Aims:
Myocardial inflammation represents a complex immune response to diverse insults that may lead to heart failure. MicroRNAs (miRNAs) are key post-transcriptional regulators influencing viral infections, immune processes, and cardiac remodeling. This study aimed to identify specific miRNA profiles distinguishing virus-negative and virus-positive inflammatory dilated cardiomyopathy (DCMi) as potential diagnostic and therapeutic biomarkers.
Methods and Results:
Serum and endomyocardial biopsy (EMB) specimens from patients with unexplained heart failure were analyzed using TaqMan® OpenArray® and qRT-PCR assays. In total, 152 serum and 75 EMB samples were examined, including virus-negative DCMi, dilated cardiomyopathy (DCM), and virus-positive myocarditis cases, along with healthy controls.
Screening of 754 circulating miRNAs revealed distinct patterns across subgroups. In virus-negative DCMi, miR-1, miR-23, miR-142-5p, miR-155, miR-193, and miR-195 were significantly downregulated (P < 0.005), distinguishing DCMi from all other cohorts with >86% specificity. In virus- and/or inflammation-associated cardiomyopathies, deregulation of let-7f, miR-197, miR-223, miR-93, and miR-379 differentiated patients from healthy donors (P < 0.05, specificity > 93%). miR-21 and miR-30a-5p expression identified DCM patients with >95% specificity. Moreover, in erythroparvovirus-positive cases, miR-98, miR-222, miR-106b, and miR-197 were upregulated (P < 0.005), discriminating active viral infection independent of inflammation (>90% specificity).
Conclusions:
This integrated miRNA profiling provides a novel, non-invasive diagnostic tool to distinguish etiological subtypes of inflammatory and viral cardiomyopathies from a single serum sample. The identified miRNAs enable early recognition of patients with intramyocardial inflammation or viral persistence, guiding biopsy decisions and etiology-driven therapy. Additionally, these signatures offer promising targets for future miRNA-based therapeutic interventions in virus-negative and virus-positive DCMi.
