Transcript Relation Between Frailty and Outcomes After Transcatheter

Relation Between Frailty and
Outcomes After Transcatheter Aortic
Valve Replacement
From the PARTNER Trial
Philip Green, MD
Columbia University
on behalf of The PARTNER Trial Investigators
and The PARTNER Publications Office
ACC 2015 | San Diego, CA | March 14-16 2015
Background
• TAVR is a worthwhile treatment for symptomatic
severe AS patients who cannot have surgery
(inoperable/extreme risk) or are at high-risk for
surgery
• However, after TAVR, the intermediate and longterm (thru 5 years) mortality is still high (>50%)
• Therefore, improving patient selection for TAVR is
an important priority
Frailty
• A syndrome of impaired physiologic reserve and
decreased resistance to stressors which is
associated with a poor prognosis…
 In the general population
 In the elderly with CAD
 In the elderly after general or cardiac surgery
 After TAVR (small single center studies)
Physical Frailty
Cardiovascular Health Study
Self Reported
Objective Measures
Unintentional 10 pound
weight loss
Low grip strength
Subjective exhaustion
• BMI and gender based cut point
Low physical activity
(survey estimated Kcal
per week)
Slow walking / gait speed
• Lowest 20% population
• Lowest 20% population
• Height and gender based cut
point
Fried LP, J Gerontol A Biol Sci Med Sci. 2001 Mar;56(3):M146
Objective
• To evaluate the prognostic value of frailty among
older adults who received TAVR in the PARTNER
Trial
• We hypothesized that frail patients who undergo
TAVR would experience:
 increased mortality
 a higher likelihood of poor clinical outcomes
Methods
• All patients in PARTNER (cohorts A & B)
randomized to TAVR and who received baseline
frailty assessment
• High enrolling sites who performed objective frailty
assessment prior to TAVR in consecutive patients
 Baylor Healthcare System, Dallas, TX (n=35)
 Mayo Clinic, Rochester, MN (n=83)
 Columbia University, New York, NY (n=126)
Primary Predictor
Frailty Score
Frailty Domain
Measure
Frailty Score
Slowness
15 foot walk gait speed (m/s)
Quartiles (0-3)
Weakness
Grip strength (kg)
Gender based
quartiles (0-3)
Wasting and
malnutrition
Serum albumin (g/dl)
Quartiles (0-3)
Inactivity
Katz ADLs (dress, bath,
transfer, feed, toilet,
continence)
Any dependence=3,
Independence=0
Score range 0-12
12 = most frail
0 = least frail
Green, Am Coll Cardiol Intv. 2012;5(9):974
Outcomes
• 1 year death from any cause
• Poor outcome (Arnold et al)
 Considers mortality and quality of life
 Success is defined as alive with acceptable or
improved QOL
 Poor outcome is defined as dead or with significant
reduction in QOL (KCCQ reduced by 10 ~ 1 NYHA
functional class) or KCCQ < 40 (class IV CHF)
Arnold SV. Circ Cardiovasc Qual Outcomes. 2013 Sep 1;6(5):591
Arnold SV. Circulation. 2014 Jun 24;129(25):2682
Poor Outcome
Arnold SV. Circ Cardiovasc Qual Outcomes. 2013 Sep 1;6(5):591
Baseline Frailty Markers
Independent in ADLs
Non-frail (n=134)
Score >= 6
Frail (n=110)
Score < 6
134 (100%)
38 (35%)
4.1 [3.8, 4.4]
3.7 [3.4, 4.0]
0.51 [0.30, 0.76]
0.27 [0.00, 0.45]
27.0 [21.3, 31.7]
18.7 [13.2, 23.2]
Albumin, g/dL
median (IQR)
Gait speed, m/s
median (IQR)
Grip strength, kg (men)
median (IQR)
Grip strength kg (women)
median (IQR)
14.0 [10.9, 16.9]
11.0 [9.0, 14.0]
Baseline characteristics (1)
Variable
Non-frail (n = 134)
Frail (n = 110)
p-value
Age (yrs)
85.4 [79.4, 89.5]
87.1 [82.7, 90.3]
0.11
55%
47%
0.22
25.8 [22.2, 29.6]
24.8 [21.9, 28.3]
0.46
46%
52%
0.39
STS Score (%)
10.5 [8.8, 12.4]
11.3 [9.6, 13.8]
0.07
NYHA Class IV
27%
29%
0.7
17%
35%
0.002
192 [122, 297]
146 [77, 238]
0.01
Male gender
Body mass index (kg/m2)
Transfemoral TAVR
6-Minute Walk Test
Could Not Perform
Total Distance Walked (m)*
11
Baseline characteristics (2)
Variable
Non-frail (n = 134)
Frail (n = 110)
p-value
Diabetes mellitus
32%
26%
0.26
CAD
85%
83%
0.62
Peripheral vascular
disease
41%
42%
0.89
Renal disease
14%
14%
0.9
Liver disease
2%
8%
0.03
COPD
43%
42%
0.91
0.63 [0.50, 0.83]
0.62 [0.51, 0.72]
0.2
AV area (cm2)
12
30 day outcomes
Non-Frail (n=134)
Frail (n=110)
p-value
Any cause
8%
10%
0.49
Cardiovascular cause
6%
7%
0.68
Repeat hospitalization*
7%
4%
0.29
Major stroke
2%
1%
0.68
Major bleeding
5%
9%
0.24
Major vascular
complications
5%
6%
0.51
Permanent pacemaker
9%
9%
0.97
Renal failure
(dialysis required)
5%
8%
0.36
Death
*Due to aortic stenosis or complications of the valve procedure.
Kaplan-Meier Survival Estimates
Stratified by Frailty Score
2.5-fold
increased
hazard of 1-year
mortality after
TAVR
(95% CI 1.40-4.35,
p=0.002).
Frailty Score < 6
Frailty Score >= 6
60
Death (%)
After adjusting for
important clinical
and demographic
characteristics,
frailty remained
independently
associated with…
P= 0.004
40
32.7%
20
15.9%
0
0
3
6
9
12
Time in Months
Number at risk:
Frailty Score < 6 134
Frailty Score >= 6 110
120
92
114
86
108
75
98
66
Poor Clinical Outcome
Dead, decrease in KCCQ > 10, or KCCQ < 40
100%
75%
50%
OR 2.2 (1.1 - 4.5)
p = 0.03
OR 2.4 (1.1 - 5.1)
p = 0.02
50%
42%
28%
32%
25%
0%
6 months
15
12 months
Frail
Not Frail
Poor Clinical Outcome
Separating death and
Poor QOL (KCCQ < 40 or decrease > 10)
100%
75%
Dead
Poor QOL
50%
33%
18%
25%
16%
13%
24%
P=0.13 15%
17% P=0.84
16%
0%
Frail
Not Frail
6 months
16
Frail
Not Frail
12 months
Markers of Frailty and
Mortality at 1 year
Variable
HR (95% CI)
p-value
Gait speed (m/s)*
1.37 [0.53-3.45]
0.51
Grip strength (kg)*
1.02 [0.99-1.05]
0.28
Albumin (g/dL)*
1.25 [0.88-1.79]
0.21
Any ADL limitation
1.59 [0.93, 2.70]
0.09
Score (continuous)*
1.12 [1.02, 1.22]
0.01
Score (≥ 6 versus < 6)
2.18 [1.27, 3.75]
0.005
* Hazard ratio is per unit decrease
17
Limitations
• Secondary analysis of a subgroup from the
PARTNER randomized trials
• Frailty composite in this analysis is a
departure from well established epidemiologic
definitions of frailty
• Very early TAVR experience with first
generation device and patients at highest risk
for poor outcomes
• No surgical or standard therapy comparisons
Conclusion
• Frailty as assessed by a composite of gait speed,
grip strength, ADLs, and serum albumin is not
associated with adverse 30-day outcomes, but is
associated with increased mortality and a higher
rate of poor clinical outcomes 1 year after TAVR.
• Frailty measurement is an essential component of
the risk assessment in older adults considering
therapy for AS
Thank you to the dedicated study
teams at all the PARTNER Sites!
Special thanks to the
participants in this writing group
Suzanne Arnold
David J Cohen
Ajay Kirtane
Susheel Kodali
David Brown
Charanjit Rihal
Ke Xu
Yang Lei
Marian Hawkey
Rebeca Kim
Maria Alu
Martin Leon
Michael Mack
Supplemental Material
Poor Outcome
• At 6-months after TAVR: occurred in 41.9% of frail
participants and 27.6% of non-frail participants.
– unadjusted OR for frailty 1.89, 95% CI 1.03-3.46, p=0.04
– After multivariable adjustment OR 2.21, 95% CI 1.09-4.46, p =
0.03
• At 12 months, a poor outcome occurred in 50.0% of
frail participants and 31.5% of non-frail participants
– unadjusted OR for frailty 2.17, 95% CI 1.16-4.07, p=0.02).
– After multivariable adjustment year OR 2.40, 95% CI 1.145.05, p = 0.02
Group A (0<= Frailty Score <=3)
Group B (4<= Frailty Score <=8)
Group C (9<= Frailty Score <=12)
40
Overall Log-Rank P-Value =0.1869
A vs B Log-Rank P-Value =0.1878
32.3%
A vs C Log-Rank P-Value =0.0641
Death (%)
B vs C Log-Rank P-Value =0.4318
24.9%
20
16.0%
0
0
3
6
9
12
60
92
31
55
86
23
Time in Months
Number at risk:
Group A
Group B
Group C
76
127
41
66
111
35
61
104
35