Echocardiographic Evaluation

All patients underwent two-dimensional and Doppler echocardiography. Recordings and measurements were obtained according to the recommendations of the American Society of Echocardiography. Measurements of LV end-diastolic diameter, interventricular septal thickness, and posterior wall thickness were made at the beginning of the QRS complex. LV mass (LVM) was calculated using Devereux’s formula and normalized to body surface area as the LVM index (LVMI). LV hypertrophy was considered to be present when LVMI was >116 g/m ² in men and >104 g/m ² in women. Relative wall thickness (RWT) was defined as the ratio (2 × posterior wall thickness)/LV end-diastolic diameter, and values ≤ 0.43 were considered normal. Patterns of LV remodeling in patients with AS were classified according to LVMI and RWT values as normal LVM and geometry (LVMI < 116 g/m ² in men, LVMI < 104 g/m ² in women, and RWT < 0.43), concentric remodeling (LVMI < 116 g/m ² in men, LVMI < 104 g/m ² in women, and RWT > 0.43), concentric hypertrophy (LVMI > 116 g/m ² in men, LVMI > 104 g/m ² in women, and RWT > 0.43), and eccentric hypertrophy (LVMI > 116 g/m ² in men, LVMI > 104 g/m ² in women, and RWT < 0.43). For the purpose of this study, we defined reverse LV remodeling as the change of preoperative type of LV remodeling by at least one pattern toward normal LVM and geometry.

Systolic LV Function

We assessed LV systolic function by evaluation of ejection fraction (EF), fractional shortening (FS), midwall FS (mwFS), and circumferential end-systolic wall stress (cESS). EF was measured using the biplane Simpson’s method, and mwFS was calculated using a previously validated formula by de Simone et al. Circumferential end-systolic wall stress was estimated at the LV midwall level using a cylindrical model described by Gaasch et al. adjusted to the intraventricular LV pressure at the end of systole, which was calculated as a sum of the cuff systolic blood pressure and maximal Doppler-driven transvalvular gradient through stenotic native valve or valve prosthesis after surgery.

Diastolic LV Function

Doppler parameters of mitral inflow such as the mitral E and A waves (early and late diastolic filling velocities), mitral E-wave deceleration time, and the isovolumic relaxation time, were measured using pulse Doppler. Pulmonary venous flow measurements included peak systolic velocity, peak diastolic velocity, and peak atrial reversal velocity. According to the Canadian consensus recommendations for the measurement and reporting of diastolic dysfunction by echocardiography, the following patterns of LV filling were classified: normal pattern of LV filling, delayed relaxation, pseudonormal filling, and restrictive filling. The average values of early mitral annular diastolic velocity (e′) were obtained from both the septal and lateral sites and averaged for further evaluation. Subsequently, the ratio of mitral peak velocity of early filling to early diastolic mitral annular velocity (E/e′) was calculated. Improvement of diastolic function was defined as the change of preoperative pattern of LV diastolic function by at least one pattern toward normal LV filling parameters.

AS Severity Assessment

Peak and mean transaortic valve pressure gradients (PGs) and velocity-time integral (VTI) of transaortic velocity were measured using continuous-wave Doppler from different windows. The highest velocity was used for tracing the VTI. Effective aortic valve area (AVA) was calculated using the continuity equation and then indexed to body surface area. The ratio of LV outflow tract (LVOT) velocity to transaortic velocity was also calculated (VTI _LVOT /VTI _Ao ). Aortic valve prostheses were evaluated on the same basis as native valves. Patient-prosthesis mismatch (PPM) was diagnosed when the effective orifice area (EOA) was <0.9 cm ² /m ² .

Ultrasonic Tissue Characterization

To assess IBS signal, two regions of interest were chosen in the parasternal long-axis view: the mid septum and the mid posterior wall. The mean value of IBS was acquired from the region of interest for each imaged frame during the cardiac cycle and averaged for end-diastole and end-systole for all cardiac cycles throughout the cine loop. The absolute intensity of IBS at end-diastole (IBS _ed ) and at end-systole (IBS _es ) was obtained for both the septum and the posterior wall. The cyclic variation of IBS (CVIBS) was calculated as the difference between end-diastolic and end-systolic values (CVIBS = IBS _ed − IBS _es ) for the septum and the posterior wall ( Figure 1 ). Additionally, we calculated the index of CVIBS (CVIBS _index ) at the septum and at the posterior wall, which were calculated by use of the formula [(IBS _ed − IBS _es )/IBS _ed ] × 100. A detailed IBS acquisition methodology was described previously. All examinations were recorded on magneto-optical disks and analyzed offline by experienced echocardiographers (M.F., A.K., and R.G.) using a Philips Sonos 5500 revision D.2 with a 3s transducer (Philips Medical Systems, Andover, MA) by means of a commercially available acoustic densitometry software package. According to a previous study, a mean value of CVIBS > 6 dB was considered normal. The mean IBS parameters (mean CVIBS, mean IBS _ed , and mean CVIBS _index ) were defined as average values obtained from both the septum and the posterior wall. Additionally, we evaluated the sensitivity and specificity of preoperative mean IBS _ed , mean CVIBS, and mean CVIBS _index different thresholds for LV reverse remodeling occurrence after aortic valve surgery. Differences of preoperative and postoperative values were also calculated for all parameters (Δ).

Example of IBS curve of a patient with AS obtained from the parasternal long-axis view.

Reproducibility Data of IBS Evaluation

Fifteen randomly selected IBS evaluations were made twice by two echocardiographers to assess interobserver and intraobserver variability. Agreement between two measurements was considered as ±0.1 dB. Intraobserver and interobserver variability were good (κ = 0.74 and κ = 0.67, respectively).

Statistical Analysis

For the statistical analysis, Statistica for Windows version 9.0 (StatSoft, Tulsa, OK) was used. Continuous data are expressed as mean ± SD. Paired t tests were used to compare preoperative and postoperative parameters. One-way analysis of variance followed by Bonferroni’s post hoc test was used to assess the statistical difference between more than two groups of continuous parameters. To measure the strength of the relation between CVIBS and other echocardiographic parameters, Pearson’s correlation coefficient was calculated. The relation between clinical improvement after AVR and echocardiographic parameters was evaluated using multiple logistic regression analysis. Receiver operating characteristic (ROC) curve analysis was generated by MedCalc version 11.2.1 ( http://www.medcalc.com ) to test the predictive discrimination of IBS parameters. A p value < .05 was considered significant. The κ statistic was used to assess intraobserver and interobserver variability for IBS measurements.

Before AVR

Preoperative and postoperative clinical data of the patients enrolled in the study are outlined in Table 1 .

Echocardiographic preoperative and postoperative data obtained during the initial and follow-up examinations are outlined in Table 2 . Forty-three patients (74%) had LV hypertrophy (mean LVM, 262 ± 88 g; mean LVMI, 143 ± 45 g/m ² ). There was no correlation between LV hypertrophy and echocardiographic parameters of AS severity such as AVA, maximal PG, or VTI _LVOT /VTI _Ao . The prevalence of different LV remodeling patterns was as follows: normal geometry in three patients (5%), concentric remodeling in 20 patients (35%), concentric hypertrophy in 28 patients (48%), and eccentric hypertrophy in seven patients (12%). There were no significant differences of AS severity parameters among particular patterns of LV remodeling.

The prevalence of different patterns of LV diastolic dysfunction was as follows: normal diastolic function in 11 patients (20%), delayed relaxation in 36 patients (62%), pseudonormal filling in six patients (10%), and restrictive filling in five patients (8%). There was no significant difference of AS severity parameters in particular patterns of diastolic dysfunction.

IBS

The preoperative mean CVIBS was 5.8 ± 1.7 dB, mean IBS _ed was 36.2 ± 5.0 dB, and mean CVIBS _index was 17.1 ± 5.0%. Significantly lower values of mean CVIBS before surgery were observed in the subgroup of patients with eccentric LV hypertrophy in comparison with patients with LV concentric remodeling or hypertrophy. Additionally, significantly higher mean IBS _ed was observed in patients with eccentric LV hypertrophy in comparison with patients with normal LVM and dimensions ( Table 3 ). There were no significant differences of mean IBS values in patients with different diastolic filling patterns. However, in the subgroup of patients with mean CVIBS ≤ 6 dB before AVR in comparison with subjects with mean CVIBS > 6 dB, the initial maximal velocity of e′ was significantly lower (6.9 ± 2.5 vs 8.3 ± 2.0 cm/s, P < .05), and the E/e′ ratio was significantly higher (13.0 ± 7.2 vs 9.6 ± 2.9, P < .05). Both CVIBS and CVIBS _index at the septum and posterior wall showed positive significant correlations with EF, FS, and e′ and negative significant correlations with cESS and LVMI. There were no significant correlations between all evaluated IBS indices and AVA or mean or maximal PG ( Table 4 ).

Table 3

Mean CVIBS, mean IBS _ed , and mean CVIBS _index in different patterns of LV remodeling before AVR

Variable	NG	CR	CH	EH
Mean IBS ed (dB)	32.4 ± 3.3	36.2 ± 4.8	36.8 ± 5.2	41.2 ± 4.7 ∗
Mean CVIBS (dB)	6.4 ± 1.6	6.3 ± 1.7	5.7 ± 1.7	3.9 ± 1.8 †
Mean CVIBS index (%)	17.2 ± 2.9	18.7 ± 5.4	16.9 ± 4.7	12.9 ± 4.9

CH , Concentric hypertrophy; CR , concentric remodeling; EH , eccentric hypertrophy; NG , normal LVM and geometry.

∗ P < .05 for EH vs NG.

† P < .05 for EH vs CR and for EH vs CH.

Table 4

Correlation matrix ( R values) of mean IBS and selected echocardiographic parameters

Variable	EF	FS	mwFS	cESS	RWT	LVMI	AVA	Mean PG	e′
Septal CVIBS	0.32 ∗	0,26 ∗	0.22	−0.36 ∗	0.04	−0.34 ∗	0.03	0.02	0.50 ∗
Posterior wall CVIBS	0.35 ∗	0.28 ∗	0.17	−0.40 ∗	0.12	−0.27 ∗	0.10	0.06	0.42 ∗
Mean CVIBS	0.36 ∗	0.29 ∗	0.20	−0.39 ∗	0.04	−0.34 ∗	0.08	0.05	0.48 ∗
Septal IBS ed	0.22	0.20	0.21	−0.14	−0.05	−0.01	0.06	0.00	0.19
Posterior wall IBS ed	0.29 ∗	0.26	0.22	−0.24	0.00	−0.09	0.05	0.05	0.29 ∗
Mean IBS ed	0.27 ∗	0.24	0.22	−0.21	−0.01	−0.12	−0.01	0.02	0.25
Septal CVIBS index	0.27 ∗	0.20	0.17	−0.26 ∗	0.03	−0.35 ∗	−0.07	0.02	0.49 ∗
Posterior wall CVIBS index	0.36 ∗	0.29 ∗	0.16	−0.44 ∗	0.17	−0.37 ∗	−0.11	0.10	0.48 ∗
Mean CVIBS index	0.29 ∗	0.23	0.17	−0.32 ∗	0.07	−0.36 ∗	−0.08	0.08	0.50 ∗

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