Impact of renal impairment on atrial fibrillation: ESC-EHRA EORP-AF Long-Term General Registry

Background: Atrial fibrillation (AF) and renal impairment share a bidirectional relationship with important pathophysiological interactions. We evaluated the impact of renal impairment in a contemporary cohort of patients with AF. Methods: We utilised the ESC-EHRA EORP-AF Long-Term General Registry. Outcomes were analysed according to renal function by CKD-EPI equation. The primary endpoint was a composite of thromboembolism, major bleeding, acute coronary syndrome and all-cause death. Secondary endpoints were each of these separately including ischaemic stroke, haemorrhagic event, intracranial haemorrhage, cardiovascular death and hospital admission. Results: A total of 9306 patients were included. The distribution of patients with no, mild, moderate and severe renal impairment at baseline were 16.9%, 49.3%, 30% and 3.8%, respectively. AF patients with impaired renal function were older, more likely to be females, had worse cardiac imaging parameters and multiple comorbidities. Among patients with an indication for anticoagulation, prescription of these agents was reduced in those with severe renal impairment, p <.001. Over 24 months, impaired renal function was associated with significantly greater incidence of the primary composite outcome and all secondary outcomes. Multivariable Cox regression analysis demonstrated an inverse relationship between eGFR and the primary outcome (HR 1.07 [95% CI, 1.01–1.14] per 10 ml/min/1.73 m2 decrease), that was most notable in patients with eGFR <30 ml/min/1.73 m2 (HR 2.21 [95% CI, 1.23–3.99] compared to eGFR ≥90 ml/min/1.73 m2). Conclusion: A significant proportion of patients with AF suffer from concomitant renal impairment which impacts their overall management. Furthermore, renal impairment is an independent predictor of major adverse events including thromboembolism, major bleeding, acute coronary syndrome and all-cause death in patients with AF

Clinical complexity and impact of the ABC (Atrial fibrillation Better Care) pathway in patients with atrial fibrillation: a report from the ESC-EHRA EURObservational Research Programme in AF General Long-Term Registry

Background: Clinical complexity is increasingly prevalent among patients with atrial fibrillation (AF). The ‘Atrial fibrillation Better Care’ (ABC) pathway approach has been proposed to streamline a more holistic and integrated approach to AF care; however, there are limited data on its usefulness among clinically complex patients. We aim to determine the impact of ABC pathway in a contemporary cohort of clinically complex AF patients. Methods: From the ESC-EHRA EORP-AF General Long-Term Registry, we analysed clinically complex AF patients, defined as the presence of frailty, multimorbidity and/or polypharmacy. A K-medoids cluster analysis was performed to identify different groups of clinical complexity. The impact of an ABC-adherent approach on major outcomes was analysed through Cox-regression analyses and delay of event (DoE) analyses. Results: Among 9966 AF patients included, 8289 (83.1%) were clinically complex. Adherence to the ABC pathway in the clinically complex group reduced the risk of all-cause death (adjusted HR [aHR]: 0.72, 95%CI 0.58–0.91), major adverse cardiovascular events (MACEs; aHR: 0.68, 95%CI 0.52–0.87) and composite outcome (aHR: 0.70, 95%CI: 0.58–0.85). Adherence to the ABC pathway was associated with a significant reduction in the risk of death (aHR: 0.74, 95%CI 0.56–0.98) and composite outcome (aHR: 0.76, 95%CI 0.60–0.96) also in the high-complexity cluster; similar trends were observed for MACEs. In DoE analyses, an ABC-adherent approach resulted in significant gains in event-free survival for all the outcomes investigated in clinically complex patients. Based on absolute risk reduction at 1 year of follow-up, the number needed to treat for ABC pathway adherence was 24 for all-cause death, 31 for MACEs and 20 for the composite outcome. Conclusions: An ABC-adherent approach reduces the risk of major outcomes in clinically complex AF patients. Ensuring adherence to the ABC pathway is essential to improve clinical outcomes among clinically complex AF patients

Impact of clinical phenotypes on management and outcomes in European atrial fibrillation patients: a report from the ESC-EHRA EURObservational Research Programme in AF (EORP-AF) General Long-Term Registry

Background: Epidemiological studies in atrial fibrillation (AF) illustrate that clinical complexity increase the risk of major adverse outcomes. We aimed to describe European AF patients\u2019 clinical phenotypes and analyse the differential clinical course. Methods: We performed a hierarchical cluster analysis based on Ward\u2019s Method and Squared Euclidean Distance using 22 clinical binary variables, identifying the optimal number of clusters. We investigated differences in clinical management, use of healthcare resources and outcomes in a cohort of European AF patients from a Europe-wide observational registry. Results: A total of 9363 were available for this analysis. We identified three clusters: Cluster 1 (n = 3634; 38.8%) characterized by older patients and prevalent non-cardiac comorbidities; Cluster 2 (n = 2774; 29.6%) characterized by younger patients with low prevalence of comorbidities; Cluster 3 (n = 2955;31.6%) characterized by patients\u2019 prevalent cardiovascular risk factors/comorbidities. Over a mean follow-up of 22.5 months, Cluster 3 had the highest rate of cardiovascular events, all-cause death, and the composite outcome (combining the previous two) compared to Cluster 1 and Cluster 2 (all P <.001). An adjusted Cox regression showed that compared to Cluster 2, Cluster 3 (hazard ratio (HR) 2.87, 95% confidence interval (CI) 2.27\u20133.62; HR 3.42, 95%CI 2.72\u20134.31; HR 2.79, 95%CI 2.32\u20133.35), and Cluster 1 (HR 1.88, 95%CI 1.48\u20132.38; HR 2.50, 95%CI 1.98\u20133.15; HR 2.09, 95%CI 1.74\u20132.51) reported a higher risk for the three outcomes respectively. Conclusions: In European AF patients, three main clusters were identified, differentiated by differential presence of comorbidities. Both non-cardiac and cardiac comorbidities clusters were found to be associated with an increased risk of major adverse outcomes

Cardiopoietic cell therapy for advanced ischemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial

Cardiopoietic cells, produced through cardiogenic conditioning of patients' mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort

Conditional source-term estimation evaluations for partially-premixed flames

Partially-premixed flames, characterised by both premixed and non-premixed flame structures, have been identified to be of particular importance within most practical combustion-powered devices. However, as most existing combustion models assume a single flame structure, the present understanding of partially-premixed flames under lean mixture conditions and high turbulence intensity is still limited, and further research is needed to better represent these processes numerically. A detailed overview of different approaches used in combustion modelling for simultaneously capturing premixed and non-premixed flames, classified as either geometrical models (relying on the laminar burning velocity) or statistical models (relying on the probability density function), is presented. A new study validating for the first time a previously developed empirical laminar burning velocity correlation from Oxford for iso-octane/ethanol fuel blends is carried out. A complementary analysis involving simplified three-dimensional spark-ignition engine simulations is also performed using the new Oxford correlation coupled with ECFM-3Z within a Reynolds-Averaged Navier-Stokes (RANS) turbulence framework. Here, the importance attributed to the laminar burning velocity in the closure of the mean chemical source-term is found to decrease the range of applicability of geometrical models significantly, motivating the use of statistical modelling. Conditional source-term estimation (CSE) is a statistical combustion model that invokes the conditional moment closure (CMC) hypothesis to approximate the mean chemical source-term in an averaged transport equation. An inversion process estimates the conditional scalar field. Previous CSE studies have shown that this model could successfully predict the characteristics of both premixed and non-premixed flames, regardless of the combustion regime. However, limited work has been undertaken to assess the modelling capabilities of CSE to account for partially-premixed structures. To investigate further, a previously developed CSE model coupled with the flamelet generated manifold (FGM) is applied to study the Engine Combustion Network (ECN) diesel \textquotedblleft Spray A\textquotedblright\hspace{1mm}case within a RANS framework. The proposed combustion model accounts for detailed chemistry and turbulence-chemistry interaction effects, essential for capturing the strong coupling between fluid dynamics and chemical kinetics. It is found that the CSE-FGM approach successfully demonstrates the capability of realistically predicting diesel-fueled transient spray combustion. However, there are slight discrepancies with experimental ignition delay times and flame lift-off lengths under low-temperature conditions within this approach due to the inclusion of a single control scalar based on mixture fraction. Adopting doubly CSE (DCSE) and, as such, two conditioning variables relying on mixture fraction and progress variable provides far greater modelling capabilities compared to the conventional CSE. However, while a generalised mixture fraction definition has been provided and well accepted by the community, various progress variable definitions have been adopted over the years for different applications. This study focuses on the effect of progress variable selection on the conditional fluctuations obtained with one-condition conditional averages and doubly conditional averages from two of the most well-known burners. Among the four progress variables tested, it is found that the definition attributed to the progress variable within a doubly conditional moment closure approach has no particular importance in the closure of the chemical source-term. The results obtained with principal component analysis promote the use of a progress variable definition based on temperature for chemistry tabulation techniques, considering that species diffusivity is often simplified by assuming unity Lewis numbers. Lastly, this work also suggests that DCSE will likely be needed for capturing partially-premixed flames, combustion under high levels of turbulence intensity (where the inclusion of turbulence-chemistry interaction is compulsory), and reactive flows encountered in practical combustion systems

Parametric studies of a novel combustion modelling approach for low temperature diesel spray simulation

Conditional Source-term Estimation (CSE) is a combustion model based on the conditional moment hypothesis where transport equations for reactive species are conditionally averaged on conserved scalars. Major advantages of this strategy are the reduced spatial dependence of the conditional averages and negligible fluctuations around the conditional averages, which considerably simplify the reaction rate closure. Historically, simulations using CSE are limited to low carbon fuels (i.e. methane and hydrogen) where the reduced chemistry manifold can be constructed through techniques including intrinsic low dimensional manifolds and trajectory generated manifolds. However, the use of such strategies to create manifolds for diesel surrogates has proven problematic. In this study, the potential of a combination of an unsteady Flamelet Generated Manifold (FGM) and the Conditional Source-term Estimation approach to predict the ignition and flame propagation on an autoigniting n-dodecane spray flame is assessed. Simulations are performed on a single-hole injection of n-dodecane under a wide range of Engine Combustion Network’s “Spray A” conditions within a Reynolds-averaged Navier-Stokes (RANS) framework. Results from parametric sweeps of ambient temperature and oxygen concentration are qualitatively validated against experimental data from the literature and compared against predictions from an industry standard well-stirred reactor model. The efficacy of the CSE-FGM RANS approach in predicting flame characteristics is evaluated and further compared with high fidelity CSE-FGM simulations using the Large Eddy Simulation (LES) turbulence model. Overall, it was found that the CSE-FGM RANS model was able to capture global flame properties — showing particular strength in predicting auto-ignition events in the low temperature region. The model was also able to satisfactorily capture details of the two-stage ignition process. The results were shown to be consistent with those of the CSE-FGM LES model, demonstrating the adaptability of the CSE-FGM approach to different turbulence modelling paradigms

Influence of stock on physical and chemical traits of fresh apricot fruit

The study was conducted to determine the effects of Myrobalan rootstock and Blackthorn interstock on fruit physical and chemical traits of five apricot cultivars. The results showed that cultivars grafted on Myrobalan rootstock appear to induce a higher fruit mass when compared with the Blackthorn interstock. Blackthorn interstock showed a tendency to induce a higher soluble solids/titratable acidity ratio than Myrobalan. Values of soluble solids content, total sugars, titratable acidity and fruit firmness between Myrobalan rootstock and Blackthorn interstock were not significant. Regarding cultivars, the greatest fruit mass observed in Roxana in both treatments, and the lowest in Biljana on Myrobalan and in Vera on Blackthorn. The lowest soluble solids, total sugars and soluble solids/titratable acidity ratio were found in Roxana in both variants of grafting, whereas the greatest titratable acidity also observed in Roxana in both cases, respectively. Based on the results from this study, the fruits of Roxana can be recommended for fresh consumption, whereas fruits of the other cultivars can be recommended for processing

On the prediction of Spray A end of injection phenomenon using conditional source-term estimation

In this study, the role of turbulence-chemistry interaction in diesel spray auto-ignition, flame stabilization and end of injection phenomena is investigated under engine relevant “Spray A” conditions. A recently developed diesel spray combustion modeling approach, Conditional Source-term Estimation (CSE-FGM), is coupled with Reynolds-averaged Navier-Stokes simulation (RANS) framework to study the details of spray combustion. The detailed chemistry mechanism is included through the Flamelet Generated Manifold (FGM) method. Both unsteady and steady flamelet solutions are included in the manifold to account for the auto-ignition process and the subsequent flame propagation in a diesel spray. Conditionally averaged chemical source terms are closed by the conditional scalars obtained in the CSE routine. Both non-reacting and reacting spray jets are computed over a wide range of Engine Combustion Network (ECN) diesel. “Spray A” conditions. The reacting spray results are compared with simulations using a homogeneous reactor combustion model and a flamelet combustion model with the same chemical mechanism. The present study represents the first application of CSE for a diesel spray. The non-reacting liquid/vapour penetration, the mean and RMS mixture fraction, the reactive region, the flame lift-off and the ignition delay show a good agreement with literature data from an optically accessible combustion vessel over a wide range of tested conditions. The CSE-FGM model also shows a better capability in predicting the end-of-injection events in diesel spray combustion. Overall, the CSE-FGM model is shown to capture the experimental trends well, both quantitatively and qualitatively

Development of a laminar burning velocity empirical correlation forcombustion of iso-octane/ethanol blends in air

This study presents the first demonstration of Marshall and Hinton’s empirical correlation for laminar burning velocity (LBV) applied to iso-octane/ethanol blends. The “Oxford” correlation is first validated for neat iso-octane and ethanol combustion against the outputs of three different chemical kinetics mechanisms and experimental data from the literature. The effects of three different mixing rules, simple energy fraction, modified Le Châtelier, and modified version of the more complex mixing law of Hirasawa, on the predicted LBVs of iso-octane/ethanol blends are evaluated. The modified Le Châtelier mixing law is used with the Oxford correlation to predict blend LBVs at various temperature and pressure conditions. The results are validated against previously unpublished data for iso-octane/ethanol binary fuels at elevated temperature and pressure (up to 10 bar) both from this group, and from the earlier experimental studies of Varea et al. (CORIA) and Broustail et al. (PRISME). The Oxford correlation is shown to perform well across a wide range of temperature and pressure conditions (respectively 298-640 K and 1-10 bar) for the single component fuels. Used in conjunction with a modified Le Châtelier mixing law, the LBVs predicted by the correlation provide an excellent match to the available experimental data across the full range of ethanol concentrations examined (25, 50, and 75% v/v)