Relationship Between Fibrosis Detected on Late Gadolinium-Enhanced Cardiac Magnetic Resonance and Re-Entrant Activity Assessed With Electrocardiographic Imaging in Human Persistent Atrial Fibrillation

Abstract

Objectives: This study sought to assess the relationship between fibrosis and re-entrant activity in persistent atrial fibrillation (AF).

Background: The mechanisms involved in sustaining re-entrant activity during AF are poorly understood.

Methods: Forty-one patients with persistent AF (age 56 ± 12 years; 6 women) were evaluated. High-resolution electrocardiographic imaging (ECGI) was performed during AF by using a 252-chest electrode array, and phase mapping was applied to locate re-entrant activity. Sites of high re-entrant activity were defined as re-entrant regions. Late gadolinium-enhanced (LGE) cardiac magnetic resonance (CMR) was performed at 1.25 × 1.25 × 2.5 mm resolution to characterize atrial fibrosis and measure atrial volumes. The relationship between LGE burden and the number of re-entrant regions was analyzed. Local LGE density was computed and characterized at re-entrant sites. All patients underwent catheter ablation targeting re-entrant regions, the procedural endpoint being AF termination. Clinical, CMR, and ECGI predictors of acute procedural success were then analyzed.

Results: Left atrial (LA) LGE burden was 22.1 ± 5.9% of the wall, and LA volume was 74 ± 21 ml/m². The number of re-entrant regions was 4.3 ± 1.7 per patient. LA LGE imaging was significantly associated with the number of re-entrant regions (R = 0.52, p = 0.001), LA volume (R = 0.62, p < 0.0001), and AF duration (R = 0.54, p = 0.0007). Regional analysis demonstrated a clustering of re-entrant activity at LGE borders. Areas with high re-entrant activity showed higher local LGE density as compared with the remaining atrial areas (p < 0.0001). Failure to achieve AF termination during ablation was associated with higher LA LGE burden (p < 0.001), higher number of re-entrant regions (p < 0.001), and longer AF duration (p = 0.008).

Conclusions: The number of re-entrant regions during AF relates to the extent of LGE on CMR, with the location of these regions clustering to LGE areas. These characteristics affect procedural outcomes of ablation.

Keywords: atrial fibrillation; atrial fibrosis; electrocardiographic mapping; magnetic resonance imaging; re-entry; rotor.

FIGURE 1. Analysis of Atrial LGE on CMR

A 61-year-old man with a history of persistent atrial fibrillation and no associated structural heart disease. On late gadolinium-enhanced (LGE) images, (A) areas of focal fibrosis are identified using manual segmentation of the atrial wall, and (B) adaptive thresholding on the histogram of myocardial voxels (yellow indicates late gadolinium enhancement). (C) The output of segmentation is a global quantification of late gadolinium enhancement expressed in a percentage of the wall and a map displaying late gadolinium-enhanced distribution over a biatrial surface (white indicates fibrosis). (D) A map of local late gadolinium-enhanced density (i.e., local burden of late gadolinium enhancement over a 5-mm neighborhood) is derived from late gadolinium-enhanced segmentation. CMR = cardiac magnetic resonance.

FIGURE 2. Analysis of Re-Entrant Activity on ECGI

A 54-year-old man with a history of persistent atrial fibrillation and no associated structural heart disease. (A) A multielectrode vest was placed on the patient’s thorax, and the position of each electrode with respect to the atria was assessed using multidetector computed tomography. This geometric information was used to solve an inverse problem to reconstruct unipolar electrograms on the atrial surface from body surface potentials. (B) A phase mapping algorithm was applied on these unipolar electrograms to visualize activation during fibrillation and to identify re-entrant activity as phase singularities (color coding indicates local phase; white line indicates depolarization; a phase singularity can be seen on the posterior left atrial wall where all colors meet). (C) Automated tracking of phase singularities was implemented to collect their trajectories over the biatrial surface (trajectories in blue) throughout the whole mapping period (14 s in this example). (D) A cumulative map displaying the likelihood of re-entry was computed. On each point of the geometry, this refers to the probability of observing a re-entry at a given time frame. This map was used to define re-entrant regions to be targeted by ablation (red regions in D). ECGI = electrocardiographic imaging.

FIGURE 3. Relationship Between Re-Entry Trajectories and Focal Fibrosis

Results of cardiac magnetic resonance and electrocardiographic imaging are shown in 4 patients with a history of persistent AF and no structural heart disease (all men, age 54, 63, 57, and 48 years for top left, top right, bottom left, and bottom right, respectively). The trajectories of phase singularities, as defined in Figure 2, are overlaid on late gadolinium-enhanced (LGE) distribution (white indicates significant late gadolinium enhancement). Each trajectory is color coded according to the persistence of phase singularities at each point of the trajectory (i.e., the percentage of time a phase singularity was observed at each specific location). Therefore, yellow trajectories indicate sites of anchoring where a re-entrant activity meanders in a confined atrial location, whereas dark red trajectories indicate transit paths where re-entrant activity simply drifts. Visual analysis shows that anchoring sites (i.e., yellow trajectories) are located at the border of fibrotic areas, whereas trajectories observed either inside (e.g., bottom right) or outside (e.g., upper left) fibrotic areas appear as drifting sites (i.e., straight dark red trajectories).

FIGURE 4. Local LGE Density in Regions With Versus. Without Re-Entrant Activity (N = 20)

LGE = late gadolinium enhancement.

FIGURE 5. Re-Entrant Activity and Left Atrial LGE in Patients With and Without Successful Termination of AF by Catheter Ablation (N = 41)

AF = atrial fibrillation; LGE = late gadolinium enhancement; MRI = magnetic resonance imaging.