Catheter Ablation in End-Stage Heart Failure With Atrial Fibrillation - CASTLE HTx

Contribution To Literature:

The CASTLE HTx trial showed that in patients with symptomatic AF and end-stage HF, catheter ablation was associated with a decrease in the composite outcome of all-cause mortality, LVAD implantation, and urgent transplantation compared with medical therapy alone.


The goal of the trial was to determine the potential therapeutic effect of catheter ablation for symptomatic atrial fibrillation (AF) in patients with end-stage heart failure with reduced ejection fraction (HFrEF).

Study Design

  • Single-center
  • Open-label

Patients with symptomatic AF and end-stage HFrEF undergoing evaluation for left ventricular assist device (LVAD) implantation or heart transplantation (HT) were randomized to undergo catheter ablation of AF and guideline-directed medical therapy (n = 97) or medical therapy alone (n = 97). The decision to ablate beyond pulmonary vein isolation or repeat ablation for AF recurrence was at the discretion of the operator. Antiarrhythmic drugs were discontinued after catheter ablation but could be resumed for AF recurrence. Patients in the medical therapy arm could undergo rhythm or rate control, as appropriate.

  • Total number of enrollees: 194
  • Median duration of follow-up: 18 months
  • Mean patient age: 62 vs. 65 years (catheter ablation vs. medical therapy, respectively)
  • Percentage female: 19.1%

Inclusion criteria:

  • Age ≥18 years
  • Symptomatic paroxysmal or persistent AF
  • Left ventricular ejection fraction (LVEF) ≤35%
  • Under evaluation for HT or LVAD implantation
  • New York Heart Association functional class II-IV
  • Presence of or indication for cardiac implantable electronic device

Exclusion criteria:

  • Life expectancy ≤12 months
  • Left atrial diameter >6 cm
  • Contraindication for chronic anticoagulation
  • Previous AF ablation
  • Presence of durable LVAD
  • “High urgent” listing for HT
  • Acute coronary syndrome, cardiac surgery, coronary revascularization, or stroke ≤2 months prior
  • Other planned cardiac intervention
  • Untreated thyroid disorder
  • End-stage renal disease requiring dialysis

Other salient features/characteristics:

  • Mean LVEF: 29% vs. 25% (catheter ablation vs. medical therapy, respectively)
  • Mean AF duration: 4 vs. 3 years (catheter ablation vs. medical therapy, respectively)
  • Mean left atrial diameter: 4.9 cm
  • Percentage nonischemic cardiomyopathy: 61%
  • Baseline amiodarone use: 46%
  • Catheter ablation was performed in 84% and 16% of the ablation and medical therapy arms, respectively

Principal Findings:

The trial was terminated early due to evidence of overwhelming efficacy in the catheter ablation arm.  

The primary outcome, composite of all-cause mortality, LVAD implantation, or urgent HT, at a median of 18 months for catheter ablation vs. medical therapy, was: 8% vs. 30% (p < 0.001).

Secondary outcomes for catheter ablation vs. medical therapy:

  • All-cause mortality: 6% vs. 20%, hazard ratio 0.29, 95% CI 0.12-0.72 (p < 0.05)
  • LVAD implantation: 1% vs. 10% (p < 0.05)
  • Urgent HT: 1% vs. 6% (p > 0.05)
  • Change in LVEF at 12 months: +7.8% vs. +1.4% (p < 0.05)
  • Change in AF burden at 12 months: -31.4% vs. -8.6% (p < 0.05)
  • Amiodarone use at 12 months: 29% vs. 57%


The CASTLE HTx trial demonstrates a reduction in the primary composite outcome of all-cause mortality, LVAD implantation, and urgent HT with catheter ablation compared with medical therapy alone in end-stage HFrEF with symptomatic AF. This effect was driven primarily by reduction in all-cause death and LVAD implantation and was observed despite significant crossover between treatment arms within weeks of randomization, prompting early termination of the trial for efficacy. The current data extend the positive findings of CASTLE-AF, which excluded patients listed for HT, to end-stage HFrEF patients referred for advanced therapies. It is unclear whether the treatment effect would be replicated in patients with asymptomatic AF, which was not studied in either trial. While the single-center nature and small sample size of this study do limit its generalizability somewhat, these findings are nevertheless promising and support further investigation into AF management in end-stage HF.


Highlighted text has been updated as of October 16, 2023.

Sohns C, Fox H, Marrouche NF, et al., on behalf of the CASTLE HTx Investigators. Catheter Ablation in End-Stage Heart Failure With Atrial Fibrillation. N Engl J Med 2023;389:1380-9.

Lewis EF. Editorial: Catheter Ablation for Atrial Fibrillation in Heart Failure — An Option to Defer Transplantation? N Engl J Med 2023;389:1429-30.

Presented by Dr. Christian Sohns at the European Society of Cardiology Congress, Amsterdam, Netherlands, August 27, 2023.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Cardiac Surgery, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Anticoagulation Management and Atrial Fibrillation, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Cardiac Surgery and Arrhythmias, Cardiac Surgery and Heart Failure, Acute Heart Failure, Heart Transplant, Mechanical Circulatory Support

Keywords: Ablation, Anticoagulants, Arrhythmias, Cardiac, Atrial Fibrillation, Catheter Ablation, ESC Congress, ESC23, Heart-Assist Devices, Heart Failure, Heart Failure, Reduced Ejection Fraction, Heart Transplantation, Stroke Volume

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