Septum, Atrial

In order to characterise the behaviour of re-entrant excitation waves in an anatomically-realistic setting, the 3D virtual human atrium [34 (link)], which is based on the visible human dataset [63 (link)], was employed, as in several of our previous modelling studies [23 (link),34 (link),36 (link)]. The 3D geometry was taken to be electrically heterogeneous, as it is segmented into distinct regions of the atria, described fully in [23 (link)] and shown in Fig 2. The CZ model incorporates a family of regional cell models, accounting for distinct electrophysiological differences in the right atrium (RA), left atrium (LA), right atrial appendage (RAA), left atrial appendage (LAA), crista terminalis (CT), pectinate muscles (PM), atrio-ventricular ring (AVR), atrial septum (AS), Bachmann’s bundle (BB), and pulmonary veins (PV). Details are provided in Supporting S1 Text, along with S1B Fig which shows model validation of regional cell models, and S2 Fig which gives a detailed validation of the PV model. In addition, a degree of fibre anisotropy along the bundles of the CT, PM, and BB is included. Re-entry was initiated using the phase distribution method [68 (link)], whereby an artificial asymmetric conduction pattern is created, leading to the development of a 3D spiral (scroll) wave (see S9 Fig and Supporting S1 Text for details). Where applicable, averaged DF and lifespan of re-entry were calculated based on time series of APs taken from several locations on the human atria geometry.

At baseline, a comprehensive clinical assessment, including medical history, current medication, physical examination, electrocardiogram, blood tests, and transthoracic echocardiography, was performed. All patients underwent a comprehensive echocardiographic examination by an experienced echocardiographer. Quantification of MR severity was based on an integrated approach as recommended^{7 (link),8 (link)}; valve morphology, cavity sizes, and LV function were assessed. Left atrial (LA) diameters are derived from apical four chamber views measured at the end of systole, the diameter being measured parallel to the interatrial septum from the plane of the mitral annulus to the roof of the atrium. A LA diameter < 51 mm was considered normal, 51–60 mm mildly enlarged, 61–70 mm moderately enlarged and ≥ 70 mm severely enlarged.

A comprehensive transthoracic echocardiographic examination was performed using the same system applied for baseline examinations (Vivid E9 system, GE Vingmed, Horton, Norway, with an M5S 1.5- to 4.5-MHz transducer). The predefined echocardiographic study protocol can be inspected in the Supplementary material. Routine echocardiographic and Doppler data were obtained in accordance with the current ASE guidelines (6 (link), 21 (link)). Standard parameters to assess diastolic function included LAVI; diastolic transmitral inflow velocities derived from pulsed wave-Doppler signal as well as the deceleration time; the septal, lateral, or average early diastolic mitral annular velocity (e′) assessed by pulsed-wave tissue Doppler; and E/e′ ratio. The RV-RA pressure difference was estimated from the maximum transvalvular velocity of the tricuspid regurgitation during systole.
2D STE strain studies were analyzed offline using the EchoPAC v203 software (GE Healthcare). Global peak systolic longitudinal LV strain (LV GLS) was determined from apical 4-chamber, 2-chamber, and long-axis views (17 segment LV model). Phasic LAS was assessed as proposed by the recent EACVI recommendations (12 (link)) from an LA focused apical 4-chamber-view, avoiding foreshortening. Three cardiac cycles were recorded for each view and stored for offline analysis. Gain, depth, and frame rate (60–80 frames/s) were optimized for image acquisition. The region of interest was placed on the atrial walls, distributing the interatrial septum and atrial free wall into six segments. LAS was analyzed QRS-triggered. LASr was identified from the plotted average strain curve as the maximum amplitude during ventricular systole. LA conduit strain (during passive LV filling; LAScd) and LA contraction strain (during peak atrial contraction; LASct) were calculated from the generated strain curve as previously described (4 (link), 12 (link), 22 (link)) (Figure 1).