Ablation Versus Medical Management of Atrial Fibrillation in HFpEF

Atrial Fibrillation Clinical Trial

— AMPERE  

Official title:

Ablation Versus Medical Management of Atrial Fibrillation in Heart Failure With Preserved Ejection fRaction and the Effects on Exercise Capacity (AMPERE)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04282850
• Other study ID #: IRB00182159
• Status: Not yet recruiting
• Phase: N/A
• Start date: July 10, 2023
• Est. completion date: January 2025

Study information

• Verified date: June 2023
• Source: Johns Hopkins University
• Contact: Eunice Yang, MD PhD
• Phone: 571-472-3270
• Email: Eunice.Yang[@]inova.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: January 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Atrial Fibrillation
• Heart Failure
• Heart Failure With Normal Ejection Fraction

Intervention

Procedure:
• Pulmonary Vein Isolation
The intervention will involve standard of care electrophysiology ablation for rhythm management of atrial fibrillation with a procedure called a pulmonary vein isolation.

Locations

Country	Name	City	State
United States	Inova Heart and Vascular Institute	Fairfax	Virginia

Sponsors (3)

Lead Sponsor	Collaborator
Johns Hopkins University	Biosense Webster, Inc., Medtronic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	3, 6, 9, and 12 months from intervention
Secondary	All-cause mortality	All deaths within 12 months of the intervention arm.	12 months
Secondary	Number of cardiovascular mortalities	The number of deaths attributable to cardiovascular causes occurring within 12 months of the intervention arm	12 months
Secondary	Number of all-cause hospitalizations	The total number of inpatient hospitalizations within 12 months following the intervention.	12 months
Secondary	Number of heart failure hospitalizations	The total number of inpatient hospitalizations attributable to heart failure exacerbations within 12 months following the intervention.	12 months
Secondary	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.	At enrollment (baseline) and 6 months following intervention
Secondary	Change in NT pro-BNP levels	Serum biomarker associated with congestive heart failure symptoms, measured in (mg/ml).	At enrollment (baseline) and 6 months following intervention
Secondary	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.	At baseline and 6 months post intervention