Peri-Atrial Inflammatory Fat and Atrial Fibrillation

NCT ID: NCT04186169

Last Updated: 2024-11-20

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-02-19
• Study Completion Date: 2024-11-12

Brief 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.

Detailed 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.

Conditions

Atrial Fibrillation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Arm 1: Paroxysmal AF - PVI arm

The subjects with paroxysmal AF undergo pulmonary vein isolation (PVI).

Group Type: PLACEBO_COMPARATOR

Catheter ablation

Intervention Type: PROCEDURE

Catheter ablation

Arm 2: Persistent AF - PVI arm

The subjects with persistent AF undergo pulmonary vein isolation (PVI).

Group Type: PLACEBO_COMPARATOR

Catheter ablation

Intervention Type: PROCEDURE

Catheter ablation

Arm 3: Persistent AF - PVI + Fat-targeted ablation

The subjects with persistent AF undergo pulmonary vein isolation (PVI) and additional ablation to target the inflammatory fat tissue

Group Type: EXPERIMENTAL

Catheter ablation

Intervention Type: PROCEDURE

Catheter ablation

Interventions

Catheter ablation

Catheter ablation

Intervention Type: PROCEDURE

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hiroshi Ashikaga, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Johns Hopkins Hospital

Baltimore, Maryland, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 31177816 (View on PubMed)

Other Identifiers

IRB00210289

Identifier Type: -

Identifier Source: org_study_id