the Pathophysiology of the Onset of Atrial Fibrillation in Obstructive Sleep Apnea

• Conditions: Atrial Fibrillation; Obstructive Sleep Apnea of Adult
• Interventions: Diagnostic Test: Polysomnography

• Registration Number: NCT06246825
• Lead Sponsor: Catharina Ziekenhuis Eindhoven

Brief Summary

Rationale: Obstructive sleep apnea (OSA) is a highly prevalent, often undiagnosed, modifiable risk factor for atrial fibrillation (AF), as well as AF-related complications and treatment effectiveness. It is unclear which OSA-related pathophysiological mechanism, i.e. intrathoracic pressure shifts, hypoxemia or sympathovagal imbalance, plays the most dominant role, and a better understanding of these mechanisms could provide valuable information in future diagnostic and therapeutic strategies in this population. Objective: The primary objective is to assess the role of OSA-related pathophysiological mechanisms in the initiation of AF by a multi-parametric strategy that combines the estimated parameters. The main hypothesis is that intrathoracic pressure fluctuations are the predominant mechanism. The secondary objective is to validate a nonobtrusive sensing technology based on photoplethysmography (PPG) and diaphragm electromyography (dEMG) measurements as surrogates for gold standard technology based on invasive intraoesophageal pressure (PES) measurement. Study population: Adult patients with paroxysmal AF with nocturnal onset and high risk of OSA based on the STOP-BANG questionnaire. Study design: An observational study in a selected cohort. Subjects are recruited from the AF outpatient clinic of the Catharina Hospital, and referred to Kempenhaeghe Centre for Sleep Medicine for a one-night full PSG, with the addition of dEMG and PPG. The acquired data will be analysed at the Eindhoven Technical University. Main study parameters/endpoints: Primary endpoint: Identification of prognostic factors for the initiation of AF in relation to OSA-related pathophysiological mechanisms..nl

Detailed Description

Not available

Study Timeline

• Study Start: 2020-12-01
• Study First Submitted: 2023-12-07
• Status Verified: 2024-01
• Study First Submitted QC: 2024-01-29
• Last Update Submitted: 2024-01-29
• Primary Completion: 2024-02-01
• Study First Posted: 2024-02-07
• Last Update Posted: 2024-02-07
• Study Completion: 2024-09-01

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 190

Inclusion Criteria

Paroxysmal or persistent AF

AND

• STOP-BANG score >5 or STOP-BANG >4 and typical nocturnal onset of AF
• A positive WATCH-PAT screening
• very high clinical suspicion of OSA, with STOP-BANG score >3

Exclusion Criteria

• current adequate treatment of OSA
• Reversible cause of AF
• severe lung disease (COPD Gold IV, pumonary fibrosis, lobectomy) wever esophageal disease (malignancy, stricture, esophagectomy)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
PARABOLA cohort	Polysomnography	Patients with paroxysmal or persistent atrial fibrillation and a high likelihood of obstructive sleep apnea

Primary Outcome Measures

Name	Time	Method
Respiratory effort	1 night, during the polysomnography	Respiratory effort is measured by thoracoabdominal respiratory inductance plethysmography belts. We will calculate the integral/area above the curve of the amount of stretch on the belt (in mV) and the duration of inspiration (in seconds).; Respiratory effort (mV\*s) will be measured during baseline breathing (i.e. the awake period before sleep onset), during hazard periods (prior to onset of arrhythmia) and during control periods (same sleep stage as hazard period).; Since respiratory effort is not standardized, the respiratory effort during control and hazard periods will be compared to baseline breathing (i.e. hazard period respiratory effort / baseline respiratory effort vs. control period / baseline respiratory effort)
Invasive respiratory effort	1 night, during the polysomnography	Invasive respiratory effort is measured by intraesophageal pressure sensor (Pes), if the patient tolerates this and can sleep with it. We will calculate the integral/area above the curve of the amount of pressure difference (in mmHg) and the duration of inspiration (in seconds).; Respiratory effort (mmHg\*s) will be measured during baseline breathing (i.e. the awake period before sleep onset), during hazard periods (prior to onset of arrhythmia) and during control periods (same sleep stage as hazard period).; Since respiratory effort is not standardized, the respiratory effort during control and hazard periods will be compared to baseline breathing (i.e. hazard period respiratory effort / baseline respiratory effort vs. control period / baseline respiratory effort). Comparable to primary outcome 1
hypoxic burden	1 night, during the polysomnography	Blood oxygen levels (SpO2) are measured transcutaneously. Hypoxic burden will be calculated by calculating the integral of time (in seconds) and SpO2 \< average SpO2, as published prior. The hypoxic burden beween hazard and control periods (see outcome 1 and 2) will be compared.
Vagal tone	1 night, during the polysomnography	The vagal tone will be assessed non-invasive through heart rate variability parameters (mainly LF/HF ratio (unitless) and RMSSD (ms\^2). The heart rate variability parameters will be compared between hazard and control periods.

Secondary Outcome Measures

Name	Time	Method
Validation of diaphragm EMG	1 night, during the polysomnography	We will validate an algorithm that will try to assess the respiratory effort based of the signals of the diaphragm EMG by either using maximum amplitude (mV) or by combining the amplitude the signal (mV) with the duration (s)

Trial Locations

Locations (1)

Catharina Ziekenhuis; 🇳🇱 Eindhoven, Netherlands