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

NCT06246825 | Unknown

• 1 other identifier: CatharinaZE_PARABOLA
• Study Type: observational
• Target: 190
• Locations: 1 country
• Sites: 1

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

Conditions

Atrial Fibrillation; Obstructive Sleep Apnea of Adult

Outcome Measures

Primary Outcomes (4)

• Respiratory effort

  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)

  1 night, during the polysomnography

• Invasive respiratory effort

  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

  1 night, during the polysomnography

• hypoxic burden

  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.

  1 night, during the polysomnography

• Vagal tone

  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.

  1 night, during the polysomnography

Secondary Outcomes (1)

• Validation of diaphragm EMG

  1 night, during the polysomnography

Study Arms (1)

PARABOLA cohort

Patients with paroxysmal or persistent atrial fibrillation and a high likelihood of obstructive sleep apnea

Diagnostic Test: Polysomnography

Interventions

Polysomnography DIAGNOSTIC_TEST

Patients with a high likelihood of having obstructive sleep apnea will undergo a polysomnography, as recommended by the guidelines

PARABOLA cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Participants will be recruited in the Cardiology department of the Catharina Hospital Eindhoven (CZE). Patients presented here are referred by general practitioners and cardiologists in neighboring hospitals (Elkerliek Helmond, St. Anna Geldrop, St Jans Gasthuis Weert, Maxima Medisch Centrum Veldhoven, Bernhoven Uden). These patients generally have a high AF burden and frequent paroxysms. Patients with frequent paroxysms are preferred, as those have the highest chance of onset of AF during the one-night PSG. A large number of patients, approximately 400 unique patients per year, visits this clinic and, based on a small sample, 38% would meet the inclusion criteria.

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Catharina Ziekenhuis Eindhoven: lead

Study Sites (1)

Catharina Ziekenhuis

Eindhoven, 5623EJ, Netherlands

Location

MeSH Terms

Conditions

Atrial Fibrillation

Interventions

Polysomnography

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Monitoring, Physiologic; Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• Lukas RC Dekker, MD, PhD, prof

  Eindhoven University of Technology / Catharina Hospital Eindhoven

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 1 Day
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Mr JLPM van den Broek, MD, Principal Investigator

Study Record Dates

• First Submitted: December 7, 2023
• First Posted: February 7, 2024
• Study Start: December 1, 2020
• Primary Completion: February 1, 2024
• Study Completion: September 1, 2024
• Last Updated: February 7, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: 20 years
• Access Criteria: Purely scientific purposes only

Locations

NL (1)