Study Population
We prospectively enrolled 160 consecutive patients who had been diagnosed with at least moderate AS (peak velocity across the aortic valve >3.0 m/s or EOA <1.5 cm2) referred for transthoracic echocardiography from May 2018 to March 2019 at Hokkaido University Hospital. After the exclusion of patients with irregular heart rhythm due to arrhythmias (N = 38) and those with poor echocardiographic images (N = 8) in whom EOA by continuous equation could not be obtained, 114 patients were included in the final analysis. In 51 of the 114 patients who also underwent transesophageal echocardiography (TEE) after transthoracic echocardiographic examination (median distance: 27 days: TEE cohort), the geometric orifice area (GOA) of the aortic valve was used as the reference for the valve area. Study approval was obtained from the institutional review board of Hokkaido University Hospital (No. 018-0179) and an opportunity to opt-out was given to each participant through a published disclosure document on the web site of the institute.
Two-Dimensional and Doppler Echocardiography
Comprehensive transthoracic echocardiography was performed in the left decubitus position using a commercially available ultrasound equipment system (Vivid E9, GE Healthcare, Horton, Norway; iE33, Philips Medical Systems, Andover, Massachusetts; Acuson SC2000 prime, Siemens Healthineers, Erlangen, Germany; Aplio Artida, Canon Medical Systems, Otawara, Japan) according to the guidelines. [9] Left ventricular (LV) mass was determined using the Devereux formula. LV ejection fraction (EF) was calculated by using the biplane method of disks. USH was defined as a ratio of upper septal wall thickness to mid-septal wall thickness ³1.3. The maximal aortic valve velocity (Vmax) was measured using continuous-wave Doppler imaging in the view that showed the highest flow velocity, and the mean transvalvular gradient was estimated based on the simplified Bernoulli equation. The LVOT diameter was measured in the parasternal long-axis view. Flow velocity at the LVOT was measured using pulsed-wave Doppler imaging in the apical long-axis view, in which the sample volume was placed just proximal to the region of flow acceleration, and the time velocity integral (TVILVOT) was measured. SV was then calculated as SVCont = (LVOT diameter / 2)2 ´ P ´ TVILVOT. EOA of the aortic valve was calculated using the continuity equation: EOACont = SV / TVIAV, where TVIAV was the time velocity integral of the maximal aortic valve flow. [3] Measurements of EOACont were performed by blinded certified sonographers (M.M., S.Y., H.N., M.N., and S.K.) and verified by a board certified reader (H.I.).
PISA Method for Estimation of EOA
Measurements of EOA by PISA methods were performed by the sonographers (M.M. or M.N) who were blinded to the results of clinical and echocardiographic parameters. To obtain a clear visualization of the proximal convergence of the aortic stenotic jet, a cut plane was selected in each patient from the apical long-axis, apical four-chamber, right parasternal long-axis, and suprasternal long-axis views (Figure 1A). Care was taken to minimize the angle between the centerline of the flow convergence and ultrasound beam. Using a magnified image, the appearance of PISA was optimized by shifting the baseline of the color Doppler scale to forward direction to adjust for aliasing velocity around 50 to 70 cm/s as appropriate. The radius of PISA (r) was then measured, and the instantaneous flow rate was calculated as 2Πr2 ´ aliasing velocity (mL/s). EOA was then calculated using the PISA method: EOAPISA =flow rate/Vmax (cm2) based on the principle of conservation of mass (Figure 1). The SV was also calculated by EOAPISA ´ TVIAV (SVPISA).
Measurement of GOA
Transesophageal echocardiographic images were obtained using an iE33 (Philips Medical Systems, Andover, Massachusetts) with X7-2t probe or an Acuson SC2000 prime (Siemens Healthineers, Erlangen, Germany) with Z6Ms probe. At first, the two-dimensional images were clearly obtained in the midesophageal long-axis and short-axis views. Then volume data sets were obtained using four-beat full-volume mode (N =38, median volume rate: 27 Hz) or the live three-dimensional zoom mode (N = 13, median volume rate: 21 Hz) focused on the aortic valve complex. During acquisition of full volume images, gain and compression settings were optimized to display a magnified image of the aortic valve. After choosing the mid-systolic frame, in which maximal aortic valve excursion was observed, fine adjustments of the short-axis plane were performed to obtain the smallest aortic valve orifice and the GOA was measured (Figure 1B). All the measurements of GOA were performed by trained cardiovascular physicians (S.I, Y.C., and S.T.) and designated by a certified reader (H.I.).
Classifications of the Patients
To test the influence of LVOT flow velocity and LV morphology on the accuracy of measuring the EOA, we divided the patients by the median value of LVOT flow velocity and the presence or absence of USH and compared the differences in EOACont to aortic valve area-related variables between the groups.
Statistical Analysis
Continuous variables are expressed as mean ± standard deviation and compared by paired or unpaired t test. Categorical data are presented as number (percentage). Agreements between aortic valve areas assessed using different methods were evaluated using Pearson’s correlation coefficient and Bland-Altman plot analysis. The Bland-Altman procedure for comparing two methods was also used to determine the bias (95% confidential interval: CI). A two-sided P value <0.05 was considered statistically significant. All statistical analyses were performed using JMP version 14.0 (SAS Institute Inc., Cary, North Carolina).