Effect of Treatment of Sleep Apnea in Patients With Paroxysmal Atrial Fibrillation

Study Overview
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Brief Summary
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Atrial fibrillation (AF) is the most common cardiac rhythm disturbance in adults, with prevalence expected to rise significantly the coming decades. The occurrence of AF is associated with significantly increased mortality as well as morbidity of which cerebrovascular accidents is the most important. Unfortunately treatment options remain limited. Anti-arrhythmic drugs are widely used but have limited efficacy and the potential for toxicity and adverse events are recognized. Recent year's catheter ablation of AF continues to gain acceptance for symptomatic treatment, but recurrence rate are high with need for continuous medication. Thus there is a need to better understand what causes development and triggers episodes of AF as well to introduce new treatment options. Cardiometabolic factors such as obesity, inactivity and sleep apnea (SA) have therefore gained interest. Many patients with AF have chronic sleep apnea, and in the present study the investigators want to explore the interaction between SA and AF. The hypothesis of the present study is that SA may trigger AF and that treatment of SA will reduce the overall burden of AF as well as reduce the recurrence of AF after pulmonary vein ablation. To test the hypothesis the investigators will implant a Reveal device that continuously records the hearts rhythm of 100 patients with paroxysmal AF and concomitant SA. Initially the influence of SA on onset of AF will be examined, and the patients will then be randomized to treatment of SA or not and the influence on total AF burden recorded both before and after ablation.

Detailed Description
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For the present project the investigators have established a research team from 2 different university hospitals. This team, including high ranked, internationally renowned scientist from both clinical and basic sciences, will make a framework for PhD candidates and will ensure the patient cohort. Patients with paroxysmal AF and SA will be examined with an extensive diagnostic battery including advanced cardiac imaging tools allowing a proper description of the heart. Then a Reveal that continuously monitor the rhythm of the heart will be inserted, allowing the influence of SA, physical activity, inflammatory parameters, and other external variables on total AF burden to be examined. The patients will then be randomized to treatment of SA with a CPAP or not, and the AF burden recorded 6 months before ablation and 6 months after. The present investigations carried out, are expected to results in better understanding of the interaction between AF and SA and may lay the scientific basis for better diagnostic and therapeutic approaches for patients with AF. In addition, given the advantage of continuous Reveal® recording of the patient's heart rhythm, the present study will examine possible triggers of AF such as activity level and inflammatory substances, and examine the role of structural abnormalities in the heart as assessed by echocardiography for the triggering of AF episodes. An overall aim is therefore a better phenotyping of the patient which could aid in a more person-specific treatment approach, with direct consequences both for the individual patient and for the society.

Official Title
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Sleep Disordered Breathing in Patients With Paroxysmal Atrial Fibrillation

Conditions
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Sleep Disordered Breathing, Sleep Apnea, Paroxysmal Atrial Fibrillation

Intervention / Treatment
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* Device: PAP (CPAP or ASV)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-75 years Male or female Patients with paroxysmal AF scheduled for first or second catheter ablation Moderate-to-severe SA defined as an AHI ≥15/h (OSA and/or CSA) Signed informed consent Exclusion Criteria: Unstable patients Patients with left ventricular ejection fraction (LV-EF) < 45% Unstable coronary artery disease, myocardial infarction or PCI within 3 months prior to the study Bypass surgery within 6 months prior to the study Patients with TIA or stroke within the previous 3 months BMI > 40kg/m2 Drowsy drivers and/or sleepy patients with ESS (Epworth Sleepiness Score) > 15 Patients with interstitial lung diseases, severe obstructive lung defects, and thoracic myopathies or severe obstructive lung defects with FEV1 < 50% of predicted Oxygen saturation < 90% at rest during the day Poor compliance Patients with single chamber pacemaker (or ICD) Current use of PAP therapy Patients using amiodarone

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: PAP-therapy (CPAP or ASV)<br>Patients are randomized to either intervention Group: Positive airway pressure therapy (PAP-therapy) or Control. Patients in the intervention arm will be treated with PAP-therapy (Continous Positive Airway Pressure (CPAP) or Adaptive Servo Ventilation (ASV). | Device: PAP (CPAP or ASV)<br>* Patients will be randomized to treatment of Sleep Apnea with a CPAP or control<br>|
| No Intervention: Control group<br>No sleep apnea treatment | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in AF Burden | Difference between PAP treatment and usual care in change of AF burden (% of time in AF, as measured by loop recorder) from baseline (one month prior to randomization) to the last three months of the five month intervention period. | Baseline (pre-randomization) was the first month of loop recorder data collection and was compared to the last three months of the intervention period. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in AF Burden | Difference between PAP treatment and usual care in change of AF burden (% of time in AF, as measured by loop recorder) from baseline (one month prior to randomization) to the last month of the intervention period. | Baseline to the last month of intervention period | 
| Change in AF Burden | Difference between PAP treatment and usual care in change of AF burden (% of time in AF, as measured by loop recorder) from baseline (one month prior to randomization) to the last five months of the intervention period (the whole intervention period). | Comparing Baseline to the last five months of the intervention period | 
| Number of Participants With More Than 25% Reduction in AF Burden | Difference between PAP treatment and usual care in the proportion of patients with at least 25% reduction of AF burden (% of time in AF, as measured by loop recorder) from baseline (one month prior to randomization) to the last three months of the intervention period. | Baseline to last three months of the intervention | 
| Change of Recurrence Rate After Ablation, as Measured by Loop Recorder | Change of recurrence rate after ablation, as measured by loop recorder, after 6 months post ablation and after 12 months post ablation. | 12 months | 
| Change in AF Symptoms as Assessed by Atrial Fibrillation Severity Scale (AFSS) | Change in AF symptoms between CPAP treatment and usual care. The questionnaire quantifies three domains of AF: event frequency (score 1-10), duration (score 1-10), and global episode severity (score 1-10). The total AF burden is calculated from the modified sum of the frequency, duration, and severity of AF (score 3-30, with higher scores indicating greater AF burden ). In addition, the AFSS assesses a symptom score based on seven items asking how bothered patients are by specified symptoms (score 0-35). Global well-being is a visual analogue scale ranging from 1 to 10 (10 indicating the best possible life). | 6 months, 12 months and 18 months | 
| Change in Quality of Life (QoL) as Assessed by Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) | Difference between CPAP and usual care in QoL as assessed by SF36, Version 1.2. Item scores are transformed into the Physical and Mental Component Summary scores (PCS and MCS). Scores range from 0 to 100, with higher scores indicating a better health state. | Assessed at baseline, 6 months, 12 months and 18 months, baseline and 6 months reported. | 
| Change in Sleep Quality and Symptoms of Sleep Apnea: Epworth Sleepiness Scale (ESS) Score | Difference between PAP treatment and usual care in Change in daytime sleepiness as measured using the Epworth Sleepiness Scale (ESS) score, with scores ranging from 0 to 24 (most sleepy) | 6 months, 12 months and 18 months. Baseline and 6 months reported | 
| Change in Symptoms of Obstructive Sleep Apnea Assessed by the Berlin Questionnaire. | Change in sleep quality and symptoms of obstructive sleep apnea as measured using the Berlin Questionnaire. Positive scores in two or more categories suggest a high risk of OSA. | 6 months, 12 months and 18 months | 
| Change in Symptoms of Sleep Apnea Using the Functional Outcomes of Sleep Questionnaire (FOSQ) | Change in sleep quality and symptoms of obstructive sleep apnea as measured using the Functional Outcomes of Sleep Questionnaire (FOSQ). Score range is 5-20 Points, with higher scores indicating better functional status. | 6 months, 12 months and 18 months. Baseline and 6 months reported. | 
| Change in Symptoms of Sleep Apnea Measured by the STOP-Bang | Change in sleep quality and symptoms of obstructive sleep apnea as measured using the STOP-Bang Questionnaire. Score between 0-8. A score of ≥3 suggest risk for OSA. | 6 months, 12 months and 18 months | 
| Change in CRP | Difference between PAP treatment and usual care in change of CRP | 6 months, 12 months and 18 months. Baseline and 6 months reported. | 
| Change in Left Ventricular Ejection Fraction | Difference between PAP treatment and usual care in change of left ventricular ejection fraction as assessed by ecco | 6 months, 12 months and 18 months. Baseline and 6 months reported. | 
| Change in the Cardiac Marker NT-proBNP. | Difference between PAP treatment and usual care in change of Cardiac marker of NT-proBNP. | 6 months, 12 months. Baseline and 6 months reported. | 
| Examine the Effect of SA Treatment on Gene Expression of White Blood Cells. | Examine the effect of SA treatment on gene Expression of white blood cells. Is paroxysmal AF Associated with specific gene Expression patterns? Examine the influence of SA treatment on the pattern of gene Expression and if this is related to reduction of atrial fibrillation burden | 6 months and 12 months | 
| Examine if Onset of Paroxysmal AF is Associated With Specific Activity Patterns, as Assessed by Garmin Vivofit2/3, Activity Recording | Examine if onset of paroxysmal AF is Associated with specific Activity patterns, as assessed by garmin Vivofit2/3, Activity recording | 6 months and 12 months | 
| Change in Body Composition as Assessed by Bioelectric Impedance Analysis (BIA) (Tanita) | Change in body composition (BMI) as assessed by Bioelectric Impedance Analysis (BIA) (Tanita) | Baseline to follow up 6 months | 
| Lung Function Test as Assessed by Spirometry | Lung function test as assessed by spirometry | Baseline, 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atrial fibrillation, CPAP, Sleep apnea, Sleep disordered breathing