Peri-Atrial Inflammatory Fat and Atrial Fibrillation

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

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.

Study Overview

• Status: Recruiting
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Procedure: Catheter ablation

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.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hiroshi Ashikaga, MD, PhD; Phone Number: 4106146076; Email: hashika1@jhmi.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287-0005
      • Recruiting
      • Johns Hopkins Hospital
      • Contact: Hiroshi Ashikaga; Phone Number: 410-955-7534; Email: hashika1@jhmi.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Arm 1: Paroxysmal AF - PVI arm; The subjects with paroxysmal AF undergo pulmonary vein isolation (PVI).	Procedure: Catheter ablation; Catheter ablation
PLACEBO_COMPARATOR: Arm 2: Persistent AF - PVI arm; The subjects with persistent AF undergo pulmonary vein isolation (PVI).	Procedure: Catheter ablation; Catheter ablation
EXPERIMENTAL: 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	Procedure: Catheter ablation; Catheter ablation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Freedom from documented AF after two ablation procedures	Freedom from documented AF after two ablation procedures	12 months
Freedom from any documented atrial arrhythmia after one ablation procedure	Freedom from any documented atrial arrhythmia after one ablation procedure	12 months
Freedom from any documented atrial arrhythmia after two ablation procedures	Freedom from any documented atrial arrhythmia after two ablation procedures	12 months
Use of antiarrhythmia drugs (AADs)	Use of antiarrhythmia drugs (AADs) will be measured as a categorical variable (Yes or No).	12 months
Procedure time	Procedure time will be measured as a continuous variable (in minutes).	12 months
Occurrence of repeat procedures	Occurrence of repeat procedures will be measured as a categorical variable (Yes or No).	12 months
Occurrence of peri-procedural complications	Occurrence of peri-procedural complications will be measured as a categorical variable (Yes or No).	30 days

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Investigators: Principal Investigator: Hiroshi Ashikaga, MD, PhD, Johns Hopkins University

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 19, 2021
• Primary Completion (ANTICIPATED): June 30, 2026
• Study Completion (ANTICIPATED): June 30, 2026

Study Registration Dates

• First Submitted: December 2, 2019
• First Submitted That Met QC Criteria: December 2, 2019
• First Posted (ACTUAL): December 4, 2019

Study Record Updates

• Last Update Posted (ACTUAL): September 14, 2022
• Last Update Submitted That Met QC Criteria: September 13, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: IRB00210289

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No