Aortic Stenosis Aortic Stenosis Etiology Congenital (bicuspid, - - PowerPoint PPT Presentation

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TAVR: Evolution and Vascular Implications

Yerem Yeghiazarians, MD Associate Professor of Medicine Leone-Perkins Family Endowed Chair in Cardiology University of California, San Francisco

Vascular Symposium April 4, 2014 Disclosures NONE

Aortic Stenosis

• Etiology

– Congenital (bicuspid, unicuspid) – Rheumatic (mixed AS/AR) – Calcific/Degenerative (risk factors – age, male, current smoking, HTN, high LDL and Lp(a), renal insufficiency, hypercalcemia) AS is present in ~25% of adults over 65 years of age

Aortic Stenosis

Gross specimen of minimally diseased aortic valve (left) and severely stenotic aortic valve (right)

Images courtesy of Renu Virmani MD at the CVPath Institute

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Aortic Stenosis

• Classification of Severity

– Mild (area 1.5 cm2, mean gradient <25 mmHg, jet velocity <3.0 m/sec) – Moderate (area 1.0-1.5 cm2, mean gradient 25-40 mmHg, jet velocity 3.0-4.0 m/sec) – Severe (area <1.0 cm2, mean gradient >40 mmHg, jet velocity >4.0 m/sec)

NOTE: Do not rely on single number; Account for BSA; Symptoms predominate

Aortic Stenosis

~1/3 of patients with severe symptomatic aortic stenosis do not undergo AVR

1. Bouma B J et al. To operate or not on elderly patients with aortic stenosis: the decision and its consequences. Heart 1999;82:143-148 2. Iung B et al. A prospective survey of patients with valvular heart disease in Europe: The Euro Heart Survey on Valvular Heart Disease. European Heart Journal 2003;24:1231-1243 (*includes both Aortic Stenosis and Mitral Regurgitation patients) 3. Pellikka, Sarano et al. Outcome of 622 Adults with Asymptomatic, Hemodynamically Significant Aortic Stenosis During Prolonged Follow-Up. Circulation 2005 4. Charlson E et al. Decision-making and outcomes in severe symptomatic aortic stenosis. J Heart Valve Dis2006;15:312-321

23 4 12 30 28 3

5 10 15 20 25 30 35

5 year survival of breast cancer, lung cancer, prostate cancer, ovarian cancer and severe inoperable aortic stenosis 8

Poor Prognosis

5-Year Survival

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Survival, %

Breast Cancer Lung Cancer Colorectal Cancer Prostate Cancer Ovarian Cancer Severe Inoperable AS*

*Using constant hazard ratio. Data on file, Edwards Lifesciences LLC. Analysis courtesy of Murat Tuczu, MD, Cleveland Clinic

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Transfemoral Transapical

TAVR Transfemoral and Transapical

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Edwards SAPIEN Transcatheter Heart Valve

Bovine pericardial tissue Leaflets matched for thickness and elasticity PET skirt Stainless steel frame

Study Devices

Edwards SAPIEN THV

23 and 26 mm valves

RetroFlex

22 and 24 F sheaths

Ascendra

24 and 26 F sheaths

Valve Size to Annulus Diameter

Annulus diameter by TEE

23 mm or 26 mm valve

• The Edwards SAPIEN transcatheter heart valve is offered in two sizes, 23 mm and 26

mm, and accommodates an annular size range of 18 mm to 25 mm 12

Ensuring the Appropriate Annular Size Range

18 mm 19 mm 20 mm 21 mm 22 mm 23 mm 24 mm 25 mm

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N = 699 N = 358 High Risk High Risk Inoperable Inoperable

PARTNER Study Design

Symptomatic Severe Aortic Stenosis

ASSESSMENT: High-Risk AVR Candidate 3,105 Total Patients Screened ASSESSMENT: High-Risk AVR Candidate 3,105 Total Patients Screened

Total = 1,057 patients 2 Parallel Trials: Individually Powered

Standard Therapy ASSESSMENT:

Transfemoral Access 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 N = 179

Inoperable PARTNER Cohort Primary Endpoint: All-Cause Mortality

Numbers at Risk TAVI 179 138 122 67 26 Standard Rx 179 121 83 41 12

Standard Rx TAVI

All-cause mortality (%) Months

∆ at 1 yr = 20.0% NNT = 5.0 pts 50.7% 30.7% HR [95% CI] = 0.54 [0.38, 0.78] P (log rank) < 0.0001

Leon et al, NEJM 2010; 363:1597-1607 N = 179

N = 358 Inoperable Inoperable

Standard Therapy ASSESSMENT:

Transfemoral Access 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 ASSESSMENT: High-Risk AVR Candidate 3,105 Total Patients Screened

Total = 1,057 patients 2 Parallel Trials: Individually Powered

N = 699 High Risk High Risk

ASSESSMENT: Transfemoral Access ASSESSMENT: Transfemoral Access Transapical (TA) Transfemoral (TF) 1:1 Randomization 1:1 Randomization Yes No

0.1 0.2 0.3 0.4 0.5 6 12 18 24 TAVR AVR

Months

348 298 260 147 67 351 252 236 139 65

• No. at Risk

TAVR AVR

26.8 24.2

Primary Endpoint: All-Cause Mortality at 1 Year

HR [95% CI] = 0.93 [0.71, 1.22] P (log rank) = 0.62

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30 Days

1 Year Outcome TAVR (N = 348) AVR (N = 351) 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) 0.04 TIA – no. (%) 3 (0.9) 1 (0.3) 0.33 7 (2.3) 4 (1.5) 0.47 All Stroke – no. (%) 16 (4.6) 8 (2.4) 0.12 20 (6.0) 10 (3.2) 0.08 Major Stroke – no. (%) 13 (3.8) 7 (2.1) 0.20 17 (5.1) 8 (2.4) 0.07 Minor Stroke – no. (%) 3 (0.9) 1 (0.3) 0.34 3 (0.9) 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

Neurological Events at 30 Days and 1 Year All Patients (N=699)

p-value p-value

Major Vascular Complications

AT Population

18

THE PARTNER TRIAL COHORT A

Courtesy of Sandeep Nathan, MD

Major Bleeding

AT Population

19

THE PARTNER TRIAL COHORT A

Courtesy of Sandeep Nathan, MD

TAVR Vascular Complications

JACC 2012; 1043-1052

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TAVR Vascular Complications

JACC 2012; 1043-1052

Vessel diameters must be a minimum of:

– ≥ 7 mm for a 23 mm valve (requires a 22F RetroFlex 3 sheath) – ≥ 8 mm for a 26 mm valve (requires a 24F RetroFlex 3 sheath)

Assessing Appropriate Vascular Access

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Courtesy of Sandeep Nathan, MD

TAVR: Present & future TAVR: Present & future

Edwards Sapien THV (1st generation) 22/24 Fr with

RetroFlex 3 delivery system

Edwards Sapien XT (2nd generation) 18/19 Fr with

NovoFlex delivery system

Medtronic CoreValve Medtronic Engager TA valve (Ventor Embracer) Boston Scientific Lotus self-exp valve (Sadra Lotus)

• St. Jude Medical

Portico valve JenaValve

Medtronic CoreValve TM Medtronic CoreValve TM

• 18 Fr delivery system
• Transfemoral or subclavian delivery
• Repositionable, self-expanding system
• Perhaps greater need for pacing afterwards

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91 year old with severe AS requiring a 26 mm Edwards valve (TAVR) Requires a 24F RetroFlex 3 sheath Right groin access Up and around angio of the left side and advancement of pigtail to the left common femoral artery for optimal TAVR access Preclose with 3 Perclose Devices Advanced a 300 cm Steel Core wire to the left SFA via a crossover sheath Successful TAVR with 26 mm valve under rapid pacing

• f 180 beats/min to induce cardiac standstill

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Advanced a 10mm x 4cm Charger balloon to the left external iliac

• ver the Steel Core wire and Perclosed the 3 Preclose devices. Then

Inflated the balloon to 1 atm for 5 mins at the femoral head

Future of TAVR – it’s very bright!

• 1. Lower profile devices
• 2. Repositionable devices
• 3. Retrievable devices
• 4. Paravalvular leak
• 5. Delivery system options
• 6. Eliminate need for pacing
• 7. Embolic protection

Courtesy of Sandeep Nathan, MD

Question 1: Is TAVR FDA approved for use in Bicuspid Aortic Valve Stenosis?

Yes No

67% 33%

• 1. Yes
• 2. No

Impact of Total AR on Mortality (AT)

TAVR Patients

131 121 114 102 93 80 63 171 146 125 117 110 94 62 34 24 21 18 15 12 9 None-Tr Mild Mod-Sev

• No. at Risk

53.7% 25.6% 32.5% 38.2% 12.3% 26.0% 60.8% 35.3% 44.6%

4/4/2014 9 Question 2: Is TAVR FDA approved for use as treatment for Aortic Valve Regurgitation?

Y e s N

• 79%

21%

• 1. Yes
• 2. No

Thank You