Paweł Rubiś

Atherosclerosis progression affects the relationship between endothelial function and aortic stiffness

Aortic stiffening is the most important determinant of elevated systolic blood pressure which in turn is the main contributor to the burden of disease attributable to hypertension. Endothelial function may affect arterial stiffening as has been shown for carotid-aorto-femoral segments in healthy humans or subjects with cardiovascular risk factors. We investigated whether this association is present selectively for aorta and whether it extends to patients with advanced atherosclerosis. Direct measurements of aortic pulse wave velocity (aPWV) to assess aortic stiffness and brachial artery flow-mediated dilatation (bFMD) tests to assess endothelial function were performed in 111 consecutive patients suspected of coronary artery disease. Progression of atherosclerosis was determined on the basis of the presence or absence of significant coronary artery stenosis, CAS (>or=50%) in angiography. bFMD was lower (P<0.001) and aPWV was higher (P<0.001) in a group of 72 patients with advanced atherosclerosis when compared with a group of 39 patients without significant CAS. bFMD was inversely associated with aPWV but only in patients without advanced atherosclerosis (r=-0.37, P=0.02), even after adjustment of confounding factors in a multivariate analysis model (R(2)=0.37, P<0.001). We concluded that endothelial function may influence aortic stiffness which is limited however by the progression of atherosclerosis.

The dynamic assessment of right-ventricular function and its relation to exercise capacity in heart failure

To evaluate right‐ventricular (RV) function during stress echocardiography (SE) and to assess its relationship with exercise capacity in heart failure (HF) patients.

Relations between circulating microRNAs (miR-21, miR-26, miR-29, miR-30 and miR-133a), extracellular matrix fibrosis and serum markers of fibrosis in dilated cardiomyopathy

Relations between circulating microRNAs (miR-21, miR-26, miR-29, miR-30 and miR-133a), extracellular matrix fibrosis and serum markers of fibrosis in dilated cardiomyopathy Paweł Rubiś ⁎, Justyna Totoń-Żurańska , Sylwia Wiśniowska-Śmiałek , Katarzyna Holcman , Maria Kołton-Wróż , Paweł Wołkow , Ewa Wypasek , Joanna Natorska , Lucyna Rudnicka-Sosin , Agnieszka Pawlak , Artur Kozanecki , Piotr Podolec a,g,1

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.

12-month patterns of serum markers of collagen synthesis, transforming growth factor and connective tissue growth factor are similar in new-onset and chronic dilated cardiomyopathy in patients both with and without cardiac fibrosis

HighlightsKinetics of collagen type I and III synthesis in DCM move in opposite directions.Production of collagen type I increases but collagen type III decreases.TGF and CTGF levels over 12‐month follow‐up had a tendency to decrease.Regardless of DCM duration or fibrosis, kinetics of fibrosis markers were similar.Improved understanding of fibrosis may translate into tailored therapy. Abstract Background: The dynamics of the extracellular matrix (ECM) fibrosis process in dilated cardiomyopathy (DCM) may be assessed non‐invasively by means of serum markers of fibrosis. Aim: To explore the kinetics of serum markers of fibrosis during a 12‐month follow‐up in DCM. Methods: We included 70 consecutive DCM patients (pts) (48 ± 12.1 years, EF 24.4 ± 7.4%) with new‐onset (n = 35, duration <6 months) and chronic DCM (n = 35, >6 months). Markers of collagen type I and III synthesis – procollagens type I and III carboxy‐ and amino‐terminal peptides (PICP, PINP, PIIICP, PIIINP), and ECM metabolism controlling factors – tumor growth factor beta‐1 (TGF1‐&bgr;), and connective tissue growth factor (CTGF) – were measured in serum at baseline, and at 3‐ and 12‐month follow‐up. All pts underwent endomyocardial biopsy to determine the presence and extent of ECM fibrosis. Results: Markers of collagen type I synthesis (PICP and PINP) were almost homogenously increased over the 3‐ and 12‐month period, whereas PIIINP values decreased and PIIICP levels were unchanged in new‐onset and chronic DCM, and in pts with and without ECM fibrosis. Both TGF‐&bgr; and CTGF levels decreased over the observation period. Kinetics of serum markers of collagen synthesis and fibrosis controlling factors did not differ between DCM pts categorized according to disease duration and fibrosis status. Conclusions: The kinetics of collagen type I and III synthesis in DCM move in opposite directions, with production of collagen type I consistently increasing, and the synthesis of collagen type III decreasing. Levels of TGF and CTGF, which are proven fibrosis‐stimulating factors, had a tendency to decrease. Regardless of disease duration or fibrosis status, the kinetics of serum markers of collagen synthesis, TGF and CTGF were similar in DCM. A better understanding of the kinetics of serum markers of fibrosis in DCM may help to develop more tailored therapeutic approaches to fibrosis.

The paramount importance of repeated left ventricular endomyocardial biopsy during the diagnosis of restrictive cardiomyopathy due to AL cardiac amyloidosis

1Department of Cardiac and Vascular Disease, John Paul II Hospital, Krakow, Poland; 2Department of Pathology, John Paul II Hospital, Krakow, Poland; 3Department of Haematology, Collegium Medicum, Jagiellonian University, Krakow, Poland; 4Faculty of Medicine and Health Science, Jan Kochanowski University, Kielce, Poland; 52nd Department of Cardiology, Swietokrzyskie Cardiology Centre, Kielce, Poland; 6Jagiellonian University, Medical College, Institute of Cardiology, Krakow, Poland

The relationship between myocardial fibrosis and myocardial microRNAs in dilated cardiomyopathy: A link between mir-133a and cardiovascular events

It is unknown whether fibrosis‐associated microRNAs: miR‐21, miR‐26, miR‐29, miR‐30 and miR‐133a are linked to cardiovascular (CV) outcome. The study evaluated the levels of extracellular matrix (ECM) fibrosis and the prevalence of particular microRNAs in patients with dilated cardiomyopathy (DCM) to investigate any correlation with CV events. Methods: Seventy DCM patients (48 ± 12 years, EF 24.4 ± 7.4%) underwent right ventricular biopsy. The control group was comprised of 7 patients with CAD who underwent CABG and intraoperative biopsy. MicroRNAs were measured in blood and myocardial tissue via qPCR. The end‐point was a combination of CV death and urgent HF hospitalization at the end of 12 months. There were differential levels of circulating and myocardial miR‐26 and miR‐29 as well as myocardial miR‐133a when the DCM and CABG groups were compared. Corresponding circulating and myocardial microRNAs did not correlate with one another. There was no correlation between microRNA and ECM fibrosis. By the end of the 12‐month period of the study, CV death had occurred in 6 patients, and a further 19 patients required urgent HF hospitalization. None of the circulating microRNAs was a predictor of the combined end‐point; however, myocardial miR‐133a was an independent predictor in unadjusted models (HR 1.53; 95% CI 1.14‐2.05; P < .004) and adjusted models (HR 1.57; 95% CI 1.14‐2.17; P < .005). The best cut‐off value for the miR‐133a level for the prediction of the combined end‐point was 0.74 ΔCq, with an AUC of 0.67. The absence of a correlation between the corresponding circulating and myocardial microRNAs calls into question their cellular source. This study sheds new light on the role of microRNAs in ECM fibrosis in DCM, which warrants further exploration.

A 34‐year‐old man with non‐obstructive apical hypertrophic cardiomyopathy (RCD code: III‐2A.1)

Hypertrophic cardiomyopathy (HCM) is a primary disease of the myocardium that is defined by the presence of regional (more frequent) or global myocardial hypertrophy, which usually re‐ sults in functional cardiac impairment. The prevalence of HCM is about 0.2% to 0.5% in the general population and affects equally men and women [2,3,4,5]. In the majority of patients of Caucasian descent, hypertrophy is local and usually confined to the basal septum. On the other hand, the morphology of cardiac hyper‐ trophy can be variable. Although hypertrophy of apical segments is rare in Europe, it is more common in patients of east Asian descent [1]. The primary causes of this disease are hereditary or newly‐created mutations of genes encoding contractile proteins of cardiac sarcomeres. These comprise over 90% of HCM cases [6]. At present there are over 600 identified mutations responsible for the disease, predominantly single‐point missense mutations in the genes coding for beta‐myosin heavy chain, myosin bind‐ ing protein C, cardiac troponin T and tropomyosin [7]. HCM is a disease characterized by unexplained, asymmetric left ven‐ tricular (LV) hypertrophy, defined as a maximal wall thickness of ≥15 mm, without any dilatation in the absence of another disease capable of inducing wall thickening [8]. HCM is divided into obstructive and non‐obstructive types, based on the blockage of blood flow out of the LV, which results in a substantial increase of the LV outflow tract (LVOT) gradi‐ ent by more than 30 mm Hg [9]. LVOT obstruction is present in two‐thirds of HCM patients – one‐third with a resting gradient and one‐third with an exercise‐induced gradient [10]. In both types of HCM the thickened muscle reduces the volume of the LV, leading to diastolic heart failure. The clinical course of HCM is variable, progressing to non‐specific cardiac symptoms such as: dyspnoea, exertional chest pain, palpitations, arrhythmias, fatigue, and syn‐ cope [11]. However, occasionally the disease can be asymptomatic – manifesting for the first time as sudden cardiac death (SCD). The annual rate of SCD is lower than 1%, but within the general population of HCM patients, there are subgroups with a much higher incidence [12].

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.

Hemangioma of the left ventricle (RCD code: VI-1B.4)

Cardiac tumors are quite rare, and differential diagnosis of them is challenging. We present the case report of a young man complaining on non specific chest pain who was reported to Cardiology Ward due to suspicion of thrombus in left ventricle. The patients echocardiography showed an additional mobile structure located in apex of left ventricle. For further investigation he had a cardiac Magnetic Resonance Imaging (MRI) performed which drew out the suspicion of rather unmalignant tumor. Ultimately patient underwent noncomplicated cardiac surgery with total excision of the tumor. Histopatology examination reveald capillary hemangioma.