Improving Echo Measurements in the Diagnosis of Aortic Stenosis

OBJECTIVES Primary Objective The primary objective of this study is to review the current
practice of transthoracic echocardiogram (TTE) imaging measurements in conjunction with
computerized tomography (CT) and to standardize these measurements in order to improve the
accuracy of the diagnosis of aortic stenosis (AS).

Secondary Objective The secondary objective of the study is to define the true incidence of
low flow, low gradient severe aortic stenosis with a normal ejection fraction (EF).

BACKGROUND In recent years, the advancement of medical technology has allowed certain
patients to undergo less invasive approaches for aortic valve replacement such as
transcatheter aortic valve replacement (TAVR). In order to appropriately select treatment
options, anatomical measurements must be accurately obtained utilizing TTE and CT.

According to the American College of Cardiology/American Heart Association Practice
Guidelines, the severity o f aortic stenosis is determined by definitions of aortic jet
velocity, mean pressure gradient, and aortic valve area (AVA) (Bonow, 2008).

Mild Moderate Severe AVA (cm2) 1.5 1.0 - 1.5 < 1.0 Mean gradient (mmHg) < 25 25 - 40 > 40
Jet velocity (m/s) < 3.0 3.0 - 4.0 > 4.0

Rationale for study

Of greatest interest to this study is the calculation of the AVA in the diagnosis of the
severity of aortic stenosis. Since the area cannot be directly measured from
echocardiographic images, it is calculated based on the diameter across the left ventricular
outflow tract (LVOT) as measured via TTE. The preferred modality for measuring AVA is the
continuity equation:

AVA=((〖Area〗_LVOT ×〖VTI〗_LVOT))/〖VTI〗_AS Where LVOT = Left Ventricular Outflow Tract, VTI =
Doppler velocity-time interval.

Using TTE, the stroke volume at the LVOT is obtained by measuring the diameter across the
LVOT. The continuity equation assumes the aortic valve annulus is a perfect circle; because
of this, any error in measuring the LVOT results in an under calculation of the aortic valve
area. It is also important to consider that the anatomy of the aortic annulus is not
circular, which also contributes to an inaccurate calculated AVA.

An underestimated valve area could lead to a diagnosis of severe aortic stenosis when not
appropriate. Recently, there has been an increase in literature published on the diagnosis
of severe aortic stenosis with a low mean gradient and preserved left ventricular function
as measured by ejection fraction (EF). It is possible that many of these patients do not
have severe AS but are misclassified as such because underestimation of the LVOT diameter
leads to underestimation of aortic valve area as calculated by the continuity equation. This
study aims to define the true incidence of these patients by ensuring the aortic valve area
is measured as accurately as possible based on current imaging procedures.

In order to determine the accuracy of TTE measurements in current practice, this study would
compare the LVOT diameter from TTE to the LVOT diameter on CT scans, which is inherently
three-dimensional and therefore more accurate.

The AVA of all subjects will be re-calculated using the continuity equation and the LVOT
diameter measured with CT. These re-calculated AVA will be compared to the original AVA
obtained via TTE. In subjects whose newly calculated AVA, utilizing CT measurements, varies
greatly from their TTE calculated AVA, the original TTE images will be re-evaluated for
correct measurements. Additionally, any subject with a TTE-measured LVOT diameter less than
2 cm will also be re-evaluated for correct measurement.

The figure below illustrates an underestimated LVOT diameter using 2D echocardiography.

Anumeha Tandon, Paul A. Grayburn, Imaging of Low-Gradient Severe Aortic Stenosis, JACC:
Cardiovascular Imaging, Volume 6, Issue 2, February 2013, Pages 184-195, ISSN 1936-878X,
http://dx.doi.org/10.1016/j.jcmg.2012.11.005.

(http://www.sciencedirect.com/science/article/pii/S1936878X12009497)

PATIENT POPULATION

This study is an observational, retrospective review of data collected as standard of care.
The study intends to review the charts of up to 400 patients over the last 5 years who
underwent both CT and TTE within a one-week timeframe as a workup for aortic valve stenosis
at The Heart Hospital Baylor Plano (THHBP) or Baylor University Medical Center (BUMC).

SUMMARY Enrollment Up to 400 patients at THHBP and BUMC Design This study is a retrospective
chart review of previously collected standard of care data.

METHODS, STATISTICAL ANALYSIS & DATA MANAGEMENT Patients will be classified as severe or
non-severe AS based on aortic valve area calculation as per ACC/AHA guidelines. Thus,
patients with AVA ≤ 1.0 cm2 will be considered severe AS. This will also be evaluated using
two other widely used criteria for aortic valve area indexed for body surface area. Severe
AS will be considered as AVAi ≤ 0.6 cm2 (guidelines) or ≤ 0.5 cm2 (Braunwald's text,
Grayburn). Using these three definitions, any patient who also has a peak velocity ≥ 4.0 m/s
or a mean gradient ≥ 40 mmHg will be considered to definitely have severe AS. Patients with
values < 4.0 m/s or < 50 mmHg will be further classified by stroke volume index < 35 mL/m2
to have low flow, low gradient severe AS. Further classification will be based on LVEF ≥ 50%
or <50%. The former will be considered to have paradoxical low flow, low gradient severe AS
with preserved LVEF (Hachicha, Circ 2007) or traditional low flow, low gradient severe AS
(Tandon, Grayburn JACC Imaging 20130> The above criteria will be used to reclassify patients
when LVOT cross-sectional area is determined by CT scan instead of echocardiography.
Reclassification will occur with CT measurements of LVOT for AVA and SVI, both of which are
dependent on LVOT area, generalized linear mixed model (GLMM) with a logistic link function
will be used to assess whether differences in classification exist.

The same multivariable model stratified by gender will be used to perform a pre-specified
subgroup analysis (re-measuring the echocardiographic LVOT diameter on all subjects who are
"re-classified" by CT). This will be done by remeasuring at the traditional LVOT diameter
located 5-10 mm below the aortic annulus and also by measuring at the juncture of the aortic
leaflets and LVOT in mid-systole (Mayo clinic way). The purpose of this analysis is to
determine if the Mayo clinic method of LVOT measurement reduces the number of
misclassifications compared to the traditional method. Finally, the investigators will also
examine the CT data for threshold values which suggest erroneous or outlier values for
echocardiography. Men and women will be assessed separately. For example, a value of 1.6 cm
is often found on echocardiography but rarely on CT scanning in their subjective clinical
experience.

Inclusion Criteria

- Adults over the age of 18.

- Any patient undergoing both TTE and CT scans within a one-week timeframe as a workup
for aortic stenosis.

Exclusion Criteria

- There are no specific exclusion criteria for this retrospective review.