Mariusz Tomaniak

Circulating microribonucleic acids miR-1, miR-21 and miR-208a in patients with symptomatic heart failure: Preliminary results

BACKGROUND Cardiomyocytes produce a wide variety of bioactive molecules that regulate numerous physiological and pathophysiological processes. Recently, it has been recognized that changes in microribonucleic acid (miRNA) expression may lead to cardiac dysfunction. AIMS To assess the expression of circulating miRNAs (miR-1, miR-21 and miR-208a) in patients with symptomatic heart failure (HF), and to investigate the relationship between expression of these miRNAs and secretion of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and galectin-3. METHODS Thirty-five patients in New York Heart Association (NYHA) class II/III (age: 68.8 ± 13.0 years) and 26 patients in NYHA class IV (age: 72.0 ± 10.4 years) hospitalized in the intensive coronary care unit participated in the study. Serum concentrations of miRNAs were measured by quantitative real-time polymerase chain reaction. Basic biochemical assays were carried out, and NT-proBNP and galectin-3 concentrations were measured in all serum samples. RESULTS miR-1 was downregulated in patients with symptomatic HF and its expression decreased with severity of NYHA class (P=0.007). In contrast, overexpression of miR-21 was seen in all patients, independent of HF severity. Results suggest no miR-208a leakage into the circulation in patients with symptomatic HF. There was an inverse relationship between miR-1 expression and NT-proBNP concentration (Spearmans rank correlation coefficient [r]=-0.389; P=0.023) in patients in NYHA class II/III. Overexpression of miR-21 correlated significantly with galectin-3 concentration (r=0.422; P=0.032). CONCLUSION Dysregulation of miR-1 and miR-21 expression may be essential for the development of HF; miR-1 might become a biomarker for predicting HF exacerbation.

A 12–month angiographic and optical coherence tomography follow-up after bioresorbable vascular scaffold implantation in patients with ST-segment elevation myocardial infarction

The aim of the study was to evaluate the healing process at 12 months after ABSORB™ bioresorbable vascular scaffold (BVS) implantation in patients with ST‐segment elevation myocardial infarction (STEMI).

A prospective randomised comparison of minor bleedings in transradial vs. transfemoral access percutaneous coronary interventions for STEMI: a new FEMORAL bleeding classification

BACKGROUND Local bleedings related to vascular access site in percutaneous procedures are relatively common complications. However, no uniform definitions exist to classify them. AIM To compare minor bleedings related to transradial (TR) and transfemoral (TF) percutaneous coronary intervention (PCI) approaches in ST elevation myocardial infarction (STEMI). In addition, a new classification of TF access-related bleeding - the FEMORAL scale - was proposed. METHODS OCEAN RACE is a prospective, randomised, open-label, clinical trial performed in STEMI patients treated with primary PCI. Patients were randomly assigned to the TR or TF arm. Bleedings related to the TR approach were assessed by the EASY scale, whereas bleedings related to the TF approach were classified according to the new FEMORAL scale. A combined analysis of all bleedings was performed using the TIMI scale. RESULTS There were 103 patients analysed, including 52 in the TR arm and 51 in the TF arm. Analysis of demographic and clinical baseline characteristics revealed no significant differences between the two study groups. In-hospital bleedings related to the access site were observed in 29.8% of patients. In the TR group, a trend towards lower risk of local bleedings was observed compared to the TF group (TR: 22.4% vs. TF: 37.7%, p = 0.081). Analysis of each class of access site bleeding according to EASY/FEMORAL scales showed that patients in the TR group had a significantly lower risk of class III local haematoma compared to the TF group (TR: 0% vs. TF: 9.8%, p = 0.027). The risk of bleeding in other classes was comparable in both groups. A trend towards less frequent minimal bleedings according to the TIMI scale was observed in the TR group (HR: 0.41, 95% CI: 0.152-1.112, p = 0.059). CONCLUSIONS TF patients had a higher risk of access-related bleedings than TR patients. The FEMORAL scale was effective in the classification of TF access-related bleedings. Although the popularity of TF access in PCI decreases, this approach is increasingly used in transcatheter aortic valve implantation, renal denervation and closure of paravalvular leaks. Therefore a scale accessing local bleeding in the TF approach may be useful.

Optimal aNtiplatelet pharmacotherapy guided by bedSIDE genetic or functional TESTing in elective PCI patients: A pilot study: ONSIDE TEST pilot

BACKGROUND Dual antiplatelet therapy (DAPT) is recommended after elective percutaneous coronary intervention (PCI) in stable coronary artery disease (SCAD) patients; however, still one-third of patients do not obtain adequate platelet inhibition that may result in increased cardiovascular risk. The aim of the ONSIDE TEST study is to evaluate the clinical impact of point-of-care genotyping- and platelet function-based personalized dual antiplatelet strategies in SCAD individuals undergoing PCI. METHODS Fifty patients were randomized to one of the three study arms: 1) genotyping, 2) platelet function testing (PFT) and 3) control. Patients were tested with point-of-care Spartan RX CYP2C19 System (group 1) and VerifyNow P2Y12 assay (group 2). In cases of inadequate response to clopidogrel, a loading dose of prasugrel was administered before PCI. The main clinical endpoint is the incidence of periprocedural myocardial injury (PMI). RESULTS Five (32%) patients in the genotyping arm and two (13%) in the in the PFT arm were identi-fied as poor clopidogrel metabolizers. The periprocedural platelet reactivity was significantly lower in the genotyping (80 ± 49.0 PRU) and PFT (36.5 ± 47 PRU) arms as compared to the control arm (176 ± 67.8 PRU), p = 0.01 and p = 0.03, respectively. PMI appeared in 17 (37%) patients of the entire study population. CONCLUSIONS Personalized DAPT results in an improved platelet inhibition. Apart from genotyping and aggregometry, it is feasible to integrate into everyday clinical practice PMI rates which are relevant when comparing different strategies.

Study design and rationale for Optimal aNtiplatelet pharmacotherapy guided by bedSIDE genetic or functional TESTing in elective percutaneous coronary intervention patients (ONSIDE TEST): a prospective, open-label, randomised parallel-group multicentre trial (NCT01930773).

BACKGROUND AND AIM High platelet reactivity (HPR) and presence of CYP2C19 loss-of-function alleles are associated with higher risk for periprocedural myocardial infarction in clopidogrel-treated patients undergoing percutaneous coronary intervention (PCI). It is unknown whether personalised treatment based on platelet function testing or genotyping can prevent such complications. METHODS The ONSIDE-TEST is a multicentre, prospective, open-label, randomised controlled clinical trial aiming to assess if optimisation of antiplatelet therapy based on either phenotyping or genotyping is superior to conventional care. Patients will be randomised into phenotyping, genotyping, or control arms. In the phenotyping group, patients will be tested with the VerifyNow P2Y12 assay before PCI, and patients with a platelet reactivity unit greater than 208 will be switched over to prasugrel, while others will continue on clopidogrel therapy. In the genotyping group, carriers of the *2 loss-of-function allele will receive prasugrel for PCI, while wild-type subjects will be treated with clopidogrel. Patients in the control arm will be treated with standard-dose clopidogrel. The primary endpoint of the study is the prevalence of periprocedural myocardial injury within 24 h after PCI in the controls as compared to the phenotyping and genotyping group. Secondary endpoints include cardiac death, myocardial infarction, definite or probable stent thrombosis, or urgent repeat revascularisation within 30 days of PCI. Primary safety outcome is Bleeding Academic Research Consortium (BARC) type 3 and 5 bleeding during 30 days of PCI. SUMMARY The ONSIDE TEST trial is expected to verify the clinical utility of an individualised antiplatelet strategy in preventing periprocedural myocardial injury by either phenotyping or genotyping. TRIAL REGISTRATION ClinicalTrials.gov: NCT01930773.

Anti-inflammatory therapy in the treatment of cardiovascular diseases.

Copyright

Delayed neointimal healing pattern after bioresorbable scaffold implantation

Fig. 1 a (Baseline) Optical coherence tomography (OCT) directly after implantation of the bioresorbable scaffold (BVS). Adequate BVS expansion and focally malapposed struts in the distal 3-mm scaffold segment (white arrow) into right coronary artery. b (1-year follow-up) Uncovered stent struts (blue arrows) at 12 months after the intervention. c (2-year follow-up) 24-month OCT revealed complete coverage of all struts with a homogeneous, bright neointimal layer and resolved malapposition in the distal segment

miR-1, miR-21, and galectin-3 in hypertensive patients with symptomatic heart failure and left ventricular hypertrophy

INTRODUCTION Left ventricular hypertrophy (LVH) is known as an independent risk factor for coronary heart disease, heart failure (HF), stroke, and sudden cardiac arrest. LVH implicates changes in the architecture of myocardial tissue, which consist of perivascular and myocardial fibrosis, as well as medial thickening of intramyocardial coronary arteries, in addition to cardiomyocyte hypertrophy [1–3]. The impact of miR-1 level on cardiac hypertrophy and cardiomyocyte apoptosis has been recently suggested [3, 4]. Also, the association between miR-21 and galectin-3 (gal-3) levels and maladaptive cardiac remodelling, fibrosis, and inflammation has been described [5, 6]. Nevertheless, the synergistic role of these molecules in LVH has not been explained to date. We analysed the expressions of miR-1, miR-21, and gal-3 concentration in patients with symptomatic HF (SHF) and a history of hypertension and LVH revealed in echocardiography.

Dysregulations of miRNAs and galectin-3 may underlie left ventricular dilatation in patients with systolic heart failure

INTRODUCTION Left ventricular (LV) adverse remodelling represents a major feature of systolic heart failure (SHF). It has been identified as a risk factor for impaired cardiac function [1]. A potential role of miR-1 and miR-21 in adverse cardiac remodelling in HF has been recognised [2, 3]. Increased concentration of galectin-3 (gal-3) in HF patients has also been observed [4, 5]. We aimed to explore the serum expression of miR-1 and miR-21, and the concentration of gal-3 in SHF patients with different degrees of LV dilatation. The concentration of N-terminal pro-B-type natriuretic peptide (NT-proBNP) was measured and compared with new, potentially clinically useful HF biomarkers.

A serial three- and nine-year optical coherence tomography evaluation of neoatherosclerosis progression after sirolimus- and paclitaxel- -eluting stent implantation

BACKGROUND Early-generation drug-eluting stents (DESs) have been shown to accelerate neoatherogenesis. Limited optical coherence tomography (OCT) data on the very long-term neoatherosclerotic progression after DES implantation are available. AIM The aim of this study was a serial OCT evaluation of neoatherosclerosis at three and nine years after implantation of sirolimus-eluting stents (SESs) and paclitaxel-eluting stents (PESs). METHODS Consecutive patients undergoing elective percutaneous coronary intervention with SES (Cypher, Cordis) or PES (Taxus, Boston Scientific) were included in this single-centre, longitudinal study. OCT analysis was performed after three and nine years by an independent core laboratory. RESULTS A total of 39 OCT recordings were assessed at three years after the index procedure; of them, 22 (eight SES and 14 PES) OCT pullbacks were evaluated in a paired analysis at three and nine years post implantation. Overall, neoatheroscle-rosis was identified in 23.1% of stents at three years and in 30.8% at nine years after the index procedure (p = 0.289). No features of significant neoatherosclerotic progression were found in either group between three- and nine-year assessment. CONCLUSIONS At nine years after implantation of early-generation DES no significant neoatherosclerotic progression was observed among patients with uneventful follow-up at three years after PCI, as assessed by OCT. These observations need to be confirmed in larger studies including the current generation of DESs.