Monocyte Titin Gene Expression as a Biomarker of Left Ventricular Dysfunction in Acute Myocarditis

TL;DR

This study suggests that higher TTN gene expression in blood cells could indicate heart dysfunction in acute myocarditis patients.

Contribution

The study introduces TTN mRNA in PBMCs as a potential novel biomarker for assessing severity and outcomes in acute myocarditis.

Findings

TTN expression in PBMCs was 2.8-fold higher in acute myocarditis patients compared to healthy controls.

TTN expression correlated strongly with heart strain impairment and moderately with heart injury markers.

The study proposes TTN as a potential biomarker for disease severity and ventricular remodeling.

Abstract

Background: Titin (TTN), a giant structural and signaling protein of striated muscle, participates in intracellular signaling networks and cytoskeletal organization, potentially influencing cell activation, trafficking, and interactions with other tissues, including the heart. Methods: In this pilot study, 29 patients with acute myocarditis and 10 healthy individuals were prospectively enrolled. Peripheral blood was obtained on the first day of hospital admission, total RNA was isolated from peripheral blood mononuclear cells (PBMCs), and TTN mRNA expression was quantified. Results: TTN expression in PBMCs was significantly higher in patients with acute myocarditis compared with healthy controls (p = 0.015), corresponding to a 2.8-fold median increase. Moreover, TTN expression showed a strong positive correlation with global longitudinal strain impairment (Spearman’s r = 0.576, p < 0.001), a moderate positive correlation with peak hs-cTnI levels (r = 0.435, p = 0.021; and a moderate inverse correlation with baseline LVEF (r = −0.421, p = 0.025). Conclusions: These findings support a pathophysiological link between TTN-related pathways in peripheral immune cells and myocardial injury in acute myocarditis and raise the hypothesis that TTN expression in PBMCs may serve as a novel biomarker of disease severity and long-term ventricular remodeling. Further studies in larger cohorts are warranted to validate these results and to elucidate the mechanistic role of titin in immune–cardiac cross-talk.

Figures