Effect of β-Blocker Withdrawal on Functional Capacity in Heart Failure and Preserved Ejection Fraction

BACKGROUND Chronotropic incompetence has shown to be associated with a decrease in exercise capacity in heart failure with preserved ejection fraction (HFpEF), yet b-blockers are commonly used in HFpEF despite the lack of robust evidence. OBJECTIVES This study aimed to evaluate the effect of b-blocker withdrawal on peak oxygen consumption (peak VO2) in patients with HFpEF and chronotropic incompetence. METHODS This is a multicenter, randomized, investigator-blinded, crossover clinical trial consisting of 2 treatment periods of 2 weeks separated by a washout period of 2 weeks. Patients with stable HFpEF, New York Heart Association functional classes II and III, previous treatment with b-blockers, and chronotropic incompetence were first randomized to withdrawing from (arm A: n ¼ 26) versus continuing (arm B: n ¼ 26) b-blocker treatment and were then crossed over to receive the opposite intervention. Changes in peak VO2 and percentage of predicted peak VO2 (peak VO2%) measured at the end of the trial were the primary outcome measures. To account for the paired-data nature of this crossover trial, linear mixed regression analysis was used. RESULTS The mean age was 72.6 13.1 years, and most of the patients were women (59.6%) in New York Heart Association functional class II (66.7%). The mean peakVO2 and peak VO2% were 12.4 2.9 mL/kg/min, and 72.4 17.8%, respectively. No significant baseline differences were found across treatment arms. Peak VO2 and peak VO2% increased significantly after b-blocker withdrawal (14.3 vs 12.2 mL/kg/min [D þ2.1 mL/kg/min]; P < 0.001 and 81.1 vs 69.4% [D þ11.7%]; P < 0.001, respectively). CONCLUSIONS b-blocker withdrawal improved maximal functional capacity in patients with HFpEF and chronotropic incompetence. b-blocker use in HFpEF deserves profound re-evaluation. (b-blockers Withdrawal in Patients With HFpEF and Chronotropic Incompetence: Effect on Functional Capacity [PRESERVE-HR]; NCT03871803; 2017-005077-39) (J Am Coll Cardiol 2021;78:2042–2056) © 2021 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation

Combining heart rate and systolic blood pressure to improve risk stratification in older patients with heart failure: Findings from the RICA Registry

Objectives: Heart rate (HR) and systolic blood pressure (SBP) are independent prognostic variables in patients with heart failure (HF). We evaluated if combining HR and SBP could improve prognostic assessment in older patients. Methods: Variables associated with all-cause mortality and readmission for HF during 9 months of follow-up were analyzed from the Spanish Heart Failure Registry (RICA). HR and SBP values were stratified in three combined groups. Results: We evaluated 1551 patients, 82 years and 56% women. Using HR strata of < 70 and ≥ 70 bpm we found mortality rates of 9.8 and 13.6%, respectively (hazard ratio 1.0 and 1.35). For SBP ≥ 140, 120–140 and < 120 mm Hg, mortality rates were 8.2, 10.4 and 20.3%. respectively (hazard ratio 1.0, 1.34 and 2.76). Using combined strata of HR < 70 bpm and SBP ≥ 140 mm Hg (n = 176; low-risk), HR < 70 and SBP < 140 + HR ≥ 70 and SBP < 120 (n = 1089; moderate-risk) and HR ≥ 70 and SBP < 120 (n = 286; high-risk) we found mortality rates of 4.5%, 11.0% and 24.0%, respectively. Multivariate Cox regression for all-cause mortality shows for low-, middle- and high-risk groups was 1 (reference), 1.93 (95% CI: 0.93–3.99, p = 0.077) and 4.32 (95% CI: 2.04–9.14, p < 0.001). BMI, NYHA, MDRD, hypertension and sodium were also independent prognostic factors. Conclusions: The combination provides better risk discrimination than use of HR and SBP alone and may provide a simple and reliable tool for risk assessment for older HF patients in clinical practice

Key Factors for Optimal Care Models for Heart Failure: An Integrative and Multidisciplinary Approach

[Resumen] Introducción y objetivos. La insuficiencia cardiaca (IC) supone un reto para los sistemas sanitarios que se puede responder a través del desarrollo de modelos integrales de atención. Un grupo multidisciplinar de expertos reflexionó sobre los factores clave para avanzar en el desarrollo de este tipo de modelos, planteando una hoja de ruta dirigida a todos los agentes (administraciones, gestores y profesionales sanitarios). Métodos. Se conformó un panel Delphi multidisciplinar integrado por un comité asesor de 15 expertos y un panel adicional de 31 expertos. A través de una revisión bibliográfica sistemática y entrevistas individuales semiestructuradas se realizó un diagnóstico e identificación de retos y áreas de mejora a lo largo del proceso asistencial. El panel Delphi consensuó y priorizó los factores clave con la metodología Delphi Rand/UCLA, valorando su adecuación y necesidad. Resultados. Tras 2 rondas de valoración Delphi se consensuó una propuesta de 7 retos y 75 factores clave para el desarrollo de modelos integrados para la IC. Los 25 factores clave considerados altamente prioritarios se relacionan con la necesidad de una mayor coordinación y planificación a nivel de gestión sanitaria, el abordaje integral durante la hospitalización y la implantación de medidas de continuidad y coordinación asistencial, garantizando que se cubren las necesidades específicas de diferentes perfiles de pacientes. Conclusiones. La propuesta y priorización de acciones para avanzar en modelos de atención integral a la IC debe surgir de reflexiones multidisciplinares y multinivel que incluyan la visión de los pacientes y cuidadores.[Abstract] Introduction and objectives. Heart failure (HF) is a challenge for health systems that can be responded through the development of comprehensive care models. A multidisciplinary group of experts reflected on the key factors that could facilitate the development of this type of models, proposing a roadmap aimed at all agents (politicians, managers, administrators, and health professional). Methods. A multidisciplinary Delphi panel was formed, made up of an advisory committee of 15 experts and an additional panel of 31 experts. After a systematic bibliographic review and semi-structured individual interviews, a diagnosis and identification of challenges and areas for improvement were made throughout the healthcare process. The Delphi panel agreed and prioritized the key factors applying Delphi Rand/UCLA methodology, assessing their appropriateness and need. Results. After 2 rounds of Delphi assessment, a proposal of 7 challenges and 75 key factors was agreed upon for the development of integrated models for HF. The 25 key factors considered high priority are related to the need for greater coordination and planning at the health management level, the comprehensive approach during hospitalization and the implementation of measures of continuity and care coordination, ensuring that the specific needs of different patient profiles. Conclusions. The proposal and prioritization of actions to advance in models of comprehensive care for HF must arise from multidisciplinary and multilevel reflections that include the vision of patients and caregivers.El proyecto MAIC ha sido financiado por Boehringer Ingelheim Españ

Carbohydrate antigen 125 and risk of heart failure readmissions in patients with heart failure and preserved ejection fraction

We aimed to assess the association between CA125 and the long-term risk of total acute heart failure (AHF) admissions in patients with an index hospitalization with AHF and preserved ejection fraction (HFpEF). We prospectively included 2369 patients between 2008 and 2019 in three centers. CA125 and NT-proBNP were measured during early hospitalization and evaluated as continuous and categorized in quartiles (Q). Negative binomial regressions were used to assess the association with the risk of recurrent AHF admission. The mean age of the sample patients was 76.7 ± 9.5 years and 1443 (60.9%) were women. Median values of CA125 and NT-proBNP were 38.3 (19.0-90.0) U/mL, and 2924 (1590-5447) pg/mL, respectively. During a median follow-up of 2.2 (0.8-4.6) years, 1200 (50.6%) patients died, and 2084 AHF admissions occurred in 1029 (43.4%) patients. After a multivariate adjustment, CA125, but not NT-proBNP, was positively and non-linearly associated with the risk of cumulative AHF-readmission (p < 0.001). Compared to Q1, patients belonging to Q2, Q3, and Q4 showed a stepwise risk increase (IRR = 1.29, 95% CI 1.08-1.55, p = 0.006; IRR = 1.35, 95% CI 1.12-1.63, p = 0.002; and IRR = 1.62, 95% CI 01.34-1.96, p < 0.001, respectively). In conclusion, CA125 predicted the risk of long-term AHF-readmission burden in patients with HFpEF and a recent admission for AHF

Tools for estimating fake/non-prompt lepton backgrounds with the ATLAS detector at the LHC

International audienceMeasurements and searches performed with the ATLAS detector at the CERN LHC often involve signatures with one or more prompt leptons. Such analysesare subject to `fake/non-prompt' lepton backgrounds, where either a hadron or a lepton from a hadron decay or an electron from a photon conversion satisfies the prompt-leptonselection criteria. These backgrounds often arise within a hadronic jet because of particle decays in the showering process, particle misidentification or particleinteractions with the detector material. As it is challenging to model these processes with high accuracy in simulation, their estimation typically uses data-driven methods.Three methods for carrying out this estimation are described, along with their implementation in ATLAS and their performance

AtlFast3: The Next Generation of Fast Simulation in ATLAS

Funder: Open access funding provided by CERN (European Organization for Nuclear Research.The ATLAS experiment at the Large Hadron Collider has a broad physics programme ranging from precision measurements to direct searches for new particles and new interactions, requiring ever larger and ever more accurate datasets of simulated Monte Carlo events. Detector simulation with GEANT4 is accurate but requires significant CPU resources. Over the past decade, ATLAS has developed and utilized tools that replace the most CPU-intensive component of the simulation -- the calorimeter shower simulation -- with faster simulation methods. Here, AtlFast3, the next generation of high-accuracy fast simulation in ATLAS is introduced. AtlFast3 combines parameterized approaches with machine-learning techniques and is deployed to meet current and future computing challenges and simulation needs of the ATLAS experiment. With highly accurate performance and a new ability to model substructure within jets, AtlFast3 is designed to be used to simulate large numbers of events for a wide range of physics processes

Measurement of the energy asymmetry in t(t)over-barj production at 13 TeV with the ATLAS experiment and interpretation in the SMEFT framework

A measurement of the energy asymmetry in jet-associated top-quark pair production is presented using 139 $\mathrm{fb}^{-1}$ of data collected by the ATLAS detector at the Large Hadron Collider during $pp$ collisions at $\sqrt{s}=13$ TeV. The observable measures the different probability of top and antitop quarks to have the higher energy as a function of the jet scattering angle with respect to the beam axis. The energy asymmetry is measured in the semileptonic $t\bar{t}$ decay channel, and the hadronically decaying top quark must have transverse momentum above $350$ GeV. The results are corrected for detector effects to particle level in three bins of the scattering angle of the associated jet. The measurement agrees with the SM prediction at next-to-leading-order accuracy in quantum chromodynamics in all three bins. In the bin with the largest expected asymmetry, where the jet is emitted perpendicular to the beam, the energy asymmetry is measured to be $-0.043\pm0.020$, in agreement with the SM prediction of $-0.037\pm0.003$. Interpreting this result in the framework of the Standard Model effective field theory (SMEFT), it is shown that the energy asymmetry is sensitive to the top-quark chirality in four-quark operators and is therefore a valuable new observable in global SMEFT fits