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Background: The CASTLE-HTx trial demonstrated the benefit of atrial fibrillation (AF) ablation compared with medical therapy in decreasing mortality, need for left ventricular assist device implantation, or heart transplantation (HTx) in patients with end-stage heart failure (HF)., Objective: This analysis aimed to identify risk factors related to adverse outcomes in patients with end-stage HF and to assess the impact of ablation., Methods: The CASTLE-HTx protocol randomized 194 patients with end-stage HF and AF to ablation vs medical therapy. We identified left ventricular ejection fraction <30%, New York Heart Association class ≥III, and AF burden >50% as predictors for the primary end point. The CASTLE-HTx risk score assigned weights to these risk factors. Patients with a risk score ≥3 were identified as high risk., Results: The patients were assigned to low-risk (89 [45.9%]) and high-risk (105 [54.1%]) groups. After a median follow-up of 18 months, a primary end point event occurred in 6 and 31 patients of the low- and high-risk groups (hazard ratio, 4.98; 95% confidence interval, 2.08-11.9). The incidence rate (IR) difference between ablation and medical therapy was much larger in high-risk patients (8/49 [IR, 11.4] vs 23/56 [IR, 36.1]) compared with low-risk patients (2/48 [IR, 2.6] vs 4/41 [IR, 6.3]). The IR difference for ablation was significantly higher in high-risk patients (24.69) compared with low-risk patients (3.70)., Conclusion: The absolute benefit of ablation is more pronounced in high-risk patients, but low-risk patients may also benefit. The CASTLE-HTx risk score identifies patients with end-stage HF who will particularly benefit from ablation., Competing Interests: Disclosures Dr Sohns received research support and lecture fees from Medtronic, Abbott, Boston Scientific, and Biosense Webster; is a consultant for Medtronic, Boston Scientific, and Biosense Webster; has received grant support from the Else Kröner-Fresenius-Stiftung and Deutsche Herzstiftung. Dr Sommer is member of the Advisory Board for Abbott, Biosense Webster, Boston Scientific, and Medtronic. Dr Crijns reports support from The Netherlands Cardiovascular Research Initiative: an initiative with support of the Dutch Heart Foundation, CVON 2014-9: reappraisal of atrial fibrillation: interaction between hypercoagulability, electrical remodelling, and vascular destabilization in the progression of AF (RACE V), outside this work. Dr Sossalla received speaker fees from AstraZeneca and Boehringer Ingelheim. Dr Marrouche has received grant support and consulting fees from Abbott, Wavelet Health, Medtronic, Vytronus, Biosense Webster, Boston Scientific, GE HealthCare, and Siemens; has received consulting fees from Preventice; and holds equity in Marrek and Cardiac Design. Dr Rudolph has received grant support from Abbott Vascular and Edwards Lifesciences. All other authors have nothing to declare., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: The role of catheter ablation in patients with symptomatic atrial fibrillation and end-stage heart failure is unknown., Methods: We conducted a single-center, open-label trial in Germany that involved patients with symptomatic atrial fibrillation and end-stage heart failure who were referred for heart transplantation evaluation. Patients were assigned to receive catheter ablation and guideline-directed medical therapy or medical therapy alone. The primary end point was a composite of death from any cause, implantation of a left ventricular assist device, or urgent heart transplantation., Results: A total of 97 patients were assigned to the ablation group and 97 to the medical-therapy group. The trial was stopped for efficacy by the data and safety monitoring board 1 year after randomization was completed. Catheter ablation was performed in 81 of 97 patients (84%) in the ablation group and in 16 of 97 patients (16%) in the medical-therapy group. After a median follow-up of 18.0 months (interquartile range, 14.6 to 22.6), a primary end-point event had occurred in 8 patients (8%) in the ablation group and in 29 patients (30%) in the medical-therapy group (hazard ratio, 0.24; 95% confidence interval [CI], 0.11 to 0.52; P<0.001). Death from any cause occurred in 6 patients (6%) in the ablation group and in 19 patients (20%) in the medical-therapy group (hazard ratio, 0.29; 95% CI, 0.12 to 0.72). Procedure-related complications occurred in 3 patients in the ablation group and in 1 patient in the medical-therapy group., Conclusions: Among patients with atrial fibrillation and end-stage heart failure, the combination of catheter ablation and guideline-directed medical therapy was associated with a lower likelihood of a composite of death from any cause, implantation of a left ventricular assist device, or urgent heart transplantation than medical therapy alone. (Funded by Else Kröner-Fresenius-Stiftung; CASTLE-HTx ClinicalTrials.gov number, NCT04649801.)., (Copyright © 2023 Massachusetts Medical Society.)