Atrial Fibrillation: Chronic Beta-blocker Use Versus As-needed Rate Control Guided by Implantable Cardiac Monitor

Phase 1

Recruiting

• Conditions: HFpEF - Heart Failure With Preserved Ejection Fraction; Diastolic Dysfunction; Atrial Fibrillation
• Interventions: Drug: As needed pharmacological rate control with beta-blocker (metoprolol tartrate, metoprolol succinate) or calcium channel blocker (diltiazem, verapamil)

• Registration Number: NCT05745337
• Lead Sponsor: University of Vermont

Brief Summary

The goal of this study is to test the feasibility of guiding as-needed pharmacological rate control of atrial fibrillation (AF) by implantable cardiac monitors and to assess the impact of continuous beta-blocker therapy versus as-needed rate control on the following outcomes:

(1) exercise capacity, (2) AF burden, (3) symptomatic heart failure, (4) biomarker assessment of cardiac filling pressures and cardio-metabolic health, and (5) quality of life in patients with atrial fibrillation and stage II or III heart failure with preserved ejection fraction.

Detailed Description

Patients ≥ 18 years of age with paroxysmal or persistent AF who have an implantable cardiac monitor (either loop recorder or pacemaker) and who are receiving daily beta-blocker therapy will be screened for meeting the inclusion/exclusion criteria.

Trial participants will then be randomized into the daily beta-blocker or as-needed pharmacological rate control.

At baseline and six months trial participants will undergo assessment of the following measures:

* Assessment of Quality of life using the Minnesota Living with Heart Failure Questionnaire and the Atrial Fibrillation Effect on Quality of life Questionnaire.

* Blood draw

* Cardiopulmonary exercise test, 6 Minute Walk Test and average daily activity level via integrated accelerometer of the implantable cardiac monitor (if available).

* Assessment of AF burden

Study participants may opt into long-term follow up visits at 12, 18 and 24 months.

Chart review will continue for up to 4 years after enrollment for the purpose of monitoring clinical endpoints:

* Heart failure events (diuretic drug change, emergency room visit, hospitalization)

* AF events (hospitalization, emergency room visit, cardioversion, antiarrhythmic medication initiation)

* Stroke or transient ischemic attack

* Myocardial infarction

Study Timeline

• Study First Submitted: 2023-01-30
• Status Verified: 2023-02
• Study Start: 2023-02-06
• Study First Submitted QC: 2023-02-15
• Study First Posted: 2023-02-27
• Last Update Submitted: 2023-02-28
• Last Update Posted: 2023-03-03
• Primary Completion: 2023-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

• Paroxysmal or persistent AF diagnosed in the past 4 weeks or longer
• Implantable cardiac monitor (either loop recorder or pacemaker)
• Current treatment with greater than minimum doses of beta-blockers OR any beta-blocker with resting sinus rhythm heart rate < 75 bpm (documented on EKG in the last 6 months OR at enrollment visit)
• Left ventricular ejection fraction ≥ 50% (reported on echocardiogram within the past 48 months)
• Echocardiographic evidence of structural changes consistent with HFpEF defined by (1) left ventricular hypertrophy (septal or posterior wall thickness > 10mm) OR (2) left atrial enlargement OR (3) diastolic dysfunction.

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Exclusion Criteria

• Long-standing persistent or permanent atrial fibrillation (Long-standing persistent AF is defined as continuous AF of > 12 months duration. Permanent AF is defined as AF accepted by the patient and physician and no further attempts to restore/maintain sinus rhythm will be undertaken).
• Echocardiographic evidence of left ventricular dilation (defined as left ventricular end diastolic volume (LVEDV) index ≥ 80ml/m2 as determined by echocardiogram within the past 48 months.
• Documentation in the electronic medical record suggesting a life expectancy less than 12 months

Minimum dosage of beta-blocker therapy to meet enrollment criterion:

Metoprolol tartrate 25mg twice daily, Metoprolol succinate 50mg daily, Carvedilol 12.5mg daily, Bisoprolol 5mg twice daily, Nebivolol 5mg daily, Atenolol 50mg daily, Labetalol 100mg twice daily, Propranolol 40mg twice daily

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
As needed rate control	As needed pharmacological rate control with beta-blocker (metoprolol tartrate, metoprolol succinate) or calcium channel blocker (diltiazem, verapamil)	Patients randomized to the experimental arm will stop their daily beta-blocker and take as needed rate control guided by their implantable cardiac monitor

Primary Outcome Measures

Name	Time	Method
Exercise capacity	At time of randomization and 6 months afterwards.	Change in peak oxygen consumption during cardiopulmonary exercise testing

Secondary Outcome Measures

Name	Time	Method
Number of participants with a composite of treatment related adverse events	At 6 months, at 12 months, at 18 months, at 24 months	Number of heart failure hospitalization, unplanned hospitalization for atrial fibrillation, stroke or transient ischemic attack, acute coronary syndrome in both treatment arms

Trial Locations

Locations (1)

University of Vermont Medical Center; 🇺🇸 Burlington, Vermont, United States