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Diagnosis of Myocarditis: Current State and Future Perspectives
PII: S0167-5273(15)01025-6
DOI: doi: 10.1016/j.ijcard.2015.05.008
Reference: IJCA 20476
Please cite this article as: Biesbroek P. Stefan, Beek Aernout M., Germans
Tjeerd, Niessen Hans W.M., van Rossum Albert C., Diagnosis of Myocarditis: Cur-
rent State and Future Perspectives, International Journal of Cardiology (2015), doi:
10.1016/j.ijcard.2015.05.008
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P. Stefan Biesbroek, MD1, 4,5; Aernout M. Beek, MD PhD1,5; Tjeerd Germans, MD PhD3; Hans W.M.
Niessen, MD, PhD2,5 ; Albert C. van Rossum, MD, PhD1,5
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1
Department of Cardiology VU University Medical Center, Amsterdam, the Netherlands
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2
Department of Pathology and Cardiac Surgery VU University Medical Center, Amsterdam, the Netherlands
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3
Medical Center Alkmaar, Alkmaar, the Netherlands
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Interuniversity Cardiology Institute of the Netherlands (ICIN), Utrecht, the Netherlands
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5
Institute for Cardiovascular Research of the Vrije Universiteit of Amsterdam (ICaR-VU), Amsterdam, the
Netherlands
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Corresponding Author:
P. Stefan Biesbroek, MD
Department of Cardiology
E-mail: p.biesbroek@vumc.nl
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Abstract
Myocarditis, i.e. inflammation of the myocardium, is one of the leading causes of sudden cardiac
death (SCD) and dilated cardiomyopathy (DCM) in young adults, and is an important cause of
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symptoms such as chest pain, dyspnea and palpitations. The pathophysiological process of disease
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progression leading to DCM involves an ongoing inflammation as a result of a viral-induced auto-
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immune response or a persisting viral infection. It is therefore crucial to detect the disease early in its
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course and prevent persisting inflammation that may lead to DCM and end-stage heart failure.
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Because of the highly variable clinical presentation, ranging from mild symptoms to severe heart
failure, and the limited available diagnostic tools, the evaluation of patients with suspected
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myocarditis represents an important clinical dilemma in cardiology. New approaches for the
diagnosis of myocarditis are needed in order to improve recognition, to help unravel its
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pathophysiology, and to develop new therapeutic strategies to treat the disease. In this review, we
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give a comprehensive overview of the current diagnostic strategies for patients with suspected
myocarditis, and demonstrate several new techniques that may help to improve the diagnostic work-
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up.
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Introduction
cardiotoxic agent(1). This inflammation can lead to acute heart failure, chest pain and life
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threatening arrhythmias(2-4). Cardiac function may rapidly deteriorate and patients may become
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hemodynamically unstable and require supportive therapy or even cardiac transplantation(5).
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Furthermore, patients with myocarditis have an increased risk of sudden cardiac death (SCD)(6-8)
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and the development of a dilated cardiomyopathy (DCM)(9). Therefore it is important to detect the
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disease early in its course. However, myocarditis is one of the most challenging diagnosis in
cardiology and is often under-recognized due to the heterogeneity of its clinical presentation that
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overlaps with other cardiac diseases, such as an acute coronary syndrome(10). Endomyocardial
biopsy (EMB) is the gold standard for diagnosing myocarditis and its underlying cause, and it may
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contribute to the selection of patients who might benefit from specific therapeutic measures.
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Although EMB is safe in experienced hands, there is a small risk of potentially serious
used for risk stratification or to predict the progression to DCM. In addition, prognosis is good in the
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majority of patients and effective therapy is not available for most causes. EMB is therefore not part
of routine clinical practice in patients with suspected myocarditis. Cardiac magnetic resonance (CMR)
is a good non-invasive alternative but with current techniques the diagnosis can still be missed(16).
Also, CMR cannot determine the underlying cause of myocarditis, and, so far, cannot be used for risk
stratification or prediction of outcome, both crucial for patient management(17). In this review, we
will discuss the current diagnostic approach in patients with suspected myocarditis and demonstrate
new techniques that may help to improve the diagnostic work-up and risk stratification.
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Symptom onset, histological features and underlying etiologic agents may each contribute to the
classification of myocarditis into distinct subtypes(1)(Table 1). Based on the onset of symptoms,
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myocarditis is divided into fulminant, acute or chronic myocarditis(18). The chronic state can be
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further subdivided according to the stage of inflammation into persistent inflammation, chronic viral
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infection (with or without inflammation) or healed inflammation (with or without irreversible
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damage to the heart) (18;19). The types of infiltrates found in EMB samples can also classify
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myocarditis, and provide important clues to an underlying etiology(20). Lymphocytic myocarditis is
by far the most common form. Histological findings may include the presence of multinucleated giant
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cells, granulomas, neutrophilic or eosinophilic granulocytes(21;22). Finally, myocarditis can be
categorized by its underlying etiology. There are numerous causes of myocarditis, yet the etiology
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remains undetermined in most cases. Viral infection of the myocardium is the most common
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identified cause of myocarditis(17). There are up to 20 known cardiotropic viruses that may elicit
myocarditis. In Europe and North America, viral genomes of parvovirus B19 (PBV19), human herpes
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virus 6 (HHV6) and enterovirus (EV) are detected in the majority of cases(23-25). An immune
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response against cardiac myocytes is another important cause of myocarditis, which may be
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triggered by the viral infection, a specific allergenic agent such as medication, or cardiac
transplantation, but is also found in systemic autoimmune disorders, such as systemic lupus
erythematosus, rheumatoid arthritis and scleroderma. In addition, toxic agents including cocaine,
amphetamines and certain cytostatic drugs can lead to myocardial inflammatory disease also. Other
less frequent causes of (toxic) myocarditis include animal bites, insect stings and heavy metals(17).
Myocarditis has a heterogeneous clinical manifestation which can be divided into the following
presentation types: acute coronary syndrome like (ACS-like) symptoms, new-onset heart failure, life
threatening arrhythmias and chronic heart failure. Symptoms or signs are not unique to myocarditis
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and initial evaluation using ECG, blood studies and echocardiography are not specific. Clinical clues to
the disease include elevated inflammatory markers and gastrointestinal or respiratory infection
preceding the onset of symptoms, however these may all be absent(2;26). Also, viral serology cannot
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be used for the diagnosis of myocardial infection(27;28).
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ACS-like presentation
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A large proportion of patients with myocarditis presents with ACS-like symptoms. Differentiating
between myocarditis and acute myocardial infarction (AMI) presents a clinical dilemma because both
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can present with ST-segment elevation, regional myocardial dysfunction and cardiac enzyme
release(29). The clinical challenge is further illustrated by the fact that even if coronary angiography
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(CAG) reveals unobstructed coronary arteries, AMI secondary to vasospasm or embolism is often
assumed to be the case in clinical practice. However, several studies using CMR demonstrated that
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myocarditis was the correct diagnosis in the majority of these patients, and not AMI(30;31).
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Pericarditis often coincides with myocarditis. In this spectrum, perimyocarditis refers to acute
dysfunction(32-34).
Patients with myocarditis may also present with symptoms and signs of heart failure. The suspicion
of myocarditis is generally raised when more common causes of heart failure like ischemic, valvular
and hypertensive heart disease are excluded(35). Echocardiography typically shows global
impairment of cardiac systolic function and in some cases a thickened ventricular wall as a result of
edema can be seen(36;37). In patients with fulminant myocarditis, cardiac function may rapidly
deteriorate leading to hemodynamic instability that requires supportive therapy, whereas patients
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Myocarditis can also result in arrhythmias and conduction disturbances, that may be severe and life
ventricular tachycardia(38;39). Myocarditis is one of the most common findings at autopsy in young
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adults who died of sudden cardiac death(6;8). Although a viral syndrome is sometimes reported,
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these individuals are usually asymptomatic until death(40). In general, the diagnostic evaluation of
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life-threatening arrhythmias includes 12 lead ECG, echocardiography and in some cases CAG.
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Myocarditis may be suspected when there is no evidence of coronary artery disease or distinct
electrophysiological abnormalities(41).
develops when the disease progresses to a persistent state of inflammation(42). These patients
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typically present to the outpatient clinic with gradual progression of heart failure. The acute phase of
myocarditis may have passed unnoticed or with mild symptoms only. Next to myocarditis, DCM can
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be the result of various other causes, and the differential diagnosis is therefore extensive(43).
Although clinical features can provide clues to the underlying cause, without EMB and/or genetic
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Diagnosis
Endomyocardial biopsy
EMB may provide information about the presence of viral genome, fibrosis, cell death, the type of
inflammatory infiltration and the deposition of iron, proteins or lipids(45). The underlying cause of
myocarditis can only be determined by an EMB because non-invasive tests are limited in their ability
to assess these features. EMB is required before targeted therapy can be initiated(17).
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experienced physician (11;47;48). Risks of major complications are comparable between right sided
EMB (RV-EMB) and left sided EMB (LV-EMB), although the types of complication are different(11;48).
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RV-EMB is associated with a higher risk of cardiac perforation while LV-EMB has a higher risk of
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stroke. There is still controversy in many medical centres about the role of EMB in the diagnosis and
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treatment of myocarditis, mostly because the procedural risks do not always outweigh the
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incremental value of EMB, as the majority of myocarditis patients have a good prognosis. The highest
yield of EMB is reached in myocarditis patients who present with acute heart failure(21). In these
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patients, EMB can exclude more aggressive disorders like giant cell myocarditis or necrotizing
granulomatous myocarditis and can guide treatment. In order to improve recognition, understanding
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and, ultimately, management of myocarditis, an ESC working group recently proposed to perform
EMB in all patients with suspected myocarditis, irrespective of clinical presentation type(17).
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Traditionally, the histological diagnosis of myocarditis was established according to the Dallas Criteria
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that were proposed in 1986(49). These criteria were based on the detection of inflammatory
infiltrates in hematoxylin-eosin stained biopsy samples. The diagnosis of acute myocarditis required
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both inflammatory infiltrates and myocyte damage of non-ischemic origin (Figure 1). Borderline
myocarditis was diagnosed when infiltrates were not accompanied by myocyte damage. The
Myocarditis is currently diagnosed when ≥ 14 leukocytes are detected per 1 mm2 in addition to
enhanced HLA expression and adjacent myocytolysis (10;53). The diagnostic potential of EMB was
further enhanced by the introduction of molecular biology methods such as polymerase chain
reaction (PCR), which enables the sensitive detection of viral genomes in biopsy samples(54). The use
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of PCR brought new challenges as PVB19 genomes are not only found in myocarditis patients, but
also in healthy controls (55-57). However, using quantitative PCR (qPCR), Bock et al(58) showed that
PVB19 viral load in biopsy samples are significantly higher in patients with acute myocarditis in
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comparison to patients with chronic myocarditis or healthy controls. This suggests that qPCR may aid
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in differentiating between active and latent PVB19 infection of the myocardium.
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Diagnostic performance
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Because EMB is considered to be the gold standard for diagnosing myocarditis, other in-vivo tests
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cannot be used as a reference of validation. For this reason EMB is compared with autopsy and
transplanted hearts. Hauck et al(14) and Chow et al(15) both evaluated the diagnostic performance
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of EMB by studying ex-vivo hearts that were either obtained at autopsy in patients diagnosed with
myocarditis or obtained after cardiac transplantation. In both studies, the diagnosis was still missed
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in approximately halve of the patients with myocarditis, even when 10 biopsy samples were analyzed
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(14). Moreover, 17 biopsies were needed to reach a sensitivity of 80% (15), indicating that sampling
error of EMB can be explained by the focal nature of inflammation as found in the majority of cases
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(14). In addition, EMB is hampered by high interobserver variability in the interpretation of biopsy
samples (13). For this reason, Baughman (12) proposed to abolish the Dallas criteria and to use both
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IHC and PCR instead. The incremental diagnostic value of IHC was demonstrated in biopsy samples
that were negative according to the Dallas criteria while IHC was able to reveal inflammatory
infiltrates in these biopsy samples (45;59). Despite the introduction of IHC and PCR, sampling error
remains an important limitation of EMB and the sensitivity of EMB is still dependent on the number
of biopsy samples. When comparing the diagnostic performance of univentricular EMB and
biventricular EMB, the highest diagnostic performance was reached with biventricular EMB(48).
However, this incremental diagnostic performance may have resulted from the higher number of
samples that were taken with biventricular EMB. The sensitivity of univentricular EMB for the
detection of inflammation seems to be higher in LV-EMB than RV-EMB, especially when RV function
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CMR is a non-invasive tomographic imaging modality that can be used to asses both the structure
and function of the heart with high accuracy(62). CMR is unique when it comes to its ability to assess
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the characteristics of the myocardial tissue, making it the noninvasive diagnostic tool of choice in
myocarditis. In addition, CMR cine imaging is considered the reference standard for the quantitative
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assessment of regional and global left and right ventricular function. Using these techniques, CMR is
able to demonstrate typical features of acute inflammation such as dysfunction, edema and necrosis.
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Tissue characterization
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Tissue characterization by CMR is based on the principle that tissues have different magnetic
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properties. CMR is able to generate images that that highlight specific soft tissues by using different
imaging techniques. With the use of a gadolinium based contrast agent (GBCA) image contrast can be
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Injured cardiac muscle cells lose their membrane integrity and GBCA that normally remains in the
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extracellular space, can now freely diffuse into the cell (4;64). After 5-15 minutes, the contrast will
have been largely washed out of the normal myocardium but will remain concentrated in the areas
of necrosis (65). GBCA affects the magnetic parameter T1 relaxation time, and regional differences in
contrast concentration can be depicted using inversion recovery T1-weighted imaging (late
gadolinium enhancement (LGE)). In fibrosis, the mechanism is similar, with the contrast agent
accumulating in the increased extracellular space in fibrotic areas. Myocardial necrosis or fibrosis is
also seen in ischemic heart disease and in many other non-ischemic cardiomyopathies (66). Regional
contrast enhancement is therefore not specific for myocarditis. However, the pattern of contrast
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enhancement is typically seen in myocarditis (Figure 2A). LGE imaging has been shown an excellent
diagnostic tool in suspected myocarditis and may show regional contrast enhancement even when
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Acute myocardial inflammation leads to myocardial edema, which profoundly affects the magnetic
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properties, especially the T2 relaxation time, and differences between normal and edematous
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myocardial tissue can be demonstrated using T2 weighted (T2w) imaging (72) (73-76). As with LGE,
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regional high signal intensity reflecting myocardial edema typically involves the subepicardial or
midwall layer of the myocardium (Figure 2B). However, in case of diffuse myocardial involvement
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with global edema, T2w imaging will not show regional differences in signal intensity. To overcome
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this drawback, the signal intensity of the skeletal muscle may be used as a reference to calculate the
edema ratio (ER), which is considered abnormal when it reaches a value of 2.0 or higher (74).
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Friedrich et al (77) have proposed to use standard T1-weighted imaging before and after contrast
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early gadolinium enhancement (EGE) technique reflects contrast distribution in the early washout
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period (62;77). The authors showed that the relative increase in signal intensities of the myocardium
compared to skeletal muscle was higher in patients with suspected myocarditis than in healthy
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control patients and proposed a ratio ≥4.0 as diagnostic for myocardial inflammation (78). However,
practical application of this approach is hindered by suboptimal image quality caused by breathing
and motion artifacts with the use of this non-breath-hold imaging sequence.
Diagnostic performance
In order to determine CMR’s diagnostic performance it needs to be compared to the gold standard,
i.e. endomyocardial biopsy. Many studies however did not validate CMR findings with histopathology
because EMB was not routinely performed (17;74-77;79). Studies that validate CMR with a biopsy
sample report sensitivity rates of 61-76%, 47-64% and 60-74% for respectively EGE, T2w and
LGE(3;16). The diagnostic performance dramatically drops in the chronic phase of myocarditis and in
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patients with borderline myocarditis(3;31). This, for example, became apparent in a study by
Baccouche et al.(31) who performed CMR and EMB in patients with suspected myocarditis and found
that 63% of the patients without LGE had borderline myocarditis on biopsy. In 2009 a combined
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approach was proposed in order to improve CMR’s diagnostic performance(78). With this combined
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approach, using EGE, T2w and LGE, myocarditis is diagnosed when 2 out of 3 techniques are positive.
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In a study by Abdel-Aty et al.(74) this yielded a sensitivity and specificity of respectively 76% and 96%
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in patients with acute biopsy proven myocarditis. Despite these criteria, the diagnosis may still be
missed in a substantial number of patients, especially in the chronic phase of myocarditis (3).
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There are a number of possible explanations for false negative CMR studies. First, the size of small
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islands of necrosis and edema may be beyond the detectability limit of CMR(16). Also imaging
artifacts can hamper the diagnostic performance of CMR, which may be prominent in the non-breath
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hold EGE sequence and in T2w imaging. Furthermore, current CMR techniques only allow for the
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Ratio’s comparing signal intensity of myocardial and skeletal muscle may overcome this problem in
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EGE and T2W imaging, however, skeletal muscle may also be involved in the disease. This became
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apparent in a study by Ferreira et al.(80) who showed that patients were misdiagnosed by their
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edema ratio because both myocardium and skeletal muscle were affected.
Clinically suspected myocarditis requires cardiac signs and/or symptoms in combination with cardiac
biomarker release, ECG changes, arrhythmias or LV dysfunction, in the absence of other cardiac
causes. CMR should be performed in all patients when clinically possible. CMR can provide strong
evidence for the diagnosis of (acute) myocarditis and allows the detailed assessment of other
underlying myocardial disease. Effective therapy is only available for a limited number of causes,
potentially detrimental in myocarditis of viral origin, and EMB is the only way to differentiate
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between viral and autoimmune-related disease, EMB is required in all patients who are
hemodynamically unstable. In addition, its use should be considered in patients with new onset heart
failure or arrhythmias whose clinical condition fails to improve or deteriorates, even when CMR does
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not show signs of myocarditis, given its lower sensitivity in this patient group (16). Patients with ACS-
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like presentation generally have excellent prognosis (2;10), and, in these, EMB is rarely required
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although it may be considered with chronic or recurrent symptoms.
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In all patients, follow-up CMR should be considered to establish the final recovery status, by showing
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A proposed diagnostic approach for the use of CMR and EMB in clinically suspected myocarditis and
Future perspectives
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EMB and CMR form the backbone of the current diagnostic work-up of patients with suspected
myocarditis. However, both EMB and CMR have a number of drawbacks. New diagnostic techniques
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face challenging requirements: they should be able to detect the disease in an early stage, to
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determine the degree of inflammatory activity and myocardial involvement, and to identify patients
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who are at risk for the development of DCM or SCD. In addition, they should be less invasive than
EMB and allow the serial assessment of the disease extent to follow the response to putative
therapeutic measures.
Recently, new CMR techniques were introduced that enable a quantitative measurement of
magnetic relaxation parameters T1 and T2 (81;82)(Figure 4). Parametric maps encoding these values
enable a more detailed tissue characterization and appear to have higher sensitivity for small regions
of edema and necrosis that would be missed by conventional CMR techniques (83-86). Furthermore,
T1 values change after contrast, and pre-contrast and post-contrast values can be used together to
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estimate the myocardial extracellular volume (ECV), i.e. the space that is not occupied by cardiac
myocytes and is replaced by collagen matrix. The ECV can be considered a surrogate marker for
interstitial fibrosis and is a promising new tool in patients with diffuse myocardial disease(87)
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Furthermore, studies elaborated to determine the diagnostic values of these techniques, report
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incremental diagnostic value compared to conventional CMR in myocarditis (80;88;89). Although the
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first results are promising, there are still some obstacles to overcome before these techniques can be
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used in clinical practice. For example, the diagnostic value of these techniques in myocarditis still
requires validation by EMB. Also, T1- and T2-values vary with the type of scanner, the magnetic field
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strength and the pulse sequence used, making it difficult to determine its normal range(85). Finally,
there is ongoing debate on what is the optimal parameter to evaluate myocardial disease (pre-
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contrast T1 or T2, post-contrast T1, or ECV).
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Blood biomarkers
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A biomarker is a biological property that can be objectively measured and used as an indicator of
pathologic processes(90). Blood is highly suitable for the identification of biomarkers because it can
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be easily obtained. Considerable effort has been devoted to the identification of blood biomarkers
that may serve as indicators of prognosis and the response to therapy in myocarditis. In this search, a
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variety of anti-heart antibodies (AHAs) have been identified in the blood of myocarditis patients and
DCM patients. AHAs are presumed to result from (auto)immune processes in the course of an
have been shown to predict the development of DCM in asymptomatic relatives of DCM patients(91).
Unfortunately, this type of antibody testing requires highly specialized laboratories and it is not yet
accessible for clinical application. The availability of such tests in routine practice will further enhance
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Since several years, there is growing interest in the utility of microRNAs as a diagnostic and
prognostic biomarker in myocarditis. MicroRNAs are important regulators of gene expression and are
involved in numerous cardiovascular diseases(92-94). Several studies have been carried out to
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determine microRNA expression profiles of EMB tissue in viral myocarditis (95-97). In these studies,
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EMB analysis with microRNA profiling appeared to be a useful marker of adverse outcome and
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inflammation activity. Recently, studies started to focus on blood microRNA with the intention to
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replace microRNA profiling in tissue samples. Although this field of research is still in the early stage,
first data seem promising as circulating microRNAs appear to be measurable in the blood and seem
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to be present in a stable form(98;99). However, data of circulating microRNA in viral myocarditis, to
The concept of skeletal muscle involvement in various cardiomyopathies dates back to the 1970s
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(100;101). In 1997 Arbustini et al(102) found enteroviral RNA and virus-like particles in the skeletal
muscle of patient with idiopathic DCM. In a subsequent study, they also described enteroviral RNA
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and virus-like particles in patients with fatal enteroviral myocarditis(103), suggesting the possibility
that skeletal muscle may reflect viral presence in the heart. In addition to viral presence, as already
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mentioned above, skeletal muscle inflammation has been shown in MRI studies (75;80). Results from
these small studies suggest that skeletal muscle reflects the pathology of the heart in viral
myocarditis. However, the potential of skeletal muscle biopsy as a more accessible diagnostic
window to viral myocarditis has never been explored. We recently found increased infiltration of
lymphocytes in quadriceps skeletal muscle obtained at autopsy in patients diagnosed with viral
myocarditis and in a mouse model for acute CVB3-induced myocarditis(104). In fact, this infiltration
of lymphocytes in the quadriceps muscle appeared to predict viral myocarditis with a sensitivity of
71% and specificity of 100%. Although results are still preliminary, a peripheral muscle biopsy may
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potentially be used as a much easier and safer alternative to EMB for the detection of inflammation
Summary
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Because symptoms and initial evaluation are not specific in myocarditis, the evaluation of patients
with suspected disease remains challenging. The diagnosis currently relies on CMR and EMB, each
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with their own benefits and drawbacks. EMB is crucial for a better understanding of pathophysiology
and the underlying causative disorder and should be considered as a standard procedure in
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suspected myocarditis in patients with other than ACS-like presentation types (17). New diagnostic
tools are being developed that may complement and improve on current diagnostic approaches for
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myocarditis. The focus of newer techniques should include the early (less invasive) detection of
disease and both short term and long term risk stratification. This should ultimately allow the
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identification of the high risk patients in whom aggressive treatment of the disease may prevent SCD
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Figure Legend:
Figure 1: Histo- and immunopathology of heart tissues. Upper left: anti-CD45 antibody staining for
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lymphocytes adherent to cardiomyocytes. Upper right image: anti-C3d antibody staining for myocyte
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damage (400x), demonstrating cell death of cardiomyocytes. Lower left image: haematoxylin-eosin
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(HE) staining (200x), showing giant cell myocarditis with diffuse inflammatory infiltrates and
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multinucleated giant cells. Lower right image: HE staining (400 x), demonstrating eosinophilic
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Figure 2: LGE, T2w and Cine imaging in acute myocarditis. Cine, LGE and T2w images both in the
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same patient with acute myocarditis, demonstrating subepicardial LGE (A), subepicardial edema (B)
and wall motion abnormality in the inferolateral wall (C= diastolic cine image, D=systolic cine image),
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typical of myocarditis.
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Figure 3: Proposed diagnostic approach for the use of CMR and EMB in clinically suspected
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myocarditis. ACS = acute coronary syndrome; HF = Heart failure; CMR = Cardiac magnetic resonance;
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techniques. CMR study in a fifty-one year old patient who presented to our hospital with acute heart
failure and severe LV dysfunction after a respiratory infection. T2w imaging did not show regional
myocardial edema (left). CMR mapping technique was performed and revealed diffuse and markedly
elevated T1 relaxation times of the myocardium suggestive of diffuse myocardial edema (right).
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Table 1.
Classification of myocarditis
Clinicopathology
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Fulminant
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Chronic
o Persistent inflammation
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o Viral infection with or without inflammation
Histology
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Lymphocytic
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Granulomatous
Eosinophilic
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Neutrophilic
Etiology
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Highlights
EMB and CMR form the backbone of the current diagnostic work-up of patients with
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suspected myocarditis.
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The diagnostic assessment of EMB samples should include histopathology,
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immunohistochemistry, and viral polymerase chain reaction.
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CMR allows for the diagnosis of myocarditis, and can be used to differentiate between other
causes of cardiomyopathy.
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The diagnosis of myocarditis remains challenging as a result of the diverse clinical
histopathological examination of skeletal muscle biopsies are exciting areas with great
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