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The lung can experience different oxygen concentrations, low as in hypoxia, high as under supplemental oxygen therapy, or oscillating during intermittent hypoxia as in obstructive sleep apnea or intermittent hypoxia/hyperoxia due to cyclic atelectasis in the ventilated patient. This study aimed to characterize the oxygen-condition-specific protein composition of extracellular vesicles (EVs) released from human pulmonary microvascular endothelial cells in vitro to decipher their potential role in biotrauma using quantitative proteomics with bioinformatic evaluation, transmission electron microscopy, flow cytometry, and non-activated thromboelastometry (NATEM). The release of vesicles enriched in markers CD9/CD63/CD81 was enhanced under intermittent hypoxia, strong hyperoxia and intermittent hypoxia/hyperoxia. Particles with exposed phosphatidylserine were increased under intermittent hypoxia. A small portion of vesicles were tissue factor-positive, which was enhanced under intermittent hypoxia and intermittent hypoxia/hyperoxia. EVs from treatment with intermittent hypoxia induced a significant reduction of Clotting Time in NATEM analysis compared to EVs isolated after normoxic exposure, while after intermittent hypoxia/hyperoxia, tissue factor in EVs seems to be inactive. Gene set enrichment analysis of differentially expressed genes revealed that EVs from individual oxygen conditions potentially induce different biological processes such as an inflammatory response under strong hyperoxia and intermittent hypoxia/hyperoxia and enhancement of tumor invasiveness under intermittent hypoxia.

Heart failure (HF) is usually suspected by clinical history, symptoms, physical examination, electrocardiogram findings, and natriuretic peptides' values. However, echocardiography and other imaging techniques play an essential role in supporting HF diagnosis. Thanks to its non-invasiveness and safety, transthoracic echocardiography is the first-level technique of choice to assess myocardial structure and function, trying to establish the diagnosis of HF with reduced, mildly reduced, and preserved ejection fraction. The role of echocardiography is not limited to diagnosis but it represents a crucial tool in guiding therapeutic decision-making and monitoring response to therapy. Over the last decades, several technological advancements were made in the imaging field, aiming at better understanding the morphofunctional abnormalities occurring in cardiovascular diseases. The purpose of this review article is to summarize the incremental role of imaging techniques (in particular cardiac magnetic resonance and myocardial scintigraphy) in HF, highlighting their essential applications to HF diagnosis and management., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The aim is to investigate, by means of speckle tracking echocardiography, left ventricular (LV) contractile function at rest and during dipyridamole stress in patients with coronary microvascular dysfunction (CMD). 59 patients (39% women, mean age 65.6 ± 6.1 years) with history of chest pain and without obstructive coronary artery disease (CAD) underwent dipyridamole stress echocardiography. Coronary flow was assessed in the left anterior descending coronary artery. Coronary flow reserve (CFR) was determined as the ratio of hyperaemic to baseline diastolic coronary flow velocity. CMD was defined as CFR < 2. Global longitudinal strain (GLS) was measured at rest and at peak dose. Nineteen patients (32%) among the overall population showed CMD. Baseline GLS was significantly lower in patients with CMD (- 16.8 ± 2.7 vs. - 19.1 ± 3.1, p < 0.01). A different contractile response to dipyridamole infusion was observed between the two groups: GLS significantly increased up to peak dose in patients without CMD (from - 19.1 ± 3.1 to - 20.2 ± 3.1, p < 0.01), and significantly decreased in patients with CMD (from - 16.8 ± 2.7 to - 15.8 ± 2.7, p < 0.01). There was a significant inverse correlation between CFR and ∆GLS (r = - 0.82, p < 0.01). Rest GLS and GLS response to dipyridamole stress are markedly impaired among patients with chest pain syndrome, non-obstructive CAD and CMD, reflecting subclinical LV systolic dysfunction and lack of LV contractile reserve due to underlying myocardial ischemia., (© 2022. Springer Japan KK, part of Springer Nature.)

Spontaneous Coronary Artery Dissection (SCAD) refers to the spontaneous separation of the layers of the vessel wall caused by intramural hemorrhage, with or without an intimal tear. The "typical" SCAD patient is a middle-aged woman with few traditional cardiovascular risk factors, and it's frequently associated with pregnancy. Because of its low incidence, its pathophysiology is not fully understood. SCAD presents as an acute coronary syndrome, with chest pain, dyspnea, syncope, or heartbeat, even if diagnosis and clinical handling are different: coronary angiography is currently the main tool to diagnose SCAD; however, in doubtful cases, the use of both invasive and noninvasive cardiovascular imaging methods such as intravascular ultrasound or optical coherence tomography may be necessary. This paper aims to review the current state of knowledge on SCAD to address its demographic features, clinical characteristics, management, and outcomes, focusing on diagnostic algorithms and main multimodality imaging techniques.

Transcranial Doppler (TCD) ultrasonography is a rapid, noninvasive, real-time, and low-cost imaging technique. It is performed with a low-frequency (2 MHz) probe in order to evaluate the cerebral blood flow (CBF) and its pathological alterations, through specific acoustic windows. In the recent years, TCD use has been expanded across many clinical settings. Actually, the most widespread indication for TCD exam is represented by the diagnosis of paradoxical embolism, due to patent foramen ovale, in young patients with cryptogenic stroke. In addition, TCD has also found useful applications in neurological care setting, including the following: cerebral vasospasm following acute subarachnoid hemorrhage, brain trauma, cerebrovascular atherosclerosis, and evaluation of CBF and cerebral autoregulation after an ischemic stroke event. The present review aimed to describe the most recent evidences of TCD utilization from neurological to cardiological setting., (© 2022 Wiley Periodicals LLC.)

Aims: The real effects of the chronic consumption of anabolic-androgenic steroids (AASs) on cardiovascular structures are subjects of intense debate. The aim of the study was to detect by speckle tracking echocardiography (STE) right ventricular (RV) and left ventricular (LV) dysfunction at rest and during exercise stress echocardiography (ESE) in athletes abusing AAS., Methods and Results: One hundred and fifteen top-level competitive bodybuilders were selected (70 males), including 65 athletes misusing AAS for at least 5 years (users), 50 anabolic-free bodybuilders (non-users), compared to 50 age- and sex-matched healthy sedentary controls. Standard Doppler echocardiography, STE analysis, and lung ultrasound at rest and at peak supine-bicycle ESE were performed. Athletes showed increased LV mass index, wall thickness, and RV diameters compared with controls, whereas LV ejection fraction was comparable within the groups. left atrial volume index, LV and RV strain, and LV E/Em were significantly higher in AAS users. Users showed more B-lines during stress (median 4.4 vs. 1.25 in controls and 1.3 in non-users, P < 0.01 vs. users). By multivariable analyses, LV E/Ea (beta coefficient = 0.35, P < 0.01), pulmonary artery systolic pressure (beta = 0.43, P < 0.001) at peak effort and number of weeks of AAS use per year (beta = 0.45, P < 0.001) emerged as the only independent determinants of resting RV lateral wall peak systolic two-dimensional strain. In addition, a close association between resting RV myocardial function and VO2 peak during ESE was evidenced (P < 0.001), with a powerful incremental value with respect to clinical and standard echocardiographic data., Conclusions: In athletes abusing steroids, STE analysis showed an impaired RV systolic deformation, closely associated with reduced functional capacity during physical effort, and-during exercise-more pulmonary congestion., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Atrial fibrillation (AF) can lead to embolic stroke and in subjects with non-valvular AF most of thrombi are sited in the left atrial appendage (LAA). LAA is a structure located in the free wall of heart with a wide variable and complex anatomy. LAA occlusion (LAAO) could be taken in consideration in subjects with non-valvular AF and who cannot have long-term anticoagulant therapy. It is a complex preventive procedure given the high variability of patients characteristics and several LAAO devices available nowadays. Moreover, the ideal postprocedural antithrombotic strategy is still unclear. In this review we aim to describe clinical features of patients committed for LAA occlusion and the function of multimodality imaging in subjects selection, procedural management and follow up., Competing Interests: The authors declare no conflict of interest., (© 2021 The Author(s). Published by IMR Press.)

Non-invasive Doppler ultrasonographic study of cerebral arteries (transcranial Doppler, TCD) has been extensively applied on both outpatient and inpatient settings. It is performed placing a low-frequency (≤2 MHz) transducer on the scalp of the patient over specific acoustic windows, in order to visualize the intracranial arterial vessels and to evaluate the cerebral blood flow velocity and its alteration in many different conditions. Nowadays a valid indication for TCD in the outpatient setting is the research of right-to-left shunting, responsible for the so-called "paradoxical embolism", most often due to patency of foramen ovale, which is responsible for the majority of cryptogenic strokes occurring in patients younger than 55 years. TCD also allows to classify the grade of severity of such shunts using the so-called "microembolic signal grading score". Therefore, TCD is an essential cardiological exam for the detection of patent foramen ovale, assuming an important role as a first-level examination to guide the subsequent diagnostic-therapeutic management. In addition, TCD has found many useful applications in neurocritical care practice. It is useful for the identification of intracranial vascular stenosis and for the assessment of critical conditions including vasospasm in subarachnoid hemorrhage, traumatic brain injury and brain stem death. It is also used to evaluate cerebral hemodynamic changes after stroke, to investigate cerebral pressure autoregulation, and for the clinical evaluation of cerebral vasomotor reactivity.

Measurement of direct oral anticoagulants (DOACs) activity is not routinely necessary. Indeed, evaluation of DOACs plasmatic concentration is discouraged for the majority of patients, due to the lack of outcome data supporting this approach. Nevertheless, DOAC measurements may be useful in emergency situations such as serious bleeding events, need for urgent invasive procedures, and acute ischemic stroke or in managing anticoagulation in "special populations" not adequately studied in clinical trials, for example the very elderly or those at the extremes of body weight. The aim of this review is to describe and summarize the methods for DOACs activity evaluation and the settings in which their plasma level measurement may be indicated, analyzing indications from scientific societies and evidence from clinical trials, as well as real world data on the usefulness of DOACs plasma levels "monitoring.", Competing Interests: None declared., (Thieme. All rights reserved.)

The integrated clinical, laboratory and ultrasound approach is essential for the diagnosis, evaluation and monitoring of the patient's therapy in coronavirus disease 2019 pneumonia. The ideal imaging approach in this context is not yet well defined. Chest X-ray is characterized by low sensitivity in identifying earlier lung changes. The "bedside" pulmonary ultrasound has an undeniable series of advantages in the patient at high infectious risk and can provide incremental data in the respiratory intensive care for the serial control of the individual patient as well as for the home delivery of the stabilized subjects. Pulmonary computed tomography shows high sensitivity but should not be routinely performed in all patients, because in the first 48 h it can be absolutely negative and in the late phase the imaging findings may not change the therapeutic approach. Echocardiography should be limited to patients with hemodynamic instability to assess ventricular function and pulmonary pressures., Competing Interests: Conflict-of-interest statement: There is no conflict of interest associated with the senior author or any of the other coauthors who contributed their efforts in this manuscript., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

The integrated clinical, laboratory and ultrasound approach is essential for the diagnosis, monitoring and evaluation of the patient's therapy in COVID-19 pneumonia. The ideal imaging strategy in this setting is not yet well defined. Bedside pulmonary ultrasound presents an undeniable series of advantages in patients at high risk of infection, and can provide incremental data in the respiratory intensive care for the serial control of the individual patient, as well as for home delivery of stabilized patients. Chest X-ray is characterized by low sensitivity in identifying earlier lung changes. Pulmonary computed tomography shows high sensitivity but should not be routinely performed in all patients, because in the first 48 h it can be absolutely negative, and in the late phase imaging findings may not change the therapeutic approach. Echocardiography should be limited to patients with hemodynamic instability.

Echocardiography is a noninvasive imaging technique useful to provide clinical data regarding physiological adaptations of athlete's heart. Echocardiographic characteristics may be helpful for the clinicians to identify structural cardiac disease, responsible of sudden death during sport activities. The application of echocardiography in preparticipation screening might be essential: it shows high sensitivity and specificity for identification of structural cardiac disease and it is the first-line imagining technique for primary prevention of SCD in athletes. Moreover, new echocardiographic techniques distinguish extreme sport cardiac remodeling from beginning state of cardiomyopathy, as hypertrophic or dilated cardiomyopathy and arrhythmogenic right ventricle dysplasia. The aim of this paper is to review the scientific literature and the clinical knowledge about athlete's heart and main structural heart disease and to describe the rule of echocardiography in primary prevention of SCD in athletes., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Cardiovascular Echography.)

Purpose: The purpose of the current study was to compare the efficacy and safety of edoxaban versus vitamin K antagonist (VKA) therapy among a cohort of elderly patients (ie, those aged ≥75 years) with atrial fibrillation (AF) in a real-life setting., Methods: A propensity score-matched cohort observational study was performed comparing the safety and efficacy of edoxaban versus VKA therapy among a cohort of elderly (aged ≥75 years) patients with AF in a real-life setting. Follow-up data were obtained through outpatient visits at 1, 3, and every 6 months. The primary safety outcome was major bleeding. The primary efficacy outcome was the composite of stroke, transient ischemic attack, and systemic embolism., Findings: A total of 130 patients receiving edoxaban 60 mg (EDO) treatment were compared with the same number of VKA recipients. The mean follow-up was 16 (2.6) months. The cumulative incidence of thromboembolic events in the EDO and VKA groups was 1.5% (2 of 130) and 2.3% (3 of 130), respectively (P < 0.6). The cumulative incidence of major bleeding events was 1.5% (2 of 130) in the EDO group and 3.1% (4 of 130) in the VKA group (P < 0.4). The total anticoagulant therapy discontinuation rate was 2.3% (3 of 130) in the EDO group and 4.6% (6 of 130) in the VKA group (P < 0.3). A nonsignificant trend in improved adherence was observed between the EDO and VKA groups (81% vs 78%; P = 0.6)., Implications: Edoxaban therapy showed a good real-life performance among elderly patients (aged ≥75 years) with AF., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Transcatheter aortic valve replacement (TAVR) is an alternative treatment in surgically intermediate- or high-risk patients with classical low-flow, low-gradient (LFLG) aortic stenosis (AS). The objective of this study was to investigate whether two-dimensional (2D) speckle-tracking echocardiography (STE) can predict left ventricular (LV) flow reserve during dobutamine stress echocardiography (DSE) and remodeling after TAVR in patients with LFLG AS., Methods: Seventy-five symptomatic patients with severe LFLG AS were recruited (mean age, 77.6 ± 8.4 years). Patients underwent a complete clinical evaluation, standard echocardiography, 2D STE, and DSE. Echocardiographic analysis was performed before and 6 months after TAVR using global longitudinal strain (GLS) measured on 2D STE., Results: All patients received self-expanding transcatheter prosthetic valves. Six months after TAVR, LV GLS (12.8 ± 3.2% vs 16.3 ± 4.2%, P < .0001) significantly increased. In a multivariate analysis, LV GLS before TAVR (P < .0001) was an independent predictor of LV flow reserve during DSE. By receiver operating characteristic curve analysis, a cutoff value for LV GLS of ≤12% well distinguished patients without significant flow reserve and with lack of positive remodeling after TAVR at follow-up. These results support the hypothesis that myocardial analysis by 2D STE at baseline can be useful for the identification of patients with LFLG AS who would benefit from TAVR., Conclusions: The results of this study underline the predictive value of LV GLS on flow reserve during DSE and on global LV remodeling after TAVR in patients with LFLG AS. Cutoff values for LV GLS could be used to identify patients responding better to TAVR., (Copyright © 2019 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

High lethality rates associated with metastatic cancer highlight an urgent medical need for improved understanding of biologic mechanisms driving metastatic spread and identification of biomarkers predicting late-stage progression. Numerous neoplastic cell intrinsic and extrinsic mechanisms fuel tumor progression; however, mechanisms driving heterogeneity of neoplastic cells in solid tumors remain obscure. Increased mutational rates of neoplastic cells in stressed environments are implicated but cannot explain all aspects of tumor heterogeneity. We present evidence that fusion of neoplastic cells with leukocytes (for example, macrophages) contributes to tumor heterogeneity, resulting in cells exhibiting increased metastatic behavior. Fusion hybrids (cells harboring hematopoietic and epithelial properties) are readily detectible in cell culture and tumor-bearing mice. Further, hybrids enumerated in peripheral blood of human cancer patients correlate with disease stage and predict overall survival. This unique population of neoplastic cells provides a novel biomarker for tumor staging, as well as a potential therapeutic target for intervention.

The aim of the study was to analyze possible correlations between strain echocardiography (STE) and PET myocardial perfusion in a population of heart transplantation (HTx) recipients showing preserved left ventricular (LV) ejection fraction. By STE, LV global longitudinal strain (LV GLS) was lower in HTx. PET showed no transient or chronic ischemia in 83 of 115 HTx (73%). Fixed perfusion defects were observed in 17% of HTx and reversible ischemia in 10%. Significant coronary stenosis was observed only in 10 cases. GLS was independently associated with age at HTx and fixed perfusion defects (HR 0.41; P<.001). Such relationships underline STE ability to early identify HTx pts with subclinical myocardial dysfunction during long-term follow-up., (© 2017, Wiley Periodicals, Inc.)

Intense exercise may cause heart remodeling to compensate increases in blood pressure or volume by increasing muscle mass. Cardiac changes do not involve only the left ventricle, but all heart chambers. Physiological cardiac modeling in athletes is associated with normal or enhanced cardiac function, but recent studies have documented decrements in left ventricular function during intense exercise and the release of cardiac markers of necrosis in athlete's blood of uncertain significance. Furthermore, cardiac remodeling may predispose athletes to heart disease and result in electrical remodeling, responsible for arrhythmias. Athlete's heart is a physiological condition and does not require a specific treatment. In some conditions, it is important to differentiate the physiological adaptations from pathological conditions, such as hypertrophic cardiomyopathy, arrhythmogenic dysplasia of the right ventricle, and non-compaction myocardium, for the greater risk of sudden cardiac death of these conditions. Moreover, some drugs and performance-enhancing drugs can cause structural alterations and arrhythmias, therefore, their use should be excluded., Competing Interests: Conflict-of-interest statement: No potential conflicts of interest exist.

Transcatheter aortic valve replacement (TAVR) has been validated as a new therapy for patients affected by severe symptomatic aortic stenosis who are not eligible for surgical intervention because of major contraindication or high operative risk. Patient selection for TAVR should be based not only on accurate assessment of aortic stenosis morphology, but also on several clinical and functional data. Multi-Imaging modalities should be preferred for assessing the anatomy and the dimensions of the aortic valve and annulus before TAVR. Ultrasounds represent the first line tool in evaluation of this patients giving detailed anatomic description of aortic valve complex and allowing estimating with enough reliability the hemodynamic entity of valvular stenosis. Angiography should be used to assess coronary involvement and plan a revascularization strategy before the implant. Multislice computed tomography play a central role as it can give anatomical details in order to choice the best fitting prosthesis, evaluate the morphology of the access path and detect other relevant comorbidities. Cardiovascular magnetic resonance and positron emission tomography are emergent modality helpful in aortic stenosis evaluation. The aim of this review is to give an overview on TAVR clinical and technical aspects essential for adequate selection., Competing Interests: Conflict-of-interest statement: The authors report no relevant conflicts of interest.

Aims: To analyse right ventricular (RV) systolic function in patients with hypertrophic cardiomyopathy (HCM) at rest and during exercise, and its possible correlation with left ventricular(LV) morphology and function., Methods and Results: Standard echo, exercise stress echo, and RV 2D speckle-tracking strain (2DSE) were performed in 45 patients with HCM and in 45 age- and sex-comparable healthy controls. RV global longitudinal strain (GLS) was calculated by averaging local strains along the entire right ventricle. LV mass index and IVS wall thickness were significantly increased in HCM, while LV ejection fraction, RV diameters, RV tissue Doppler systolic peak and the RV end-systolic pressure-area relationship at rest were comparable between the two groups. Conversely, all transmitral Doppler indexes were significantly impaired in HCM. In addition, RV GLS and regional peak myocardial RV strains were significantly reduced in patients with HCM (all P<0.001). During physical effort, LV ejection fraction was comparable between the two groups. Conversely, LV E/E m ratio was significantly increased in HCM. Increase in TAPSE and RV tissue Doppler Sm peak velocity during effort were similar between the two groups. Conversely, increases of RV end-systolic pressure-area, regional and global RV strain were significantly lower in HCM patients (RV lateral strain: 10.3±3.5% of increase in HCM vs 20.5±4.5% in controls; p<0.0001). Multivariable analysis detected independent associations of RV lateral strain at peak stress with LV IVS thickness, maximal workload during exercise, and LV E/E m ratio during effort (all p<0.0001). An RV lateral 2DSE cut-off point of -14% differentiated controls and HCM with an 86%sensitivity and a 92% specificity., Conclusions: RV contractile reserve for HCM is impaired and this suggests that the lower resting values of RV in HCM may represent early subclinical myocardial damage, closely associated with exercise capacity., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

During last decades, most studies have examined the exercise-induced remodeling defined as "athlete's heart". During exercise, there is an increased cardiac output that causes morphological, functional, and electrical modification of the cardiac chambers. The cardiac remodeling depends also on the type of training, age, sex, ethnicity, genetic factors, and body size. The two main categories of exercise, endurance and strength, determine different effects on the cardiac remodeling. Even if most sport comprise both strength and endurance exercise, determining different scenarios of cardiac adaptation to the exercise. The aim of this paper is to assemble the current knowledge about physiologic and pathophysiologic response of both the left and the right heart in highly trained athletes.

Cardiac changes in athletes involve the left ventricle and atrium. Mild left atrial enlargement is common among competitive athletes, possibly a physiologic adaptation to exercise conditioning. The prevalence of this remodeling and the association with supraventricular arrhythmias has not been systematically addressed. Echocardiography screens for patients with disease involving the left atrium. New techniques like speckle tracking can recognize early atrial dysfunction and assess left atrial myocardial function in patients with either physiologic or pathologic left ventricular hypertrophy. This article reviews echocardiographic techniques in delineating the athlete's morphology and functional properties of the left atrium., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Non-invasive Doppler ultrasonographic study of cerebral arteries [transcranial Doppler (TCD)] has been extensively applied on both outpatient and inpatient settings. It is performed placing a low-frequency (≤ 2 MHz) transducer on the scalp of the patient over specific acoustic windows, in order to visualize the intracranial arterial vessels and to evaluate the cerebral blood flow velocity and its alteration in many different conditions. Nowadays the most widespread indication for TCD in outpatient setting is the research of right to left shunting, responsable of so called "paradoxical embolism", most often due to patency of foramen ovale which is responsable of the majority of cryptogenic strokes occuring in patients younger than 55 years old. TCD also allows to classify the grade of severity of such shunts using the so called "microembolic signal grading score". In addition TCD has found many useful applications in neurocritical care practice. It is useful on both adults and children for day-to-day bedside assessment of critical conditions including vasospasm in subarachnoidal haemorrhage (caused by aneurysm rupture or traumatic injury), traumatic brain injury, brain stem death. It is used also to evaluate cerebral hemodynamic changes after stroke. It also allows to investigate cerebral pressure autoregulation and for the clinical evaluation of cerebral autoregulatory reserve.

Transcranial Doppler (TCD) ultrasonography is a noninvasive ultrasound study, which has been extensively applied in both outpatient and inpatient settings. Its main use in current clinical practice is the research for "Paradoxical Embolism," due to migration of thromboembolic material from systemic venous circulation to the left cardiac chambers and arterial circulation through cardiopulmonary shunts such as patent foramen ovale which represents an important cause of cryptogenic stroke, especially in patients under 55 years of age. In this review, we shall describe the incremental diagnostic role in cryptogenic stroke for this imaging modality. TCD not only can be used to detect right-left cardiopulmonary shunts but it also allows to classify the grade of severity of such shunts using the so-called "Microembolic Signals grading score.", Competing Interests: There are no conflicts of interest.

Binge drinking is an increasing problem in Western societies, but we are still only beginning to unravel the effects of binge drinking on a cognitive level. While common sense suggests that all cognitive functions are compromised during high-dose ethanol intoxication, several studies suggest that the effects might instead be rather specific. Moreover, some results suggest that the degrees of automaticity and complexity of cognitive operations during response control modulate effects of binge drinking. However, this has not been tested in detail. In the current study, we therefore parametrically modulate cognitive/"mental" workload during response inhibition and examine the effects of high-dose ethanol intoxication (~1.1 ‰) in n = 18 male participants. The results suggest that detrimental effects of high-dose ethanol intoxication strongly depend on the complexity of processes involved in response inhibition. The results revealed strong effects (η (2) = .495) and are in line with findings showing that even high doses of ethanol have very specific effects on a cognitive level. Opposed to common sense, more complex cognitive operations seem to be less affected by a high-dose ethanol intoxication. Complementing this, high-dose ethanol intoxication is increasingly detrimental for action control, as stronger automated response tendencies are in charge and need to be controlled. Binge-like ethanol intoxication may take a heavier toll on cognitive control processes than on automated responses/response tendencies. Therefore, ethanol effects are more pronounced in supposedly "easier" control conditions because those facilitate the formation of automated response tendencies.

Transcranial Doppler (TCD) ultrasonography is a noninvasive ultrasound study, which has been extensively applied on both outpatient and inpatient settings. It involves the use of a low-frequency (≤2 MHz) transducer, placed on the scalp, to insonate the basal cerebral arteries through relatively thin bone windows and to measure the cerebral blood flow velocity and its alteration in many different conditions. In neurointensive care setting, TCD is useful for both adults and children for day-to-day bedside assessment of critical conditions including vasospasm in subarachnoid hemorrhage, traumatic brain injury, acute ischemic stroke, and brain stem death. It also allows to investigate the cerebrovascular autoregulation in setting of carotid disease and syncope. In this review, we will describe physical principles underlying TCD, flow indices most frequently used in clinical practice and critical care applications in Neurocritical Unit care., Competing Interests: There are no conflicts of interest.

Aims: To elucidate right ventricular (RV) function in patients with idiopathic pulmonary fibrosis (IPF) with and without pulmonary hypertension (PH) and its relation to other features of the disease., Methods and Results: Clinical evaluation, standard Doppler echo, Doppler myocardial imaging (DMI), and 2D strain echocardiography (STE) of RV septal and lateral walls were performed in 52 IPF patients (66.5 ± 8.5 years; 27 males) and in 45 age- and sex-comparable controls using a commercial US system (MyLab Alpha, Esaote). Pulmonary artery mean pressure (mPAP) was estimated by standard echo Doppler. RV global longitudinal strain (RV GLS) was calculated by averaging RV local strains. The IPF patients were divided into 2 groups by noninvasive assessment of PH: no PH (mPAP<25 mmHg; 36 pts) and PH (mPAP ≥25 mmHg; 16 pts). Left ventricular diameters and ejection fraction were comparable between controls and IPF, while GLS was impaired in IPF (P < 0.01). RV end-diastolic diameters, wall thickness andmPAP were increased in IPF patients with PH. In addition, pulsed DMI detected in PH IPF impaired myocardial RV early diastolic (Em) peak velocity. Also peak systolic RV strain was reduced in basal and middle RV lateral free walls in IPF, as well as RV GLS (P < 0.0001). The impairment in RV wall strain was more evident when comparing controls with the no PH group than comparing the no PH group with the PH group. By multivariate analysis, independent association of RV strain with both six-minute walking test distance (P < 0.001), mPAP (P < 0.0001), as well as with forced vital capacity (FVC) % (P < 0.005) in IPF patients were observed., Conclusions: Impaired RV diastolic and systolic myocardial function were present even in IPF patients without PH, which indicates an early impact on RV function and structure in patients with IPF., (© 2015, Wiley Periodicals, Inc.)

Several studies have described the adaptive remodeling of the heart during exercise. In some more practiced endurance athletes, there is a disproportionate load on the right ventricle (RV), at least during exercise, and this might be the basis for a chronic pro-arrhythmic RV remodeling. Especially, in these kinds of athletes the recovery after detraining might be incomplete, in particular for RV changes. The observation of acute myocardial injury based on transient elevation of biomarkers and chronic myocardial scar, not completely reversible changes of the RV and an increased prevalence of some arrhythmias support the existence of an "exercise-induced cardiomyopathy." The aim of this paper is to review current knowledge about changes in the right heart in highly trained athletes and how these change influence cardiac function., Competing Interests: There are no conflicts of interest.

Aims: Transcatheter aortic valve implantation (TAVI) is an alternative treatment in surgically high-risk or inoperable patients with severe aortic stenosis (AS). The objective of this study was to analyze the effects of TAVI on left ventricular (LV) and left atrial (LA) longitudinal function assessed by speckle tracking echocardiography (2DSTE) in patients with AS., Methods: In our prospectively conducted study, a total of 55 symptomatic (New York Heart Association class II or higher) patients with severe AS, considered to be at increased risk for undergoing surgical aortic valve replacement, were recruited (age: 78.6 ± 7.4 year). Patients underwent a complete clinical and laboratory evaluation, in addition to standard echocardiography and 2DSTE. Echocardiographic analysis was performed before and 6 months after TAVI. 2DSTE measured segmental and global longitudinal strain (GLS) and radial strain., Results: All the patients received the CoreValve self-expanding prosthesis. Six months after TAVI, patients showed a significant reduction in mean transaortic gradient (52.1 ± 15.8 vs. 11.2 ± 3.3 mmHg, P < 0.0001), LV mass, LA volume index, and an improvement of ejection fraction (P < 0.0001). In addition, LV GLS (-11.8 ± 3.2 vs. -16.3 ± 4.2%; P < 0.0001) and LA longitudinal strain (14.2 ± 5.4 vs. 26.6 ± 10.8%, P < 0.0001) significantly increased after TAVI. In a stepwise forward multiple logistic regression analysis, LV mass before TAVI (P < 0.001) and peak CK MB mass after TAVI (P < 0.0001) were powerful independent predictors of lower improvement of LV GLS. Moreover, LV mass index (P < 0.001) and LV GLS strain (P < 0.001) before TAVI were powerful independent predictor of LA longitudinal strain after TAVI CONCLUSIONS: TAVI in patients with AS resulted in geometric changes known as "reverse remodelling," and improved LV and LA function assessed by 2DSTE., (© 2014, Wiley Periodicals, Inc.)

Obesity has become an important public health issue in Western and developing countries, with well known metabolic and cardiovascular complications. In the last decades, evidence have been growing about the active role of adipose tissue as an endocrine organ in determining these pathological consequences. As a consequence of the expansion of fat depots, in obese subjects, adipose tissue cells develope a phenotypic modification, which turns into a change of the secretory output. Adipocytokines produced by both adipocytes and adipose stromal cells are involved in the modulation of glucose and lipid handling, vascular biology and, moreover, participate to the systemic inflammatory response, which characterizes obesity and metabolic syndrome. This might represent an important pathophysiological link with atherosclerotic complications and cardiovascular events. A great number of adipocytokines have been described recently, linking inflammatory mileu and vascular pathology. The understanding of these pathways is crucial not only from a pathophysiological point of view, but also to a better cardiovascular disease risk stratification and to the identification of possible therapeutic targets. The aim of this paper is to review the role of Adipocytokines as a possible link between obesity and vascular disease.

Background: Although transthoracic echocardiography (TTE) is an excellent noninvasive screening test for pulmonary hypertension, the physiologic range of Doppler echocardiography-derived pulmonary pressures remains not completely investigated. The aim of the present study was, therefore, to explore the full spectrum of pulmonary pressures and right ventricular (RV) functional indexes by TTE in healthy subjects and to investigate clinical and echocardiographic correlates., Methods: A random sample of 1,480 healthy individuals (mean age, 36.1 ± 15.5 years; range, 20-80 years; 905 men) underwent a comprehensive TTE. Pulmonary artery systolic pressure (PASP), mean pressure, and pulmonary vascular resistance were estimated by standard Doppler echocardiography formulas. In addition, RV diastolic (Doppler transtricuspid inflow measurements) and systolic indexes (RV fractional area change, RV tissue Doppler peak systolic velocity, tricuspid annular plane systolic excursion) were calculated., Results: PASP and mean pulmonary artery pressure values were significantly higher in subjects aged &gt; 50 years and in those with a BMI &gt; 30 kg/m2. In particular, a PASP &gt; 40 mm Hg was found in 118 subjects (8%) of those aged &gt; 50 years and in 103 (7%) of those with a BMI &gt; 30 kg/m2. No differences by age were registered in RV systolic indexes and in pulmonary vascular resistances. On multivariate analysis, in the overall study population, age, BMI, mitral E/e' ratio, and left ventricular stroke volume were the only independent predictors of PASP., Conclusions: This study delineates an estimate of pulmonary hemodynamics in a wide age range cohort of healthy subjects. Pulmonary pressures increased with age and BMI, as expected.

Cardiotrophin-1 (CT-1) is a member of the interleukin (IL-6) family of cytokines. Plasma CT-1 levels correlate with the left ventricle mass index in patients with dilatated cardiomyopathy and congestive heart failure (CHF). The aim of this paper was to evaluate CT-1 plasma levels, before and after cardiac resynchronization therapy CRT, and to characterizeits prognostic role in patients with CHF. Fifty-two consecutive patients (M/F = 39/13; 56 ± 11 years old) underwent clinical and echocardiographic evaluation, and blood sample collection at baseline. The same evaluation was repeated 6.4 ± 0.79 months after CRT. Patients with a decreased LV end-systolic volume by at least 15% (reverse remodeling) were considered echo responders to CRT. Twenty-nine patients (56%) were responders to CRT. After CRT, only 15 patients (29%) showed increased CT-1 after CRT. They were all non responders to CRT. A multivariate, logistic model showed CT-1 as an independent predictor of CRT echo response (p = 0.005; OR 0.97). During follow-up (18 ± 7 months), 21 cardiac events in 18 patients occurred. A Cox multivariable model showed plasma BNP pre-CRT (p = 0.02; CI 1.2-5.6; OR 3.1) and CT1 post-CRT (p = 0.01; CI 1.4-4.3; OR 2.7) as independent predictors of cardiac events. Analysis of CT-1 plasma levels deserves future consideration for larger, longitudinal studies in patients with CHF.

Left atrial (LA) size is related to cardiovascular morbidity and mortality. The relative role of multiple determinants of LA morphology in healthy subjects remains incompletely defined. The aim of this study is to define normal ranges for LA diameters and volume index (LAVi), and to investigate clinical and echocardiographic correlates. A total of 1480 healthy individuals (mean age 36.1 ± 15.5 years, range 20-80; 61% males) underwent a comprehensive transthoracic echocardiography exam including assessment of LAVi calculated using the biplane area-length method at the apical four-chamber and two-chamber views at ventricular end systole (maximum LA size) and indexed for body surface area (BSA). Mean LAVi in the overall population was 29.5 ± 10.8 mL/m(2) (range: 26.1-41.8 mL/m(2) ). Distinct higher values were found in subjects ≥50 years as compared with those <50 years of age (33.4 ± 12.5 vs. 29.1 ± 13.5; P < 0.001). On univariate analysis, LA volume was significantly associated with age (r = 0.48, P < 0.0001), male gender (r = 0.28, P < 0.05), BSA (r = 0.51, P < 0.0001), mitral E/E' (r = 0.47, P < 0.0001), LV end-diastolic volume (r = 0.52, P < 0.0001), and LV mass index (r = 0.31, P < 0.05). Multivariable analysis identified age, BSA, LV end-diastolic volume, and mitral E/E' ratio as the only independent determinants of LA volume (model R(2) = 0.54, P < 0.0001). Gender was an independent predictor of most absolute LA volume, but following normalization to BSA, some associations became nonsignificant. In healthy individuals LAVi vary significantly by age, BSA, diastolic function, and LV dimensions, with lesser effects of gender., (© 2013, Wiley Periodicals, Inc.)

Background: The right heart is a major determinant of prognosis in cardiac transplant recipient patients., Aim: To investigate right ventricular morphology and function and their relationship with exercise capacity in cardiac transplant recipient patients using standard tranthoracic echocardiography and a new three-dimensional echocardiographic software adapted for right ventricular analysis., Methods: One hundred fifteen relatively stable cardiac transplant recipient patients (71 men; 58.3 ± 5.8 years; 7.8 ± 4.5 years after transplantation) and 80 healthy age-comparable and sex-comparable controls underwent standard echocardiography, tissue Doppler imaging (TDI), and three-dimensional echocardiography, focused on the right ventricular analysis. Along with left heart parameters, right ventricular measurements included end-diastolic diameters at basal and mid-cavity level; base-to-apex length; tricuspid annulus plane systolic excursion (TAPSE); TDI right ventricular systolic peak velocity (Sm); and three-dimensional ejection fraction. Using the peak systolic tricuspid regurgitation velocity (TRV) and the end-diastolic pulmonary regurgitation velocity, the modified Bernoulli equation was used to calculate the pulmonary artery systolic (PASP) and diastolic pressures. Pulmonary artery vascular conductance (PAVC) was estimated by left ventricular stroke volume/4 × (TRV - pulmonary regurgitation velocity)., Results: Left ventricular diameters and ejection fraction did not significantly differ between the two groups, whereas mass index was increased in cardiac transplant recipient patients (P < 0.01). Right ventricular diameters were significantly increased (P < 0.001), whereas TAPSE and right ventricular Sm were significantly lower in cardiac transplant recipient patients. Conversely, in cardiac transplant recipient patients, three-dimensional right ventricular ejection fraction (RVEF) was not significantly reduced (P < 0.001), whereas both PASP and PAVC were impaired. By multivariable analysis, age at transplantation (P < 0.01) and pulmonary artery mean pressure (P < 0.001) were the only independent determinants of right ventricular diameters and RVEF in cardiac transplant. Furthermore, RVEF measured by real-time three-dimensional echocardiography was a powerful independent determinant of functional capacity in cardiac transplant recipient patients., Conclusion: Despite the reduction of right ventricular performance along the long axis suggested by TAPSE and right ventricular Sm, the increased right ventricular diameters along with absence of a decrease in three-dimensional RVEF support the hypothesis of geometrical rather than functional changes of the right ventricle in cardiac transplant recipient patients.

Objectives: To explore the full range of right heart dimensions and the impact of long-term intensive training in athletes., Background: Although echocardiography has been widely used to distinguish the athlete's heart from pathologic left ventricular (LV) hypertrophy, only few reports have described right ventricular (RV) and right atrial (RA) adaptations to extensive physical exercise., Methods: 650 top-level athletes [395 endurance- (ATE) and 255 strength-trained (ATS); 410 males (63.1%); mean age 28.4 ± 10.1; 18-40 years] and 230 healthy age- and sex-comparable controls underwent a transthoracic echocardiographic exam. Along with left heart parameters, right heart measurements included: RV end-diastolic diameters at the basal and mid-cavity level; RV base-to-apex length; RV proximal and distal outflow tract diameters; RA long and short diameters; and RA area. Tricuspid annular plane systolic excursion and RV tissue Doppler systolic peak velocity were assessed as indexes of RV systolic function. Pulmonary artery systolic pressure (PASP) was estimated from the peak tricuspid regurgitant velocity., Results: ATS showed increased sum of wall thickness and relative wall thickness, whereas left atrial volume, LV end-diastolic volume, LV stroke volume and PASP were significantly higher in ATE. RV and RA measurements were all significantly greater in ATE than in ATS and controls. ATE also showed improved early diastolic RV function, whereas RV systolic indexes were comparable among groups. On multivariate analysis, type and duration of training (p<0.01), PASP (p<0.01) and LV stroke volume (p<0.001) were the only independent predictors of the main RV and RA dimensions in athletes., Conclusions: This study delineates the upper limits of RV and RA dimensions in highly-trained athletes. Right heart measurements were all significantly greater in elite endurance-trained athletes than in age- and sex-matched strength athletes and controls. This should be considered as a "physiologic phenomenon" when evaluating athletes for sports eligibility., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Aims: Asynchronous myocardial contraction adversely influences left ventricular (LV) function and is therefore associated with a poor prognosis in heart failure. Exercise-induced change in ventricular dyssynchrony may be an important determinant of dynamic changes in cardiac output and mitral regurgitation., Methods and Results: A prospective, longitudinal study was designed with pre-defined dyssynchrony index and outcome variables to test the hypothesis that dynamic dyssynchrony is associated with worse long-term event-free survival in patients with dilated cardiomyopathy (DCM) and 'narrow' QRS complex. One-hundred eighty patients (62 ± 8 years; 110 males) with NYHA class II-III, idiopathic DCM, ejection fraction ≤35%, and QRS duration <120 ms were selected. All the patients underwent standard Doppler echo, colour tissue velocity imaging (DTI), and supine bicycle exercise stress echocardiography. Cardiac synchronicity was defined, at rest and at peak exercise, as DTI velocity opposing-wall delay (significant if ≥65 ms). Outcome was defined as freedom from death, heart transplantation, or LV-assist device implantation, over a median follow-up of 48 months, and a Cox proportional hazards model was used for survival analysis. At baseline examination, DCM patients showed a reduced LV ejection fraction (31 + 4%). A significant electromechanical delay in 58 patients (32%). At the peak of physical exercise, a significant electromechanical delay was detected in 103 patients (57%). There were 41 events during the follow-up (23%): 28 cardiac deaths, 8 heart transplantations, and 5 LV-assist device implantations over 4 years. When adjusted for confounding baseline variables, LV end-diastolic volume, restrictive mitral flow pattern, severity of mitral regurgitation, and the presence of exercise-induced intraventricular dyssynchrony were the only independent determinants of an adverse outcome., Conclusion: In patients with idiopathic DCM and narrow QRS, the increase in echocardiographic dyssynchrony during exercise was the strongest predictor of less favourable event-free survival.

Background: Our objective was to explore the right ventricular (RV) dimensions and function and the effect of long-term intensive training in a large population of top level athletes using real-time three-dimensional (3D) echocardiography., Methods: A total of 430 top-level athletes (220 endurance-trained athletes [ETAs] and 210 strength-trained athletes; 265 men [61.6%]; mean age 27.4 ± 10.1 years, range 18-40) and 250 healthy controls underwent a transthoracic echocardiographic examination. Three-dimensional RV measurements included serial short-axis reconstructions of the RV volumetric data sets, and the RV endocardial contour was traced with cross-reference to the long-axis images for identification of the tricuspid annulus. The end-diastolic and end-systolic RV volumes and ejection fraction were calculated off-line using the method of the summation of discs., Results: The strength-trained athletes had a greater heart rate, body surface area, and systolic blood pressure at rest than the ETAs and controls. All RV diameters and 3D volumes and all transmitral and transtricuspid Doppler indexes were greater in the ETAs. Also, the left ventricular stroke volume, cardiac index, and pulmonary artery systolic pressure were greater in the ETAs, and all two-dimensional and 3D RV systolic indexes were comparable. On univariate analysis, the 3D RV end-diastolic volume was significantly associated with advanced age, male gender, duration of training, endurance training, increased left ventricular stroke volume, and pulmonary artery systolic pressure. On multivariate analysis, in the overall study population, the type and duration of training (P < .01), pulmonary artery systolic pressure (P < .01), and left ventricular stroke volume (P < .001) were the only independent predictors of RV end-diastolic volume., Conclusions: The results of the present study have delineated the upper limits of the RV dimensions in highly trained athletes as measured by real-time 3D echocardiography. The RV end-diastolic volume was significantly greater in the ETA than in the strength-trained athletes and controls., (Copyright © 2012 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

Background: Although cardiac adaptation to different sports has been extensively described, the potential relationship of training with aortic root (AR) elastic properties and diameters in top-level athletes remains not fully investigated. The aims of this study were to compare AR morphology and stiffness between highly trained athletes and sedentary subjects and to assess the independent determinants of AR stiffness and distensibility in athletes., Methods: Four hundred ten elite athletes (220 endurance-trained athletes [ATE] and 190 strength-trained athletes [ATS]; 290 men; mean age, 28.3 ± 13.6 years; age range, 18-40 years) and 240 healthy controls underwent standardized comprehensive transthoracic echocardiography, including Doppler studies. End-diastolic AR diameters were measured at four locations: the aortic annulus, the sinuses of Valsalva, the sinotubular junction, and the maximal diameter of the proximal ascending aorta. The aortic distensibility index was calculated as 2 × (systolic proximal ascending aortic diameter - diastolic proximal ascending aortic diameter)/(diastolic proximal ascending aortic diameter) × (pulse pressure) (cm(-2)·dyn(-1)·10(-6)). AR stiffness index was defined as (systolic blood pressure/diastolic blood pressure)/(systolic proximal ascending aortic diameter - diastolic proximal ascending aortic diameter)/diastolic proximal ascending aortic diameter. Analysis of variance was performed to evaluate differences among groups., Results: Left ventricular (LV) mass index did not significantly differ between the two groups of athletes but was lower in controls. ATS showed higher body surface area, sum of wall thickness (septum plus LV posterior wall), and circumferential end-systolic stress, while LV stroke volume and LV end-diastolic volume were greater in ATE. AR diameters at all levels and AR stiffness were significantly greater in ATS than in ATE and controls, while AR distensibility was significantly higher in ATE. However, AR dilatation was observed only in four male power athletes (1%). By multivariate analyses, in the overall population of athletes, age, LV stroke volume, endurance training, and duration of training were the only independent determinant of higher AR distensibility. On the other hand, age, circumferential end-systolic stress, strength training, and duration of training were independently associated with AR stiffness in ATS., Conclusions: AR diameters and stiffness were significantly greater in strength-trained athletes, while aortic distensibility was higher in endurance athletes compared with age- and sex-matched healthy controls., (Copyright © 2012 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

Aims: To test whether two-dimensional longitudinal strain (2DSE) performed after revascularization by percutaneous coronary intervention (PCI) could predict left ventricular (LV) remodeling in patients with recent non-ST elevation myocardial infarction (NSTEMI)., Methods: In 70 patients (62.7 ± 8.7 years) with recent NSTEMI (between 72 hours and 14 days), undergoing coronary angiography for recurrent angina, myocardial deformation parameters were measured by 2DSE before and 24 hours after reperfusion therapy. Strain in all LV segments was averaged to obtain a global value (Global longitudinal Strain--GLS). Infarct size was estimated by clinical parameters and cardiac markers. After 6 months from intervention, LV negative remodeling was defined as lack of improvement of LV function, with increase in LV end-diastolic volume of greater than or equal than 15%., Results: At follow-up, patients were subdivided into remodeled (n=32) and non-remodeled (n = 38) groups. Patients with negative LV remodeling had significantly lower baseline LV ejection fraction (44.8±6.9 vs. 48.7 ± 5.5 %; p < 0.05), higher peak troponin I (p < 0.001) and reduced GLS (- 10.6±6.1 vs - 17.6 ± 6.7 % p < 0.001) than those without LV remodeling. GLS showed a close correlation with peak troponin I after PCI (r = 0.64, P < 0.0001) and LV WMSI (r = 0.42, p < 0.01). By multivariable analysis, diabetes mellitus (P < 0.005), peak of Troponin I after PCI (P < 0.0005), GLS at baseline (OR: 4.3; p < 0.0001), and lack of improvement of GLS soon after PCI (OR: 1.45, P < 0.01) were powerful independent predictors of negative LV remodelling at follow-up. In particular, a GLS ≤ 12 % showed a sensitivity and a specificity respectively of 84.8% and 87.8% to predict negative LV remodelling at follow-up., Conclusions: in patients with recent NSTEMI, longitudinal LV global and regional speckle-tracking strain measurements are powerful independent predictors of LV remodeling after reperfusion therapy., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To detect right ventricular myocardial function in dilated cardiomyopathy (DCM) using two-dimensional strain echocardiography (2DSE) and to evaluate the relationship between right ventricular dysfunction and response to cardiopulmonary exercise test (CPET)., Methods: Seventy-five DCM patients (44 idiopathic and 31 ischemic) without clinical signs of right ventricular failure underwent standard echo, 2DSE analysis of right ventricle and bicycle CPET., Results: The two groups were comparable for clinical and standard two-dimensional echocardiographic and Doppler variables, except for right ventricular diameters that were mildly increased in patients with idiopathic DCM. Right ventricular global longitudinal strain (RV GLS) and regional peak myocardial right ventricular strain were significantly impaired in patients with idiopathic DCM compared with ischemic DCM (both P<0.001). A significant correlation was detectable among RV GLS and VO2 peak percentage (r= -0.65, P<0.0001), VE/VCO2 slope (r=0.35, P<0.01), maximum work rate percentage (r= -0.55, P<0.001) and peak circulatory power (r=0.53, P<0.001). These correlations with RV GLS remained significant even in multivariate analysis., Conclusion: 2DSE represents a promising noninvasive technique to assess right ventricular myocardial function in patients with DCM. Reduced right ventricular myocardial deformation is related to decreased ability to perform aerobic exercise and work rate, and to impaired ventilatory response.

Background: Although the physiologic range of pulmonary artery systolic pressure (PASP) has been reported, data on how it is manifested in athletes are limited. The aim of the present study was to explore the full spectrum of PASP and the long-term training impact in a large population of highly trained athletes., Methods: Six hundred fifteen consecutive athletes (370 endurance-trained athletes [ATEs] vs 245 strength-trained athletes [ATSs]; 28.4 ± 10.1 years old) and 230 healthy control subjects (27.5 ± 11.3 years old) underwent transthoracic echocardiography. PASP was estimated by measuring maximal tricuspid regurgitant jet velocity (TRV) with the modified Bernoulli equation. The ratio of TRV to right ventricular outflow tract time-velocity integral (TRV/RVOTTVI) was obtained as a correlate of pulmonary vascular resistance (PVR)., Results: Left ventricular (LV) mass index and ejection fraction did not differ significantly between the two groups of athletes. Conversely, ATSs showed an increased sum of wall thickness and relative wall thickness, whereas LV end-diastolic diameter, LV stroke volume, peak TRV, and PASP were significantly higher in ATEs. The ratio between transmitral E wave and tissue Doppler e' wave was not different among the three groups. The ratio TRV/RVOTTVI was ≤ 0.2 (ie, normal PVR) in all subjects. A TRV value > 2.5 m/s was observed in 76 athletes (12.3%). By multivariable analysis, age (P < .01), type and duration of training (P < .01), and LV stroke volume (P < .001) were the only independent predictors of PASP in athletes., Conclusions: This study delineates the full range of resting TRV and derived PASP in highly trained athletes. The upper physiologic limit of PASP in endurance athletes may reach 40 mm Hg, in line with the greater increase in stroke volume. This should be considered a "physiologic phenomenon" when evaluating athletes for sports eligibility.

Background: The aim of the study was to detect if right ventricular (RV) ejection fraction assessed by real-time 3-dimensional echocardiography (RT3DE) could predict patients with dilated cardiomyopathy (DCM) with greater functional impairment in response to cardiopulmonary exercise., Methods and Results: Seventy chronic heart failure patients with DCM (55.5 ± 9.1 years; 48 males; 30 ischemic; New York Heart Association Class III: 48) underwent both left ventricular (LV) and RV analysis by RT3DE. Postprocessing software provided data of RT3DE systolic dyssynchrony index of 16 LV segments (systolic dyssynchrony index [SDI]) and of both LV and RV ejection fraction. Cardiac magnetic resonance was performed in a subgroup of 40 DCM patients to confirm RT3DE measurements. All the patients underwent also bicycle cardiopulmonary exercise test with evaluation of oxygen consumption (VO2) peak% (percentage of the predicted value), VE/VCO2 slope, and circulatory power (CP). Mean LV ejection fraction was 29.8 ± 4.6%. RT3DE LV SDI index was 8.4.4 ± 4.2, and RV ejection fraction was 51.3 ± 4.6%. By cardiopulmonary test, mean VO2 peak was 15.2 ± 4.4 mL·kg·min, and mean CP was 2.1 ± 0.8. By univariable analyses, significant correlations were detectable between SDI index and VO2 peak% (r = -0.56; P < .0001) and peak CP (r = -0.48; P < .0005). Also RV ejection fraction directly correlated with VO2 peak% (r = 0.58; P < .0001) and inversely with VE/VCO2 slope (r = -0.44; P < .001). By multivariable analysis, SDI index (β coefficient = -0.46; P < .001) and 3D RV ejection fraction (β coefficient = 0.42; P < .001) emerged as the only independent determinants of VO2 peak% during cardiopulmonary test., Conclusions: Increased LV electromechanical dyssynchrony and impaired RV function in DCM patients are independently associated with worse ability to perform aerobic exercise., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: Atherosclerosis is characterized by endothelial inflammation and dysfunction. Adipose tissue has increasingly been recognized as an active endocrine organ secreting so-called adipokines. Among these, resistin--recently described, but not yet extensively studied--has been defined as a novel inflammatory marker in atherosclerosis. The pathophysiology underlying this interplay, however, remains to be fully characterized. The aim of the study is to determine whether resistin might affect prothrombotic characteristics of human coronary artery endothelial cells (HCAECs)., Methods and Results: Incubation of HCAECs with resistin caused upregulation of tissue factor (TF) expression as demonstrated by FACS analysis. Moreover, TF activity was induced in a dose-dependent manner, as shown by real-time PCR and colorimetric assay. Resistin-induced TF expression was mediated by oxygen free radicals through the activation of the transcription factor nuclear factor-κB (NF-κB), as demonstrated by electrophoretic mobility shift assay and by suppression of TF expression by superoxide dismutase, catalase, and the NF-κB inhibitors PDTC and BAY 11-7082., Conclusions: These data confirm the hypothesis that resistin may contribute to atherothrombosis, exerting direct effects on HCAECs by promoting TF expression; thus, it represents an effector molecule able to induce a prothrombotic phenotype in cells present in the vessel wall., (Copyright © 2010 S. Karger AG, Basel.)

Background: The aim of this study was to define the range of left ventricular (LV) velocities and deformation indexes in highly trained athletes, analyzing potential differences induced by different long-term training protocols., Methods: Standard echocardiography, pulsed-wave tissue Doppler echocardiography, and two-dimensional strain echocardiography of the interventricular septum and lateral wall were performed in 370 endurance athletes and 280 power athletes. Using pulsed-wave tissue Doppler, the following parameters of myocardial function were assessed: systolic peak velocities (S(m)), early (E(m)) and late (A(m)) diastolic velocities, and the E(m)/A(m) ratio. By two-dimensional strain echocardiography, peaks of regional systolic strain and LV global longitudinal strain were calculated., Results: LV mass index and ejection fraction did not significantly differ between the two groups. However, power athletes showed an increased sum of wall thicknesses (P < .01) and relative wall thickness, while LV stroke volume and LV end-diastolic diameter (P < .001) were greater in endurance athletes. By pulsed-wave tissue Doppler analysis, E(m) and E(m)/A(m) at both the septal and lateral wall levels were higher in endurance athletes. By two-dimensional strain echocardiography, myocardial deformation indexes were comparable between the two groups. E(m)/A(m) ratios ≥ 1 were found in the overall population, while 90 % of athletes had an E(m) ≥ 16 cm/sec, S(m) ≥ 10 cm/sec, and global longitudinal strain ≤ -16%. Multivariate analyses evidenced independent positive association between Em peak velocity and LV end-diastolic volume (P < .001) and an independent correlation of global longitudinal strain with the sum of LV wall thicknesses (P < .005)., Conclusions: This study describes the full spectrum of systolic and diastolic myocardial velocities and deformation indexes in a large population of competitive athletes., (Copyright © 2010 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

Aims: To analyse right ventricular (RV) myocardial deformation in patients with left ventricular (LV) hypertrophy secondary to either hypertrophic cardiomyopathy (HCM) or athlete's competitive endurance training., Methods and Results: Standard Doppler echo, exercise stress echo, and 2D speckle-tracking strain echocardiography (2DSE) of RV longitudinal deformation in RV septal and lateral walls were performed in 50 top-level endurance athletes and in 35 patients with HCM, all men, having evidence of LV hypertrophy. Right ventricular global longitudinal strain (GLS) was calculated by averaging local strains along the entire right ventricle. The two groups were comparable for age and blood pressure, whereas athletes showed lower heart rate and increased body surface area than HCM. Interventricular septal thickness was higher in HCM, whereas both LV and RV end-diastolic diameters (LVEDD and RVEDD) and LV stroke volume were increased in athletes. Right ventricular tricuspid annulus systolic excursion was comparable between the two groups. Conversely, RV GLS and regional peaks of RV myocardial strain were significantly impaired in patients with HCM (all P < 0.001). Multiple linear regression models detected an independent association between RV GLS and LVEDD (beta-coefficient = -0.68, P < 0.0001) in athletes, as well as an independent correlation of the same RV GLS with septal thickness (beta = 0.63, P < 0.0001) in HCM. An RV GLS cut-off value of -0.16% differentiated athletes and HCM with an 86% sensitivity and a 92% specificity. Furthermore, in the overall population, RV GLS (beta = 0.51, P < 0.0001) was a powerful independent predictor of maximal workload during exercise stress echo., Conclusion: Right ventricular myocardial systolic deformation is positively influenced by preload increase in athletes and negatively associated with increased septal thickness in HCM. Therefore, 2DSE may represent a useful tool in the differential diagnosis between athlete's heart and HCM, underlining the different involvement of RV myocardial function in either physiological or pathological LV hypertrophy.

Although cardiac adaptation to different sports has been extensively described, the potential effect of top-level training on the aortic root dimension remains not investigated fully. To explore the full range of aortic root diameters in athletes, 615 elite athletes (370 endurance-trained athletes and 245 strength-trained athletes; 410 men; mean age 28.4 +/- 10.2 years, range 18 to 40) underwent transthoracic echocardiography. The end-diastolic aortic diameters were measured at 4 locations: (1) the aortic annulus, (2) the sinuses of Valsalva, (3) the sinotubular junction, and (4) the maximum diameter of the proximal ascending aorta. Ascending aorta dilation at the sinuses of Valsalva was defined as a diameter greater than the upper limit of the 95% confidence interval of the overall distribution. The left ventricular (LV) mass index and ejection fraction did not significantly differ between the 2 groups. However, the strength-trained athletes had an increased body surface area, sum of wall thickness (septum plus LV posterior wall), LV circumferential end-systolic stress, and relative wall thickness. In contrast, the left atrial volume index, LV stroke volume, and LV end-diastolic diameter were greater in the endurance-trained athletes. The aortic root diameter at all levels was significantly greater in the strength-trained athletes (p <0.05 for all comparisons). However, ascending aorta dilation was observed in only 6 male power athletes (1%). Mild aortic regurgitation was observed in 21 athletes (3.4%). On multivariate analyses, in the overall population of athletes, the body surface area (p <0.0001), type (p <0.001) and duration (p <0.01) of training, and LV circumferential end-systolic stress (p <0.01) were the only independent predictors of the aortic root diameter at all levels. In conclusion, the aortic root diameter was significantly greater in elite strength-trained athletes than in age- and gender-matched endurance athletes. However, significant ascending aorta dilation and aortic regurgitation proved to be uncommon., (Copyright 2010 Elsevier Inc. All rights reserved.)

Background: Increase of left atrial (LA) diameter in trained athletes has been regarded as another component of the "athlete's heart"., Aims: To evaluate the possible impact of competitive training on LA volume and to define reference values of LA volume index in athletes., Methods and Results: Six hundred fifteen consecutive elite athletes (370 endurance- [ATE] vs 245 strength-trained athletes [ATS]; 385 men; 28.4 +/- 10.2 years, range 18-40 years) underwent a comprehensive transthoracic echocardiography exam. LA maximal volume was measured at the point of mitral valve opening using the biplane area-length method, and corrected for body surface area. LA mild dilatation was defined as a LA volume index between 29 and 33 mL/m(2), while a moderate dilatation was identified by a LA volume index > or =34 mL/m(2). Left ventricular (LV) mass index and ejection fraction did not significantly differ between the 2 groups. Conversely, ATS showed increased body surface area, sum of wall thickness (septum + LV posterior wall), LV circumferential end-systolic stress (ESSc) and relative wall thickness, whereas LA volume index, LV stroke volume and LV end-diastolic volume were greater in ATE. The range of LA volume index was 26 to 36 mL/m(2) (mean 28.2 +/- 9.2) in men and 22 to 33 mL/m(2) (mean 26.5 +/- 7.2) in women (P < .01). LA volume index was mildly enlarged in 150 athletes (24.3%) and moderately enlarged only in 20, all males (3.2%). Mild mitral regurgitation was observed in 64 athletes (10.3%). LA volume index was significantly greater in ATE (P < .01). By multivariate analysis, the overall population type (P < .01) and duration (P < .01) of training and LV end-diastolic volume (P < .001) were the only independent predictors of LA volume index., Conclusions: In a large population of highly trained athletes, a mild enlargement of LA volume index was relatively common and may be regarded as a physiologic adaptation to exercise conditioning., (Copyright 2010 Mosby, Inc. All rights reserved.)

Aims: To evaluate right atrial (RA) morphology and deformation in patients with dilated cardiomyopathy (DCM)., Methods and Results: A total of 130 patients with either idiopathic (n = 70) or ischaemic (n = 60) DCM, and 60 controls underwent clinical examination, standard echocardiography, and RA two-dimensional strain echocardiography (2DSE). Six months after implantation of a cardiac resynchronization therapy (CRT) device, the DCM patients were re-evaluated, if their left ventricular (LV) end-systolic volume had decreased by at least 15% they were defined as echocardiographic responders. All DCM patients were in NYHA class III before CRT, with a mean LV ejection fraction of 29.2 +/- 5.5%. After CRT, 94 patients were in NYHA functional class I-II. The patients were subdivided into echocardiographic responders (n = 85) and non-responders (n = 45). Both RA area index (19.7 +/- 5.5 cm(2)/m in non-responders vs. 13.2 +/- 4.4 cm(2)/m in responders; P < 0.001) and RA strain of lateral wall (24.3 +/- 10.2% in non-responders vs. 40.2 +/- 8.9% in responders; P < 0.001) were significantly different between the two groups. A RA area index >or=16 cm(2)/m showed a sensitivity and specificity of 87.1 and 95.4%, respectively (P < 0.0001) to predict a negative response to CRT. By multivariable analysis, increased RA area index (P < 0.001), ischaemic aetiology of DCM (P < 0.01), and less severe radial intraventricular dyssynchrony were independent determinants of an unfavourable response to CRT., Conclusion: Right atrial area index was increased and RA myocardial deformation was impaired in patients with DCM who were non-responders to CRT.

Objective: In dilated cardiomyopathy (DCM), right ventricular (RV) dysfunction has been reported and attributed both to altered loading conditions and to RV involvement in the myopathic process. The aim of the study was to detect RV myocardial function in DCM using two-dimensional (2D) strain echocardiography and to assess the effects of cardiac resynchronization therapy (CRT) on RV myocardial strain during a 6-month follow-up., Methods and Results: A total of 110 patients (mean age: 55.4 +/- 11.2 years) with either idiopathic (n = 60) or ischemic (n = 50) DCM, without overt clinical signs of RV failure, underwent standard echo and 2D strain analysis of RV longitudinal strain in RV septal and lateral walls. The two groups were comparable for clinical variables (New York Heart Association class III in 81.8%). Left ventricular volumes, ejection fraction, stroke volume, and mitral valve effective regurgitant orifice were similar between the two groups. No significant differences were evidenced in Doppler mitral and tricuspid inflow measurements. RV diameters were mildly increased in patients with idiopathic DCM, while RV tricuspid annulus systolic excursion and Tei-index were comparable between the two groups. RV global longitudinal strain and regional peak myocardial strain were significantly impaired in patients with idiopathic DCM compared with those having ischemic DCM (all P < 0.001). Using left ventricular end-systolic volume as marker for response to CRT, 70 patients (63.3%) were long-term responders. Ischemic DCM patient responders to CRT showed a significant improvement in RV peak systolic strain. Conversely, in patients with idiopathic DCM and in ischemic patients nonresponders to CRT, no improvement in RV function was evidenced. By multivariable analysis, in the overall population, ischemic etiology of DCM (P < 0.0001), positive response to CRT (P < 0.001), and longitudinal intraventricular dyssynchrony (P <0.01) emerged as the only independent determinants of RV global longitudinal strain after CRT., Conclusions: Two-dimensional strain represents a promising noninvasive technique to assess RV myocardial function in patients with DCM. RV myocardial deformation at baseline and after CRT are more impaired in idiopathic compared with ischemic DCM patients. Future longitudinal studies are warranted to understand the natural history of RV myocardial function, the extent of reversibility of RV dysfunction with CRT, and the possible prognostic impact of such indexes in patients with congestive heart failure.