Atrial Fibrosis Progression in Sleep Apnea Patients: A Pilot Study

Atrial Fibrillation Clinical Trial

Official title:

Atrial Fibrosis Progression in Sleep Apnea Patients: A Pilot Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04814420
• Other study ID #: 2019-2081
• Status: Recruiting
• Phase: N/A
• Start date: July 12, 2021
• Est. completion date: December 2024

Study information

• Verified date: December 2023
• Source: Tulane University
• Contact: Quintrele Jones, MPH
• Phone: 504-988-3063
• Email: qjones1[@]tulane.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The investigators hypothesize that Obstructive Sleep Apnea (OSA) is an independent risk factor for atrial fibrosis development. The investigators aim to prove the presence and progression of atrial fibrosis on Delayed Enhancement Magnetic Resonance Imaging (DE-MRI) in OSA patients without atrial fibrillation (AF).

The investigators will also investigate the correlation between OSA metrics (nocturnal oxygen saturation and Apnea Hypopnea Index (AHI)) and degree of fibrosis at baseline and its progression.

Description:

This is a prospective observational pilot study. Fifteen mild to severe OSA patients and five age- and Body Mass Index (BMI)-matched controls will undergo a DE-MRI. Demographics, medical history and polysomnography results will be collected. Patients diagnosed with obstructive sleep apnea have undergone a polysomnography before the study and were diagnosed based on this test. The investigators will not be performing a polysomnography for any of the patients, just collecting the previous results from their medical charts to confirm they have a true OSA diagnosis for their inclusion in the study.

Patients will be followed over a period of 6 months with a wearable device (WATCHPAT 300) that will record a home sleep apnea study biweekly, including OSA metrics like AHI and nocturnal oxygen variations. Patients will also use an ElectroCardioGram (ECG) Check device for arrhythmia detection.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Experimental group: (15 patients)

• 18-75-year-old, AND

• With mild to severe OSA (mild: Apnea Hypopnea Index: AHI between 5-15, Moderate AHI= 15-30, severe AHI>30), diagnosed by polysomnography.

• Patient with a creatinine measurement within the last 6 months.

• Control group (5 patients): patients with no lung or heart disease, matched by age and BMI.

Exclusion Criteria:

• History of chronic heart failure (Left Ventricle Ejection fraction (LVEF) < 50%), AF, myocardial infarction, valvular disease.

• Prior cardiac or chest surgery.

• Other advanced pulmonary disease (severe Chronic Obstructive Pulmonary Disease (COPD) or asthma, pulmonary hypertension) or central sleep apnea.

• Contraindications to DE-MRI (e.g. allergy to gadolinium, pacemakers, defibrillators (ICD's), other devices/implants contraindicated for MRI, glomerular filtration rate <30 ml/min, etc.).

• BMI > 35 kg/m2 (affects DE-MRI quality).

• Pregnancy.

• Contraindications to WATCHPAT device (peripheral neuropathy).

• Use of one of the following medications: alpha blockers, short acting nitrates (less than 3 hours before the use of WATCHPAT).

• Inability to give informed consent.

• No access to proper smartphone technology and/or internet.

• Inability to return to follow up visit.

Related Conditions & MeSH terms

• Apnea
• Atrial Fibrillation
• Fibrosis
• Obstructive Sleep Apnea
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive

Intervention

Device:
• Delayed enhancement magnetic resonance imaging (DE-MRI)
The patient will be injected with late gadolinium enhancement (0.01 mmol/kg standard dosage), which is a contrast agent used in clinical practice in MRI imaging studies. The contrast agent is used to enhance specific regions/tissues on MRI and, in this study, will allow the investigators to identify fibrotic tissue within the heart. The patient then undergoes the MRI sequence, which lasts approximately 20-25 minutes. Images will be reviewed for quality by trained technicians. This will be repeated after 6 months.

Locations

Country	Name	City	State
United States	Tulane University Medical Center	New Orleans	Louisiana

Sponsors (1)

Lead Sponsor	Collaborator
Tulane University

Country where clinical trial is conducted

United States, 

References & Publications (14)

Anter E, Di Biase L, Contreras-Valdes FM, Gianni C, Mohanty S, Tschabrunn CM, Viles-Gonzalez JF, Leshem E, Buxton AE, Kulbak G, Halaby RN, Zimetbaum PJ, Waks JW, Thomas RJ, Natale A, Josephson ME. Atrial Substrate and Triggers of Paroxysmal Atrial Fibrillation in Patients With Obstructive Sleep Apnea. Circ Arrhythm Electrophysiol. 2017 Nov;10(11):e005407. doi: 10.1161/CIRCEP.117.005407. — View Citation

Dimitri H, Ng M, Brooks AG, Kuklik P, Stiles MK, Lau DH, Antic N, Thornton A, Saint DA, McEvoy D, Antic R, Kalman JM, Sanders P. Atrial remodeling in obstructive sleep apnea: implications for atrial fibrillation. Heart Rhythm. 2012 Mar;9(3):321-7. doi: 10.1016/j.hrthm.2011.10.017. Epub 2011 Oct 19. — View Citation

Gal P, Marrouche NF. Magnetic resonance imaging of atrial fibrosis: redefining atrial fibrillation to a syndrome. Eur Heart J. 2017 Jan 1;38(1):14-19. doi: 10.1093/eurheartj/ehv514. Epub 2015 Sep 25. — View Citation

Gami AS, Hodge DO, Herges RM, Olson EJ, Nykodym J, Kara T, Somers VK. Obstructive sleep apnea, obesity, and the risk of incident atrial fibrillation. J Am Coll Cardiol. 2007 Feb 6;49(5):565-71. doi: 10.1016/j.jacc.2006.08.060. Epub 2007 Jan 22. — View Citation

Gami AS, Pressman G, Caples SM, Kanagala R, Gard JJ, Davison DE, Malouf JF, Ammash NM, Friedman PA, Somers VK. Association of atrial fibrillation and obstructive sleep apnea. Circulation. 2004 Jul 27;110(4):364-7. doi: 10.1161/01.CIR.0000136587.68725.8E. Epub 2004 Jul 12. — View Citation

Iwasaki YK, Kato T, Xiong F, Shi YF, Naud P, Maguy A, Mizuno K, Tardif JC, Comtois P, Nattel S. Atrial fibrillation promotion with long-term repetitive obstructive sleep apnea in a rat model. J Am Coll Cardiol. 2014 Nov 11;64(19):2013-23. doi: 10.1016/j.jacc.2014.05.077. Epub 2014 Nov 3. — View Citation

Kanagala R, Murali NS, Friedman PA, Ammash NM, Gersh BJ, Ballman KV, Shamsuzzaman AS, Somers VK. Obstructive sleep apnea and the recurrence of atrial fibrillation. Circulation. 2003 May 27;107(20):2589-94. doi: 10.1161/01.CIR.0000068337.25994.21. Epub 2003 May 12. — View Citation

King JB, Azadani PN, Suksaranjit P, Bress AP, Witt DM, Han FT, Chelu MG, Silver MA, Biskupiak J, Wilson BD, Morris AK, Kholmovski EG, Marrouche N. Left Atrial Fibrosis and Risk of Cerebrovascular and Cardiovascular Events in Patients With Atrial Fibrillation. J Am Coll Cardiol. 2017 Sep 12;70(11):1311-1321. doi: 10.1016/j.jacc.2017.07.758. — View Citation

Linz D, Brooks AG, Elliott AD, Nalliah CJ, Hendriks JML, Middeldorp ME, Gallagher C, Mahajan R, Kalman JM, McEvoy RD, Lau DH, Sanders P. Variability of Sleep Apnea Severity and Risk of Atrial Fibrillation: The VARIOSA-AF Study. JACC Clin Electrophysiol. 2019 Jun;5(6):692-701. doi: 10.1016/j.jacep.2019.03.005. Epub 2019 May 1. — View Citation

Marrouche NF, Wilber D, Hindricks G, Jais P, Akoum N, Marchlinski F, Kholmovski E, Burgon N, Hu N, Mont L, Deneke T, Duytschaever M, Neumann T, Mansour M, Mahnkopf C, Herweg B, Daoud E, Wissner E, Bansmann P, Brachmann J. Association of atrial tissue fibrosis identified by delayed enhancement MRI and atrial fibrillation catheter ablation: the DECAAF study. JAMA. 2014 Feb 5;311(5):498-506. doi: 10.1001/jama.2014.3. Erratum In: JAMA. 2014 Nov 5;312(17):1805. — View Citation

May AM, Van Wagoner DR, Mehra R. OSA and Cardiac Arrhythmogenesis: Mechanistic Insights. Chest. 2017 Jan;151(1):225-241. doi: 10.1016/j.chest.2016.09.014. Epub 2016 Sep 29. — View Citation

Ng CY, Liu T, Shehata M, Stevens S, Chugh SS, Wang X. Meta-analysis of obstructive sleep apnea as predictor of atrial fibrillation recurrence after catheter ablation. Am J Cardiol. 2011 Jul 1;108(1):47-51. doi: 10.1016/j.amjcard.2011.02.343. Epub 2011 Apr 29. — View Citation

Oakes RS, Badger TJ, Kholmovski EG, Akoum N, Burgon NS, Fish EN, Blauer JJ, Rao SN, DiBella EV, Segerson NM, Daccarett M, Windfelder J, McGann CJ, Parker D, MacLeod RS, Marrouche NF. Detection and quantification of left atrial structural remodeling with delayed-enhancement magnetic resonance imaging in patients with atrial fibrillation. Circulation. 2009 Apr 7;119(13):1758-67. doi: 10.1161/CIRCULATIONAHA.108.811877. Epub 2009 Mar 23. — View Citation

Otto ME, Belohlavek M, Romero-Corral A, Gami AS, Gilman G, Svatikova A, Amin RS, Lopez-Jimenez F, Khandheria BK, Somers VK. Comparison of cardiac structural and functional changes in obese otherwise healthy adults with versus without obstructive sleep apnea. Am J Cardiol. 2007 May 1;99(9):1298-302. doi: 10.1016/j.amjcard.2006.12.052. Epub 2007 Mar 20. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent change of atrial fibrosis measured by DE-MRI	The percent change will be measured via DE-MRI. The purpose of DE-MRI is to quantify the degree of atrial structural remodeling or fibrosis.	Baseline, 6 months
Secondary	The occurrence of arrhythmia	The patients will use ECG check device to detect the arrhythmia occurrence.	From baseline to 6 months