Clinical trial NCT02727192: Effect of Treatment of Sleep Apnea in Patients With Paroxysmal Atrial Fibrillation
Official title: Sleep Disordered Breathing in Patients With Paroxysmal Atrial Fibrillation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Sleep Disordered Breathing
Sleep Apnea
Paroxysmal Atrial Fibrillation
Keywords: Atrial fibrillation
CPAP
Sleep apnea
Sleep disordered breathing
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
Collaborators: name: Norwegian Health Association
name: Medtronic
name: ResMed
First posted: 2016-04-04
Enrollment: 109
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in AF Burden
timeFrame: 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 outcomes:
measure: Change in AF Burden
timeFrame: Baseline to the last month of intervention period
measure: Change in AF Burden
timeFrame: Comparing Baseline to the last five months of the intervention period
measure: Number of Participants With More Than 25% Reduction in AF Burden
timeFrame: Baseline to last three months of the intervention
measure: Change of Recurrence Rate After Ablation, as Measured by Loop Recorder
timeFrame: 12 months
measure: Change in AF Symptoms as Assessed by Atrial Fibrillation Severity Scale (AFSS)
timeFrame: 6 months, 12 months and 18 months
measure: Change in Quality of Life (QoL) as Assessed by Medical Outcomes Study 36-item Short-Form Health Survey (SF-36)
timeFrame: Assessed at baseline, 6 months, 12 months and 18 months, baseline and 6 months reported.
measure: Change in Sleep Quality and Symptoms of Sleep Apnea: Epworth Sleepiness Scale (ESS) Score
timeFrame: 6 months, 12 months and 18 months. Baseline and 6 months reported
measure: Change in Symptoms of Obstructive Sleep Apnea Assessed by the Berlin Questionnaire.
timeFrame: 6 months, 12 months and 18 months
measure: Change in Symptoms of Sleep Apnea Using the Functional Outcomes of Sleep Questionnaire (FOSQ)
timeFrame: 6 months, 12 months and 18 months. Baseline and 6 months reported.
measure: Change in Symptoms of Sleep Apnea Measured by the STOP-Bang
timeFrame: 6 months, 12 months and 18 months
measure: Change in CRP
timeFrame: 6 months, 12 months and 18 months. Baseline and 6 months reported.
measure: Change in Left Ventricular Ejection Fraction
timeFrame: 6 months, 12 months and 18 months. Baseline and 6 months reported.
measure: Change in the Cardiac Marker NT-proBNP.
timeFrame: 6 months, 12 months. Baseline and 6 months reported.
measure: Examine the Effect of SA Treatment on Gene Expression of White Blood Cells.
timeFrame: 6 months and 12 months
measure: Examine if Onset of Paroxysmal AF is Associated With Specific Activity Patterns, as Assessed by Garmin Vivofit2/3, Activity Recording
timeFrame: 6 months and 12 months
measure: Change in Body Composition as Assessed by Bioelectric Impedance Analysis (BIA) (Tanita)
timeFrame: Baseline to follow up 6 months
measure: Lung Function Test as Assessed by Spirometry
timeFrame: Baseline, 6 months
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: Oslo University Hospital
Study officials:
affiliation: Oslo University Hospital
name: Lars Gullestad, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Traaen GM, Aakeroy L, Hunt TE, Overland B, Bendz C, Sande LO, Aakhus S, Fagerland MW, Steinshamn S, Anfinsen OG, Massey RJ, Broch K, Ueland T, Akre H, Loennechen JP, Gullestad L. Effect of Continuous Positive Airway Pressure on Arrhythmia in Atrial Fibrillation and Sleep Apnea: A Randomized Controlled Trial. Am J Respir Crit Care Med. 2021 Sep 1;204(5):573-582. doi: 10.1164/rccm.202011-4133OC.
citation: Traaen GM, Aakeroy L, Hunt TE, Overland B, Lyseggen E, Aukrust P, Ueland T, Helle-Valle T, Steinshamn S, Edvardsen T, Khiabani Zare H, Aakhus S, Akre H, Anfinsen OG, Loennechen JP, Gullestad L. Treatment of sleep apnea in patients with paroxysmal atrial fibrillation: design and rationale of a randomized controlled trial. Scand Cardiovasc J. 2018 Dec;52(6):372-377. doi: 10.1080/14017431.2019.1567933. Epub 2019 Feb 5.