update on low risk trials: current indications and guidelines ......state of aortic valve...

Update on Low Risk Trials:Update on Low Risk Trials:Current Indications andCurrent Indications and

Guidelines for TAVRGuidelines for TAVR

SCRIPPS CLINIC

Paul S. Teirstein

Chief of Cardiology

Director, Interventional Cardiology

Scripps Clinic

Disclosure Statement of Financial InterestDisclosure Statement of Financial Interest

Within the past 12 months, I or my spouse/partner have had a financialinterest/arrangement or affiliation with the organization(s) listed below.

Affiliation/Financial Relationship Company

Grant/Research Support Boston, Abbott, Medtronic, Edwards

Consulting Fees/Honoraria Boston, Abbott, Medtronic, Edwards

President (unpaid) NBPAS

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Things that upset me, pretty much every day

• Our new “EPIC” electronic health record• My cable bill• My wife’s driving• ….• Pretty much everyday…I say to myself…

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• Pretty much everyday…I say to myself…“Why didn’t I invent TAVR?”

STATE OF TAVR IN THE USDRAMATIC GROWTH

24,927

38,159

42,605

30,000

35,000

40,000

45,000

Commercial TAVR Cases(TVT-R)

24,927

38,159

42,605

29,829 30,26528,493

25,58030,000

35,000

40,000

45,000

AVR and TAVR Volumes(STS & TVT-R)

TAVR

AVR

4

4,503

8,977

16,308

24,927

0

5,000

10,000

15,000

20,000

25,000

30,000

2012 2013 2014 2015 2016 2017

16,308

24,927 25,580

0

5,000

10,000

15,000

20,000

25,000

30,000

2014 2015 2016 2017E*

Source: STS/ACC TVT Registry Database as of 3-1-18, presented by Carroll, CRT 2018

Transcatheter Valve Hemodynamics | May 2018

STATE OF AORTIC VALVE REPLACEMENT IN THE US31% GROWTH IN TOTAL AORTIC VALVE PROCEDURES SINCE 2014 (TAVR &SAVR)

64,085

84,095

50,000

60,000

70,000

80,000

90,000

Total AVRs

5

-

10,000

20,000

30,000

40,000

50,000

2014 2017



STATE OF TAVR IN THE USMEAN AGE IS DROPPING

82

81 81

82

83

Mean Patient Age

6

81 81

80

79

80

81

2014-R4Q 2015-R4Q 2016-R4Q 2017-Q2R4Q



CONTINUED TAVR EXPANSIONONGOING STUDIES IN YOUNGER & HEALTHIER PATIENTS

7

*Investigational use only

*


Low Risk/TF ASSESSMENT by Heart TeamLow Risk/TF ASSESSMENT by Heart Team(STS < 4%)(STS < 4%)

1:1 Randomization1:1 Randomization

Symptomatic Severe Aortic Stenosis

PARTNER 3 Study Design3 Study Design

1:1 Randomization1:1 Randomization10001000 PatientsPatients

TAVR(SAPIEN 3 THV)

Surgery(Surgical Bioprosthetic Valve)

Follow-up: 30 day, 6 mos, and annually through 10 years

PRIMARY ENDPOINT:Composite of all-cause mortality, stroke, or CV re-hospitalization

at 1 year post-procedure

Primary Endpoint

TAVRSurgery

De

ath

,S

tro

ke

,o

rR

eh

osp

(%)

Pnon-inferiority< 0.001

Upper 95% CI ofrisk diff = -2.5%

8.5%8.5%9.3%

15.1%

10

20

0 3 6 9 12

496 475 467 462 456454 408 390 381 377

Number at risk:Number at risk:

TAVRSurgery

Months after Procedure

451374

Psuperiority= 0.001

HR [95% CI] =0.54 [0.37, 0.79]

De

ath

,S

tro

ke

,o

r

4.2%4.2%

0

All-Cause MortalityC

au

se

Mo

rta

lity

(%)

10

20HR [95% CI] =

0.41 [0.14, 1.17]

P = 0.09

TAVRSurgery

All-

Ca

use

Mo

rta

lity

(%)

494 494 493 492454 445 438 433 431

488427

Months from ProcedureNumber at risk:Number at risk:

1.0%1.0%1.1% 2.5%

00.4%0.4%

496TAVRSurgery

0 3 6 9 12

All StrokeA

llS

tro

ke

(%)

HR [95% CI] =0.38 [0.15, 1.00]

P = 0.04

10

20

TAVRSurgery

All

Str

oke

(%)

491 491 489 487454 435 427 423 421

484417

Months from ProcedureNumber at risk:Number at risk:

496TAVRSurgery

1.2%

2.4% 3.1%

00.6%0.6%0 3 6 9 12

Primary Results From the Evolut Low Risk TrialPrimary Results From the Evolut Low Risk Trial

Michael J. Reardon, MD, FACCHouston Methodist DeBakey Heart & Vascular Institute, Houston, TXFor the Evolut Low Risk Trial Investigators

Evolut Low Risk Trial

*Additional patients were randomized to permit completion of the LTI substudy and to enroll a Japanese cohort.

6.4%8%

10%

12%

Clinical ImplicationsDeath, Disabling Stroke and Heart Failure Hospitalizations to 1 Year

Esti

mat

edK

Mra

tes,

%

Composite Rates

TAVR SAVR Difference = –4.5%

5.6% 10.2% P = 0.002

2.3%[VALUE]

0.7%

2.3%3.1%

0%

2%

4%

6%

TAVR SAVR

Esti

mat

edK

Mra

tes,

%

Death

Disabling Stroke

HF Hospitalization

Bayesian rates as %TAVR

(N=725)SAVR

(N=678)(95% BCI forDifference)

All-cause mortality or disabling stroke 2.9 4.6 (-4.0, 0.4)

All-cause mortality 2.4 3.0 (-2.6, 1.3)

Cardiovascular mortality 1.7 2.6 (-2.7, 0.7)

All stroke 4.1 4.3 (-2.4, 1.9)

Disabling stroke* 0.8 2.4 (-3.1, -0.3)

Clinical Outcomes at 1 Year

Disabling stroke* 0.8 2.4 (-3.1, -0.3)

Transient ischemia attack 1.7 1.8 (-1.6, 1.3)

Myocardial infarction 1.7 1.6 (-1.3, 1.5)

Endocarditis 0.2 0.4 (-0.9, 0.5)

Valve thrombosis 0.2 0.3 (-0.9, 0.5)

Aortic valve reintervention 0.7 0.6 (-1.0, 0.9)

Heart failure hospitalization* 3.2 6.5 (-5.9, -1.0)

* Significantly favors TAVR BCI = Bayesian credible interval

• TAVR a clear cut overall winner over SAVR

• What’s left?• Long term results

• Expanded indications, improved technique, improved TAVR devices

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Structural Valve Deterioration

Meta analysis of 12 studiesDefinitions of structural valve deterioration varied somewhat

FiveFive--Year Outcomes after RandomizationYear Outcomes after Randomizationto Transcatheter or Surgical Aortic Valveto Transcatheter or Surgical Aortic ValveReplacement: Final Results of TheReplacement: Final Results of ThePARTNER 1 TrialPARTNER 1 TrialPARTNER 1 TrialPARTNER 1 Trial

Michael J. Mack, MDMichael J. Mack, MDon behalf of The PARTNER Trial Investigators

ACC 2015 | San Diego | March 15, 2015

N = 358InoperableInoperable

ASSESSMENT:ASSESSMENT:

PARTNER Study DesignPARTNER 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 patients2 Parallel Trials:

Individually Powered

N = 699 High RiskHigh Risk

ASSESSMENT:ASSESSMENT:Yes No

N = 179

StandardTherapy

ASSESSMENT:

Transfemoral AccessASSESSMENT:

Transfemoral Access

Not In Study

TF TAVR

Primary Endpoint: All-Cause MortalityOver 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 SAVR

Primary Endpoint: All-Cause Mortality at 1 yr(Non-inferiority)

TA TAVR SAVRVSVS

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

ASSESSMENT:

Transfemoral AccessASSESSMENT:

Transfemoral Access

Transapical (TA)Transfemoral (TF)

1:1 Randomization1:1 Randomization

Yes No

AllAll--Cause Mortality (ITT)Cause Mortality (ITT)All PatientsAll Patients

HR [95% CI] =1.04 [0.86, 1.24]

p (log rank) = 0.76

62.4%

67.8%

No. at Risk

TAVR 348 262 228 191 154 61

SAVR 351 236 210 174 131 64

Error Bars Represent95% Confidence Limits

Aortic Valve AreaAortic Valve Area

Error Bars =Error Bars = ±± 1 Std Dev1 Std Devp < 0.0001

TAVR 304 211 151 106 79 53

SAVR 294 154 121 84 60 46

5-Year Outcomes from the Randomized CoreValveUS Pivotal High Risk Trial: Final ResultsUS Pivotal High Risk Trial: Final Results

Thomas G. Gleason, MD; Michael J. Reardon, MD; Jeffrey J. Popma, MD; Joon

Sup Lee, MD; Steven J. Yakubov, MD; Neal S. Kleiman, MD; Stan Chetcuti,

MD; G. Michael Deeb, MD; David H. Adams, MD

for the CoreValve US Pivotal High Risk Trial Investigators

55--Year AllYear All--Cause MortalityCause Mortality –– High Risk PtsHigh Risk PtsCoreValve US Pivotal High Risk Trial

TAVR 391 336 301 253 205 135

SAVR 359 284 241 199 162 101

No. at risk

23[95% confidence intervals]

Valve PerformanceValve Performance

1.7 1.71.8

1.9 1.9

1.61.5 1.5

1.61.7

49.4

48.6

30.0

40.0

50.0

60.0

1.5

2.0

2.5

3.0TAVR

SAVR

no

Effe

ctiv

eO

rifi

ceA

rea,

cm2 M

eanG

radien

t,mm

Hg

P < 0.01 for TAVR vs. SAVR at all follow-up time points

CoreValve US Pivotal High Risk Trial

24

0.7

0.7

8.9 8.4 7.7 7.4 7.1

12.211.9 11.4 11.2 10.9

0.0

10.0

20.0

Baseline 1 Year 2 Years 3 Years 4 Years 5 Years0.0

0.5

1.0

Effe

ctiv

eO

rifi

ceA

rea,

cmM

eanG

radien

t,mm

Hg

TAVR AVG 391 303 250 193 152 112

SAVR AVG 359 230 188 141 114 88

TAVR EOA 384 284 238 182 144 99

SAVR EOA 353 210 174 134 106 84

2018 AATS/ACC/SCAI/STS Expert Consensus Systems of Care Document:

TAVR Guidelines

• There are currently 587 sites in the U.S. performing TAVR, up from just 156 in 2012

• Recommendation: Existing TAVR programs meet certain requirements. Specifically, at least50 TAVRs per year, or 100 over two years, and at least 30 SAVRs over one year, or 60 overtwo years. This is an increase from the current NCD that specifies 20 annual TAVRs.

• Beyond number of procedures performed, centers must now track the number of other

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• Beyond number of procedures performed, centers must now track the number of otherquality metrics focused on morbidity, mortality, and quality of life at certain time points post-TAVR.

• Recommendation: Centers implement a quality assessment and improvement processincluding active participation in a registry, quarterly meetings of the multidisciplinary team,and documentation of appropriate-use criteria in the patient selection process.

• Two-surgeon sign-off requirement dropped…only one surgeon sign off required.• But why don’t we need an interventional cardiologist to sign off on SAVR?

• TAVR institution must have a trained TAVR physician on the heart team. Either acardiothoracic surgeon or an interventionalist, should have at least 100 transfemoral TAVRprocedures under their belt, with at least 50 of those as the primary operator. Themultidisciplinary heart team also needs to include a cardiac surgeon who has performed atleast 100 SAVRs over their lifetime or 50 SAVRs over two years, with at least 20 of those inthe previous year. This cardiac surgeon also must spend at least half their active practicetime with the TAVR program.

2018 AATS/ACC/SCAI/STS Expert Consensus Systems of Care Document:

TAVR Guidelines

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time with the TAVR program.

• The multidisciplinary heart team also needs to include a cardiac surgeon who has performedat least 100 SAVRs over their lifetime or 50 SAVRs over two years, with at least 20 of thosein the previous year.

The patient must be under the care of a Heart Team

The heart team includes the following:

Cardiac surgeon and an interventional cardiologist experienced in the care and treatment of aorticstenosis who have:

a. independently examined the patient face-to-face, evaluated the patient’s suitability for surgicalaortic valve replacement (SAVR), TAVR or medical or palliative therapy;

CMS National Coverage Decision: 2019

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aortic valve replacement (SAVR), TAVR or medical or palliative therapy;b. documented and made available to the other heart team members the rationale for their clinical

judgment.Providers from other physician groups as well as advanced patient practitioners, nurses, researchpersonnel and administrators.

The heart team's interventional cardiologist(s) and cardiac surgeon(s) must jointly participate in the intra-operative technical aspects of TAVR

Qualifications to begin a TAVR program for hospitals without TAVR experience:The hospital program must have the following:

a.≥ 50 open heart surgeries in the previous year prior to TAVR program initiation, and;b.≥ 20 aortic valve related procedures in the 2 years prior to TAVR program initiation, and;c.≥ 2 physicians with cardiac surgery privileges, and;d.≥ 1 physician with interventional cardiology privileges, and;e.≥ 300 percutaneous coronary interventions (PCIs) per year.


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e.≥ 300 percutaneous coronary interventions (PCIs) per year.

The heart team must include:a.Cardiovascular surgeon with:

a. ≥ 100 career open heart surgeries of which ≥ 25 are aortic valve related; and,b.Interventional cardiologist with:

a. Professional experience of ≥ 100 career structural heart disease procedures; or, ≥ 30 left-sided structural procedures per year; and,

b. Device-specific training as required by the manufacturer.

Qualifications for hospital programs with TAVR experience:

The hospital program must maintain the following:

a.≥ 50 AVRs (TAVR or SAVR) per year including ≥ 20 TAVR procedures in the prior year ; or,b.≥ 100 AVRs (TAVR or SAVR) every 2 years, including ≥ 40 TAVR procedures in the prior 2 years; and,c.≥ 2 physicians with cardiac surgery privileges; and,d.≥ 1 physician with interventional cardiology privileges, and


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d.≥ 1 physician with interventional cardiology privileges, ande.≥300 percutaneous coronary interventions (PCIs) per year;and,

1.The heart team and hospital are participating in a prospective, national, audited registry that: 1)consecutively enrolls TAVR patients; 2) accepts all manufactured devices; 3) follows the patient for atleast one year

2.The following outcomes must be tracked by the registry;

1. Stroke;


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1. Stroke;2. All-cause mortality;3. Transient Ischemic Attacks (TIAs);4. Major vascular events;5. Acute kidney injury;6. Repeat aortic valve procedures;7. New permanent pacemaker implantation;8. Quality of Life (QoL).

The registry shall collect all data necessary and have a written executable analysis plan in place toaddress the following questions…

i.When performed outside a controlled clinical study, how do outcomes and adverse events compare tothe pivotal clinical studies?

ii.What is the long term durability of the device?iii.What are the long term outcomes and adverse events?


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iii.What are the long term outcomes and adverse events?iv.What morbidity and procedure-related factors contribute to TAVR patients outcomes?

TVT Registry Report Example

From: Bob Strange [[email protected]]Sent: Monday, December 10, 2018 9:31 PMTo: Stinis, Curtiss T; Lutes, JenniferSubject: [External] Thanks for the TAVR procedure Dr. Stinis

WARNING! External email. Handle links and/orattachments with caution. IS Service Desk @ 858-678-7500

May 8th, immediately after my TAVR procedure, you told me that I could do anything I wanted after one week forthe groin stitches to heal. I walked several blocks every day, even the first morning home from my overnight stay atScripps.

Weightlifting Workouts at the gym also went well the 8th day.I prepared and painted the complete exterior of our stucco exterior home with a roller and brush during the rest ofMay.

This photo of an 80 Kilo overhead clean and jerk was taken of me at a national USA masters Olympic weightliftingcompetition November 2nd at Salt Lake City. I also did a 60 kilo Olympic snatch.This is not much weight for a young athlete, but both lifts and the total are national records for a male in the 80-85age group weighing less than 89 kilos. The records are kept by age and weight classes. I was awarded best lifter forthe entire competition involving several hundred competitors.

Thank you and your team for providing me an extension of an active, healthy lifestyle far beyond what would haveoccurred without your TAVR procedure.

82 yo 6 months post TAVR

update on low risk trials: current indications and guidelines ......state of aortic valve...

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