Clinical trial NCT04186169: Peri-Atrial Inflammatory Fat and Atrial Fibrillation
Official title: Preliminary Studies to Evaluate the Impact of Peri-Atrial Inflammatory Fat Tissue on Atrial Fibrillation Using Ultra-High Resolution CT
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Atrial Fibrillation
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
First posted: 2019-12-04
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Arm 1: Paroxysmal AF (n=100). Observational. Arm 2: Persistent AF (n=50). PVI arm Arm 3: Persistent AF (n=50). PVI + fat-targeted ablation arm
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Freedom from any documented episode of AF
timeFrame: 12 months
Secondary outcomes:
measure: Freedom from documented AF after two ablation procedures
timeFrame: 12 months
measure: Freedom from any documented atrial arrhythmia after one ablation procedure
timeFrame: 12 months
measure: Freedom from any documented atrial arrhythmia after two ablation procedures
timeFrame: 12 months
measure: Use of antiarrhythmia drugs (AADs)
timeFrame: 12 months
measure: Procedure time
timeFrame: 12 months
measure: Occurrence of repeat procedures
timeFrame: 12 months
measure: Occurrence of peri-procedural complications
timeFrame: 30 days
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Hiroshi Ashikaga, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.