Impact of New Onset Atrial Fibrillation in Hospitalized Patients with COVID-19. Results of the "ACO-VID" Registry.

OBJECTIVE: To assess the impact of new-onset atrial fibrillation (AF) on patients hospitalized with coronavirus disease 2019 (COVID-19). METHODS: Multicenter and retrospective study that included subjects >55 years hospitalized with COVID-19 from March to October 2020 in Spanish hospitals. Patients were divided into 3 groups (no AF, new-onset AF, and preexisting AF) and followed-up to 90 days. RESULTS: A total of 668 patients were included, of whom 162 (24.3%) had no AF, 107 (16.0%) new-onset AF and 399 (59.7%) preexisting AF. Compared to patients without AF, those patients with new-onset AF were older and had more comorbidities, but without differences with preexisting AF. During hospitalization, in the univariate analysis, compared to patients without AF, major bleeding and cardiovascular mortality were more frequent in patients with new-onset AF (10.3% vs 0.6%; P < .001; 2.8% vs 0.6%; P = .025, respectively), with a trend toward more stroke (1.9% vs 0%; P = .085). Outcomes were similar between AF groups, but the length of stay was greater in preexisting AF patients. Among patients with new-onset AF taking reduced doses of anticoagulant treatment was associated with higher risks of stroke and major bleeding. CONCLUSIONS: In COVID-19 hospitalized patients, new-onset AF may be associated with worse outcomes, but influenced by the dose of anticoagulants.

Impact of atrial fibrillation and anticoagulation on the risk of death, thromboembolic disease and bleeding in patients with COVID-19: the ACO-VID Registry.

OBJECTIVE: To describe the clinical profile, risk of complications and impact of anticoagulation in COVID-19 hospitalized patients, according to the presence of atrial fibrillation (AF). METHODS: Multicenter, retrospective, and observational study that consecutively included patients >55 years admitted with COVID-19 from March to October 2020. In AF patients, anticoagulation was chosen based on clinicians' judgment. Patients were followed-up for 90 days. RESULTS: A total of 646 patients were included, of whom 75.2% had AF. Overall, mean age was 75 ± 9.1 years and 62.4% were male. Patients with AF were older and had more comorbidities. The most common anticoagulants used during hospitalization in patients with AF were edoxaban (47.9%), low molecular weight heparin (27.0%), and dabigatran (11.7%) and among patients without AF, these numbers were 0%, 93.8% and 0%. Overall, during the study period (68 ± 3 days), 15.2% of patients died, 8.2% of patients presented a major bleeding and 0.9% had a stroke/systemic embolism. During hospitalization, patients with AF had a higher risk of major bleeding (11.3% vs 0.7%; p < .01), COVID-19-related deaths (18.0% vs 4.5%; p = .02), and all-cause deaths (20.6% vs 5.6%; p = .02). Age (HR 1.5; 95% CI 1.0-2.3) and elevated transaminases (HR 3.5; 95% CI 2.0-6.1) were independently associated with all-cause mortality. AF was independently associated with major bleeding (HR 2.2; 95% CI 1.1-5.3). CONCLUSIONS: Among patients hospitalized with COVID-19, patients with AF were older, had more comorbidities and had a higher risk of major bleeding. Age and elevated transaminases during hospitalization, but not AF nor anticoagulant treatment increased the risk of all-cause death.

Multifaceted role of silver salts as ligand scavengers and different behavior of nickel and palladium complexes: beyond halide abstraction.

The reaction of [NiArBr(PPh3)2] with AgBF4 brings about the abstraction of both the halide and phosphine from the nickel center by silver. When the reaction is carried out in CH2Cl2/toluene a mixture of the cationic aquo derivatives [NiAr(H2O)(PPh3)2]BF4 (2) and [NiAr(H2O)2(PPh3)]BF4 (3) is formed, along with AgBr and [Ag(PPh3)n]BF4. When the same reaction is carried out in acetone as the solvent, it leads to the completely different complex [NiAr(κ2-O, O-MeC(O)CH2C(OH)Me2)(PPh3)] (5), bearing a chelating ligand formed by the aldol self-condensation of acetone. Phosphine abstraction by silver is less favorable for the analogous palladium(II) complexes and only occurs if a large excess of AgBF4 is used. Thus, silver salts can be safely used as halide scavengers for palladium derivatives. However, the generation of cationic Ni complexes from neutral precursors by halide extraction with a silver salt may produce naked species, different than those expected, and highly reactive in certain media.

A different polynorbornene backbone by combination of two polymer growth pathways: vinylic addition and ring opening via ß-C elimination.

A new polynorbornene skeleton has been found that contains bicyclic norbornane units and cyclohexenyl methyl linkages. The polymers have been synthesized using a nickel catalyst in the presence of a controlled amount of ligands with low or moderate coordination ability. The backbone structure is the result of a vinylic addition polymerization, via sequential insertions of norbornene into a Ni-C bond (bicyclic units) combined with an unusual ring opening of the norbornene structure by a ß-C elimination (cyclohexenyl methyl units) to give a new Ni-C(alkyl) bond that continues the polymerization. The ring opening events are favored when the rate of propagation of the vinylic addition polymerization decreases, and this can be modulated by making the coordination of norbornene to the metal center less favorable using additional ligands.

Dabigatran in patients with atrial fibrillation after COVID-19 hospitalization: an update of the ANIBAL protocol.

COVID-19 increases the risk of atrial fibrillation (AF) and thrombotic complications, particularly in severe cases, leading to higher mortality rates. Anticoagulation is the cornerstone to reduce thromboembolic risk in patients with AF. Considering the risk of hepatotoxicity in patients with severe COVID-19 as well as the risk of drug-drug interactions, drug-induced hepatotoxicity and bleeding, the ANIBAL protocol was developed to facilitate the anticoagulation approach at discharge after COVID-19 hospitalization. However, since the publication of the original algorithm, relevant changes have occurred. First, treatment of COVID-19 pneumonia has been modified with the use of dexamethasone or remdesivir during the first week in patients that require oxygen therapy, and of dexamethasone and/or tocilizumab or baricitinib during the second week in patients that necessitate supplementary oxygen or with a high inflammation state, respectively. On the other hand, metabolic syndrome is common in patients with AF as well as metabolic-associated fatty liver disease, and this could negatively impact the prognosis of patients with COVID-19, including high transaminase levels in patients treated with immunomodulators. The EHRA guidelines update also introduce some interesting changes in drug-drug interaction patterns with the reduction of the level of the interaction with dexamethasone, which is of paramount importance in this clinical context. Considering the new information, the protocol, named ANIBAL II, has been updated. In this new protocol, the anticoagulant of choice in patients with AF after COVID-19 hospitalization is provided according to three scenarios: with/without dexamethasone treatment at discharge and normal hepatic function, transaminases ≤2 times the upper limit of normal, or transaminases >2 times the upper limit of normal.

Non fluoroscopic ablation of different arrhythmic structures in an electrophysiology unit. Assessment of efficiency and security.

BACKGROUND: Electroanatomical mapping systems (EMS) reduce fluoroscopy dose for the ablation. Higher costs and longer procedure times are the drawbacks associated with EMS. Our objective was to validate the efficiency of the EMS. OBJECTIVE: To demonstrate that using EMS is more efficient and as secure as the traditional system of ablation. METHODS: From April 2013 to June 2018, all patients were included into two groups, according to the intention of ablation with or without fluoroscopy. Right, left, supraventricular and ventricular ablation were included. We compared procedure variables (fluoroscopy, radiofrequency and procedure times, ablation results, complication rates and costs of the procedure) that included material and detrimental effect of fluoroscopy. RESULTS: A total of 105 were included in the fluoroscopy group and 287 in the without fluoroscopy group. We found an important reduction in time and radiation dose in all the ablation procedures studied, without increasing the procedure time. No differences in ablation results nor complications rate were found. We found lower costs in the flutter ablation without fluoroscopy, similar costs in the right focal tachycardia ablation group and higher costs in the without fluoroscopy group for the AVNRT and left accessory pathway. When detrimental effect of fluoroscopy was added, all procedures without fluoroscopy were significantly more efficient than the ones performed with it. CONCLUSIONS: Ablation without fluoroscopy is a technique as safe and effective as the conventional technique. Our study suggests that the radiation dose delivered to the patient and staff might be reduced, without increasing the total procedure time, being even more efficient.

Dabigatran, the oral anticoagulant of choice at discharge in patients with non-valvular atrial fibrillation and COVID-19 infection: the ANIBAL protocol.

Atrial fibrillation is a frequent complication among patients with severe coronavirus disease-2019 (COVID-19) infection. Both direct and indirect mechanisms through COVID-19 have been described to explain this relationship. COVID-19 infection increases the risk of developing both arterial and venous thrombotic complications through systemic coagulation activation, leading to increased mortality. Chronic oral anticoagulation is essential to reduce the thromboembolic risk among AF patients. Switching to low-molecular-weight heparin has been recommended during hospitalization for COVID-19 infection. Of note, at discharge, the prescription of direct oral anticoagulants may offer some advantages over vitamin K antagonists. However, oral anticoagulants should only be prescribed after the consideration of drug-drug interactions with antiviral therapies as well as of the risk of hepatotoxicity, which is common among individuals with severe COVID-19 pneumonia. Not all anticoagulants have the same risk of hepatotoxicity; dabigatran has shown a good efficacy and safety profile and could have a lower risk of hepatotoxicity. Furthermore, its metabolism by cytochrome P450 is absent and it has a specific reversal agent. Therefore, dabigatran may be considered as a first-line choice for oral anticoagulation at discharge after COVID-19 infection. In this review, the available information on the antithrombotic management of AF patients at discharge after COVID-19 infection is updated. In addition, a practical algorithm, considering renal and liver function, which facilitates the anticoagulation choice at discharge is presented.

Trispyrazolylborate Ligands Supported on Vinyl Addition Polynorbornenes and Their Copper Derivatives as Recyclable Catalysts.

Polynorbornenes prepared by vinyl addition polymerization and bearing pendant alkenyl groups serve as skeletons to support trispyrazolylborate ligands (Tpx ) built at those alkenyl sites. Reaction with CuI in acetonitrile led to VA-PNB-Tpx Cu(NCMe) (VA-PBN=vinyl addition polynorbornene) with a 0.8-1.4 mmol incorporation of Cu per gram of polymer. The presence of tetracoordinated copper(I) ions was been assessed by FTIR studies on the corresponding VA-PNB-Tpx Cu(CO) adducts, in agreement with those on discrete Tpx Cu(CO). The new materials were employed as heterogeneous catalysts in several carbene- and nitrene-transfer reactions, showing a behavior similar to that of the homogeneous counterparts but also being recycled several times maintaining a high degree of activity and selectivity. This is the first example of supported Tpx ligands onto polymeric supports with catalytic applications.

Respuesta al ECG de mayo de 2018 / Response to ECG, May 2018

No disponible

ECG de mayo de 2018 / ECG, May 2018

No disponible

In vitro pharmacodynamic modelling of anidulafungin against Candida spp.

The aim of this study was to fit anidulafungin in vitro static time-kill data from nine strains of Candida with a pharmacodynamic (PD) model in order to describe the antifungal activity of this drug against Candida spp. Time-kill data from strains of Candida albicans, Candida glabrata and Candida parapsilosis clades were best fit using an adapted sigmoidal Emax model and resulted in a set of PD parameters (Emax, EC50 and Hill factor) for each fungal strain. The data were analysed with NONMEM 7. Anidulafungin was effective in a species- and concentration-dependent manner against the strains of C. glabrata and C. parapsilosis clades as observed with the EC50 estimates. Maximum killing rate constant (Emax) values were higher against C. glabrata and C. parapsilosis complex strains. In conclusion, we demonstrated that the activity of anidulafungin against Candida can be accurately described using an adapted sigmoidal Emax model.

Registro Español de Ablación con Catéter. XIV Informe Oficial de la Sección de Electrofisiología y Arritmias de la Sociedad Española de Cardiología (2014) / Spanish Catheter Ablation Registry. 14th Official Report of the Spanish Society of Cardiology Working Group on Electrophysiology and Arrhythmias (2014)

Introducción y objetivos: Se detallan los resultados del Registro Español de Ablación con Catéter año 2014. Métodos: La recogida de datos se llevó a cabo mediante dos sistemas: retrospectivo, mediante cumplimentación de un formulario, y prospectivo, a través de una base de datos común. La elección de uno u otro fue voluntaria de cada uno de los centros. Resultados: Se recogieron datos de 85 centros. El número total de procedimientos de ablación fue 12.871, con una media de 149,5 ± 103 procedimientos. Los tres sustratos abordados con más frecuencia fueron la taquicardia intranodular (n = 3.026; 23,5%), la ablación del istmo cavotricuspídeo (n = 2.833; 22,0%) y la fibrilación auricular (n = 2.498; 19,4%). La ablación de arritmias ventriculares ha permanecido estable, con un ligero incremento de todos los sustratos ventriculares, en especial las taquicardias ventriculares idiopáticas y las asociadas a cicatriz tras infarto. La tasa total de éxito fue del 95%; la de complicaciones mayores, del 1,3% y la de mortalidad, del 0,02%. Conclusiones: En el registro del año 2014 se mantiene una línea de continuidad ascendente en el número de ablaciones realizadas y muestra, en líneas generales, una elevada tasa de éxito y bajo número de complicaciones. Continúa el aumento del abordaje de sustratos más complejos (AU)

Introduction and objectives: This report presents the findings of the 2014 Spanish Catheter Ablation Registry. Methods: For data collection, each center was allowed to choose freely between 2 systems: retrospective, requiring the completion of a standardized questionnaire, and prospective, involving reporting to a central database. Results: Data were collected from 85 centers. A total of 12 871 ablation procedures were performed, for a mean of 149.5 ± 103 procedures per center. The ablation targets most frequently treated were atrioventricular nodal reentrant tachycardia (n = 3026; 23.5%), cavotricuspid isthmus (n = 2833; 22.0%), and atrial fibrillation (n = 2498; 19.4%). The number of ablation procedures for ventricular arrhythmias was similar to that of 2013, but there was a slight increase in the treatment of all the ventricular substrates, especially those associated with idiopathic ventricular tachycardia and scarring following myocardial infarction. The overall success rate was 95%, the rate of major complications was 1.3%, and the mortality rate was 0.02%. Conclusions: The 2014 registry shows that the number of ablation procedures performed continued its upward trend and that, overall, the success rate was high and the number of complications low. Ablation of complex conditions continued to increase (AU)

Spanish Catheter Ablation Registry. 14th Official Report of the Spanish Society of Cardiology Working Group on Electrophysiology and Arrhythmias (2014).

INTRODUCTION AND OBJECTIVES: This report presents the findings of the 2014 Spanish Catheter Ablation Registry. METHODS: For data collection, each center was allowed to choose freely between 2 systems: retrospective, requiring the completion of a standardized questionnaire, and prospective, involving reporting to a central database. RESULTS: Data were collected from 85 centers. A total of 12 871 ablation procedures were performed, for a mean of 149.5±103 procedures per center. The ablation targets most frequently treated were atrioventricular nodal reentrant tachycardia (n=3026; 23.5%), cavotricuspid isthmus (n=2833; 22.0%), and atrial fibrillation (n=2498; 19.4%). The number of ablation procedures for ventricular arrhythmias was similar to that of 2013, but there was a slight increase in the treatment of all the ventricular substrates, especially those associated with idiopathic ventricular tachycardia and scarring following myocardial infarction. The overall success rate was 95%, the rate of major complications was 1.3%, and the mortality rate was 0.02%. CONCLUSIONS: The 2014 registry shows that the number of ablation procedures performed continued its upward trend and that, overall, the success rate was high and the number of complications low. Ablation of complex conditions continued to increase.

Registro Español de Ablación con Catéter. XIII Informe Oficial de la Sección de Electrofisiología y Arritmias de la Sociedad Española de Cardiología (2013) / Spanish Catheter Ablation Registry. 13th Official Report of the Spanish Society of Cardiology Working Group on Electrophysiology and Arrhythmias (2013)

Introducción y objetivos: Se detallan los resultados del Registro Español de Ablación con Catéter del año 2013. Métodos: La recogida de datos se llevó a cabo mediante dos sistemas. De forma retrospectiva con la cumplimentación de un formulario y de forma prospectiva a través de una base de datos común. La elección de una u otra fue voluntaria para cada uno de los centros. Resultados: Se recogieron datos de 80 centros. El número total de procedimientos de ablación fue 11.987, con una media de 149±105 procedimientos. Los tres sustratos abordados con más frecuencia fueron la taquicardia intranodular (n=2.959; 24,6%), la ablación del istmo cavotricuspídeo (n=2.700; 22,5%) y la fibrilación auricular (n=2.201; 18,4%). La ablación de arritmias ventriculares ha permanecido estable, pero han aumentado discretamente los procedimientos sobre las asociadas a cicatriz tras infarto. La tasa total de éxito fue del 94,4%; la de complicaciones mayores, del 1,8% y la de mortalidad, del 0,03%. Conclusiones: En el registro del año 2013 se mantiene una línea de continuidad ascendente en el número de ablaciones realizadas y muestran, en líneas generales, una elevada tasa de éxito y bajo número de complicaciones. Continúa el aumento del abordaje de sustratos más complejos

Introduction and objectives: This report presents the results of the 2013 Spanish Catheter Ablation Registry. Methods: Data were collected using 2 systems: retrospectively by completing a dedicated form and prospectively by reporting to a central database. Each participating center chose 1 of the 2 data collection methods. Results: Eighty centers voluntarily contributed data to the registry. A total of 11 987 ablation procedures were performed, with a mean (standard deviation) of 149 (105) procedures per center. The 3 main arrhythmic substrates treated were atrioventricular nodal reentrant tachycardia (n=2959; 24.6%), cavotricuspid isthmus ablation (n=2700; 22.5%), and atrial fibrillation (n=2201; 18.4%). The number of ventricular ablation procedures was similar to the 2012 activity, but there was a slight increase in procedures for scar-related postmyocardial infarction ventricular tachycardia. The success rate was 94.4%, major complications occurred in 1.8%, and the mortality rate was 0.03%. Conclusions: In line with previous reports, the data from the 2013 registry show a continuing increase in the number of ablations performed. Overall, there was a high success rate and few complications. Ablation of complex substrates has continued to increase

Spanish Catheter Ablation Registry. 13th Official Report of the Spanish Society of Cardiology Working Group on Electrophysiology and Arrhythmias (2013).

INTRODUCTION AND OBJECTIVES: This report presents the results of the 2013 Spanish Catheter Ablation Registry. METHODS: Data were collected using 2 systems: retrospectively by completing a dedicated form and prospectively by reporting to a central database. Each participating center chose 1 of the 2 data collection methods. RESULTS: Eighty centers voluntarily contributed data to the registry. A total of 11 987 ablation procedures were performed, with a mean (standard deviation) of 149 (105) procedures per center. The 3 main arrhythmic substrates treated were atrioventricular nodal reentrant tachycardia (n=2959; 24.6%), cavotricuspid isthmus ablation (n=2700; 22.5%), and atrial fibrillation (n=2201; 18.4%). The number of ventricular ablation procedures was similar to the 2012 activity, but there was a slight increase in procedures for scar-related postmyocardial infarction ventricular tachycardia. The success rate was 94.4%, major complications occurred in 1.8%, and the mortality rate was 0.03%. CONCLUSIONS: In line with previous reports, the data from the 2013 registry show a continuing increase in the number of ablations performed. Overall, there was a high success rate and few complications. Ablation of complex substrates has continued to increase.

Integration of preclinical and clinical knowledge to predict intravenous PK in human: bilastine case study.

Modern pharmacometrics can integrate and leverage all prior proprietary and public knowledge. Such methods can be used to scale across species or comparators, perform clinical trial simulation across alternative designs, confirm hypothesis and potentially reduce development burden, time and costs. Crucial yet typically lacking in integration is the pre-clinical stage. Prediction of PK in man, using in vitro and in vivo studies in different animal species, is increasingly well theorized but could still find wider application in drug development. The aim of the present work was to explore methods for bridging pharmacokinetic knowledge from animal species (i.v. and p.o.) and man (p.o.) into i.v. in man using the antihistamine drug bilastine as example. A model, predictive of i.v. PK in man, was developed on data from two pre-clinical species (rat and dog) and p.o. in man bilastine trials performed earlier. In the knowledge application stage, two different approaches were used to predict human plasma concentration after i.v. of bilastine: allometry (several scaling methods) and a semi-physiological method. Both approaches led to successful predictions of key i.v. PK parameters of bilastine in man. The predictive i.v. PK model was validated using later data from a clinical study of i.v. bilastine. Introduction of such knowledge in development permits proper leveraging of all emergent knowledge as well as quantification-based exploration of PK scenario, e.g. in special populations (pediatrics, renal insufficiency, comedication). In addition, the methods permit reduction or elimination and certainly optimization of learning trials, particularly those concerning alternative off-label administration routes.

Symmetry-induced pinning-depinning transition of a subharmonic wave pattern.

The stationary to drifting transition of a subharmonic wave pattern is studied in the presence of inhomogeneities and drift forces as the pattern wavelength is comparable with the system size. We consider a pinning-depinning transition of stationary subharmonic waves in a tilted quasi-one-dimensional fluidized shallow granular bed driven by a periodic air flow in a small cell. The transition is mediated by the competition of the inherent periodicity of the subharmonic pattern, the asymmetry of the system, and the finite size of the cell. Measurements of the mean phase velocity of the subharmonic pattern are in good agreement with those inferred from an amplitude equation, which takes into account asymmetry and finite-size effects of the system, emphasizing the main ingredients and mechanism of the transition.