Efficacy of Early Rhythm Control Therapy in Patients With Subclinical Atrial Fibrillation

Overview

The goal of this study to find out the efficacy of early rhythm therapy in patients with subclinical atrial fibrillation detected by Cardiac Electronic Implantable Devices. Early rhythm therapy includes antiarrhythmic drug, cardioversion, and catheter ablation. The general control group receives general management without the above atrial fibrillation rhythm control treatment. Researchers will compare early rhythm control groups to general control groups to see if early rhythm therapy works to reduce the atrial fibrillation burden by 50% or more, or decrease the incidence of clinical AF documentation. Participants will: * Randomly allocated to two groups at a 1:1 ratio. * Receive the treatment according to their assigned group. * Visit the clinic once every three months for checkups and tests.

Detailed description

There have been reports that early rhythm control therapy reduces various heart events in patients with atrial fibrillation. The definition of "early" atrial fibrillation defined in this study was defined as a patient within one year of diagnosis. This means clinical atrial fibrillation diagnosed by 12-lead electrocardiogram.

Atrial high rate episode (AHRE) may be found through various Cardiac Electronic Implantable Devices (CIED), which is defined as subclinical atrial fibrillation. There have been many studies on the risk of such subclinical atrial fibrillation causing cerebral infarction, and meta-analysis results show that there is a high risk of thromboembolism if there is an episode of 30 seconds or the sum of duration is more than 24 hours. However, there is no research on the rhythm control therapy for patients with subclinical atrial fibrillation, and this study might be considered as an important factor in determining the truly early atrial fibrillation treatment guideline. Therefore, this study aims to find out the efficacy of early rhythm therapy in patients with subclinical atrial fibrillation detected by Cardiac Electronic Implantable Devices.

This study is a randomized, multicenter, prospective, interventional study to observe the efficacy of early rhythm control treatment compared to general control treatment in patients with subclinical atrial fibrillation. According to the electronic random assignment program, it is divided into two groups (early rhythm control group, general control group) and allocated at a 1:1 ratio. This study is open-label study. Early rhythm control groups get rhythm control treatment for atrial fibrillation based on guidelines. This includes antiarrhythmic drug, cardioversion, and catheter ablation. The general control group receives general management (observation, heart rate control treatment if necessary) without the above atrial fibrillation rhythm control treatment. In both groups, appropriate anticoagulant treatment is given if there is an indication of cerebral infarction prevention associated with atrial fibrillation.

Interventions

• Drug early rhythm control group
  flecainide, propafenone, pilsicainide, sotalol, amiodarone, dronedarone and so on
• Procedure cardioversion, catheter ablation
  only when clinical atrial fibrillation (if atrial fibrillation continued for more than 30 seconds on a 12-lead electrocardiogram or holter monitoring) is confirmed
• Other general control
  General management without atrial fibrillation rhythm control treatment.(Observation without additional medication, or heart rate control treatment if necessary) Heart rate control drugs such as beta-blockers, calcium channel blockers (Non-dihydropyridine CCB), and digoxin are used for heart rate control according to the doctor's prescription.

Primary outcome measures

• Less than 50% reduction in atrial fibrillation(AF) burden or clinical AF documentation Incidence Rate (AF recurrence rate) [Time frame: From enrollment to 1 year]
• side effects related to medication or other treatments [Time frame: From enrollment to 1 year]

Secondary outcome measures (6)

• Atrial fibrillation effect on quality-of-life questionnaire score [Time frame: From enrollment to 1 year]
• cardiovascular death, cerebral infarction, hospitalization due to heart failure aggravation [Time frame: From enrollment to 1 year]
• NTproBNP(pg/ml) [Time frame: From enrollment to 1year]
• Korean Montreal Cognitive Assessment (K-MoCA) [Time frame: From enrollment to 1 year]
• Left ventricular ejection fraction(LVEF) [Time frame: From enrollment to 1 year]
• Diastolic function assessment [Time frame: From enrollment to 1year]

Eligibility criteria

Inclusion criteria

• Among patients with Cardiac implantable electronic device (CIED), subjects with atrial high rate episodes found Cardiac implantable electronic devices: implantable loop recorder, pacemaker, implantable cardioverter defibrillator(ICD), cardiac resynchronized therapy(CRT)
• Patients aged 19 or older who have agreed to the study (if voluntary consent is deemed difficult, consent from legal representatives is obtained together)
• If the accumulated period of the atrial high rate episode during the three-month observation period is more than 21 hours
• Patients whose atrial fibrillation has not been confirmed by electrocardiogram or holter monitoring within the past year from the time atrial high rate episode was detected

However, enrollment is possible even if it includes one of the following two cases ⓐ Patients diagnosed and recorded as atrial fibrillation on medical records but not confirmed by electrocardiogram or holter monitoring

ⓑ If there is a record of atrial fibrillation, but Paroxysmal AF less than 30 seconds

Exclusion criteria

• Patients deemed inappropriate to participate in the study by the investigator
• Patients diagnosed with atrial fibrillation with 12-lead electrocardiogram or holter within the past year prior to participation in the study
• Patients taking Class Ic, III of antiarrhythmic drugs prior to study participation
• Patients who have had rhythm control treatments such as Radiofequency catheter ablation (RFCA), Total thoracoscopic ablation (TTA), Maze procedure (MAZEop), and antiarrhythmic treatment due to atrial fibrillation (except for CTI ablation with AFL)
• Patients whose life expectancy is less than one year (e.g., patients who can't even have a heart transplant, patients who receive DNR, Patients in hospice wards who refuse life-sustaining treatment, terminal cancer patients who cannot receive radiation or chemotherapy, etc.)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

South Korea · 1 center

• Samsung Medical Center — Seoul

Publications

• Sagris D, Georgiopoulos G, Pateras K, Perlepe K, Korompoki E, Milionis H, Tsiachris D, Chan C, Lip GYH, Ntaios G. Atrial High-Rate Episode Duration Thresholds and Thromboembolic Risk: A Systematic Review and Meta-Analysis. J Am Heart Assoc. 2021 Nov 16;10(22):e022487. doi: 10.1161/JAHA.121.022487. Epub 2021 Nov 10. PMID 34755543
• Hindricks G, Potpara T, Dagres N, Arbelo E, Bax JJ, Blomstrom-Lundqvist C, Boriani G, Castella M, Dan GA, Dilaveris PE, Fauchier L, Filippatos G, Kalman JM, La Meir M, Lane DA, Lebeau JP, Lettino M, Lip GYH, Pinto FJ, Thomas GN, Valgimigli M, Van Gelder IC, Van Putte BP, Watkins CL; ESC Scientific Document Group. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed PMID 32860505
• Kirchhof P, Camm AJ, Goette A, Brandes A, Eckardt L, Elvan A, Fetsch T, van Gelder IC, Haase D, Haegeli LM, Hamann F, Heidbuchel H, Hindricks G, Kautzner J, Kuck KH, Mont L, Ng GA, Rekosz J, Schoen N, Schotten U, Suling A, Taggeselle J, Themistoclakis S, Vettorazzi E, Vardas P, Wegscheider K, Willems S, Crijns HJGM, Breithardt G; EAST-AFNET 4 Trial Investigators. Early Rhythm-Control Therapy in Pa PMID 32865375

Identifiers

NCT: NCT07447297 · SMC2023-07-195 · KCT0009027

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗