The Effect of Beta-blocker on Chronotropic Response and Cardiorespiratory Fitness in Patients With Atrial Fibrillation

The Effect of Beta-blocker on Chronotropic Response and Cardiorespiratory Fitness in Patients With Atrial Fibrillation: a Crossover Randomized Controlled Trial.

This is a prospective study to evaluate changes in exercise capacity and chronotropic response to exercise before and after beta-blocker dosage reduction in patients with atrial fibrillation (AF).

Study Overview

• Status: Recruiting
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Drug: Reduced dosage of beta-blocker

Detailed Description

Rate control therapy is the first-line treatment for atrial fibrillation (AF). Resting heart rate(HR) is the treatment target of rate control therapy in current clinical practice; However, the optimal value for resting heart rate in AF remained unclear. Beta-blocker(BB) is widely used as rate-control agent. It is concerned that excessive use of BB might lead to a negative effect on exercise capacity in patients with AF. The aim of this study is to explore the effect of Beta-blocker on hemodynamic parameters and peak oxygen uptake during cardiopulmonary exercise test (CPET).

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hung-Jui Chuang, MD; Phone Number: 67034 00886-2-23123456; Email: 103311@ntuh.gov.tw

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Hung-Jui Chuang, MD; Phone Number: 67034 00886-2-23123456; Email: 103311@ntuh.gov.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. > 20 years of age.
2. Clinically stable patients with persistent atrial fibrillation using beta-blocker as rate-control agent without dosage adjustment for at least 3 months.
3. Resting heart rate < 80 bpm.
4. Left ventricular ejection fraction > 50%.

Exclusion Criteria:

1. Beta-blocker usage due to indications other than rate control for atrial fibrillation.
2. Inability to perform a cardiopulmonary exercise testing.
3. Presence of contraindications for cardiopulmonary exercise testing according to the American College of Sports Medicine's Guidelines for Exercise Testing and Prescription.
4. Patients with implantable cardioverter defibrillator or pacemaker.
5. Pregnancy.
6. Inability to provide informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A; Phase I : Participants will undergo first CPET (Day 0) at trough concentration of BB. After 7-day regular usage of BB, the second CPET(Day 7) will be performed at peak concentration of BB. Participants will enter the second phase if the results of CPET fulfill the pre-determined conditions as follows: (1) Chronotropic index < 0.8 at peak level of BB, (2) Resting HR < 110 bpm at trough level of BB, (3) Absent of unstable arrhythmia or unstable hemodynamics during CPET at trough level. Phase II: BB dosage will be reduced. Daily blood pressure, heart rate and adverse event will be recorded. If participants remained clinically stable, the third CPET(Day 21) will be performed 14 days after the reduction of dosage. If participants' resting heart rate exceed 110 bpm, the dosage will be adjusted to the original level.	Drug: Reduced dosage of beta-blocker; Phase I: CPET performed at trough BB concentration: participants will undergo CPET at least 30 hours after last beta-blocker usage.; CPET performed at peak BB concentration : participants will undergo CPET at 3 hours after last beta-blocker usage. Phase II: BB dosage will be reduced.
Active Comparator: Arm B; Phase I : Participants will undergo first CPET(Day 0) at peak concentration of BB. After 7-day regular usage of BB, the second CPET(Day 7) will be performed at trough concentration of BB. Participants will enter the second phase if the results of CPET fulfill the pre-determined conditions as follows: (1) Chronotropic index < 0.8 at peak level of BB, (2) Resting HR < 110 bpm at trough level of BB, (3) Absent of unstable arrhythmia or unstable hemodynamics during CPET at trough level. Phase II: BB dosage will be reduced. Daily blood pressure, heart rate and adverse event will be recorded. If participants remained clinically stable, the third CPET(Day 21) will be performed 14 days after the reduction of dosage. If participants' resting heart rate exceed 110 bpm, the dosage will be adjusted to the original level.	Drug: Reduced dosage of beta-blocker; Phase I: CPET performed at trough BB concentration: participants will undergo CPET at least 30 hours after last beta-blocker usage.; CPET performed at peak BB concentration : participants will undergo CPET at 3 hours after last beta-blocker usage. Phase II: BB dosage will be reduced.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak oxygen intake	Peak oxygen intake will be assessed with symptom-limited cardiopulmonary exercise testing.	The change in peak oxygen uptake will be measured at day 0 , day 7 and day 21.
Chronotropic response to exercise	Plasma norepinephrine level was obtained before and immediately after cardiopulmonary exercise testing to assess the relationship of beta-blocker, circulating norepinephrine level and chronotropic response to exercise.	The change in chronotropic response to exercise will be measured at day 0 , day 7 and day 21.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
European Heart Rhythm Association (EHRA) symptom scale	The investigators will assess the change in EHRA symptom scale. The EHRA score ranges from 1 to 4. Higher scores indicate more severe symptoms.	The change in European Heart Rhythm Association (EHRA) score will be measured at day 0 , day 7 and day 21.
Cardiac output and stroke volume	Cardiac output and stroke volume during incremental exercise testing will be assessed by impedance cardiography.	The change in cardiac output and stroke volume will be measured at day 0 , day 7 and day 21.
Cognitive function	The investigators will assess the change in Montreal Cognitive Assessment (MoCA). The total score of MoCA ranges from 0 to 30. Higher scores indicate better cognitive function.	The change in MoCA will be measured at day 0 , day 7 and day 21.
NT-proBNP	NT-proBNP level will be assessed before and immediate after the cardiopulmonary exercise test.	The change in NT-proBNP will be measured at day 0 , day 7 and day 21.
Quality of life evaluation	The investigators will assess the change in 36-Item Short Form Survey (SF-36). SF-36 consists of eight domains of health status. The score of each domain ranges from 0 to 100. Higher scores indicate a better outcome.	The change in SF-36 will be measured at day 0 , day 7 and day 21.

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: Hung-Jui Chuang, MD, Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2025
• Primary Completion (Estimated): July 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: April 10, 2022
• First Submitted That Met QC Criteria: April 10, 2022
• First Posted (Actual): April 18, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 19, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Atrial Fibrillation; Cardiorespiratory fitness; Chronotropic response; Beta-blocker
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Adrenergic Agents; Adrenergic Antagonists; Adrenergic beta-Antagonists
• Other Study ID Numbers: 202201028MINB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No