Left atrial effective conducting size predicts atrial fibrillation vulnerability in persistent but not paroxysmal atrial fibrillation

Abstract

Background: The multiple wavelets and functional re-entry hypotheses are mechanistic theories to explain atrial fibrillation (AF). If valid, a chamber's ability to support AF should depend upon the left atrial size, conduction velocity (CV), and refractoriness. Measurement of these parameters could provide a new therapeutic target for AF. We investigated the relationship between left atrial effective conducting size (LA_ECS ), a function of area, CV and refractoriness, and AF vulnerability in patients undergoing AF ablation.

Methods and results: Activation mapping was performed in patients with paroxysmal (n = 21) and persistent AF (n = 18) undergoing pulmonary vein isolation. Parameters used for calculating LA_ECS were: (a) left atrial body area (A); (b) effective refractory period (ERP); and (c) total activation time (T). Global CV was estimated as $\surd A/T$ . Effective atrial conducting size was calculated as ${\mathrm{LA}}_{\text{ECS}}=A/\left(\mathrm{CV}\times \mathrm{ERP}\right)$ . Post ablation, AF inducibility testing was performed. The critical LA_ECS required for multiple wavelet termination was determined from computational modeling. LA_ECS was greater in patients with persistent vs paroxysmal AF (4.4 ± 2.0 cm vs 3.2 ± 1.4 cm; P = .049). AF was inducible in 14/39 patients. LA_ECS was greater in AF-inducible patients (4.4 ± 1.8 cm vs 3.3 ± 1.7 cm; P = .035, respectively). The difference in LA_ECS between inducible and noninducible patients was significant in patients with persistent (P = .0046) but not paroxysmal AF (P = .6359). Computational modeling confirmed that LA_ECS > 4 cm was required for continuation of AF.

Conclusions: LA_ECS measured post ablation was associated with AF inducibility in patients with persistent, but not paroxysmal AF. These data support a role for this method in electrical substrate assessment in AF patients.

Keywords: atrial fibrillation vulnerability; conduction velocity; left atrial effective conducting size; refractoriness.

Figure 1

Estimation of post‐ablation LA body area and the typical site for ERP measurement. LA body area was calculated from Carto shells by subtracting the area of the isolated pulmonary veins (shaded), the left atrial appendage, and the mitral annulus from the total area of the LA shell. The yellow tag indicates the site at which ERP measurements and AF induction protocol were performed. The activation map was recorded during coronary sinus pacing. AF, atrial fibrillation; ERP, effective refractory period; LA, left atrial

Figure 2

LA body area, calculated wavelength, and effective conducting size in patients with paroxysmal and persistent AF. A, LA body area was significantly greater in patients with persistent AF than paroxysmal AF. B, There was no significant difference in the calculated wavelength between patients with paroxysmal and persistent AF. C, Effective conducting size was significantly greater in patients with persistent than paroxysmal AF. AF, atrial fibrillation; LA, left atrium; LA_ECS, LA effective conducting size; PAF, paroxysmal AF; PsAF, persistent AF

Figure 3

LA body area, calculated wavelength, and effective conducting size in patients with and without inducible AF. A, LA body area was significantly greater in patients with inducible vs. noninducible AF. B, There was no significant difference in wavelength between patients who were and were not AF inducible. C, Effective conducting size was significantly greater in patients with inducible vs noninducible AF. AF, atrial fibrillation; LA, left atrium; LA_ECS, LA effective conducting size; PAF, paroxysmal AF; PsAF, persistent AF

Figure 4

LA body area, calculated wavelength, and effective conducting size in patients with and without inducible AF, by AF class. There was no significant difference in LA body area (A), wavelength (B) or left atrial effective conducting size (C) between paroxysmal AF cases who were and were not AF inducible. LA body area (D) and left atrial effective conducting size (F) was significantly greater, and calculated wavelength (E) was significantly smaller in persistent AF cases who were AF inducible compared to those who were not AF inducible. AF, atrial fibrillation; LA, left atrium; LA_ECS, LA effective conducting size; PAF, paroxysmal AF; PsAF, persistent AF

Figure 5

Relationship between induction of AF and LA body area, calculated wavelength and effective conducting size. A, LA body area is plotted on the x‐axis and calculated wavelength (see text) on the y‐axis for all patients in the study. B, Isolines represent LA_ECS. Patients with paroxysmal AF who were both AF inducible (D) and AF noninducible (C) localized around the 2 to 4 cm LA_ECS region (shaded). Patients with persistent AF who were noninducible occupied a larger range of effective conducting size from 1.3 to 10 cm (E). Patients with persistent AF who were AF inducible largely fell within the >4 cm range for LA_ECS. AF, atrial fibrillation; LA, left atrium; LA_ECS , LA effective conducting size; PAF, paroxysmal AF; PsAF, persistent AF

Figure 6

Effect of ablation and antiarrhythmic drugs on effective conducting size. Computational modeling confirmed that a critical LA_ECS > 4 cm was required for sustained multiple wavelet re‐entry. A, Re‐entry was sustained with LA_ECS = 6.18 cm (hexagon in “D”). B, Effect of reducing the atrial area to 80 cm² (top row, continued AF, LA_ECS = 4.5 cm, closed circle in D) and 70 cm² (bottom row, AF termination, LA_ECS = 3.94 cm, open circle in D). C, Effect of increasing sotalol doses on LA_ECS. AF continued when LA_ECS > 4 cm (top row, closed triangle in D) but terminated with LA_ECS = 4.0 cm (bottom row, open triangle in D). D, Illustrates how ablation or antiarrhythmic drugs could be applied to alter LA_ECS and remove patients from the region of vulnerability (shaded grey). Ablation would reduce left atrial body area with a corresponding reduction in LA_ECS (red arrow). Conversely, antiarrhythmic drugs to prolong refractoriness could be applied to increase LA wavelength (green arrow) and decrease LA_ECS. AF, atrial fibrillation; LA_ECS , LA effective conducting size

Figure 7

Effect of left atrial effective conducting size on arrhythmia inducibility in patient‐specific simulations. A, For the smallest anatomy (area 75 cm²), AF is noninducible for an ERP value of 250 milliseconds and LA_ECS = 3.90 cm. Isopotential plots are shown for time points at 250 milliseconds intervals. B, For the same anatomy as “A”, AF is inducible for an ERP value of 240 milliseconds and LA_ECS = 4.06 cm. C, For the medium anatomy (area 103 cm²), AF is inducible for a longer ERP (270 milliseconds) than for the smallest anatomy shown in “B”. D, For the largest anatomy (area 140 cm²), AF is inducible for all tested values of ERP. The example here is for an ERP of 250 milliseconds (as in “A”) and LA_ECS = 7.27 cm. E, LA_ECS, left atrial body area and ERP are shown for inducible and noninducible simulations. Median LA_ECS is significantly lower for noninducible cases (3.85 cm vs 5.52 cm; P < .001), median left atrial body area is significantly lower for noninducible cases (75 cm² vs 103 cm²; P < .001) and median ERP is significantly higher for noninducible cases (260 milliseconds vs 240 milliseconds; P < .001). AF, atrial fibrillation; ERP, effective refractory period; LA_ECS , LA effective conducting size

Figure 8

Left atrial effective size‐based arrhythmia therapy insights from patient‐specific simulations. A, AF is inducible post‐pulmonary vein isolation for the largest anatomy (area 140 cm²) with an ERP of 270 milliseconds (LA_ECS = 6.73 cm). Isopotential plots are shown for time points at 250 milliseconds intervals. B, AF is inducible after applying the smallest box isolation ablation to the largest anatomy (remaining left atrial body area, 121 cm²) with an ERP of 270 milliseconds (LA_ECS = 5.82 cm). C, AF is noninducible after applying the largest box isolation ablation to the largest anatomy (remaining left atrial body area, 82 cm²) with an ERP of 270 milliseconds (LA_ECS = 3.94 cm). Together “B” and “C” show that reducing the remaining left atrial body area is a viable therapeutic strategy to reduce LA_ECS and AF inducibility. D, AF is inducible after applying the largest box isolation ablation to the medium anatomy (remaining left atrial body area, 74 cm²) with an ERP of 230 milliseconds (LA_ECS = 4.18 cm). E, Modifying the ERP to 250 milliseconds for the case in “D” results in non‐inducibility (LA_ECS = 3.84 cm). Together “D” and “E” show that in certain cases combined the use of ablation and antiarrhythmic drugs may be needed to achieve the necessary reduction in LAECS and prevent AF inducibility. Dotted red lines indicate ablation lesion trajectories. “A”‐“C” (largest anatomy) are shown in posteroanterior orientation. D‐E, (medium anatomy) are shown in anteroposterior orientation with cranial tilt. AF, atrial fibrillation; ERP, effective refractory period; LA_ECS, LA effective conducting size