0. Evaluation of Initial Surgical Versus Conservative Strategies in Patients With Asymptomatic Severe Aortic Stenosis: -Results from the CURRENT AS registry-
Tomohiko Taniguchi, MD
Kyoto University Graduate School of Medicine
Takeshi Morimoto, MD, MPH; Hiroki Shiomi, MD; Kenji Ando, MD; Norio Kanamori, MD; Koichiro Murata, MD; Takeshi Kitai, MD; Yuichi Kawase, MD; Chisato Izumi, MD; Makoto Miyake, MD; Hirokazu Mitsuoka, MD; Masashi Kato, MD; Yutaka Hirano, MD; Shintaro Matsuda, MD; Kazuya Nagao, MD; Tsukasa Inada, MD; Tomoyuki Murakami, MD; Yasuyo Takeuchi, MD; Keiichiro Yamane, MD; Mamoru Toyofuku, MD; Mitsuru Ishii, MD; Eri Minamino-Muta, MD; Takao Kato, MD; Moriaki Inoko, MD; Tomoyuki Ikeda, MD ; Akihiro Komasa, MD; Katsuhisa Ishii, MD; Kozo Hotta, MD; Nobuya Higashitani, MD; Yoshihiro Kato, MD; Yasutaka Inuzuka, MD; Chiyo Maeda, MD: Toshikazu Jinnai, MD; Yuko Morikami, MD; Ryuzo Sakata, MD and
Takeshi Kimura, MD
On behalf of the CURRENT AS registry Investigators

1. Disclosure Statement of Financial Interest
I have nothing to declare.
This study was funded by
Kyoto University graduate School of Medicine,
Department of Cardiovascular Medicine.

2. Current Guidelines Recommendations on Timing of AVR in Asymptomatic Patients with Severe AS
Strategy of watchful waiting for AVR until symptoms emerge,
except for several subgroups of patients such as those with
left ventricular dysfunction or very severe AS.
Limitations
1. Based on previous small single-center studies evaluating symptoms and/or AVR,
but not mortality as the outcome measures.
2. No previous large-scale multicenter study comparing the initial AVR strategy
with the conservative strategy. 2

3. CURRENT AS registry: Flow Chart Multi-center, retrospective registry
3815 consecutive patients with severe AS
(Jan Dec 2011, 27 centers in Japan)
Peak aortic jet velocity > 4.0m/s
or mean aortic pressure gradient > 40mmHg,
or aortic valve area < 1.0cm2
Asymptomatic
1808 patients
Conservative group
1517 patients
Initial AVR group
291 patients
Symptomatic
2005 patients
1100 patients
905 patients
Unknown symptomatic
status: 2 patients
Angina
Syncope
Heart failure * *
Follow-up interval (median): 3.7 years
2-year follow-up: 90% 3

4. Baseline Characteristics in the entire cohort
Initial AVR group
Conservative group
P value
No. of patients
291
1517
Age (years)
71.6 ± 8.7
77.8 ± 9.4
<0.001
Age ≥80 years
17%
46%
Male
43%
40%
0.27
Prior stroke (symptomatic) 9%
15%
0.004
Coronary artery disease
21%
28%
0.01
STS score (PROM), %
2.0 ( )
3.5 ( )
LVEF (%)
67 ± 10
66 ± 11
0.11
Peak aortic valve velocity (m/s)
4.8 ± 0.8
3.8 ± 0.7
Mean aortic valve gradient (mmHg)
54 ± 20
33 ± 14
AVA (cm2)
0.67 ± 0.16
0.79 ± 0.16 4

5. Main Analysis Set: Propensity-score Matched Cohort
3815 consecutive patients with severe AS
(Jan Dec 2011, 27 centers in Japan)
Peak aortic jet velocity >4.0m/s
or mean aortic pressure gradient >40mmHg,
or aortic valve area <1.0cm2
Asymptomatic
1808 patients
Conservative group
1517 patients
Initial AVR group
291 patients
Symptomatic
2005 patients
1100 patients
905 patients
Unknown symptomatic
status: 2 patients
Propensity-score matched cohort
Initial AVR group
291 patients
Conservative group
291 patients 5

6. Baseline Characteristics in the Propensity-score Matched Cohort
Initial AVR group
Conservative group
P value
No. of patients
291
Age (years)
71.6 ± 8.7
73.1 ± 9.3
0.047
Age ≥80 years
17%
16%
0.91
Male
43%
0.87
Prior stroke (symptomatic) 9% 8%
0.88
Coronary artery disease
21%
25%
0.20
STS score (PROM), %
2.0 ( )
2.4 ( )
0.007
LVEF (%)
67 ± 10
68 ± 8
0.06
Peak aortic valve velocity (m/s)
4.8 ± 0.8
4.4 ± 0.9
<0.001
Mean aortic valve gradient (mmHg)
54 ± 20
45 ± 20
AVA (cm2)
0.67 ± 0.16
0.75 ± 0.18 6

7. Indications for AVR in the initial AVR group
291 patients in the initial AVR group
Formal Indications for AVR
Class-I
LVEF <50%
Very severe AS
No formal
indication;
37%
N=107
Formal
Indications;
63%
N=184
Number of patients 7

8. Outcome Measures and Analysis
Primary Outcome Measures
All-cause death
Heart failure hospitalization
Secondary Outcome Measures
Cardiovascular death
Non-cardiovascular death
Sudden death
Emerging symptoms related to AS
Analysis was performed in the intention-to-treat principle regardless of the actual performance of AVR. . 8

9. Surgical AVR or TAVI Initial AVR group 97.5% 287/291 patients (99%)
100
Initial AVR group
Conservative group
97.5%
287/291 patients (99%)
AVR/TAVI interval: 44 days (median) 80
Cumulative incidence (%) 60
Log-rank P<0.001
118/291 patients (41%)
AVR/TAVI interval: 780 days (median) 40 20
3.7%
0.5 1 2 3 4 5
Years after diagnosis
Interval 0d
30d
180d 1y 3y 5y
Conservative group
N of patients with at least 1 event 10 24 84
106
N of patients at risk
291
279
258
229
117 38
Cumulative incidence 0%
3.7%
9.1%
35.8%
52.6%
Initial AVR group 87
281
287
204 9 1
30.0%
97.5%
99.7% 9

10. Primary outcome measure
All-cause death
100 80
Crude HR 0.60 ( ), P=0.009
Adjusted HR 0.64 ( ), P=0.02
Cumulative incidence(%) 60
Log-rank P=0.009 40
26.4%
Conservative group 20
15.4%
Initial AVR group 1 2 3 4 5
Years after diagnosis
Interval 0d
30d 1y 3y 5y
Conservative group
N of patients with at least 1 event 3 20 48 60
N of patients at risk
291
279
252
178 72
Cumulative incidence
1.1%
7.2%
17.9%
26.4%
Initial AVR group 1 14 25 33
286
266
188 75
0.3%
4.9%
9.0%
15.4%
The results from the adjusted analysis conducted as a sensitivity analysis were fully consistent with those from the unadjusted analysis. 10

11. Heart failure hospitalization
Primary outcome measure
Heart failure hospitalization
100 80
Crude HR 0.18 ( ), P<0.001
Adjusted HR 0.19 ( ), P<0.001
Log-rank P<0.001 60
Cumulative incidence (%) 40
19.9%
Conservative group 20
3.8%
Initial AVR group 1 2 3 4 5
Years after diagnosis
Interval 0d
30d 1y 3y 5y
Conservative group
N of patients with at least 1 event 8 31 39
N of patients at risk
291
279
246
161 63
Cumulative incidence 0%
3.0%
13.0%
19.9%
Initial AVR group 3 6
286
264
185 75
1.1%
2.4%
3.8%
The results from the adjusted analysis conducted as a sensitivity analysis were fully consistent with those from the unadjusted analysis. 11

12. Secondary outcome measures
Cumulative 5-Year Incidence
Initial AVR group
(N=291)
Conservative group
Adjusted HR
(95% CI)
P value
Cardiovascular death
9.9%
18.6%
0.59 ( )
0.03
Aortic valve-related death
5.3%
13.5%
0.42 ( )
0.006
Sudden death
3.6%
5.8%
0.43 ( )
0.049
Non-cardiovascular death
6.1%
9.6%
0.74 ( )
0.38
Emerging symptoms
3.2%
46.3%
0.06 ( )
<0.001
Initial AVR Strategy Better
Conservative Strategy Better 12

13. Adjusted Hazard Ratio for the Primary Outcome Measures
Propensity-score matched cohort and Entire cohort
Endpoints
Adjusted HR
P value
All-cause death
Propensity-score matched cohort
0.64
0.02
Entire cohort
0.51
<0.001
Heart failure hospitalization
0.19
0.21
Initial AVR Strategy Better
Conservative Strategy Better
The favorable effect of the initial AVR compared with the conservative strategy was seen in both propensity-score matched cohort and the entire cohort. 13

14. Types of emerging symptoms and outcomes in the conservative group
Conservative group (N=1517)
Emerging
symptoms
Heart Failure
NYHA unknown
AVR
AVR
71%
AVR Rate
No symptom
Angina
Syncope
NYHA-2
NYHA-3
NYHA-4
(%)
Mortality 14

15. Limitations
1. Retrospective study design and variable patient follow-up
We were unable to exclude the possibility of ascertainment bias for
symptoms related to AS at the baseline.
Patient follow-up might have been variable among participating centers.
2. Selection bias and residual confounding
Propensity-score matching did not completely eliminate the impact of
differences in the two groups. However, the results from the adjusted
analysis were fully consistent with those from unadjusted analysis. 15

16. Conclusion
The long-term outcome of asymptomatic patients with severe AS was dismal when managed conservatively in the real clinical practice, which might be substantially improved by the initial AVR strategy. 16

17. Manuscript
Just Accepted
In JACC!
To be coming soon ! 17