Subjects and Protocol

We recruited 147 consecutive patients aged >20 years who had SEM with grade ≥2 or known AS and were referred to the echocardiography laboratory at the Osaka City General Hospital. Patients with atrial fibrillation or any other significant murmurs louder than SEM were excluded. Patients were also excluded if there was technical difficulty in observing the aortic valve cusps on pocket-sized echocardiography or in evaluating the aortic valve area (AVA) using the continuity equation with high-end echocardiography. Furthermore, patients with bicuspid aortic valves or those with any other significant disease leading to SEM, such as left ventricular (LV) outflow tract obstruction, were also excluded. The study protocol was approved by the institutional review board of the Osaka City General Hospital, and written informed consent was obtained from all patients. Subjects underwent cardiac physical examination, pocket-sized echocardiography, and high-end echocardiography in sequence.

Physical Examination

Subjects underwent cardiac physical examinations in the supine position. Physical examinations were performed by an experienced cardiologist, who was blinded to all other patient information. The presence or absence of the following physical examination findings was assessed: transmission of SEM to the neck, late peaking of SEM, a diminished second heart sound, delayed carotid artery upstroke, and carotid artery shudder. Transmission of SEM to the neck was judged at the right carotid artery. Late peaking of SEM was judged as present if SEM had its peak intensity in mid-systole or later at the location with the maximal murmur intensity. A diminished second heart sound was considered present if the aortic component of the second heart sound was significantly smaller than the first heart sound at the second or third left intercostal space. During normal breathing, the aortic component of the second heart sound was identified by its temporal relation to the pulmonary component that occurs later in the inspiratory period. To assess the carotid artery pulse, the examiner applied both light and firm pressure over the carotid artery on the side where the carotid pulse was most palpable and determined whether there was a delayed carotid artery upstroke and carotid artery shudder.

Pocket-Sized Echocardiography

Pocket-sized echocardiography was performed using a Vscan (GE Healthcare, Little Chalfont, United Kingdom) by an expert sonographer corresponding to level 3, who was blinded to all other patient information. The device weighs 390 g, including the phased-arrayed probe, which measures 135 × 73 × 28 mm. The device does not offer continuous-wave or pulsed-wave Doppler analysis but only two-dimensional grayscale imaging and color Doppler imaging. The image sector for echocardiographic imaging is 758. The bandwidth ranges from 1.7 to 3.8 MHz and is automatically adjusted. Subjects underwent a semicomprehensive cardiac screening protocol with the pocket-sized device in the left lateral decubitus position, focusing on visual assessment of LV systolic function and valves.

First, we imaged the aortic valve in the parasternal short-axis view and adjusted the transducer orientation and image display so that the valve was centered in the display. We visualized lines between each of the three commissures, as illustrated in Figure 1 A. We then scored each aortic cusp’s opening visually as follows: 0 = not restricted, 1 = restricted, or 2 = severely restricted. When a cusp did not open over the line between the commissures, the cusp’s opening was classified as restricted. When a cusp’s systolic motion was severely reduced or absent, the cusp’s opening was classified as severely restricted. Examples of normal, restricted, and severely restricted cusp motion are demonstrated in Figures 1 A–1D and Videos 1A to 1D (available at www.onlinejase.com ). We defined the sum of the scores for the three cusps as the visual AS score (range, 0–6). Then, the degree of calcification of the aortic valve was also scored as follows: 1 = no calcification, 2 = mildly calcified (small isolated spots), 3 = moderately calcified (multiple larger spots), or 4 = heavily calcified (extensive thickening and calcification of all cusps).

Visual AS score obtained by pocket-sized echocardiography. Each aortic cusp’s opening was visually scored as follows: 0 = not restricted, 1 = restricted, or 2 = severely restricted. The sum of the scores for the three cusps was defined as the visual AS score (range, 0–6). Examples are demonstrated in (A) through (D) and in Videos 1A through 1D . Also see the text.

After the assessment of the aortic valve cusps, we visually evaluated the presence or absence of regional LV systolic dysfunction and global LV systolic dysfunction from images in the parasternal long-axis, parasternal short-axis, apical four-chamber, apical two-chamber, and apical long-axis views. Aortic, mitral, and tricuspid valvular regurgitations were qualified as none, mild, moderate, or severe by visual assessment of color Doppler imaging. We also screened for any other significant abnormalities leading to SEM, such as LV outflow tract obstruction. Other unexpected abnormalities were also sought. The time required for examination using the pocket-sized device was measured in each subject.

High-End Echocardiography

Subjects underwent complete examination with high-end echocardiography performed by another level 3 sonographer, who was blinded to all other patient information. The iE33 (Philips Medical Systems, Bothell, WA), Acuson Sequoia 512 (Siemens Medical Systems, Mountain View, CA), or Aplio SSA-700A (Toshiba Medical Systems, Tokyo, Japan) was used for high-end echocardiography with second-harmonic mode. LV diastolic dimension, LV systolic dimension, LV mass index, and LV ejection fraction were evaluated according to the guidelines of the American Society of Echocardiography. LV ejection fraction was evaluated using the biplane method of disks. Doppler flow data were obtained from the LV outflow tract region in pulsed-wave mode and from the aortic valve in continuous-wave mode using multiple transducer positions to obtain the maximal velocity. LV outflow tract diameter was measured in the parasternal long-axis view at the position used to obtain the pulsed-wave Doppler data. AVA was calculated using the continuity equation (AVA = area _outflow × velocity-time integral _outflow /velocity-time integral _valve ). The AVA index (AVAI) was obtained by dividing AVA by body surface area, and an AVAI <0.60 cm ² /m ² and an AVAI of 0.60 to 0.85 cm ² /m ² were considered to indicate severe AS and moderate AS, respectively.

Statistical Analysis

Data are presented as absolute values, percentages, or mean ± SD, as appropriate. In analyzing the trend according to AS severity (none to mild, moderate, and severe), the Cochran-Armitage trend test was used to compare categorical variables, and the Jonckheere-Terpstra trend test was used to compare continuous variables. Linear regression analysis was applied to study the correlation between visual AS score and AVAI. Sensitivities, specificities, positive likelihood ratios, and negative likelihood ratios for diagnosing severe and moderate to severe AS were calculated using standard methods. The best combination of sensitivity and specificity was defined as the combination with the highest sum of sensitivity and specificity. Sensitivities and specificities were compared using McNemar’s test. The areas under the two receiver operating characteristic curves were compared using a nonparametric approach. P values < .05 were considered statistically significant.

A test-retest analysis was performed to assess the interobserver agreement for the visual AS score. Another level 3 sonographer, who was blinded to all patient information, performed pocket-sized echocardiography for the interobserver analysis. The visual AS score was assessed not only with pocket-sized echocardiography but also with high-end echocardiography, and agreement in the visual AS score between pocket-sized echocardiography and high-end echocardiography was also assessed. Agreement was assessed as the percentage and/or the κ value, as appropriate. Kappa values of <0.20, 0.21 to 0.40, 0.41 to 0.60, 0.61 to 0.80, and 0.81 to 1.0 were considered to indicate poor, fair, moderate, good, and very good agreement, respectively.