Aortic Stenosis and TAVR 5/3/2017 TranscatheterAortic ......Two TAVR Options Edwards Sapien3 Valve Stainless Steel Frame Better for severe bulky calcification. Medtronic CoreValve

Aortic Stenosis and TAVR 5/3/2017

1

Transcatheter Aortic Valve Replacement

Stan Watkins, MD MHS FACC

Feb 3, 2017

Disclosure of Financial Interest

2

Partner at Alaska Heart Institute

No financial relationships with device manufacturers

Member of medical staff PAMC, ARH, ANMC, MSRMC

Aortic Stenosis


2

3 Major Etiologies for Aortic StenosisMajor Risk Factors

Independent clinical factors associated with degenerative aortic valve disease include the following:4

Increasing age

Male gender

Hypertension

Smoking

Elevated LDL cholesterol

6


3

Population at Risk for Aortic Stenosis is Increasing

Aortic stenosis is estimated to be prevalent in up to 7% of the population over the age of 652

Between 1990 and 2020, the US population from 65 – 74 years will increase 74%

Currently 38,000 Alaskans over 70yo, by 2042 est. 120,000

In Alaska population over age 75 will triple in next 30 yrs

7

Source: US Census Bureau, (US Census, 2010)1

Signs and Symptoms• Heart Failure• Angina• Syncope

• Carotid Parvus et Tardus• Laterally displaced PMI• Soft A2• Crescendo-Decrescendo

systolic murmur• Timing of peak murmur

predicts severity

Aortic Stenosis Is Life Threatening and Progresses Rapidly

Survival after onset of symptoms is 50% at 2 years and 20% at 5 years1

Surgical intervention for severe aortic stenosis should be performed promptly once even minor symptoms occur1


4

23

4

12

30 28

3 0

5

10

15

20

25

30

35

Prognosis

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

10

5-Year Survival8

Survival, %

BreastCancer

LungCancer

ColorectalCancer

ProstateCancer

OvarianCancer

SevereInoperable AS*

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

Trans-thoracic

Echo (TTE)

Chest X-ray

Electro-cardiogram

Cardiac Cath.

Auscultation

Multiple Modalities May Be Used to Diagnose Severe Aortic Stenosis6

11


5

*

Echocardiographic Guidelines are the Gold Standard in Assessing Severe Aortic Stenosis6

According to the 2014 ACC/AHA guidelines, severe aortic stenosis is defined as: Aortic valve area (AVA) less than 1.0 cm2

Mean gradient greater than 40 mmHg or jet velocity greater than 4.0 m/s

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*Doppler‐Echocardiographic measurements

Paradoxical Low Flow and/or Low Gradient Severe Aortic Stenosis10

Dobutamine stress echocardiography can be used to differentiate between true and pseudo severe aortic stenosis Better define the severity of the

aortic stenosis Accurately assess contractile/pump

reserve

Some patients with severe aortic stenosis based on valve area have a lower than expected gradient (e.g. mean gradient < 30 mmHg) despite preserved LV ejection fraction (e.g. EF > 50%) Up to 35% of patients with severe

aortic stenosis present with low flow, low gradient

These low gradients often lead to an underestimation of the severity of the disease, so many of these patients do not undergo surgical aortic valve replacement

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Dobutamine stress in low gradient, low ejection fraction AS Chambers, Heart. 2006 April; 92(4): 554–558

0102030405060708090

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Surv

ival

, %

AVR, no Sx

AVR, Sx

No AVR, no Sx

No AVR, Sx

Aortic Valve Replacement Greatly Improves Survival

Study data demonstrate that early and late outcomes were similarly good in both symptomatic and asymptomatic patients

It is important to note that among asymptomatic patients with SAS, omission of surgical treatment was the most important risk factor for late mortality

15

Patient Survival16AVR, No Symptoms

AVR, Symptoms

No AVR, No Symptoms

No AVR, Symptoms

Years


6

Options for Aortic Valve Replacement

16

Tilting Disc Valve

21 mm

18

Bio‐prosthetic Valve


7

Surgical Treatment

Studies show at least 40% of patients with severe AS are not treated with an AVR

19

Aortic Valve ReplacementNo Aortic Valve Replacement

Aortic Valve ReplacementNo Aortic Valve Replacement

What is TAVR-Transcatheter Aortic Valve Replacement?

An aortic valve replacement as an alternative to traditional thoracotomy.

Less invasive than traditional thoracotomy currently reserved for patients considered high risk for traditional surgery.

20

Alain Cribier: First Human TranscatheterValve Replacement (2002)

21


8

Two TAVR Options

Edwards Sapien 3 Valve

Stainless Steel Frame

Better for severe bulky calcification.

Medtronic CoreValve

Nitinol Frame-self expanding

Less Aortic Regurg, More heart block/PPM

Transfemoral Procedural Animation

23

N = 179

N = 358InoperableInoperable

StandardTherapy

ASSESSMENT: Transfemoral

Access


Access

Not In Study

TF TAVR

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

Co-Primary Endpoint: Composite of All-Cause Mortalityand 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

VSVS

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

PARTNER Study Design

Symptomatic Severe Aortic Stenosis

ASSESSMENT: High‐Risk AVR Candidate3,105 Total Patients Screened

ASSESSMENT: High‐Risk AVR Candidate3,105 Total Patients Screened

Total = 1,057 patients

2 Parallel Trials: Individually Powered

N = 699 High RiskHigh Risk


Access


Access

Transapical (TA)Transfemoral (TF)

1:1 Randomization1:1 Randomization

Yes No

Cohort A Cohort B


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Partner Trial

71.8%

93.6%

All-C

ause

Mor

talit

y (%

)

Months

HR [95% CI] = 0.50 [0.39, 0.65]p (log rank) < 0.0001

Standard Rx (n = 179)

TAVR (n = 179)

30.7%

50.8%

43.0%

68.0%

64.1%

87.5%

53.9%

80.9%

* In an age and gender matched US population without comorbidities, the mortality at 5 years is 40.5%.

Median Survival

Months

11.1 Months

29.7 Months

p (log rank) < 0.0001

Cohort B HF Improvement

27THE PARTNER TRIAL COHORT B


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Mean Gradient & Valve Area

159 86 70 44 31 15163 91 71 46 31 15

Mea

n G

radi

ent (

mm

Hg) Valve Area (cm

²)

N =

EOAMean Gradient

Error bars = ± 1 Std Dev

Complications

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Stroke was defined as follows: Neurological deficit lasting ≥ 24 hours or lasting less than 24 hours with a brain imaging study showing an infarction.

Major vascular complications were defined as any thoracic aortic dissection, access site or access‐related vascular injury (dissection, stenosis, perforation, rupture, arterio‐venous fistula, pseudoaneurysm, or hematoma) leading to either death, need for significant blood transfusion (> 3 units), or percutaneous or surgical intervention, and/or distal embolization (non‐cerebral) from a vascular source requiring surgery or resulting in amputation or irreversible end‐organ damage.

Bleeding event is defined as ≥ 2 units within the index procedure.

THE PARTNER TRIAL COHORT B

Reduction in Vascular Complications

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Major vascular complications reduced by 25% with next generation device

Sheath Size Comparison

eSheathRetroFlex 3Introducer Sheath

22F 16F

Events

SAPIEN(n=271)

SAPIEN XT(n=282)

n % n %

Vascular:Major 43 15.9 32 11.3

Bleeding:

Disabling 34 12.6 22 7.8

PARTNER II Trial Cohort B - Incidence data for this figure only contains data from 23 mm and 26 mm valve sizes and does not include 29 mm.


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TAVR 348 298 261 239 222 187 149

AVR 351 252 236 223 202 174 142

Cohort A: All-Cause Mortality

No. at Risk

HR [95% CI] =0.93 [0.74, 1.15]

p (log rank) = 0.483

26.8%

24.3%

34.6%

33.7%

44.8%

44.2%

The PARTNER 2A and S3i TrialsStudy Design

Intermediate Risk Symptomatic Severe Aortic Stenosis

Intermediate Risk ASSESSMENT by Heart Valve TeamIntermediate Risk ASSESSMENT by Heart Valve Team

TF TAVRSAPIEN 3

TA/TAo TAVRSAPIEN 3

P2 S3in = 1078P2 S3in = 1078

ASSESSMENT: Optimal Valve

Delivery Access

ASSESSMENT: Optimal Valve

Delivery Access

Transapical /Transaortic (TA/TAo)Transfemoral (TF)

Surgical AVR

Surgical AVR

P2An = 2032

P2An = 2032


Access


Access

Transapical /TransAortic (TA/TAo)Transfemoral (TF)

1:1 Randomization1:1 Randomization

Yes No

TF TAVR SAPIEN XT VS VSTA/Tao TAVR

SAPIEN 3

Primary Endpoint: All-Cause Mortality, All Stroke, or Mod/Sev AR at One Year (Non-inferiority Propensity Score Analysis)

ValveTechnology

SAPIEN SAPIEN XT SAPIEN 3

Sheath Compatibility

Available Valve Sizes

23 mm 26 mm 20 mm 23 mm 26 mm 29 mm

SAPIEN Platforms in PARTNER

22-24F 16-20F 14-16F

23 mm 26 mm 29 mm


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Events (%) 30 Days 1 YearTAVR Surgery TAVR Surgery

Death

All-cause 1.1 4.0 7.4 13.0Cardiovascular 0.9 3.1 4.5 8.1

Neurological Events

Disabling Stroke 1.0 4.4 2.3 5.9

All Stroke 2.7 6.1 4.6 8.2

All-cause Death and Disabling Stroke 2.0 8.0 8.4 16.6

Unadjusted Clinical EventsAt 30 Days and 1 Year (AT)

Mortality

1077 1043 1017 991 963944 859 836 808 795

All-C

ause

Mor

talit

y (%

)

0

10

20

30

40

7.4%

13.0%

1.1%

4.0%

Number at risk:

S3 TAVRP2A Surgery

Months from Procedure0 3 6 9 12

SAPIEN 3 TAVRP2A Surgery

Stroke

All S

trok

e (%

)

1077 1012 987 962 930944 805 786 757 743

4.6%

8.2%

2.7%

6.1%

0

10

20

30

40

0 3 6 9 12

Number at risk:

S3 TAVRP2A Surgery

Months from Procedure

SAPIEN 3 TAVRP2A Surgery


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Paravalvular Leak Significant difference

with surgery 25-50% have mild or

greater PVL Newer devices <5%

Mod AI in TAVR pts carries poor prognosis

Careful valve sizing decreases risk of significant PVL

≥ Moderate8.0%

0%

20%

40%

60%

80%

100%

TAVR Surgery TAVR Surgery

Severe

Moderate

Mild

None/Trace

P < 0.001 P < 0.001

No. of echos 30 Days 2 YearsTAVR 872 600Surgery 757 514

Mild26.8%

≥ Moderate 0.6%Mild 3.5%

Paravalvular RegurgitationSapien XT

0%

20%

40%

60%

80%

100%

TAVR Surgery TAVR Surgery

Severe

Moderate

Mild

None/Trace

Paravalvular RegurgitationSapien 3

P < 0.001 P < 0.001

No. of echos 30 Days 1 YearP2A Surgery 755 610

S3i TAVR 992 875

Mild39.8%

≥ Moderate1.5%


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2012 2013 2014 2015 Total

Number 4627 9052 16027 24808 54782

30dMortality

7.5 7.1 6.0 4.6

30d CVA 2.3 2.3 2.2 1.9

Major bleed 6.0 5.0 4.2 3.9

PPM - 9.0 11.9 12.0

>Mild AR 10.8 6.6 7.3 6.2

GETA 98 98 93 83

TVT Registry

10.1016/j.jacc.2016.11.033

Case Presentation

HS 94 yo male Offered evaluation at TAVR center 2013,

2014 Unwilling to travel outside for

evaluation/treatment Very willing to undergo eval and

treatment here


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Who Qualifies for TAVR? Symptomatic aortic stenosis

AVA< 1cm AND○ Mean AV gradient >40○ Peak AV velocity > 4m/s

Intermediate-high risk for standard AVR STS > 3

Estimated life expectancy of >1yr


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TAVR Evaluation Echo, carotid duplex, CTA heart, CTA

abdominal aorta, ECG Coronary angiogram Sizing: CTA/echo Clinical evaluation by 2 CV surgeons, 1

cardiologist Review at multidisciplinary valve

conference

Siemens Flash Dual Source CT

Can scan entire heart in single heart beat

Markedly improved spatial resolution

Decreases artifact from arrythmia

75% reduction in radiation

Operational 3/17


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TAVR in Alaska First cases done April 2015

Majority of initial patients were extreme risk/non-surgical candidates

Median length of stay 2d Procedure times < 45mins

Future: Expanding patient population including

intermediate risk (9/16), low risk trial underway

Move procedure to cath lab from OR

TAVR Patients

2015 43

2016 58

2017 25

Total 126

AGE

Median 84

Max 94

Min 54

Type of TAVR ValveEdwards Sapien XT

25

Edwards Sapien 3 92Medtronic Valves

VIV patients 107

Anesthesia

General 59

Conscious sedationStarted 3/22/16 67

Change from Sapien XT to Sapien 3/6/15 (Sheath size decrease)TAVR approved for Intermediate risk 9/8/16

TAVR in Alaska TVT Registry


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Length of Stay Procedure Time

Procedure time is from the time of Lidocaine injection to the time the patient leaves the OR room

Complications for 2016

o Complications In Hospitalo 1 Pacemakero 3 minor vascular complicationo 1 retroperitoneal bleedo 1- 2upc transfusion


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The Future Valve-in-valve-Transcatheter repair of degenerated bioprostheticsurgical valve-Indicated for bioprostheticfailure by stenosis or regurgitation-Expanding usage of bioprosthetic valves in younger patients


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Following Patient Referral, the TAVR Team will Perform Further Evaluation

63

Confirm the patient is diagnosed with severe symptomatic native

aortic stenosis

Confirm the patient has been

independently evaluated by two

cardiac surgeons and meets the indication

for TAVR

Evaluate the aortic valvular complex using

echocardiography

Evaluate the peripheral

vasculature and aortic valvular complex

using MDCT

Evaluate the peripheral vasculature and aortic valvular complex using

catheterization

Note: Evaluation using CT is typically not done unless the Heart Team confirms that patient is a candidate for TAVR

4 531 2


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Alaska TAVR Heart TeamValve Coordinators: Leslie Barnard, Deni Callahan 212-TAVR

PhysiciansStan Watkins, MD Bob Pease, MD Bill Curtis, MDTom Kramer, MD Steve Rosenfield, MD Pedro Valdes, MDJon McDonagh, MD Barb Chen, MD Ursula McVeigh, MD

Kirsten Randall, MD

Key Takeaways

Aortic Stenosis is prevalent with a high morbidity and mortality when symptomatic and aortic valve replacement is the only treatment associated with improved outcomes.

Symptomatic (and some asymptomatic) low risk patients will benefit from surgical AVR.

TAVR is a safe and effective alternative to traditional aortic valve surgery

65

Thank You!


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Documents

Aortic Stenosis and TAVR 5/3/2017 TranscatheterAortic ......Two TAVR Options Edwards Sapien3 Valve Stainless Steel Frame Better for severe bulky calcification. Medtronic CoreValve