Supplementary Table 1. Studies on the percentage of severe AS patients experiencing symptoms
I. Severe AS and symptomatic
Symptoms linked to
Author
Year
Study Design
Population
Definition severe AS
Numerator
Denominator
severe AS
205 - 44
Median 78
Bouma
Prospective registry,
1991-
1999
asymptomatic= 161
years
AVA≤1.0 cm2 or
Asymptomatic: no angina
36% male
gradient ≥50 mm Hg
or dyspnea (NYHA I)
205 patients;
1993
symptomatic severe
(35)
3 academic centers, the Netherlands
Iung
Prospective registry
Mean 80 years
AVA≤0.6 cm2/m2 of
5001 VHD patients;
47% male
BSA and/or gradient ≥50
2005
2001
(22)
AS
92 centers, 25 European countries
Asymptomatic: NYHA I
216 symptomatic
or II and no angina
severe AS
284 severe AS
mm Hg
740 – 338
Retrospective database
Pai
exertional angina,
1993-
740 patients;
Mean 71 years
asymptomatic = 402
AVA≤0.8 cm2
2006
2003
1 academic center, Loma Linda
shortness of breath, or
51% male
syncope
CA, US
1997-
Retrospective database
AS
Mean 73 years
71% of 140
AVA≤1.0 cm2
2010
740 severe AS
symptomatic severe
(36)
Bakaeen
205 severe AS
2008
345 patients;
Gender NR
NR
345 severe AS
medically treated and
1
(37)
1 VA center, Houston TX, US
96% of 205 SAVR
treated are
symptomatic296
symptomatic severe
AS
Retrospective database
Dua
exertional angina, syncope,
2006-
187 patients;
Mean 74 years
147 symptomatic
AVA≤1.0 cm2
2011
2008
1 academic center, Loma Linda
presyncope, heart failure
56% male
187 severe AS
severe AS
(38)
symptoms
CA, US
Retrospective database
AVA≤1.0 cm2, gradient
Badran
2008-
178 patients;
Mean 79 years
146 symptomatic
≥40 mm Hg, or ‘visually
2012
2010
1 academic center, Southampton,
Dyspnea, syncope, angina
48% male
178 severe AS
severe AS
severe’
(39)
UK
Moderate/severe AS, at
least one:
One of:
Babcock
20082012
Mean 73 years
833 patients;
2010
(40)
AVA<1.0 cm2, gradient
Retrospective database
52% male
1 academic center, Jacksonville FL
Angina, syncope or
133 symptomatic
dyspnea consistent with
moderate/severe AS
>40 mm Hg,
179 severe AS
Vmax>4m/s, or
NYHA II
“dimensionless index
≤0.25)
2
AS, aortic stenosis; AVA, aortic valve area; BSA, body surface area; echo, echocardiography; NR, not reported; NYHA, New York
Heart Association; US, United States, UK, United Kingdom; VA, Veterans Affairs; VHD, valvular heart disease; Vmax, peak velocity.
3
Supplementary Table 2. Studies on percentage of symptomatic severe AS patients who did not undergo SAVR and are potential
TAVR candidates
II. Not treated with SAVR, potentially treatable with
TAVR
Symptoms linked to
Author
Years
Study Design
Population
Definition severe AS
Numerator
Denominator
severe AS
Prospective registry,
Median 78
Bouma
1991-
205 patients;
years
AVA≤1.0 cm2 or
1999 (35)
1993
Three academic centers, the
36% male
gradient ≥50 mm Hg
Asymptomatic: no
135-79=56 not
135
angina or dyspnea
treated with SAVR
symptomatic
(NYHA I)
severe AS
Netherlands
Prospective registry
Mean 80 years
AVA≤0.6 cm2/m2 of
Iung
2001
5001 VHD patients;
47% male
216
Asymptomatic: NYHA
72 not treated with
I or II and no angina
SAVR
BSA and/or gradient
2005 (22)
symptomatic
≥50 mm Hg
92 centers, 25 European countries
severe AS
73
Retrospective database
Charlson
1995-
Angina, CHF, dyspnea,
Mean 81 years
AVA≤0.8 cm2 or
124 patients;
2006 (41)
1997
29 not treated with
symptomatic
SAVR
severe AS
syncope, fatigue,
35% male
gradient ≥50 mm Hg
Two academic centers, US
exercise intolerance
above 80 year
Pai
1993-
Retrospective database
Mean 71 years
AVA≤0.8 cm2
Exertional angina,
402-188=214 not
402
4
2006 (36)
2003
740 patients;
51% male
shortness of breath, or
one academic center, Loma Linda
treated with SAVR
syncope
symptomatic
severe AS
CA, US
Prospective registry
Descoutures
2006-
66
Mean 83 years
AVA≤0.7 cm2
66 patients;
2008 (42)
2007
66-31=35 not treated
NR
58% male
symptomatic
with SAVR
one academic center, Paris, France
severe AS
AVA≤0.9 cm2 ,
Retrospective database
Bach
369 patients;
297
Three (VA, academic, private)
Angina, syncope,
or “clinical impression
(pre)syncope, dyspnea,
consistent with severe
heart failure symptoms
Mean NR#
2005
2009 (43)
gradient ≥40 mm Hg,
% male NR#
126 not treated with
symptomatic
SAVR
severe AS ***
centers, US
AS”
71% of non-SAVR
Retrospective database
Bakaeen
1997-
296
Mean 73 years
AVA≤1.0 cm2
345 patients;
2010 (37)
2008
group was
NR
Gender NR
symptomatic
symptomatic:
One VA center, Houston TX, US
severe AS
0.71*140=99
Retrospective database
71% of non-SAVR
Exertional angina,
Dua
2006-
187 patients;
Mean 74 years
AVA≤1.0 cm2
2011 (38)
2008
One academic center, Loma Linda
147
group was
(pre)syncope, heart
56% male
symptomatic
symptomatic:
failure symptoms
CA, US
Chitzas
2000-
Retrospective database
severe AS
0.71*81=58
Mean 73 years
AVA≤1.0 cm2 or
Angina, dyspnea on
77% of non-SAVR
130
5
2011 (44)
2007
132 patients;
100% male
gradient ≥40 mm Hg
One VA center, San Francisco CA,
exertion, shortness of
group was
symptomatic
breath, syncope
symptomatic:
severe AS***
US
0.77*56=43
Prospective registry
Pierard
2000-
192 patients;
Mean 83 years
AVA≤1.0 cm2 and
Angina, NYHA III/IV,
66 not treated with
2011 (45)
2007
One academic center, Brussels,
44% male
gradient ≥30 mm Hg
syncope
SAVR
163
Belgium
Moderate/severe AS, at
least one of:
Retrospective database
One of:
133
AVA<1.0 cm2,
Babcock
2008-
833 AS patients;
Mean 73 years
Angina, syncope or
50 not treated with
symptomatic
dyspnea consistent
SAVR
moderate/seve
gradient >40 mm Hg,
2012 (40)
2010
One academic center, Jacksonville
52% male
Vmax>4m/s, or
FL, US
with NYHA II
re AS
“dimensionless index
≤0.25)
***Based on Dua et al and Bakaeen et al. We assumed that 4% of the SAVR patients were asymptomatic. #The total unoperated group
(191) had a mean age of 73 years and 62% were males.
6
AS, aortic stenosis; AVA, aortic valve area; BSA, body surface area; CHF, congestive heart failure; NR, not reported; NYHA,
New York Heart Association; SAVR, surgical aortic valve replacement; TAVR, transcatheter aortic valve replacement; US, United
States, UK, United Kingdom; VA, Veterans Affairs; VHD, valvular heart disease; echo, echocardiography; Vmax, peak velocity
7
Supplementary Table 3. Studies on the percentage of potential TAVR candidates that received TAVR
III. Treated with TAVR
Symptoms linked
Author
Years
Study Design
Population
Definition severe AS
Numerator
Denominator
to severe AS
Prospective registry
“Compassionate use or meeting
Dewey
2005-
Mean 80 years
AVA<1.0 cm2 and
current trial inclusion criteria”
2008 (46)
2007
105 referred for
NR
48% male
21 underwent TAVR
Vmax>3.5m/s
TAVR
105 patients
One academic center, Dallas TX, US
Prospective registry
Otten
2005-
100 patients
Mean 82 years
100 referred for
NR
2008 (47)
2007
One academic center, Rotterdam, the
NR
39 underwent TAVR
43% male
TAVR
Netherlands
39 with a
Prospective registry
Descoutures
2006-
2008 (42)
EuroSCORE≥2
Mean 83 years
AVA≤0.7 cm2
66 patients;
2007
NR
12 underwent TAVR
58% male
0 were assessed
one academic center, Paris, France
for TAVR
Kapadia
2006-
Prospective registry
Mean 81 years
NR
NR
18 underwent TAVR
92 referred for
8
2009 (48)
2007
“REVIVAL trial inclusion criteria”
55% male
TAVR
(inoperable and STS-PROM>15)
92 patients
One academic center, Cleveland OH,
US
Prospective registry
Saia
200798 patients
2010 (49)
AVA≤0.75 cm2 and
Angina (CCS ≥3),
AVA≤0.4 cm2/m2 of
syncope, dyspnea
BSA
(NYHA III/IV)
Mean 82 years
2008
98 referred for
45 underwent TAVR
40% male
One academic center, Bologna, Italy
TAVR
Prospective registry
Screening for trial
Ben-Dor
2007-
469 were
Mean 81 years
AVA<0.8 cm2
469 patients
2010 (50)
2009
107 were enrolled in
NR
46% male
screened for
TAVR trial
One academic center, Washington
TAVR trial
DC, US
Prospective registry
Screening for trial
Bavaria
153 were enrolled in
681 patients
2011 (51)
496 (153+343)
2007NR
AVA<0.8 cm2
NR
2010
screened for
TAVR trial
One academic center, Philadelphia
TAVR trial
PA, US
Ben-Dor
2007-
Prospective registry
Mean 82 years
AVA<1.0 cm2, or
900 screened for
NR
2011 (52)
2011
Screening for trial, but also continued
45% male
gradient >40 mm Hg
159 underwent TAVR
TAVR trial
9
access
900 patients
One academic center, Washington
DC, US
Moderate/severe AS,
Retrospective database; fitting the
at least one of:
One of:
PARTNER trial criteria
AVA<1.0 cm2,
Angina, syncope
gradient >40 mm Hg,
or dyspnea
One academic center, Jacksonville
Vmax>4m/s, or
consistent with
FL, US
“dimensionless index
NYHA II
50 screened
Babcock
2008-
Mean 73 years
833 AS patients;
2012 (40)
2010
according to
18 TAVR candidates
52% male
PARTNER trial
criteria
≤0.25)
AS, aortic stenosis; AVA, aortic valve area; BSA, body surface area; CCS, Canadian Cardiovascular Society class; CHF, congestive
heart failure; NR, not reported; NYHA, New York Heart Association; PARTNER, Placement of AoRTic TraNscathetER Valve trial;
REVIVAL, Transcatheter Endovascular Implantation of Valves trial; SAVR, surgical aortic valve replacement; TAVR, transcatheter
aortic valve replacement; US, United States, UK, United Kingdom; VA, Veterans Affairs; VHD, valvular heart disease; echo,
echocardiography; implantation; Vmax, peak velocity.
10
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13