DISCUSSION
In this study we documented for the first time that both SVD and LVEDD
(or LVEDV) were significantly correlated with LVOTD in addition to
patient BSA and height (or gender) in patients undergoing
echocardiography. SVD had the strongest association with LVOTD. On the
basis of these observations, we derived a comprehensive equation
including SVD, LVEDD and patient BSA and height, which showed a high
correlation with LVOTDM and better performance than
LVOTDBSA in a validation patient cohort. Alternative
equations including LVEDV instead of LVEDD with/without gender were also
obtained but did not improve the results of the primary analysis.
Limits of anthropometric variables in determining chamber and
aortic root dimensions in adults. Aortic root normal-reference studies
have notoriously shown low correlation between anthropometric variables
(mainly BSA and height) and SVD in adults (18,19). For example, in the
EACVI NORRE aortic root study, linear models considering age, gender,
and body size barely explained around one-quarter of the total variance
in determining aortic root dimension in adults (19). This is why
regression equations for prediction of aortic size (and derived
nomograms) based only on these parameters should be interpreted with
caution, taking into account this limitation (19). In our derivation
study, BSA showed moderate correlation with LVOTD and low correlation
with SVD. Even in our validation study, LVOTDBSA had
moderate correlation with LVOTDM, reflecting moderate
correlation between BSA and LVOTD. These observations are in line with
previously reported correlations (14,18,19). All these findings indicate
that the wide biological variability in aortic and LVOT dimension is not
entirely explained by simple demographic and anthropometric variables
(19).
In our study, a regression equation including anthropometric and
biologic (LV and aortic root) dimensions had high correlation with
LVOTDM in the validation group. These results may be
explained by a proximity anatomical effect in distorting the LVOT
independently from BSA. To our knowledge, this correlation has never
been explored before. Interestingly, both intra-and inter-observer
variability of LVOT area derived from regression equations were lower
than those related to the measured LVOT, which were similar to previous
findings (22). This may be due to the well-known amplification of the
error derived from squaring the LVOTD measurement when calculating the
LVOT area.
Clinical implications and perspectives . There are two main
clinical messages from this study: 1) measures of LV output and aortic
stenosis severity that avoid use of LVOTD measurement may be misleading
in particular anatomical conditions, namely abnormal LV and aortic root
dimensions; 2) a well-performing formula for predicting LVOTD is now
available accounting not only for anthropometric data but also for LV
and aortic root dimensions.
Regarding the first message, it should be underlined that, while LVOT is
a BSA-dependent measure (14,15), LVOT velocity-time integral (or stroke
distance) has been hypothesized to be independent on BSA and to
represent, therefore, a SVI analog (15). However, two issues limit this
assumption. Firstly, the BSA independency was originally supposed in
normal individuals (15): in these subjects a minor role of LV cavity and
aortic root dimension is expected. However, in patients with aortic root
enlargement, normal BSA and reduced stroke distance suggesting a low
flow status, a relatively high LVOTD assures a normal SVI. For example,
with a BSA of 1.8 m2, a stroke distance of 12 cm and a
LVOTD of 27 mm, SVI is 38 ml/m2. Secondly, the
accuracy of stroke distance has never been compared for assessing LV
output with invasive measurement, whereas SV (or other LVOTD-including
measures such as cardiac output) has shown high correlation with the
invasive measurement in several studies (22-31). In addition, comparing
the usefulness of SVI and stroke distance as prognostic markers, a
better stratification capability of SVI was shown in one study (16).
The LVOTD measurement is also avoided in the aortic dimensionless index,
which has been proposed in addition to aortic valve area calculation for
aortic stenosis grading (7). Although the dimensionless index has shown
prognostic value in asymptomatic and minimally symptomatic patients with
aortic stenosis with preserved LV ejection fraction and without
significant valve regurgitation (32), it was not better than other
markers of aortic stenosis severity, including aortic valve area, for
grading aortic valve stenosis in another study (33).
Our findings evidence pathophysiological reasons to encourage
calculation of SVI and aortic valve area over stroke distance and
dimensionless index whenever possible in the assessment of LV output and
aortic stenosis severity grading. In particular, the interpretation of
LVOTD-free indexes should be taken with caution in cases of abnormal LV
and aortic root dimensions.
Previous studies tried to overcome the limits of LVOTD measurement by
using alternative techniques, such as three-dimensional echocardiography
(34) and multidetector computed tomography (35) for the assessment of
aortic stenosis severity. However, it should be noticed that different
techniques could imply different cut-off values to refer to for
prognostic assessment: for example, an aortic valve area cut-off value
of 1.2 cm2 should be used for assessing aortic
stenosis severity with a hybrid multidetector computed
tomography-Doppler approach rather than the established 1
cm2 obtained with the standard ultrasound method
(7,35). Thus, in current clinical echocardiographic practice measuring
LVOTD remains an almost inevitable, although sometimes difficult task.
Study limitations. 1) We recognize that our formula uses four
different variables (BSA, height, SVD and LVEDD), thus it might seem too
complicated for clinical practice. However, those measures are commonly
obtained in standard echocardiography and the equation could be easily
integrated in the echocardiograph to give an automatic response once all
the measurements are performed, without additional time consume. In
addition, many reporting software can provide derived calculations (such
as the aortic valve area) automatically and could therefore integrate
our formula as an assistance tool for cases in which LVOTD is scarcely
or incorrectly visualized. 2) Our formula includes both BSA and height.
Although height is one of the variables used for the calculation of BSA,
there was no significant multicollinearity in the regression model
(variance inflation factor for height and BSA were 2.2 and 2.1,
respectively), thus both variables were included in the formula. 3)
Multidetector computed tomography was not performed in this study as an
external reference for TTE LVOTD evaluation. However, we documented that
in our patients the LVOTD measurements at TTE and TEE were similar, thus
indicating accuracy of TTE measurements. Our data are in line with those
of Leye et al., who showed a very high correlation between TTE and TEE
for measuring the LVOTD (R=0.95, P<0.001; P=0.26 for
difference between techniques) (14). 4) LVEDD was chosen as LV dimension
parameter for the primary endpoint rather than LVEDV because of the
proximity between LVEDD and LVOTD measurement sites (the basal LV and
the LVOT, respectively). Whether three-dimensional echocardiography
would have given a higher correlation between LV volumes and LVOTD is
unknown. However, the regression equation including LVEDD had the
highest correlation with LVOTDM. 5) In the present study
LVOTD was measured at the level of the annulus, which is considered the
preferred site by current guidelines on aortic stenosis assessment (7),
even though there is lack of general consensus and some laboratories use
a more proximal site (up to 1 cm apical to the annulus) for this
measure. Our findings may not be applied to predicting LVOTD at
different levels of the LVOT. Evidences in support of the measurement at
the level of the aortic annulus have been recently reviewed (36), in
addition to a very recent phase-contrast cardiovascular magnetic
resonance comparative study (37).
Conclusions . We documented that aortic root and LV dimensions
affect LVOTD independently from anthropometric data in an adult heart
failure patient cohort. On this ground, it is evident that bypassing
LVOTD measurement with surrogate markers of LV output (stroke distance)
and dimensionless indexes in aortic stenosis severity grading may be
misleading, especially in presence of abnormal LV cavity and aortic root
dimensions. A comprehensive equation for predicting LVOTD, including
aortic root and LV dimensions, was derived and validated in the present
study to help the physician in the calculation of LVOTD when it is
difficult to calculate. Further multicenter investigations are needed to
support a more extensive application of our formula in routine
echocardiographic clinical practice.
Conflicts of Interest: Nothing to disclose.