MicroRNAs in myocarditis: promising biological signals, but not yet a clinical test

MicroRNAs in myocarditis: promising biological signals, but not yet a clinical testMyocarditis remains one of the most challenging syndromes in cardiovascular medicine.Its presentation ranges from an incidental increase in cardiac troponin to infarct-like chest pain, ventricular arrhythmias, advanced heart failure, cardiogenic shock, or sudden cardiac death.Moreover, myocarditis is not a single disease, but a heterogeneous inflammatory myocardial syndrome caused by infectious, immune-mediated, toxic, genetic, and occasionally overlapping mechanisms [1][2][3].Current diagnostic pathways therefore rely on the integration of clinical presentation, electrocardiography, circulating biomarkers, echocardiography, cardiovascular magnetic resonance (CMR), coronary assessment when appropriate, and endomyocardial biopsy (EMB) in selected high-risk or diagnostically uncertain cases [1,[4][5][6].None of these tools is perfect.Cardiac troponin identifies myocardial injury but is neither sufficiently sensitive nor specific for myocarditis.CMR can non-invasively demonstrate oedema and non-ischaemic myocardial injury, but its diagnostic performance depends on timing, protocols, disease phenotype, and local expertise.EMB provides unique histological, immunohistochemical, and molecular information, but its use is necessarily selective because it is invasive and affected by sampling error [1,6].Against this background, circulating microRNAs (miRNAs) are attractive biomarker candidates.These small non-coding RNA molecules regulate post-transcriptional gene expression and participate in inflammatory signalling, immune-cell differentiation, cardiomyocyte injury, fibrosis, and ventricular remodelling [7,8].Their relative stability in blood, particularly when transported within extracellular vesicles, offers the prospect of a biologically informative "liquid biopsy".In their systematic review and meta-analysis, Martinez Holst and colleagues examined 26 studies evaluating miRNAs in clinically diagnosed viral myocarditis [9].They identified 42 differentially expressed miRNAs and reported an exploratory pooled diagnostic area under the curve (AUC) of 0.897, with pooled sensitivity of 0.758 and specificity of 0.881.The pooled AUC for discrimination of fulminant myocarditis was 0.883.Exosomal and circulating cell-free miRNAs showed broadly similar summary performance.These findings are encouraging, but their clinical meaning requires careful interpretation.