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Stress echocardiography (SE) is a well established and valid technique, widely used for the diagnostic evaluation of patients with ischemic and nonischemic cardiac diseases. This statement of the Echocardiography Working Group of the Hellenic Society of Cardiology summarizes the consensus of the writing group regarding the applications of SE, based on the expertise of their members and on a critical review of present medical literature. The main objectives of the consensus document include a comprehensive review of SE methodology and training-which focus on the preparation, the protocols used, the analysis of the SE images, and updated, evidence-based knowledge about SE applications on ischemic and nonischemic heart diseases, such as in cardiomyopathies, heart failure, and valvular heart disease., (Copyright © 2021 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

Background: Myocardial iron overload in patients with thalassemia major (TM) is one of the most important complications. The purpose of the study was to identify advanced echocardiography parameters for early identification of myocardial dysfunction during follow-up of patients with TM., Methods: Forty TM patients who were 41 ± 5 years old were included in the study and divided into two groups according to cardiac magnetic resonance T2* results (Group 1: Τ2* > 25 ms, Group 2: Τ2* ≤ 25 ms). Liver T2* parameters were also measured. Conventional and deformational echocardiographic parameters were measured at baseline and approximately 2 years later., Results: Thirty-two patients had Τ2* = 34 ± 4 ms (Group 1), and 8 had Τ2* = 17 ± 9 ms (Group 2). Blood consumption was 185 ± 60 and 199 ± 37 ml/kg/yr (p = 0.64), and liver T2* was 4 ± 5 and 17 ± 21 ms (p = 0.01) in Groups 1 and 2, respectively. At baseline, Group 1 had better left ventricular global longitudinal strain (GLS) (- 22 ± 3 vs. - 18 ± 5, p = 0.01) and similar left ventricular ejection fraction (LVEF) (62 ± 5% vs. 58 ± 10%, p = 0.086) than Group 2. At the 28 ± 11-month follow-up, LVEF, GLS, and T2* values in Group 1 (63 ± 3%, - 21 ± 3%, 34 ± 4 ms) and Group 2 (56 ± 11%, - 17 ± 4%, 17 ± 9 ms) did not change significantly compared to their corresponding baseline values. In 8 patients from Group 1, a worsening (> 15%) in LS (p = 0.001) was detected during follow-up, with a marginal reduction in LVEF., Conclusions: GLS seems to be an efficient echocardiographic parameter for detecting hemochromatosis-related cardiac dysfunction earlier than LVEF. It also seems to be affected by other factors (free radical oxygen, immunogenetic mechanisms or viral infections) in a minority of patients, underscoring the multifactorial etiology of cardiomyopathy.

Congestion is one of the most prominent characteristics of patients presented with decompensated heart failure and it implies unfavorable prognosis for the heart failure patient. Neurohumoral and immuno-inflammatory activation secondary to cardiac dysfunction constitute the pivotal mechanisms driving the heart failure syndrome that results in progressive fluid accumulation. In addition, fluid redistribution between different vascular compartments in human body guided from sympathetic activity constitutes another mechanism for heart failure decompensation. Ultrasound applied in the form of echocardiography provides invaluable data for the assessment of intracardiac filling pressures. The type of renal venous flow can provide the degree of renal congestion and probably insight into the pathophysiology of the decompensation of heart failure. Assessment of lung congestion in the patient with heart failure can be accomplished by lung ultrasonography. Additionally, clinical studies on the role of ultrasound in the management and prognosis of the congested patient are reviewed. Special heart failure population supported with left ventricular assist devices and extracorporeal membrane oxygenation support constitute an area where ultrasound guidance of fluid management has gained important role.

Intimal sarcomas are a very rare medical entity and usually arise from the pulmonary artery or the thoracic aorta. Sarcomas should be considered in the differential diagnosis in patients with suspected mitral valve disease. Echocardiography should be performed as early as possible to establish a prompt diagnosis and management.

Electronic cigarettes (ECs) are nicotine delivery devices that are proposed as tobacco harm reduction products to smokers. Nicotine delivery from ECs is potentially important in their efficacy as smoking substitutes. Herein, nicotine delivery from using a new-generation EC device (variable-wattage, set at 9 W) was evaluated, comparing experienced (vapers) with naïve users (smokers). Twenty-four vapers and 23 smokers participated to the study. They were asked to obtain 10 puffs in 5 minutes and then use the EC ad lib for 60 more minutes (total duration of use: 65 minutes). An 18 mg/mL nicotine-containing liquid was used. Blood samples were obtained at baseline, 5-minutes and every 15 minutes thereafter, while number of puffs and average puff duration were recorded. Although at baseline both groups had similar plasma nicotine levels, smokers consistently exhibited lower levels at all time-periods; at 5-minutes the levels were lower by 46%, while during the subsequent period they were lower by 43% (at 65-minutes) to 54% (at 20-minutes). Both groups took similar number of puffs, but smokers had average puff duration of 2.3 s compared to 3.5 s in vapers. Even in vapers, plasma nicotine levels at 5 minutes were lower than those observed after smoking 1 tobacco cigarette.

Background: Electronic cigarettes have been developed and marketed in recent years as smoking substitutes. However, no studies have evaluated their effects on the cardiovascular system. The purpose of this study was to examine the immediate effects of electronic cigarette use on left ventricular (LV) function, compared to the well-documented acute adverse effects of smoking., Methods: Echocardiographic examinations were performed in 36 healthy heavy smokers (SM, age 36 ± 5 years) before and after smoking 1 cigarette and in 40 electronic cigarette users (ECIG, age 35 ± 5 years) before and after using the device with "medium-strength" nicotine concentration (11 mg/ml) for 7 minutes. Mitral flow diastolic velocities (E, A), their ratio (E/A), deceleration time (DT), isovolumetric relaxation time (IVRT) and corrected-to-heart rate IVRT (IVRTc) were measured. Mitral annulus systolic (Sm), and diastolic (Em, Am) velocities were estimated. Myocardial performance index was calculated from Doppler flow (MPI) and tissue Doppler (MPIt). Longitudinal deformation measurements of global strain (GS), systolic (SRs) and diastolic (SRe, SRa) strain rate were also performed., Results: Baseline measurements were similar in both groups. In SM, IVRT and IVRTc were prolonged, Em and SRe were decreased, and both MPI and MPIt were elevated after smoking. In ECIG, no differences were observed after device use. Comparing after-use measurements, ECIG had higher Em (P = 0.032) and SRe (P = 0.022), and lower IVRTc (P = 0.011), MPI (P = 0.001) and MPIt (P = 0.019). The observed differences were significant even after adjusting for changes in heart rate and blood pressure., Conclusions: Although acute smoking causes a delay in myocardial relaxation, electronic cigarette use has no immediate effects. Electronic cigarettes' role in tobacco harm reduction should be studied intensively in order to determine whether switching to electronic cigarette use may have long-term beneficial effects on smokers' health., Trial Registration: Current Controlled Trials ISRCTN16974547.

Background: Electronic cigarette (EC) use has grown exponentially over the past few years. The purpose of this survey was to assess the characteristics and experiences of a large sample of EC users and examine the differences between those who partially and completely substituted smoking with EC use., Methods: A questionnaire was prepared, translated into 10 different languages and uploaded in an online survey tool. EC users were asked to participate irrespective of their current smoking status. Participants were divided according to their smoking status at the time of participation in two subgroups: former smokers and current smokers., Results: In total, 19,414 participants were included in the analysis, with 88 of them (0.5%) reported not being smokers at the time of EC use initiation. Complete substitution of smoking was reported by 81.0% of participants (former smokers) while current smokers had reduced smoking consumption from 20 to 4 cigarettes per day. They were using ECs for a median of 10 months. They initiated EC use with a median of 18 mg/mL nicotine-concentration liquids; 21.5% used higher than 20 mg/mL. Only 3.5% of participants were using 0-nicotine liquids at the time of the survey. Former smokers were highly dependent (Fagerström Test for Cigarette Dependence = 7) and were heavier smokers (21 cigarettes per day when smoking) compared to current smokers. The most important reasons for initiating EC use for both subgroups was to reduce the harm associated with smoking and to reduce exposure of family members to second-hand smoking. Most considered ECs as less harmful than tobacco cigarettes, while 11.0% considered them absolutely harmless. Side effects were reported by more than half of the participants (59.8%), with the most common being sore/dry mouth and throat; side effects were mild and in most cases were subsequently resolved (partially or completely). Participants experienced significant benefits in physical status and improvements in pre-existing disease conditions (including respiratory disease such as asthma and chronic obstructive lung disease). Being former smoker was independently associated with positive effects in health and improvements in disease conditions., Conclusions: The results of this worldwide survey of dedicated users indicate that ECs are mostly used to avoid the harm associated with smoking. They can be effective even in highly-dependent smokers and are used as long-term substitutes for smoking. High levels of nicotine are used at initiation; subsequently, users try to reduce nicotine consumption, with only a small minority using non-nicotine liquids. Side effects are minor and health benefits are substantial, especially for those who completely substitute smoking with EC use. Further population and interventional studies are warranted.

Introduction: Myxomas are the most common benign tumors of the heart. They vary widely in size, and little is known about their growth rate. The present case report is, we believe the first in bibliography that provides images of an apical left ventricular myxoma from transthoracic echocardiography and computed tomography scans taken a year apart., Case Presentation: We present the rare case of a 65-year-old asymptomatic Caucasian man with an apical left ventricular myxoma that grew over a 12-month period. Our patient underwent successful surgical excision of the tumor and had an uneventful postsurgical recovery period., Conclusions: Left ventricular myxomas are benign and curable tumors. They do not usually present with systemic symptomatology and most of them are diagnosed as sequelae of syncope caused by left ventricular outflow tract obstruction or systemic embolization. Because they are usually removed after diagnosis, the growth rate of myxomas is generally unknown. We present a rare case of the asymptomatic presentation of a left ventricular myxoma and its documented growth during a 12-month period.

Background: A major characteristic of the electronic cigarette (EC) market is the availability of a large number of different flavours. This has been criticised by the public health authorities, some of whom believe that diverse flavours will attract young users and that ECs are a gateway to smoking. At the same time, several reports in the news media mention that the main purpose of flavour marketing is to attract youngsters. The importance of flavourings and their patterns of use by EC consumers have not been adequately evaluated, therefore, the purpose of this survey was to examine and understand the impact of flavourings in the EC experience of dedicated users., Methods: A questionnaire was prepared and uploaded in an online survey tool. EC users were asked to participate irrespective of their current smoking status. Participants were divided according to their smoking status at the time of participation in two subgroups: former smokers and current smokers., Results: In total, 4,618 participants were included in the analysis, with 4,515 reporting current smoking status. The vast majority (91.1%) were former smokers, while current smokers had reduced smoking consumption from 20 to 4 cigarettes per day. Both subgroups had a median smoking history of 22 years and had been using ECs for 12 months. On average they were using three different types of liquid flavours on a regular basis, with former smokers switching between flavours more frequently compared to current smokers; 69.2% of the former subgroup reported doing so on a daily basis or within the day. Fruit flavours were more popular at the time of participation, while tobacco flavours were more popular at initiation of EC use. On a scale from 1 (not at all important) to 5 (extremely important) participants answered that variability of flavours was "very important" (score = 4) in their effort to reduce or quit smoking. The majority reported that restricting variability will make ECs less enjoyable and more boring, while 48.5% mentioned that it would increase craving for cigarettes and 39.7% said that it would have been less likely for them to reduce or quit smoking. The number of flavours used was independently associated with smoking cessation., Conclusions: The results of this survey of dedicated users indicate that flavours are marketed in order to satisfy vapers' demand. They appear to contribute to both perceived pleasure and the effort to reduce cigarette consumption or quit smoking. Due to the fact that adoption of ECs by youngsters is currently minimal, it seems that implementing regulatory restrictions to flavours could cause harm to current vapers while no public health benefits would be observed in youngsters. Therefore, flavours variability should be maintained; any potential future risk for youngsters being attracted to ECs can be sufficiently minimized by strictly prohibiting EC sales in this population group.

Background: Electronic cigarettes (ECs) have been marketed as an alternative-to-smoking habit. Besides chemical studies of the content of EC liquids or vapour, little research has been conducted on their in vitro effects. Smoking is an important risk factor for cardiovascular disease and cigarette smoke (CS) has well-established cytotoxic effects on myocardial cells. The purpose of this study was to evaluate the cytotoxic potential of the vapour of 20 EC liquid samples and a "base" liquid sample (50% glycerol and 50% propylene glycol, with no nicotine or flavourings) on cultured myocardial cells. Included were 4 samples produced by using cured tobacco leaves in order to extract the tobacco flavour., Methods: Cytotoxicity was tested according to the ISO 10993-5 standard. By activating an EC device at 3.7 volts (6.2 watts-all samples, including the "base" liquid) and at 4.5 volts (9.2 watts-four randomly selected samples), 200 mg of liquid evaporated and was extracted in 20 mL of culture medium. Cigarette smoke (CS) extract from three tobacco cigarettes was produced according to ISO 3308 method (2 s puffs of 35 mL volume, one puff every 60 s). The extracts, undiluted (100%) and in four dilutions (50%, 25%, 12.5%, and 6.25%), were applied to myocardial cells (H9c2); percent-viability was measured after 24 h incubation. According to ISO 10993-5, viability of <70% was considered cytotoxic., Results: CS extract was cytotoxic at extract concentrations >6.25% (viability: 76.9 ± 2.0% at 6.25%, 38.2 ± 0.5% at 12.5%, 3.1 ± 0.2% at 25%, 5.2 ± 0.8% at 50%, and 3.9 ± 0.2% at 100% extract concentration). Three EC extracts (produced by tobacco leaves) were cytotoxic at 100% and 50% extract concentrations (viability range: 2.2%-39.1% and 7.4%-66.9% respectively) and one ("Cinnamon-Cookies" flavour) was cytotoxic at 100% concentration only (viability: 64.8 ± 2.5%). Inhibitory concentration 50 was >3 times lower in CS extract compared to the worst-performing EC vapour extract. For EC extracts produced by high-voltage and energy, viability was reduced but no sample was cytotoxic according to ISO 10993-5 definition. Vapour produced by the "base" liquid was not cytotoxic at any extract concentration. Cell survival was not associated with nicotine concentration of EC liquids., Conclusions: This study indicates that some EC samples have cytotoxic properties on cultured cardiomyoblasts, associated with the production process and materials used in flavourings. However, all EC vapour extracts were significantly less cytotoxic compared to CS extract.

Background: Electronic cigarettes (ECs) are alternative-to-smoking nicotine delivery devices; consumers (commonly called vapers) use them in order to reduce or completely substitute smoking. The European Commission has released a proposal for a new Tobacco Product Directive that might reduce availability of nicotine-containing products, including ECs. In this study, the EC use patterns in subjects who have completely substituted smoking with EC use were examined by personal interviews. The study focused on nicotine levels used in order to achieve smoking cessation, reported benefits, associated side effects, and estimation of EC dependence compared with smoking., Methods: Participants were 111 subjects who had completely substituted smoking with EC use for at least 1 month. Smoking abstinence was validated by measuring blood carboxyhemoglobin levels. Nicotine levels at initiation of EC use, at time of smoking cessation, and at time of interview were recorded. Dependence potential was assessed by asking the first question of the Fagerström Test for Cigarette Dependence (time until smoking the first cigarette and until first use of EC in the morning) and questions about perceived past dependence on tobacco cigarettes and present dependence on EC., Results: Forty-two percent of participants reported quitting smoking during the first month of EC use. Liquids with nicotine concentration >15 mg/mL were used by 74% of users at initiation of EC use, while 16.2% had to increase the initial nicotine levels in order to achieve complete smoking abstinence. Seventy-two participants (64.9%) reported that from the time of smoking cessation to the time of the interview (8 months median duration of EC use) they reduced the nicotine concentration they were consuming; however, only 12% of the total sample was using ≤5 mg/mL nicotine concentration at the time of the interview. Side effects were mild and temporary. The vast majority of participants reported better exercise capacity and improved olfactory and gustatory senses. Perceived EC dependenct was significantly lower compared to smoking., Conclusions: Nicotine levels appear to play an important role in achieving and maintaining smoking cessation in the group of motivated subjects studied. High nicotine-containing liquids were used while few mild and temporary side effects were reported. Proposals about regulation should consider the pragmatic use patterns of ECs, especially in consumers who have completely substituted smoking.

Background: Although millions of people are using electronic cigarettes (ECs) and research on this topic has intensified in recent years, the pattern of EC use has not been systematically studied. Additionally, no comparative measure of exposure and nicotine delivery between EC and tobacco cigarette or nicotine replacement therapy (NRTs) has been established. This is important, especially in the context of the proposal for a new Tobacco Product Directive issued by the European Commission., Methods: A second generation EC device, consisting of a higher capacity battery and tank atomiser design compared to smaller cigarette-like batteries and cartomizers, and a 9 mg/mL nicotine-concentration liquid were used in this study. Eighty subjects were recruited; 45 experienced EC users and 35 smokers. EC users were video-recorded when using the device (ECIG group), while smokers were recorded when smoking (SM-S group) and when using the EC (SM-E group) in a randomized cross-over design. Puff, inhalation and exhalation duration were measured. Additionally, the amount of EC liquid consumed by experienced EC users was measured at 5 min (similar to the time needed to smoke one tobacco cigarette) and at 20 min (similar to the time needed for a nicotine inhaler to deliver 4 mg nicotine)., Results: Puff duration was significantly higher in ECIG (4.2 ± 0.7 s) compared to SM-S (2.1 ± 0.4 s) and SM-E (2.3 ± 0.5 s), while inhalation time was lower (1.3 ± 0.4, 2.1 ± 0.4 and 2.1 ± 0.4 respectively). No difference was observed in exhalation duration. EC users took 13 puffs and consumed 62 ± 16 mg liquid in 5 min; they took 43 puffs and consumed 219 ± 56 mg liquid in 20 min. Nicotine delivery was estimated at 0.46 ± 0.12 mg after 5 min and 1.63 ± 0.41 mg after 20 min of use. Therefore, 20.8 mg/mL and 23.8 mg/mL nicotine-containing liquids would deliver 1 mg of nicotine in 5 min and 4 mg nicotine in 20 min, respectively. Since the ISO method significantly underestimates nicotine delivery by tobacco cigarettes, it seems that liquids with even higher than 24 mg/mL nicotine concentration would be comparable to one tobacco cigarette., Conclusions: EC use topography is significantly different compared to smoking. Four-second puffs with 20-30 s interpuff interval should be used when assessing EC effects in laboratory experiments, provided that the equipment used does not get overheated. Based on the characteristics of the device used in this study, a 20 mg/mL nicotine concentration liquid would be needed in order to deliver nicotine at amounts similar to the maximum allowable content of one tobacco cigarette (as measured by the ISO 3308 method). The results of this study do not support the statement of the European Commission Tobacco Product Directive that liquids with nicotine concentration of 4 mg/mL are comparable to NRTs in the amount of nicotine delivered to the user.

Background: The purpose of the study was to evaluate the acute and chronic effect of smoking on left ventricular function in healthy heavy smokers by conventional Doppler flow, tissue Doppler, and two-dimensional speckle tracking echocardiography (2D-STE)., Methods: Echocardiograms were performed in 42 healthy heavy (>20 cigarettes/day) smokers (age 34 ± 5 years), before (group SM-1), 15 minutes (SM-2) and 30 minutes (SM-3) after starting smoking 2 cigarettes. Nonsmokers (n = 41, age 33 ± 4 years) served as controls. Transmitral flow, isovolumetric relaxation time (IVRT), and myocardial performance index (MPI) were measured. Tissue velocity measurements were averaged from lateral and septal mitral annulus. Longitudinal strain (GS), systolic (SRs), early diastolic (SRe), late diastolic (SRa), and isovolumetric relaxation (SRivr) strain rate were measured. The percent change in strain from end-systole to the first one-third of diastole (SI-DI = [(GS - strain at one-third diastole)/GS] × 100) was also measured., Results: IVRT and MPI were increased and early diastolic mitral annular velocity was decreased in SM-2; they returned to baseline in SM-3. There was no difference in GS and SRs. SRe and SRivr were reduced in SM-1 (P < 0.05), and remained significantly reduced in SM-2 and SM-3. SI-DI was lower in SM-1 (P = 0.011) and was further reduced in SM-2 and SM-3 (P < 0.001)., Conclusion: Acute and chronic smoking inhalation has adverse effects on myocardial function in healthy heavy smokers. 2D-STE is able to detect both baseline differences and late acute effects of smoking., (© 2012, Wiley Periodicals, Inc.)

Beta-thalassemia major (beta-TM), patients, asymptomatic and with preserved left ventricular ejection fraction (LVEF) were studied echocardiographically. Group A (26 patients), on deferiprone (L1) and deferoxamine (DFO) combination therapy (L1: 80 +/- 27 mg/kg/day, DFO: 160 +/- 87 mg/kg/week) and group B (35 patients) on DFO monotherapy (240 +/- 40 mg/kg/week) for the last 2 years were compared. Another group, C (14 patients), switched to L1 (74 +/- 15 mg/kg/day) plus DFO (158 +/- 48 mg/kg/week) for 20-30 months, was prospectively studied for 2 years. In group A, MRI T2* values were increased and improved in group C during follow-up. The LVEF was better in group A than in group B, while such an improvement was also detected in the group C follow-up study. The Tissue Doppler study E' velocity and E/E' ratio was not different. Similarly, in the group C follow-up no significant change in E/E' ratio was detected. It seems that although LVEF significantly improves with combined therapy, diastolic function indexes do not show a similar change.

Background: Although the superiority of low-osmolar over high-osmolar contrast agents in prevention of contrast-induced acute kidney injury (CI-AKI) is generally accepted, the relative nephrotoxicity of iso-osmolar over low-osmolar agents has not yet clearly defined. We examined the incidence of CI-AKI according to the type of contrast agent used in a randomized study of ascorbic acid for CI-AKI prevention., Methods: A total of 222 patients with baseline serum creatinine >or=1.2 mg/dL who were undergoing a coronary procedure and who were randomized to receive ascorbic acid or placebo were evaluated. The iso-osmolar agent iodixanol was used in 144 patients, whereas low-osmolar non-ionic agents were used in 78 patients (iomeprol, n = 40; iobitridol, n = 30; iopentol, n = 8). CI-AKI was defined by an absolute serum creatinine increase of >or=0.5 mg/dL or a relative increase of >or=25% measured 2 to 5 days after the procedure., Results: The groups of patients who received iso-osmolar and low-osmolar non-ionic agents were well balanced in terms of demographic, clinical, and procedural characteristics. The overall CI-AKI incidence was 14.6% for the iso-osmolar iodixanol versus 14.1% for the combined low-osmolar non-ionic agents (iomeprol, 10%; iobitridol, 10%; iopentol, 50%). For iodixanol, the incidence of CI-AKI was 7.4% for patients randomized to receive ascorbic acid and 21.6% for placebo (P = 0.02). The corresponding incidences for the low-osmolar non-ionic agents were 9.1% and 20.6%, respectively (P = 0.19)., Conclusion: No differences in CI-AKI incidence were apparent among patients receiving non-ionic iso-osmolar iodixanol and non-ionic low-osmolar contrast agents. The preventative effect of ascorbic acid was also similar.

Purpose: To investigate the effect of heart rate frequency (HRF) and heart rate variability (HRV) on radiation exposure, image quality, and diagnostic performance to help detect significant stenosis (> or =50% lumen diameter reduction) by using adaptive electrocardiographic (ECG) pulsing at dual-source (DS) spiral computed tomographic (CT) coronary angiography., Materials and Methods: Institutional review committee approval and informed consent were obtained. No prescan beta-blockers were applied. Unenhanced CT and CT coronary angiography with adaptive ECG pulsing were performed in 927 consecutive patients (600 men, 327 women; mean age, 60.3 years +/- 11.0 [standard deviation]) divided in three HRF groups: low, intermediate, and high (< or =65, 66-79, and > or =80 beats/min, respectively), and four HRV groups given mean interbeat difference (IBD) during CT coronary angiography: normal, minor, moderate, and severe (IBDs of 0-1, 2-3, 4-10, and >10, respectively). Radiation exposure and image quality were also evaluated. In 444 of these, diagnostic performance was presented as sensitivity, specificity, positive predictive values (PPVs), and negative predictive values and likelihood ratios with corresponding 95% confidence intervals by using quantitative coronary angiography as the reference standard., Results: CT coronary angiography yielded good image quality in 98% of patients and no significant differences in image quality were found among HRF and HRV groups. Radiation exposure was significantly higher in patients with low versus high HRF and in patients with severe versus normal HRV. No significant differences among HRF and HRV groups in image quality and diagnostic performance were found. A nonsignificant trend was found toward a lower specificity and PPV in patients with a high HRF or severe HRV when compared with low HRF or normal HRV in patients with a low calcium score (Agatston score <100)., Conclusion: DS spiral CT coronary angiography performed with adaptive ECG pulsing results in preserved diagnostic image quality and performance independent of HRF or HRV at the cost of limited dose reduction in arrhythmic patients.

Computed tomographic coronary angiography (CTCA) can noninvasively identify calcified and noncalcified coronary plaques. The aim of this study was to compare the phenotypes of all plaques and of culprit plaques between patients with unstable angina pectoris (UAP) and those with stable angina pectoris (SAP), because plaque characteristics may differ between these patients. In 110 patients with UAP and 189 with SAP from a multicenter study comparing 64-slice CTCA with conventional coronary angiography, the number and phenotypes (noncalcified, mixed, and calcified) of coronary plaques were compared. In a subanalysis in 50 patients with UAP and 64 with SAP, culprit plaque characteristics, including culprit plaque cross-sectional area relative to total vessel cross-sectional area, culprit plaque length, remodeling index, and spotty calcification, were determined. Odds ratios for the presence of UAP, adjusted for clinical variables and the total number of plaques, were calculated for plaque characteristics on CTCA. Although the number of plaques was similar for patients with UAP and those with SAP, plaques in patients with UAP were more frequently noncalcified than in patients with SAP. The odds ratio for UAP was 1.3 (95% confidence interval [CI] 1.1 to 1.5) per noncalcified plaque. In the culprit plaque subanalysis, odds ratios for UAP were 0.99 (95% CI 0.96 to 1.01) per millimeter culprit plaque length, 2.7 (95% CI 1.2 to 6.4) for noncalcified culprit plaque, and 1.06 (95% CI 0.99 to 1.13) per percentage relative culprit plaque cross-sectional area. No significant relation was found between remodeling index or spotty calcification and UAP. In conclusion, noncalcified plaques and large noncalcified culprit plaques are more frequently found in patients with UAP than in those with SAP.

Purpose: To evaluate the effects of standard and optimal electrocardiographic (ECG) pulsing on diagnostic performance, radiation dose, and cancer risk in symptomatic patients in a "real-world" clinical setting., Materials and Methods: The institutional review board approved the study, and all patients gave informed consent. Dual-source computed tomographic (CT) coronary angiography was performed in 436 symptomatic patients (301 men, 135 women; mean age, 61.6 years +/- 10.6 [standard deviation]; age range, 23-89 years) referred for conventional coronary angiography. Standard and optimal ECG pulsing was performed in 327 and 109 patients, respectively. The diagnostic performance of dual-source CT coronary angiography for detection of significant stenosis (>or=50 luminal diameter reduction), with quantitative coronary angiography as the reference standard, was reported as sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios. The mean effective radiation dose, additional fatal cancer risk, and age- and sex-specific cancer risks related to one CT coronary angiographic examination were determined from data averaged over the study population., Results: Mean effective doses with standard and optimal ECG pulsing were 14.2 mSv +/- 3.2 and 10.7 mSv +/- 3.6, respectively. Optimal ECG pulsing resulted in a 43% overall reduction in mean effective radiation dose and cancer risk compared with a nonpulsing protocol (18.8 mSv +/- 3.5) and a 25% overall reduction in mean effective dose compared with the standard pulsing protocol. At patient-by-patient analysis, CT coronary angiography with standard ECG pulsing yielded sensitivity, specificity, and positive and negative predictive values of 100% (95% confidence interval [CI]: 99%, 100%), 85% (95% CI: 81%, 88%), 94% (95% CI: 91%, 96%), and 99% (95% CI: 98%, 100%), respectively, for detection of significant stenosis. Optimal ECG pulsing yielded similar results: Sensitivity, specificity, and positive and negative predictive values were 100% (95% CI: 100%, 100%), 88% (95% CI: 82%, 94%), 97% (95% CI: 93%, 100%), and 100%, respectively., Conclusion: Compared with a nonpulsing protocol, optimal ECG pulsing resulted in significant (P < .001) reductions in patient radiation dose and cancer risk (up to 55% reduction in patients with high heart rates) while preserving the diagnostic performance of dual-source CT coronary angiography., ((c) RSNA, 2009.)

Background: Ischemia modified albumin (IMA) is considered a biomarker of myocardial ischemia. We sought to investigate whether IMA plasma levels change during pharmacological stress test, in patients with stable coronary artery disease., Methods: We studied 37 patients undergoing non-invasive evaluation with a pharmacological stress test, either with radionuclide myocardial perfusion imaging with adenosine or stress echocardiography with dobutamine. Peripheral venous samples were collected before the stress test (baseline), at the end of adenosine infusion or at the peak dose of dobutamine and 60 min after the completion of the stress test for IMA measurement., Results: IMA plasma levels significantly increased at peak vs. baseline (91.28+/-9.59 U/ml vs. 97.97+/-9.69 U/ml, p<0.0001) and subsequently, decreased significantly at 60 min compared to peak (97.97+/-9.69 U/ml vs. 94+/-15.22 U/ml, p=0.016), returning to values similar to those at baseline (p=0.134). Similarly, in patients with a negative stress test, IMA significantly increased at peak compared to baseline (91.08+/-10.03 U/ml vs. 99.58+/-8.43 U/ml, p=0.006) and returned to baseline at 60 min (99.58+/-8.43 U/ml vs. 91.83+/-7.93 U/ml, p=0.019), the 60 minute levels being similar to baseline values (p=0.212). Conversely, in patients with a positive stress test, IMA significantly increased at peak compared to baseline (91.38+/-10.13 U/ml vs. 97.17+/-10.34 U/ml, p=0.006) and although decreased at 1 h, this did not reach statistical significance compared either to the baseline or to the peak values (95.04+/-17.76 U/ml vs. 91.38+/-10.13 U/ml, p=0.315 and 95.04+/-17.76 U/ml vs. 97.17+/-10.34 U/ml, p=0.235, respectively)., Conclusion: IMA plasma levels change significantly during pharmacologic stress testing, in patients with coronary artery disease, but with no difference between the positive and the negative tests.

Objective: We investigated the relation between the endothelin system and atrial fibrillation., Background: Endothelin has been implicated in the pathophysiology of atrial fibrillation, but the exact role of A- and B-receptors is unknown., Methods: We obtained right atrial biopsies from patients in sinus rhythm and preserved left ventricular function, undergoing off-pump coronary artery bypass grafting. The expression of endothelin, A- and B-receptors was measured using real time reverse-transcribed polymerase chain reaction., Results: We studied 52 patients (45 male, mean age 66+/-1 years, mean ejection fraction 52+/-1%). During a 5-day post-operative period, persistent atrial fibrillation occurred in 15 patients (28.8%). Endothelin mRNA expression was comparable in patients who subsequently developed atrial fibrillation and in those maintaining sinus rhythm. However, the former group displayed down-regulation of endothelin A- (by approximately 60%, p=0.0059) and of B-receptors (by approximately 40%, p=0.0084). The decreased endothelin A-receptor expression could predict atrial fibrillation occurrence (Wilks lambda=0.86, F=6.16, p=0.017)., Conclusion: Decreased endothelin A- and B-receptor expression is associated with atrial fibrillation after bypass surgery.

Background: Several indices have been proposed in order to better evaluate chronic mitral regurgitation, however, none of them is unique, thus underlying the diagnostic deficiency. We aimed to investigate the role of long axis contraction in both ventricles in patients with non-ischemic asymptomatic mitral regurgitation (MR)., Methods: Eighty-nine patients (40 men, mean age 59.9+/-13.5 years) with non-ischemic asymptomatic MR along with 50 healthy controls were studied. An echocardiographic, including tissue Doppler imaging study, an exercise radionuclide cineangiography and a cardiac catheterization were also performed., Results: Fifty of 89 patients (56.2%) had a normal response of left ventricular (LV) ejection fraction on exercise. LV end-diastolic diameter and volume index were significantly higher in patients with an impaired LV response. Moreover, systolic wave maximal velocity and systolic wave slope both at the lateral wall and at the inter-ventricular septum were significantly lower in patients with an impaired LV response. Systolic wave maximal velocity at the lateral wall was the index that best predicted LV response to exercise; while a cutoff value of 9.5 cm/s predicted an impaired LV response with a sensitivity of 96% and a specificity of 100%. MR as defined by the width of vena contracta, was mild/moderate in 78% of patients with a systolic wave maximal velocity at the lateral wall >9.5 cm/s and severe in 69.2% of patients with a velocity <9.5 cm/s., Conclusion: In patients with asymptomatic non-ischemic MR, the evaluation of LV long axis contraction at rest can unmask a subnormal LV functional status.

Background: The aim of this study was to determine if stent length is by itself a risk factor for intimal proliferation and restenosis. Long lesions represent an independent risk factor for restenosis after coronary stent implantation. A longer stented segment might result in a higher probability of restenosis., Methods: Twenty-two 7-month-old male farm pigs underwent implantation of two steel stents, one short (8 mm length) and one long (16 mm length), in the right coronary artery. The pigs were sacrificed 28 days after stent implantation and histomorphometric analysis of the coronary arteries was performed for neointimal area proliferation and area stenosis evaluation., Results: Seventeen short stents and 19 long stents were finally implanted. There were no differences in neointimal proliferation (1.84 +/- 0.64 mm2 vs. 1.81 +/- 0.94 mm2, p = 0.84), area stenosis (40 +/- 9% vs. 41 +/- 19%, p = 0.86) and lumen area (2.96 +/- 1.30 mm2 vs. 2.51 +/- +/- 1.18 mm2, p = 0.21) between the short stent group and the long stent group, respectively., Conclusions: These data suggest that stent length by itself does not influence restenosis extent in the porcine model.

Background: Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis and is implicated in the development of diabetic microvascular and macrovascular disease., Methods: The expression of total VEGF, VEGF splice variants (VEGF(121), VEGF(145), VEGF(148), VEGF(165), VEGF(183) and VEGF(189)), VEGFR-1 and VEGFR-2, was investigated in biopsies from the right atrium and left internal mammary artery (LIMA) of 32 non-diabetic and 20 diabetic patients undergoing coronary artery bypass grafting., Results: Diabetes was independently negatively correlated to total VEGF mRNA expression in atrium. Total VEGF, VEGF(121) and VEGF(165) mRNA levels were upregulated in the LIMA of diabetics vs. non-diabetics. The expression of VEGF receptors in atrium and LIMA was similar between these groups. VEGF(121) and VEGF(165) were the major variants expressed, followed by VEGF(189) and VEGF(183), while VEGF(148) and VEGF(145) were detected in small amounts. The expression profile of VEGF splice variants displayed significant heterogeneity between the examined tissues., Conclusions: This is the first study to quantify VEGF splice variants expression in cardiac and vascular tissue. Our results could help elucidate the role of VEGF splice variants in diabetic complications.

The long-term prognostic significance of left ventricular (LV) long-axis contraction was investigated prospectively in 65 consecutive patients aged 58+/-15 years with asymptomatic aortic regurgitation, normal LV ejection fraction at rest, and no coronary artery or aortic root disease. A complete transthoracic echocardiographic study was performed at baseline and 12 months later. In 24 of 65 patients with peak systolic wave velocity at the lateral mitral annulus (LatS)<9 cm/s, LV diameter (p<0.01), volume (por=9 cm/s, none of these parameters was significantly affected during follow-up. Aortic valve replacement was performed in 6 of 24 patients (25%) with peak systolic wave velocity at the lateral mitral annulus<9 cm/s and none with peak systolic wave velocity at the lateral mitral annulus>or=9 cm/s. In patients with peak systolic wave velocity at the lateral mitral annulus<9 cm/s, a cut-off value of 6.25 cm/s predicted aortic valve replacement within the next year with 97% sensitivity and 83% specificity. In conclusion, ventricular long-axis contraction seems to be a reliable indicator for outcome prediction in patients with asymptomatic aortic regurgitation.

Objective: Attempts to demonstrate preconditioning during repeated angioplasty balloon inflations (BIs) have not been universally successful. The main obstacle is that the first BI is unreliable, due to the variable degrees of occlusion by the deflated balloon. In the present study, we examined whether ST segment elevation decreases and evaluated its relation to collateral recruitment during repeated angioplasty BIs in the pig., Methods and Results: Twenty male pigs, 7 months old, under general anesthesia, underwent 3 repeated BIs of 120 s, with a 5-min interval between them, in the left anterior descending artery or the right coronary artery. A pressure wave wire was used for the measurement of coronary wedge pressure and to obtain the intracoronary ST segment elevation. Intracoronary ST segment elevation was 1.97 +/- 0.76 mV during the 1st BI, 2.09 +/- 0.82 mV during the 2nd BI and 1.84 +/- 0.82 mV during the 3rd BI (p = n.s.). Coronary wedge pressure was 12 +/- 6, 18 +/- 18 and 20 +/- 20 mm Hg (p < 0.05 vs. 1st BI) during the 3 BIs, respectively., Conclusion: Repeated BIs do not diminish ST segment elevation in the pig model, even though coronary collateral recruitment is promoted., ((c) 2007 S. Karger AG, Basel.)

Background: Endothelial dysfunction and oxidative stress are believed to be central mechanisms in atherogenesis. We aimed to determine the effects of tirofiban on oxidative stress and neutrophil-endothelium interaction markers in patients with acute coronary syndromes (ACS)., Materials and Methods: We measured malondialdehyde (MDA), interleukin-6 (IL-6) and soluble endothelial intercellular and vascular adhesion molecules (sICAM-1 and sVCAM-1) on admission, at 48 and 72 h and on 5th day of hospitalization in 34 patients (age 66.5+/-1.8 years) with ACS. Patients with recurrent angina, changes on the electrocardiogram and/or elevated troponin I received intravenously tirofiban for 48 h and the others received normal saline., Results: Baseline concentrations of all markers did not differ significantly and compared with placebo, tirofiban infusion markedly reduced MDA, IL-6, sICAM-1 and sVCAM-1 at 48 h (-31+/-6% vs. 84+/-49%, p=0.007, -12+/-14% vs. 23+/-10%, p=0.05, -20+/-6% vs. 36+/-25%, p=0.04 and -10+/-5% vs. 6+/-5%, p=0.02, respectively). Relative to baseline, significant reductions were observed for all 4 markers at 72 h and day 5 (p<0.05)., Conclusion: Tirofiban potentiates the decline in oxidative stress and may reverse abnormal endothelial activation in patients with ACS. This benefit seems to remain over the following 5 days.

Aim: To investigate whether remote ischaemic preconditioning (RIPC) can attenuate the inflammatory response and enzyme leakage that can occur after uncomplicated routine percutaneous coronary intervention (PCI)., Methods: 41 consecutive normotensive patients with stable angina and single-vessel disease were assigned to be exposed to RIPC (n = 20) or not (control group; n = 21) before elective PCI with stent implantation. RIPC was induced by three cycles of 5-min ischaemia-reperfusion of both upper limbs (inflation/deflation of blood pressure cuff). C reactive protein (CRP), creatine phosphokinase (CK), CK cardiac isoenzyme (CK-MB) and troponin I (TNI) were serially measured for 48 h., Results: No difference in baseline values was observed between the groups. The CRP rose significantly (p<0.001) and at 48 h was similarly increased (>fourfold) in both groups (15.7 (2.6) v 14.0 (3.3) mg/l, RIPC v control; p = NS). However, sub-group analysis on the basis of statin use showed that the highest rise was in the group of patients with RIPC not taking statins and was significantly greater than in patients with RIPC taking statins (23.8 (3.71) v 11.4 (3.0) mg/l, respectively, p<0.01). Both CK-MB and TNI leakage were raised (slightly but significantly) after PCI in controls at 24 h compared with baseline values. However, this small rise was significantly worse after RIPC (CK-MB, 1.33 (0.27) v 3.57 (0.97) ng/ml, p<0.01; TNI, 0.255 (0.059) v 0.804 (0.232) ng/ml, p<0.05, respectively at 24 h). The increase was more marked in the RIPC subgroup not taking statins., Conclusions: RIPC does not reduce, but exacerbates, the enzyme and TNI release from the heart after single-vessel angioplasty with stent. Furthermore, the increased circulating CRP remains raised. It seems that there is an enhanced inflammatory response after RIPC in the absence of statin treatment.

Background: 17-Beta-estradiol inhibits smooth muscle cell proliferation and migration and accelerates endothelial cell repair in response to balloon injury. The aim of this study was to determine whether administration of estrogen is associated with decreased neointimal hyperplasia after stenting in the porcine model., Methods and Results: Twenty-two farm female pigs 7 months old were oophorectomized and at the third day normal saline (11 pigs) or 20 mg of estradiol valerate (11 pigs), modified release, were administered intramuscularly. At the 10th day after oophorerectomy, 1 or 2 stainless steel stents were implanted in the right coronary artery in each pig, and at the 17th day, normal saline or 10 mg estradiol valerate, modified release, were administered intramuscularly in the two groups. Pigs were sacrificed 28 days after stent implantation and histomorphometric analysis of the coronary arteries was performed (20 stents from the estrogen and 18 stents from the control groups). In the estrogen group, neointimal proliferation area was 1.42+/-0.55 mm(2), whereas in the control group, 1.96+/-0.89 mm(2) (p=0.02). Area stenosis was 39+/-13% and 49+/-16% in the two groups, respectively (p=0.07). Re-endothelialization was 2.67+/-0.34 and 2.22+/-0.46 in the two groups, respectively (p<0.010). The injury score was similar between the two groups., Conclusions: These data suggest that intramuscular administration of estrogen accelerates the endothelial cell repair in response to injury and reduces intimal hyperplasia in the porcine model.

Aim: We examined whether there is a differential effect of endothelin-A antagonism on coronary artery compliance in type 2 diabetes mellitus compared to non-diabetic patients., Patient and Methods: We examined 32 patients, 11 type 2 diabetes mellitus and 21 non-diabetic patients, with atherosclerotic epicardial arteries free of significant luminal stenoses. Intracoronary BQ-123 (6 micromol), an endothelin-A receptor antagonist, was infused over 20 min. The artery lumen area in the proximal arterial segment was measured at end diastole and end systole before and after BQ-123 administration using an intravascular ultrasound catheter. Calculations were made of normalized arterial compliance index, in mm Hg(-1) x 10(3) and of arterial stiffness index beta., Results: Pulse pressure and heart rate did not change after BQ-123. In type 2 diabetes mellitus, normalized compliance index decreased from 1.79+/-1.36 at baseline to 1.29+/-0.82 after BQ-123 administration, whereas in non-diabetic patients it increased from 2.10+/-1.36 to 3.00+/-2.07 (p<0.05 versus baseline) (F=6.39, p=0.02). In type 2 diabetes mellitus, beta index increased from 1.97+/-0.53 to 2.46+/-0.95, whereas in non-diabetic patients it decreased from 1.83+/-0.95 to 1.63+/-0.84 (F=7.80, p=0.009). Big endothelin-1 at baseline was correlated with the baseline beta index (p<0.0001, r=0.68)., Conclusions: Big endothelin-1 is correlated with the coronary artery stiffness. The effect of endogenous endothelin-1 on coronary artery stiffness is impaired in type 2 diabetes mellitus. This may have important therapeutic implications with respect to the introduction of endothelin receptor antagonists as cardiovascular therapeutic agents.