Treatment for Atrial Fibrillation in Heart Failure with Preserved Function

A Phase 4, Randomized, Open Label, Multicenter Prospective Comparative Study To Evaluate The Treatment Of Atrial Fibrillation In Preserved Cardiac Function Heart Failure

This study tests whether a procedure called catheter ablation works better than medication for treating atrial fibrillation in people with heart failure who still have good heart function.

Quick facts

• Phase: PHASE4
• Study type: Interventional
• Enrollment: 360 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Electrophysiology Research Foundation (other)
• Locations: 9 sites (Flagstaff, Arizona and 8 other locations)
• Trial ID: NCT04160000 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of catheter ablation versus antiarrhythmic drug therapy in patients with atrial fibrillation and preserved systolic cardiac function who have experienced heart failure events. The study is divided into two phases: the first phase compares the safety and efficacy of the two treatment strategies, while the second phase evaluates the impact of wireless pulmonary artery pressure monitoring on heart failure therapy optimization. Patients will be followed for a minimum of six months to assess event rates and treatment outcomes.

Who should consider this trial

Good fit: Ideal candidates include outpatients aged 50 and older with symptomatic heart failure and documented atrial fibrillation.

Not a fit: Patients with heart failure and reduced ejection fraction or those not experiencing atrial fibrillation may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new effective treatment option for patients with atrial fibrillation and heart failure with preserved ejection fraction.

How similar studies have performed: While catheter ablation and antiarrhythmic drugs have been used in other heart failure populations, this specific approach in patients with preserved ejection fraction is novel and has not been widely tested.

Eligibility criteria

Inclusion Criteria: Patient with symptomatic Heart Failure with preserved systolic cardiac function \& paroxysmal or persistent atrial fibrillation who meet the following criteria

1. Subjects must be willing and able to give written informed consent
2. Outpatients ≥ 50 years of age, male or post- menopausal female patients; premenopausal female patients who are on and will maintain continuous birth control therapy during the study.
3. Subjects must have documented HFpEF \& paroxysmal or persistent AF and satisfy one of the following inclusion criteria a) Consecutive patients with AF, symptomatic heart failure requiring diuretic therapy for at least 30 days prior to study entry b) Hospitalization for HF and/or AF in the past 12 months prior to catheter ablation with documented NT-pro BNP \>200pg/ml for patients not in AF or \> 600 pg/ml for patients in AF on screening ECG or NYHA class 2, 3 or ambulatory class 4 heart failure documented NT-pro BNP \>300pg/ml for patients not in AF or \> 900 pg/ml for patients in AF on screening ECG c).Evidence of structural heart disease defined as by at least 1 of the following echocardiography findings (any local measurement made during the screening epoch or within the 6 months prior to screening visit): 1) LA enlargement defined by at least 1 of the following: LA width (diameter) \>3.8 cm or LA length \>5.0 cm or LA area \>20 cm2 or LA volume \>55 ml or LA volume index \>29 ml/m2 2) LVH defined by septal thickness or posterior wall thickness \>1.1 cm d).Left ventricular ejection fraction \> 45% using standard imaging techniques at enrollment for study or in prior 6 months e).ECG documented paroxysmal or persistent atrial fibrillation f).Patients are candidates for a clinically indicated catheter ablation procedure, and Rate or Rhythm control antiarrhythmic drug therapy
4. Patients should be on one or more standard heart failure drug therapy (ies) for heart failure with preserved cardiac function for at least 30 days
5. Written informed consent for the clinically indicated study procedures
6. Patients must be candidates for long-term OAC therapy based on clinical practice guidelines for treatment of AF. Guidelines for GFR as established for DOACSs will be applicable to all subjects.

Exclusion Criteria:

1. Patients with HFpEF who were not on any drug therapy for HF or have uncontrolled hypertension defined as systolic BP \>180 mm Hg at screening or \>150 mm Hg on three or more antihypertensive drugs
2. Patients with QRS duration of \>120 ms and intraventricular conduction defects who are or maybe candidates for or have received ventricular resynchronization therapy
3. Recent (\<1 month) myocardial infarction or acute coronary syndrome
4. Recent (\<3 months) coronary revascularization procedures
5. Documented LA thrombus on TEE or any LVEF measurement \<40%
6. Patients who are not candidates for Rate or Rhythm control drug therapy for AF
7. Dilated cardiomyopathy due to potentially reversible cause e.g. myocarditis
8. Contraindications to anticoagulant therapy or adverse event with prior Warfarin or DOAC therapy
9. Creatinine clearance \<30ml/min or \>95ml/min
10. Advanced hepatic disease, pulmonary disease clinically significant congenital heart disease, clinically significant pericardial constriction, hypertrophic cardiomyopathy, infiltrative cardiomyopathy, decompensated valvular heart disease likely to require surgical or percutaneous intervention during the trial
11. Recent stroke (\<3 months) or thromboembolic event, transient ischemic attack or carotid angioplasty in the prior 3 months
12. Recent (\<3 months) intracranial or other major bleeding event
13. Candidates for heart or any other organ transplantation or left ventricular assist devices, recent (\< 3 months) valve or other cardiac surgery
14. Patients requiring ACE inhibitor or ARB drug therapy for any reason
15. History of hypersensitivity to antiarrhythmic drugs
16. Patients with other clinically significant medical condition that precludes study participation
17. Patients with life expectancy \< 1 year
18. Premenopausal female patients, who are not on continuous birth control therapy or are likely to discontinue it at any time during the entire duration of study enrollment.
19. Pregnant or nursing lactating mothers or women of childbearing potential who are not on effective contraceptive therapy
20. Patients who have been noncompliant with medical regimens or have social or other issues precluding regular follow up, history of alcohol or drug abuse in past 12 months.

Where this trial is running

Flagstaff, Arizona and 8 other locations

• Northern Arizona Health Care — Flagstaff, Arizona, United States (RECRUITING)
• St. Bernards Heart and Vascular Center — Jonesboro, Arkansas, United States (RECRUITING)
• South Denver Cardiology — Littleton, Colorado, United States (RECRUITING)
• Kansas City Heart Rhythm Institute — Overland, Missouri, United States (RECRUITING)
• Electrophysiology Research Foundation — Warren Township, New Jersey, United States (RECRUITING)
• Hospital of the University of Pennsylvania — Philadelphia, Pennsylvania, United States (RECRUITING)
• TCAI at St. David's Hospital — Austin, Texas, United States (RECRUITING)
• Peter Osypka Herzzentrum — Munich, Bavaria, Germany (NOT_YET_RECRUITING)
• Hopitaux Universitaires de Geneve — Geneva, Canton of Geneva, Switzerland (RECRUITING)

Study contacts

• Study coordinator: SANJEEV SAKSENA, MD

Conditions: Atrial Fibrillation, Heart Failure, Diastolic Heart Failure, Atrial fibrillation, Heart failure, Diastolic heart failure, Catheter Ablation, Antiarrhythmic Drugs