Tomasz Mazurek

Pericoronary Adipose Tissue: A Novel Therapeutic Target in Obesity-Related Coronary Atherosclerosis

Inflammation plays a crucial role in the development and destabilization of atherosclerotic plaques in coronary vessels. Adipose tissue is considered to act in paracrine manner, which modulates a number of physiological and pathophysiological processes. Perivascular adipose tissue has developed specific properties that distinguish it from the fat in other locations. Interestingly, its activity depends on several metabolic conditions associated with insulin resistance and weight gain. Particularly in obesity perivascular fat seems to change its character from a protective to a detrimental one. The present review analyzes literature in terms of the pathophysiology of atherosclerosis, with particular emphasis on inflammatory processes. Additionally, the authors summarize data about confirmed paracrine activity of visceral adipose tissue and especially about pericoronary fat influence on the vascular wall. The contribution of adiponectin, leptin and resistin is addressed. Experimental and clinical data supporting the thesis of outside-to-inside signaling in the pericoronary milieu are further outlined. Clinical implications of epicardial and pericoronary adipose tissue activity are also evaluated. The role of pericoronary adipose tissue in obesity-related atherosclerosis is highlighted. In conclusion, the authors discuss potential therapeutical implications of these novel phenomena, including adipokine imbalance in pericoronary adipose tissue in the setting of obesity, the influence of lifestyle and diet modification, pharmaceutical interventions and the growing role of microRNAs in adipogenesis, insulin resistance and obesity. Key teaching points: • adipose tissue as a source of inflammatory mediators • changes in the vascular wall as a result of outside-to-inside signaling • anatomy, physiology, and clinical implications of epicardial and pericoronary adipose tissue activity • adipokines and their role in obesity-related atherosclerosis • therapeutic perspectives and future directions

Inflammatory activity of pericoronary adipose tissue may affect plaque composition in patients with acute coronary syndrome without persistent ST-segment elevation: preliminary results

BACKGROUND The extravascular expression of inflammatory mediators may adversely influence coronary lesion formation and plaque stability through outside-to-inside signalling. It has been shown that the maximal standardised uptake value (SUV) of 18-fluorodeoxyglucose detected by positron emission tomography (PET/CT) is proportional to macrophage density. AIM To investigate whether the inflammatory activity of pericoronary adipose tissue (PVAT) may influence plaque composition in acute coronary syndrome without persistent ST-segment elevation (NSTE-ACS) patients. METHODS In a prospective study, 36 coronary arteries (LM, RCA, LCX, LAD) were investigated in non-diabetic patients with a low or intermediate risk of NSTE-ACS (GRACE ≤ 140). SUV was measured in fat surrounding coronary arteries on the sections corresponding to proximal and medial segments (Siemens biograph 64-PET/CT system). Additionally, SUV was measured in subcutaneous fat (SC), visceral thoracic fat (VS), and epicardial fat over the right ventricle (EPI). Virtual histology intravascular ultrasound (VH-IVUS) was performed to assess plaque composition (Volcano, USA). PET/CT sections were further examined in segments corresponding to coronary plaques. RESULTS PVAT SUV in NSTE-ACS patients was significantly greater than in other fat locations (LM SUV: 1.60; RCA SUV: 1.54; LCX SUV: 1.94; LAD SUV: 2.37 vs. SC SUV 0.57; VS SUV: 0.77; EPI SUV: 0.98; p < 0.001; ANOVA). PVAT SUV positively correlated with plaque burden (r = 0.49, p < 0.05) and necrotic core plaque rate (r = 0.68, p < 0.05), and negatively correlated with fibrous plaque rate (r = -0.52, p < 0.05). CONCLUSIONS The inflammatory activity of PVAT reflected by SUV is greater than in subcutaneous, visceral thoracic, or epicardial tissue in NSTE-ACS patients; PVAT SUV correlates with the plaque burden and necrotic core component of coronary plaque.

Access for percutaneous coronary intervention in ST segment elevation myocardial infarction: radial vs. femoral ??? a prospective, randomised clinical trial (OCEAN RACE)

BACKGROUND Percutaneous treatment of patients with ST segment elevation myocardial infarction (STEMI) has become the standard and default mode of management as recommended by the European Society of Cardiology guidelines for managing acute myocardial infarction in patients presenting with STEMI. The choice of vascular access is made by the operator and has a potential impact on the safety and efficacy of the procedure and outcomes. AIM To understand the influence of a radial approach on bleeding complications and angiographic success, we performed a prospective, controlled randomised trial. METHODS Patients were allocated to radial (TR) or femoral (TF) vascular access. The primary endpoints were major bleeding by the REPLACE-2 scale and minor bleeding by the EASY scale (TR arm) or the FEMORAL scale (TF arm). Other outcomes included procedural data, in-hospital and long-term survival. RESULTS There were 103 patients analysed in total, 52 in the TR arm and 51 in the TF arm. The demographic and clinical baseline characteristics were well matched between the two study groups. The frequency of the primary endpoint was the same in both arms (TR: 25.0% vs. TF: 33.3%, p = 0.238). In per protocol analysis, there was a significant benefit of the TR approach among independent operators (17.4% vs. 36.8%, p = 0.038). Major bleeding by the REPLACE-2 scale occurred in 4.2% of patients (TR: 5.8% vs. TF: 3.9%, p = 0.509). There were no differences in terms of the rate of major cardiac adverse events, which happened in 10.7% of the study population (TR: 9.6% vs. TF: 11.8%, p = 0.48). In the TF arm, there was a trend towards a higher risk of local bleedings (TR: 22.4% vs. TF: 37.7%, p = 0.081) and a significantly higher frequency of local haematoma (class III, EASY/FEMORAL) (TR: 0% vs. TF: 9.8%, p = 0.027). CONCLUSIONS There were no significant differences between the TR and TF approaches in terms of clinical efficacy and patient safety. However, patients treated by independent operators might benefit from TR access. The overall complication risk of percutaneous coronary intervention treatment of STEMI patients remains low.

Pre-procedural dual antiplatelet therapy and bleeding events following transcatheter aortic valve implantation (TAVI)

INTRODUCTION Transcatheter aortic valve implantation (TAVI) is associated with bleeding that increases mortality. Dual antiplatelet therapy (DAPT) is recommended in TAVI, however little is known about pre-procedural DAPT use and its impact on hemostasis. We sought to determine the frequency, predictors and bleeding events in patients receiving DAPT before TAVI. METHODS Three-hundred-and-three (n=303, 78.6±7.6years, 49% female, EuroScore 23.1±16.9) consecutive patients undergoing TAVI were prospectively analyzed and followed for in-hospital events. According to pre-procedural antiplatelet status study population was divided into 2 groups: patients receiving aspirin and clopidogrel (DAPT) and those on aspirin only or no antiplatelet therapy (noDAPT). RESULTS Pre-procedural DAPT was used in 139 cases (46%). Previous PCI (OR 4.8, [2.8-8.3], p<0.0001), implantation of self-expandable prosthesis (OR 2.2, [1.2-4], p=0.007) femoral access (OR 2.2, [1.1-4.5], p=0.029) and platelet count (OR 1.006, [1.002-1.01], p=0.002) were identified as independent predictors of pre-procedural DAPT. No difference was observed in the rates of any bleeding (23% in DAPT vs. 24.4% in noDAPT, p=0.930) or major/life-threatening bleeding (12.2% in DAPT vs. 14.7% in noDAPT, p=0.715). Propensity-score matching analysis did not alter the results. GFR <30ml/min was the strongest predictor of bleeding (OR 4.3, [1.9-9.9], p=0.0005). There was a trend towards lower frequency of MI and stroke/TIA in DAPT as compared with noDAPT (3.6% vs. 9.8%, p=0.082). CONCLUSIONS Pre-procedural DAPT is frequent and does not increase short-term bleeding complications or need for transfusion following TAVI. Possible impact of DAPT use before TAVI on ischemic complications needs to be investigated in larger populations.

Myocardial viability assessment in 18FDG PET/CT study (18FDG PET myocardial viability assessment).

Accurate identification of viable myocardium is crucial in patient qualification for medical or surgical treatment. Only persons with confirmed cardiac viability will benefit from revascularization procedures. It is also well known, that the amount of viable myocardium assessed preoperatively is the best indicator of long term cardiac event free survival after cardiac intervention.There are several diagnostic approaches used in current clinical practice for assessment of myocardial viability. Analysis of wall thickness or myocardial contraction, evaluation of cardiac perfusion or metabolism can be assessed using following modalities: Echocardiography, Cardiac Molecular Imaging techniques (PET, SPECT), Cardiovascular MR or Cardiovascular CT. The article describes the methods and problems of viability assessment in 18FDG PET study. PET imaging has proved its accuracy and reproducibility for myocardial ischemia and viability assessment. However this unique in its ability for showing the particular substrate metabolism technique has unfortunately some disadvantages: currently achieved PET resolution is 0.4 cm. However the combined devices multislice computed tomography scanners with PET (PET/CT) are now widely used in clinical practice. This combination allows for wider morphologic assessments: coronary calcium scoring and non-invasive coronary angiography may be added to myocardial perfusion/metabolic imaging if necessary.

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.

Simplified protocol of cardiac 18F-fluorodeoxyglucose positron emission tomography viability study in normoglycemic patients with known coronary artery disease ☆

PURPOSE The purpose was to evaluate quality of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) myocardial scans and its correlation with background glucose (BG) after simplified 5% intravenous glucose load protocol. METHODS An intravenous glucose load protocol was applied in 69 normoglycemic patients with confirmed coronary artery disease. The blood glucose level was measured every 15 min. RESULTS Eighty-four percent of images were optimal, 8.7% suboptimal, and 7.3% uninterpretable. The quality of 18F-FDG-PET was BG independent and body mass index dependent (P=.0007). CONCLUSIONS Simplified glucose load protocol is a safe and efficient method of preparation for FDG cardiac viability study in patients with normoglycemia.

Arteriovenous oscillations of the redox potential: Is the redox state influencing blood flow?

Objective: Studies on the regulation of human blood flow revealed several modes of oscillations with frequencies ranging from 0.005 to 1 Hz. Several mechanisms were proposed that might influence these oscillations, such as the activity of vascular endothelium, the neurogenic activity of vessel wall, the intrinsic activity of vascular smooth muscle, respiration, and heartbeat. These studies relied typically on non-invasive techniques, for example, laser Doppler flowmetry. Oscillations of biochemical markers were rarely coupled to blood flow. Methods: The redox potential difference between the artery and the vein was measured by platinum electrodes placed in the parallel homonymous femoral artery and the femoral vein of ventilated anesthetized pigs. Results: Continuous measurement at 5 Hz sampling rate using a digital nanovoltmeter revealed fluctuating signals with three basic modes of oscillations: ∼ 1, ∼ 0.1 and ∼ 0.01 Hz. These signals clearly overlap with reported modes of oscillations in blood flow, suggesting coupling of the redox potential and blood flow. Discussion: The amplitude of the oscillations associated with heart action was significantly smaller than for the other two modes, despite the fact that heart action has the greatest influence on blood flow. This finding suggests that redox potential in blood might be not a derivative but either a mediator or an effector of the blood flow control system.

Assessment of the myocardial FDG-PET image quality with the use of maximal Standardized Uptake Value myocardial to background index. Application of the results in regard to semiquantitative assessment of myocardial viability with cardiac dedicated softwar

BACKGROUND The objective of this study was to semiquantitatively assess the degree of myocardial fluorodeoxyglucose (FDG) uptake in glucose-loaded myocardial viability positron emission tomography/computed tomography (PET/CT) scans, to calculate the myocardial to background index, and correlate the index with image quality assessed on the basis of visual qualitative assessment. MATERIAL AND METHODS The myocardial FDG-PET/CT study was carried out in 69 non-diabetic patients, who had known coronary artery disease, by intravenous injection of 250 ± 70 MBq (range: 180-320 MBq) FDG. Images were interpreted visually and patients were divided into three groups according to the grade of myocardial uptake: optimal, suboptimal, and uninterpretable. Semiquantitative analysis was performed by calculating the standardized uptake value (SUVmax) for myocardium and background (blood pool) activity, and expressed as the myocardial to background (M/B) activity ratio. RESULTS On the basis of visual (qualitative) analysis, 60/69 (86.96%) patients showed optimal quality of FDG cardiac uptake, 3/69 (4.35%) were suboptimal, and uninterpretable FDG PET scan results were found in 6/69 (8.70%) patients. The M/B index was found to be significantly higher in images of optimal vs. suboptimal quality (6.87 ± 3.99 vs. 1.65 ± 0.78 respectively; p < 0.0001). CONCLUSIONS The index ratio of 2.2, which is consistent with the upper borderline value for visually uninterpretable images, was considered the cut-off value for scans of optimal and non-optimal quality.

Insufficient physical activity increases cardiovascular risk in women with low birth mass

Summary Study aim: The aim of the study was to evaluate the relationship between low birth mass and concentration of high-sensitivity C-reactive protein (hsCRP) as a cardiovascular risk factor in young women with various levels of physical activity. Materials and methods: 102 female students aged 19.7 ± 0.8 (18.6-23.0) were included. The study group was divided according to the declared physical activity: high physical activity (HPA, n = 69) and low physical activity (LPA, n = 33). Anthropometric indices were measured: body mass, height, hip and waist circumference. hsCRP levels were obtained from venous blood samples. Birth body mass (BBM) and birth height were collected from medical documentation. Results: Women with low BBM and LPA had a significantly higher concentration of hsCRP than women with low BBM and HPA, as well as women with normal BBM. Conclusions: Low birth mass together with low physical activity is a strong predictor of raised concentration of hsCRP, which correlates with an increased risk of cardiovascular and metabolic diseases. Regular physical activity in women with low birth mass may prevent an increased hsCRP concentration, and as a result decrease the risk of cardiovascular and metabolic diseases.