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Effects of Atrial Fibrillation Ablation for Heart Failure With Preserved Ejection Fraction: Insights From CABANA
No full textBACKGROUND Atrial fibrillation (AF) ablation is Class I recommendation in selected heart failure (HF) patients with reduced ejection fraction; less is known in heart failure with preserved ejection fraction (HFpEF). OBJECTIVES The aim of this study was to investigate the effects of AF ablation in patients with HFpEF. METHODS The CABANA (Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation) trial randomized patients with cardiovascular risk factors for stroke to AF ablation vs drug therapy. The presence of a high likelihood of HFpEF at enrollment was determined by a modified H2FPEF score of >= 6. Treatment effects of baseline HFpEF likelihood on the AF ablation for death and cardiovascular admission, AF recurrence, and functional status were assessed. RESULTS A total of 1,763 patients were included in the analysis. A high modified H2FPEF score (55% of the entire cohort) resulted in a significant treatment effect modulation (P for interaction 1/4 0.027), with a lower risk for cardiovascular hospitalization or death in patients with a high likelihood of HFpEF (HR: 0.82 [95% CI: 0.69-0.98]; P 1/4 0.025), but not in patients without (HR: 1.00 [95% CI: 0.82-1.22]; P 1/4 0.987). Although patients with a high likelihood of HFpEF were at a higher risk for AF recurrence, the greatest treatment effect of AF ablation on AF recurrence was observed in patients with a high likelihood of HFpEF (P for interaction 1/4 0.035). In a sensitivity analysis in a subset of patients with echocardiographic evidence of HFpEF (n 1/4 225), a similar treatment interaction was found. CONCLUSIONS In patients undergoing AF ablation, the presence of underlying HFpEF (either by HFpEF probability or defined by echocardiography) was associated with a larger benefit with AF ablation on clinical outcome, AF recurrence, and functional status. (Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation [CABANA]; NCT00911508) (JACC Heart Fail. 2025;13:785-794) (c) 2025 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Dr Martens is supported by a grant from BAEF (Belgian American Educational Foundation) and by the Frans Van de Werf Fund. The BioLINCC (Biologic Specimen and Data Repository Information Coordinating Center) is funded by the National Institutes of Health. Dr Tang is a consultant for Sequana Medical, Cardiol Therapeutics Inc, Genomics plc, Zehna Therapeutics, Boston Scientific, WhiteSwell, Intellia Therapeutics, CardiaTec Biosciences, Bristol Myers Squibb, Alleviant Medical, Alexion Pharmaceuticals, Salubris Biotherapeutics, and BioCardia Inc; and has received honorarium from Springer, Belvoir Media Group, and the American Board of Internal Medicine. All
other authors have reported that they have no relationships relevant to the contents of this paper to disclose
3-Year Clinical Outcomes Comparing the Amulet vs Watchman FLX for Left Atrial Appendage Closure in Patients With Atrial Fibrillation Results From the SWISS-APERO Randomized Clinical Trial
No full textBackground: No study thus far has compared Amulet with Watchman FLX for clinical outcomes beyond 1 year after percutaneous left atrial appendage closure (LAAC). Objectives: The goal of this study was to compare Amulet and Watchman FLX in terms of 3-year clinical outcomes. Methods: In the investigator-initiated SWISS-APERO (Comparison of Amplatzer Amulet and Watchman Device in Patients Undergoing Left Atrial Appendage Closure) trial, patients with atrial fibrillation and high bleeding risk undergoing LAAC were randomly assigned (1:1) to receive Amulet or Watchman/FLX across 8 centers. Study endpoint included the composite of cardiovascular death, stroke, transient ischemic attack, or systemic embolism at 3 years. Analyses were repeated in the as-treated (AT) and per-protocol (PP) populations. Results: Of the 221 patients randomized to treatment, 220 completed LAAC and 3 patients randomized to receive the Amulet device received the Watchman FLX device. The follow-up rate at 3 years was 96.4% in the Amulet group and 97.3% in the Watchman group. The composite ischemic endpoint occurred numerically less frequently in the Amulet group compared with the Watchman group (18.2% vs 31.0%; HR: 0.58; 95% CI: 0.33-1.03; P = 0.06). In both the AT (17.0% vs 31.1%; HR: 0.53; 95% CI: 0.30-0.96; P = 0.035) and PP (16.2% vs 29.2%; HR: 0.54; 95% CI: 0.29-1.00; P = 0.049) populations, the composite ischemic endpoint was significantly lower in the Amulet group compared with the Watchman group. Conclusions: At 3 years after LAAC, there was no significant difference in the ischemic risk between the Amulet and the Watchman FLX groups. The lower occurrence of the ischemic composite endpoint observed in the Amulet group in both the AT and PP analyses is hypothesis generating and emphasizes the need for further studies. (Comparison of Amplatzer Amulet and Watchman Device in Patients Undergoing Left Atrial Appendage Closure [SWISS-APERO]; NCT03399851). (c) 2025 by the American College of Cardiology Foundation.Abbott; Swiss Heart Foundation; Abbott and Boston Scientific; Baye
Semi-Invasive Pressure-Flow Plots Obtained Using Exercise Echocardiography Relate to Clinical Status and Exercise Capacity in Patients With a Fontan Circulation
No full textAims: Exercise echocardiography with peripheral venous pressure measurement (CPETecho-PVP) may provide superior insights into the pathophysiology of Fontan failure compared to standard cardiopulmonary exercise testing. Accordingly, we assessed (1) the clinical and hemodynamic correlates of pressure-flow plots obtained from CPETecho-PVP in Fontan patients and (2) the relationship between pressure-flow plots and exercise capacity. Methods: Forty-one consecutive Fontan patients underwent CPETecho-PVP. Peripheral venous pressure was measured in the distal upper extremity using an 18- to 20-gauge intravenous line. A multipoint PVP/cardiac output (CO) slope was calculated as a linear approximation using linear regression analysis from individual pressure-flow plots. A PVP/CO >3 mm Hg/L/min was considered elevated. Results: Median age was 28 (range, 17-60) years; left ventricle dominance was present in 32 (78%) patients. Compared to patients with a PVP/CO slope 3 mm Hg/L/min were more likely to have New York Heart Association functional class III to IV (P = .005), lung pathology (P = .004), history of atrial arrhythmia (P = .009), or thromboembolism (P = .02). Additionally, a PVP/CO slope >3 mm Hg/L/min was associated with higher N-terminal prohormone of natriuretic peptide levels (325.0 [176.3-590.0] vs 150.5 [61.3-255.0] ng/L; P = .034), lower peak oxygen consumption (peak VO2) 48.7% +/- 13.3% vs 65.2% +/- 15.3% predicted; P = .003), lower heart rate reserve (65% [42%-105%] vs 100% [75%-127%] predicted; P = .010), and lower peak cardiac index (3.8 +/- 0.8 vs 6.3 +/- 1.5 L/min.m(2); P < .001). Rest-to-peak change in heart rate (P < .001) and cardiac index (P = .006), percentage predicted forced vital capacity (P = .044), and PVP/CO slope (P = .009) were all related to percentage predicted peak VO2. Conclusions: A steeper PVP/CO plot is associated with worse clinical status, including lower exercise capacity. This supports the notion of implementing the CPETecho-PVP in the standard of care for Fontan patients
The NEO-MINDSET trial: immediate aspirin withdrawal after percutaneous coronary intervention for acute coronary syndrome-remains a therapeutic no-man's land
No full textAssessment of Local Influence in the Fitting of Lactation Curves Using Nonlinear Mixed Models
No full textThe identification of highly influential animals in the estimation of model parameters is fundamental to understanding individual variation in lactation patterns and to identifying unique profiles, helping the researcher to gain insight into the phenomenon under investigation. In this study, we analyzed the lactation curves of 30 Saanen goats using a nonlinear mixed-effects model derived from Wood's lactation model and applied a local influence diagnostic tool to detect animals that may disproportionately affect parameter estimates. The data comes from an unbalanced experiment designed to study the effect of cumulative stress on the average weekly milk production. The diagnostic of local influence enabled the identification of some animals with an unusual profile. Through the parameters of the fitted model, we identified that the treatment effect was not statistically significant during the experimental week, but negatively affected milk production throughout the lactation period.This work was supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) under Grant 001
Bidirectional Associations Between Physical Activity, Sedentary Behavior, and Daily Symptoms in Patients With Chronic Obstructive Pulmonary Disease: Longitudinal Observational Study
No full textBackground: Questionnaire-based symptom assessment may introduce recall bias and lacks bidirectional exploration. This is particularly relevant, given the unclear direction of the associations between physical activity (PA), sedentary time (ST), and symptoms in patients with chronic obstructive pulmonary disease (COPD). Understanding these associations could inform symptom management strategies and improve patient quality of life. Objective: This study aimed to investigate the direction of the association between PA, ST, and symptoms in patients with COPD using accelerometry and ecological momentary assessment (EMA). Methods:A subsample from the FAntasTIGUE study answered 8 randomly timed EMA questionnaires daily for 5 days. Ten symptoms were rated on a 7-point Likert scale: "I feel relaxed, short of breath, energetic, cheerful, insecure, irritated, satisfied, anxious, tired, and mentally fit." Concurrently, step count and ST were measured using the ActiGraph GT9X Link placed on the right hip. Step count and ST 15 and 30 minutes pre- and post-EMA were used in multilevel models, controlled for pre-EMA steps and ST, and the previous EMA score. Significant confounders were used as covariates, and patient ID was used as random intercept. Results: Thirty-four patients (19/34, 56% men, mean age 66, SD 7 years; forced expiratory volume in 1 second 52 +/- 20% predicted; 1035 EMA responses) were included. Feeling more relaxed was associated with a higher step count 15 minutes post-EMA (beta=5.1; 95% CI 0.9 to 10.1; P=.046). Conversely, higher step count 15 and 30 minutes pre-EMA was associated with feeling less relaxed (beta=-5.2x10(-4); 95% CI -9.7x10(-4) to -7.0x10(-5); P=.02; and beta=-3.2x10(-4); 95% CI -5.6x10(-4) to -7.9x10(-5); P=.009), more short of breath (beta=8.5x10(-4); 95% CI 4.7x10(-4) to 1.2x10(-3); P<.001; and beta=4.6x10(-4); 95% CI 2.6x10(-4) to 6.6x10(-4); P<.001), and tired (beta=5.1x10(-4); 95% CI 7.2x10(-5) to 9.4x10(-4); P=.02; and beta=2.9x10(-4); 95% CI 5.3x10(-5) to 5.2x10(-4); P=.02). Higher ST 15 and 30 minutes pre-EMA was associated with feeling more anxious (beta=1.7x10(-4); 95% CI 1.7x10(-5) to 3.2x10(-4); P=.03; and beta=8.5x10(-5); 95% CI 2.5x10(-6) to 1.7x10(-4); P=.04). Conclusions: A bidirectional association of feeling relaxed with PA was found in patients with COPD. Higher step count was related to feeling more short of breath and tired, whereas higher ST was associated with heightened anxiety.Lung Foundation Netherlands, Leusden, the Netherlands [4.1.16.085]
Validation of the Chimeric Fluorescent Reporter mClYFP-GlyRα2 for Nanoscale Activity Mapping of the Glycine Receptor alpha2
No full textHet behouden van excitatie/inhibitie (E/I) balans is cruciaal voor correcte informatieverwerking in de hersenen. Verstoring van deze balans speelt een rol bij diverse psychiatrische en neurologische aandoeningen. Glycinereceptoren (GlyRs), ligand-gated chloridekanalen die neuronale excitabiliteit moduleren, zijn hierbij essentieel. Hun werking is sterk contextafhankelijk en wordt bepaald door hun celtypespecifieke verdeling over subcellulaire compartimenten. Inzicht in hun subcellulaire lokalisatie is daarom van groot belang voor het begrijpen van hun (patho)fysiologische rol en voor het ontwikkelen van gerichte therapieën. Daarom werd een chimere fluorescente reporter, mClYFP-GlyRα2, ontwikkeld door GlyRα2 te fuseren met een gele fluorescerende chloride-sensor. Dit hulpmiddel maakt het mogelijk om GlyRα2 met hoge resolutie in levende cellen te visualiseren en gelijktijdig receptoractiviteit te meten. Het doel van deze studie was het valideren van mClYFP-GlyRα2. Single-channel patch-clampmetingen toonden aan dat het chimere eiwit de eigenschappen van het natieve kanaal behoudt. Live-cell TIRF-imaging bevestigde dat mClYFP zijn chloridegevoeligheid behoudt en real-time detectie van receptoractivatie mogelijk maakt. Deze resultaten valideren mClYFP-GlyRα2 als betrouwbare tool voor lokalisatie- en activiteitsonderzoek van GlyRα2 in levende cellen. Toepassing hiervan zal inzicht geven in de rol van GlyRα2 in uiteenlopende (patho)fysiologische contexten en bijdragen aan therapieontwikkeling
