Levels of Circulating Intermediate Monocytes Decrease after Aortic Valve Replacement in Patients with Severe Aortic Stenosis.

Aortic valve stenosis (AS) is a chronic inflammatory disease. We have previously shown that severe AS is associated with increased levels of circulating intermediate monocytes. Haemodynamics are considered to influence levels of circulating monocyte subsets; we therefore hypothesized that aortic valve replacement may result in changes in the distribution of circulating monocyte subsets. In the present study, we evaluated levels of circulating monocyte subsets in patients with severe AS undergoing surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR). Levels of classical (CD14++CD16­), intermediate (CD14++CD16+), and non-classical (CD14+CD16++) CD86-positive monocytes were determined by flow cytometry in peripheral blood of patients with severe AS before (baseline) and at 3- and 6-month follow-ups (FUP) after SAVR (n = 25 patients) or TAVR (n = 44 patients). Absolute and relative levels of circulating intermediate monocytes decreased from median 39.9/µL (interquartile range [IQR]: 31.7­53.6/µL) and 6.7% (5.6­8.1%) at baseline to 31.6/µL (24.3­42.4/µL; p < 0.001) and 5.4% (4.4­6.7%; p < 0.001) at 6-month FUP after aortic valve replacement, respectively. The decrease in levels of circulating intermediate monocytes appeared earlier (between baseline and 3-month FUP) in the TAVR group compared with the SAVR group (between 3- and 6-month FUP). In conclusion, levels of circulating intermediate monocytes decrease after SAVR or TAVR in patients with severe AS.

Immunoproteasome subunit ß5i/LMP7-deficiency in atherosclerosis.

Management of protein homeostasis by the ubiquitin-proteasome system is critical for atherosclerosis development. Recent studies showed controversial results on the role of immunoproteasome (IP) subunit ß5i/LMP7 in maintenance of protein homeostasis under cytokine induced oxidative stress. The present study aimed to investigate the effect of ß5i/LMP7-deficiency on the initiation and progression of atherosclerosis as a chronic inflammatory, immune cell driven disease. LDLR-/-LMP7-/- and LDLR-/- mice were fed a Western-type diet for either 6 or 24 weeks to induce early and advanced stage atherosclerosis, respectively. Lesion burden was similar between genotypes in both stages. Macrophage content and abundance of polyubiquitin conjugates in aortic root plaques were unaltered by ß5i/LMP7-deficiency. In vitro experiments using bone marrow-derived macrophages (BMDM) showed that ß5i/LMP7-deficiency did not influence macrophage polarization or accumulation of polyubiquitinated proteins and cell survival upon hydrogen peroxide and interferon-γ treatment. Analyses of proteasome core particle composition by Western blot revealed incorporation of standard proteasome subunits in ß5i/LMP7-deficient BMDM and spleen. Chymotrypsin-, trypsin- and caspase-like activities assessed by using short fluorogenic peptides in BMDM whole cell lysates were similar in both genotypes. Taken together, deficiency of IP subunit ß5i/LMP7 does not disturb protein homeostasis and does not aggravate atherogenesis in LDLR-/- mice.

Tea-induced improvement of endothelial function in humans: No role for epigallocatechin gallate (EGCG).

Consumption of tea is inversely associated with cardiovascular diseases. However, the active compound(s) responsible for the protective effects of tea are unknown. Although many favorable cardiovascular effects in vitro are mediated by epigallocatechin gallate (EGCG), its contribution to the beneficial effects of tea in vivo remains unresolved. In a randomised crossover study, a single dose of 200 mg EGCG was applied in three different formulas (as green tea beverage, green tea extract (GTE), and isolated EGCG) to 50 healthy men. Flow-mediated dilation (FMD) and endothelial-independent nitro-mediated dilation (NMD) was measured before and two hours after ingestion. Plasma levels of tea compounds were determined after each intervention and correlated with FMD. FMD significantly improved after consumption of green tea containing 200 mg EGCG (p < 0.01). However, GTE and EGCG had no significant effect on FMD. NMD did not significantly differ between interventions. EGCG plasma levels were highest after administration of EGCG and lowest after consumption of green tea. Plasma levels of caffeine increased after green tea consumption. The results show that EGCG is most likely not involved in improvement of flow-mediated dilation by green tea. Instead, other tea compounds, metabolites or combinations thereof may play a role.

Severe Aortic Valve Stenosis in Adults is Associated with Increased Levels of Circulating Intermediate Monocytes.

Individual monocyte subsets have been associated with atherosclerotic disease, but their distribution has not been evaluated in aortic valve stenosis (AS) so far. In the present study, we have asked whether levels of the circulating intermediate monocyte subset are increased in AS. Classical (CD14++CD16-), intermediate (CD14++CD16+), and non-classical (CD14+CD16++) CD86-positive monocytes and monocyte activation (intensity of CD11b expression) were determined by flow cytometry in peripheral blood of patients with severe AS (n = 100) and matched AS-free controls (n = 75). AS patients exhibited significantly higher levels of circulating intermediate monocytes, while levels of circulating classical and non-classical monocytes or monocyte activation did not differ compared to controls. The difference in levels of intermediate monocytes between groups was independent of age, gender, BMI, LDL-C, NT-proBNP, NYHA functional class, or creatinine levels. The present pilot study provides evidence of an association of severe AS with increased levels of circulating intermediate monocytes. Further studies need to clarify whether this finding is related to the inflammatory status and hemodynamic disturbances associated with severe AS.

Mid-regional pro-adrenomedullin (MR-proADM) and mid-regional pro-atrial natriuretic peptide (MR-proANP) in severe aortic valve stenosis: association with outcome after transcatheter aortic valve implantation (TAVI).

BACKGROUND: This study aimed to assess the association of mid-regional (MR) pro-adrenomedullin (MR-proADM) and MR-pro-A-type natriuretic peptide (MR-proANP) in comparison to N-terminal pro-natriuretic peptide (NT-proBNP) with outcome in patients with aortic stenosis (AS) treated with transcatheter aortic valve implantation (TAVI). METHODS: One hundred consecutive TAVI patients were included in this prospective study. Association of preinterventional levels of MR-proADM, MR-proANP, NT-proBNP, C-reactive protein (CrP), and high-sensitive cardiac Troponin T (hsTN) with 30-day and 1-year outcome was analyzed. RESULTS: There was no association with 30-day outcome, but all markers were associated with 1-year cardiovascular events and all-cause mortality. The combined biomarker analysis further improved risk prediction. CONCLUSIONS: In TAVI patients MR-proADM, MR-proANP, and NT-proBNP are promising predictors of adverse events within 1 year. Integration of these biomarkers into decision pathways may help to identify patients at higher risk.

Improved Left Ventricular Structure and Function After Successful Kidney Transplantation.

BACKGROUND/AIMS: Cardiac changes observed in chronic kidney disease patients are of multifactorial origin including chronic uremia, hemodynamics or inflammation. Restoration of renal function by kidney transplantation (KTX) may reverse cardiac changes. Novel echocardiographic methods such as speckle tracking echocardiography (STE) allow early and sensitive detection of subtle changes of cardiac parameters. We evaluated changes of cardiac structure and function after KTX by advanced echocardiographic modalities. METHODS: Thirty-one KTX recipients (female n=11) were evaluated by medical examination, laboratory testing and echocardiography before and after KTX (median follow-up 19 months). Left ventricular (LV) and right ventricular (RV) diameters and function were assessed by echocardiographic standard parameters. Longitudinal 2D strain of the LV (GLPS) and left atrium (LA) was determined by 2D STE. RESULTS: After KTX, median serum creatinine level was 1.3 mg/dl (IQR, 1.2-1.5). Systolic blood pressure decreased significantly after KTX. Echocardiography showed a significant reduction in LV end-diastolic septal and posterior wall thickness and LV mass index after KTX, which was accompanied by an improvement of GLPS. There were no relevant changes in parameters of LA (reservoir, conduit or contractile) function, LV diastolic or RV function after KTX. CONCLUSION: LV hypertrophy reversed after successful KTX and was accompanied by an improvement in longitudinal LV function as assessed by STE. Diastolic function and STE-derived LA function parameters did not change significantly after KTX.

Magnetic Particle Spectroscopy Reveals Dynamic Changes in the Magnetic Behavior of Very Small Superparamagnetic Iron Oxide Nanoparticles During Cellular Uptake and Enables Determination of Cell-Labeling Efficacy.

In vivo tracking of nanoparticle-labeled cells by magnetic resonance imaging (MRI) crucially depends on accurate determination of cell-labeling efficacy prior to transplantation. Here, we analyzed the feasibility and accuracy of magnetic particle spectroscopy (MPS) for estimation of cell-labeling efficacy in living THP-1 cells incubated with very small superparamagnetic iron oxide nanoparticles (VSOP). Cell viability and proliferation capacity were not affected by the MPS measurement procedure. In VSOP samples without cell contact, MPS enabled highly accurate quantification. In contrast, MPS constantly overestimated the amount of cell associated and internalized VSOP. Analyses of the MPS spectrum shape expressed as harmonic ratio A5/A3 revealed distinct changes in the magnetic behavior of VSOP in response to cellular uptake. These changes were proportional to the deviation between MPS and actual iron amount, therefore allowing for adjusted iron quantification. Transmission electron microscopy provided visual evidence that changes in the magnetic properties correlated with cell surface interaction of VSOP as well as with alterations of particle structure and arrangement during the phagocytic process. Altogether, A5/A3-adjusted MPS enables highly accurate, cell-preserving VSOP quantification and furthermore provides information on the magnetic characteristics of internalized VSOP.

Galectin-3 and prediction of therapeutic response to renal sympathetic denervation.

The profibrotic mediator Galectin-3 (Gal-3) has been associated with aldosterone-mediated vascular inflammation, fibrosis, and stiffness. We evaluated whether the Gal-3 levels and change in Gal-3 as associated with renal denervation can serve as prediction of therapeutic response to renal denervation. A total of 42 patients with resistant hypertension undergoing renal sympathetic denervation (RDN) were included. Blood pressure was evaluated by 24-h ambulatory measurement before RDN and 1, 3 and 6 months after RDN. Treatment response was defined as a drop in systolic ambulatory blood pressure of >5 mm Hg after 6 months. Blood samples were assessed for Gal-3 levels. For the entire group, a significant drop in mean systolic ambulatory blood pressure of 5.2 ± 18.6 mm Hg was observed (p = 0.032). The responder rate was 50% (n = 21). At baseline, Gal-3 levels were significantly higher in responders (14.5 ± 6.0 vs. 10.95 ± 4.6 ng/ml, p = 0.017). There were no significant changes of Gal-3 levels during the follow-up period. The profibrotic biomarker may help to identify patients suitable for RDN.

Left Atrial Function in Preclinical Diastolic Dysfunction: Two-Dimensional Speckle-Tracking Echocardiography-Derived Results from the BEFRI Trial.

BACKGROUND: Patients with preclinical left ventricular (LV) diastolic dysfunction (DD) are prone to develop heart failure with preserved ejection fraction. Although left atrial (LA) enlargement and deterioration of LA function in apparent DD and heart failure with preserved ejection fraction have been previously described, data regarding phasic LA strain (LAS) in preclinical DD are scarce. METHODS: In a cross-sectional trial, echocardiographic parameters of DD, LA volume index, and global LA reservoir, conduit, and pump function were prospectively analyzed in 473 women from the general population in Berlin, Germany (BErlin Female RIsk evaluation (BEFRI) study), using standard and two-dimensional speckle-tracking echocardiography. RESULTS: One hundred thirty-one women (29.7%) showed early-stage DD (impaired relaxation [DD1]) and 22 (5.0%) showed an echocardiographically more advanced stage of DD (pseudonormal filling [DD2]). Compared with women with normal diastolic function (DD0), those with DD1 displayed lower LA reservoir and conduit function (DD0, 43.2 ± 8.5% and 27.2 ± 8.0%; DD1, 33.3 ± 8.0% and 16.1 ± 7.1%; P < .001) but significantly higher LA pump function (DD0, 17.6 ± 5.4%; DD1, 18.9 ± 5.5%; P < .05). In patients with DD2, all three phases of LAS were markedly impaired compared with those with DD0 (reservoir, conduit, and pump function, 29.0 ± 6.3%, 15.1 ± 5.4% [P < .001], and 14.9 ± 4.1% [P < .05], respectively). LA reservoir and conduit function was significantly associated with DD; in receiver operating characteristic curve analysis, these parameters showed higher diagnostic accuracy in detecting early DD compared with LA volume index. In multivariate analysis, LA reservoir strain remained significantly associated with DD. CONCLUSIONS: All three components of LAS showed specific alterations in different stages of DD. LA reservoir and conduit function was markedly reduced before symptoms, LA enlargement, and elevations of noninvasively estimated LV filling pressures occurred. Analysis of LA function featured higher discriminative strength in diagnosing early-stage DD compared with the well-established parameter LA volume index. Assessment of LAS allows diagnosis of impaired LA function and DD in a subclinical stage and might enable timely preventive and therapeutic interventions.

Epigenetic suppression of iNOS expression in human endothelial cells: A potential role of Ezh2-mediated H3K27me3.

OBJECTIVE: Cytokines strongly induce expression of the inducible nitric oxide synthase (iNOS) in rodent but not in human endothelial cells. We recently identified NOS2 as a potential target of the histone methyltransferase enhancer of zeste homolog 2 which mediates trimethylation of histone 3 at lysine 27 (H3K27me3). METHODS AND RESULTS: Compared to an unspecific IgG control, chromatin immunoprecipitation using a H3K27me3-specific antibody followed by DNA quantification by PCR showed a strong DNA enrichment - indicating that NOS2 is associated with H3K27me3 in human umbilical vein endothelial cells (HUVEC). siRNA-mediated knock down of Ezh2 diminished NOS2 DNA enrichment - suggesting that the association of NOS2 with H3K27me3 is mediated by Ezh2. Ezh2 knock down, however, was not sufficient to increase iNOS expression after stimulation of HUVEC. CONCLUSION: NOS2 is associated with Ezh2-mediated H3K27me3 in HUVEC. This might contribute to an epigenetic suppression of iNOS inducibility in human endothelial cells.

Comparison of effects of OSA treatment by MAD and by CPAP on cardiac autonomic function during daytime.

PURPOSE: The present study compared the effects of mandibular advancement therapy (MAD) with continuous positive airway pressure therapy (CPAP) on daytime cardiac autonomic modulation in a wide range of obstructive sleep apnea (OSA) patients under controlled conditions in a randomized, two-period crossover trial. METHODS: Forty OSA patients underwent treatment with MAD and with CPAP for 12 weeks each. At baseline and after each treatment period, patients were assessed by polysomnography as well as by a daytime cardiac autonomic function test that measured heart rate variability (HRV), continuous blood pressure (BP), and baroreceptor sensitivity (BRS) under conditions of spontaneous breathing, with breathing at 6, 12, and 15/min. RESULTS: Both CPAP and MAD therapy substantially eliminated apneas and hypopneas. CPAP had a greater effect. During daytime with all four conditions of controlled breathing, three-minute mean values of continuous diastolic BP were significantly reduced for both MAD and CPAP therapy. At the same time, selective increases due to therapy with MAD were found for HRV high frequency (HF) values. No changes were observed for BRS in either therapy mode. CONCLUSIONS: These findings indicate that both MAD and CPAP result in similar beneficial changes in cardiac autonomic function during daytime, especially in blood pressure. CPAP is more effective than MAD in eliminating respiratory events.

Staged Catheter-Based Valve Treatment of Severe Carcinoid Heart Disease.

PURPOSE: Carcinoid heart disease (CHD) with severe valve destruction represents the major cause of high morbidity and mortality in patients with carcinoid syndrome. In this paper, we present a novel interventional treatment approach and report the first clinical result achieved in a patient with extensive CHD. METHODS AND RESULTS: A woman with an ileal neuroendocrine tumour (G2, Ki67: 5%) presented with severe CHD (NYHA IV) affecting both the pulmonary and the tricuspid valve. First, a balloon-expandable 23-mm Edwards SAPIEN™ was successfully implanted percutaneously into the pulmonary valve. Since no catheter-based techniques were available for the replacement of the native tricuspid valve, we implanted an Edwards SAPIEN 26-mm valve into the vena cava inferior between the right atrium and the ostium of the hepatic veins to reduce abdominal congestion. The implantation was technically successful and completely prevented regurgitation into the vena cava inferior and abdominal veins. After this procedure, the patient's clinical condition improved significantly, and she achieved near-normal exercise tolerance (VO2 max: 24.4 ml O2/kg/min, NYHA II). CONCLUSION: We demonstrated that percutaneous valve implantation may offer a novel, minimally invasive option in high-risk patients with severe CHD.

Cardiac and renal function in a large cohort of amateur marathon runners.

BACKGROUND: Participation of amateur runners in endurance races continues to increase. Previous studies of marathon runners have raised concerns about exercise-induced myocardial and renal dysfunction and damage. In our pooled analysis, we aimed to characterize changes of cardiac and renal function after marathon running in a large cohort of mostly elderly amateur marathon runners. METHODS: A total of 167 participants of the Berlin-Marathon (female n = 89, male n = 78; age = 50.3 ± 11.4 years) were included and cardiac and renal function was analyzed prior to, immediately after and 2 weeks following the race by echocardiography and blood tests (including cardiac troponin T, NT-proBNP and cystatin C). RESULTS: Among the runners, 58% exhibited a significant increase in cardiac biomarkers after completion of the marathon. Overall, the changes in echocardiographic parameters for systolic or diastolic left and right ventricular function did not indicate relevant myocardial dysfunction. Notably, 30% of all participants showed >25% decrease in cystatin C-estimated glomerular filtration rate (GFR) from baseline directly after the marathon; in 8%, we observed a decline of more than 50%. All cardiac and renal parameters returned to baseline ranges within 2 weeks after the marathon. CONCLUSIONS: The increase in cardiac biomarkers after completing a marathon was not accompanied by relevant cardiac dysfunction as assessed by echocardiography. After the race, a high proportion of runners experienced a decrease in cystatin C-estimated GFR, which is suggestive of transient, exercise-related alteration of renal function. However, we did not observe persistent detrimental effects on renal function.

Does cellular sex matter? Dimorphic transcriptional differences between female and male endothelial cells.

OBJECTIVE: Significant sex differences exist in cardiovascular diseases. Although an impact of gonadal hormones is presumed, it is largely unknown whether sexually dimorphic gene expression also plays a role and whether cells themselves show intrinsic sex differences. METHODS: We performed whole genome expression analyses in human umbilical vein endothelial cells (HUVEC) from 20 male and 20 female donors and compared levels of gene transcription between the sexes. To further assess whether there is a sex-specific response to stress, we subjected male and female HUVEC to shear for 24 h and analysed changes in gene expression. RESULTS: Genes indicative for greater immune responsiveness were stronger expressed in female compared to male HUVEC. There was a significant enrichment of 77 immune-related genes in female HUVEC. These increased transcriptional levels in female cells were verified for 20 genes by real-time RT-PCR. 6.7% of all mRNAs were regulated by shear stress. Female HUVEC showed a more pronounced transcriptional response to shear than did their male counterparts. In addition to quantitative differences, a number of genes were regulated in the opposite direction between the two sexes by shear stress. Functionally, female HUVEC showed a higher cell viability after serum starvation and an increased tube formation capacity compared to male cells. CONCLUSION: These findings underscore the importance for differentiation between male and female cells in cell culture experiments. This may apply not only to endothelial cells but might be generalized to other cell types as well. The observed sexual dimorphisms in gene expression in endothelial cells may contribute to sex differences between males and females in endothelial function.

Endothelial NO Production Is Mandatory for Epigallocatechin-3-Gallate-induced Vasodilation: Results From eNOS Knockout (eNOS-/-) Mice.

The underlying mechanisms for the vasodilating effects of the tea catechin epigallocatechin-3-gallate (EGCG) are still not fully understood. Besides nitric oxide (NO)-dependent effects, other modes of action are discussed. To elucidate whether the NO pathway is a prerequisite in mediating vasodilating effects, we investigated EGCG-induced vasorelaxation in isolated aortic rings of endothelial nitric oxide knockout (eNOS) mice. Vasodilation to acetylcholine was fully prevented in aortic rings of eNOS mice, confirming lack of vascular NO production. Vasodilation to the exogenous NO donor sodium nitroprusside was preserved in eNOS mice aortic rings. Low concentrations of EGCG (5-15 µM) resulted in strong vasorelaxation in aortic rings of wild type mice, whereas it was completely absent in eNOS mice. In corroboration, relaxation in response to green tea was significantly inhibited in aortic rings of eNOS mice. These results demonstrate that EGCG-induced vasodilation strongly relies on functional NO synthase in endothelial cells and subsequent stimulation of NO production in vessels.

Glucagonoma-induced acute heart failure.

UNLABELLED: Neuroendocrine tumours (NETs) represent a broad spectrum of tumours, of which the serotonin-producing carcinoid is the most common and has been shown to cause right ventricular heart failure. However, an association between heart failure and NETs other than carcinoid has not been established so far. In this case report, we describe a 51-year-old patient with a glucagon-producing NET of the pancreas who developed acute heart failure and even cardiogenic shock despite therapy. Heart failure eventually regressed after initialising i.v. treatment with the somatostatin analogue octreotide. Chromogranin A as a tumour marker was shown to be significantly elevated, and it decreased with clinical improvement of the patient. The effects of long-time stimulation of glucagon on the myocardium have not been studied yet; however, sarcoplasmic reticulum calcium leak can be discussed as a possible mechanism for glucagon-induced heart failure. LEARNING POINTS: Glucagonoma can be a cause for heart failure.i.v. infusion of octreotide can be successfully used to treat glucagonoma-induced acute heart failure.We suggest that cardiac function should be monitored in all NET patients.

Galectin-3 predicts short- and long-term outcome in patients undergoing transcatheter aortic valve implantation (TAVI).

Until now, no reliable biomarker has become available for short- or long-term outcome prediction in patients undergoing transcatheter aortic valve implantation (TAVI). Our goal was to investigate whether galectin-3 is also suited for risk assessment in TAVI patients. Galectin-3, a novel marker indicative for myocardial fibrosis, has prognostic value in heart failure. We included 101 patients undergoing TAVI in this prospective, single-center, observational study. Baseline galectin-3 levels were correlated to the VARC 30-day safety and one-year efficacy endpoint as well as to total mortality and cardiovascular events at one year. At baseline, mean galectin-3 level for the entire group was 18.1 (± 11.1) ng/ml. Of the 101 patients, 36 had a galectin-3 value above the cut off value of 17.8 ng/ml. These patients had significantly higher systolic pulmonary artery and capillary wedge pressures. The hazard ratio in patients with galectin-3 > 17.8 ng/ml was 3.36 (95% confidence interval, CI: 1.47-7.69; p=0.004) for the VARC 30-day safety endpoint, 5.12 (95% CI: 2.10-12.47; p<0.001) for one-year cardiovascular events, and 4.48 (95% CI: 1.56-12.91; p=0.005) for all-cause mortality. This prediction remained stable even after adjusting for possible confounders including age, sex, glomerular filtration rate, and NT-proBNP. Furthermore, the prediction was even more valuable when combining galectin-3 with NTproBNP. In summary elevated galectin-3 levels are associated with adverse outcome after TAVI. Combining galectin-3 with NT-proBNP provides additive predictive value of risk stratification.

Electrocardiographic monitoring during marathon running: a proof of feasibility for a new telemedical approach.

OBJECTIVE: There is a risk for sudden cardiac death and nonfatal arrhythmias for marathon runners. A new telemedical approach to prevent sudden cardiac death could be online electrocardiogram monitoring during endurance sport events, which would allow the emergency services located along the running track to initiate instantaneous therapy. In a first proof-of-concept study we evaluate the feasibility of recording, transferring and analysing an electrocardiogram via a mobile phone (electrocardiogram streaming) and compare the quality to a conventional Holter electrocardiogram during marathon running. METHODS: A total of 10 recreational endurance runners are equipped with a Holter Tele-electrocardiogram and a standard smartphone connected via Bluetooth to each other in order to continuously record an electrocardiogram during a first marathon event (five runners) and a second marathon event (five runners). All streaming electrocardiogram data were transferred from the device to our telemedicine centre (Charité Campus Mitte, Berlin, Germany); the data were monitored live and stored for a subsequent offline analysis. The primary endpoint was the percentage of successful transfer time of the streaming electrocardiogram compared with Holter electrocardiogram; the secondary endpoint was the percentage of correctly identified arrhythmias in the observed period. RESULTS: It is technically feasible to stream an electrocardiogram during marathon running in the presence of thousands of mobile phone users. In addition, the identification of arrhythmias during a marathon is possible by electrocardiogram streaming. However, during the first race, the data transfer quality was low. After improvement of the software, in the subsequent race there was an extremely good quality in the data transfer via the mobile phone network (89%) and 100% of the rhythm disturbances could be detected in the streamed electrocardiogram. CONCLUSION: Online electrocardiogram surveillance during marathon running is a promising preventive concept. Intensive further technical development is needed first before further studies with clinical endpoints can start.

Influence of sex on outcome following transcatheter aortic valve implantation (TAVI): systematic review and meta-analysis.

BACKGROUND: Sex differences exist in pathogenesis, clinical presentation, and outcome in aortic stenosis (AS). However, only limited information is available concerning sex differences in transcatheter aortic valve implantation (TAVI). The aim of the present study is a comprehensive meta-analysis of studies that investigate differences between men and women in outcome after TAVI. METHODS: We screened PUBMED, MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. Inclusion criteria were: AS treated with all forms of TAVI, studies specifically targeting sex/gender differences, and at least 2 of the following outcome data: 30-day all-cause death, mortality during follow-up, major vascular complications, major bleeding, pacemaker, or stroke rate (<30 days). Studies were excluded if they considered female gender merely in subgroup analysis. RESULTS: We included 14 observational studies with a total of 7,973 patients (4,242 women, 3,731 men). At 30 days (12 studies, 3,044 women, 2,784 men), female sex was associated with a significantly lower mortality rate (odds ratio [95% confidence interval] 0.78 [0.64, 0.96]). Of the 14 studies included for analysis, 12 provided data on mortality during follow-up that likewise show a survival advantage for women (OR 0.70 [0.59, 0.82]). Whereas the major vascular complication rate was greater in women (11 studies, 3,731 women, 3,342 men; OR 1.72 [1.41, 2.09]), major bleeding (8 studies, 2,124 women, 2,100 men; OR 1.13 [0.95, 1.33]) was not. Pacemaker and stroke rate were not significantly different between the groups. CONCLUSION: In treatment with TAVI, there is evidence for a significantly greater overall survival benefit in women over men.

The activity of catechol-O-methyltransferase (COMT) is not impaired by high doses of epigallocatechin-3-gallate (EGCG) in vivo.

Catechol-O-methyltransferase (COMT) inactivates many endogenous and exogenous compounds by O-methylation. Therefore, it represents a major enzyme of the metabolic pathway with important biological functions in hormonal and drug metabolism. The tea catechin epigallocatechin-3-gallate (EGCG) is known to inhibit COMT enzymatic activity in vitro. Based on beneficial in vitro results, EGCG is extensively used in human intervention studies in a variety of human diseases. Owing to its low bioavailability, rather high doses of EGCG are frequently applied that may impair COMT activity in vivo. Enzymatic activities of four functional COMT single-nucleotide polymorphisms (SNPs) were determined in red blood cells (RBCs) in 24 healthy human volunteers (14 women, 10 men). The subjects were supplemented with 750 mg of EGCG and EGCG plasma levels and COMT enzyme activities in erythrocytes were measured before and 2 h after intervention. The homozygous Val→Met substitution in the SNP rs4680 resulted in significantly decreased COMT activity. Enzymatic COMT activities in RBCs were also affected by the other three COMT polymorphisms. EGCG plasma levels significantly increased after intervention. They were not influenced by any of the COMT SNPs and different enzyme activities. Ingestion of 750 mg EGCG did not result in impairment of COMT activity. However, COMT activity was significantly increased by 24% after EGCG consumption. These results indicate that supplementation with a high dose of EGCG does not impair the activity of COMT. Consequently, it may not interfere with COMT-mediated metabolism and elimination of exogenous and endogenous COMT substrates.