Effects of hemodialysis on blood volume, macro- and microvascular function.

BACKGROUND: Vascular dysfunction is considered to spur the progression of cardiovascular disease in hemodialysis (HD) patients. Whether the HD procedure itself contributes to vascular dysfunction remains incompletely investigated. The present study sought to comprehensively assess the effects of HD on arterial and venous function along with concomitant changes in blood volume (BV). METHODS AND RESULTS: We determined BV with high-precision, automated carbon monoxide-rebreathing, arterial stiffness using applanation tonometry and intrinsic microvascular function via retinal vessel analysis prior to and after conventional 4-hour HD in fasting-controlled conditions in 10 patients. All HD patients were non-smokers and non-obese (body mass index = 22.8 ±â€¯2.8 m·kg-2). Hypertension (70%), coronary artery disease (40%) and diabetes mellitus (20%) were the most prevalent comorbidities. Prior to HD, all patients presented with hypervolemia (+2208 ±â€¯1213 ml). HD decreased body weight (-1.72 ±â€¯1.25 kg, P = 0.002) and plasma volume (-689 ±â€¯566 ml, P = 0.004), while hematocrit (Hct) was concomitantly increased (+4.8 ±â€¯4.5%, P = 0.009). HD did not affect large elastic artery stiffness, as determined by carotid-femoral pulse wave velocity (P = 0.448) and carotid distensibility (P = 0.562). In contrast, flicker light-induced retinal venular dilation was reduced by three-fourths after HD (-2.4 ±â€¯1.7%, P = 0.039), in parallel to increased retinal venular diameter (+11.2 ±â€¯4.9 µm, P = 0.002). In regression analyses, a negative association was observed between HD-induced changes in Hct and retinal venular dilation (r ≥ -0.89, P ≤ 0.045). CONCLUSION: Conventional HD resulting in substantial plasma volume removal do not alter large artery elastic properties, whereas intrinsic microvascular venular dilator function is markedly impaired, an effect directly associated with the increase in hemoconcentration.

Retinal microvascular dysfunction in heart failure.

Aims: Retinal vessel analysis (RVA) represents a novel, non-invasive, and reliable method to study the microcirculation in the eye. The goal of this study was to assess the extent of retinal microvascular dysfunction in patients with chronic heart failure (CHF) compared to controls and established measures of vascular function. Methods and results: In this prospective, single-centre, observational study, 74 patients with compensated CHF (mean age 63.5 ± 11.2 years, 32% female, mean left-ventricular ejection fraction 37 ± 12.8%), 74 patients with cardiovascular risk factors (CVRF; 64.1 ± 12.7 years, 34% female), and 74 healthy controls (HC; 57.8 ± 14.2 years, 35% female) were included. The primary endpoint, flicker-induced dilatation of retinal arterioles (FIDart), was significantly reduced in patients with CHF compared to CVRF and HC (mean FIDart 0.9 ± 0.2 vs. 2.3 ± 0.3 and vs. 3.6 ± 0.3%, respectively, both P < 0.001 before and after propensity score-weighted analysis). Similar differences were seen for venular FID. FIDart was less impaired in patients with dilated compared to ischaemic cardiomyopathy. No significant differences were observed for arteriovenous ratio and flow-mediated dilatation. Impaired FIDven was associated with echocardiographically estimated systolic pulmonary artery pressure and left atrial volume index. Conclusion: Retinal microvascular dilatation in response to flicker light is impaired in CHF. RVA may represent a new and useful method to non-invasively monitor microvascular abnormalities in heart failure in an easy and standardized way without the use of radiation.

AAV6.ßARKct cardiac gene therapy ameliorates cardiac function and normalizes the catecholaminergic axis in a clinically relevant large animal heart failure model.

AIMS: G protein-coupled receptor kinase 2 (GRK2), which is markedly upregulated in failing human myocardium, has been implicated as a contributing factor or consequence of heart failure (HF). Importantly, cardiac-specific GRK2 knockout mice have recently proved the pathological nature of GRK2 in HF. Targeted inhibition of GRK2 is possible using a peptide inhibitor known as the ßARKct, which has rescued several disparate small animal HF models. This study was designed to evaluate long-term ßARKct expression in a clinically relevant large animal HF model, using stable myocardial gene delivery with adeno-associated virus serotype 6 (AAV6). METHODS AND RESULTS: A porcine model of HF subsequent to left ventricular (LV) myocardial infarction (MI) was used to study the effects of retrograde injection into the anterior interventricular vein of either AAV6.ßARKct or AAV6.luciferase as a control 2 weeks after MI. Echocardiography and LV hemodynamics were performed before and 6 weeks after gene transfer. Robust and long-term ßARKct expression was found after AAV6-mediated delivery, leading to significant amelioration of LV haemodynamics and contractile function in HF pigs compared with AAV6.luciferase-treated control animals that showed a continued decline in cardiac function. Interestingly, the neurohormonal axis was virtually normalized in AVV6.ßARKct-treated HF animals, represented by reductions in plasma norepinephrine levels, whereas AAV6.luciferase-treated pigs showed further increases in plasma catecholamine levels. As a result, LV remodelling and foetal gene expression was reversed by AVV6.ßARKct gene therapy. CONCLUSION: These data--showing sustained amelioration of cardiac function in a post-MI pig HF model--demonstrate the therapeutic potential of ßARKct gene therapy for HF.

Endocrine hormone imbalance in heart failure with reduced ejection fraction: A cross-sectional study.

Background and Aims: Sustained neurohormonal activation plays a central role in the progression of heart failure (HF). Other endocrine axes may also be affected. It was the aim of this study to examine the endocrine profile (thyroid, parathyroid, glucocorticoid, and sex hormones) in a contemporary sample of patients with HF and reduced ejection fraction (EF) on established disease-modifying therapy. Methods: This study prospectively measured morning fasting hormones in 52 ambulatory and stable HF patients with EF < 50% on disease-modifying therapy (mean age 63 ± 11 years, 29% female, mean LVEF 32 ± 9.6%) and compared them to 54 patients at elevated risk for HF (61 ± 12 years, 28% female) and 62 healthy controls (HC; 61 ± 13 years, 27% female). Main comparisons were performed using one-way analysis of variance. Associations with biomarkers were studied with linear regression. Results: HF patients showed a reduced free triiodothyronine (fT3)/free thyroxine (fT4) ratio compared to HC (0.30 ± 0.06 vs. 0.33 ± 0.05, p = 0.046). Parathyroid hormone (PTH) and cortisol were increased in HF compared to both HC (median [IQR] 59 [50-84] vs. 46 [37-52] ng/L, p < 0.001 and 497 ± 150 vs. 436 ± 108 nmol/L, p = 0.03, respectively) and patients at risk (both p < 0.001). Total testosterone was reduced in male HF compared to HC (14.4 ± 6.6 vs. 18.6 ± 5.3 nmol/L; p = 0.01). No differences in TSH, estradiol, progesterone, and prolactin were found. Lower fT3 levels were found in HF with EF < 40% versus EF 40%-49% (4.6 ± 0.3 vs. 5.2 ± 0.7 pmol/L, p = 0.009). In HF patients, fT3 was an independent predictor of NT-proBNP and high-sensitivity troponin T in multiple regression analysis. PTH was positively associated with NT-proBNP. Conclusion: There is evidence of endocrine hormonal imbalance in HF with reduced EF beyond principal neurohormones and despite the use of disease-modifying therapy.

Eyes on amyloidosis: microvascular retinal dysfunction in cardiac amyloidosis.

AIMS: Cardiac involvement in systemic amyloidosis is a marker of particularly poor prognosis. Cardiac amyloidosis (CA) is characterized by extracellular amyloid deposits inducing heart failure and symptoms of cardiac microvascular disease. While amyloid deposition is most common in the myocardium but also seen in pericardium and endocardium, atria, and vasculature, the role of (micro-)vascular dysfunction in CA pathophysiology remains still elusive. Because vascular function is associated with cardiovascular risk and severity of heart failure and represents a potential therapeutic target in CA, the present study investigated retinal vascular function, flow-mediated dilatation (FMD), and pulse-wave analysis and velocity (PWA/PWV) in patients with CA. METHODS AND RESULTS: Flicker-induced arterial dilatation (FIDa) was measured using dynamic retinal vessel analysis additionally to FMD and PWA/PWV. Thirty-three patients with CA [age 67 years [interquartile range, IQR, 62, 74], 14 with amyloid light-chain (AL) and 19 with transthyretin (ATTR) amyloidosis] were prospectively included in this cross-sectional, observational study and 70 healthy individuals (age 53 years [IQR 39, 67]) served as control. Potential confounders were balanced using entropy balancing propensity score analysis [inverse probability weighting (IPW)]. FIDa was reduced in CA patients (1.52 ± 1.73% vs. 3.09 ± 1.96%, P < 0.001, after IPW). While PWV was increased (8.74 ± 2.34 m/s vs. 7.49 ± 1.65 m/s, P = 0.018, after IPW), no difference in FMD was observed. FIDa was significantly associated with prognostic biomarkers of CA [estimated glomerular filtration rate (r = 0.33; P < 0.001), log-scaled troponin T (r = -0.49; P < 0.001), and N-terminal pro-B-type natriuretic peptide (r = -0.51; P < 0.001)]. CONCLUSIONS: Retinal vascular function is impaired, associated with cardiac and renal biomarkers of CA severity, and may represent a potential therapeutic target in patients with amyloidosis.

Does an undetected obstructive sleep apnea influence the natural course and success of cardiac rehabilitation after cardiac surgery?

BACKGROUND: Obstructive Sleep Apnea (OSA) is common in patients with cardiovascular diseases (CVD) and can negatively impact the course of CVD. However, scarce data are available for patients before or after cardiac surgery (CS) in the context of OSA. AIM: This study investigated the impact of an undetected OSA on the results of cardiac rehabilitation (CR) in patients after CS. DESIGN: Observational study over a period of 3 months following CS. SETTING: The setting of this study was inpatient CR after CS or cardiac interventions. POPULATION: CS cohort referred to a CR program to an inpatient rehabilitation clinic in Switzerland. METHODS: In this prospective observational study 256 patients were screened for OSA at the entry of CR via a level III screening device (ApneaLink AirTM, Resmed, San Diego, CA, USA). They were stratified into two groups: apnea hypopnea index (AHI) >15 or <15/h. A comprehensive assessment was performed at entry and end of CR including six-minute walk test (6-MWT), Functional Independence Measure (FIM), Hospital Anxiety and Depression Scale, MacNewHeart (MNH), STOP-Bang Questionnaire (SBQ) and Epworth Sleepiness Scale (ESS).All patients participated in a comprehensive CR program with a mean duration of approximately 3 weeks. Another OSA screening was performed at the end of the PR program and after 3 months in order to observe the clinical course of OSA. RESULTS: An AHI>15/h was found in 133 patients (59%) at baseline, 54% after 3 weeks and 43% after 3 months. The AHI>15/h-group was older, had a higher BMI, more frequent hypertension and coronary artery disease, and higher ESS and SBQ scores compared to the AHI<15/h-group. The results of the STOP-Bang and ESS questionnaires showed a statistically significant but weak positive correlation with AHI. However, in both groups ESS did not improve from baseline to the end of CR. A multivariable logistic regression model confirmed age and ESS as independent positive predictors of OSA. No differences were found between both groups according to the results of the 6-MWT, HADS and MNH. CONCLUSIONS: OSA had a high prevalence in a large CS cohort referred to CR. However, moderate-severe OSA, though symptomatic, had no significant influence on the outcome during CR and on the parameters representing success. CLINICAL REHABILITATION IMPACT: In our study the improvements during CR after CS were not influenced by the presence of significant OSA which is remarkable since the presence of OSA is thought to be associated with increased rates of cardiovascular adverse events after cardiovascular intervention or CS. This is true at least for the success of CR after CS. The long-term consequences of untreated OSA in CVD remain unclear and are still the subject of current research.

BRENDA, AMENDA and FRENDA: the enzyme information system in 2007.

The BRENDA (BRaunschweig ENzyme DAtabase) enzyme information system (http://www.brenda.uni-koeln.de) is the largest publicly available enzyme information system worldwide. The major parts of its contents are manually extracted from primary literature. It is not restricted to specific groups of enzymes, but includes information on all identified enzymes irrespective of the enzyme's source. The range of data encompasses functional, structural, sequence, localisation, disease-related, isolation, stability information on enzyme and ligand-related data. Each single entry is linked to the enzyme source and to a literature reference. Recently the data repository was complemented by text-mining data in AMENDA (Automatic Mining of ENzyme DAta) and FRENDA (Full Reference ENzyme DAta). A genome browser, membrane protein prediction and full-text search capacities were added. The newly implemented web service provides instant access to the data for programmers via a SOAP (Simple Object Access Protocol) interface. The BRENDA data can be downloaded in the form of a text file from the beginning of 2007.

SYSTOMONAS--an integrated database for systems biology analysis of Pseudomonas.

To provide an integrated bioinformatics platform for a systems biology approach to the biology of pseudomonads in infection and biotechnology the database SYSTOMONAS (SYSTems biology of pseudOMONAS) was established. Besides our own experimental metabolome, proteome and transcriptome data, various additional predictions of cellular processes, such as gene-regulatory networks were stored. Reconstruction of metabolic networks in SYSTOMONAS was achieved via comparative genomics. Broad data integration is realized using SOAP interfaces for the well established databases BRENDA, KEGG and PRODORIC. Several tools for the analysis of stored data and for the visualization of the corresponding results are provided, enabling a quick understanding of metabolic pathways, genomic arrangements or promoter structures of interest. The focus of SYSTOMONAS is on pseudomonads and in particular Pseudomonas aeruginosa, an opportunistic human pathogen. With this database we would like to encourage the Pseudomonas community to elucidate cellular processes of interest using an integrated systems biology strategy. The database is accessible at http://www.systomonas.de.

Hypovolemia and reduced hemoglobin mass in patients with heart failure and preserved ejection fraction.

A fundamental tenet of heart failure (HF) pathophysiology hinges on a propensity for fluid retention leading to blood volume (BV) expansion and hemodilution. Whether this can be applied to heart failure patients with preserved ejection fraction (HFpEF) remains uncertain. The present study sought to determine BV status and key hormones regulating fluid homeostasis and erythropoiesis in HFpEF patients. BV and hemoglobin mass (Hbmass ) were determined with high-precision, automated carbon monoxide (CO) rebreathing in 20 stable HFpEF patients (71.5 ± 7.3 years, left ventricular ejection fraction = 55.7 ± 4.0%) and 15 healthy age- and sex-matched control individuals. Additional measurements comprised key circulating BV-regulating hormones such as pro-atrial natriuretic peptide (proANP), copeptin, aldosterone and erythropoietin (EPO), as well as central hemodynamics and arterial stiffness via carotid-femoral pulse wave velocity (PWV). Carotid-femoral PWV was increased (+20%) in HFpEF patients versus control individuals. With respect to hematological variables, plasma volume (PV) did not differ between groups, whereas BV was decreased (-14%) in HFpEF patients. In consonance with the hypovolemic status, Hbmass was reduced (-27%) in HFpEF patients, despite they presented more than a twofold elevation of circulating EPO (+119%). Plasma concentrations of BV-regulating hormones, including proANP (+106%), copeptin (+99%), and aldosterone (+62%), were substantially augmented in HFpEF patients. HFpEF patients may present with hypovolemia and markedly reduced Hbmass , underpinned by a generalized overactivation of endocrine systems regulating fluid homeostasis and erythropoiesis. These findings provide a novel perspective on the pathophysiological basis of the HFpEF condition.

Age-dependent impairment of the erythropoietin response to reduced central venous pressure in HFpEF patients.

Despite growing research interest in the pathophysiology of heart failure with preserved ejection fraction (HFpEF), it remains unknown whether central hemodynamic alterations inherently present in this condition do affect blood pressure and blood volume (BV) regulation. The present study sought to determine hemodynamic and endocrine responses to prolonged orthostatic stress in HFpEF patients. Central venous pressure (CVP) assessed via the internal jugular vein (IJV) aspect ratio with ultrasonography, arterial pressure and heart rate were determined at supine rest and during 2 hours of moderate (25-30°) head-up tilt (HUT) in 18 stable HFpEF patients (71.2 ± 7.3 years), 14 elderly (EC), and 10 young (YC) healthy controls. Parallel endocrine measurements comprised main BV-regulating hormones: pro-atrial natriuretic peptide, copeptin, aldosterone, and erythropoietin (EPO). At supine rest, the IJV aspect ratio was higher (>30%) in HFpEF patients compared with EC and YC, while mean arterial pressure was elevated in HFpEF patients (98.0 ± 13.1 mm Hg) and EC (95.6 ± 8.3 mm Hg) versus YC (87.3 ± 5.0 mm Hg) (P < 0.05). HUT increased heart rate (+10%) and reduced the IJV aspect ratio (-52%), with similar hemodynamic effects in all groups (P for interaction ≥ 0.322). The analysis of endocrine responses to HUT revealed a group×time interaction for circulating EPO, which was increased in YC (+10%) but remained unaltered in HFpEF patients and EC. The EPO response to a given reduction in CVP is similarly impaired in HFpEF patients and elderly controls, suggesting an age-dependent dissociation of EPO production from hemodynamic regulation in the HFpEF condition.

Comprehensive cardiac phenotyping in large animals: comparison of pressure-volume analysis and cardiac magnetic resonance imaging in pig post-myocardial infarction systolic heart failure.

Large animal ischemic cardiomyopathy models are widely used for preclinical testing of promising novel therapeutic approaches. Pressure volume (PV) loop analysis and cardiac magnetic resonance imaging (CMRI) allow functional and morphological phenotyping. In this study we performed a comparative analysis of both methods highlighting the strength of each and their synergistic potential. Myocardial infarction (MI) was created in German farm pigs (German Landrace) by 2 h LCX occlusion (n = 11) and subsequent reperfusion. Cardiac function was assessed by PV-loops and CMRI 56 and 112 days post-MI. Two hours occlusion of the LCX led to mid-size left ventricular (LV) MI represented by high-sensitive troponin T (hsTnT) 3 days post-MI, correlating well with cardiac CMRI late enhancement. CMRI determined end-diastolic and end-systolic volumes significantly increased post-MI, while ejection fraction was reduced in infarcted animals compared to the sham group (n = 6). PV-loop derived preload-insensitive parameters of systolic and diastolic function were diminished post-MI compared to sham animals while preload-dependent parameters only deteriorated in advanced HF. PV-loop analysis significantly correlates with CMRI analysis of cardiac function in pig post-MI ischemic cardiomyopathy. PV-Loop analysis accurately quantifies LV volumetry and function in post-MI HF, and thus eccentric LV morphology. PV-loop analysis correlates well to cardiac MRI. Preload-insensitive parameters show high sensitivity to quantify HF while preload-sensitive parameters are not able to quantify early-stages of LV HF.

Retinal microvascular dysfunction in patients with coronary artery disease with and without heart failure: a continuum?

AIMS: Dynamic retinal vessel analysis is a novel, non-invasive method to assess microvascular function. The primary aim of this study was to investigate whether retinal microcirculation is impaired in patients with stable coronary artery disease (CAD) compared to patients with heart failure due to CAD (ischaemic heart failure, IHF). METHODS AND RESULTS: A total of 150 adults were enrolled to prospectively assess micro- and macrovasculature. The pre-defined primary outcome was flicker-induced arterial dilatation (FIDa) in patients with CAD [n = 40; median age 63 years, interquartile range (IQR) 53-70] and IHF (n = 40; median age 63 years, IQR 59-71) compared to healthy controls (HC, n = 70; median age 57 years, IQR 41-69). Secondary outcomes included arterial stiffness, flow-mediated dilatation, biomarkers, and ergospirometry parameters. Patients with CAD demonstrated impairment in FIDa that was even more pronounced in patients with IHF (CAD: 1.93 ± 0.28% vs. IHF: 0.41 ± 0.28%, P < 0.001; FIDa in HC: 3.69 ± 0.21%, both P < 0.001) adjusting for age, sex, concomitant medication, and co-morbidities. While pulse wave velocity was increased and flow-mediated dilatation reduced in CAD and IHF patients (both P < 0.001 compared to HC), neither differed between CAD and IHF patients. N-terminal pro-B-type natriuretic peptide (r = -0.49, P < 0.001,) and high-sensitivity troponin T (r = -0.28, P = 0.003) correlated with FIDa. Intriguingly, mean metabolic equivalents (5.3 ± 2.3 kcal/kg/h, n = 39) showed a positive correlation with FIDa (r = 0.58, P < 0.001). CONCLUSION: This study demonstrates a decline of retinal arterial function in CAD patients that is significantly more pronounced in the presence of reduced left ventricular ejection fraction, suggesting a continuum of microvascular damage.

Polyphenols: Anti-Platelet Nutraceutical?

BACKGROUND: Coronary artery disease (CAD) is a disease progressing over many years. Genetic factors, as well as the exposure to risk factors, are continuously leading to endothelial dysfunction, vascular alterations and, eventually, organ damage, major cardiovascular events and deaths. Oxidative stress, platelet hyperactivity and low-grade inflammation are important modulators in this context, contributing to plaque formation. Since platelet activation plays a critical role in the development and progression of atherothrombotic events, the inhibition of platelet hyperactivity may contribute to decreased atherothrombotic risk. The consumption of bioactive foods, and plant-derived polyphenols in particular, might impart anti-thrombotic and cardiovascular protective effects. METHODS: Aim of this work is to focus on the potential of dietary derived polyphenols to reduce platelet hyperactivity or hypercoagulability in addition to discussing their possible complementary anti-platelet therapeutic potential. All the relevant publications on this topic were systematically reviewed. RESULTS: Various studies demonstrated that polyphenol supplementation affects platelet aggregation and function in vitro and in vivo, mainly neutralizing free radicals, inhibiting platelet activation and related signal transduction pathways, blocking thromboxane A2 receptors and enhancing nitric oxide production. Experimental data concerning the effect of dietary polyphenols on platelet aggregation in vivo are poor, and results are often conflicting. Only flavanols clearly mirrored in vivo showed the efficacy in vitro in modulating platelet function. CONCLUSION: Dietary polyphenols, and above all flavanols contained in cocoa and berries, reduce platelet activation and aggregation via multiple pathways. However, more controlled interventional studies are required to establish which doses are required as well as what circulating concentrations are sufficient to induce functional antiplatelet effects.

Retinal microvascular dysfunction in hypercholesterolemia.

BACKGROUND: Hypercholesterolemia is one of the most important contributors to atherosclerosis. Whether hypercholesterolemia also affects the retinal microcirculation is unclear. OBJECTIVE: The goal of our study was to assess the association of cholesterol levels with retinal microvascular function using dynamic and static retinal vessel analysis (RVA) in a primary prevention setting. METHODS: This cross-sectional, observational study prospectively recruited 67 patients with hypercholesterolemia without known cardiovascular disease (mean age 64.4 ± 10.4 years; 45% female) and 78 healthy controls (mean age 61.8 ± 11.2 years; 45% female). The primary end point of the study was flicker-induced dilatation of retinal arterioles (FIDart) with secondary exploratory outcomes including venular FID (FIDven), arteriovenous ratio, flow-mediated dilatation and arterial stiffness as measured with augmentation index and pulse wave velocity. Multiple regression analysis was performed to study the association of cholesterol levels with retinal microvascular function. RESULTS: FIDart was significantly impaired in patients with hypercholesterolemia compared with healthy controls (mean FIDart 2.1 ± 1.8 vs 3.1 ± 1.8%, P = .001). This association remained when analysis was restricted to dyslipidemic patients without coexisting hypertension or lipid-lowering therapy. No significant differences remained for FIDven, flow-mediated dilatation, arteriovenous ratio, or arterial stiffness between the groups. Low-density lipoprotein, but not high-density lipoprotein, cholesterol was a significant negative predictor of FIDart in multiple regression analysis. CONCLUSION: Hypercholesterolemia is associated with significant retinal microvascular dysfunction as evidenced by a reduction in flicker-induced dilatation of retinal arterioles. Dynamic RVA may be a promising method for the study of retinal microvascular dysfunction in populations at elevated cardiovascular risk.

Endothelial dysfunction in cardiovascular disease and Flammer syndrome-similarities and differences.

The endothelium has increasingly been recognized as a smart barrier and a key regulator of blood flow in micro- and macrovascular beds. Endothelial dysfunction marks a stage of atherosclerosis and is an important prognostic marker for cardiovascular disease. Yet, some people who tend to be slim and physically active and with rather low blood pressure show a propensity to respond to certain stimuli such as emotional stress with endothelial-mediated vascular dysregulation (Flammer syndrome). This leads to characteristic vascular symptoms such as cold hands but also a risk for vascular-mediated diseases such as normal-tension glaucoma. It is the aim of this review to delineate the differences between Flammer syndrome and its "counterpart" endothelial dysfunction in the context of cardiovascular diseases.

Cocoa, Blood Pressure, and Vascular Function.

Cardiovascular disease (CVD) represents the most common cause of death worldwide. The consumption of natural polyphenol-rich foods, and cocoa in particular, has been related to a reduced risk of CVD, including coronary heart disease and stroke. Intervention studies strongly suggest that cocoa exerts a beneficial impact on cardiovascular health, through the reduction of blood pressure (BP), improvement of vascular function, modulation of lipid and glucose metabolism, and reduction of platelet aggregation. These potentially beneficial effects have been shown in healthy subjects as well as in patients with risk factors (arterial hypertension, diabetes, and smoking) or established CVD (coronary heart disease or heart failure). Several potential mechanisms are supposed to be responsible for the positive effect of cocoa; among them activation of nitric oxide (NO) synthase, increased bioavailability of NO as well as antioxidant, and anti-inflammatory properties. It is the aim of this review to summarize the findings of cocoa and chocolate on BP and vascular function.

Computed Tomography Angiography of Coronary Artery Bypass Grafts: Low Contrast Media Volume Protocols Adapted to Tube Voltage.

OBJECTIVE: The aim of this study was to evaluate the potential of contrast media (CM) reduction in computed tomography angiography (CTA) of coronary artery bypass grafts (CABGs) when adapting CM volume to automatically selected tube voltages. MATERIAL AND METHODS: Sixty consecutive patients (mean age, 71 ± 14.5 years) with a total of 176 CABGs (692 bypass segments) underwent contrast-enhanced prospectively electrocardiography-gated high-pitch CTA with automated, attenuation-based tube voltage selection (100 ref. peak kilovoltage [kVp], 200 ref. mAs, tube voltages from 70-150 kVp in 10-kVp steps) using a third-generation 192-slice dual-source computed tomography scanner. Volume and flow of CM (370 mg/mL iodine) was adapted according to the tube voltages using iodine attenuation-curves derived from a foregoing phantom study. In patients, CM volumes ranged from 80 mL (flow rate, 7 mL/s) at 120 kVp to 48 mL (flow rate, 4.2 mL/s) at 80 kVp. Two independent, blinded readers evaluated subjective image quality of the proximal anastomosis, bypass graft, distal anastomosis, and postanastomotic native coronary artery using a 3-point Likert scale. Objective image quality (attenuation of graft and noise) was determined and contrast-to-noise ratio (CNR) was calculated. Volume computed tomography dose index and dose-length product of each CTA examination were noted. Cohen κ was used to define interreader agreement of subjective image quality. Regression analysis was used to determine relationships between tube voltage and vascular attenuation, image noise, and CNR. RESULTS: Using attenuation-based tube voltage selection, 5 patients (8%) were scanned at 80 kVp, 22 (37%) at 90 kVp, 11 (18%) at 100 kVp, 10 (17%) at 110 kVp, and 12 (20%) at 120 kVp. Agreement in subjective image quality between readers was good (κ = 0.678). Diagnostic image quality was achieved in 679 of 692 (98%) bypass segments in 169 of 176 bypass grafts (96%). Thirteen of 692 bypass segments (2%) in 7 of 176 bypass grafts (4%) were rated as nondiagnostic because of severe artifacts caused by motion or beam hardening (2 proximal anastomoses of sequential bypasses, 3 graft bodies, 5 distal anastomoses, and 3 postanastomotic coronary artery segments). Regression analysis revealed no significant relationship between the automatically selected tube voltages and objective image quality parameters (bypass graft attenuation: P = 0.315; noise: P = 0.433; and CNR: P = 0.168), indicating homogenous attenuation, noise, and CNR across tube voltage levels. Mean volume computed tomography dose index was 4.0 ± 0.9 mGy, and mean dose length product was 135.0 ± 29.6 mGy*cm. CONCLUSION: Adapting CM protocols to automatically selected tube voltage levels allows for low-volume CM CTA examinations of CABG grafts with diagnostic image quality.

Current challenges in interventional mitral valve treatment.

Transcatheter mitral valve therapies have emerged as an alternative option in high surgical risk or inoperable patients with severe and symptomatic mitral regurgitation (MR). As multiple technologies and different approaches will become available in the field of mitral valve interventions, different challenges are emerging, both patient- (clinical challenges) and procedure-related (technical challenges). This review will briefly explore the current open challenges in the evolving fields of interventional mitral valve treatment.