Identify the first biomarker in blood that differentiates myocarditis from acute myocardial infarction


New developments around cardiovascular diseases. A recent study has identified a substance in the blood that allows, among other aspects, to differentiate myocarditis of other pathologies of the heart.

Specifically, myocarditis is an inflammatory disease of the heart caused by infectious pathogens, toxins, drugs or autoimmune disorders, which if left untreated can progress to a cardiomyopathy dilated and this leads to the need to receive a heart transplant or even cause death. Its actual prevalence remains uncertain due to the difficulty of achieving, in many cases, a confirmatory diagnosis.

Non-invasive early diagnosis

Researchers from the National Center for Cardiovascular Research (CNIC), including its director of Clinical Research, Dr. Borja Ibáñez, also an interventional cardiologist of the Jiménez Díaz Foundation, have identified the first blood biomarker for myocarditis, a pathology of the heart whose symptoms and signs are very similar to those of a myocardial infarction.

It should be noted, and so the specialists comment, that it is a great advance, especially because we must bear in mind that at this time there is no non-invasive test capable of differentiating between both pathologies and, therefore, in the vast majority of cases it is necessary to perform an urgent catheterization (invasive test) in order to make a correct diagnosis.

Substance in the blood that only patients with myocarditis have

The study, which has been led by the Dr. Pilar Martín and has been published in the magazine The New England Journal of Medicine, has identified the presence of a biomarker, a new microRNA (human miR-721 homologue) in blood exclusively in patients with acute myocarditis.

The results of this work, as explained by Dr. Valentin Fuster, general director of the CNIC, have a great relevance, since they validate the first marker in blood that presents a high sensitivity and specificity (greater than 90%) to diagnose myocarditis and discriminate patients with this disease from others with different cardiomyopathies such as acute myocardial infarction and also from other inflammatory diseases of autoimmune origin.

«Our finding may become a useful new tool in clinical practice that allows an accurate and non-invasive diagnosis of myocarditis with just a drop of blood.», Explains Dr. Martín, whose project is funded by the Leonardo Grant for Researchers from the BBVA Foundation.

The diagnosis of myocarditis remains a challenge and the availability of a sensitive and specific marker of acute myocardial inflammation could have a great clinical impact in improving the diagnosis of acute myocarditis in general, and early diagnosis in particular, the researchers emphasize.

Myocarditis, says the CNIC researcher Rafael Blanco-Domínguez, «Is a frequent final diagnosis in patients with acute myocardial infarction without obstructive atherosclerotic coronary artery disease (MINOCA), a clinical entity that occurs in about 10-20% of patients who meet criteria for myocardial infarction».

The diagnosis of myocarditis is usually established after ruling out coronary artery disease using invasive coronary angiography or computed tomography (CT) and subsequent confirmation by endomyocardial biopsy (“gold standard” diagnostic test).

Less testing

Because cardiac biopsy is aggressive, it is usually reserved for severe cases. An alternative to biopsy is cardiac magnetic resonance imaging (CMR), which, however, is not available in all centers. In this context, “Having a validated blood marker is very relevant, since it would help to make a quick, non-invasive diagnosis and avoid another battery of tests», Says Dr. Martín.

In addition, it explains the Dr. Raquel Sánchez-Díaz, a CNIC researcher, “although the most frequent cause of myocarditis is a viral infection, it can also be secondary to some treatments for other pathologies. In fact, myocarditis is a side effect that, although very rare, is potentially serious in cancer patients who are receiving treatment with the immunotherapy called immune checkpoint inhibitors. However, there are also no specific markers to diagnose patients susceptible to developing myocarditis during cancer treatment with immunotherapy.

«The discovery of the miR-721 took place in the plasma of mice with autoimmune and viral myocarditis. This miRNA is synthesized by Th17 autoimmune cells that recognize cardiac antigens derived from proteins such as alpha-myosin and they attack the myocardium, being responsible to a great extent for the pathophysiology of the disease ”, explain Blanco-Domínguez and Dr. Sánchez-Díaz, the first authors of the work.

It also identified, cloned and validated the homologous miRNA human miR-721, which was not described, showing that it is synthesized by Th17 cells of patients with myocarditis and that its expression is exclusive to the plasma of these patients.

Contribute to the welfare of society

The researchers note that efuture studies with the biomarker will evaluate its potential to predict risk in the short and long term, as well as monitoring the persistence of myocardial inflammation and the risk of recurrence, clinical progression or adverse ventricular remodeling.

The CNIC is the sole owner of a patent related to the biomarker and its use for the diagnosis of myocarditis. The CNIC is currently in contact with industrial partners interested in its license that can contribute to the development and commercialization so that the technology reaches patients.

For Dr. Fuster, «this work is a paradigm of how the basic research carried out at the CNIC contributes to the well-being of society by transferring the research we carry out in the centre’s laboratories to the clinic ”.

The study has been funded by the Ministry of Science and Innovation (MICINN) through the Carlos III Health Institute (ISCIII) – Health Research Fund; the Center for Biomedical Research in the Cardiovascular Diseases Network (CIBERCV); the Community of Madrid; the Leonardo Grant for Researchers from the BBVA Foundation; the Fundació La Marató TV3; the European Research Council grants ERC-2011-AdG 294340-GENTRIS to FS-M., and ERC-2018-CoG 819775-MATRIX to BI, and the Ministry of Science and Innovation (MICINN).

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