A Phase 4, Randomized, Open Label, Multicenter Prospective Comparative Study To Evaluate The Treatment Of Atrial Fibrillation In Preserved Cardiac Function Heart Failure
Heart failure (HF) with preserved left ventricular function (pEF) is difficult clinical syndrome to treat effectively with few evidence based therapies. Atrial fibrillation (AF) is now an important co-morbidity being observed in 43% of patients with HFpEF. Rhythm control has not been studied in this population. Catheter ablation and antiarrhythmic drugs are rhythm control therapies that have been used for treatment of AF without HF or HF with reduced systolic function but have not been widely applied in HFpEF. No controlled comparative evaluation has been performed in HFpEF. The introduction of wireless pulmonary artery hemodynamic monitoring has permitted optimization of HF therapy in patients with chronic HF with reduced and preserved EF. Reduction in HF hospitalizations has been observed in post hoc analyses of HFpEF patients but has not been systematically applied in AF patients with HFpEF. In this study, we propose to study both rhythm control and optimized HF therapeutic approaches in an AF with HFpEF study population in a pilot study using a sequential two phase randomized controlled clinical trial design.
• Subjects must be willing and able to give written informed consent
• 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.
• 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
• 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
• Written informed consent for the clinically indicated study procedures
• 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.