Aortic stenosis (AS) has been associated with impaired fibrinolysis and increased oxidative stress. This study aimed to investigate whether oxidative stress could alter fibrin clot properties in AS. We studied 173 non-diabetic patients, aged 51–79 years, with isolated AS. We measured plasma protein carbonylation (PC) and thiobarbituric acid reactive substances (TBARS), along with plasma clot permeability (K_s), thrombin generation, and fibrinolytic efficiency, which were evaluated by two assays: clot lysis time (CLT) and lysis time (Lys50). Coagulation factors and fibrinolytic proteins were also determined. Plasma PC showed an association with AS severity, reflected by the aortic valve area and the mean and maximum aortic gradients. Plasma PC was positively correlated with CLT, Lys50, plasminogen activator inhibitor-1 (PAI-1), and tissue factor (TF) antigens. TBARS were positively correlated with maximum aortic gradient, Lys50, and TF antigen. Regression analysis showed that PC predicted prolonged CLT (>104 min; odds ratio (OR) 6.41, 95% confidence interval (CI) 2.58–17.83, p < 0.001) and Lys50 (>565 s; OR 5.83, 95% CI 2.23–15.21, p < 0.001). Multivariate regression analysis showed that mean aortic gradient, PC, α2-antiplasmin, PAI-1, and triglycerides were predictors of prolonged CLT, while PC, α2-antiplasmin, and fibrinogen were predictors of Lys50. Our findings suggest that elevated oxidative stress contributes to impaired fibrinolysis in AS and is associated with AS severity.

Galectin-3 is an emerging biomarker in cardiovascular disease. Myocardial galectin-3 is involved in the pathology of cardiac fibrosis; however, the role of circulating galectin-3 is not yet established. To assess the relationships between circulating galectin-3, fibrosis and outcomes in dilated cardiomyopathy (DCM). We included 70 patients (age: 48 ±12.1 years, ejection fraction (EF) 24.4 ±7.4%) with new-onset DCM (n = 35, ≤6 months). Galectin-3 and procollagen type I and III (PICP, PINP, PIIICP, and PIIINP), transforming growth factor β (TGF-β), connective tissue growth factor (CTGF), osteopontin (OPN), matrix metalloproteinases (MMP-2 and -9), and tissue inhibitor (TIMP-1) were determined in serum at baseline and after 3 and 12 months. Patients underwent endomyocardial biopsy. The endpoint was a combination of death and urgent hospitalization at 12 months. Galectin-3 did not correlate with biopsy-determined fibrosis. Baseline galectin-3 correlated with OPN,, TIMP-1, PIIICP, and MMP-2. In new-onset DCM, galectin-3 levels at baseline were higher than at 3 and 12 months, whereas in chronic DCM there was no difference. Galectin-3 was a predictor of the endpoint (hazard ratio (HR) = 1.115; 95% confidence interval (95% CI) = 1.009-1.231; p < 0.05). The best cut-off value was 14.54 ng/mL (area under the curve (AUC) = 0.67). Patients with galectin-3 ≥14.54 ng/mL had an increased risk of events (HR = 2.569; 95% CI = 1.098-6.009; p < 0.05). Circulating galectin-3 is unrelated to fibrosis. Serial measurements of galectin-3 correlated with markers of fibrosis, including markers of collagen synthesis and OPN. Circulating galectin-3 was independently associated with cardiovascular (CV) outcomes in DCM.

Non-sustained ventricular tachycardia (nsVT) creates the electrical basis for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM). We aimed to evaluate the relationship between interstitial fibrosis on cardiac magnetic resonance (CMR) and nsVT in HCM. A total of 50 HCM patients underwent CMR with a 3 T scanner to determine the presence of replacement fibrosis expressed by late gadolinium enhancement (LGE), and interstitial fibrosis expressed by native T₁, post-contrast T₁, and extracellular volume (ECV). The incidence of nsVT was assessed by Holter monitoring. We detected nsVT in 14 (28%) out of 50 HCM patients. Replacement fibrosis expressed by LGE was present in 37 (74%) patients and only showed a trend towards a differentiation between the groups with and without nsVT (p = 0.07). However, the extent of LGE was clearly higher in the nsVT group (3.8 ± 4.9% vs. 7.94 ± 4.5%, p = 0.002) and was an independent predictor of nsVT in a multivariable regression analysis (OR 1.2; 95%CI 1.02–1.4; p = 0.02). No relationship was observed between interstitial fibrosis and nsVT. To conclude, it was found that it is not the mere presence but the actual extent of LGE that determines the occurrence of nsVT in HCM patients; the role of interstitial fibrosis remains unclear.

Pulmonary hypertension (PH) in patients with heart failure (HF) contributes to a poorer prognosis. However, in those with dilated cardiomyopathy (DCM), the true prevalence and role of PH is unclear. Therefore, this study aimed to analyze the profile of DCM patients at various levels of PH risk, determined via echocardiography, and its impact on outcomes. The 502 DCM in- and out-patient records were retrospectively analyzed. Information on patient status was gathered after 45.9 ± 31.3 months. Patients were divided into 3 PH-risk groups based on results from echocardiography measurements: low (L, n = 239, 47.6%), intermediate (I, n = 153, 30.5%), and high (H, n = 110, 21.9%). Symptom duration, atrial fibrillation, ventricular tachyarrhythmia, ejection fraction, right atrial area, and moderate or severe mitral regurgitation were found to be independently associated with PH risk. During the follow-up period, 83 (16.5%) DCM patients died: 29 (12.1%) in L, 31 (20.3%) in I, and 23 (20.9%) in H. L-patients had a significantly lower risk of all-cause death (L to H: HR 0.55 (95%CI 0.32–0.98), p = 0.01), while no differences in prognosis were found between I and H. In conclusion, over one in five DCM patients had a high PH risk, and low PH risk was associated with better prognoses.

Left ventricular reverse remodeling (LVRR) determines clinical status and outcomes in dilated cardiomyopathy (DCM). The extent of myocardial fibrosis is connected to the systolic function of the heart. The recent discovery of the contribution of microRNAs (miRs) to the regulation of cardiac remodeling, LVRR and fibrosis warrants exploration. The aim of the study was to examine the predictive value of circulating and myocardial miR expression for LVRR in DCM. Seventy consecutive DCM patients (age 48 ±12.1 years, 90% male, ejection fraction (EF) 24.4% ±7.4%) were included in the study. At baseline, all patients underwent clinical assessment, echocardiography, venous blood sampling, and right ventricular endomyocardial biopsy. Circulating and myocardial miRs (miR-21, -26, -29, -30, -133a, and -423) were measured with quantitative real-time polymerase chain reaction (qRT-PCR). LVRR was defined as an increase in EF ≥ 10%, accompanied by a decrease in left ventricle end-diastolic diameter (LVEDd) ≥10% or LVEDd ≤ 33 mm/m2 between baseline and 3-month follow-up. At the 3-month follow-up, 4 patients had died and 3 patients had incomplete data. The remaining patients were divided according to the presence of LVRR into LVRR-present (n = 32, 51%) and LVRR-absent (n = 31, 49%) groups. Out of all the circulating and tissue miRs under study, only myocardial expression of miR-133a significantly differed between the LVRR-present and LVRR-absent group (1.22 (0.47-1.90) vs 0.61 (0.25-0.99) ΔCq, respectively, p < 0.01). miR-133a was found to be a significant LVRR predictor in unadjusted (odds ratio (OR) = 2.81 (1.23-6.40), p < 0.05) and adjusted for duration of disease, left ventricle end-diastolic (LVED) volume (LVEDvol), hs-troponin-T, and NT-proBNP (OR = 5.20 (1.13-24.050, p < 0.05) models. From all of the circulating and tissue miRs, only myocardial miR-133a showed increased expression in LVRR-present patients and was found an independent LVRR predictor. This indicates a link between miR-133 and cardiac remodeling in DCM.

Background: Fibrosis of the extracellular matrix (ECM) in dilated cardiomyopathy (DCM) is common and compromises both systolic and diastolic function. The aim of this study was to investigate the kinetics of ECM fibrosis markers over a 12 month follow-up in patients with DCM based on the severity of diastolic dysfunction (DD). Methods: Seventy consecutive DCM patients (48 ± 12.1 years, ejection fraction 24.4 ± 7.4%) were included in the study. The grade of DD was determined using the ASE/EACVI algorithm. Markers of ECM fibrosis were measured at baseline and at 3 and 12 month follow-ups: collagen type I and III (PICP, PINP, PIIICP, PIIINP), tumor growth factor beta-1 (TGF1-β), connective tissue growth factor (CTGF) and galectin-3 were measured. Results: Patients were divided into three groups according to DD severity: 30 patients with grade I, 18 with grade II and 22 with grade III of DD. Levels of PICP, PINP were increased over a 12-month period, while PIIINP decreased and PIIICP unchanged. Levels of TGF1-β decreased from the 3 to the 12-month points in grade I and II DD, and in grade III they remained unchanged. Levels of CTGF decreased over 12 months in grade III DD but were unchanged in grades I and II. Galectin-3 levels remained the same over all observation periods, irrespective of DD grade. Conclusions: Regardless of the DD grade, markers of collagen type I synthesis increased, markers of collagen type III decreased. Levels of TGF and CTGF had a tendency to decrease. Galectin-3 was revealed not to be a marker discriminating the severity of DD. Background: Fibrosis of the extracellular matrix (ECM) in dilated cardiomyopathy (DCM) is common and compromises both systolic and diastolic function. The aim of this study was to investigate the kinetics of ECM fibrosis markers over a 12 month follow-up in patients with DCM based on the severity of diastolic dysfunction (DD). Methods: Seventy consecutive DCM patients (48 ± 12.1 years, ejection fraction 24.4 ± 7.4%) were included in the study. The grade of DD was determined using the ASE/EACVI algorithm. Markers of ECM fibrosis were measured at baseline and at 3 and 12 month follow-ups: collagen type I and III (PICP, PINP, PIIICP, PIIINP), tumor growth factor beta-1 (TGF1-β), connective tissue growth factor (CTGF) and galectin-3 were measured. Results: Patients were divided into three groups according to DD severity: 30 patients with grade I, 18 with grade II and 22 with grade III of DD. Levels of PICP, PINP were increased over a 12-month period, while PIIINP decreased and PIIICP unchanged. Levels of TGF1-β decreased from the 3 to the 12-month points in grade I and II DD, and in grade III they remained unchanged. Levels of CTGF decreased over 12 months in grade III DD but were unchanged in grades I and II. Galectin-3 levels remained the same over all observation periods, irrespective of DD grade. Conclusions: Regardless of the DD grade, markers of collagen type I synthesis increased, markers of collagen type III decreased. Levels of TGF and CTGF had a tendency to decrease. Galectin-3 was revealed not to be a marker discriminating the severity of DD.