The clinical equipoise in the treatment of Atrial Fibrillation (AF) in patients with Heart Failure with mildly reduced Ejection Fraction/Heart Failure with Preserved Ejection Fraction (HFmrEF/HFpEF) reflects the scarcity of randomized trials on different treatment modalities. By generating high-quality, evidence-based, randomized data on the impact of treatment on hard outcomes, Catheter Ablation Versus Standard Conventional Treatment in Atrial Fibrillation Patients with Heart Failure with Preserved Ejection Fraction (CASTLE-HFpEF) will provide clinical decision-making guidance and help physicians in the management of patients with HFmrEF/HFpEF and AF.
The main hypothesis is that Catheter Ablation (CA) for AF is associated with improved clinical outcomes in patients with HFmrEF/HFpEF and AF compared to medical AF treatment strategies on top of optimal medical HF treatment. CASTLE-HFpEF aims to study these hard clinical outcomes in a randomized cohort of patients with AF and HFmrEF/HFpEF.
≥18 years of age at screening visit.
Clinical signs and symptoms of HF (26).
Left ventricular ejection fraction (LVEF) >40% within the past 12 months (most recent LVEF measurement)
For patients in normal sinus rhythm (NSR) at the time of blood sampling: NT proBNP ≥300 pg/mL
Previous catheter ablation for AF.
Known infiltrative cardiomyopathy, hypertrophic cardiomyopathy and amyloidosis.
Documented left atrial diameter >6cm.
Any contraindication for chronic anticoagulation therapy or heparin, including hypersensitivity to any of the components.
Parallel
Catheter ablation
Procedure/SurgeryA catheter ablation (CA) is a minimally invasive medical procedure for treatment of cardiac arrhythmias. Rhythm control of AF is attempted by pulmonary vein isolation (PVI) and posterior wall isolation (PWI). During the procedure, a catheter is guided to the heart through a blood vessel, which is either the femoral vein or a central vein, in order to ablate abnormal conductive heart tissue that causes the arrhythmias. Ablation is achieved either by thermal (cauterization by radiofrequency (RF) ablation / freezing by cryoballoon) or non-thermal mechanisms (primarily irreversible electroporation (IRE) through pulsed field ablation (PFA)). In case of successful ablation, a normal heart rhythm (sinus rhythm) can be restored.
Composite endpoint of all-cause mortality, stroke or transient ischemic attack (TIA), and hospitalizations for worsening HF and clinically relevant decrease of NT proBNP (after 12 months)
Hierarchical composite endpoint of the hard outcomes all-cause mortality, stroke or TIA, and hospitalizations for worsening HF (all after 36 months), and clinically relevant decrease of NT proBNP (after 12 months), analyzed using the Win Ratio method for each AF treatment arm (PFA-based CA versus conventional therapy). The Win Ratio is a statistical method designed to analyze composite outcomes with hierarchical clinical priorities, such as death, hospitalization, and functional status. Each patient in the treatment group is then compared to each patient in the control group, forming all possible unmatched pairs. Within each pair, the patient who experiences the more favorable outcome at the highest priority level is declared the "winner." The Win Ratio is calculated as the total number of wins in the treatment group divided by the number of wins in the control group, providing a clinically intuitive summary of net benefit.
Combined hard outcomes (all-cause mortality, stroke or TIA, hospitalizations for worsening HF; time to first event)
The combined hard outcome is defined as the time to the first occurrence of any of the three specified components, and will be analyzed using Kaplan-Meier survival curves and the log-rank test to compare event-free survival between groups.
Total HF-related events (hospitalization for worsening HF and outpatient worsening HF events)
The investigators will count the total HF-related events (hospitalization for worsening HF and outpatient worsening HF events) until the end of study. It will be tested via Poisson regression or negative binomial regression, according to the data distribution. Which model to use will be determined from the likelihood ratio test. To analyze how often the HF-related events happen. Depending on how the data looks, the investigators will choose between two models - one called Poisson regression and the other called negative binomial regression. To decide which model fits the data better, the investigators will use a statistical method called a "likelihood ratio test," which compares the two models and tells the investigators which one works best for the data.
Kansas City Cardiomyopathy Questionnaire (KCCQ) score
Kansas City Cardiomyopathy Questionnaire (KCCQ) score will be tested by t-test or the Wilcoxon test, according to normal distribution or not determined by the Wil-Shapiro test. KCCQ is a validated, patient-reported outcome measure designed to assess health status in individuals with heart failure. It evaluates multiple domains, including physical limitation, symptom frequency and severity, social function, self-efficacy, and quality of life. Scores range from 0 to 100, with higher scores indicating better health status. The KCCQ is sensitive to clinical changes and is widely used in both clinical trials and practice to measure the impact of heart failure treatments from the patient's perspective. A change of 5-10 points is generally considered clinically meaningful.
All-cause mortality (time to event)
All-cause mortality will be tested via Kaplan-Meier curve and Log-rank test. The investigators will measure the survival rate based on the time to event.
Click on the lead sponsor to view all of their trials.
This trial is not recruiting at the moment. You can still explore other options:
