Background
Myocarditis is a direct inflammation of the heart musculature. Infections are the most common cause. Patients present with a variety of symptoms from asymptomatic to an acute onset of heart failure.
OUTLINE
PATHOGENESIS CHARACTERIZATION VIRUS
- Overexpression of tumor necrosis factor (TNF)alpha and TNFalpha receptor I in human viral myocarditis: clinicopathologic correlations.
Calabrese F, Carturan E, Chimenti C, Pieroni M, Agostini C, Angelini A, Crosato M, Valente M, Boffa GM, Frustaci A, Thiene G.
Department of Pathological Anatomy, University of Padua Medical School, Padua, Italy.
Mod Pathol. 2004 Sep;17(9):1108-18. Abstract quote
Proinflammatory cytokines, including tumor necrosis factor (TNF)alpha, have been recognized as important physiopathogenetic factors in the initiation and continuation of inflammatory cardiomyopathies. Experimental and preliminary human studies have demonstrated that TNFalpha plays a crucial role in enteroviral-induced myocarditis.
In this study, we investigated the expression of TNFalpha and both its receptors (TNFRI and TNFRII) in both viral and nonviral myocarditis. Myocardial expression of TNFalpha was then correlated with different clinical and pathologic findings. TNFalpha expression was investigated in endomyocardial biopsies obtained from 38 patients with myocarditis and from eight control subjects by using reverse transcriptase-polymerase chain reaction (PCR) and immunohistochemistry. Viral etiology was diagnosed by PCR in 20 cases: enterovirus in seven, Epstein-Barr virus in four, hepatitis C virus in three, adenovirus in two, influenza virus in two, cytomegalovirus in one, and double infection adenovirus and enterovirus in one. Immunohistochemistry was also used to analyze both TNFalpha receptors (RI and RII). A semiquantitative analysis was employed (score 0-3) for necrosis, inflammation, fibrosis and immunohistochemical findings. TNFalpha mRNA and TNFalpha protein were significantly more present in viral myocarditis than in nonviral myocarditis (16/20 vs 3/18, P=0.001). Remarkable immunostaining was observed for both receptors, particularly TNFRI. Histological analysis revealed that myocardial necrosis (mean score 1.89 vs 1.15, P=0.01) and cellular infiltration (mean score 2.26 vs 1.78, P=0.05) were more prominent in TNFalpha-positive cases. Among TNFalpha-positive cases, the greater TNFalpha mRNAs, the more impaired was cardiac function.
Our findings suggest that the expression of TNFalpha may play an important role in the pathogenesis of viral myocarditis of any etiology and may influence the severity of cardiac dysfunction. Cytokine effects are more strictly linked to overexpression of TNFRI.
Histologic and in situ viral findings in the myocardium in cases of sudden, unexpected death.Cioc AM, Nuovo GJ.
Department of PathologyOhio State University Medical Center, Columbus, Ohio.
Mod Pathol 2002 Sep;15(9):914-22 Abstract quote The purpose of this study was to do in situ viral detection in myocardial tissues of individuals who suffered sudden unexpected death and to correlate the results with the postmortem histopathologic findings.
Thirteen cases were identified and the heart tissues were analyzed for adenovirus, cytomegalovirus, Epstein Barr virus, herpes simplex virus 1 and 2, human immunodeficiency virus 1 (HIV-1), influenza A, influenza B, parvovirus, rotavirus, picornavirus (including separate primers for enterovirus and Coxsackie virus A and B), varicella zoster virus, and respiratory syncytial virus. Thirteen individuals aged 2 to 67 years were studied. In each case, polymerase chain reaction-amplified viral RNA was detected in situ: Coxsackie virus B (5 cases), rotavirus (4 cases), HIV-1 (2 cases), influenza A (1 case), and influenza B (1 case).
Immunohistochemical detection of viral proteins was found in the five Coxsackie virus cases and four rotavirus cases. The mononuclear inflammatory infiltrate was diffuse and marked only in the cases of influenza A and HIV-1, as well as one of the Coxsackie virus and rotavirus cases, respectively. Immunohistochemical analysis showed that the most common cell type in the inflammatory infiltrates was CD68-positive macrophages. Direct myocyte infection was most prominent in the cases of Coxsackie virus infection. In summary, in situ viral detection was documented in each case of idiopathic myocarditis associated with sudden, unexpected death; in 6/13 cases, the myocarditis was focal and minimal.
Although Coxsackie virus was, as expected, the most common virus noted, other viruses including rotavirus and HIV-1 were also observed, highlighting the need for comprehensive viral and histologic analyses in such cases.
CLINICAL VARIANTS CHARACTERIZATION FATAL MYOCARDITIS
Histopathologic, immunohistochemical, and polymerase chain reaction assays in the study of cases with fatal sporadic myocarditis. Guarner J, Bhatnagar J, Shieh WJ, Nolte KB, Klein D, Gookin MS, Peñaranda S, Oberste MS, Jones T, Smith C, Pallansch MA, Zaki SR.Infectious Disease Pathology Branch, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
Hum Pathol. 2007 Sep;38(9):1412-9. Abstract quot
Paraffin tissue blocks from 27 cases with sporadic myocarditis were collected during a 12-year period at a single medical examiner's office. Blocks were studied by using histopathology; immunohistochemistry for viruses (adenovirus, enterovirus, influenza A and B, and human herpes types 4 and 5), bacteria (Neisseria menigitidis, Ehlichia sp, spotted fever group Rickettsia) and parasites (Toxoplasma gondii and Trypanosoma cruzi); and polymerase chain reaction (PCR)/RT-PCR for adenovirus and enterovirus.
We identified enterovirus in 5 (18.5%) cases and Sarcocystis in a 36-year-old woman who had focal inflammation and myocyte necrosis. Immunohistochemical evidence of enteroviruses was found in the myocytes of 2 patients less than 6 months old who had diffuse mononuclear myocardial inflammation, interstitial pneumonitis; one also had encephalitis. In these 2 patients, the presence of enterovirus was confirmed by RT-PCR targeting the 5' nontranslated region and was serotyped as coxsackievirus B2 by sequencing the VP1 capsid region. In another 3 cases (ages 12, 47, and 54), enterovirus was detected by the 5' nontranslated region region; VP1 sequencing identified these as echoviruses 6, 13, and 7, respectively.
Accurately identifying an infectious agent is the foundation for clinical and public health interventions. Despite using multiple diagnostic methods, an organism could only be detected in a small proportion of sporadic myocarditis cases.
- Diagnosis and presentation of fatal myocarditis.
Kyto V, Saukko P, Lignitz E, Schwesinger G, Henn V, Saraste A, Voipio-Pulkki LM.
Department of Anatomy, Institute of Biomedicine, University of Turku, 20520 Turku, Finland.
Hum Pathol. 2005 Sep;36(9):1003-7. Abstract quote
The clinical presentation of myocarditis is highly variable, and histopathology is thus considered to be the cornerstone of diagnosis.
We studied how accurately myocarditis was diagnosed in a series of routine autopsies and how fatal myocarditis presents clinically. All death certificates with myocarditis recorded as the underlying cause of death in Finland in 1970 to 1998 were collected retrospectively (N = 639). All cases with cardiac autopsy samples and clinical data available (n = 142; median age, 51 years) were included in this study. The cardiac samples were reexamined for the presence of myocarditis by 3 experienced independent pathologists using the Dallas criteria. The clinical data were evaluated for the presenting signs and symptoms of myocarditis. Histopathologic reanalysis showed that only 32% of the 142 subjects met the Dallas criteria for myocarditis (75% of pediatric and 28% of adult patients, P = .001). Clinicians had suspected myocarditis in only one third of the hospitalized Dallas-positive patients. Dallas-positive patients presented more often with features of myocardial infarction (26% versus 9%, P = .026) or heart failure (35% versus 10%, P = .001) than Dallas-negative subjects. The signs and symptoms of infectious disease were also more common in Dallas-positive patients (61% versus 23%, P < .001). In contrast, Dallas-negative subjects died suddenly or were found dead more frequently (68% versus 39%, P = .004). The most evident cause of death in the Dallas-negative subjects was ischemic heart disease (n = 78, 55% of all cases).
Our study provides evidence that myocarditis is overdiagnosed on routine autopsies, particularly in patients who have died suddenly or are found dead. Fatal myocarditis appears to present equally often as heart failure, sudden death, or mimicking myocardial infarction.
HISTOLOGICAL TYPES CHARACTERIZATION General Active phase has interstitial infiltrate of usually mononuclear cells associated with focal myocyte necrosis VARIANTS Hypersensitivity myocarditis Interstitial infiltrates and perivascular with lymphocytes, macrophages, and eosinophils Giant cell myocarditis Widespread inflammatory infiltrate with multinucleate giant cells with lymphocytes, eosinophils, plasma cells and macrophages
Focal but extensive necrosis
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Last Updated September 18, 2007
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