(1) Background: Left ventricular hypertrophy, myocardial disarray and interstitial fibrosis are the hallmarks of hypertrophic cardiomyopathy (HCM). Access to the myocardium for diagnostic purposes is limited. Circulating biomolecules reflecting the myocardial disease processes could improve the early detection of HCM. Circulating miRNAs have been found to reflect disease processes in several cardiovascular diseases. (2) Methods: We quantified circulating miRNA molecules in the plasma of 24 HCM and 11 healthy controls using the Human v3 miRNA Expression Assay Kit Code set (Nanostring Tech., Seattle, WA, USA) and validated differentially expressed miRNAs using RT-PCR. (3) Results: In comparison to healthy controls, the levels of six miRNAs (miR-1, miR-3144, miR-4454, miR-495-3p, miR-499a-5p and miR-627-3p) were higher in the plasma of HCM patients than healthy individuals (p < 0.05). Of these, higher levels of miR-1, miR-495 and miR-4454 could be validated by real-time PCR. In addition, elevated miR-4454 levels were significantly correlated with cardiac fibrosis, detected by magnetic resonance imaging in HCM patients. (4) Conclusions: Circulating miR-1, miR-495-3p and miR-4454 levels are elevated in the plasma of HCM patients. To the best of our knowledge, this is the first report showing a correlation between miR-4454 levels and cardiac fibrosis in HCM. This suggests miR-4454 as a potential biomarker for fibrosis in these patients.

Despite genetic heterogeneity, early manifestation of diastolic dysfunction (DD) is common in hypertrophic cardiomyopathy (HCM). Nitric oxide (NO) may contribute to myocardial relaxation. NO synthases (NOS) use l-arginine (Arg) as a substrate, as asymmetric dimethylarginine (ADMA) is a direct endogenous inhibitor of NOS. This study aimed to analyze the association of Arg and its derivates, i.e., l-homoarginine (hArg), ADMA and symmetric dimethylarginine (SDMA), with DD in HCM patients. In 215 HCM patients (mean age 54 ± 15 years, 58% male) transmitral and mitral annulus velocities were echocardiographically analyzed. Plasma concentrations of Arg derivatives were measured by liquid chromatography tandem-mass spectrometry. In 143 (70%) patients suffering from DD, ADMA showed the strongest association with DD (0.66 ± 0.16, 0.72 ± 0.24, and 0.76 ± 0.26 µmol/L, p < 0.01 for trend). In linear regression analyses, positive association per standard deviation increase of ADMA was found with E-wave (beta coefficient (95% confidence interval): 4.72 (0.43–9.01); p < 0.05) and mean E/E’ (1.76 (0.73–2.79) p < 0.001). Associations were adjusted for age, sex, body mass index (BMI), diabetes mellitus, coronary artery disease, and arterial hypertension. Elevated ADMA is associated with the severity of DD in HCM. Higher ADMA level might lead to decreased NO production and thus an impaired myocardial relaxation pattern.