Kinetics of selected serum markers of fibrosis in patients with dilated cardiomyopathy and different grades of diastolic dysfunction of the left ventricle

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), transforming growth factor beta-1 (TGF1-b), 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-b 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

Fibrosis of extracellular matrix is related to the duration of the disease but is unrelated to the dynamics of collagen metabolism in dilated cardiomyopathy

Background Fibrosis of extracellular matrix (ECM) in dilated cardiomyopathy (DCM) corresponds to the myocardial over-production of various types of collagens. However, mechanism of this process is poorly understood. Objective To investigate whether enhanced metabolism of ECM occur in DCM. Methods Seventy consecutive DCM patients (pts) (48 ± 12.1 years, EF 24.4 ± 7.4 %) and 20 healthy volunteers were studied. Based on symptoms duration, pts were divided into new-onset (n = 35, 6 months) and chronic DCM (n = 35, >6 months). Markers of collagen type I and III synthesis-procollagen type I carboxy- and amino-terminal peptides (PICP and PINP) and procollagen type III carboxy- and amino-terminal peptides (PIIICP and PIIINP), collagen 1 (col-1), ECM metabolism controlling factors-tumor growth factor beta-1 (TGF1-b), connective tissue growth factor (CTGF), and ECM degradation enzymes-matrix metalloproteinases (MMP-2, MMP-9) and their tissue inhibitor (TIMP-1) were measured in serum. All pts underwent right ventricular endomyocardial biopsy to study ECM fibrosis. Results The presence of fibrosis was detected in 24 (34.3 %) pts and was more prevalent in chronic DCM [17 (48.6 %) vs. 7 (20 %), p\0.01]. The levels of PIIINP [4.41 (2.17-6.08) vs. 3.32 (1.69-5.02) ng/ml, p\0.001], CTGF [3.82 (0.48-23.87) vs. 2.37 (0.51-25.32) ng/ml, p\0.01], MMP-2 [6.06 (2.72-14.8) vs. 4.43 (2.27=7.4) ng/ml, p\0.001], MMP-9 [1.98 (0.28-9.25) vs. 1.01 (0.29-3.59) ng/ml, p\0.002)], and TIMP-1 [15.29 (1.8-36.17) vs. 2.61 (1.65-24.09) ng/ml, p\0.004] were significantly higher in DCM, whereas levels of col-1 [57.7 (23.1-233.4) vs. 159.4 (31.2-512.9) pg/ml, p\0.001] were significantly lower in DCM compared to controls. There were no differences in all measured serum markers of ECM metabolism between newonset and chronic DCM and as well as fibrosis positive and negative pts. Fibrosis was weakly correlated only with the duration of DCM (r = 0.23, p\0.05), however, not a single serum marker of fibrosis correlated with fibrosis. Neither unadjusted nor adjusted models, constructed from serum markers of ECM metabolism, predicted the probability of myocardial fibrosis. Conclusions Dynamics of ECM turnover in DCM is high, which is reflected by the increased levels CTGF and degradation enzymes. Synthesis of collagen type III prevailed over collagen type I. ECM metabolism was not different in DCM regardless of the duration of the disease and status of myocardial fibrosis. Serum markers of ECM metabolism were found not to be useful for the prediction of myocardial fibrosis in DCM

Clinical outcomes in patients after surgical and transcatheter aortic valve replacement

INTRODUCTION Transcatheter aortic valve implantation (TAVI) and minimally invasive aortic valve replacement (minithoracotomy and ministernotomy) have become a valuable alternative to conventional surgical treatment of severe aortic stenosis (AS) in high-risk patients. OBJECTIVES The aim of the study was to evaluate long-term results and complications in patients with symptomatic AS treated with TAVI, surgical aortic valve replacement (SAVR), minithoracotomy, or ministernotomy. PATIENTS AND METHODS A total of 173 patients with symptomatic AS were enrolled to the study between the years 2011 and 2013. Propensity scores were calculated for TAVI and each surgical method separately. Differences in clinical outcomes between patients treated with TAVI and those treated with surgical methods were adjusted for propensity scores using a logistic regression analysis and presented as adjusted odds ratios with 95% confidence intrervals. RESULTS A median follow-up was 583.5 days (interquartile range, 298–736 days). Before aortic valve replacement (AVR), no significant differences in ejection fraction (EF) were observed between the groups. At 1 week after AVR, mean EF values were significantly higher in patients after TAVI in comparison with the other groups (TAVI, 50.2% ±13.1%; minithoracotomy, 44.1% ±13.4%; ministernotomy, 37.8% ±12.8%; SAVR, 40.3% ±12.5%; P = 0.001). There were no differences in the longest available follow-up mortality between the analyzed groups (P = 0.8). To our best knowledge, this is the first study comparing minithoracotomy, ministernotomy, and SAVR with TAVI in terms of long-term outcomes such as the longest available follow-up mortality, left ventricular (LV) function, complications after the procedure, and conduction disturbances and arrhythmias after the procedure. CONCULSIONS Patients undergoing TAVI show more beneficial long-term outcomes in comparison with patients undergoing minithoracotomy, ministernotomy, and SAVR and do not differ in terms of the longest available follow-up mortality. TAVI seems to have a more favorable effect on LV function and an increase in EF in comparison with the surgical methods