Stroke risk in patients with device-detected atrial high-rate episodes

Cardiovascular implantable electronic devices (CIEDs) can detect atrial arrhythmias, i.e. atrial high-rate episodes (AHRE). The thrombo-embolic risk in patients showing AHRE appears to be lower than in patients with clinical atrial fibrillation (AF) and it is unclear whether the former will benefit from oral anticoagulants. Based on currently available evidence, it seems reasonable to consider antithrombotic therapy in patients without documented AF showing AHRE >24 hours and a CHA(2)DS(2)-VASc score (congestive heart failure, hypertension, age >= 75 years [doubled], diabetes mellitus, prior stroke [doubled], vascular disease, age 65-74 years and female sex) >= 1, awaiting definite answers from ongoing randomised clinical trials. In patients with AHR

Stochastic series expansion method for quantum Ising models with arbitrary interactions

A quantum Monte Carlo algorithm for the transverse Ising model with arbitrary short- or long-range interactions is presented. The algorithm is based on sampling the diagonal matrix elements of the power series expansion of the density matrix (stochastic series expansion), and avoids the interaction summations necessary in conventional methods. In the case of long-range interactions, the scaling of the computation time with the system size N is therefore reduced from N^2 to Nln(N). The method is tested on a one-dimensional ferromagnet in a transverse field, with interactions decaying as 1/r^2.Comment: 9 pages, 5 figure

Gut-microbe derived TMAO and its association with more progressed forms of AF:Results from the AF-RISK study

Introduction: The importance of gut microbiome in cardiovascular disease has been increasingly recognized. Trimethylamine N-oxide (TMAO) is a gut microbe-derived metabolite that is associated with cardiovascular disease, including atrial fibrillation (AF). The role of TMAO in clinical AF progression however remains unknown. Methods and results: In this study we measured TMAO and its precursor (betaine, choline, and L- carnitine) levels in 78 patients using plasma samples from patients that participated in the AF-RISK study. 56 patients suffered from paroxysmal AF and 22 had a short history of persistent AF. TMAO levels were significantly higher in patients with persistent AF, as compared to those with paroxysmal AF (median [IQR] 5.65 [4.7–9.6] m/z versus 4.31 [3.2–6.2] m/z, p < 0.05), while precursor levels did not differ. In univariate analysis, we observed that for every unit increase in TMAO, the odds for having persistent AF increased with 0.44 [0.14–0.73], p < 0.01. Conclusion: These results suggest that higher levels of TMAO are associated with more progressed forms of AF. We therefore hypothesize that increased TMAO levels may reflect disease progression in humans. Larger studies are required to validate these preliminary findings.Trial Registration number: Clinicaltrials.gov NCT01510210

Dronedarone in patients with congestive heart failure: insights from ATHENA

Dronedarone is a new multichannel blocking antiarrhythmic drug for treatment of atrial fibrillation (AF). In patients with recently decompensated congestive heart failure (CHF) and depressed LV function, the drug was associated with excess mortality compared with a placebo group. The present study aimed to analyse in detail the effects of dronedarone on mortality and morbidity in AF patients CHF. We performed a post hoc analysis of ATHENA, a large placebo-controlled outcome trial in 4628 patients with paroxysmal or persistent AF, to evaluate the relationship between clinical outcomes and dronedarone therapy in patients with stable CHF. The primary outcome was time to first cardiovascular (CV) hospitalization or death. There were 209 patients with NYHA class II/III CHF and a left ventricular ejection fraction &lt;0.40 at baseline (114 placebo, 95 dronedarone patients). A primary outcome event occurred in 59/114 placebo patients compared with 42/95 dronedarone patients [hazard ratio (HR) 0.78, 95% CI = 0.52-1.16]. Twenty of 114 placebo patients and 12/95 dronedarone patients died during the study (HR 0.71, 95% CI = 0.34-1.44). Fifty-four placebo and 42 dronedarone patients were hospitalized for an intermittent episode of NYHA class IV CHF (HR = 0.78, 95% CI = 0.52-1.17). In this post-hoc analysis of ATHENA patients with AF and stable CHF, dronedarone did not increase mortality and showed a reduction of CV hospitalization or death similar to the overall population. However, in the light of the ANtiarrhythmic trial with DROnedarone in Moderate to severe CHF Evaluating morbidity DecreAse study, dronedarone should be contraindicated in patients with NYHA class IV or unstable NYHA classes II and III CHF

Increased plasma levels of NT-proBNP, Troponin T and GDF-15 are driven by persistent AF and associated comorbidities:Data from the AF-RISK study

Atrial fibrillation (AF) is a progressive disease, and early recognition and management may reflect an important strategy to reduce its disease burden. In this study, we evaluated plasma levels of three biomarkers - N-terminal pro-brain natriuretic peptide (NTproBNP), Troponin-T, and growth differentiation factor-15 (GDF-15) - in patients with paroxysmal AF (pAF) (≤7 days of continuous AF, n = 323) and persistent AF ((AF duration &gt; 7 days and &lt; 1 year, n = 84) using patients from AF RISK study (NCT01510210). In this AF-RISK sub-study, patients with persistent AF experienced more symptoms (higher European Heart Rhythm Association class (p &lt; 0.001)), had a higher comorbidity burden (p &lt; 0.001), and had more unfavorable echocardiographic parameters (p &lt; 0.001). All three biomarker levels were significantly higher in patients with persistent AF as compared to those with pAF (p &lt; 0.001). Multivariate linear regression analyses showed that age (beta-coefficient for NTproBNP: 0.21; GDF-15: 0.41; Troponin-T: 0.23) and CHA2DS2-VASc (beta-coefficient for NTproBNP: 0.20; GDF-15: 0.25; Troponin-T: 0.27) were determinants of all three biomarkers, and that persistent AF determined NTproBNP (beta-coefficient: 0.34), but not Troponin-T and GDF-15. More detailed analysis of CHA2DS2-VASc score showed that for all three biomarkers age, coronary artery disease and heart failure were determinants of plasma biomarkers levels, whereas sex determined NTproBNP and Troponin T, and hypertension determined NTproBNP and GDF15. Overall, this study therefore suggests that in AF, Troponin T and GDF15, and especially NTproBNP could be used to detect those patients with more persistent form of AF that may warrant more aggressive treatment of AF and concomitant comorbidities. Future studies, however, are essential to evaluate if more aggressive AF treatment and risk factor management will reduce disease progression and holds a novel therapeutic intervention to reduce the burden of AF.</p

Modest effect of p53, EGFR and HER-2/neu on prognosis in epithelial ovarian cancer: a meta-analysis

Background: P53, egfr and her-2/neu are the most frequently studied molecular biological parameters in epithelial ovarian cancer, but their prognostic impact is still unequivocal. We performed a meta-analysis to more precisely estimate their prognostic significance. Methods: Published studies that investigated the association between p53, egfr and her-2/neu status and survival were identified. Meta-analysis was performed using a dersimonian-laird model. Publication bias was investigated using funnel plots and sources of heterogeneity were identified using meta-regression analysis. Results: A total of 62 studies were included for p53, 15 for egfr and 20 for her-2/neu. P53, egfr and her-2/neu status had a modest effect on overall survival (Pooled hr 1.47, 95% Ci 1.33-1.61 For p53; Hr 1.65, 95% Ci 1.25-2.19 For egfr and hr 1.67, 95% Ci 1.34-2.08 For her-2/neu). Meta-regression analysis for p53 showed that figo stage distribution influenced study outcome. For egfr and her-2/neu, considerable publication bias was present. Conclusions: Although p53, egfr and her-2/neu status modestly influences survival, these markers are, by themselves, unlikely to be useful as prognostic markers in clinical practice. Our study highlights the need for well-defined, prospective clinical trials and more complete reporting of results of prognostic factor studies. British journal of cancer ( 2009) 101, 149-159. Doi: 10.1038/Sj.Bjc.6605112 Www.Bjcancer.Com published online 9 june 2009 (C) 2009 Cancer research uk

Association of ECG characteristics with clinical and echocardiographic outcome to CRT in a non-LBBB patient population

Purpose: Effectiveness of cardiac resynchronization therapy (CRT) in patients without left bundle branch block (non-LBBB) QRS morphology is limited. Additional selection criteria are needed to identify these patients. Methods: Seven hundred ninety consecutive patients with non-LBBB morphology, who received a CRT-device in 3 university centers in the Netherlands, were selected. Pre-implantation 12-lead ECGs were evaluated on morphology, duration, and area of the QRS complex, as well as on PR interval, left ventricular activation time (LVAT), and the presence of fragmented QRS (fQRS). Association of these ECG features with the primary endpoint: a combination of left ventricular assist device (LVAD) implantation, cardiac transplantation and all-cause mortality, and secondary endpoint—echocardiographic reduction of left ventricular end-systolic volume (LVESV)—were evaluated. Results: The primary endpoint occurred more often in non-LBBB patients with with PR interval ≥ 230ms, QRS area < 109μVs, and with fQRS. Multivariable regression analysis showed independent associations of QRS area (HR 2.33 [1.44, 3.77], p = 0.001) and PR interval (HR 2.03 [1.51, 2.74], p < 0.001) only. Mean LVESV reduction was significantly lower in patients with baseline RBBB, QRS duration < 150 ms, PR interval ≥ 230 ms, and in QRS area < 109 μVs. Multivariable regression analyses only showed significant associations between QRS area ≥ 109 μVs (OR 2.00 [1.09, 3.66] p = 0.025) and probability of echocardiographic response to CRT. Conclusions: In the heterogeneous non-LBBB patient population, QRS area and PR prolongation rather than traditional QRS duration and morphology are associated to both clinical and echocardiographic outcomes of CRT