The Clinical Outcomes and Therapeutic Effects in Patients With Cardiac Implantable Electronic Device-detected Subclinical and Clinical Atrial Fibrillation. (AHRE)

National Tawan University Hospital

Atrial high-rate episodes (AHREs) detected by cardiac implantable electronic devices (CIEDs) are associated with an increased risk of progression to clinical atrial fibrillation (AF), stroke, heart failure, and mortality. However, optimal management strategies for patients with AHREs lasting between 6 minutes and 24 hours remain uncertain. Current guidelines recommend risk factor modification, but the role of early rhythm-control therapy in preventing AHRE progression has not been well established.

This prospective, randomized, open-label study aims to evaluate whether a rhythm-control strategy combined with optimal risk factor management can reduce progression to sustained AHREs (≥24 hours) or clinical AF compared with optimal risk factor management alone in patients with device-detected AHREs. Eligible participants with CIED-detected AHREs lasting 6 minutes to 24 hours and without prior clinical AF will be randomly assigned to either a rhythm-control group or a usual-care group. The primary endpoint is progression to AHRE duration ≥24 hours or documented clinical AF. Secondary endpoints include stroke, systemic embolism, heart failure hospitalization, cardiovascular death, and all-cause mortality.

Study Overview

• Status: Recruiting
• Conditions: Cardiac Arrhythmias; Subclinical Atrial Fibrillation
• Intervention / Treatment: Other: Early Rhythm Control Strategy; Other: Usual Care

Detailed Description

Atrial high-rate episodes (AHREs) detected by cardiac implantable electronic devices (CIEDs) are increasingly recognized as an early stage of atrial fibrillation (AF) and are associated with an elevated risk of AF progression, stroke, heart failure, and mortality. However, the optimal management of patients with device-detected AHREs remains uncertain, particularly for individuals with episodes lasting between 6 minutes and 24 hours. Current management strategies generally focus on risk factor modification and clinical surveillance, while evidence supporting early rhythm-control intervention in this population is limited.

Observational studies have demonstrated that progression from shorter-duration AHREs to sustained AHREs (≥24 hours) is associated with substantially worse clinical outcomes and may represent an important stage in the evolution of atrial cardiomyopathy. Preventing progression of AHREs may therefore provide an opportunity to alter the natural history of AF and reduce future cardiovascular complications.

This prospective, randomized, open-label, controlled trial is designed to evaluate whether an early rhythm-control strategy can reduce progression of device-detected AHREs compared with usual care. Eligible participants are adults with CIED-detected AHREs lasting between 6 minutes and 24 hours and without a prior diagnosis of clinical atrial fibrillation. Participants will be randomly assigned in a 1:1 ratio to either a rhythm-control strategy or usual care.

The rhythm-control strategy may include antiarrhythmic drug therapy, catheter ablation, or other guideline-directed rhythm-control interventions at the discretion of the treating physician. Both groups will receive comprehensive management of cardiovascular risk factors according to contemporary clinical practice guidelines.

The primary endpoint is a composite of progression to sustained AHREs (≥24 hours) or development of clinically documented atrial fibrillation during follow-up. Secondary endpoints include changes in AHRE burden, ischemic stroke, systemic embolism, heart failure hospitalization, cardiovascular death, all-cause mortality, and treatment-related adverse events.

Participants will undergo regular device interrogation and clinical follow-up throughout the study period. The study aims to determine whether early rhythm-control intervention can delay AF progression and improve long-term cardiovascular outcomes in patients with device-detected AHREs.

• Study Type: Interventional
• Enrollment (Estimated): 450
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Research Coordinator Huang; Phone Number: +886-23123456; Email: hchuangster@gmail.com

Study Locations

• Taiwan
  • Taipei, Taiwan
    • Recruiting
    • National Taiwan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria Age ≥18 years. Presence of a cardiac implantable electronic device (CIED), including permanent pacemaker, implantable cardioverter-defibrillator (ICD), or cardiac resynchronization therapy (CRT) device.

Device-detected atrial high-rate episodes (AHREs) lasting ≥6 minutes and <24 hours.

Ability to provide written informed consent. Willingness and ability to comply with study procedures and follow-up visits. Exclusion Criteria Prior diagnosis of clinical atrial fibrillation, atrial flutter, or atrial tachycardia requiring treatment.

Device-detected AHRE ≥24 hours before enrollment. Current treatment with class I or class III antiarrhythmic drugs for atrial arrhythmias.

Previous catheter ablation for atrial fibrillation or atrial flutter. Planned catheter ablation within the next 3 months. Contraindication to rhythm-control therapy as determined by the treating physician.

Life expectancy less than 1 year. Severe comorbid illness that may interfere with study participation or follow-up.

Pregnancy or breastfeeding. Participation in another interventional clinical trial that may affect study outcomes.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rhythm Control Strategy; Participants will receive an early rhythm-control strategy including antiarrhythmic drug therapy, in addition to comprehensive cardiovascular risk factor management.	Other: Early Rhythm Control Strategy; Participants assigned to the early rhythm-control strategy will receive antiarrhythmic drug therapy according to contemporary clinical practice guidelines and physician discretion. Comprehensive cardiovascular risk factor management will be provided throughout the study.
Active Comparator: Arm2 (Usual care); Participants will receive standard clinical care and cardiovascular risk factor management according to contemporary clinical practice guidelines.	Other: Usual Care; Standard clinical management and cardiovascular risk factor management according to contemporary clinical practice guidelines without a protocol-mandated rhythm-control strategy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression to Sustained AHRE or Clinical Atrial Fibrillation	Composite endpoint of progression to device-detected atrial high-rate episodes lasting 24 hours or longer, or development of clinically documented atrial fibrillation confirmed by electrocardiography, ambulatory rhythm monitoring, or physician-adjudicated rhythm recordings.	Up to 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ischemic Stroke or Systemic Embolism	Ischemic Stroke or Systemic Embolism	Up to 36 months
Cardiovascular Death	Cardiovascular Death	36 months
Heart Failure Hospitalization	Heart Failure Hospitalization	36 months

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: Hui-Chun Huang, National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: June 11, 2026
• First Submitted That Met QC Criteria: June 11, 2026
• First Posted (Actual): June 16, 2026

Study Record Updates

• Last Update Posted (Actual): June 16, 2026
• Last Update Submitted That Met QC Criteria: June 11, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Cardiac Implantable Electronic Device; Atrial High-Rate Episodes (AHRE); Early Rhythm Control
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Pathological Conditions, Signs and Symptoms; Arrhythmias, Cardiac
• Other Study ID Numbers: 202503151MINC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data that underlie the results reported in publications, including demographic characteristics, baseline clinical variables, device interrogation data, and outcome measures, will be made available upon reasonable request to the corresponding investigator after publication of the primary study results.
• IPD Sharing Time Frame: Beginning 6 months after publication of the primary results and ending 5 years after publication.
• IPD Sharing Access Criteria: Data will be available to qualified researchers whose proposed use of the data has been approved by the study investigators. Requests should be directed to the corresponding investigator. A data use agreement may be required.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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