CPAP in AF Patients With OSA (CPAPAF)

The Effect of Continuous Positive Airway Pressure in Patients With Obstructive Sleep Apnea and Paroxysmal Atrial Fibrillation

Obstructive sleep apnea is associated with atrial fibrillation. This study is to evaluate the effect of continuous positive airway pressure on the burden of atrial fibrillation in the patients with obstructive sleep apnea and paroxysmal atrial fibrillation.

Study Overview

• Status: Recruiting
• Conditions: Atrial Fibrillation; Sleep Apnea
• Intervention / Treatment: Device: continuous positive airway pressure; Device: Placebo

Detailed Description

Traditional risk factors for AF were established from the original Framingham Heart Study cohort which showed aging, hypertension, congestive heart failure, coronary artery disease, valvular heart disease and diabetes mellitus (DM) as independent risk factors. In the past decade, several important risk factors not encompassed in previous studies have also been found to have a link with AF. One of these newly-identified risk factors is obstructive sleep apnea (OSA), which has been listed as one of the risk factor needed to be assessed and treated in AF patients.

OSA and AF often co-exist and indeed share some risk factors, such as hypertension. AF Patients are more likely to have OSA, with reported prevalence rates of OSA (apnea-hypopnea index [AHI] ≥15) as high as 62% in AF cohorts from hospital-based studies. In community-based cohort studies, a cross-sectional analysis from sleep heart health study (SHSS) found those with sleep-disordered breathing(SDB)/sleep apnea (SA) (respiratory disturbance index [RDI] ≥ 30) had four times the odds of a polysomnography (PSG)-detected nocturnal AF as compared to those without SDB/SA after adjusting confounders. Following from this, a cross-sectional study on Outcomes of Sleep Disorders in Older Men Study (MrOS Sleep Study) showed a dose-response association between RDI and AF.

There are several pathophysiological mechanisms by which OSA could potentially increase the risk of development of new AF, or trigger a recurrence of AF in a patient with an established history of AF. OSA is characterized by repetitive collapse of the upper airway (UA) during sleep. The UA collapses when sleep-related loss in UA dilator muscle tone is superimposed upon a narrow and/or collapsible airway. These obstructive apneas or hypopneas, characterized by unsuccessful inspiratory efforts against an occluded airway, lead to 1) exaggerated negative intrathoracic pressure swings 2) hypoxia, and 3) co-activation of sympathetic and parasympathetic systems, all of which have been shown to potentiate a pro-arrhythmic state. Given that these mechanisms are pro-arrhythmic, CPAP (continuous positive airway pressure), the gold standard therapy for OSA, works by splinting the upper airway open during sleep with subsequent abolition of swings in pressure, hypoxia and arousals, can potentially modify the risk of development of AF or recurrence of AF in OSA patients.

There is a growing body of literature supporting that OSA being as a risk factor for recurrence of AF after cardioversion or ablation and treatment of OSA with CPAP decreased the risk of recurrence of AF. Nevertheless, all of the aforementioned studies are observational or retrospective in nature. Recently, Caples et al. conducted the first randomized control trial using CPAP in patients with AF and OSA but failed to find a difference of recurrence of AF between those treated with CPAP versus usual care. Notably, there are several issues in the study design and methodology that do not allow for firm conclusion from the results of this study. It was a single-center study, enrolling very small number of patients, and used a low cut-off AHI>5/h as inclusion criteria. More importantly, only patients with persistent AF scheduled for cardioversion were included. Given the natural time-course from paroxysmal AF to persistent AF, long-term remodeling or established atrial arrythmogenic substrate in persistent AF may be less or not reversible even when the initial risk factor is removed. In this regard, early intervention with CPAP in patients with paroxysmal AF and OSA, which has never been done in previous studies, should confer a better antiarrythmic effect. Therefore, the investigators aim to test the hypothesis that treatment of OSA with CPAP would reduce the burden of AF in patients with paroxysmal AF.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chih-Chieh C Yu, MD.PhD; Phone Number: 65257 886-2-23123456; Email: sweetchieh@gmail.com

Study Locations

• Taiwan
  • Taipei, Taiwan
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Chih-Chieh Yu, MD.PhD.; Phone Number: 65257 886-2-23123456; Email: sweetchieh@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. men or women aged 20 to 65 years
2. paroxysmal AF, diagnosed based on the ACC/AHA/HRS 2014 guideline, and is defined as AF that terminates spontaneously or with intervention within 7 d of onset either by 12-lead EKG, 24-hr Holter, or 14-day ECG monitor.
3. OSA, defined as an AHI>15/hr of sleep, of which >50% of events are obstructive.
4. Informed consent signed

Exclusion Criteria:

1. Moderate-severe valvular heart diseases (regurgitation or stenosis)
2. post heart surgery
3. Uncontrolled systemic hypertension or pulmonary hypertension
4. Use of psychoactive or other drugs that could influence breathing patterns
5. Current use of CPAP treatment
6. Epworth sleepiness scale>10
7. Congestive heart failure (LVEF≦45%)
8. Chronic obstructive pulmonary disease
9. History of stroke or neuromuscular disease
10. Severe insomnia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CPAP treatment for 12 months	Device: continuous positive airway pressure; CPAP treatment at night. Treat AF as cardiologist's discretion.
Placebo Comparator: Placebo; observation	Device: Placebo; Observation. Treat AF as cardiologist's discretion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of AF burden	The duration in AF on 14-day ECG monitor (percent)	0, 6, 12 months
change of left atrium volume	LA volume index measured by ultrasonocardiography	0, 6, 12 months
change of Quality of Life	Questionnaire (Short Form Health Survey-36); higher scores means a better quality of life; maximal score 100%	0, 6, 12 months
Number of participants hospitalized for cardiovascular or all causes	Hospitalization for cardiovascular or all causes within the follow-up period	12 months

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2020
• Primary Completion (Anticipated): December 31, 2026
• Study Completion (Anticipated): December 31, 2026

Study Registration Dates

• First Submitted: August 6, 2020
• First Submitted That Met QC Criteria: August 12, 2020
• First Posted (Actual): August 14, 2020

Study Record Updates

• Last Update Posted (Actual): April 27, 2023
• Last Update Submitted That Met QC Criteria: April 25, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Atrial Fibrillation; sleep apnea
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Arrhythmias, Cardiac; Sleep Apnea Syndromes; Apnea; Atrial Fibrillation
• Other Study ID Numbers: 202002128RINC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No