## Background

Left ventricular outflow tract (LVOT) geometry is variable and often elliptical, which can affect aortic valve area calculation in patients with aortic stenosis (AS). Specific differences in LVOT geometry and dynamics between patients with AS and normal control subjects have not been described. The aim of this study was to test the hypothesis that differences in LVOT geometry in patients with AS might relate to variable LVOT remodeling and stiffness relative to normal control subjects.

## Methods

In 54 patients with severe AS and 33 control subjects without AS, LVOT geometry, dynamics, remodeling, and stiffness were assessed by three-dimensional transesophageal echocardiography. LVOT stiffness was measured by calculating the distensibility coefficient, defined as the percentage change in LVOT area relative to change in left ventricular pressure. LVOT remodeling was assessed by measuring the posterior LVOT wall thickness. Multivariate linear regression analysis was used to determine independent associations with peak systolic LVOT ellipticity. LVOT area by three-dimensional transesophageal echocardiographic planimetry was compared with areas obtained assuming circular or elliptical geometry.

## Results

At end-diastole, LVOT geometry was similar between patients with AS and normal control subjects. In patients with AS, however, the percentage change in cross-sectional area (7.5% vs 14.7%, *P *< .001) from end-diastole to peak systole was lower compared with normal control subjects, while peak systolic ellipticity index was higher in patients with AS (1.18 vs 1.08, *P *< .001). Compared with control subjects, patients with AS had lower distensibility coefficients (4.7 ± 1.9 × 10 ^{4 }vs 12.5 ± 5.3 × 10 ^{4 }mm Hg ^{−1 }, *P *< .001) and higher posterior LVOT wall thickness (3.5 ± 0.8 vs 2.3 ± 0.5 mm, *P *< .001). In multivariate analysis, posterior LVOT wall thickness and distensibility coefficient were independently associated with peak systolic LVOT ellipticity index. LVOT area underestimation by transthoracic echocardiography was higher in patients with AS when assuming circular geometry (20% vs 12%, *P *= .001).

## Conclusions

The LVOT is less distensible and undergoes remodeling in severe AS. These changes lead to greater peak systolic ellipticity and greater LVOT cross-sectional area underestimation relative to normal control subjects. These findings have important implications for the assessment of AS severity.

Current guidelines define severe aortic stenosis (AS) as an aortic valve area (AVA) < 1.0 cm ^{2} , a cutoff based on the assumption of circular left ventricular outflow tract (LVOT) geometry when using the continuity equation to determine AVA. However, recently published data using three-dimensional (3D) echocardiography, cardiac computed tomography, and cardiac magnetic resonance imaging have demonstrated that the LVOT in patients with AS is, in fact, often elliptical, with a smaller dimension in the anteroposterior plane. In these cases, the calculated LVOT cross sectional area (CSA), and therefore, the continuity equation–derived AVA assuming circular geometry could significantly underestimate the true LVOT CSA and AVA, respectively.

Importantly, many patients with AS have discordant parameters of AS severity whereby AVA by the continuity equation is < 1.0 cm ^{2} , yet the peak velocity and mean gradient are in the mild or moderate range. In these patients, LVOT CSA and, therefore, AVA, underestimation due to elliptical LVOT geometry may be the cause of discrepant indices of AS severity and subsequent clinical uncertainty. We hypothesized that fibrocalcific remodeling and altered systolic LVOT dynamics affect peak systolic LVOT geometry. We sought to evaluate LVOT geometry, dynamics, stiffness, and remodeling in both patients with AS and normal control subjects without structural heart disease by 3D transesophageal echocardiography (TEE). Last, we determined the average degree of LVOT CSA underestimation when assuming circular or elliptical LVOT geometry relative to 3D transesophageal echocardiographic planimetry.

## Methods

## Patient Population

Fifty-eight patients with severe AS who were referred to our institution for transcatheter aortic valve replacement between 2008 and 2010 were retrospectively identified. Patients underwent comprehensive two-dimensional (2D) transthoracic echocardiography (TTE) within 1 week and 3D TEE using an iE33 system (Philips Medical Systems, Andover, MA) at the time of the procedure. A second cohort of 33 patients without AS or other structural heart disease who underwent 2D TTE and 3D TEE for varying indications between 2006 and 2013 were included as a control population. Indications for TEE in control patients included assessment for patent foramen ovale, atrial septal defect, or source of embolus in the setting of stroke or transient ischemic attack. None of the patients in the control group had greater than mild valvular regurgitation or stenosis of any kind or reduced left ventricular systolic function (defined as ejection fraction < 50%). Patients with known bicuspid aortic valves or dilated left ventricles (defined as end-diastolic dimension > 55 mm) were excluded from both groups. Baseline demographic, clinical, and imaging data were collected and complete for all patients.

## Three-Dimensional Transesophageal Echocardiographic Image Acquisition and Analysis

Three-dimensional transesophageal echocardiographic images of the LVOT and aortic valve were acquired in either 3D zoom or single-beat full-volume mode. The lateral width, elevation width, and depth were optimized to maximize spatial and temporal resolution before image acquisition. The minimum temporal resolution of all images analyzed was ≥10 Hz, as previously recommended. Patients with arrhythmias were not excluded, because multiple-beat 3D acquisitions were not used in the analysis. Offline multiplanar reconstruction of 3D transesophageal echocardiographic data sets was performed for quantitative analysis of the LVOT.

## LVOT Geometry and Dynamics

The LVOT anteroposterior diameter was measured during peak systole in all patients by 2D TTE and used to calculate the LVOT CSA assuming circular geometry according to current guidelines. Using 3D TEE, LVOT geometry was assessed with offline multiplanar reconstruction of 3D data sets. The cropping plane was first aligned to the LVOT 4 mm below the aortic annulus at end-diastole (defined as immediately before the R wave) and during peak systole (defined as maximal aortic valve opening) to create a cross-sectional view of the LVOT. The LVOT minor axis (anteroposterior dimension), major axis (medial-lateral dimension), and CSA by direct planimetry were measured at both end-diastole and peak systole. The LVOT CSA was also determined by 3D TEE–derived measurements assuming circular (CSA = π *r *^{2 }, where is *r *is the LVOT radius) and elliptical geometry (CSA = π · *r *_{1 }· *r *_{2 }, where *r *_{1 }and *r *_{2 }are the LVOT semimajor and semiminor axes, respectively). The LVOT ellipticity index (EI) was calculated as the ratio of the major and minor axes. LVOT dynamics were assessed by determining the percentage change in LVOT geometric indices (i.e., the deformation of the LVOT) from end-diastole to peak systole.

## LVOT Stiffness

Within a subset of 48 subjects (28 patients with AS and 20 control subjects), LVOT stiffness was evaluated by calculating the distensibility coefficient (DC), which represents the relative change in LVOT CSA, respectively, for a given change in left ventricular pressure. The DC is calculated as follows:

DC = ( CSA S − CSA D ) / CSA D LVP S − LVP D ,

_{S }is peak systolic LVOT area, CSA

_{D }is end-diastolic LVOT area, LVP

_{S }is systolic left ventricular pressure, and LVP

_{D }is diastolic left ventricular pressure. The compliance coefficient, which represents the absolute change in LVOT CSA for a given change in left ventricular pressure, was also similarly determined. LVOT CSA by 3D transesophageal echocardiographic planimetry was used for both indices. Left ventricular pressure was invasively determined immediately before transcatheter aortic valve replacement in all patients with AS at the time of 3D transesophageal echocardiographic image acquisition. In non-AS control subjects, systolic blood pressure at the time of TEE was used to approximate left ventricular systolic pressure, while left ventricular diastolic pressure was assumed to be 10 mm Hg in these patients.

## LVOT Remodeling

As an index of LVOT remodeling, we measured the thickness of the intervalvular fibrosa, which comprises the posterior aspect of the LVOT wall. Two measurements were made and averaged for each patient at peak systole with the 3D image magnified and gain optimized at a level 4 mm below the level of the aortic annulus. Posterior LVOT wall thickness measurements were also confirmed by 2D imaging. The basal interventricular septum (which makes up the anterior LVOT border) and the ratio of the interventricular septum to the posterior wall (as a marker of upper septal hypertrophy) was also assessed by 2D TTE for all patients. Upper septal hypertrophy was defined as a ratio of interventricular septum to posterior wall thickness of ≥1.3, as previously defined. We also determined the frequency of visible LVOT calcification in the AS group by 3D TEE. LVOT calcification was considered present if there was clear evidence of focal hyperreflectance with an associated region of thickening measuring ≥2 mm.

## LVOT CSA Underestimation

The average degree of LVOT CSA underestimation assuming circular or elliptical geometry to the true LVOT CSA by 3D transesophageal echocardiographic planimetry was calculated in both groups. The percentage LVOT CSA underestimation is equivalent to continuity equation–derived AVA underestimation in patients with AS and was determined as follows:

% Underestimation = 100 × ( CSA P − CSA X CSA P ) ,