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Background: Hemodynamic alterations in Fontan patients (FP) are associated with hemostatic dysbalance and Fontan-associated liver disease. Studies of other hepatopathologies indicate an interplay between cholestasis, tissue factor (TF), and von Willebrand factor (VWF). Hence, we hypothesized a relationship between the accumulation of bile acids (BA) and these hemostatic factors in FP. Methods: We included 34 FP (Phenprocoumon n = 15, acetylsalicylic acid (ASA) n = 16). BA were assessed by mass spectrometry. TF activity and VWF antigen (VWF:Ag) were determined by chromogenic assays. VWF collagen-binding activity (VWF:CB) was assessed via ELISA. Results: Cholestasis was observed in 6/34 FP (total BA ≥ 10 µM). BA levels and TF activity did not correlate (p = 0.724). Cholestatic FP had lower platelet counts (p = 0.013) from which 5/6 FP were not treated with ASA. VWF:Ag levels were increased in 9/34 FP and significantly lower in FP receiving ASA (p = 0.044). Acquired von Willebrand syndrome (AVWS) was observed in 10/34-FP, with a higher incidence in cholestatic FP (4/6) (p = 0.048). Conclusions: Cholestasis is unexpectedly infrequent in FP and seems to be less frequent under ASA therapy. Therefore, ASA may reduce the risk of advanced liver fibrosis. FP should be screened for AVWS to avoid bleeding events, especially in cholestatic states.

Right heart dysfunction and failure is the principal determinant of adverse outcomes in patients with pulmonary arterial hypertension (PAH). In addition to right ventricular (RV) dysfunction, systemic congestion, increased afterload and impaired myocardial contractility play an important role in the pathophysiology of RV failure. The behavior of the RV in response to the hemodynamic overload is primarily modulated by the ventricular interaction and its coupling to the pulmonary circulation. The presentation can be acute with hemodynamic instability and shock or chronic producing symptoms of systemic venous congestion and low cardiac output. The prognostic factors associated with poor outcomes in hospitalized patients include systemic hypotension, hyponatremia, severe tricuspid insufficiency, inotropic support use and the presence of pericardial effusion. Effective therapeutic management strategies involve identification and effective treatment of the triggering factors, improving cardiopulmonary hemodynamics by optimization of volume to improve diastolic ventricular interactions, improving contractility by use of inotropes, and reducing afterload by use of drugs targeting pulmonary circulation. The medical therapies approved for PAH act primarily on the pulmonary vasculature with secondary effects on the right ventricle. Mechanical circulatory support as a bridge to transplantation has also gained traction in medically refractory cases. The current review was undertaken to summarize recent insights into the evaluation and treatment of RV dysfunction and failure attributable to PAH.

The aim of this review is to highlight the strengths and limitations of major echocardiographic biventricular repair (BVR) prediction models for borderline left ventricle (LV) in complex congenital heart disease (CHD). A systematic search in the National Library of Medicine for Medical Subject Headings and free text terms including echocardiography, CHD, and scores, was performed. The search was refined by adding keywords for critical aortic stenosis (AS), borderline LV, complex left ventricular outflow tract (LVOT) obstruction, hypoplastic left heart syndrome/complex (HLHS/HLHC), and unbalanced atrio-ventricular septal defects (uAVSD). Fifteen studies were selected for the final analysis. We outlined what echocardiographic scores for different types of complex CHD with diminutive LV are available. Scores for CHD with LVOT obstruction including critical AS, HLHS/HLHC, and aortic arch hypoplasia have been validated and implemented by several studies. Scores for uAVSD with right ventricle (RV) dominance have also been established and implemented, the first being the atrioventricular valve index (AVVI). In addition to AVII, both LV/RV inflow angle and LV inflow index have all been validated for the prediction of BVR. We conclude with a discussion of limitations in the development and validation of each of these scores, including retrospective design during score development, heterogeneity in echocardiographic parameters evaluated, variability in the definition of outcomes, differences in adopted surgical and Interventional strategies, and institutional differences. Furthermore, scores developed in the past two decades may have little clinical relevance now. In summary, we provide a review of echocardiographic scores for BVR in complex CHD with a diminutive LV that may serve as a guide for use in modern clinical practice.

Background Postexercise release of cardiac troponin (cTn) is a well-known phenomenon, although the influence of various confounders remains unclear. The aim of this critical review was to analyze the postexercise release of cTn according to age, sex, different types of sport, exercise intensity and duration, and training level. Data sources A literature search was performed within the National Library of Medicine using the following keywords: cTn, peak, release, and exercise. The search was further refined by adding the keywords athletes, children/adolescents, and sport. Main results For final analysis, 52 studies were included: 43 adult studies, 4 pediatric studies, and 5 with a mixed population of adults and children. Several studies have investigated the kinetics of cTn response after exercise with different biomarkers. The current evidence suggests that sport intensity and duration have significant effects on postexercise cTn elevation, whereas the influence of the type of sport, age, and sex have been not completely defined yet. Most data were obtained during endurance races, whereas evidence is limited (or almost absent), particularly for mixed sports. Data on young adults and professional athletes are limited. Finally, studies on women are extremely limited, and those for non-White are absent. Conclusions Postexercise release of cTn can be observed both in young and master athletes and usually represents a physiological phenomenon; however, more rarely, it may unmask a subclinical cardiac disease. The influence of different confounders (age, sex, sport type/intensity/duration, and training level) should be better clarified to establish individualized ranges of normality for postexercise cTn elevation.

While invasive assessment of hemodynamics and testing of acute vasoreactivity in the catheterization laboratory is the gold standard for diagnosing pulmonary hypertension (PH) and pulmonary vascular disease (PVD) in children, transthoracic echocardiography (TTE) serves as the initial diagnostic tool. International guidelines suggest several key echocardiographic variables and indices for the screening studies when PH is suspected. However, due to the complex anatomy and special physiological considerations, these may not apply to patients with congenital heart disease (CHD). Misinterpretation of TTE variables can lead to delayed diagnosis and therapy, with fatal consequences, or–on the other hand-unnecessary invasive diagnostic procedures that have relevant risks, especially in the pediatric age group. We herein provide an overview of the echocardiographic workup of children and adolescents with PH with a special focus on children with CHD, such as ventricular/atrial septal defects, tetralogy of Fallot or univentricular physiology. In addition, we address the use of echocardiography as a tool to assess eligibility for exercise and sports, a major determinant of quality of life and outcome in patients with PH associated with CHD.

Background To report first clinical experience on three cases of congenital complete heart block and the use of a pacemaker system with a maximum lower rate interval of 95 beats per minute. Methods We retrospectively analyzed three patients treated with a pacemaker system with a maximum lower rate interval of 95 beats per minute suffering from congenital complete heart block. We report a follow up period of 2.9 years, focusing on the patients’ growth, development, and adverse events, as well as pacemaker function. Results In all three patients pacemaker function was impeccable, including minute ventilation sensor rate adaption. All patients showed limited growths as expected, adequate development, good feeding tolerability and circadiane heart rate adaption. One patient experienced skin traction and revision. All patients showed high aortic velocity time integral values after birth. Conclusion The use of a pacemaker system with a maximum lower rate interval of 95 beats per minute in infants suffering from congenital complete heart block and showing high aortic VTI values seems to be feasible and to result in limited growths but adequate development. Electronic supplementary material The online version of this article (10.1186/s12887-019-1494-7) contains supplementary material, which is available to authorized users.

Anomalous aortic origin of coronary arteries (AAOCA) represents a rare congenital heart disease. However, this disease is the second most common cause of sudden cardiac death in apparently healthy athletes. The aim of this systematic review is to analyze the feasibility and the detection rate of AAOCA by echocardiography in children and adults. A literature search was performed within the National Library of Medicine using the following keywords: coronary artery origin anomalies and echocardiography; then, the search was redefined by adding the keywords: athletes, children, and high take-off. Nine echocardiographic studies investigating AAOCA and a total of 33,592 children and adults (age range: 12–49 years) were included in this review. Of these, 6599 were athletes (12–49 years). All studies demonstrated a high feasibility and accuracy of echocardiography for the evaluation of coronary arteries origin as well as their proximal tracts. However, some limitations exist: the incidence of AAOCA varied from 0.09% to 0.39% (up to 0.76%) and was lower than described in computed tomography series (0.3–1.8%). Furthermore, echocardiographic views for the evaluation of AAOCA and the definition of “minor” defects (e.g., high take-off coronary arteries) have not been standardized. An echocardiographic protocol to diagnose the high take-off of coronary arteries is proposed in this article. In conclusion, the screening of AAOCA by echocardiography is feasible and accurate when appropriate examinations are performed; however, specific acoustic windows and definitions of defects other than AAOCA need to be standardized to improve sensitivity and specificity.

BACKGROUND: Pulmonary arterial hypertension (PAH) is common in congenital heart disease (CHD). Because clinical-trial data on PAH associated with CHD (PAH-CHD) remain limited, registry data on the long-term course are essential. This analysis aimed to update information from the COMPERA-CHD registry on management strategies based on real-world data. METHODS: The prospective international pulmonary hypertension registry COMPERA has since 2007 enrolled more than 10,000 patients. COMPERA-CHD is a sub-registry for patients with PAH-CHD. RESULTS: A total of 769 patients with PAH-CHD from 62 specialized centers in 12 countries were included into COMPERA-CHD from January 2007 through September 2020. At the last follow-up in 09/2020, patients [mean age 45.3±16.8 years; 512 (66%) female] had either post-tricuspid shunts (n=359; 46.7%), pre-tricuspid shunts (n=249; 32.4%), complex CHD (n=132; 17.2%), congenital left heart or aortic valve or aortic disease (n=9; 1.3%), or miscellaneous CHD (n=20; 2.6%). The mean 6-minute walking distance was 369±121 m, and 28.2%, 56.0%, and 3.8% were in WHO functional class I/II, III or IV, respectively (12.0% unknown). Compared with the previously published COMPERA-CHD data, after 21 months of follow-up, the number of included PAH-CHD patients increased by 91 (13.4%). Within this group the number of Eisenmenger patients rose by 39 (16.3%), the number of "Non-Eisenmenger PAH" patients by 45 (26.9%). Currently, among the 674 patients from the PAH-CHD group with at least one follow-up, 450 (66.8%) received endothelin receptor antagonists (ERA), 416 (61.7%) PDE-5 inhibitors, 85 (12.6%) prostacyclin analogues, and 36 (5.3%) the sGC stimulator riociguat. While at first inclusion in the COMPERA-CHD registry, treatment was predominantly monotherapy (69.3%), this has shifted to favoring combination therapy in the current group (53%). For the first time, the nature, frequency, and treatment of significant comorbidities requiring supportive care and medication are described. CONCLUSIONS: Analyzing "real life data" from the international COMPERA-CHD registry, we present a comprehensive overview about current management modalities and treatment concepts in PAH-CHD. There was an trend towards more aggressive treatment strategies and combination therapies. In the future, particular attention must be directed to the "Non-Eisenmenger PAH" group and to patients with complex CHD, including Fontan patients. TRIAL REGISTRATION: www.clinicaltrials.gov, study identifier: Clinicaltrials.gov NCT01347216. ispartof: CARDIOVASCULAR DIAGNOSIS AND THERAPY vol:11 issue:6 pages:1255-1268 ispartof: location:China status: published

We report applications of novel high-frame rate blood speckle tracking (BST) echocardiography in a series of infants with congenital heart disease (CHD). BST echocardiography was highly feasible, reproducible, and fast. High-frame rate BST provided complimentary information to conventional color-Doppler data enhancing the visualization and understanding of anomalous blood trajectories (e.g., shunt direction, regurgitant volumes, and stenotic jets) and vortex formation. High-frame rate BST echocardiography is a new, promising imaging tool that may be helpful for deeper understanding of complex CHD physiology.

Background: It has been reported that women have a higher number of heart attacks in the &ldquo, follicular phase&rdquo, of the menstrual cycle. We, therefore, tested the hypothesis that women in the follicular phase exhibit higher coagulability. As lower body negative pressure (LBNP) has been used previously to assess coagulation changes in whole blood (WB) samples in men and women, effects of menstrual phase on coagulation was assessed during LBNP. Methods: Seven women, all healthy young participants, with no histories of thrombotic disorders and not on medications, were tested in two phases of the menstrual cycle (early follicular (EF) and mid-luteal (ML)). LBNP was commenced at &minus, 10 mmHg and increased by &minus, 10 mmHg every 5 min until a maximum of &minus, 40 mmHg. Recovery up to 10 min was also monitored. Blood samples were collected at baseline, at end of LBNP, and at end of recovery. Hemostatic profiling included comparing the effects of LBNP on coagulation values in both phases of the menstrual cycle using standard coagulation tests, calibrated automated thrombogram, thrombelastometry, impedance aggregometry, and markers of thrombin formation. Results: LBNP led to coagulation activation determined in both plasma and WB samples. During both phases, coagulation was affected during LBNP, as reflected in their decreased partial thromboplastin time (PTT) and elevated coagulation factor VIII FVIII, F1 + 2, and thrombin-antithrombin (TAT) levels. Additionally, during the ML phase, greater PT [%] and shorter time to peak (ttPeak) values (implying faster maximum thrombin formation) suggest that women in the ML phase are relatively hypercoagulable compared to the early follicular phase. Conclusions: These results suggest that thrombosis occurs more during the midluteal phase, a finding with substantial medical implications.

Introduction: Pulmonary hypertension (PH) is a common complication in patients with congenital heart disease (CHD), aggravating the natural, post-operative, or post-interventional course of the underlying anomaly. The various CHDs differ substantially in characteristics, functionality, and clinical outcomes among each other and compared with other diseases with pulmonary hypertension. Objective: To describe current management strategies and outcomes for adults with PH in relation to different types of CHD based on real-world data. Methods and results: COMPERA (Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension) is a prospective, international PH registry comprising, at the time of data analysis, &gt, 8200 patients with various forms of PH. Here, we analyzed a subgroup of 680 patients with PH due to CHD, who were included between 2007 and 2018 in 49 specialized centers for PH and/or CHD located in 11 European countries. At enrollment, the patients&acute, median age was 44 years (67% female), and patients had either pre-tricuspid shunts, post-tricuspid shunts, complex CHD, congenital left heart or aortic disease, or miscellaneous other types of CHD. Upon inclusion, targeted therapies for pulmonary arterial hypertension (PAH) included endothelin receptor antagonists, PDE-5 inhibitors, prostacyclin analogues, and soluble guanylate cyclase stimulators. Eighty patients with Eisenmenger syndrome were treatment-na&iuml, ve. While at inclusion the primary PAH treatment for the cohort was monotherapy (70% of patients), with 30% of the patients on combination therapy, after a median observation time of 45.3 months, the number of patients on combination therapy had increased significantly, to 50%. The use of oral anticoagulants or antiplatelets was dependent on the underlying diagnosis or comorbidities. In the entire COMPERA-CHD cohort, after follow-up and receiving targeted PAH therapy (n = 511), 91 patients died over the course of a 5-year follow up. The 5-year Kaplan&ndash, Meier survival estimate for CHD associated PH was significantly better than that for idiopathic PAH (76% vs. 54%, p &lt, 0.001). Within the CHD associated PH group, survival estimates differed particularly depending on the underlying diagnosis and treatment status. Conclusions: In COMPERA-CHD, the overall survival of patients with CHD associated PH was dependent on the underlying diagnosis and treatment status, but was significantly better as than that for idiopathic PAH. Nevertheless, overall survival of patients with PAH due to CHD was still markedly reduced compared with survival of patients with other types of CHD, despite an increasing number of patients on PAH-targeted combination therapy.

Pulmonary hypertension (PH) is a progressive disease affecting patients across the life span. The pathophysiology primarily involves the pulmonary vasculature and right ventricle (RV), but eventually affects the left ventricular (LV) function as well. Safe, accurate imaging modalities are critical for diagnosis, serial monitoring, and tailored therapy. While cardiac catheterization remains the conventional modality for establishing diagnosis and serial monitoring, noninvasive imaging has gained considerable momentum in providing accurate assessment of the entire RV-pulmonary axis. In this state-of-the-art review, we will discuss the most recent developments in echocardiography, magnetic resonance imaging, and computed tomography in PH evaluation from pediatric to adult population.

Background Left ventricular (LV) volumes are basic parameters used to estimate ventricular size and function; however, normal values are not available in children. The aim of our study is to provide normal values for LV volumes (measured with the biplane Simpson method) in healthy children. Materials and methods We prospectively studied 1320 healthy Caucasian Italian children (age 0 days-17 years, 49.4% female). Echocardiographic measurements on LV volumes were performed. Age, heart rate (HR), and body surface area (BSA) were used as independent variables in different analyses to predict the mean values of each measurement. Results Models with exponential (ln[y] = a + b*ln[x]) equations resulted in the best fit for LV volumes. The association with BSA was found to be stronger than the association of HR and age. Thus BSA was used for normalization of our data. Predicted values and Z-score boundaries by BSA are provided. Conclusions We report normal values for 2D biplane LV volumes in a population of healthy children. These data cover a gap in current pediatric echocardiographic nomograms and may serve as baseline for evaluation of children with cardiac defects characterized by LV dilatation or hypoplasia.

Background: Lung ultrasound (LUS) in pediatric cardiac surgery is gaining consensus. We (1) evaluated the prognostic value of a new LUS-score in pediatric cardiac surgery, and (2) compared LUS-score to conventional risk factors including age, The Society of Thoracic Surgeons/European Association of Cardio-Thoracic Surgery (STAT) score, cardiopulmonary bypass time, and prognostic biomarkers including brain natriuretic peptide and cystatin-C. Methods: LUS examinations were performed in 237 children (median age, 0.55 years; interquartile range, 0.09-4.15 years) at 12 to 36 hours after surgery. For each hemithorax, 3 areas (anterior/lateral/posterior) were evaluated in the upper and lower halves, constituting 12 total scanning areas. For each site a score was assigned: 0 (rare B lines), 1 (separated B lines), 2 (coalescent B lines), 3 (loss of aeration), and total LUS score was calculated as sum of all sites. The primary endpoints were intensive care unit length of stay and extubation time. Results: The mean total LUS score was 12.88 ± 6.41 (range, 0-26) and was higher in newborns (16.77 ± 5.25) compared with older children (5.36 ± 5.57; P < .001). On univariate analysis, LUS score was associated inversely with age (beta 0.26; P = .004) and body surface area (beta 3.41 P = .006) and positively with brain natriuretic peptide (beta 1.65; P < .001) and cystatin-C (beta 2.41; P < .001). The LUS score, when added as continuous predictor to a conventional risk model (age, STAT score, and cardiopulmonary bypass time) emerged significant both for intensive care unit length of stay (beta 0.145, P = .047) and extubation time (beta 1.644; P = .024). When single quadrants were analyzed, only anterior LUS score was significant (intensive care unit length of stay beta, 0.471; P = .020; extubation time beta 5.530; P = .007). Conclusions: Our data show the prognostic incremental value of a new LUS score over traditional risk factors in pediatric cardiac surgery.

The European Pediatric Pulmonary Vascular Disease Network is a registered, non-profit organization that strives to define and develop effective, innovative diagnostic methods and treatment options in all forms of pediatric pulmonary hypertensive vascular disease, including pulmonary hypertension (PH) associated with bronchopulmonary dysplasia, PH associated with congenital heart disease (CHD), persistent PH of the newborn, and related cardiac dysfunction. The executive writing group members conducted searches of the PubMed/MEDLINE bibliographic database (1990-2018) and held face-to-face and web-based meetings. Ten section task forces voted on the updated recommendations, based on the 2016 executive summary. Clinical trials, meta-analyses, guidelines, and other articles that include pediatric data were searched using the term "pulmonary hypertension" and other keywords. Class of recommendation (COR) and level of evidence (LOE) were assigned based on European Society of Cardiology/American Heart Association definitions and on pediatric data only, or on adult studies that included >10% children or studies that enrolled adults with CHD. New definitions by the World Symposium on Pulmonary Hypertension 2018 were included. We generated 10 tables with graded recommendations (COR/LOE). The topics include diagnosis/monitoring, genetics/biomarkers, cardiac catheterization, echocardiography, cardiac magnetic resonance/chest computed tomography, associated forms of PH, intensive care unit/lung transplantation, and treatment of pediatric PH. For the first time, a set of specific recommendations on the management of PH in middle- and low-income regions was developed. Taken together, these executive, up-to-date guidelines provide a specific, comprehensive, detailed but practical framework for the optimal clinical care of children and young adults with PH.

Determination of biventricular dimensions, function, and ventricular–ventricular interactions (VVI) is an essential part of the echocardiographic examination in adults with pulmonary hypertension (PH); however, data from according pediatric studies are sparse. We hypothesized that left and right heart dimensions/function and VVI variables indicate disease severity and progression in children with PH. Left heart, right heart, and VVI variables (e.g. end-systolic LV eccentricity index [LVEI], right ventricular [RV]/left ventricular [LV] dimension ratio) were echocardiographically determined in 57 children with PH, and correlated with New York Heart Association (NYHA) functional class (FC), N-terminal-pro brain natriuretic peptide (NT-proBNP), and invasive hemodynamic variables (e.g. pulmonary vascular resistance index [PVRi]). Clinically sicker patients (higher NYHA FC) had lower LV ejection fraction (LVEF) and higher LVEI – a surrogate of LV compression. In PH children, the ratio of systolic pulmonary arterial pressure divided by systolic systemic arterial pressure (sPAP/sSAP) and the PVRi correlated well with the LVEI ( P

We here report a neonate with prenatal echocardiographic diagnosis of tricuspid atresia, with normally related great vessels, and large ventricular septal defect. This diagnosis could be confirmed with echocardiography at birth. An additional double mitral orifice was also seen. This is a very rare association.

BACKGROUND: Echocardiographic determination of RV end‐systolic base/apex (RVES b/a) ratio was proposed to be of clinical value for assessment of pulmonary arterial hypertension (PAH) in adults. HYPOTHESIS: We hypothesized that the RVES b/a ratio will be affected in children with PAH and aimed to correlate RVES b/a ratio with conventionally used echocardiographic and hemodynamic variables, and with New York Heart Association (NYHA) functional class. METHODS: First we determined normal pediatric values for RVES b/a ratio in 157 healthy children (68 males; age range, 0.5–17.7 years). We then conducted an echocardiographic study in 51 children with PAH (29 males; age range, 0.3–17.8 years). RESULTS: RVES b/a ratio was lower compared with age‐ and sex‐matched healthy controls (P < 0.001). In children with PAH, RVES b/a ratio decreased with worsening NYHA class. RVES b/a ratio inversely correlated with RV/LV end‐systolic diameter ratio (ρ = −0.450, P = 0.001) but did not correlate with RV systolic function parameters (eg, tricuspid annular plane systolic excursion) and correlated with cardiac catheterization–determined pulmonary vascular resistance index (ρ = −0.571, P < 0.001). ROC analysis unraveled excellent performance of RVES b/a ratio to detect PAH in children (AUC: 0.95, 95% CI: 0.89–1.00, P < 0.001). CONCLUSIONS: The RVES b/a ratio decreased in children with PAH compared with age‐ and sex‐matched healthy subjects. The RVES b/a ratio inversely correlated with both echocardiographic and hemodynamic indicators of increased RV pressure afterload and with NYHA class, suggesting that RVES b/a ratio reflects disease severity in PAH children.

Background The sub-costal examination of the heart is part of routine examination in pediatric echocardiography, and has the advantage to visualize also the infundibulum part of the right ventricle (RV). Despite this fact, currently nomograms for sub-costal RV dimensions are lacking. Methods We prospectively studied healthy Caucasian Italian children by two-dimensional echocardiography. Measurements included: sub-costal end diastolic basal-apical and latero-lateral diameters, end diastolic and end systolic area, 4 chamber end diastolic and end systolic area and length, end diastolic basal (RV1) and mid-cavity (RV2) diameters. Age, weight, height, heart rate (HR), and body surface area (BSA) were used as independent variables in different analyses to predict the mean values of each measurement. Structured Z scores were then computed. Agreement of RV diameters and areas in subcostal view and 4-chamber view were investigated. Results 732 subjects (age 0 days-17 years; 48% female; BSA 0.12-2.12 m2) were studied. The Haycock formula was used when presenting data as predicted values (mean ± 2 SDs) for a given BSA and within equations relating echocardiographic measurements to BSA. The predicted values and Z-score boundaries for all measurements are presented. Excellent correlations were found among two-dimensional diameters and area calculated in sub-costal view with those evaluated in 4-chamber view. Conclusions We report echocardiographic nomograms for RV diameters and areas measured in the sub-costal view. Our data may implement normative data for 2D echocardiography evaluation of the RV in children.

Background Ethyl pyruvate (EP) exerts anti-inflammatory and anti-oxidative properties. The aim of our study was to investigate whether EP is capable of inhibiting the oxidation of LDL, a crucial step in atherogenesis. Additionally, we examined whether EP attenuates the cytotoxic effects of highly oxidized LDL in the human vascular endothelial cell line EA.hy926. Methods Native LDL (nLDL) was oxidized using Cu2+ ions in the presence of increasing amounts of EP. The degree of LDL oxidation was quantified by measuring lipid hydroperoxide (LPO) and malondialdehyde (MDA) concentrations, relative electrophoretic mobilities (REMs), and oxidation-specific immune epitopes. The cytotoxicity of these oxLDLs on EA.hy926 cells was assessed by measuring cell viability and superoxide levels. Furthermore, the cytotoxicity of highly oxidized LDL on EA.hy926 cells under increasing concentrations of EP in the media was assessed including measurements of high energy phosphates (ATP). Results Oxidation of nLDL using Cu2+ ions was remarkably inhibited by EP in a concentration-dependent manner, reflected by decreased levels of LPO, MDA, REM, oxidation-specific epitopes, and diminished cytotoxicity of the obtained oxLDLs in EA.hy926 cells. Furthermore, the cytotoxicity of highly oxidized LDL on EA.hy926 cells was remarkably attenuated by EP added to the media in a concentration-dependent manner reflected by a decrease in superoxide and an increase in viability and ATP levels. Conclusions EP has the potential for an anti-atherosclerotic drug by attenuating both, the oxidation of LDL and the cytotoxic effect of (already formed) oxLDL in EA.hy926 cells. Chronic administration of EP might be beneficial to impede the development of atherosclerotic lesions.

Albumin is the most abundant plasma protein. Critical illness is often associated with altered, predominately decreased, serum albumin levels. This hypoalbuminaemia is usually corrected by administration of exogenous albumin. This study aimed to track the concentration-dependent influence of albumin on blood coagulation in vitro. Whole blood (WB) samples from 25 volunteers were prepared to contain low (19.3 ± 7.7 g/L), physiological (45.2 ± 7.8 g/L), and high (67.5 ± 18.1 g/L) levels of albumin. Haemostatic profiling was performed using a platelet function analyzer (PFA) 200, impedance aggregometry, a Cone and Platelet analyzer (CPA), calibrated automated thrombogram, and thrombelastometry (TEM). Platelet aggregation-associated ATP release was assessed via HPLC analysis. In the low albumin group, when compared to the physiological albumin group, we found: i) shortened PFA 200-derived closure times indicating increased primary haemostasis; ii) increased impedance aggregometry-derived amplitudes, slopes, ATP release, as well as CPA-derived average size indicating improved platelet aggregation; iii) increased TEM-derived maximum clot firmness and alpha angles indicating enhanced clot formation. TEM measurements indicated impaired clot formation in the high albumin group compared with the physiological albumin group. Thus, albumin exerted significant anticoagulant action. Therefore, low albumin levels, often present in cancer or critically ill patients, might contribute to the frequently occurring venous thromboembolism.

Immobilization in hospitalized medical patients or during simulation of spaceflight induced deconditioning has been shown to be associated with loss of muscle mass and bone. Resistance vibrating exercise (RVE) and/or high protein diet are countermeasures, which are capable of mitigating the adverse effects of immobilization. We investigated the effect of these countermeasures on the coagulation system. Two groups of volunteers, each of whom performed such countermeasures, were enrolled in the study. Volunteers, who did nothing while bed rested, served as controls. The berest and the intervention protocols were carried out at Clinique d’ Investigation, MEDES, Toulouse, France. Eleven healthy men volunteered for this randomized crossover study. The subjects underwent 21 day of 6° head down bed rest (HDBR) followed by a washout period of 4 months. The first group followed an exercise schedule using resistance-vibrating exercise (RVE group). The second group also used the RVE but complemented it with high-protein supplement diet (NeX group). The third group only did bed rest. The highly sensitive methods calibrated automated thrombography (CAT) and thrombelastometry (TEM) were applied to monitor hemostatic changes. In all 3 groups, the hemostatic system shifted toward hypocoagulability during bed rest. For example, peak and thrombin formation velocity (VELINDEX) reduced in this period. Interestingly, a tendency toward hypercoagulation was observed during re-ambulation. In all 3 groups, ttPeak and StartTail were reduced, and Peak and VELINDEX (except in the RVE group) were significantly higher in relation to baseline values. Influence of bed rest on the coagulation system in the 2 groups performing countermeasures (RVE and NeX group) was the same as in the control bed-rested group. Clotting does not seem to be worsened by prolonged immobilization, or by countermeasures such as RVE/exercise or high-protein supplementation during immobilization. Therefore, only hospitalized medical patients at an elevated risk for thrombosis should be treated with anticoagulants. However, clinicians have to be aware that the re-ambulation period following immobilization might be associated with an elevated risk of thrombotic events.

Laser acupuncture bears a potential risk for the skin surface, especially in neonates whose skin has histological and physiological peculiarities. We evaluated thermal changes of skin temperature in neonates during laser acupuncture by using a thermal camera (Flir i5, Flir Systems Inc., Portland, USA). Laserneedles (Laserneedle GmbH, Glienicke/Nordbahn, Germany) were fixed to the skin at Large Intestine 4 (LI 4,Hegu), bilaterally. Before application of laser acupuncture (685 nm, 15 mW, 500 μm), as well as after 1, 5, and 10 min, thermographic pictures of both hands were taken. The measuring was carried out on the 23rd day after birth (20 neonates, mean postmenstrual gestational age 38 + 2, mean weight 2604 g). Compared to the initial temperature of 34.2°C on the right hand, the skin temperature had increased to 35.3°C (P<0.05) after 5 min and up to 36.1°C (P<0.05) after 10 min of stimulation. Equally, on the left hand, an increase of the skin temperature from 34.5°C to 35.9°C (P<0.05) and 35.9°C (P<0.05) was measured. The highest measured skin temperature after 10 min of stimulation amounted to 38.7°C, without any clinically visible changes on the skin surface.

Editor: We read with great interest the article “Magnetic Resonance Imaging of the Right Ventricle in Pediatric Pulmonary Arterial Hypertension” by Blalock et al.1 They present highly valuable cardiac magnetic resonance (CMR) data on children with idiopathic pulmonary arterial hypertension (IPAH) without a secondary cause of PAH, such as congenital heart disease (CHD). It has recently been shown that in patients with chronic pressure overload the resulting right ventricular (RV) myocardial damage can be demonstrated by an impaired RV long-axis function.2 Blalock and colleagues found an impaired RV function in children with IPAH. They describe an increased indexed RV end-diastolic volume (RVEDVi) and a reduced RV ejection fraction in comparison to healthy controls. For the convenience of the audience of Pulmonary Circulation, we want to add that their data are in agreement with results obtained in patients with PAH secondary to CHD (PAH-CHD).3,4 However, we find a higher RVEDVi in PAH-CHD patients, which might be related to their multiple surgical procedures. It has been shown that echocardiographic measures of systolic RV function, such as tricuspid annular peak systolic velocity and tricuspid annular plane systolic excursion, correlate with CMR data on patients with PAH-CHD.3,4 Considering that about half of PAH patients in childhood have underlying CHD,5 the CMR results of Blalock and colleagues and the respective echocardiographic results of Kassem et al.6 in patients with IPAH add up to our data in PAH-CHD patients and together provide a compact image of RV function in pediatric PAH patients. We want to thank the authors for addressing the need to investigate RV function parameters in children with IPAH. In the future, with increasing data in pediatric PAH patients, echocardiography, in addition to the gold standard method, CMR, may become the technique of choice for routine assessment of systolic RV function in the follow-up of patients with PAH.