1. Transcatheter Aortic Valve Replacement
Todd M Dewey, MD
Surgical Director of Structural Heart disease
Medical City Dallas Hospital

2. Our Last Presentation On TAVR
American Geriatric Society Meeting 2012

3. Patient With Aortic Stenosis
84 yr old with AS
Hx lymphoma with XRT
Echo:
Vmax- 5.2 m/s
Peak Gradient: 90 mmHg
Mean gradient: 40 mmHg
Ao valve area: 0.6 cm2
Cr 1.0
FEV1 95% predicted
STS-Prom: 3.5

4. CT of Chest

5. Therapeutic Options?
Aortic valve replacement under circulatory arrest with replacement of Ascending aorta and proximal arch
Apical – aortic conduit
Medical management with BAV

6. Best Option

7. TAVR promises to be a “game changer
1. Allows us to treat the “untreatable”
2. Much less invasive
Off pump, closed chest replacement of the aortic valve
3. Compels us to re-evaluate how we manage valvular heart disease

8. We Have An Aging Population
-Population ≥65 will double in next 20 years - By out of 5 Americans will be > 65 - By 2050, 20 million in U S> 85 years of age

9. Prevalence of Aortic Stenosis
16.5 Million People in US
Over the Age of 652
Aortic stenosis is estimated to be prevalent in up to 7% of the population over the age of 651
It is more likely to affect men than women; 80% of adults with symptomatic aortic stenosis are male3
Percentage Diagnosed with Aortic Stenosis
Aortic stenosis is a common public health problem affecting millions of people in the United States. It is estimated to be prevalent in up to 7% of the population over the age of It is also more likely to affect men than women; 80% of adults with symptomatic aortic stenosis are male.

10. Age Distribution of AVR Pts STS Database (2002-6)
(years)
Isolated AVR
(67,292 pts)
AVR + CABG
(66,074)
Average (133,366 pts)
< 55
19.7%
4.5%
12.1%
55 – 64
19.3%
13.8%
16.6%
65 – 74
27.2%
32.3%
29.8%
≥ 75
33.9%
49.4%
41.7%
Ann Thorac Surg 2009; 88: 23-42, 43-62

11. Isolated AVR Mean Age * Median * 73 * 67 * 57 1987 – 1989 (n=49)

12. Mortality With Standard Therapy Is Worse Than With Certain Metastatic Cancers
Survival, %
5-Year Survival
Breast
Cancer*
Lung
Colorectal
Prostate
Ovarian
Severe
Inoperable AS†
Looking at the gravity of the disease another way, if the results of the PARTNER Trial were extrapolated out to 5 years, the survival of an inoperable patient with severe aortic stenosis that did not receive treatment is only 3% - shockingly low compared to many of the most serious metastatic cancers.
* National Institutes of Health. National Cancer Institute. Surveillance Epidemiology and End Results. Cancer Stat Fact Sheets. Accessed November 16, 2010.
† Using constant hazard ratio. Data on file, Edwards Lifesciences LLC. Analysis courtesy of Murat Tuczu.

14. Primary Endpoint: All-Cause Mortality at 1 Year
HR [95% CI] = 0.93 [0.71, 1.22]
P (log rank) = 0.62
0.5
TAVR
AVR
0.4
26.8
0.3
0.2
24.2
0.1 6 12 18 24
No. at Risk
Months
TAVR
348
298
260
147 67
351
252
236
139 65
AVR

15. All-Cause Mortality Transfemoral (N=492)
HR [95% CI] = 0.83 [0.60, 1.15]
P (log rank) = 0.25
26.4
22.2
No. at Risk
Months
TAVR
244
215
188
119 59
248
180
168
109 56
AVR

16. All-Cause Mortality Transapical (N=207)
HR [95% CI] = 1.22 [0.75, 1.98]
P (log rank) = 0.41
29.0
27.9
No. at Risk
Months
TAVR
104 83 72 28 8
103 68 30 9
AVR

17. Neurological Events at 30 Days and 1 Year All Patients (N=699)
30 Days
1 Year
Outcome
TAVR (N = 348)
AVR (N = 351)
All Stroke or TIA – no. (%)
19 (5.5)
8 (2.4)
0.04
27 (8.3)
13 (4.3)
TIA – no. (%)
3 (0.9)
1 (0.3)
0.33
7 (2.3)
4 (1.5)
0.47
All Stroke – no. (%)
16 (4.6)
0.12
20 (6.0)
10 (3.2)
0.08
Major Stroke – no. (%)
13 (3.8)
7 (2.1)
0.20
17 (5.1)
0.07
Minor Stroke – no. (%)
0.34
2 (0.7)
0.84
Death/maj stroke – no. (%)
24 (6.9)
28 (8.2)
0.52
92 (26.5)
93 (28.0)
0.68
p-value
p-value

18. All-Cause Mortality or Stroke All Patients (N=699)
HR [95% CI] = 0.95 [0.73, 1.23]
P (log rank) = 0.70
28.0
26.5
No. at Risk
Months
TAVR
348
289
252
143 65
351
247
232
138 63
AVR

19. March 26, 2012 on NEJM.org

20. All-Cause Mortality (AT)
Due to more withdrawals and patient refusals in the surgery, the as treated analysis is presented for comparison. Similar to the ITT, there is no difference in mortality with a HR Two year KM estimates for mortality were 33.9% in the TAVR arm and 32.7% in the AVR arm.
TAVR
AVR
HR [95% CI] = 0.95 [0.74, 1.22]
p (log rank) = 0.692

21. TAVR Has Changed the Referral Paradigm for Aortic Valve Disease
Transformation in Traditional referral pattern
PCP
Cardiologist
Surgeon

22. A New Paradigm for Aortic Valve Disease
TAVR has created increased collaboration between CV surgery and cardiology
Advanced the concept of the “Valve Clinic”
Valve Clinic
Surgeon
Cardiologist
Research nurses
Imaging specialist
Geriatrician
PCP
Cardiology
CV Surgery

23. Integrated Disease Management
The model of Disease Management for valvular heart disease
Creating Combined Valve clinics
Shortens work-up times and expedites decision making
Fosters collegiality
Creates a cohesive approach to valvular heart disease
Leverages the expertise of different specialties

24. TAVR Has Changed Our Approach to Aortic Valve Disease
Specialization within the practice
The association between procedure volumes and operative outcomes has been well described using administrative databases
Birkmeyer reported a 30-40% reduction in mortality for high volume versus low volume surgeons
Coronary artery bypass grafting (CABG)
Aortic valve replacement (AVR)
Increased emphasis on Frailty Assessment to improve patient selection

25. Who Is Too Sick for TAVR?
Patients in whom the presence of multiple comorbidities, especially frailty, overwhelm the likelihood of functional recovery despite successful TAVR
TAVR
Medical therapy
Porcelain aorta
Hostile chest
RIMA/LIMA anatomy
Severe COPD
Liver cirrhosis
Dementia
Severe frailty

26. Is it a risk/benefit predictor or an outcome?
Age (yrs)
Life Years Remaining
Frailty Prevalence
>65
>25
~8% 70
19.3
15% 75
11.7
28% 80
8.9
32% 85
6.6
38% 90
4.8
40%
Gladys Burhill, Age 92, Keizo Miura, Age 100, Jeanne Calment, Age 118
Operative risk increases with age– yet chronologic age and comobidities may be inadequate for complete risk assessment…is frailty the answer?
How can it be measured?
Is it a risk/benefit predictor or an outcome?
Does AS confound assessment of frailty?
Clearly surgeons and cardiologists are going to be caring for more elderly over time.
The current life expectancy at birth is 78.6 years, but at age 75 there are ……..
Incidence of frailty ~7% per year in community older populations.
Given that most outcome studies are 3-5 years at most, this is ample time to accumulate benefits from interventions in compressing morbidity.
Need to understand heterogeneity..can we measure age in the right units?
Extreme examples:
Gladys Burhill: age 92, finished the Honolulu marathon in just under 10 hrs. First marathon attempt, age 86 years old.
Keizo Miura: Japanese skiing legend and oldest active skier in the world. He skied the Swiss Alps in his 90s and helped spread the popularity of the sport in Japan. He died of multiple organ failure age 101, just 41 days shy of his 102nd birthday
Jeanne Calment: Longest lived human on record – from Arles France, smoked until her 100th birthday, lived to 122.

27. Frailty Loss of redundancy, complex adaptations, catabolic state
Physiology
Diminished mitochondrial function
Response to oxidative stress
Cell senescence
Telomere shortening
Changes in brain neurotransmitters
Altered inflammation and coagulation pathways
Pathology
Sarcopenia
Osteopenia
Subclinical organ dysfunction (C-statin, Lung FVC, brain white matter grade)
Physiologic state marked by an increased vulnerability to stressors
Frailty is loosely defined as a biological syndrome of decreased reserve and resistance to stressors, resulting from cumulative declines across multiple physiological systems, and causing vulnerability to adverse outcome

28. How Do You Define “Frailty” ?
Same age (90) and predicted risk (12%)
One passes the “eyeball test”; one doesn’t

29. NOT FRAIL !

30. FRAIL !

31. MAYBE FRAIL ?

32. MAYBE FRAIL ?

33. Frailty How are we currently assessing frailty for TAVR?
Gait Speed-Timed 5 meter walk
Hand grip
Katz ADL’s
Serum albumin
Eyeball Test

34. Conclusions
Gait speed is a simple and effective test that may identify a subset of vulnerable elderly patients at incrementally higher risk or mortality and major morbidity after cardiac surgery.

35. Frailty Testing- 5 Meter Walk
3 Repetitions
Cut off time to meet Frailty Criteria
Men
Height ≤ 173 cm ≥ 7 sec
Height ≥ 173 cm ≥ 6 sec
Women
Height ≤ 159 cm ≥ 7 sec
Height ≥ 159 cm ≥ 6 sec
5 Meter Walk

36. Frailty Testing- Grip Strength
Average of 3 separate attempts
Men Frailty cutoff (Kg)
BMI ≤ ≤ 29
BMI 24.1 – ≤ 30
BMI > ≤ 32
Women
BMI ≤ ≤ 17
BMI ≤ 18
BMI > ≤ 21
Grip Strength

37. Frailty Testing- Katz ADL’s
A score of:
6- indicates full function
4- indicates moderate impairment
2- or less indicates severe functional impairment.

38. Ultimate Goal-Identify those Patients Considered “Cohort C”
In other words:
Try to distinguish those patients who are dying from aortic stenosis from those patients who are dying with aortic stenosis

39. Frailty Key Points
The clinical implications of identifying frailty remain unclear: How should we use this information?
Should it be used to determine operability?
Frailty has not been shown to be unequivocally associated with adverse outcomes
Some Frail patients do well
Should it steer patients away from surgical AVR towards TAVR,
Or between TAVR or no TAVR
Psychological resilience may be equally or more essential than physical resilience and remains un-tested