the Pathophysiology of the Onset of Atrial Fibrillation in Obstructive Sleep Apnea (PARABOLA)

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

Study Overview

• Status: Enrolling by invitation
• Conditions: Atrial Fibrillation; Obstructive Sleep Apnea of Adult
• Intervention / Treatment: Diagnostic test: Polysomnography

• Study Type: Observational
• Enrollment (Estimated): 190

Contacts and Locations

Study Locations

• Netherlands
  • Eindhoven, Netherlands, 5623EJ
    • Catharina Ziekenhuis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• 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.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
PARABOLA cohort; Patients with paroxysmal or persistent atrial fibrillation and a high likelihood of obstructive sleep apnea	Diagnostic test: Polysomnography; Patients with a high likelihood of having obstructive sleep apnea will undergo a polysomnography, as recommended by the guidelines

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Validation of diaphragm EMG	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)	1 night, during the polysomnography

Collaborators and Investigators

• Sponsor: Catharina Ziekenhuis Eindhoven
• Investigators: Study Chair: Lukas RC Dekker, MD, PhD, prof, Eindhoven University of Technology / Catharina Hospital Eindhoven

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2020
• Primary Completion (Estimated): February 1, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: December 7, 2023
• First Submitted That Met QC Criteria: January 29, 2024
• First Posted (Actual): February 7, 2024

Study Record Updates

• Last Update Posted (Actual): February 7, 2024
• Last Update Submitted That Met QC Criteria: January 29, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• 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; Sleep Apnea, Obstructive; Apnea; Atrial Fibrillation
• Other Study ID Numbers: CatharinaZE_PARABOLA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonimized, full PSG data can be shared for scientific purposes only.
• IPD Sharing Time Frame: 20 years
• IPD Sharing Access Criteria: Purely scientific purposes only
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

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