Insulin-Like Growth Factor-Binding Protein-7 and risk of congestive heart failure hospitalization in patients with atrial fibrillation.

BACKGROUND The occurrence of congestive heart failure (CHF) hospitalization among patients with atrial fibrillation (AF) is a poor prognostic marker. OBJECTIVE To assess whether Insulin-Like Growth Factor-Binding Protein-7 (IGFBP-7), a marker of myocardial damage, identifies AF patients at high risk for this complication. METHODS We analyzed two prospective multicenter observational cohort studies including 3,691 AF patients. Levels of IGFBP-7 and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured from frozen plasma samples at baseline. The primary endpoint was hospitalization for CHF. Multivariable adjusted Cox-regression analyses were constructed. RESULTS Mean age was 69±12 years, 1,028 (28%) were females and 879 (24%) had a history of CHF. The incidence per 1,000 patient-years across increasing IGFBP-7 quartiles was 7, 10, 32 and 85. The corresponding multivariable adjusted hazard ratios (aHRs) [95%CI] were 1.0, 1.05 [0.63;1.77], 2.38 [1.50;3.79], and 4.37 [2.72;7.04] (p for trend <0.001). In a subgroup of 2,812 patients without pre-existing CHF at baseline, the aHRs were 1.0, 0.90 [0.47;1.72], 1.69 [0.94;3.04], and 3.48 [1.94;6.24] (p for trend <0.001). Patients with IGFBP-7 and NT-proBNP levels above the biomarker-specific median had a higher risk of incident CHF hospitalization (aHR 5.20 [3.35; 8.09]) compared to those with only one elevated marker (elevated IGFBP-7 aHR 2.17[1.30;3.60]; elevated NT-proBNP aHR 1.97[1.17;3.33]) or no elevated marker (reference). CONCLUSION Higher plasma levels of IGFBP-7 were strongly and independently associated with CHF hospitalization in AF-patients. The prognostic information provided by IGFBP-7 was additive to that of NT-proBNP

A Very Intense Neutrino Super Beam Experiment for Leptonic CP Violation Discovery based on the European Spallation Source Linac: A Snowmass 2013 White Paper

Very intense neutrino beams and large neutrino detectors will be needed in order to enable the discovery of CP violation in the leptonic sector. We propose to use the proton linac of the European Spallation Source currently under construction in Lund, Sweden to deliver, in parallel with the spallation neutron production, a very intense, cost effective and high performance neutrino beam. The baseline program for the European Spallation Source linac is that it will be fully operational at 5 MW average power by 2022, producing 2 GeV 2.86 ms long proton pulses at a rate of 14 Hz. Our proposal is to upgrade the linac to 10 MW average power and 28 Hz, producing 14 pulses/s for neutron production and 14 pulses/s for neutrino production. Furthermore, because of the high current required in the pulsed neutrino horn, the length of the pulses used for neutrino production needs to be compressed to a few $\mu$s with the aid of an accumulator ring. A long baseline experiment using this Super Beam and a megaton underground Water Cherenkov detector located in existing mines 300-600 km from Lund will make it possible to discover leptonic CP violation at 5 $\sigma$ significance level in up to 50% of the leptonic Dirac CP-violating phase range. This experiment could also determine the neutrino mass hierarchy at a significance level of more than 3 $\sigma$ if this issue will not already have been settled by other experiments by then. The mass hierarchy performance could be increased by combining the neutrino beam results with those obtained from atmospheric neutrinos detected by the same large volume detector. This detector will also be used to measure the proton lifetime, detect cosmological neutrinos and neutrinos from supernova explosions. Results on the sensitivity to leptonic CP violation and the neutrino mass hierarchy are presented.Comment: 28 page

Sex-specific association of cardiovascular drug doses with adverse outcomes in atrial fibrillation.

OBJECTIVES Sex differences occur in atrial fibrillation (AF), including age at first manifestation, pathophysiology, treatment allocation, complication rates and quality of life. However, optimal doses of cardiovascular pharmacotherapy used in women with AF with or without heart failure (HF) are unclear. We investigated sex-specific associations of beta-blocker and renin-angiotensin system (RAS) inhibitor doses with cardiovascular outcomes in patients with AF or AF with concomitant HF. METHODS We used data from the prospective Basel Atrial Fibrillation and Swiss Atrial Fibrillation cohorts on patients with AF. The outcome was major adverse cardiovascular events (MACEs), including death, myocardial infarction, stroke, systemic embolisation and HF-related hospitalisation. Predictors of interest were spline (primary analysis) or quartiles (secondary analysis) of beta-blocker or RAS inhibitor dose in per cent of the maximum dose (reference), in interaction with sex. Cox models were adjusted for demographics, comorbidities and comedication. RESULTS Among 3961 patients (28% women), MACEs occurred in 1113 (28%) patients over a 5-year median follow-up. Distributions of RAS inhibitor and beta-blocker doses were similar in women and men. Cox models revealed no association between beta-blocker dose or RAS inhibitor dose and MACE. In a subgroup of patients with AF and HF, the lowest hazard of MACE was observed in women prescribed 100% of the RAS inhibitor dose. However, there was no association between RAS dose quartiles and MACE. CONCLUSIONS In this study of patients with AF, doses of beta-blockers and RAS inhibitors did not differ by sex and were not associated with MACE overall

Neurocognitive function in patients with atrial fibrillation undergoing pulmonary vein isolation.

BACKGROUND Atrial fibrillation (AF) is associated with cognitive dysfunction. However, neurocognitive function in AF patients undergoing pulmonary vein isolation (PVI) has not been well studied. The aim of this analysis is to compare neurocognitive function in patients who did or did not undergo PVI. MATERIALS AND METHODS We used data from the Swiss Atrial Fibrillation Cohort study (Swiss-AF), a prospective, observational, multicenter study in Switzerland. Patients with documented AF were enrolled and data of 1,576 patients without history of PVI and with complete information on PVI status and neurocognitive function were used. Information on PVI was collected at baseline and during 1 year of follow-up. Neurocognitive testing was performed at baseline and after 1 year of follow-up, using the Montreal Cognitive Assessment (MoCA), trail making test (TMT) A and B, digit symbol substitution test (DSST) and semantic fluency test (SFT). To investigate the association of PVI with neurocognitive function, we use propensity score matching (1:3) and inverse probability of treatment weighting (IPTW). RESULTS The mean age of this population was 74 ± 8 years, 27.1% were women. Overall, 88 (5.5%) patients underwent PVI during 1 year of follow-up. Using ITPW (n = 1576), PVI was weakly associated with the MoCA score after adjusting for time since PVI, baseline MoCA score and other covariates (β (95%CI) 1.19 (0.05; 2.32), p = 0.04). In the propensity matched comparison (n = 352), there was no significant association between PVI and the MoCA score (β (95%CI) 1.04 (-0.19; 2.28), p = 0.1). There were no significant associations between PVI and cognitive function when using the TMT A and B, DSST or SFT independent of the method used. CONCLUSION In this population of AF patients, there was no consistent evidence of an association between PVI and neurocognitive function. CLINICAL TRIAL REGISTRATION [https://clinicaltrials.gov/], identifier [NCT02105844]

Semi-Dense 3D Reconstruction with a Stereo Event Camera

Event cameras are bio-inspired sensors that offer several advantages, such as low latency, high-speed and high dynamic range, to tackle challenging scenarios in computer vision. This paper presents a solution to the problem of 3D reconstruction from data captured by a stereo event-camera rig moving in a static scene, such as in the context of stereo Simultaneous Localization and Mapping. The proposed method consists of the optimization of an energy function designed to exploit small-baseline spatio-temporal consistency of events triggered across both stereo image planes. To improve the density of the reconstruction and to reduce the uncertainty of the estimation, a probabilistic depth-fusion strategy is also developed. The resulting method has no special requirements on either the motion of the stereo event-camera rig or on prior knowledge about the scene. Experiments demonstrate our method can deal with both texture-rich scenes as well as sparse scenes, outperforming state-of-the-art stereo methods based on event data image representations.Comment: 19 pages, 8 figures, Video: https://youtu.be/Qrnpj2FD1e

Validation of a clinical model for predicting left versus right ventricular outflow tract origin of idiopathic ventricular arrhythmias.

BACKGROUND Prediction of the chamber of origin in patients with outflow tract ventricular arrhythmias (OTVA) remains challenging. A clinical risk score based on age, sex and presence of hypertension was associated with a left ventricular outflow tract (LVOT) origin. We aimed to validate this clinical score to predict an LVOT origin in patients with OTVA. METHODS In a two-center observational cohort study, unselected patients undergoing catheter ablation (CA) for OTVA were enrolled. All procedures were performed using an electroanatomical mapping system. Successful ablation was defined as a ≥80% reduction of the initial overall PVC burden after 3 months of follow-up. Patients with unsuccessful ablation were excluded from this analysis. RESULTS We included 187 consecutive patients with successful CA of idiopathic OTVA. Mean age was 52 ± 15 years, 102 patients (55%) were female, and 74 (40%) suffered from hypertension. A LVOT origin was found in 64 patients (34%). A score incorporating age, sex and presence of hypertension reached 73% sensitivity and 67% specificity for a low (0-1) and high (2-3) score, to predict an LVOT origin. The combination of one ECG algorithm (V2 S/V3 R-index) with the clinical score resulted in a sensitivity and specificity of 81% and 70% for PVCs with R/S transition at V3 . CONCLUSION The published clinical score yielded a lower sensitivity and specificity in our cohort. However, for PVCs with R/S transition at V3, the combination with an existing ECG algorithm can improve the predictability of LVOT origin

Physical activity and brain health in patients with atrial fibrillation

Background and purpose: Vascular brain lesions, such as ischemic infarcts, are common among patients with atrial fibrillation (AF) and are associated with impaired cognitive function. The role of physical activity (PA) in the prevalence of brain lesions and cognition in AF has not been investigated. Methods: Patients from the multicenter Swiss‐AF cohort study were included in this cross‐sectional analysis. We assessed regular exercise (RE; at least once weekly) and minutes of weekly PA using a validated questionnaire. We studied associations with ischemic infarcts, white matter hyperintensities, cerebral microbleeds, and brain volume on brain magnetic resonance imaging and with global cognition measured with a cognitive construct (CoCo) score.ResultsAmong 1490 participants (mean age = 72 ± 9 years), 730 (49%) engaged in RE. In adjusted regression analyses, RE was associated with a lower prevalence of ischemic infarcts (odds ratio [OR] = 0.78, 95% confidence interval [CI] = 0.63–0.98, p = 0.03) and of moderate to severe white matter hyperintensities (OR = 0.78, 95% CI = 0.62–0.99, p = 0.04), higher brain volume (β‐coefficient = 10.73, 95% CI = 2.37–19.09, p = 0.01), and higher CoCo score (β‐coefficient = 0.08, 95% CI = 0.03–0.12, p < 0.001). Increasing weekly PA was associated with higher brain volume (β‐coefficient = 1.40, 95% CI = 0.65–2.15, p < 0.001). Conclusions: In AF patients, RE was associated with a lower prevalence of ischemic infarcts and of moderate to severe white matter disease, with larger brain volume, and with better cognitive performance. Prospective studies are needed to investigate whether these associations are causal. Until then, our findings suggest that patients with AF should be encouraged to remain physically active

Mid-term changes in cognitive functions in patients with atrial fibrillation: a longitudinal analysis of the Swiss-AF cohort.

BACKGROUND Longitudinal association studies of atrial fibrillation (AF) and cognitive functions have shown an unclear role of AF-type and often differ in methodological aspects. We therefore aim to investigate longitudinal changes in cognitive functions in association with AF-type (non-paroxysmal vs. paroxysmal) and comorbidities in the Swiss-AF cohort. METHODS Seven cognitive measures were administered up to five times between 2014 and 2022. Age-education standardized scores were calculated and association between longitudinal change in scores and baseline AF-type investigated using linear mixed-effects models. Associations between AF-type and time to cognitive drop, an observed score of at least one standard deviation below individual's age-education standardized cognitive scores at baseline, were studied using Cox proportional hazard models of each cognitive test, censoring patients at their last measurement. Models were adjusted for baseline covariates. RESULTS 2,415 AF patients (mean age 73.2 years; 1,080 paroxysmal, 1,335 non-paroxysmal AF) participated in this Swiss multicenter prospective cohort study. Mean cognitive scores increased longitudinally (median follow-up 3.97 years). Non-paroxysmal AF patients showed smaller longitudinal increases in Digit Symbol Substitution Test (DSST), Cognitive Construct Score (CoCo)and Trail Making Test part B (TMT-B) scores vs. paroxysmal AF patients. Diabetes, history of stroke/TIA and depression were associated with worse performance on all cognitive tests. No differences in time to cognitive drop were observed between AF-types in any cognitive test. CONCLUSION This study indicated preserved cognitive functioning in AF patients, best explained by practice effects. Smaller practice effects were found in non-paroxysmal AF patients in the DSST, TMT-B and the CoCo and could indicate a marker of subtle cognitive decline. As diabetes, history of stroke/TIA and depression-but not AF-type-were associated with cognitive drop, more attention should be given to risk factors and underlying mechanisms of AF