Myocarditis other diagnostic studies

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Homa Najafi, M.D.[2]

Overview

There are no other diagnostic studies associated with [disease name].

OR

[Diagnostic study] may be helpful in the diagnosis of [disease name]. Findings suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

OR

Other diagnostic studies for [disease name] include [diagnostic study 1], which demonstrates [finding 1], [finding 2], and [finding 3], and [diagnostic study 2], which demonstrates [finding 1], [finding 2], and [finding 3].

Other Diagnostic Studies

Endomyocardial biopsy (EMB)

EMB is a gold standard tool for diagnosis of myocarditis. However, the usage of EMB is limited.

The Diagnosis of active myocarditis by EMB is based on the Dallas criteria which is inflammatory infiltrates in the myocardium accompanied by myocyte injury and necrosis that can not contributed to ischemic event.

Based on the latest ESC guideline for diagnosis of myocarditis all specimens that

2007 AHA/ACCF/ESC Scientific Statement of The Role of Endomyocardial Biopsy in the Management of Cardiovascular Disease

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)

Endomyocardial biopsy confirms the diagnosis of myocarditis and identifies the underlying aetiology and the type of inflammation (e.g. giant cell, eosinophilic myocarditis, sarcoidosis) which imply different treatments and prognosis (Figure 1).1–3,11,14–16 Importantly, EMB is also the basis for safe (infection negative) immunosuppression and antiviral treatment. If EMB is performed by experienced teams, its complication rate is low (0–0.8).9,18,139,148

The recent scientific statement on EMB gave highest levels of recommendations in the life-threatening clinical presentations.120 However, the diagnostic, prognostic, and therapeutic value of EMB was based on the Dallas histopathologic criteria and did not include immunohistochemistry and viral genome analysis (Figure 1). These are established tools which should be used to achieve an aetiological diagnosis.9,14–16,18,19,22,26,30–32,100,101,103,133,137,138

To optimize diagnostic accuracy and reduce sampling error in focal myocarditis, EMB should be performed early in the course of the disease and multiple specimens should be taken.2 At least three samples, each 1–2 mm in size, should be taken (from the right or from the left ventricle) and immediately fixed in 10% buffered formalin at room temperature for light microscopy; additional samples should be snap frozen in liquid nitrogen and stored at −80°C or stored in RNA later tubes at room temperature for viral PCR.2,149 With respect to left or right heart biopsy, some patients may clinically present with exclusive left or right heart failure and myocarditis. In such cases, decision for left or right heart biopsy should be made according to the additional clinical information. To increase the diagnostic sensitivity of immunohistochemistry, use of a large panel of monoclonal and polyclonal antibodies (including anti-CD3, T lymphocytes; anti-CD68, macrophages; and anti HLA-DR) is mandatory for the identification and characterization of the inflammatory infiltrate and for the detection of HLA-DR upregulation on EMB tissue sections as marker of infectious-negative autoimmune myocarditis where immunosuppression may be considered.2,14,15 Other immunofluorescence stains used to define humoral rejection in heart transplant EMB, such as C3d and C4d, have been recently reported as promising markers of immune activation in patients with inflammatory cardiomyopathy; a limitation of these stains is that they require frozen material.40

The diagnostic contribution of EMB is enhanced by molecular analysis with DNA–RNA extraction and RT-PCR amplification of viral genome.16 In order to exclude systemic infection, peripheral blood should be investigated in parallel with EMB2,9; quantification of virus load and determination of virus replication may add diagnostic value.22

Suggested primer sets and PCR protocols are detailed in the supplementary DataSupplementary Data. The main technical requirements are as follows:

RT-PCR detection of viral DNA or RNA in the heart should always be controlled by amplifying adequate positive samples containing different viral copy numbers as well as negative controls.2 Sequencing of the amplified viral gene product is mandatory in order to identify virus subtypes and recognize contaminations.

Blood samples should be tested by RT-PCR to detect acute systemic virus infection, and to exclude persistently/latently infected blood cells which might contaminate heart tissue samples but do not indicate virus infection of the myocardium.2

The detection of replicative forms of viral nucleic acids in the heart supports a pathogenic role of virus in myocarditis; however, detection of viral mRNA by RT-PCR may be difficult to establish in EMB due to low amounts of viral mRNA especially in longstanding chronic myocarditis.