ACC 2015 | San Diego, CA | March 14-16 2015 Relation Between Frailty and Outcomes After...
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Transcript of ACC 2015 | San Diego, CA | March 14-16 2015 Relation Between Frailty and Outcomes After...
ACC 2015 | San Diego, CA | March 14-16 2015
Relation Between Frailty and Outcomes After Transcatheter Aortic Valve Replacement
Philip Green, MD
Columbia Universityon behalf of The PARTNER Trial Investigatorsand The PARTNER Publications Office
From the PARTNER Trial
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 long-term (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 FrailtyCardiovascular Health Study
Self ReportedUnintentional 10 pound weight loss
Subjective exhaustion
Low physical activity (survey estimated Kcal per week)
Objective MeasuresLow grip strength
• Lowest 20% population
• BMI and gender based cut point
Slow walking / gait speed
• 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 PredictorFrailty 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 0-1212 = most frail0 = 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):591Arnold 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
Non-frail (n=134)Score >= 6
Frail (n=110)Score < 6
Independent in ADLs 134 (100%) 38 (35%)
Albumin, g/dL
median (IQR) 4.1 [3.8, 4.4] 3.7 [3.4, 4.0]
Gait speed, m/s
median (IQR) 0.51 [0.30, 0.76] 0.27 [0.00, 0.45]
Grip strength, kg (men)
median (IQR) 27.0 [21.3, 31.7] 18.7 [13.2, 23.2]
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
Male gender 55% 47% 0.22
Body mass index (kg/m2) 25.8 [22.2, 29.6] 24.8 [21.9, 28.3] 0.46
Transfemoral TAVR 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
6-Minute Walk Test
Could Not Perform 17% 35% 0.002
Total Distance Walked (m)* 192 [122, 297] 146 [77, 238] 0.01
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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
AV area (cm2) 0.63 [0.50, 0.83] 0.62 [0.51, 0.72] 0.2
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30 day outcomes
Non-Frail (n=134) Frail (n=110) p-value
Death
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
*Due to aortic stenosis or complications of the valve procedure.
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 1.40-4.35, p=0.002).
De
ath
(%
)
0
20
40
60
Time in Months0 3 6 9 12
134 120 114 108 98110 92 86 75 66
Number at risk:Frailty Score < 6Frailty Score >= 6
P= 0.004
15.9%
32.7%
Frailty Score < 6Frailty Score >= 6
Poor Clinical OutcomeDead, decrease in KCCQ > 10, or KCCQ < 40
OR 2.2 (1.1 - 4.5)p = 0.03
15
6 months 12 months0%
25%
50%
75%
100%
42%50%
28% 32%
FrailNot Frail
OR 2.4 (1.1 - 5.1) p = 0.02
Poor Clinical OutcomeSeparating death and Poor QOL (KCCQ < 40 or decrease > 10)
6 months16
12 months
Frail Not Frail Frail Not Frail0%
25%
50%
75%
100%
24%15% 17% 16%
18%
13%
33%
16%
DeadPoor QOL
P=0.84P=0.13
Markers of Frailty and Mortality at 1 year
17
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
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 ArnoldDavid J CohenAjay KirtaneSusheel Kodali David BrownCharanjit RihalKe XuYang Lei
Marian HawkeyRebeca KimMaria AluMartin LeonMichael 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 1.14-5.05, p = 0.02
Dea
th (
%)
0
20
40
Time in Months
0 3 6 9 12
76 66 61 60 55
127 111 104 92 86
41 35 35 31 23
Number at risk:
Group A
Group B
Group C
Overall Log-Rank P-Value =0.1869
A vs B Log-Rank P-Value =0.1878
A vs C Log-Rank P-Value =0.0641
B vs C Log-Rank P-Value =0.4318
16.0%
24.9%
32.3%
Group A (0<= Frailty Score <=3)Group B (4<= Frailty Score <=8)Group C (9<= Frailty Score <=12)