Effects of Detraining in Endurance Athletes With Atrial Fibrillation

Study Overview
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Brief Summary
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Atrial fibrillation (AF) affects more than 43 million people worldwide, but specific exercise recommendations do not exist for this group of patients. Despite a lack of evidence, athletes are often advised to reduce exercise intensity (detraining) after being diagnosed with AF. This randomized controlled trial will be the first study that investigates effects of detraining in endurance athletes. Participants will be randomized to an intervention group that will be instructed to refrain from high intensity exercise, and a control group. The study aims to clarify whether detraining might reduce the burden of AF and has the potential to guide development of exercise guidelines for AF patients.

Detailed Description
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Atrial fibrillation (AF) affects more than 43 million people worldwide, but specific exercise recommendations do not exist for this group of patients. Despite a lack of evidence, athletes are often advised to reduce exercise intensity (detraining) after being diagnosed with AF. This randomized controlled trial will be the first study that investigates effects of detraining in endurance athletes. Participants will be included at Bærum Hospital, St.Olavs Hospital, Trondheim, Baker Institute, Melbourne, Leuven University Hospital, Antwerp University Hospital, AZ Jan Palfijn Gent and Jessa Hospital Hasselt, Belgium. In total 120 participants will be monitored with a chest-strap heart rate (HR) monitor and sportswatch (exercise intensity), and an Insertable Cardiac Monitor (ICM, AF burden). Participants will be randomized to an intervention group (n=60) that will be instructed to refrain from high intensity exercise (H) >75% of maximal HR (HRmax)) for a period of 16 Weeks, or a control group (n=60) that will be instructed to perform at least three weekly sessions of high intensity training (HR ≥85% of HRmax. The primary endpoint will be AF burden, as measured by continuous monitoring with ICMs and calculated as the cumulative duration of all AF episodes lasting ≥30sec divided by total duration of monitoring. The study aims to clarify whether detraining might reduce the burden of AF and has the potential to guide development of exercise guidelines for AF patients. The investigators will also study exercise-induced cardiac remodeling, aiming to improve the understanding of underlying pathophysiological mechanisms for AF.

Official Title
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Effects of Detraining in Endurance Athletes With Atrial Fibrillation (NEXAF Detraining)

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Behavioral: Detraining group
* Behavioral: Control group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent Age ≥ 18 years Diagnosed with paroxysmal atrial fibrillation (verified by electrocardiogram) Report >5 (running, rowing) or >8 (cycling, cross-country skiing), weekly hours, respectively, of endurance sport At least two anamnestic (self-reported) episodes of atrial fibrillation, of which one during the last six months Use a smartphone and agree to connect their sportswatch with a web-based platform for monitoring of exercise Exclusion Criteria: Permanent atrial fibrillation Cardiac conditions (including valvular heart disease of moderate or greater severity, symptomatic ischemic heart disease) Left ventricular ejection fraction <45% Hypertension (>140/90) Diabetes mellitus Hyperthyroidism Smoking during the last 5 years Alcohol intake >20 alcohol units/week Use of illegal or performance enhancing drugs Body mass index >30kg/m2 Injuries preventing physical exercise Pregnancy Participation in conflicting intervention research studies Planned atrial fibrillation ablation within the next six months The individual refuses to have an insertable cardiac monitor, blood samples taken or be part of the detraining group

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Two-arm international multicenter open-label randomized (1:1) controlled trial with blinded end-point evaluation.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Detraining group<br>Will be instructed to avoid high-intensity exercise corresponding to a heart rate >75% of maximum heart rate, and a total duration of exercise (hours/week) corresponding to >80% of the self-reported average weekly amount of exercise (hours/week) during the past six months, for a period of 16 week. | Behavioral: Detraining group<br>* Detraining is defined as exercise corresponding to a heart rate ≤75% of maximum heart rate and ≤80% of the self-reported average weekly amount of exercise (hours/week) during the past six months, for a period of 16 weeks.<br>|
| Experimental: Control group<br>Will be instructed to perform at least three weekly sessions of high intensity exercise, corresponding to a HR ≥85% of maximum heart rate, and otherwise continue endurance exercise as usual. | Behavioral: Control group<br>* At least three weekly sessions of high intensity exercise, corresponding to a heart rate ≥85% of maximum heart rate, and otherwise continue endurance exercise as usual.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Atrial fibrillation burden | Atrial fibrillation burden (time with atrial fibrillation) as measured by continuous monitoring with insertable cardiac monitor and calculated as the cumulative duration of all atrial fibrillation episodes lasting ≥30sec divided by total duration of monitoring and reported as percentages. | Measured during the last 4 weeks (week 13-16) of the 16-week intervention period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Atrial fibrillation burden | Atrial fibrillation burden as measured by continuous monitoring with insertable cardiac monitor and calculated as the cumulative duration of all atrial fibrillation episodes lasting ≥30sec divided by total duration of monitoring. | Measured during the first 4 weeks (week 1-4) of the 16-week intervention period | 
| Atrial fibrillation burden | Atrial fibrillation burden as measured by continuous monitoring with insertable cardiac monitor and calculated as the cumulative duration of all atrial fibrillation episodes lasting ≥30sec divided by total duration of monitoring. | Measured during week 5-8 of the 16-week intervention period | 
| Atrial fibrillation burden | Atrial fibrillation burden as measured by continuous monitoring with insertable cardiac monitor and calculated as the cumulative duration of all atrial fibrillation episodes lasting ≥30sec divided by total duration of monitoring. | Measured during week 9-12 of the 16-week intervention period | 
| Cumulative atrial fibrillation burden | Atrial fibrillation burden as measured by continuous monitoring with insertable cardiac monitor and calculated as the cumulative duration of all atrial fibrillation episodes lasting ≥30sec divided by total duration of monitoring. | Measured during the entire 16-week intervention period | 
| Atrial fibrillation episode duration | Mean duration of atrial fibrillation episodes lasting ≥30sec | Measured during the 16-week intervention period | 
| Atrial fibrillation episodes | Number of atrial fibrillation episodes lasting ≥30sec, as measured by insertable cardiac monitor | Measured during the first 4 weeks (week 1-4) of the 16-week intervention period | 
| Atrial fibrillation episodes | Number of atrial fibrillation episodes lasting ≥30sec, as measured by insertable cardiac monitor | Measured during week 5-8 of the 16-week intervention period | 
| Atrial fibrillation episodes | Number of atrial fibrillation episodes lasting ≥30sec, as measured by insertable cardiac monitor | Measured during week 9-12 of the 16-week intervention period | 
| Atrial fibrillation episodes | Number of atrial fibrillation episodes lasting ≥30sec, as measured by insertable cardiac monitor | Measured during the last 4 weeks (week 13-16) of the 16-week intervention period | 
| Cumulative atrial fibrillation episodes | Number of atrial fibrillation episodes lasting ≥30sec, as measured by insertable cardiac monitor | Measured during the 16-week intervention period | 
| Days with atrial fibrillation | Days with at least one episode of atrial fibrillation lasting ≥30sec | Measured during the 16-week intervention period | 
| Days without atrial fibrillation | Days without atrial fibrillation episodes | Measured during the 16-week intervention period | 
| Relative change in atrial fibrillation burden | Relative change in atrial fibrillation burden as measured by continuous monitoring with insertable cardiac monitor and calculated as the cumulative duration of all atrial fibrillation episodes lasting ≥30sec divided by total duration of monitoring | Measured during the 4-week baseline period prior to randomization and during the last 4 weeks of the 16-week intervention period | 
| Relative change in atrial fibrillation burden | Relative change in atrial fibrillation burden as measured by continuous monitoring with insertable cardiac monitor and calculated as the cumulative duration of all atrial fibrillation episodes lasting ≥30sec divided by total duration of monitoring | Measured during the 4-week baseline period prior to randomization and during the first 4 weeks of the 16-week intervention period | 
| Relative change in atrial fibrillation burden | Relative change in atrial fibrillation burden as measured by continuous monitoring with insertable cardiac monitor and calculated as the cumulative duration of all atrial fibrillation episodes lasting ≥30sec divided by total duration of monitoring | Measured during the 4-week baseline period prior to randomization and during the entire 16-week intervention period | 
| Adherence to prescribed exercise | Adherence to prescribed exercise (>80% of exercise with ≥85% and ≤75% of maximum heart rate, respectively) | 16 weeks | 
| Exercise capacity | Peak oxygen uptake (VO2peak) | Measured at the baseline study visit and at the final study visit after the 16-week intervention period | 
| Atrial volumes | Right and left atrial volumes measured with echocardiography | Measured at the baseline study visit and at the final study visit after the 16-week intervention period | 
| Ventricular volumes | Right and left ventricular volumes measured with echocardiography | Measured at the baseline study visit and at the final study visit after the 16-week intervention period | 
| Atrial function | Left atrial function measured by strain with echocardiography | Measured at the baseline study visit and at the final study visit after the 16-week intervention period | 
| Ventricular function | Right and left ventricular function measured by strain with echocardiography | Measured at the baseline study visit and at the final study visit after the 16-week intervention period | 
| Systolic function | Left ventricular ejection fraction measured by strain with echocardiography | Measured at the baseline study visit and at the final study visit after the 16-week intervention period | 
| Atrial fibrillation symptoms | Self-reported number of symptomatic atrial fibrillation episodes | Measured by questtionnaire at the baseline study visit and at the final study visit after the 16-week intervention period | 
| Atrial Fibrillation Effect on QualiTy-of-life questionnaire | Measured with the Atrial Fibrillation Effect on QualiTy-of-life questionnaire (AFEQT). Minimum score 0, maximum score 100, higher values indicate better quality of life | Measured at the baseline study visit and at the final study visit after the 16-week intervention period | 
| Atrial fibrillation hospitalizations | Number of unplanned hospitalizations due to atrial fibrillation cardioversion or ablation | Throughout study completion, an average of 22 weeks | 
| Modified European Heart Rhythm Association Symptom Scale (mEHRA) symptom classification | Modified European Heart Rhythm Association Symptom Scale (mEHRA) questionnaire. The scale ranges from minimum 1 to maxiumum 4, a higher score indicates a worse symptom burden | Measured at the baseline study visit and at the final study visit after the 16-week intervention period | 
| Number of ventricular arrhythmias | Ventricular arrhythmias lasting ≥12 ventricular complexes as measured by continuous monitoring with insertable cardiac monitor | Throughout study completion, an average of 22 weeks | 
| Number of adverse events | Any unfavorable and unintended sign, symptom or illness that develops or worsens during the trial period will be reported as adverse events (AE). A serious adverse event (SAE) is defined as death, any life-threatening event or any inpatient hospitalisation | Throughout study completion, an average of 22 weeks | 
| Cardiovascular risk factors measured by blood pressure | Measure of blood pressure (mmHg) | Measured at baseline and after the 16-week intervention period | 
| Cardiovascular risk factors measured by blood lipids | Blood lipids (mmol/L) | Measured at baseline and after the 16-week intervention period | 
| Cardiovascular risk factors measured by weight | Weight (kg) | Measured at baseline and after the 16-week intervention period | 
| Cardiovascular risk factors measured by BMI | BMI (weight and height will be combined to report BMI in kg/m^2) | Measured at baseline and after the 16-week intervention period | 
| Cardiovascular risk factors measured by smoking | Smoking (pack years) | Measured at baseline and after the 16-week intervention period | 
| Cardiovascular risk factors measured by alcohol units | Alcohol use (units) | Measured at baseline and after the 16-week intervention period | 
| Cardiovascular biomarkers - inflammation markers | Markers for inflammation markers; interleukines and hrCRP (mg/L) | Measured at baseline and after the 16-week intervention period | 
| Cardiovascular biomarkers - markers for myocardial damage | Markers for myocardial damage, measured by troponin T (ng/L) and NT-ProBNP (ng/L) | Measured at baseline and after the 16-week intervention period | 
| Immediate effects on arrhythmia burden of high-intensity exercise | Ahrrythmias measured with 24-hour electrocardiogram after peak exercise testing | 24 hours after after peak exercise testing | 
| Immediate effects on biomarkers of exercise | Blood sampling at peak exercise for analyses of cardiac Troponins, NT-pro-BNP, interleukins, C-reactive protein | At peak exercise during cardiopulmonary exercise testing | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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heart