Chamber-specific wall thickness features in human atrial fibrillation

Abstract

Persistent atrial fibrillation (AF) is not effectively treated due to a lack of adequate tools for identifying patient-specific AF substrates. Recent studies revealed that in 30-50% of patients, persistent AF is maintained by localized drivers not only in the left atrium (LA) but also in the right atrium (RA). The chamber-specific atrial wall thickness (AWT) features underlying AF remain elusive, though the important role of AWT in AF is widely acknowledged. We aimed to provide direct evidence of the existence of distinguished RA and LA AWT features underlying AF drivers by analysing functionally and structurally mapped human hearts ex vivo. Coronary-perfused intact human atria (n = 7, 47 ± 14 y.o.; two female) were mapped using panoramic near-infrared optical mapping during pacing-induced AF. Then the hearts were imaged at approximately 170 µm³ resolution by 9.4 T gadolinium-enhanced MRI. The heart was segmented, and 3D AWT throughout atrial chambers was estimated and analysed. Optical mapping identified six localized RA re-entrant drivers in four hearts and four LA drivers in three hearts. All RA AF drivers were anchored to the pectinate muscle junctions with the crista terminalis or atrial walls. The four LA AF drivers were in the posterior LA. RA (n = 4) with AF drivers were thicker with greater AWT variation than RA (n = 3) without drivers (5.4 ± 2.6 mm versus 5.0 ± 2.4 mm, T-test p < 0.05; F-test p < 0.05). Furthermore, AWT in RA driver regions was thicker and varied more than in RA non-driver regions (5.1 ± 2.5 mm versus 4.4 ± 2.2 mm, T-test p < 0.05; F-test p < 0.05). On the other hand, LA (n = 3) with drivers was thinner than the LA (n = 4) without drivers. In particular, LA driver regions were thinner than the rest of LA regions (3.4 ± 1.0 mm versus 4.2 ± 1.0 mm, T-test p < 0.05). This study demonstrates chamber-specific AWT features of AF drivers. In RA, driver regions are thicker and have more variable AWT than non-driver regions. By contrast, LA drivers are thinner than non-drivers. Robust evaluation of patient-specific AWT features should be considered for chamber-specific targeted ablation.

Keywords: atrial fibrillation; atrial wall thickness; cardiac arrhythmogenesis; human atria.

Figure 1.

Seven human atria ex vivo were imaged by 9.4 T CE-MRI and used for 3D AWT analysis of RA versus LA. (a) The human atria (H1) were visualized in 3D at a lateral RA view. Four typical 2D raw CE-MRI images and AWT from the posterior to the anterior of the 3D atria are displayed. Of note, the CT is much thicker than the rest of the tissue. (b) Top: The right lateral view of a 3D human RA endocardial surface (heart H1) with colour-coded for AWT. Blue indicates the thin region, while red is for thick atrial tissue. RA AWT distribution is plotted in the right-hand panel. The mean and standard deviation (STD) of the AWT distribution are shown here (black dashed lines). Bottom: The posterior view of 3D human LA endocardial surface (H1) and its AWT distribution. (c) The distribution of 3D AWT: RA (top) versus LA (bottom) in the seven explanted human atria. Black dashed lines indicate the mean and STD of the wall thickness distribution. The RA had a secondary peak due to the presence of the CT. In addition, RA had a higher tissue percentage with AWT > 7.2 mm than LA (15.9% versus 7.7%). CE-MRI, contrast-enhanced magnetic resonance imaging; CT, crista terminalis; IAS, interatrial septum; S/IVC, superior/inferior vena cava; LA/RA, left/right atrium; LAA/RAA, left/right atrial appendage; PV, pulmonary vein; L/R PV, left/right superior and inferior PVs; AWT, atrial wall thickness; PM, pectinate muscle; AF, atrial fibrillation.

Figure 2.

Analysis of chamber-specific AWT with and without mapped AF drivers and AWT features in driver regions in explanted human atria (n = 7). (a) The distribution of optically mapped AF drivers in LA versus RA for the seven heart hearts. All the RA drivers were anchored on the CT region at both the superior and inferior sections of the RA. (b) A typical RA driver of the human atria (H1) is superimposed on the atrial epicardium and co-located with AWT variation (c). The white arrow indicates an optically mapped re-entrant driver. It can be seen that this driver is anchored on the thicker (in red) CT and thin (blue) tissue region. (d) AWT distribution for RA with and without optically mapped AF drivers, and for RA driver regions and the rest of the RA with AF drivers. RA driver regions specifically had a much larger secondary peak in the distribution due to their co-location with the thick CT regions. (e) AWT distribution for LA with and without optically mapped drivers, and for LA driver regions and the rest of the LA. LA driver regions had a much thinner AWT than the rest of the LA tissue. For abbreviations, see figure 1.