Differentiating acute myocarditis from myocardial infarction (MI) requires either an invasive biopsy or cardiac MRI—technology that is not always available—so the possibility that a microRNA biomarker in circulating T cells could be used to confirm myocarditis is appealing.
Identifying that novel miRNA was the goal of Rafael Blanco-Dominguez, MSc, of the Vascular Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares in Madrid, and a team of international researchers, who started by inducing autoimmune myocarditis or myocardial infarction in mice to identify the microRNA found in Th17 cells in plasma of mice with acute myocarditis—either autoimmune or virus-induced.
In the murine experiments, Blanco-Dominguez and colleagues observed a significant increase in circulating Th17 cells 14 days after either myocarditis or MI, but the “number of Th17 cells was not significantly increased at days 3 or 7 after myocardial infarction (the time of peak biomarker elevation). Therefore, Th17 cells appear to be characteristic of the acute phase of myocardial injury in myocarditis (on day 21) but not the acute phase of myocardial injury in myocardial infarction (on day 3),” they wrote in The New England Journal of Medicine.
Thus, the study team was able to focus its search on Th17 and specifically microRNA mmu-miR-721, which is synthesized by Th17 cells. The next step was to identify a human homologue, which they designated hsa-miR-Chr8:96.
The clinical study included a cohort of 132 patients with suspected “acute myocarditis and myocardial injury, ventricular dysfunction or both.” The researchers used cardiac MRI to confirm myocarditis in 42 of the patients, and MI was confirmed in 90 patients. The MI patients were used as comparators and 80 healthy participants were included as additional controls.
Hsa-miR-Chr8:96 was validated for diagnosis of human myocarditis using the following additional patient cohorts:
- Validation cohort 1: Partners Biobank (Boston)—included 34 patients with an established diagnosis of acute myocarditis and 11 patients with myocardial infarction as comparators.
- Validation cohort 2: Center for Molecular Cardiology of the University Hospital Zurich (Switzerland)—35 patients with acute myocarditis and 20 with MI with non-obstructive coronary arteries (MINOCA).
- Validation cohort 3: University of Padua (Italy)—40 patients selected from a prospective cohort r with a biopsy-proven diagnosis of myocarditis.
- Validation cohort 4: Biobank Regional Platform (Murcia, Spain)—49 patients with acute MI.
“Finally, as a control cohort, we included samples obtained from patients with Th17-related immunologic diseases without cardiac involvement,” they wrote.
The researchers performed qPCR on plasma samples from the main cohort of patients and found the “expression of the novel miRNA in plasma was greater in patients with myocarditis than in either patients with myocardial infarction or healthy controls. The novel miRNA was specifically synthesized by Th17 cells obtained from patients with myocarditis ROC curves were generated to determine the diagnostic characteristics of hsa-miR-Chr8:96 expression measured in plasma. Among the patients with myocarditis, the area under the ROC curve was 0.927 (95% confidence interval [CI], 0.879 to 0.975) as compared with patients with myocardial infarction and 0.988 (95% CI, 0.970 to 1.006) as compared with healthy controls).”
In analysis with the validation cohorts, the “ability of the novel miRNA to distinguish acute myocarditis from myocardial infarction remained significant after adjustment for age, sex, ejection fraction, and serum troponin level.”
The authors concluded that they successfully identified a novel miRNA in humans that can be used to distinguish myocarditis from MI; however, more work is needed before it can be used as a diagnostic test for myocarditis. Until that work is completed, endomyocardial biopsy should remain the reference standard.
“This miRNA has not yet been evaluated in other cardiac disorders, such as dilated cardiomyopathy, from which myocarditis must be distinguished in the clinical setting,” they wrote. “In addition, in our study, we note great variability in the expression of hsa-miR-Chr8:96, which remains unexplained; it is not clear whether this variation reflects the severity of the disease or is attributable to some other factor.”
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Researchers have identified a novel microRNA in both mice and humans that can distinguish myocarditis from myocardial infartion.
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Be aware the additional research is needed to evaluate the miRNA in other cardiac disorders and to understand the significance of variability in expression of hsa-miR-Chr8:96.
Peggy Peck, Editor-in-Chief, BreakingMED™
The study was funed by the Spanish Ministry of Science and Innovation and others.
Blanco-Domínguez is supported by a grant (FPU16/02780) from the Formación de Profesorado Universitario program of the Spanish Ministry of Education, Culture, and Sports.
Cat ID: 914
Topic ID: 74,914,521,728,791,730,914,192,925
