Atrial fibrillation (AF) in the context of heart failure (HF) is associated with a markedly poor prognosis. Catheter ablation has been shown to improve outcomes in this population, enhancing ablation success rates in these patients is critical for further reducing morbidity and mortality. We conducted this multicenter, randomized clinical trial to systematically evaluate the optimal ablation strategy in patients with heart failure and persistent AF.

Atrial fibrillation (AF) in the context of heart failure (HF) is associated with a markedly poor prognosis, with one-year all-cause mortality rates approaching 34% and substantially elevated risks of stroke and rehospitalization. Catheter ablation has been shown to improve outcomes in this population, as evidenced by numerous pivotal studies, such as CASTLE-AF. It is well recognized that the majority of patients with HF and AF exhibit persistent AF; however, the underlying mechanisms responsible for sustaining persistent AF in this population remain to be fully elucidated. Thus, enhancing ablation success rates in these patients is therefore critical for further reducing morbidity and mortality.

Building on prior research, we have identified driver regions as critical determinants in the maintenance of persistent atrial fibrillation. Moreover, our randomized controlled trials have demonstrated that electro-anatomical ablation may represent the optimal strategy for persistent AF. Based on these findings, we conducted a multicenter, randomized clinical trial to systematically evaluate the optimal ablation strategy in patients with heart failure and persistent AF.

Inclusion Criteria:

• All inclusion criteria must be met to be included in the study.

  1. Age: Patients aged 18-80 years, with persistent atrial fibrillation (AF) and heart failure (HF), regardless of ejection fraction (EF).

  2. Diagnosis of Heart Failure:

     Heart Failure with Reduced Ejection Fraction (HFrEF): LVEF ≤ 40%. Heart Failure with Preserved Ejection Fraction (HFpEF): LVEF > 40%, including HFmrEF (LVEF 41-50%).

  3. Symptomatic Atrial Fibrillation: Patients with symptomatic persistent AF who have failed or are intolerant to at least one antiarrhythmic drug.

  4. NYHA Class II-III: Patients with heart failure classified as NYHA class II-III, who are symptomatic despite optimal medical therapy. Informed Consent: Able to provide written informed consent for participation in the study.

  5. Guideline-Recommended Pharmacologic Therapy: Patients who have received and are currently on guideline-recommended pharmacologic therapy for heart failure, including but not limited to ACE inhibitors, beta-blockers, diuretics, and mineralocorticoid receptor antagonists (MRAs).

Exclusion Criteria:

• Any of the following criteria shall be excluded.

  1. End-Stage Heart Failure: Patients with heart failure classified as NYHA class IV or with LVEF ≤ 20%.
  2. Severe Comorbidities:
  3. Patients with severe pulmonary disease (e.g., COPD, severe restrictive lung disease).
  4. Severe renal dysfunction (eGFR < 30 mL/min/1.73m²) or advanced liver disease.
  5. Active malignancy or other terminal illnesses with a prognosis of less than one year.
  6. Inability to Tolerate Ablation:
  1. Patients unable to undergo catheter ablation due to anatomical or procedural issues.
  2. Patients with contraindications to the procedure, including allergy to contrast agents or inability to tolerate anesthesia.
  3. Left atrial thrombus confirmed by preoperative esophageal ultrasound; 7. Uncontrolled Arrhythmias: Patients with persistent or paroxysmal AF who are unable to maintain sinus rhythm despite optimal medical therapy or require frequent hospitalization for arrhythmia control.

  8. Pregnancy: Pregnant or breastfeeding women. 9. Contraindications to Anticoagulation: 10. Patients who are contraindicated for anticoagulation therapy (e.g., history of major bleeding or bleeding diathesis).

  11. History of Severe Valve Disease: Patients with a history of severe valve disease and/or prosthetic valve replacement.

  12. Recent Myocardial Infarction or Stroke: Patients who have had a myocardial infarction or stroke within the past 3 months.

  13. Contrast Agent Allergy: Patients with a known allergy to contrast agents. 14. Contraindications for Cardiac Catheterization: Any contraindications for cardiac catheterization, including inability to safely perform the procedure.

  15. Atrial Fibrillation Ablation: Patients who have previously undergone atrial fibrillation ablation.

  16. Cardiac Surgery: Patients who have undergone any cardiac surgery within the last 2 months.

  17. Life Expectancy: Patients with a life expectancy of less than 1 year.

The individual participant data (IPD) from this study will not be shared publicly due to concerns regarding patient confidentiality and the sensitive nature of medical data. Given the potential risks of identifying participants from detailed clinical information, the data will remain confidential and will not be made available for public sharing. Additionally, the study involves proprietary methodologies and ongoing analyses that are part of the intellectual property of the institution. As such, sharing the IPD at this stage could compromise the integrity of the study's findings and its future applications.