inflammatory cells that release chemicals to fight the infection. These inflammatory cells enter the myocardium (heart muscle) where the infection resides. However, the chemicals produced by an immune response can damage the heart muscle (myocardium). As a result, the heart can become damaged, enlarged, and weak. This damage to the myocardium leads to symptoms of heart failure.

Epidemiology and Demographics

In developed countries, myocarditis is generally due to viral infections such as coxsackie B, enterovirus,adenovirus, parvovirus B19, hepatitis C, and herpes virus 6. In developing countries, myocarditis is generally due to HIV and rheumatic heart disease.

Natural History, Complications & Prognosis

Myocarditis is usually self limiting and is associated with a good prognosis especially if it is secondary to a viral infection. Patients rarely develop cardiac failure, pulmonary edema, arrhythmias or cardiogenic shock. In some instances, myocarditis may be associated with sudden death. Patients with fulminant myocarditis have a good long term prognosis if they survive the acute phase of the disease [1] . The prognosis of fulminant myocarditis is better than that of either acute myocarditis or giant cell myocarditis.

The presence of left bundle branch block, q waves, AV block, syncope and a left ventricular ejection fraction < 40% are associated with sudden death and cardiac transplantation[2].

Clinicopathological classification[3]

  • Fulminant myocarditis - Fulminant myocarditis occurs following a viral prodrome. Fulminant myocarditis presents as acute severe cardiovascular compromise with ventricular dysfunction. The prognosis is good if the patient survives the acute illness[1]. On endomyocardial biopsy, there are multiple focci of inflammation.
  • Acute myocarditis - Acute myocarditis presents with a less distinct onset of the illness. When the patient does present, there is already a decline in left ventricular dysfunction. Acute myocarditis may progress to dilated cardiomyopathy.
  • Chronic active myocarditis Chronic active myocarditis has a less distinct onset of the illness. There are clinical and histologic relapses and the development of ventricular dysfunction. Histologically, chronic inflammatory changes with mild to moderate fibrosis may be present.
  • Chronic persistent myocarditis - Chronic persistent myocarditis has a less distinct onset ff the illness. Histologically it is characterized by persistent infiltration and myocyte necrosis. Despite the presence of symptoms, ventricular dysfunction is absent.

Symptoms

The symptoms and the intensity of symptoms associated with myocarditis are variable. Myocarditis may be associated with no symptoms. If symptoms are present,they may be similar to the flu. Patients may present with chest pain as a result of the inflammatory process involving the myocardium or with symptoms of congestive heart failure. Patients may complain of palpitations, a racing heart or syncope. In fulminant myocarditis, patients present with the abrupt onset of flu-like symptoms and the abrupt onset of heart failure symptoms. In chronic and acute myocarditis, the onset of symptoms may be more insidious. Symptoms may include:

Diagnosis

Physical examination

Physical examination in patients with myocarditis may reveal tachycardia, a cardiac gallop, mitral regurgitation and pulmonary edema suggestive of cardiac failure. A pericardial friction rub may be noted in presence of concomitant pericarditis, a condition sometimes referred to as myopericarditis.

Electrocardiographic Findings

Common ECG findings in myocarditis include[4]:

ST segment elevation may also be seen in pericarditis. PR depression is also present, however, in patients with pericarditis.

Echocardiography

Echocardiography in patients with myocarditis allows for serial assessment of left ventricular dysfunction. [5].

Endomyocardial Biopsy

Endomyocardial biopsy remains the gold standard test to evaluate for the presence of and to subclassify the type of myocarditis. A small tissue sample of the endocardium and myocardium is obtained via right sided cardiac catheterization. The sample is then evaluated by a pathologist and if necessary using immunochemistry and special staining techniques. Histopathological features include abundant edema in the myocardial interstitium and an inflammatory infiltrate which is rich in lymphocytes and macrophages. Focal destruction of myocytes as a result of the inflammatory process explains the myocardial pump failure.[4]

Coronary Angiography

Coronary angiography may be helpful in excluding either myocardial ischemia or infarction as the cause of ST segment elevation, elevated cardiac biomarkers, or left ventricular dysfunction.

Cardiac Magnetic Resonance Imaging

Myocardial inflammation associated with myocarditis appears as a high intensity signal with delayed gadolinium hyperenhancement on cardiac MRI (cMRI). [6]. While the cMRI pattern of gadolinium hyperenhancement in ST segment elevation myocardial infarction is transmural and extends from the endocardium to the epicardium, the patchy, non-segmental hyperenhancement pattern in myocarditis in contrast involves the epicardium and spares the subendocardium[7].

Laboratory Findings

Myocardial inflammation can be suspected on the basis of the clinical history along with elevations of[4]:

Differentiating Myocarditis from Pericarditis and Myocardial Infarction

Myocarditis presents with chest pain and ST segment elevation. Myocarditis must be distinguished from pericarditis and the life threatening condition of ST elevation myocardial infarction.

Differentiating Myocarditis from ST Segment Elevation Myocardial Infarction

Both diseases present with chest pain, elevated cardiac biomarkers, and focal left ventricular dysfunction. There are two studies that can be used to distinguish the two syndromes:

Coronary Angiography

Coronary angiography can be performed to distinguish myocarditis from ST segment elevation myocardial infarction. ST segment elevation myocardial infarction is associated with either complete or subtotal occlusion of an epicardial coronary artery on coronary angiography.

Cardiac Magnetic Resonance Imaging

Cardiac magnetic resonance imaging is also useful in distinguishing between the two syndromes as well. On cardiac MRI, myocarditis is associated with patchy, non-sentimental, hyperenhancement which is confined to the epicardial layer of the myocardium. In contrast, in ST segment elevation myocardial infarction there is confluent hyperenhancement extending from the endocardium in a distribution that mimics the distribution of the epicardial coronary arteries.

Differentiating Myocarditis from Pericarditis

Both diseases present with chest pain and ST segment elevation. The two conditions can be distinguished by the following studies:

Electrocardiogram

While both disorders are associated with ST segment elevation, pericarditis is also associated with PR segment depression.

Cardiac Biomarkers

Myocarditis is associated with elevations of the CK-MB and the troponin, while pericarditis is not. If pericarditis is associated with underlying inflammation of the myocardium, then this is called myopericarditis. If there is concomitant involvement of both the pericardium and myocardium in myopericarditis, then there are elevations of the cardiac biomarkers.

Echocardiography

In patients with myocarditis there will be a focal wall motion abnormalities, while these will be absent in the patient with pericarditis. There may be a pericardial effusion in the patient with pericarditis, while myocarditis is not associated with a pericardial effusion.

Treatment

Insofar as most viral infections cannot be treated with directed therapy, symptomatic treatment is the mainstay of therapy for patients with viral myocarditis. Supportive therapy includes diuretics and inotropes for left ventricular failure. ACE inhibitor therapy may aid in left ventricular remodeling after the inflammation has begun to resolve. in patients with fulminant myocarditis, placement of an intra-aortic balloon pump or a left ventricular assist device may be necessary as bridge to recovery.

According to 2010 HFSA guidelines[8], routine use of immunosuppressive therapies in management of myocarditis is not recommended (Strength of Evidence A). Immunotherapy is beneficial in giant cell myocarditis. Finally, cardiac transplantation can be performed in patients with severe myocarditis who fail to recover.

Bacterial infections are treated with antibiotics the selection of which is based upon the nature of the pathogen and its sensitivity to antibiotics.

References

  1. 1.0 1.1 McCarthy RE, Boehmer JP, Hruban RH, Hutchins GM, Kasper EK, Hare JM; et al. (2000). "Long-term outcome of fulminant myocarditis as compared with acute (nonfulminant) myocarditis". N Engl J Med. 342 (10): 690–5. doi:10.1056/NEJM200003093421003. PMID 10706898.
  2. Scartazzini R, Schneider P, Bickel H (1975). "[New beta-lactam antibiotics. Functionalisation of the cephem 3-position with sulfur or nitrogen bearing substituents (author's transl)]". Helv Chim Acta. 58 (8): 2437–50. doi:10.1002/hlca.19750580824. PMID 1194054.
  3. Lieberman EB, Hutchins GM, Herskowitz A, Rose NR, Baughman KL (1991). "Clinicopathologic description of myocarditis". J Am Coll Cardiol. 18 (7): 1617–26. PMID 1960305.
  4. 4.0 4.1 4.2 Feldman AM, McNamara D (2000). "Myocarditis". N Engl J Med. 343 (19): 1388–98. doi:10.1056/NEJM200011093431908. PMID 11070105.
  5. Felker GM, Boehmer JP, Hruban RH, Hutchins GM, Kasper EK, Baughman KL; et al. (2000). "Echocardiographic findings in fulminant and acute myocarditis". J Am Coll Cardiol. 36 (1): 227–32. PMID 10898439.
  6. Abdel-Aty H, Boyé P, Zagrosek A, Wassmuth R, Kumar A, Messroghli D; et al. (2005). "Diagnostic performance of cardiovascular magnetic resonance in patients with suspected acute myocarditis: comparison of different approaches". J Am Coll Cardiol. 45 (11): 1815–22. doi:10.1016/j.jacc.2004.11.069. PMID 15936612.
  7. Skouri HN, Dec GW, Friedrich MG, Cooper LT (2006). "Noninvasive imaging in myocarditis". J. Am. Coll. Cardiol. 48 (10): 2085–93. doi:10.1016/j.jacc.2006.08.017. PMID 17112998.
  8. Heart Failure Society of America. Lindenfeld J, Albert NM, Boehmer JP, Collins SP, Ezekowitz JA; et al. (2010). "HFSA 2010 Comprehensive Heart Failure Practice Guideline". J Card Fail. 16 (6): e1–194. doi:10.1016/j.cardfail.2010.04.004. PMID 20610207.

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