Laboratory examination consists of basic examinations and the detection of biomarkers of the myocardial damage, heart failure and inflammation. The testing of anti-myocardial autoantibodies is recommended by the European Society of Cardiology ([24], more in chapter Autoantibodies), on the contrary, routine serological testing is not recommended, because of its low contribution to the diagnosis [24, 108]. It is pointed out in a number of references that negativity of inflammation markers and biomarkers of the myocardial necrosis does not exclude the diagnosis of myocarditis [43, 96, 99, 100].
Biomarkers of the myocardial necrosis and heart failure
There are several biomarkers of the myocardial necrosis used in clinical practice – levels of troponin T or I, creatine kinase (CK), primarily its myocardial form (CK-MB), alternatively of myoglobin [26]. As a biomarker of heart failure, detection of natriuretic B peptides (BNP) or their prohormone (pro-BNP) is used.
Level of troponin in serum was in the case of myocarditis/ICMP in several studies established as a useful indicator of prognosis, mortality risk and of the extent of the myocardial damage [26, 109, 111, 112, 169]. Its sensitivity for the detection of myocarditis was in one study 53 % and specificity was up to 94 % [111]. Higher level was detected primarily in fulminant and fatal myocarditis cases [112]. A low troponin elevation was often detected even when the EMB result was negative. It could probably come in the situation when mild forms of inflammation with localized myocardial damaged are not caught by the EMB. On the contrary, the troponin level in serum was often in reference values even when there was a bioptical confirmation of myocarditis [111]. Elevation of troponin is detected approximately in 33 to 50 % of patients [43]. When comparing with the myocardial infarction, in myocarditis, it is common that it can be detected for a longer period of time and that its decrease is slower [99]. Troponin may be positive even several weeks from the initial manifestation of the disease.
CK and CK-MB are together with troponin and myoglobin other biomarkers of the myocardial damage, even though their detection in myocarditis was in some studies much lower than in troponin. In an American study [111], when troponin I elevation was proved in 53 % of patients, higher levels of CK and CK-MB were detected just in 8 % or 2 % respectively. On the other hand, CK-MB level higher than 29,5 ng/ml was marked as a mortality indicator with the sensitivity 83 % and specificity 73 % [26].
Natriuretic peptides have similar to troponin diagnostical and prognostic value in the case of development of heart failure [113] and determine its severity. Even in myocarditis, high level of BNP is described as a predictor of a worse prognosis and higher mortality [114].
Biomarkers of inflammation
Nonspecific markers of inflammation – leucocytosis, higher CRP levels, and erythrocytes sedimentation rate may be present in myocarditis and ICMP, however, they have love specificity in their diagnosis [26, 43]. Leucocytosis is for example detected in just 20 to 25 % of patients [43]. In differential count, most frequently, there are higher levels of lymphocytes and neutrophils, alternatively of eosinophils in eosinophilic myocarditis [43, 102].
Autoantibodies
In patients with myocarditis and/or DCMP, there have been discovered a large number of antibodies specific for myocarditis/DCMP [24]. Their testing is even recommended by the European Society of Cardiology [24]. Considering a vast number of identified autoantibodies, there are described in this chapter just some of them, primarily those marked as cardiac and specific for myocarditis/DCMP or as negative predictors [24].
It is for example detection of cardiac autoantibodies of IgG class in up to 59 % of patients with myocarditis and 20 % of patients with idiopathic DCMP [115] when according to the resources this finding identifies patients in which the cardiac dysfunction is a result of the immune system activity. Different anti-sarcolemma antibodies and even organ non-specific antibodies were represented in varying degrees in patients with myocarditis in another study [116]. In this study, the level of antibodies against sarcolemma of cardiomyocytes corresponded with the extent of cytolytic damage of the myocardium.
Further, the detection of beta-adrenergic antibodies was described by a number of studies in both patients with myocarditis and with DCMP [24]. In patients with DCMP, their positivity was connected with distinctively worse left ventricular function [117].
Alike beta-adrenergic autoantibodies, even antibodies against alpha/beta-myosin [24, 118], troponin I and T [24, 119] etc. were marked as negative predictors. List of other antibodies may be found in these references [24], [120].
Microbiology and serology
Routine serological examination of antibodies against the agent of myocarditis is not, with a few exceptions, recommended in the present [24]. In the Czech Republic, there are usually examined just antibodies against HIV, hepatitis viruses and Borrelia burgdorferi [24, 99].
A research from 2011 proved that viral serology has in the diagnosis of myocarditis only 9 % sensitivity and 77 % specificity [108].
Possibilities of serological examination are complicated by a lot of factors including primarily the incidence of viruses associated with myocarditis in the population, and the delay between the viral infection and performed serological examination [21]. Even under these circumstances, the isolation of a virus or direct detection of the virus is sometimes described as a useful diagnostic tool which points to a viral infection [121].
When investigating the aetiology of myocarditis and ICMP, primarily samples from EMB are used when some agents are examined with PCR (in the Czech Republic most frequently herpes simplex virus, EBV, CMV, HHV-6, Coxsackie, echoviruses, adenoviruses, PVB19 and Borrelia burgdorferi), [28, 99]. Other methods may be electron microscopy or in situ hybridization [98].
Others
Even other substances have been described as predictors of a higher risk of mortality in myocarditis – Fas ligand and IL-10 (together with other cytokines described in chapter Pathogenesis), [26]. In a study of children patients, higher levels of lactate, creatinine, and AST have been associated with higher mortality [110]. Some already implemented researches of myocarditis described different transcription of some genes and changes in the levels of specific miRNA [100, 122] where there is described their influence on both inflammatory activity (and so on the heart function) and on viral activity [122] within the meaning of inhibition and “support.” They are described not just as a possible diagnostic tool, however also as a potential therapy aim what has already been researched in several studies with positive results [122].
Author of the opening picture: Thomas Splettstoesser
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