1

Transcatheter Aortic Valve Replacement: Current and Future Devices: How do They

Work, Eligibility, Review of Data

Jonathan J. Passeri, M.D.

Co-Director, Heart Valve Program

Director, Interventional Echocardiography

Echo Florida 2013

Disclosures

• Edwards LifeSciences

Current and Future Devices

2

Transcatheter Aortic Valve Replacement

• Anderson et al, 1992

– Swine model

• Bonhoeffer et al, 2000

– First human use of stent mounted bioprosthesis for pulmonary valve regurgitation

• Cribier et al, 2002

– First-in-man percutaneous aortic valve implantation

– Antegrade transvenous delivery

• Webb et al, 2006

– Retrograde via femoral artery

– Also transapical LV delivery

Transcatheter Valve Technology

• April 23, 2002

• First Heart Valve Replacement Without Open Heart Surgery

• SOURCE: Percutaneous Valve Technologies, Inc. (PVT) Experimental Device Developed By Percutaneous Valve Technologies May Provide Alternative to Open Heart Surgery In the United States

• “The 57 year old male patient that received the aortic valve procedure had a failing heart and was refused for surgery by three surgical teams because of his deteriorating condition and complicated vascular disease,” said Dr. Alain Cribier. “Lacking any other clinical solution for this patient, the PVT valve was a life saving technology. We are pleased to be the world's first clinical site to utilize this device.”

SAPIEN Transcatheter Heart Valve

Collapsed Expanded 26 mm 23 mm

3

Percutaneous Aortic Valve

Implantation Via Antegrade Approach

Balloon valvuloplasty followed by

stented valve deployment during rapid

ventricular pacing

Cribier et al, JACC 2004;43:698-703

Webb et al. Circulation 2006; 113:842-850

Transfemoral Retrograde Approach for

Transcatheter Aortic Valve Replacement

Alternative Mode of Transcatheter

Deployment: Transapical Antegrade

Approach

4

Direct Aortic Approach

Sapien THV and Delivery systems

Edwards SAPIEN THV 23 and 26 mm valves

RetroFlex 22 and 24 F sheaths

Ascendra 24 and 26 F sheaths

The Next Generation: SAPIEN XT THV

5

NovaFlex Delivery System

CoreValve

Sapien and CoreValve

Edwards Sapien CoreValve

6

CoreValve

Emerging Transcatheter Heart Valves

a | Direct Flow Medical® valve (Direct Flow Medical, Santa Rosa, CA, USA).

b | HLT valve (Heart Leaflet Technologies, Maple Grove, MN, USA). c | Innovare valve (Braile Biomedical, São José do Rio Preto, Brazil).

d | JenaValve® (JenaValve Technology, Munich, Germany).

e | Portico® valve (St-Jude Medical, St Paul, MN, USA). f | Sadra® Lotus Medical valve (Boston Scientific SciMed Inc, Maple Grove, MN, USA).

g | Symetis® Accurate valve (Symetis SA, Lausanne, Switzerland).

h | Engager® valve (Medtronic Inc., Minneapolis, MN, USA).

Rodés-Cabau, J. (2011) Transcatheter aortic valve implantation: current and future approaches

Nat. Rev. Cardiol. doi:10.1038/nrcardio.2011.164

Who is Eligible?

• Medical Eligibility

• Anatomic Eligibility

7

N = 179

N = 358 Inoperable

Standard

Therapy

ASSESSMENT:

Transfemoral

Access

Not In Study

TF TAVR

Primary Endpoint: All-Cause Mortality

Over Length of Trial (Superiority) Co-Primary Endpoint: Composite of All-Cause Mortality

and Repeat Hospitalization (Superiority)

1:1 Randomization

VS

Yes No

N = 179

TF TAVR AVR

Primary Endpoint: All-Cause Mortality at 1 yr

(Non-inferiority)

TA TAVR AVR VS

VS

N = 248 N = 104 N = 103 N = 244

PARTNER Study Design

Symptomatic Severe Aortic Stenosis

ASSESSMENT: High-Risk AVR Candidate

3,105 Total Patients Screened

Total = 1,057 patients

2 Parallel Trials: Individually Powered

N = 699 High Risk

ASSESSMENT:

Transfemoral

Access

Transapical (TA) Transfemoral (TF)

1:1 Randomization 1:1 Randomization

Yes No

N = 179

N = 358 Inoperable

Standard

Therapy

ASSESSMENT:

Transfemoral

Access

Not In Study

TF TAVR

Primary Endpoint: All-Cause Mortality

Over Length of Trial (Superiority) Co-Primary Endpoint: Composite of All-Cause Mortality

and Repeat Hospitalization (Superiority)

1:1 Randomization

VS

Yes No

N = 179

PARTNER Study Design: Inoperable

Patients

Symptomatic Severe Aortic Stenosis

ASSESSMENT: High-Risk AVR Candidate

3,105 Total Patients Screened

Inclusion Criteria: Inoperable Group

• Severe Aortic Stenosis: Echo-derived AVA < 0.8 cm2 (or AVA index < 0.5 cm2/m2) and mean AVG > 40 mm Hg or peak jet velocity > 4.0 m/sec.

• Cardiac Symptoms: NYHA Functional Class II or greater

• Inoperable: Predicted risk of death or serious irreversible morbidity must exceed 50%

8

Transfemoral Transapical

TAVR: Transfemoral Delivery

All Cause Mortality (ITT)

All

Ca

use

Mo

rta

lity (%

)

Months

Standard Rx

TAVR

∆ at 2 yr = 24.7% NNT = 4.0 pts

68.0%

43.3%

∆ at 1 yr = 20.0% NNT = 5.0 pts

50.7%

30.7%

Numbers at Risk

TAVR 179 138 124 110 83 47 14

Standard Rx 179 121 85 62 42 19 5

HR [95% CI] = 0.57 [0.44, 0.75]

p (log rank) < 0.0001

FDA Approval

November 2, 2011:

Edwards SAPIEN THV via Transfemoral Delivery

approved by FDA for Inoperable patients

9

Who is Eligible?

• Medical Eligibility

– Symptomatic Severe Calcific Aortic Stenosis

• Inoperable in estimation of two cardiac surgeons

• Implantation route via FDA labeling

TF TAVR AVR

Primary Endpoint: All-Cause Mortality at 1 yr

(Non-inferiority)

TA TAVR AVR VS

VS

N = 248 N = 104 N = 103 N = 244

PARTNER Study Design: High Risk

Surgical Group

Symptomatic Severe Aortic Stenosis

ASSESSMENT: High-Risk AVR Candidate

3,105 Total Patients Screened

N = 699 High Risk

ASSESSMENT:

Transfemoral

Access

Transapical (TA) Transfemoral (TF)

1:1 Randomization 1:1 Randomization

Yes No

Inclusion Criteria: High-Risk Surgical

Group

• Severe Aortic Stenosis: Echo-derived AVA < 0.8 cm2 (or AVA index < 0.5 cm2/m2) and mean AVG > 40 mm Hg or peak jet velocity > 4.0 m/sec.

• Cardiac Symptoms: NYHA Functional Class II or greater

• High Surgical Risk: Predicted risk of operative mortality ≥ 15% (determined by site surgeon and cardiologist); guideline = STS score ≥ 10

10

Transfemoral Transapical

TAVR:

Transfemoral or Transapical Delivery

ACC 2012: All-Cause Mortality at 2 Years

Kodali SK et al. N Engl J Med 2012;366:1686-1695.

Who is Eligible?

• Medical Eligibility

– Symptomatic Severe Aortic Stenosis

• Inoperable in estimation of two cardiac surgeons

• Implantation route via FDA labeling

• High risk surgical candidates soon to come?

• Meets eligibility for ongoing clinical trial (PARTNER

II, CoreValve U.S. Pivotal)

11

Medical Eligibility: Contraindications and

Cautions

• Non-calcified aortic valve

• Bicuspid aortic valve

• Severe aortic regurgitation

• Severe mitral regurgitation

• Poor prognosis from non-cardiac disease (advanced

malignancy, very severe COPD

Transcatheter Aortic Valve Replacement: Outcomes of

Patients With Moderate or Severe Mitral Regurgitation

J Am Coll Cardiol. 2012;59(23):2068-2074. doi:10.1016/j.jacc.2012.02.020

Kaplan-Meier Curves for All-Cause Mortality in Patients With Mild or Less, Moderate, and Severe MR at Baseline

Survival in patients with mild or less, moderate, and severe mitral regurgitation (MR) at baseline was 92.5%, 86.5%, and 83.7% at 30 days; 79.0%, 76.2%, and 64.5% at 1 year; and 66.2%, 67.9%, and 58.5% at 2 years, respectively. TAVR = transcatheter aortic va lve

replacement.

Source XT: Improvement in Mitral

Regurgitation

Presented by H Baumgartner PCR London Valves 2012

12

Medical Eligibility: Areas of Uncertainty

• Understanding Frailty

• Mild or Moderate Dementia

• End-Stage Renal Disease

• Low-gradient Aortic Stenosis (without contractile reserve)

• Very Low Ejection Fraction

Anatomic Eligibility

• Aortic valve morphology

• Annulus size

• Determining route of vascular access for implantation

– Not always about vessel size

– Minimize risk of stroke and vascular complications

• LVOT and aortic root anatomy/pathology

– HOCM

– Narrowed and circumferentially calcified STJ

Relation of Paravalvular Aortic Regurgitation to All-Cause Mortality in the TAVR As-Treated Population.

Kodali SK et al. N Engl J Med 2012;366:1686-1695.

13

CTA

Bicuspid Aortic Valve

Bicuspid Aortic Valve: TAVR

14

Bicuspid Aortic Valve: TAVR

How to Assess Eligibility

• Comprehensive medical evaluation

• Echocardiogram

• CTA

• Cardiac catheterization

• Transesophageal echocardiography

THANK YOU!