search
Back to results

Ablation Versus Medical Management of Atrial Fibrillation in HFpEF (AMPERE)

Primary Purpose

Atrial Fibrillation, Heart Failure With Normal Ejection Fraction

Status
Not yet recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Pulmonary Vein Isolation
Sponsored by
Johns Hopkins University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Atrial Fibrillation

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Inova Heart and Vascular Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Pulmonary Vein Isolation (PVI) Group

Medical Management

Arm Description

Subjects randomized to this treatment arm will undergo atrial fibrillation ablation, and undergo routine post-procedural follow-up.

Subjects randomized to this treatment arm will undergo medical management of the arrhythmia, but will not undergo invasive electrophysiologic procedures to address subject's AF.

Outcomes

Primary Outcome Measures

Change in AF burden as assessed by difference in percentage of time an individual is in AF
AF burden, described as the percentage of time an individual is in AF relative to the total amount of time analyzed. This outcome will be assessed at multiple intervals following intervention arm, using a continuous, implantable heart rhythm monitor. The investigators' focus will be on the change between pre-intervention AF burden and AF burden at 6 month follow-up.

Secondary Outcome Measures

All-cause mortality
All deaths within 12 months of the intervention arm.
Number of cardiovascular mortalities
The number of deaths attributable to cardiovascular causes occurring within 12 months of the intervention arm
Number of all-cause hospitalizations
The total number of inpatient hospitalizations within 12 months following the intervention.
Number of heart failure hospitalizations
The total number of inpatient hospitalizations attributable to heart failure exacerbations within 12 months following the intervention.
Change in patient-reported quality of life as assessed by Kansas City Cardiomyopathy Questionnaire
The Kansas City Cardiomyopathy Questionnaire is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. A change of 10 points or more is considered not only clinically significant but also carries prognostic implications for event-free survival in heart failure patients.
Change in NT pro-BNP levels
Serum biomarker associated with congestive heart failure symptoms, measured in (mg/ml).
Change in exercise capacity as assessed by the 6 minute walk distance test
Pre-intervention arm and 6 month post-procedural exercise capacity will be assessed using change in 6 minute walk distance, defined as the total distance (in meters) traversed during 6 minutes of time. This is well-validated measure of functional capacity and prognostic marker in patients with heart failure.

Full Information

First Posted
February 21, 2020
Last Updated
June 22, 2023
Sponsor
Johns Hopkins University
Collaborators
Biosense Webster, Inc., Medtronic
search

1. Study Identification

Unique Protocol Identification Number
NCT04282850
Brief Title
Ablation Versus Medical Management of Atrial Fibrillation in HFpEF
Acronym
AMPERE
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

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
July 10, 2023 (Anticipated)
Primary Completion Date
January 2025 (Anticipated)
Study Completion Date
January 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Johns Hopkins University
Collaborators
Biosense Webster, Inc., Medtronic

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atrial Fibrillation, Heart Failure With Normal Ejection Fraction

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
2:1 randomization to catheter ablation (PVI) or to medical management.
Masking
Outcomes Assessor
Masking Description
Serum biomarkers, atrial fibrillation burden, anatomical and functional echocardiographic parameters, and exercise capacity will all be measured and analyzed by study personnel blinded to the patient's intervention.
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Pulmonary Vein Isolation (PVI) Group
Arm Type
Experimental
Arm Description
Subjects randomized to this treatment arm will undergo atrial fibrillation ablation, and undergo routine post-procedural follow-up.
Arm Title
Medical Management
Arm Type
No Intervention
Arm Description
Subjects randomized to this treatment arm will undergo medical management of the arrhythmia, but will not undergo invasive electrophysiologic procedures to address subject's AF.
Intervention Type
Procedure
Intervention Name(s)
Pulmonary Vein Isolation
Other Intervention Name(s)
Atrial fibrillation ablation
Intervention Description
The intervention will involve standard of care electrophysiology ablation for rhythm management of atrial fibrillation with a procedure called a pulmonary vein isolation.
Primary Outcome Measure Information:
Title
Change in AF burden as assessed by difference in percentage of time an individual is in AF
Description
AF burden, described as the percentage of time an individual is in AF relative to the total amount of time analyzed. This outcome will be assessed at multiple intervals following intervention arm, using a continuous, implantable heart rhythm monitor. The investigators' focus will be on the change between pre-intervention AF burden and AF burden at 6 month follow-up.
Time Frame
3, 6, 9, and 12 months from intervention
Secondary Outcome Measure Information:
Title
All-cause mortality
Description
All deaths within 12 months of the intervention arm.
Time Frame
12 months
Title
Number of cardiovascular mortalities
Description
The number of deaths attributable to cardiovascular causes occurring within 12 months of the intervention arm
Time Frame
12 months
Title
Number of all-cause hospitalizations
Description
The total number of inpatient hospitalizations within 12 months following the intervention.
Time Frame
12 months
Title
Number of heart failure hospitalizations
Description
The total number of inpatient hospitalizations attributable to heart failure exacerbations within 12 months following the intervention.
Time Frame
12 months
Title
Change in patient-reported quality of life as assessed by Kansas City Cardiomyopathy Questionnaire
Description
The Kansas City Cardiomyopathy Questionnaire is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. A change of 10 points or more is considered not only clinically significant but also carries prognostic implications for event-free survival in heart failure patients.
Time Frame
At enrollment (baseline) and 6 months following intervention
Title
Change in NT pro-BNP levels
Description
Serum biomarker associated with congestive heart failure symptoms, measured in (mg/ml).
Time Frame
At enrollment (baseline) and 6 months following intervention
Title
Change in exercise capacity as assessed by the 6 minute walk distance test
Description
Pre-intervention arm and 6 month post-procedural exercise capacity will be assessed using change in 6 minute walk distance, defined as the total distance (in meters) traversed during 6 minutes of time. This is well-validated measure of functional capacity and prognostic marker in patients with heart failure.
Time Frame
At baseline and 6 months post intervention

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Eunice Yang, MD PhD
Phone
571-472-3270
Email
Eunice.Yang@inova.org
First Name & Middle Initial & Last Name or Official Title & Degree
Tracy Plummer
Email
Tracy.Plummer@inova.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Brett Atwater, MD
Organizational Affiliation
Inova Heart and Vascular Institute
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Eunice Yang, MD PhD
Organizational Affiliation
Inova Heart and Vascular Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Inova Heart and Vascular Institute
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eunice Yang, MD PhD
Phone
571-472-3270
Email
Eunice.Yang@inova.org
First Name & Middle Initial & Last Name & Degree
Brett Atwater, MD
Email
Brett.Atwater@inova.org
First Name & Middle Initial & Last Name & Degree
Brett Atwater, MD
First Name & Middle Initial & Last Name & Degree
Eunice Yang, MD
First Name & Middle Initial & Last Name & Degree
Marc Wish, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Ablation Versus Medical Management of Atrial Fibrillation in HFpEF

We'll reach out to this number within 24 hrs