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

St. Olavs Hospital, Baker Heart and Diabetes Institute, Universitaire Ziekenhuizen KU Leuven, University Hospital, Antwerp, AZ Jan Palfijn Gent, Jessa Hospital

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.

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.

Two-arm international multicenter open-label randomized (1:1) controlled trial with blinded end-point evaluation.

Open label study and participants are not blinded to group allocation. Researchers and staff are unblinded during all procedures. AF burden will be adjudicated by a blinded endpoint committee and researchers will be blinded to group allocation when performing statistical analyses.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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 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 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 (>80% of exercise with ≥85% and ≤75% of maximum heart rate, respectively)

Measured at the baseline study visit and at the final study visit after the 16-week intervention period

Measured at the baseline study visit and at the final study visit after the 16-week intervention period

Measured at the baseline study visit and at the final study visit after the 16-week intervention period

Measured at the baseline study visit and at the final study visit after the 16-week intervention period

Measured at the baseline study visit and at the final study visit after the 16-week intervention period

Measured at the baseline study visit and at the final study visit after the 16-week intervention period

Measured by questtionnaire at the baseline study visit and at the final study visit after the 16-week intervention period

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

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

Ventricular arrhythmias lasting ≥12 ventricular complexes as measured by continuous monitoring with insertable cardiac monitor

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

Blood sampling at peak exercise for analyses of cardiac Troponins, NT-pro-BNP, interleukins, C-reactive protein

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