ONLINE APPENDIX
Aortic Valve Area Calculation in Aortic Stenosis: Is Computed Tomography
Superior to Doppler Echocardiography?
Marie-Annick Clavel, DVM, PhD1, Joseph Malouf, MD1, David Messika-Zeitoun, MD,
PhD2,3, Phillip A. Araoz, MD1, Hector I. Michelena, MD1, Maurice Enriquez-Sarano,
MD1
METHODS
Scanning parameters:
The scanning parameters were 120kVP and 650mAs. Standard LVOT assessment
involved storage of high-quality static images of the LVOT, with careful positioning of
the imaging plane at the bottom of aortic cusps and orthogonal to its long-axis, using
electrocardiographic gating at 70% of the RR interval and reconstructed with a slice
width of 0.75 mm.
Charlson score index:
The age weighted Charlson score index was created to predict the risk of death from
comorbidities in longitudinal studies. The index takes into account the number but also
the seriousness of comorbid diseases (Charlson J. Chronic Dis. 1987).
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End-point:
Online Table 1: Summary of end-points, follow-up measurements and events.
Time
Endpoint
start
End
(whichever
comes first)
AVR
Death
End FU
Event noted
Event
Excluded event
Death only
Death after AVR
AVR
378
Pt-yr
55
Not counted
as event
Measured
Time Events
Survival under
medical management
Diagnosis
Total Mortality
Diagnosis
Death
End FU
Death only
No death excluded
AVR
826
Pt-yr
90
Death or AVR
Diagnosis
AVR
Death
End-FU
Death
AVR
Death after AVR
(AVR counted as
the earlier event)
--
378
Pt-yr
201
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RESULTS
Echocardiographic and Dynamic MDCT measurements of LVOT/Annulus and AVA
In patients in whom dynamic MDCT measurements were available (n=135), the correlation
between phasic measurements of LVOTArea by MDCT was excellent (r=0.90; p<0.0001). These
LVOTArea measures by MDCT showed reasonable correlations with the area calculated by
echocardiography (both r≥0.71; all p<0.0001). However, LVOTArea by echo (3.86±0.71 cm2)
was smaller (all p<0.001) than LVOTArea by CT. Dynamic 4D-MDCT showed slight variations
in phasic measurement of LVOT eccentricity with less eccentricity in systole (eccentricity index:
0.83±0.07 vs. 0.77±0.09; p<0.001). The phasic differences reached significance (p<0.001) but the
higher measurement in systole was minimal in magnitude (4.74±0.98 vs. 4.46±0.95 cm2).
Fig.SM1 shows correlation and agreement between the different technics used to calculate AVA.
Fig.SM2 shows correlation and agreement between AVAEcho and AVACT in the whole cohort.
Relationship between Mean Gradient and Indexed AVACT or Indexed AVAEcho
The correlation between mean gradient and Indexed AVA was better (Wolfe-p=0.001) for
Indexed AVAEcho (r=-0.65; p<0.0001) than Indexed AVACT (r=-0.60; p<0.0001).
Spline curve analysis and threshold definition:
The definition of threshold for excess mortality was done with the use of spline curve of
mortality (y-axis: relative risk of mortality within the series; y-axis: AVA Echo or CT – Fig. 6).
The interception between the spline curve itself and the relative risk of 1 (mean risk for the
series) was the best cut-off value to define excess mortality. Interestingly, this intercept was for
AVAEcho of 1cm2, which also is the cut point used in the guidelines and was for AVACT of 1.2
cm2.
A second threshold of 0.8 cm2 for AVAEcho and 1cm2 for AVACT represent the intersection
between the lowest 95% confidence interval of the spline curves and the relative risk of 1. This
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second threshold was also analyzed due to the intense controversy on appropriate AVA
thresholds to define excess mortality in aortic stenosis.
Discordance in AS severity grading by AVACT or AVAEcho
Our series comprised 205 patients with preserved LV ejection fraction (≥50%). Among those, 27
(13%) had a low ΔP despite tight AVA by echocardiography (AVAEcho≤1cm2). For AVACT,
using the threshold for tight AVA of AVACT≤1.2 cm2 defined in the survival analysis (see
below), low ΔP affected 25 (12%) patients, a proportion identical (p=0.75) to that defined by
AVAEcho≤1cm2. The eccentricity index by MDCT did not affect the concordance Mean GradientAVAEcho and was equivalent (p=0.50) between patients with discordant AS severity
echocardiographic grading (0.80±0.07) vs. those with concordant moderate (0.80±0.07) or severe
(0.80±0.08) AS. Thus, in all subsets and with any threshold, AVACT did not improve the
concordance of AS severity grading.
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Impact of AVAEcho and AVACT on survival in AS: Net reclassification index
In order to assess the potential superiority of AVACT we calculated the net
reclassification index (NRI) at 1 year using AVACT instead of AVAEcho. Among our
patients, 13 (5%) were classified as non-severe AS with AVAEcho and were reclassified as
severe AS with the use of AVACT, while 21 (8%) were classified as severe AS with
AVAEcho and were reclassified as non-severe AS with the use of AVA-CT.
Online Table 2: Classification of AS severity according to AVAEcho and AVACT in
deceased and alive patients at 1 year:
62 Deceased patients at 1 year:
AVAEcho>1.0cm2
AVAEcho≤1.0cm2
AVACT>1.2cm2
4
8
AVACT≤1.2cm2
1
49
AVAEcho>1.0cm2
AVAEcho≤1.0cm2
AVACT>1.2cm2
54
8
AVACT≤1.2cm2
6
37
105 Alive patients at 1 year:
Thus the NRI at 1 year was -9%, that representing a “worsening” of classification, while
didn’t reach statistical significance (p=0.81) with regards to survival prediction.
Online Figure 1: Correlations (Panels A, C, E and G) and agreements (Bland-Altman
plot; Panels B, D, F and H) between the Echocardiography and Multi-detector Computed
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Tomography for estimation of aortic valve area in the subset of 135 patients with all
measurements.
Online Figure 2: Correlation (Panel A) and agreement (Bland-Altman plot; Panel B)
between the Echocardiography and Multi-detector Computed Tomography for estimation
of aortic valve area in the whole cohort (n=269)
Online Figure 3: Correlations between mean gradient and indexed aortic valve area in
the whole cohort. Indexed AVA was calculated by Doppler-echocardiography (Indexed
AVAEcho: Panel A), MDCT with LVOT measurement (Indexed AVACT: Panel B).
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Online Figure 1
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Online Figure 2
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Online Figure 3
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