(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.

Serum biomarkers such as N-terminal prohormone of the brain natriuretic peptide (NT-proBNP) and cardiac troponins are elevated in patients with hypertrophic cardiomyopathy (HCM). At present, it is not clear if these markers are associated with distinct clinical alterations in HCM, such as left ventricular hypertrophy, outflow tract obstruction, myocardial fibrosis and/or diastolic dysfunction (DD), which are associated with adverse cardiovascular outcome. Here we evaluate the association of NT-proBNP and high sensitivity cardiac troponin T (hs-cTnT) to a variety of cardiac imaging parameters in HCM patients in a multivariable regression analysis. This retrospective cross-sectional study included 366 HCM patients who underwent transthoracic echocardiography (TTE), 218 of whom also obtained cardiovascular magnetic resonance (CMR) to assess focal myocardial fibrosis by LGE. Multivariable regression analyses revealed the strongest association of the DD parameters E/E′ mean and E/E′ septal with NT-proBNP (b = 0.06, 95%-CI [0.05–0.07], p < 0.001, R² = 0.28; b = 0.08, 95%-CI [0.06–0.1], p < 0.001, R² = 0.25) and LGE size showed the strongest association with hs-cTnT (b = 0.20, 95%-CI [0.15–0.24], p < 0.001, R² = 0.28). This study indicates that NT-proBNP and hs-cTnT are associated with structural and functional alterations in HCM. NT-proBNP is a stronger predictor for DD, while hs-cTnT is associated with the extent of focal myocardial fibrosis. Both biomarkers might be useful in the diagnostic procedure in addition to imaging parameters.

Background: Fabry disease (FD) is characterized by early development of vasculopathy and endothelial dysfunction. However, it is unclear whether these findings also play a pivotal role in cardiac manifestation. As Fabry cardiomyopathy (FC) is the leading cause of death in FD, we aimed to gather a better insight in pathological mechanisms of the disease. Methods: Serum samples were obtained from 17 healthy controls, 15 FD patients with and 7 without FC. FC was defined by LV wall thickening of >12 mm in cardiac magnetic resonance imaging and serum level of proBNP, high sensitive Troponin T (hsT), and globotriaosylsphingosine (lyso-GB3) were obtained. A multiplex ELISA-Assay for 23 different angiogenesis markers was performed in pooled samples. Markers showing significant differences among groups were further analyzed in single samples using specific Elisa antibody assays. L-homoarginine (hArg), L-arginine, asymmetric (ADMA), and symmetric Dimethylarginine (SDMA) were quantified by liquid chromatography—mass spectrometry. Results: Angiostatin and matrix metalloproteinase 9 (MMP-9) were elevated in FD patients compared to controls independently of the presence of FC (angiostatin: 98 ± 25 vs. 75 ± 15 ng/mL; p = 0.001; MMP-9: 8.0 ± 3.4 vs. 5.0 ± 2.4 μg/mL; p = 0.002). SDMA concentrations were highest in patients with FC (0.90 ± 0.64 μmol/l) compared to patients without (0.57 ± 0.10 μmol/l; p = 0.027) and vs. controls (0.58 ± 0.12 μmol/l; p = 0.006) and was positively correlated with indexed LV-mass (r = 0.61; p = 0.003), hsT (r = 0.56, p = 0.008), and lyso-Gb3 (r = 0.53, p = 0.013). Accordingly, the ratio of L-homoarginine to SDMA (hArg/SDMA) was lowest in patients with FC (2.63 ± 1.78) compared to controls (4.16 ± 1.44; p = 0.005). For L-arginine, hArg and ADMA no significant differences among groups could be detected, although a trend toward higher ADMA and lower hArg levels could be observed in the FC group. Furthermore, a significant relationship between kidney and cardiac function could be revealed (p = 0.045). Conclusion: Elevated MMP-9 and angiostatin levels suggest an increased extracellular matrix turnover in FD patients. Furthermore, endothelial dysfunction may also be involved in FC, as SDMA and hArg/SDMA are altered in these patients.