Impact of Peri-Atrial Inflammatory Fat Tissue on Atrial Fibrillation Using Ultra-High Resolution CT

2019-12-10 01:20:59 | BioPortfolio


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 (Ciuffo at el., Circ Cardiovasc Imaging 2019;12:e008764). In this protocol, investigators will investigate the clinical significance of peri-atrial inflammatory fat tissue in AF using ultra-high resolution CT.


This protocol entails preliminary studies to demonstrate feasibility and inform effect size, sample size and power estimates for future studies designed to test the efficacy of inflammatory fat-targeted ablation in a larger prospective randomized study.

Investigators will prospectively enroll 300 patients referred to the Johns Hopkins Hospital for catheter ablation of AF, consisting of patients with paroxysmal AF (n=100), persistent AF (n=100) and recurrent AF/AFL post-AF ablation (n=100) (Figure 3). All the patients will undergo pre-procedural CT using the ultra-high resolution CT scanner. If the ultra-high resolution CT is not available on the day of the CT scan, the patient may instead undergo pre-procedural CT using a standard CT scanner. The CT protocol will be the standard prospectively-gated CT scan to minimize radiation exposure to the patient. No functional information is needed. Compared with the standard CT scanner, the ultra-high resolution CT is expected to provide finer details of inflammatory fat structure and distribution over the per-atrium.

The patients with paroxysmal AF will receive the standard of care, which is PVI, and the clinical outcome will be followed up to 12 months post-procedure. For the patients with persistent AF and recurrent AF/ Atrial Flutter (AFL), there is no standard of care as to how to perform ablation beyond repeating PVI. In an attempt to reduce the likelihood of recurrence, most electrophysiologists combine PVI with additional empiric ablation strategies to modify the underlying arrhythmic substrate, such as linear lesions (e.g. roof lines, mitral isthmus lines), focal ablation to eliminate complex fractionated atrial electrograms (CFAE) and rotating drivers. Nevertheless, prospective randomized studies demonstrate that these empiric ablation strategies do not improve clinical outcomes compared with PVI alone. In this protocol, the patients with persistent AF and recurrent AF/AFL will be randomly split into two groups: 1) PVI group, and 2) PVI + fat ablation group, where additional ablation is performed to target the inflammatory fat tissue. The clinical outcome will be followed up to 12 months post-procedure.

In all the patients, two sets of blood specimens (total <20 mL) will be collected at the time of the procedure: one set is from the peripheral venous blood, and the other from the coronary sinus blood. Those samples will be sent to quantify the fat and inflammatory biomarkers (e.g. adipokines, cytokines, high-sensitivity troponin T [hsTnT]) to evaluate the local and systemic effect of inflammation.

Study Design


Atrial Fibrillation


Catheter ablation


Not yet recruiting


Johns Hopkins University

Results (where available)

View Results


Published on BioPortfolio: 2019-12-10T01:20:59-0500

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Medical and Biotech [MESH] Definitions

Rapid, irregular atrial contractions caused by a block of electrical impulse conduction in the right atrium and a reentrant wave front traveling up the inter-atrial septum and down the right atrial free wall or vice versa. Unlike ATRIAL FIBRILLATION which is caused by abnormal impulse generation, typical atrial flutter is caused by abnormal impulse conduction. As in atrial fibrillation, patients with atrial flutter cannot effectively pump blood into the lower chambers of the heart (HEART VENTRICLES).

Long-term changes in the electrophysiological parameters and/or anatomical structures of the HEART ATRIA that result from prolonged changes in atrial rate, often associated with ATRIAL FIBRILLATION or long periods of intense EXERCISE.

A cardiotonic glycoside obtained mainly from Digitalis lanata; it consists of three sugars and the aglycone DIGOXIGENIN. Digoxin has positive inotropic and negative chronotropic activity. It is used to control ventricular rate in ATRIAL FIBRILLATION and in the management of congestive heart failure with atrial fibrillation. Its use in congestive heart failure and sinus rhythm is less certain. The margin between toxic and therapeutic doses is small. (From Martindale, The Extra Pharmacopoeia, 30th ed, p666)

The pressure within the CARDIAC ATRIUM. It can be measured directly by using a pressure catheter (see HEART CATHETERIZATION). It can be also estimated using various imaging techniques or other pressure readings such as PULMONARY CAPILLARY WEDGE PRESSURE (an estimate of left atrial pressure) and CENTRAL VENOUS PRESSURE (an estimate of right atrial pressure).

Removal of tissue with electrical current delivered via electrodes positioned at the distal end of a catheter. Energy sources are commonly direct current (DC-shock) or alternating current at radiofrequencies (usually 750 kHz). The technique is used most often to ablate the AV junction and/or accessory pathways in order to interrupt AV conduction and produce AV block in the treatment of various tachyarrhythmias.

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