Artur Kozanecki

Prognostic value of fibrosis-related markers in dilated cardiomyopathy: A link between osteopontin and cardiovascular events

INTRODUCTION Serum markers of fibrosis provide an insight into extracellular matrix (ECM) fibrosis in heart failure (HF) and dilated cardiomyopathy (DCM). However, their role as predictors of cardiovascular (CV) events in DCM is poorly understood. METHODS This is an observational, prospective cohort study. 70 DCM patients (48±12.1years, ejection fraction - EF 24.4±7.4) were recruited. Markers of collagen type I and III synthesis - procollagen type I and III carboxy- and amino-terminal peptides (PICP, PIIICP, PINP, PIIINP), fibrosis controlling factors - ostepontin (OPN), transforming growth factor (TGF1-β) and connective tissue growth factor (CTGF), and matrix metalloproteinases (MMP-2, MMP-9) and tissue inhibitor (TIMP-1), were measured in serum. All patients underwent endomyocardial biopsy. The end-point was combined with CV death and urgent HF hospitalization. Patients were divided into two groups: those who did (group 1, n=45) and did not reach (group 2, n=25) an end-point. RESULTS Over a 12-month period of observation, 6 CV deaths and 19 HF hospitalizations occurred. Qualitative and quantitative measures of ECM fibrosis were similar in both groups. The levels of all of the markers of collagen synthesis, TGF1-β, MMP-9 and TIMP-1 were similar, however, OPN, CTGF and MMP-2 were significantly lower in group 1. CONCLUSIONS Invasively-determined fibrosis levels were not related with CV outcomes in DCM. Out of the 11 markers of fibrosis under study, only OPN was found to be related to CV outcomes. OPN is not only the pivotal protein controlling fibrosis, but may also serve as a biomarker associated with prognosis.

Temporal changes in the pattern of invasive angiography use and its outcome in suspected coronary artery disease: implications for patient management and healthcare resource utilization

Introduction Invasive coronary angiography (CAG), the ‘gold standard’ in coronary artery disease (CAD) diagnosis, requires hospitalization, is not risk-free, and engages considerable healthcare resources. Aim To assess recent (throught out 10 years) evolution of ‘significant’ (≥ 50% stenosis(es)) CAD prevalence in subjects undergoing CAG for CAD diagnosis in a high-volume tertiary referral center. Material and methods Anonymized medical records were compared for the last vs. the first 2-years of the decade (June 2007 to May 2018). Referrals for suspected CAD were 2067 of 4522 hospitalizations (45.7%) and 1755 of 5196 (33.8%) respectively (p < 0.001). Results The median patient age (64 vs. 68 years) and the prevalence of heart failure (24.1% vs. 42.2%) increased significantly (p < 0.001). The CAG atherosclerotic lesions, for all stenosis categories (< 50%; ≥ 50%; ≥ 70%; occlusion(s)), were significantly more prevalent in men. The proportion of subjects with any atherosclerosis on CAG increased (80.7% vs. 77.6%, p = 0.015). However, in the absence of any gross change in, for instance, the fraction of women (40.4% vs. 41.8%), the proportion of CAGs with significant CAD (lesion(s) ≥ 50%) decreased from 55.2% in 2007/2008 to below 1 in every 2 angiograms (48.9%) in 2017/2018 (p < 0.001). This unexpected finding occurred consistently across nearly all CAG referral categories. Conclusions Despite more advanced age and a higher proportion of subjects with ‘any’ coronary atherosclerosis on CAG, the likelihood of a ‘negative’ angiogram (lesion(s) < 50%; no further evaluation/intervention) has increased significantly over the last decade. The exact nature of this phenomenon requires further investigation, particularly as a reverse trend would be expected with the growing role (and current high penetration) of contemporary non-invasive diagnostic tools to rule out significant CAD.

RELATIONS BETWEEN FIBROSIS-LINKED MICRORNAS (MIR-21, MIR-26, MIR-29, MIR-30 AND MIR-133A) AND RIGHT VENTRICULAR MORPHOLOGY AND FUNCTION IN DILATED CARDIOMYOPATHY

Background: Relations between right ventricle (RV) and microRNAs in dilated cardiomyopathy (DCM) are poorly understood. Methods: We studied 70 DCM patients (pts) (48 ± 12.1 years, EF 24.4 ± 7.4%). Basal RV (RVd1) > 41 mm and/or mid-cavity RV dimension (RVd2) > 35 mm was diagnostic for RV

EXTRACELLULAR MATRIX TURNOVER IS NOT RELATED TO THE DURATION OF THE DISEASE IN DILATED CARDIOMYOPATHY

Fibrosis of extracellular matrix (ECM) is a hallmark of dilated cardiomyopathy (DCM). The relation between ECM turnover and duration of DCM is unknown. Since July 2014 till April 2015 we included 53 consecutive DCM patients (pts) (47.4 ± 12.4 years, EF 24.2 ± 7.6%). Pts were divided into early (