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

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

AV area (cm2) 0.63 [0.50, 0.83] 0.62 [0.51, 0.72] 0.2

12

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)