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ONLINE APPENDIX
Echocardiography
LV end-diastolic and end-systolic diameters and septal and posterior wall thicknesses were
measured from parasternal long-axis views using M-mode echocardiography. LV volumes
and LV ejection fraction were measured using the Simpson biplane method from twochamber and four-chamber apical views. Mitral inflow recordings were obtained with pulsed
Doppler and used to quantify early and late wave peak velocities and the early-to-late
diastolic flow ratio. Tissue Doppler imaging at the lateral and septal mitral annulus was
performed to measure the ratio between early transmitral flow and mean lateral and septal
early diastolic peak tissue velocity used as an estimate of LV filling pressure. Systolic
pulmonary arterial pressure was estimated by applying the modified Bernoulli equation to the
maximal tricuspid regurgitation velocity assessed by conventional Doppler imaging. LS was
computed from the standard LV apical views (two, three, and four chambers) using 2D
speckle-tracking echocardiography analysis by automated function imaging (AFI, ECHO-Pac,
GE Healthcare). For LS processing, the R wave peak on the electrocardiogram was taken to
indicate the end of diastole. Briefly, after manual initialization of the end-systolic endocardial
border, the region of interest was automatically positioned to track the LV speckles frame by
frame throughout the cardiac cycle. Endocardial contour and width were adjusted manually
when necessary to provide optimal tracking. Segments with poor-quality tracking were
discarded manually.
Cardiac magnetic resonance imaging (MRI)
MRI was performed within 5 days after echocardiography, using a 1.5-T machine (Magnetom
Avanto, Siemens Healthcare, Erlangen, Germany). All acquisitions were recorded during a
breath-hold, and balanced steady-state free precession sequences were synchronized to the
electrocardiogram. Data analysis was performed offline on a dedicated computer workstation
(Argus, Siemens Medical Systems, Malvern, PA, USA) by two experienced radiologists (JFD
and JT) blinded to the patients’ clinical data. Semi-automated software was used to compute
LV ejection fraction from consecutive short-axis slices. The end-systolic and end-diastolic
phases were defined, and an auto-level function was then applied for automatic endocardial
contour detection. If necessary, the contours of key areas were corrected manually. Special
care was taken to avoid partial volume effects at valve planes, and papillary muscles and
trabecular structures were included in the ventricular volume. LGE was defined as abnormal
myocardial hyperintensity on inverse recovery sequences 10 minutes after an intravenous
injection of 0.2 mmol/Kg gadolinium (Dotarem, Guerbet, Aulnay-sous-Bois, France). To
determine the optimal inversion recovery time, a specific scouting sequence was acquired
before the LGE images. Phase-sensitive inversion recovery images were acquired routinely
after the LGE images (repetition time, 835 ms; echo time, 3.3 ms; flip angle, 10°; matrix size,
256x156; field of view, 300x270 mm; slice thickness, 8 mm; and GRAPPA acceleration
factor, 2). The image acquisition time ranged from 12 to 20 seconds depending on heart rate.
Five phase-sensitive inversion recovery images were acquired in the short-axis plane
encompassing the LV. A single slice was acquired in the four-chamber and two-chamber
views. Each of the 17 LV segments was evaluated separately for LGE.