1. A Survival Analysis of Subjects With Transthyretin Amyloid Cardiomyopathy from the Transthyretin Amyloidosis Outcomes Survey
Martha Grogan, Martin Carlsson, Michelle Stewart, Jennifer Schumacher, Angela Dispenzieri

2. Conflicts of interest and acknowledgements
MG and AD are members of the Scientific Board of THAOS. MC, JS, and MS are employees of Pfizer.
The authors thank all THAOS patients and investigators for their important contributions to this study. The THAOS registry and this analysis were sponsored by Pfizer. Medical writing support was provided by David Wateridge, PhD, of Engage Scientific Solutions and was funded by Pfizer.

3. Background
Patients with the rare, progressive, and debilitating disease of transthyretin (TTR) amyloidosis can develop a fatal cardiomyopathy caused by the accumulation of amyloid fibrils composed of misfolded TTR monomers
TTR cardiomyopathy is increasingly recognized as an important cause of heart failure and atrial arrhythmias, especially in older men.
TTR amyloid fibrils can develop in patients with a wild-type TTR genotype as part of the natural aging process (ATTRwt), and can also form due to amyloidogenic TTR mutations that destabilize the structure of native TTR tetramers
Grogan M, et al. Poster presented at the 21st Annual Meeting of the HFSA, September 16–19, 2017, Grapevine, TX, USA

4. Rapezzi et al. European Heart
Journal (2013) 34, 520–528

5. To characterize the survival of subjects with ATTRwt or
Objectives
To characterize the survival of subjects with
ATTRwt or
ATTRm, restricted to mutations considered to be associated with a primarily cardiac phenotype:
Val122Ile, Thr60Ala, Leu111Met, Ile68Leu
Grogan M, et al. Poster presented at the 21st Annual Meeting of the HFSA, September 16–19, 2017, Grapevine, TX, USA

6. Methods
All symptomatic subjects enrolled in THAOS with a diagnosis of ATTR amyloidosis meeting following criteria
ATTRwt or ATTRm (limited to Val122Ile, Thr60Ala, Leu111Met, or Ile68Leu mutations)
At least 1 follow-up visit prior to January 30, 2017
No disease-modifying therapies allowed
Non-parametric Kaplan–Meier delayed-entry methodology was used to estimate median survival from the time of diagnosis.
What happened to those who did not have a follow-up visit?
Grogan M, et al. Poster presented at the 21st Annual Meeting of the HFSA, September 16–19, 2017, Grapevine, TX, USA

7. Characteristics of the study population
Results
Characteristics of the study population
A total of 421 subjects were included:
275 with ATTRwt
37 Thr60Ala
81 Val122Ile
Compare to Mauer publication, his n for overall population was 166 WT and 77 Val122Ilewas for overall survival 119 WT and 60 ValI22Ile
J A C C V O L , NO . 2 , Maurer et al.
J U L Y 1 2 , : – 7 2
146 with ATTRm
9 Leu111Met
19 Ile68Leu
Grogan M, et al. Poster presented at the 21st Annual Meeting of the HFSA, September 16–19, 2017, Grapevine, TX, USA

8. *Val122Ile, Thr60Ala, Leu111Met, or Ile68Leu.
Clinical characteristic at enrollment
ATTRwt
ATTRm* N
275
146
Age at diagnosis, years†
75 (47, 89)
67 (35, 85)
Male gender, % 95 76
Race, %
White
92.7
46.6
Black
2.9
42.5
Other
3.6
6.2
Missing
0.7
4.8
NYHA Class, %
No heart failure reported 10 17
I / II
6 / 46
7 / 27
III IV
29 / 4
23 / 5
5.1
21.2
Time from symptom onset to
diagnosis, years†
3.8 (0.9, 9.9)
3.0 (0.6, 8.4)
*Val122Ile, Thr60Ala, Leu111Met, or Ile68Leu.
†Values are presented as median (Interquartile range). NYHA, New York Heart Association.
Overall, age at diagnosis was higher in the ATTRwt group vs the ATTRm group, but time from symptom onset to diagnosis was similar between groups.
Compare to Mauer publication, his n was 119 WT and 60 ValI22Ile
Grogan M, et al. Poster presented at the 21st Annual Meeting of the HFSA, September 16–19, 2017, Grapevine, TX, USA

9. *Val122Ile, Thr60Ala, Leu111Met, or Ile68Leu.
Clinical characteristic at enrollment
ATTRwt
ATTRm*
Age
< 70
≥ 70 N 67
208 92 54
Age at diagnosis, years†
66 (47, 70)
77 (70, 89)
61 (35, 70)
74 (70, 85)
Male gender, %
92.5
95.7
79.3
70.4
Race, %
White
91.0
93.3
55.4
31.5
Black
3.0
2.9
33.7
57.4
Other
4.5
3.4
5.5
7.4
Missing
1.5
0.5
5.4
3.7
NYHA Class, %
No heart failure reported
11.3
9.8
31.0
6.3
I / II
5 / 45
7 / 42
7 / 13
4 / 39
III / IV
23 / 5
30 / 3
15 / 7
40 / 0 11 8 26 10
Time from symptom onset
to diagnosis, years†
4.0
(0.8, 10.2)
3.8
(0.9, 9.1)
2.2
(0.4, 6.6)
(1.3, 10.2)
*Val122Ile, Thr60Ala, Leu111Met, or Ile68Leu.
†Values are presented as median (Interquartile range). NYHA, New York Heart Association.
For wt 24% under age 70 vs, 63% of mut under age 70
Grogan M, et al. Poster presented at the 21st Annual Meeting of the HFSA, September 16–19, 2017, Grapevine, TX, USA

10. Age at diagnosis and time from symptom onset to diagnosis varied according to the specific TTR mutation carried
Grogan M, et al. Poster presented at the 21st Annual Meeting of the HFSA, September 16–19, 2017, Grapevine, TX, USA

11. Survival from time of diagnosis, stratified according to TTR genotype
Median survival from diagnosis in the ATTRwt and ATTRm groups was 3.1 and 3.7 years, respectively
ATTRwt
N=421
N=275
N=146
ATTRwt
Grogan M, et al. Poster presented at the 21st Annual Meeting of the HFSA, September 16–19, 2017, Grapevine, TX, USA

12. Survival from time of diagnosis, stratified according to TTR genotype and age at diagnosis
Survival from time of diagnosis was more dependent on age at diagnosis than whether patients were ATTRwt or ATTRm
< 70 y: ATTRm, n=92
< 70 y: ATTRwt, n=67
≥ 70 y: ATTRwt, n=208
≥ 70 y: ATTRm, n=54
Median OS
6.7 years
4.4 years
2.9 years
3.0 years
Grogan M, et al. Poster presented at the 21st Annual Meeting of the HFSA, September 16–19, 2017, Grapevine, TX, USA

13. Published THAOS Data Maurer JACC 68 (2), 2016;161-72

14. Conclusions
Symptomatic subjects with ATTR amyloidosis due to either ATTRwt or ATTRm predisposing to a cardiac phenotype had a median delay ≥3.0 years from symptom onset to diagnosis.
The majority of subjects diagnosed with ATTRm at age ≥70 years were black; whereas the majority diagnosed with ATTRm aged <70 years were white.
In general, median survival estimates from diagnosis were similar for subjects with ATTRwt or ATTRm predisposing to a cardiac phenotype when stratified according to age at diagnosis.
Grogan M, et al. Poster presented at the 21st Annual Meeting of the HFSA, September 16–19, 2017, Grapevine, TX, USA

15. Limitations
Short follow-up
Exclusion of lost to follow-up patients