Peri-Atrial Inflammatory Fat and Atrial Fibrillation

Atrial Fibrillation Clinical Trial

Official title:

Preliminary Studies to Evaluate the Impact of Peri-Atrial Inflammatory Fat Tissue on Atrial Fibrillation Using Ultra-High Resolution CT

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04186169
• Other study ID #: IRB00210289
• Status: Recruiting
• Phase: N/A
• Start date: February 19, 2021
• Est. completion date: June 30, 2026

Study information

• Verified date: November 2023
• Source: Johns Hopkins University
• Contact: Hiroshi Ashikaga, MD, PhD
• Phone: 4106146076
• Email: hashika1[@]jhmi.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Atrial fibrillation (AF) impacts the lives of 30 million people worldwide. Pulmonary vein isolation (PVI) by catheter ablation is effective for paroxysmal AF, but the success rate remains marginal at 60-80%. For persistent AF, defined as continuous AF that sustains longer than 7 days, the success rate is even lower. The low success rate of AF ablation reflects the fact that there is no effective target identified to modify the underlying substrate beyond PVI. Recently, investigators have made an exciting discovery that higher mean CT attenuation values of peri-atrial fat tissue, correlated with inflammatory fat, are associated with higher incidence of recurrence after AF ablation. In this protocol, investigators will investigate the clinical significance of peri-atrial inflammatory fat tissue in AF using ultra-high resolution CT.

Description:

Investigators will prospectively enroll 200 adult participants referred to the Johns Hopkins Hospital for catheter ablation of atrial fibrillation (AF). Investigators will first enroll participants with paroxysmal AF (n=100) to complete sensitivity analysis of inflammatory fat and potential target identification before enrolling participants with persistent AF (n=100). All participants (n=200) will undergo pre-procedural CT using the ultra-high resolution CT scanner 3-4 days prior the ablation procedure to allow a sufficient amount of time for image processing. In all participants (n=200), blood specimens will be collected immediately prior to the ablation procedure. The participants with paroxysmal AF (n=100) will receive the standard of care, which is PVI, and the clinical outcome will be followed up to 12 months post-procedure. In this group, investigators will conduct a sensitivity analysis to define the range of peri-left atrial (LA) fat tissue (in HU) that is associated with AF recurrence. Investigators will also conduct computation of source-sink mismatch arising from wall thinning due to fat infiltration into the myocardium that favors functional block and local reentry. For participants with persistent AF (n=100), investigators will conduct an exploratory clinical trial where the participants will be randomly assigned to 1) PVI group (n=50), or 2) PVI + inflammatory fat-targeted ablation group (n=50). In the latter group, additional focal ablation will be performed beyond PVI to target the inflammatory fat tissue based on the result of the sensitivity analysis. Randomization will be performed with the use of an automated computer-generated randomization algorithm. The participants will be unaware of the group assignment, but the operators will not be blinded (single-blinded design). In all patients, no ablation strategies beyond PVI except cavotricuspid isthmus (CTI) ablation for typical atrial flutter (AFL) will be allowed, such as linear lesions (e.g. roof lines, mitral isthmus lines), and focal ablation to eliminate complex fractionated atrial electrograms (CFAE) and rotating drivers.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: June 30, 2026
• Est. primary completion date: June 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

Inclusion criteria:

• Ages 18 to 100 years

• Adult men and women undergoing the first catheter ablation of AF for whom cardiac CT is clinically indicated to guide the procedure.

Exclusion criteria:

• Inability to provide consent

• Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m^2

• Known history of anaphylaxis to radiocontrast

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

Procedure:
• Catheter ablation
Catheter ablation

Locations

Country	Name	City	State
United States	Johns Hopkins Hospital	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Johns Hopkins University

Country where clinical trial is conducted

United States, 

References & Publications (1)

Ciuffo L, Nguyen H, Marques MD, Aronis KN, Sivasambu B, de Vasconcelos HD, Tao S, Spragg DD, Marine JE, Berger RD, Lima JAC, Calkins H, Ashikaga H. Periatrial Fat Quality Predicts Atrial Fibrillation Ablation Outcome. Circ Cardiovasc Imaging. 2019 Jun;12(6):e008764. doi: 10.1161/CIRCIMAGING.118.008764. Epub 2019 Jun 10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Freedom from any documented episode of AF	Freedom from any documented episode of AF lasting longer than 30 seconds after the performance of a single ablation procedure without the use of antiarrhythmic drugs (AADs). No episode of AF occurring within the initial 3-month blanking period after ablation will be counted. An episode of AF will be considered part of the primary outcome analyses if it lasts longer than 30 seconds and is documented by any form of monitoring, regardless of symptoms. A repeat left atrial (LA) ablation procedure at any time will also be considered to constitute a recurrence for the purpose of the outcome analyses. Participants who complete fewer than 3 months of follow-up and thus do not complete the blanking period will be excluded from endpoint analysis. There will be no blanking period after a second procedure.	12 months
Secondary	Freedom from documented AF after two ablation procedures	Freedom from documented AF after two ablation procedures	12 months
Secondary	Freedom from any documented atrial arrhythmia after one ablation procedure	Freedom from any documented atrial arrhythmia after one ablation procedure	12 months
Secondary	Freedom from any documented atrial arrhythmia after two ablation procedures	Freedom from any documented atrial arrhythmia after two ablation procedures	12 months
Secondary	Use of antiarrhythmia drugs (AADs)	Use of antiarrhythmia drugs (AADs) will be measured as a categorical variable (Yes or No).	12 months
Secondary	Procedure time	Procedure time will be measured as a continuous variable (in minutes).	12 months
Secondary	Occurrence of repeat procedures	Occurrence of repeat procedures will be measured as a categorical variable (Yes or No).	12 months
Secondary	Occurrence of peri-procedural complications	Occurrence of peri-procedural complications will be measured as a categorical variable (Yes or No).	30 days