Clinical trial NCT04282850: Ablation Versus Medical Management of Atrial Fibrillation in HFpEF
Official title: Ablation Versus Medical Management of Atrial Fibrillation in Heart Failure With Preserved Ejection fRaction and the Effects on Exercise Capacity (AMPERE)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Atrial Fibrillation
Heart Failure With Normal Ejection Fraction
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: Biosense Webster, Inc.
name: Medtronic
First posted: 2020-02-25
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 2:1 randomization to catheter ablation (PVI) or to medical management.
Primary purpose: TREATMENT

Brief summary: This is a prospective non-blinded randomized control pilot study comparing the effect of pulmonary vein isolation against medical management of atrial fibrillation in patients with Heart Failure with preserved Ejection Fraction (HFpEF).

Detailed description: Recent studies using PVI for rhythm control in patients with heart failure with reduced ejection fraction (HFrEF) have shown improvement in systolic ejection fraction, exercise capacity, quality of life, and a significant reduction in all-cause mortality. The PVI procedure has been shown to be safe and comparably effective in treating Atrial Fibrillation (AF) in HFpEF patients, but no studies have yet demonstrated the effects of catheter ablation on exercise capacity or clinical outcomes.

The investigators propose a prospective, non-blinded randomized control pilot study to assess the feasibility of conducting larger scale studies to determine if there are differences between catheter ablation with medical management on exercise capacity and quality of life in HFpEF patients with AF. The investigators' study will be powered for AF burden reduction, and the investigators hope to use the effect size on exercise capacity and heart failure events to help determine power for larger clinical studies that will follow to shed light on how invasive management of atrial fibrillation may impact the natural history of individuals with these two cardiovascular conditions.

Eligibility criteria: Inclusion Criteria:

* between 18 to 90 years of age, male or female
* Left Ventricular Ejection Fraction (LVEF) \> 50% by echocardiogram during routine screening or within 12 months prior to enrollment day.
* Symptoms of heart failure requiring treatment with diuretic therapy for at least 30 days preceding enrollment.
* Symptomatic paroxysmal or persistent atrial fibrillation.
* Paroxysmal atrial fibrillation defined as recurrent AF (at least 2 episodes) that terminated spontaneously within 7 days
* Persistent AF was defined as AF which is sustained beyond 7 days, or lasting less than 7 days but necessitating pharmacologic or electrical cardioversion
* Included within the category of persistent AF is "long-standing persistent AF" defined as continuous AF of greater than 1 year in duration
* AF episodes had to be documented in the last 3 months prior to enrollment by ECG, Holter monitor, Loop recorder, memory of the implanted device, or any suitable device.
* Current symptoms of heart failure (NYHA II-IV) at the enrollment visit (Visit 1)
* Structural heart disease evidenced by one or both of the following echocardiographic findings (done during the transthoracic echocardiography (TTE) within 6 months of enrollment)
* Left atrial enlargement (LAE) defined as LA width \> 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. (of note, LA length greater than 6.0 cm will be excluded)
* Left ventricular hypertrophy (LVH) defined by septal thickness or posterior wall thickness \> 1.0 cm
* And at least one of the following:
* A heart failure hospitalization lasting over 12 hours and including intravenous diuretics at a healthcare facility within 12 months prior to the enrollment visit.
* An elevated pro-brain natriuretic peptide (BNP) (\>100 pg/mL, or N-terminal pro b-type natriuretic peptide (NT-proBNP)\>300 pg/mL)
* Hemodynamic testing consistent with HFpEF physiology including pulmonary capillary wedge pressure (PCWP) (or LVEDP) ≥ 15 mmHg.

Exclusion Criteria:

* Previous left heart ablation procedure for AF
* Contraindication to chronic anticoagulation therapy or heparin
* Longstanding atrial fibrillation, defined here as greater than 3 years of persistent atrial fibrillation
* Severe left atrial dilatation, with LA length \> 6.0 cm, optimally from parasternal long view
* Acute coronary syndrome within 4 weeks as defined by electrocardiographic (ECG) ST segment depression or prominent T-wave inversion and/or positive biomarkers of necrosis (e.g. troponin) in the absence of ST-segment elevation and in an appropriate clinical setting (chest discomfort or angina equivalent).
* Cardiac surgery, angioplasty, or cerebrovascular accident within 4 weeks prior to enrollment.
* Planned cardiovascular intervention
* Listed for heart transplant
* Cardiac assist device implanted or need for mechanical hemodynamic support or inpatient admission
* Life expectancy less than 1 year
* Uncontrolled hypertension, defined as resting systolic blood pressure \>190 and/or resting diastolic pressure\>110
* Chronic Kidney Disease (CKD) stage 4-5 (GFR\<25 ml/min/1.73m2), or on hemodialysis
* Cardiac diagnosis in addition to or other than HFpEF:
* Active myocarditis
* Hypertrophic obstructive cardiomyopathy
* Severe valvular disease
* Restrictive or constrictive cardiomyopathy, including known amyloidosis, sarcoidosis, hemochromatosis
* Complex congenital heart disease
* Constrictive pericarditis
* Severe pulmonary hypertension (RVSP \> 60 mmHg), not secondary to HFpEF
* Non-cardiac pulmonary edema
* Clinical evidence of digoxin toxicity
* Sepsis
* Inability to comply with planned study procedures
* Pregnancy or nursing mothers
* Uncontrolled hypothyroidism or hyperthyroidism
* BMI of \>65 kg/m2

Primary outcomes:
measure: Change in AF burden as assessed by difference in percentage of time an individual is in AF
timeFrame: 3, 6, 9, and 12 months from intervention
Secondary outcomes:
measure: All-cause mortality
timeFrame: 12 months
measure: Number of cardiovascular mortalities
timeFrame: 12 months
measure: Number of all-cause hospitalizations
timeFrame: 12 months
measure: Number of heart failure hospitalizations
timeFrame: 12 months
measure: Change in patient-reported quality of life as assessed by Kansas City Cardiomyopathy Questionnaire
timeFrame: At enrollment (baseline) and 6 months following intervention
measure: Change in NT pro-BNP levels
timeFrame: At enrollment (baseline) and 6 months following intervention
measure: Change in exercise capacity as assessed by the 6 minute walk distance test
timeFrame: At baseline and 6 months post intervention
Other outcomes:
Locations:
city: Fairfax
country: United States
facility: Inova Heart and Vascular Institute
state: Virginia
Study officials:
affiliation: Inova Heart and Vascular Institute
name: Brett Atwater, MD
role: STUDY_CHAIR
affiliation: Inova Heart and Vascular Institute
name: Eunice Yang, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: