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Use of MicroRNA to Detect Acute Myocarditis
Quick Takes
- In mouse models of autoimmune and viral myocarditis, levels of a specific microRNA were significantly elevated in acute myocarditis compared to acute myocardial infarction and controls.
- A human homologue to this microRNA was identified, which was able to distinguish acute myocarditis from acute myocardial infarction (and other comparison groups), possibly adding to our future ability to distinguish between these clinical entities.
Study Questions:
Can microRNA (miRNA) be used as a noninvasive and possibly widely available diagnostic tool for identifying the acute phase of autoimmune or viral myocarditis?
Methods:
Mouse model:
- Autoimmune and viral myocarditis mouse models were used for this study (compared to a myocardial infarction model and healthy controls).
- miRNA expression in sorted CD4+ T cells and type 17 helper T cells (Th17) were assessed. Th17 has been previously identified as playing a key role in the development of myocarditis.
Human model:
- After identification of a murine miRNA for acute myocarditis, a human miRNA homologue was identified.
Main study cohort:
- This human miRNA was assessed in a main study cohort consisting of patients with myocarditis (n = 42), myocardial infarction (ST-segment elevation myocardial infarction [STEMI] [n = 45], non–ST-segment elevation myocardial infarction [NSTEMI] [n = 45]), and healthy controls (n = 80).
- Area under the receiver-operating-characteristic (AUROC) curves for diagnostic characteristics were generated as well.
Validation cohorts:
- Diagnostic ability was further validated in four distinct cohorts.
- Cohort 1–34 patients with acute myocarditis and 11 patients with myocardial infarction.
- Cohort 2–35 patients with acute myocarditis and 20 patients with myocardial infarction with nonobstructive coronary arteries.
- Cohort 3–40 patients with biopsy-proven myocarditis and 49 patients with acute myocardial infarction.
- Cohort 4–Patients with Th17-related immunologic diseases but without evidence of cardiac disease.
Results:
Mouse model:
- A miRNA from peripheral blood samples was identified (mmu-miR-721), which was produced by Th17 cells and was highly expressed in the autoimmune and viral myocarditis models compared to the myocardial infarction and control groups.
- Specifically, miRNA levels were compared in the acute phase of myocarditis or myocardial infarction (timing was based on the changes in biomarkers of myocardial injury and in left ventricular ejection fraction).
Human model:
- A novel human miRNA homologue was identified (designated hsa-miR-Chr8:96).
Main study cohort:
- In plasma samples, hsa-miR-Chr8:96 expression was significantly higher in patients with acute myocarditis compared to STEMI, NSTEMI, and healthy controls.
- Myocarditis vs. myocardial infarction: AUROC curve, 0.927 (95% confidence interval [CI], 0.879-0.975).
- Myocarditis vs. healthy controls: AUROC curve, 0.988 (95% CI, 0.970-1.006).
- Diagnostic accuracy remained high after adjusting for age, sex, left ventricular ejection fraction, and troponin level.
Validation cohorts:
- hsa-miR-Chr8:96 expression in plasma was higher in patients with acute myocarditis vs. comparison groups in all four cohorts.
Conclusions:
Expression of a novel miRNA (hsa-miR-Chr8:96) in blood samples of human patients with acute myocarditis is significantly higher compared to patients with myocardial infarction. This may represent a future diagnostic tool for differentiating between these clinical entities.
Perspective:
The diagnosis of myocarditis can be challenging given the broad differential for causes of left ventricular dysfunction and myocardial injury. Endomyocardial biopsy remains the gold standard for diagnosing myocarditis, though it is reserved for a small subset of patients for which a definitive diagnosis would alter management strategies. Cardiac magnetic resonance imaging can be used for diagnosis as well, but is not universally available.
The ability to differentiate acute myocarditis from acute myocardial infarction remains a clinical dilemma, but would be helped if reliable serum testing were widely available to distinguish the two. This study highlights a potential for such a test with a novel circulating miRNA. Future studies will still need to address generalizability and accuracy in larger prospective cohorts, comparisons to other clinical conditions that may mimic myocarditis, issues of interpreting testing outside of the acute phase of myocarditis, and ultimately how testing would impact management and outcomes.
Clinical Topics: Acute Coronary Syndromes, Cardiovascular Care Team, Heart Failure and Cardiomyopathies, Noninvasive Imaging, ACS and Cardiac Biomarkers, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Magnetic Resonance Imaging
Keywords: Acute Coronary Syndrome, Biomarkers, Biopsy, CD4-Positive T-Lymphocytes, Diagnostic Imaging, Heart Failure, Immune System Diseases, Magnetic Resonance Imaging, MicroRNAs, Myocardial Infarction, Myocarditis, Plasma, Stroke Volume, Th17 Cells, Troponin, Ventricular Dysfunction, Left, Ventricular Function, Left
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