Optimal Ablation Strategies for Persistent AF With HF

Not Applicable

Active, not recruiting

• Conditions: Persistent Atrial Fibrillation; Heart Failure

• Registration Number: NCT07153718
• Lead Sponsor: Xu Liu

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study Start: 2021-01-01
• Status Verified: 2025-08
• Study First Submitted: 2025-08-26
• Study First Submitted QC: 2025-08-26
• Last Update Submitted: 2025-08-26
• Study First Posted: 2025-09-04
• Last Update Posted: 2025-09-04
• Primary Completion: 2026-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 300

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:
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  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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
a composite of cardiovascular mortality, hospitalization or urgent visits	12, 18, 24, 36, 46, 60months	The primary endpoint was the incidence of a composite of cardiovascular mortality, hospitalization or urgent visits due to worsening heart failure during the follow-up period after a single catheter ablation procedure
freedom from any documented AF/AT	12, 18, 24, 36, 48, 60months	freedom from any documented AF/AT episode lasting more than 30 seconds after the blanking period without anti-arrhythmic drug treatment

Secondary Outcome Measures

Name	Time	Method
Change in 6-minute walk test	12, 24, 36, 48, 60 months after a single procedure	Change in 6-minute walk test from baseline to Month 3, 12, 24, 36, 48, 60 months after a single procedure
AF burden <1%	12, 24, 36, 48, 60 months after a single procedure	AF burden \<1% after a single ablation procedure, as measured by Holter monitoring or device-recorded data (Patients who remained in persistent AF throughout follow-up were assigned AF burden=100%. Both ends of the distribution (burden=0% and burden=100%) were included in statistical analysis.).
Improvement in New York Heart Association (NYHA) functional class	12, 24, 36, 48, 60 months after a single procedure	Improvement in New York Heart Association (NYHA) functional class by at least one grade
Change in N-terminal pro-B type natriuretic peptide (NT-proBNP)	Month 3,12, 24, 36, 48, 60 after a single procedure	Change in N-terminal pro-B type natriuretic peptide (NT-proBNP) from baseline to Month 3,12, 24, 36, 48, 60 after a single procedure
Incidence of procedure-related complications	30 days after a single procedure	Incidence of procedure-related complications, including but not limited to: vascular complications (e.g., hematoma, pseudoaneurysm), cardiac tamponade, stroke or transient ischemic attack (TIA), phrenic nerve injury, atrioesophageal fistula, procedure-related death within 30 days.

Trial Locations

Locations (10)

The PLA Navy Anqing Hospital; 🇨🇳 Anqing, Anhui, China

The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology; 🇨🇳 Wuhan, Hubei, China

Changshu Hospital of Traditional Chinese Medicine; 🇨🇳 Changshu, Jiangsu, China

Xuzhou Central Hospital; 🇨🇳 Xuzhou, Jiangsu, China

Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine; 🇨🇳 Jinan, Shandong, China

Jinan City People's Hospital; 🇨🇳 Jinan, Shandong, China

Affiliated Hospital of Jining Medical University; 🇨🇳 Jining, Shandong, China

Yuhuan Second People's Hospital; 🇨🇳 Yuhuan, Zhejiang, China

Shanghai Jiao Tong University School of Medicine, Shanghai Chest Hospital; 🇨🇳 Shanghai, China

Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine; 🇨🇳 Shanghai, China