1. Howard C. Herrmann, MD University of Pennsylvania Philadelphia
Treating the Inoperable – Tools to Make a Decision on Who Will or Will Not Benefit from TAVR
Howard C. Herrmann, MD
University of Pennsylvania
Philadelphia

2. Disclosure Statement of Financial Interest
Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below.
Institutional Grant/Research Support
Abbott Vascular
Edwards Lifesciences
St. Jude Medical
Medtronic
Gore
Bayer
Boston Scientific
Regado Biosci
Corvia
Cardiokinetx
Univ Laval
Claret Medical
Consulting Fees/Honoraria
Edwards Lifesciences
Bayer
Leerink
Wells Fargo
Major Stock Shareholder/Equity
Microinterventional Devices
Discussion may include unapproved and off-label devices, procedures, and indications

3. Treating the Inoperable – Tools to Make a Decision on Who Will or Will Not Benefit from TAVR
Woody Allen
I don’t want to achieve immortality through my work.
I want to achieve it by not dying!

4. More Questions and Issues Than Answers
Treating the Inoperable – Tools to Make a Decision on Who Still Benefits from TAVR
More Questions and Issues Than Answers
Do we know who doesn’t benefit from TAVR?
Are there any tools that we can use to determine who doesn’t benefit from TAVR?
Do these patients benefit more from SAVR?
Are we comparing TAVR to TAVR w/o risk factor or TAVR to MM?
What is the proper metric for outcome (survival or QOL)?

5. Do we know who doesn’t benefit from TAVR?
All Cause Mortality (ITT) P1cohort B Crossover Patients Censored at Crossover
Do we know who doesn’t benefit from TAVR?
Standard Rx
HR [95% CI] = 0.53 [0.41, 0.68]
p (log rank) <
TAVR
80.9%
68.0%
26.8%
50.8%
25.0%
All Cause Mortality (%)
54.1%
20.1%
43.0%
30.7%
Updated WNA to Oct 9 data
Point-in-time at 2 yrs: p <
Months
Numbers at Risk
Standard Rx
179
121 85 62 46 27 17
TAVR
138
124
110
101 88 70

6. Factors Associated with Poor Outcome
NON-CARDIAC
CARDIAC
PROCEDURAL
COPD
CKD DM
Prior CVA
Liver disease
Coagulopathy
BMI
Male
Frailty
Dementia
Low EF
Pul HTN
Severe MR
CAD
AKI AR
Stroke
Vascular
CPS
Valve re-intervention
Rodes-Cabau J Am Coll Cardiol. 2010;55:
Moat NE J Am Coll Cardiol. 2011;58:
Tamburino C Circulation. 2011;123:
Thomas M Circulation. 2011;124:
Green P JACC Cardiovasc Interv. 2012;5:
Pilgrim T Circ Cardiovasc Interv. 2012;5:
Rodes-Cabau Nat Rev Cardiol. 2012;9:15-29
Dewey TM Ann Thorac Surg. 2010;89:
Beohar et al, TVT presentation, submitted

7. Frailty Assessment Components
ADLs (Activities of Daily Living)
6/6 is normal (not Frail)
Dress yourself unassisted
Feed unassisted
Ambulate unassisted
Use the toilet (and clean) unassisted
Bath Unassisted
Do own hygiene unassisted
Serum Albumin Level
Normal range: 3.5 – 5.0 g/dL
Grip Strength
5MWT (5 meter walk test)
Men
Cutoff for grip strength (Kg)
BMI ≤ 24
≤ 29
BMI 24.1 – 28
≤ 30
BMI > 28
≤ 32
Women
Cutoff for grip strength (Kg)
BMI ≤ 23
≤ 17
BMI 23.1 – 26
≤ 17.3
BMI 26.1 – 29
≤ 18
BMI > 29
≤ 21
Men
Cutoff time to walk 15 ft.
Height ≤ 173 cm
≥ 7 seconds
Height > 173 cm
≥ 6 seconds
Women
Cutoff time to walk 15 ft.
Height ≤ 159 cm
≥ 7 seconds
Height > 159 cm
≥ 6 seconds

8. Kaplan-Meier Survival Estimates Stratified by Frailty Score
After adjusting for important clinical and demographic characteristics, frailty remained independently associated with…
2.5-fold increased hazard of 1-year mortality after TAVR
(95% CI , p=0.002).
Death (%) 20 40 60
Time in Months 3 6 9 12
134
120
114
108 98
110 92 86 75 66
Number at risk:
Frailty Score < 6
Frailty Score >= 6
P= 0.004
15.9%
32.7%

9. Patients with Chronic Lung Disease (CLD) Have Higher Mortality After TAVR (data from Partner and NCAR)
Independent predictors of mortality:
Short 6MWT*
Oxygen dependency*
Renal disease
Lower BMI*
Higher PAP*
Lower AoV gradient
* Included in the PBOSS score
Dvir et al, JACC 2014;63:269-79

10. TAVR vs Std Therapy TAVR vs SAVR
Cohort B: Cohort A:
TAVR vs Std Therapy TAVR vs SAVR
Dvir et al, JACC 2014;63:269-79

11. Dvir et al, JACC 2014;63:269-79

12. Survival After the Initial Diagnosis of Alzheimer Disease
Larson et al, Ann Int Med 2004;140:501
Greta Rait et al. BMJ 2010;341:bmj.c3584
Dementia and TAVR
Despite the high incidence of microemboli with TAVR, most studies have generally shown cognitive improvement or preservation!
Rodes-Cabau et al, JACC
TAVR made me smarter

13. Difficult to use binary risk factors as a litmus test
TAVR
NO TAVR

14. All-Cause Mortality Stratified by STS Score (ITT)
Months
STS < 5
STS 5-15
STS > 15
100%
55.9%
93.3%
73.7%
75.2%
93.4%
p (log rank) =
p (log rank) =
p (log rank) =
Standard Rx (n = 123)
TAVR (n = 113)
Standard Rx (n = 12)
TAVR (n = 28)
Standard Rx (n = 43)
TAVR (n = 38)

15. Problems with the STS DataBase
Voluntary data submission
Operated patients only
Morbidity also important
Doesn’t include all risk factors:
Porcelain Aorta
Previous Mediastinal Radiation (Lymphoma)
Multiple Previous Sternotomies With Open Grafts
Advanced Liver Disease/ Cirrhosis
Frailty/ Debility/ Immobility
Dementia

16. ACC/AHA Guideline – Risk Levels

17. FRANCE 2: Risk Factors for TAVR Early Mortality
3,833 patients analyzed to develop, validate a risk score for 30-day and in-hospital mortality using patient-specific variables. .
Data from 2,552 patients were used to identify predictive factors and develop the score; the rest provided validation
Low BMI, critical state, respiratory insufficiency, transapical approach among most important predictors of early mortality
Overall, score showed moderate discrimination with a c-index of 0.67 in the developmental cohort, 0.59 in validation cohort
Implications: In prognostic scoring, low body mass, comorbidities contributed significantly to risk of 30-day mortality after TAVR.
Iung B, et al. Heart.
2014;Epub ahead of print.

19. Case Presentation 74 yo with RHD 1996: s/p #23 SJM AVR
2013: OLT c/b renal failure
2014: recurrent ascites, pul htn, mitral stenosis
redo MVR (#27 bio), TV repair
Now, pleural mass -> bx HCC (metastatic)
Referred for off-label TMVR with VIV
Oncologist:
“Median survival 24 mos, but hard to prognosticate beyond 6 mos at this time”
“Why not just do it for symptomatic benefit?”

20. Poor outcome should include both a mortality and a QOL component
Poor outcome was defined in 463 Partner patients as any of the following at 6 months after TAVR :
Death (19%)
KCCQ score <45 (≈NYHA Class IV) or
Decrease ≥10 points in KCCQ score
Poor outcome occurred in 35%
16%
Circ Cardiovasc Qual Outcomes 2013;6:591-7

21. Overall, 62% alive with reasonable QOL 38% had poor 1-year outcome:
Kansas City Cardiomyopathy Score –overall score
(0-100, higher scores indicate less symptom burden and better QOL)
Overall, 62% alive with reasonable QOL
38% had poor 1-year outcome:
19% mortality
17% persistent poor QOL (<50)
5% decline in score
JAMA Cardiol. Published online February 01, doi: /jamacardio

22. Conclusions
Mortality in extreme risk patients is high even after “successful” TAVR
Societal/economic perspective (cost-effectiveness)
Life expectancy ~3 years (cost per life-year gained = $50,000)
Mortality alone may not be the best indicator of acceptable outcome (include QOL) – “TAVR only treats symptoms that are due to AS”
Individual patient perspective
No single risk factor is sufficient to identify futility or serve as a litmus test
Combination of risk factors (STS and new TAVR scores) improve prediction, but have limitations and still may not be sufficient.
Need to not only improve patient selection, but optimize post procedure care to get the best QOL possible in survivors
The heart team approach is best suited to balancing patient risk, the role of evolving technology, and QOL. It may be the best reason we have for keeping the heart valve team intact in the future.