1. Transcatheter Aortic Valve Implantation: Current Use and Future Directions
Alan Zajarias
Assistant Professor of Medicine
Washington University School of Medicine
St. Louis

2. I have no financial conflicts of interest to disclose
I will be discussing treatments that are experimental and currently not FDA approved

3. Question 1
The treatment of a 88 y/o male with severe aortic stenosis, coronary artery disease s/p CABG, mild COPD, insulin dependent diabetes mellitus who complains of worsening lower extremity edema, orthopnea and syncope is:
Routine follow up
Add digoxin to improve heart failure symptoms
Aortic valve replacement
Bi-V pacemaker implantation

4. Question 2 Transcatheter aortic valve implantation:
Can be performed in patients with bicuspid aortic valve.
Is an experimental treatment that can be utilized in patients with aortic insufficiency.
Is commercially available in the US for any patients with severe symptomatic aortic calcific stenosis.
Is an experimental treatment that is being evaluated in patients with severe symptomatic aortic stenosis who have an elevated (STS PROM>10%) surgical risk.

5. Objectives
Review the concept of transcatheter aortic valve implantation (TAVI)
Describe the evaluation process of patients considered for TAVI
Review the short and mid-term results following TAVI
Identify future applications of transcatheter valve implantation

6. Natural History of Aortic Stenosis (AS)
740 pts with severe AS
AVA < 0.8 cm2
451 had non surgical treatment
Mean age: 75+13yrs
LVEF < 40%: 33%
CHF: 42%
Ann Thorac Surg 2006; 82: 6

7. ACC/AHA recommendations for AVR
Class I
Symptomatic severe AS
Asymptomatic severe AS undergoing CABG
Severe AS undergoing surgery of the aorta or other valves
Severe AS and LV dysfunction (EF<50%)
Class IIa
Moderate AS and patients undergoing CABG
J Am Coll Cardiol 2008;52:e1-e142

8. Operative Mortality for AVR
AVR in octogenarians
220 pts
Op mortality 13% if AVR
Op mortality 24% if AVR + CABG
Morbidity 60%
Survival 85%, 80%, 73% (1,3,5 yrs)
Benefits of AVR in octogenarians
81% no/mild disability for daily activities
93% feel less disabled
93% reassured to have access to treatment despite their age
STS2001
(%)
UKCSR (%)
EHS 2001
AVR
3.7
3.1
2.7
AVR + CABG
6.3 7
4.3
Eur J Cardio Thorac Surg 2007;31: Eur J Cardio Thorac Surg 2007;31: Euro J Cardiothorac Surg 2006; 30: 8

9. Many patients are not surgically treated!
Severe AS* - Percent of Patients Treated
J Heart Valve Dis2006;15: ; Circulation 2005;
European Heart Journal 2003;24: ;
Heart 1999;82: 9

10. Surgical risk evaluation
Operative risk calculators
STS risk calculator
EuroSCORE
Not designed for valvular surgery
Do not include many variables that would increase risk of complications (ie: porcelain aorta, cirrhosis, previous mediastinal radiation, history of mediastinits)
Reflection of true risk?
High risk: >10% risk of operative mortality
Preprocedural functional status influences outcomes*
*Buellesfeld et al. Euro Heart J 2009 in press

11. Is there a treatment for patients with severe symptomatic AS whose surgical is prohibitive or who have a frank contraindication to surgical AVR?

12. Transcatheter Aortic Valve Implantation (TAVI)
1993: Andersen
First description of valve sutured in stent
Animal model
Encountered 2 major limitations
Removal of the native valve
Obstruction of coronary ostia

13. First human implantation: Bovine pericardium valve
April 16, 2002 (Rouen – France)
Bovine pericardium valve
23mm in diameter

14. Transcatheter Aortic Valve Implantation (TAVI)
Placement of a prosthetic valve mounted inside stent/frame in the aortic valve position via a transarterial (retrograde) or transapical (antegrade) approach.
CoreValve Revalving system
Edwards SAPIEN valve

15. Differences between the SAPIEN and Surgical Implanted Valves
Magna
Freestyle
EOA (cm2)
1.6
1.2
1.38
Mean Gradient (mmHg) 10 13 14
Absence of AI
12%
62%
66%
J Am Coll Cardiol 2009;52: 15

16. Patient Evaluation Multidisciplinary approach
Cardiac Surgery
Cardiology
Valvular Heart Disease Clinic
Patients are seen simultaneously by surgeons and cardiologists to assess:
Operative candidacy
Symptom severity
Frailty
Patient interest
Is aortic valve replacement going to improve their quality of life?

17. Patient Selection Inclusion Criteria Operable vs. Inoperable
Symptomatic patients with severe AS (AVA<0.8 cm2)
High risk AVR (STS >10%)
NYHA >2
Operable vs. Inoperable
Exclusion Criteria
AMI < 1 month
Bicuspid aortic valve
Non-revascularized CAD
Existing valvular prosthesis or valvular surgery, > 3+ MR, > 3+ AI
HOCM
Creatinine > 3 mg/dl
Hgb < 9
GI bleed < 3 months
Cardiogenic Shock
TIA or CVA < 6 months
Life expectancy < 12 months
AAA
Vascular access

18. Screening Echocardiography
Transthoracic Echocardiogram
Determine severity of AS
Confirm annular dimension
Evaluate LVEF
Characterize other valvular disease
Transesophageal Echocardiogram
Annulus confirmation
Evaluate severity of MR
Controversy in measurements of TTE and TEE*
Consider DSE to assess contractile reserve

19. Screening Angiogram Aortic angiogram
Identify ideal projection where all aortic leaflets are in plane with the image intensifier
Identify characteristics of the aortic arch and ascending aorta that may complicate the procedure

21. Screening Angiogram Iliac angiogram
Gross marker of peripheral vascular disease
Rudimentary assessment of arterial tortuosity, calcification, and diameter to determine patient candidacy for large sheath insertion.
EuroIntervention Sep;5(4):438-42

22. Patient Evaluation CT Angiogram Arterial calcification
Arterial tortuosity
Minimal luminal diameter 22

23. CT Angiography Contrast vs. non-contrast
Intra-arterial contrast decrease contrast volume required
Automated vs. manual diameter determination
Large arteries determination is similar
Smaller, calcified arteries there is a marked difference

24. Screening CT Distance from coronary artery to aortic annulus
Aortic annulus dimension
LVOT and sino-tubular dimension

25. Screening CT
Prediction of angle of incidence to limit radiation and contrast
Lack of concordance in measurements in the sagital or coronal projections with echocardiography
Messika, J Am Coll Cardiol. 2010;55(3): Kurra JACC Cardiovasc Interv. 2010;3(1):105-13

26. Transfemoral Approach

27. CoreValve

28. Transfemoral Approach Sapien Valve
RetroFlex 3 Delivery System
Edwards SAPIEN THV
RetroFlex Balloon Catheter
RetroFlex 3 introducer Sheath Set
Atrion
Inflation Device
Crimper
RetroFlex Dilator Kit 28 28

29. Transfemoral Approach
Aortic Angiogram

30. Transfemoral Approach
Balloon Aortic Valvuloplasty

31. Transfemoral Approach
Valve Deployment
Aortic Pressure
RV pacing: 200/min

32. Transfemoral Approach
Aortic Angiogram

33. Transfemoral Approach
Femoral Angiogram

34. Transapical Approach

35. Ascendra™ Transapical Approach
Ascendra™ Introducer Sheath Set
Edwards SAPIEN™ THV
Ascendra™ Delivery System
Atrion Inflation Device
Ascendra™ Valvuloplasy Catheter 35
Crimper 35

36. Transapical Approach
Direct left ventricular puncture

37. Transapical Approach
Aortic Valvulopalsty

38. Transapical Approach
Placement and valve deployment

39. Transapical Approach
Aortogram

40. Intra-Procedural Echo
Valve placement
Early detection of complications
Aortic insufficiency
Central
Peri-valvular
Discrepancy with fluoroscopy?

41. Results

42. Results Sapien CoreValve
Procedural success: 94% 97% Aortic valve area: 1.56 cm2 NR Mean gradient(mmHg): Aortic insufficiency > 2: 4% 0% Coronary obstruction: 0.6% 0% Prosthesis migration: 0.3% NR Surgical conversion: 2.7% 1.4% Malposition: 1.5% NR Valve in valve: NR 2.6%
NR: not reported
Circulation 2009;119:3009 Eurointervention 2008;4:

43. Functional Class Sapien CoreValve* European registry (not published)
Circulation 2009;119:3009

44. Complications
Sapien
CoreValve
Procedural Mortality: % % Mortality (30 d): % 8-12% MACE: 14% 9.3% MI: 1% % CVA: % % Pacemaker: 5.4% 10-33% Vascular complications: 6.6% % Cardiac tamponade: 2.4% % Aortic dissection: 0% %
Am Heart J 2009;157:860-6; Source Registry
Eurointervention 2008;4:242-49
Circulation 2009;119:3009

45. Pacemaker Incidence of AV block varies between prostheses
Occurs in first 7 days
Dependent on:
Final valve position
Pre-existing conduction defects
JACC Intervention 2008;1: Am Heart J 2009;157:860-6

46. TAVI and CVA Clinical CVA: 1-10% Subclinical CVA due to:
CoreValve: 72%
CVA due to:
Aortic root passage
Crossing the valve
Valve deployment
Is the incidence different with the Sapien valve?
J Am Coll Cardiol 2010;55:

47. 1 Year Survival
Circulation 2009;119:3009

48. Mortality Transapical has a higher mortality rate
Higher risk cohort
Steep learning curve
More invasive arm
To date, the transapical approach has only been offered as a alternative to those who are not a transfemoral candidates.
Circulation 2009;119:3009
JACC 2010;55:

49. Mortality Procedural death 1.7% Post procedural 8.7% 30 day 10.4%
Vascular access complications 13%
JACC 2010;55:

50. Factors Associate with Mortality
30 day
GFR<60
Pulmonary HTN
Severe MR
Hemodynamic support during procedure
Late mortality
Hemodynamic support
Sepsis
Pulmonary hypertension
COPD
Chronic kidney disease
JACC 2010;55:

51. Porcelain Aorta and Frailty
Younger
No difference in mortality
CVA: 1.6%
Frailty
Similar mortality rate
JACC 2010;55:

52. TAVI vs. AVR
When compared to partial upper sternotomy, transapical AVR provides:
Shorter ICU stay
Shorter ventilator time
Shorter OR time
Similar 30 day morbidity/mortality
Thorac Cardiovasc Surg Nov;138(5):

53. Acute Kidney Injury post TAVI
Incidence: 12%
Dialysis 1.4%
Mortality: 28% vs. 7%
TAVI vs. SAVR
Acute Kidney Injury: 9.2% vs. 25%
Dialysis: 2.5% vs. 8.7%
Risk Factors:
Hypertension OR= 4.66
COPD OR= 2.64
Transfusion OR= 3.47
E Heart J 2010 in press

54. TAVI in Degenerated Bioprostheses
Aortic
Capable with CoreValve and Sapien
Bioprosthesis only
Annular/Size diameter
CoreValve: not in annulus < 21mm
Mitral
Transapical approach
Sapien only
Pulmonary
Khawaja et al. J Am Coll Cardiol 2010;55:97-101
Wegamer, et al. J Am Coll Cardiol Img 2010;3:

55. Future Directions
FDA approval of TAVI will depend on the results of the PARTNER trial
Initiation of the CoreVALVE randomized trial and PARTNER II
TAVI modifications
Smaller sheaths
Repositionable
Multi-modality imaging
Numerous other valves in development and their introduction will depend on the results and information obtained from the ongoing trials

56. Unanswered Questions What is the in vivo durability?
What is the role of TAVI in low-gradient AS?
Which institutions should be qualified to perform TAVI if it is marketed?
Should younger patients receive a surgical bioprosthesis in order to avoid long term use of oral anticoagulation, planning that they may receive a TAVI for prosthesis degeneration?
Will there be a use of catheter valve implantation in lower risk population?

57. Conclusion
Surgical AVR is the treatment of choice in patients with severe AS. Early detection and treatment of these patients would decrease their surgical risk.
TAVI is an exciting new field which opens therapeutic options to patients who were previously not eligible for treatment.
The success of any program involved in TAVI will depend on the close interaction of ALL members of the team.
Results of the PARTNER trial are eagerly accepted in order to guide the next steps in the development of transcatheter valvular therapy.