transcatheter aortic valve replacement: emerging … - new and...transcatheter aortic valve...

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Transcatheter Aortic Valve Replacement:Emerging Devices, Indications, and Techniques

Howard C. Herrmann, MD, FACC, MSCAI

John Bryfogle Professor of Cardiovascular Medicine and Surgery

Health System Director for Interventional Cardiology

Director, Cardiac Cath Labs, Hospital of the Univ of PA

Perelman School of Medicine

University of Pennsylvania

Philadelphia

Disclosure Statement of Financial InterestWithin the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below.

Discussion may include unapproved and off‐label devices, procedures, and indications

Equity

MicrointerventionalDevices

Consulting Fees/Honoraria

Edwards LifesciencesBayerWells FargoLeerink

Grant/Research Support

Abbott Vascular

Edwards Lifesciences

St. Jude Medical

Medtronic

Gore

Siemens

Bayer

Boston Sci

Corvia

Cardiokinetx

Univ Laval

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0

50

100

150

200

250

300

350

400

2008 2009 2010 2011 2012 2013 2014 2015 2016

2137

55

114

229 218

323328

390

Penn TAVR Program: Growth in Procedures

~2000

# Cum

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Penn TAVR Program Has High Visibility and Prestige

More than 50 publications in major journals, including NEJM, Circulation, Lancet, JACC

One of the 5 largest programs in the US

Sought after participant in national trials of new devices, adjunctive therapies

• 4 major devices

• Embolic protection trial

• Anticoagulation post TAVR trial

• Membership on steering committees

• Presentations at multiple national meetings

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Future of Transcatheter Aortic Therapies

• New Devices• Portico• Lotus• Jenavalve

• New Indications• Low Risk • Aortic Regurgitation• Bicuspid aortic valves• Asymptomatic AS• Low Flow vs Pseudo AS• Moderate AS / LV dysfunction

• New Techniques• Conscious Sedation / MAC / Fast Track• Post TAVR anticoagulation• Cerebral Embolic Protection

New Devices: Lotus

Valve elongated in catheter for delivery

Step 1: Unsheathing

Valve unsheathed

into intermediate configuration

Step 2 : Locking

Valve expands radially as it shortens and locks into final configuration

~70mm

19mm

• Valve deployed via controlled mechanical expansion. It is neither balloon

expandable nor self expanding.

• No rapid pacing during deployment

• Valve functions early enabling controlled deployment

• No valve movement on release

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7

Lotus Deployment

8

Lotus Results: Respond Extension Study

Permanent pacemaker implantation

All patients (n=50) 16% (8)

Pacemaker-naïve patients (n=45) 17.8% (8)

Perc

enta

ge o

f Ev

alua

ble

Echo

card

iogr

ams

20.5

67.631.8

17.631.8

14.713.62.3

0

20

40

60

80

100

Baseline Discharge

Paravalvular Leak (PVL)

Aortic Regurgitation

None

Trace

Mild

Moderate

Severe

Core Lab-Adjudicated Data

(n=44) (n=34)

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Low Risk TAVR Trials

* Source: Clinicaltrials.gov

Sponsor Edwards (NCTO2675114)* Medtronic (NCTO2701283)*

Device Sapien 3 Evolut R / EnVeo R

Design Prospective, randomized Prospective, randomized

Comparator 1:1 to SAVR 1:1 to SAVR

Analysis Non-inferiority Non-inferiority

N 1228 1250

Inclusion Heart team risk <4% Heart team risk <3%

Substudy Leaflet mobility (n=400) Leaflet mobility (n=400)

PI Leon / Mack Popma / Reardon

10 endpoint All-cause mort / all stroke / rehosp. (1 year)

All-cause mort / disabling stroke (2 year adaptive)

Key differences Excludes EF <45%, age<65Includes Asx with +ETT

Can include Asx AS with >5.0 m/s, +ETT

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The data already support TAVR in extreme and high risk patients, but the main reason that TAVR will eventually replace open surgery in intermediate and low risk patients is:

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TAVR for Pure Native Aortic Regurgitation

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13

JACC Intv 2016;9:2308

• 237 Patients

• 79% SE and 21% BE

• Device success lower

• Second valve implanted in 7%

• Moderate or severe AR persisted at 30d in 9%

• Conclusion: Feasible

JenaValve Pericardial THVEYELETS &

INTERMEDIATE STRUTS

THV PORCINE PERICARDIALTISSUE CUSPS

TA AND TF DELIVERY

LOCATORS

Courtesy of U.Schaefer, MD. Hamburg UKE

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• Higher rates of:• PVL• PPM• Early mortality

• Issues include:• Incomplete prosthesis expansion• Leaflet asymmetry• Annular disruption

• Future measurements:• Intercommissural distance• Raphe length, width, Ca++• Sinus asymmetry• Leaflet asymmetry

Sievers JTCVS 2007;133:1226Jilaihawi JACC Imag 2016;9:1145Popma JACC Imag 2016;9:1159

Bicuspid Aortic Valve (BAV): Imaging for TAVR

Balloon sizing with BAV

Annulus measured 620 mm2 (#29 Sapien 3)

Balloon valvuloplasty with 20 mm (6 cm) Tyshak-X

Downsized to #26 Sapien 3

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• 301 patient registry: Results are improving with later generation devices

JACC 2016;68:1195

Recommendations and Levels of Evidence for Diagnosis, Follow-up, and Timing of Aortic Valve Replacement in Patients With Asymptomatic Severe Aortic Stenosis

ACC/AHA ESC/EACTSIndications for aortic valve replacement

Left ventricular ejection fraction 50% I, B I, C

Undergoing other cardiac surgery I, B I, C

Symptoms on exercise test clearly related to aortic stenosis I, B I, C

Decreased exercise tolerance IIa, B IIa, C

Exercise fall in systolic blood pressure IIa, B IIa, C

Very severe AS (PV5.0 m/s [ACC]; >5.5m/s [ESC] and low surgical risk IIa, B IIa, C

Rate of PV progression ≥0.3 m/s per year and low surgical risk IIb, C IIa, C

Repeatedly markedly elevated natriuretic peptide and low surgical risk - IIb, C

Increase of MG with exercise by >20 mmHg and low surgical risk - IIb, C

Excessive LVH in the absence of hypertension and low surgical risk - IIb, C

Diagnostic

Transthoracic echocardiography as the initial diagnostic modality I, B -

Exercise testing IIa, B -

Exercise echocardiography IIa, B -

Follow-up

Echocardiography every 6-12 months 1, C -ACC = American College of Cardiology; AHA = American Heart Association; EACTS = European Association for Cardio-Thoracic Surgery; European ESC = European Society of Cardiology

Nishimura et al. J Am Coll Cardiol. 2014; 63(22):e57-185

Vahanian et al. Eur Heart J. 2012; 33(19):2451-96

3 Class I indications…3 Class IIa indications…Level of evidence B or C

No Randomized trial

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Asymptomatic Severe Aortic Stenosis May Not Be as Benign as Previously Thought

Heart Failure HospitalizationAll-Cause Mortality

Presented at TCT 2015: T. Taniguchi et al. Evaluation of Initial Surgical Versus Conservative Strategies in Patients With Asymptomatic Severe Aortic Stenosis. JACC. 2015; 21881.

• Japan multicenter registry• 1,808 asymptomatic patients• Two groups of initial AVR and conservative strategy

In the conservative group, AVR was performed in 41% of patients during follow-up

EARLY- TAVR Trial in planning stages

ACC/AHA ESC/EACTS

Indications for aortic valve replacementLeft ventricular ejection fraction 50% I, B I, CUndergoing other cardiac surgery I, B I, CSymptoms on exercise test clearly related to aortic stenosis I, B I, CDecreased exercise tolerance IIa, B IIa, CExercise fall in systolic blood pressure IIa, B IIa, CVery severe AS (PV5.0 m/s [ACC]; >5.5m/s [ESC] and low surgical risk

IIa, B IIa, C

Rate of PV progression ≥0.3 m/s per year and low surgical risk

IIb, C IIa, C

Repeatedly markedly elevated natriuretic peptide and low surgical risk

- IIb, C

Increase of MG with exercise by >20 mmHg and low surgical risk

- IIb, C

Excessive LVH in the absence of hypertension and low surgical risk

- IIb, C

Note: ACC, American College of Cardiology; AHA = American Heart Association; EACTS, European Association for Cardio-Thoracic Surgery; ESC, European Society of Cardiology; AS, Aortic stenosis; PV, Peak velocity

Recommendations and Levels of Evidence for Timing of Aortic Valve Replacement in Patients With Asymptomatic Severe AS

3 Class I Indications…3 Class IIa Indications…Level of Evidence B or C

No Randomized Trial

Nishimura et al. J Am Coll Cardiol. 2014; 63(22):e57-185 Vahanian et al. Eur Heart J. 2012; 33(19):2451-2496

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Sudden Death

Severe Asymptomatic AS

~1-2%/year

Peri-operative Mortality

SAVR

~1-5%

Why Early SAVR In Asymptomatic Severe AS is Rarely Performed?

TAVR may be a better option for Asymptomatic patients

Généreux et al. J Am Coll Cardiol 2016;67:2263–88; Thourani et al. Lancet 2016; 387: 2218–25; Thyregod et al. J Am Coll Cardiol 2015;65:2184–94

30-day MortalityPARTNER trial 2A Intermediate PM

Sapien 3 TAVR SAVR

1.1% 4.0%

30-day MortalityNotion Trial all-comers

Core Valve TAVR SAVR

2.1% 3.7%

Why Early SAVR in Asymptomatic Severe AS is Rarely Performed?

22Note: AVR, aortic valve replacement; AS, Aortic stenosis

Sudden Death Rate Peri-operative Mortality

Severe Asymptomatic AS

~1% to 2% /year

SAVR

~1-5%

Généreux et al. J Am Coll Cardiol 2016; 67:2263–2288 Thourani et al. Lancet 2016; 387:2218–2225

Thyregod et al. J Am Coll Cardiol 2015; 65:2184–2194

30-day MortalityPARTNER Trial 2A Intermediate PM

30-day MortalityNotion Trial All-comers

SAPIEN 3 TAVR SAVR CoreValve TAVR SAVR

1.1% 4.0% 2.1% 3.7%

TAVR may be a better option for asymptomatic patients

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Prevalence of Asymptomatic Severe AS

• From Echocardiographic Databases / Laboratory:

• Approx. 46-52% of all severe AS were asymptomatic

• Approx. 22% of all severe AS were isolated asymptomaticsevere AS

• Approx. 500,000 patients >65 years old in US

23

Pellikka et al. Circulation. 2005;111:3290-3295 Kitai et al. Heart 2011;97:2029-2032

Pai et al. Ann Thorac Surg 2006;82:2116 –2122 Source U.S. Census Bureau, 2014 National Projections

Study Objective and Design

Note: OUS, Outside US; THV, transcatheter heart valve; TAVR, Transcatheter aortic valve replacement

Study Objective: To establish the safety and effectiveness of the Edwards SAPIEN 3Transcatheter Heart Valve (THV) compared with clinical surveillance(CS) in asymptomatic patients with severe, calcific aortic stenosis.

Study design: Prospective, randomized, controlled, multi-center study

Sample size: 1109 patients

Study sites: Up to 65 US sites

Randomization: TAVR arm vs. Clinical Surveillance arm in 1:1 ratio

Registry: Patients meet all other criteria in study screening but with a positiveresult in the treadmill stress test

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Study Flowchart

25

Commercial AVR (TAVR or SAVR), Clinical Trial (P3), etc.

Symptomatic N=1,000 ptsPositive stress test

ScreeningNot eligible if <65, has Class 1 indication for AVR, bicuspid valve, not suitable for TF access or STS > 10

Asymptomatic Severe, Calcific AS

Asymptomatic N=1,109 ptsNegative stress test OR confirmation via med history*

TF- TAVR Clinical Surveillance

Registry

Primary Endpoint (superiority): 2-year composite of all-cause death, all stroke, and

unplanned cardiovascular hospitalization

Clinical and Echo Follow-up: 30 days (TAVR only), 1, 2, 3 and 5 years Telephone Follow-up:

1, 2, 3 and 5 years

Randomization 1:1Stratified by ability to perform stress test

Principal Investigator:Philippe Généreux, MD,

Chair: Martin B. Leon, MD

NCT03042104; 1st patient consented March 16th

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EARLY TAVR: Conclusion

• EARLY TAVR trial is a strategy trial aiming to establish the safety and effectiveness of early TAVR among patients with severe asymptomatic AS compared to clinical surveillance/delayed AVR

• EARLY TAVR registry is a prospective registry aiming to follow patients with severe AS initially deemed asymptomatic but with symptoms unmasked by stress testing

Practical Issues with “Watchful Waiting” Strategy

• Clinicians still have a fear of stress test with Severe AS patients; low penetration and underused; missing Class 1 indication for AVR

• Stress Imaging requires expertise and specific set-up that most community hospitals don’t have

• Sub-optimal follow-up and lost of follow-up are frequent

• Many sudden deaths occurred in Asx patients with no Class I indication of AVR and no preceding symptoms

• “Wishful Thinking” Strategy…

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All Aortic Stenoses Are Not Created Equal

Anjan and Herrmann, JACC 2015;65:654-6

Numbers at Risk

LF LEF LG 225 177 154 142 128 119 100NF LEF NG 304 214 213 193 179 162 134

Numbers at Risk

LF LEF LG 147 115 100 94 83 76 67NF LEF NG 78 62 54 48 45 43 33

Pre-TAVR effect on outcome KM mortality for LF vs NF

0%

10%

20%

30%

40%

50%

60%

70%

0 4 8 12 16 20 24

HR: 1.52 [95% CI: 1.24, 1.87]Log-Rank p= <.001

47.2%

33.9%

2-Y

r D

eath

(%

)

Months

0 4 8 12 16 20 24

2-Y

r D

eath

(%

)

0%

10%

20%

30%

40%

50%

60%

70%HR: 0.97 [95% CI: 0.65, 1.44]

Log-Rank p= 0.886

48.0%

50.9%

LF LEF LGLF LEF NG

2-Y

r D

eath

(%

)

0%10%20%30%40%50%60%70%80%

0 4 8 12 16 20 24

HR: 1.07 [95% CI: 0.83, 1.37]Log-Rank p= 0.616

48.9%

46.1%

LF LEFLF NEF

Numbers at Risk

LF 530 422 368 336 308 282 235NF 441 368 342 317 300 274 239

Months

Months

ITT - Cohorts A & B

ITT - Cohorts A & B

ITT - Cohorts A & B

LF (Low Flow)NF (Normal Flow)

Herrmann et al, Circulation 2013;127:2316

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How to confirm severe AS when gradient, flow, or EF are reduced?

Dobutamine stress echo to increase flow, observe an increase in gradient with minimal increase in AVA (classical LF LG AS)

Dimensionless index <0.25 useful in paradoxical LF LG AS1

MDCT aortic valve calcification (total or density; gender specific)2

When flow is normal (incorporates SVI and EF), AVA is true3:

1Rusinaru, JACC Cardiol Img 2015;8:766-752Cueff, Heart 2011;97:721-7263Chahal, JACC CV Imag 4.21.2015 online

Procedural ResultsOutcomes in LF vs NF by Treatment Received (Cohort A)

0 60 120 180 240 300 360 420 480 540 600 660 7200%

5%

10%

15%

20%

25%

30%

35%

40%45%

39.3%

38.1%

25.4%

28.9%

log rank p= 0.030LF – A - TAVRLF – A - SurgeryNF – A - TAVRNF – A - Surgery

2-Y

ear

Dea

th (

%)

Numbers at Risk

LF – A – TAVR 170 152 143 127 123 116 109 102 86LF – A – Surgery 180 138 127 123 119 115 111 105 90NF – A – TAVR 152 139 135 124 120 117 110 107 95NF – A – Surgery 145 119 110 106 102 97 95 89 77

Days

Herrmann et al, Circulation 2013;127:2316

LF

NF

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Studies of Outcomes of Surgery in Classical LF LG severe AS

Series N Peri-op or 30 day Mortality*

LF, LG, LEF

LF, LG, LEF

*Percentages approximated by extrapolation from KM curves; #~50% AVR

Blitz, 1998 52 11%Monin, 2003 95 14%

Kulik, 2006 79 8%

Clavel, 2008 44 18%Levy, 2008 217 16%

1-year (Mortality) 5-year

Blitz, 1998 52 29% 34%Monin, 2003 95 25%

41 (no AVR) 60%Kulik, 2006 79 11% 24%Clavel, 2008 44 30%

57 (no AVR) 30%Levy, 2008 217 25% 51%

How does TAVR differ from Surgery?

• TAVR is less invasive:– Faster recovery– Less pericardial irritation with potential for less AF– Less healing, risk for infection– Shorter ventilator dependency

• Cardiopulmonary bypass can be detrimental:– Systemic inflammatory response syndrome

· Inflammatory activation by membrane oxygenator, heparin-coated circuits, UF· Ischemia-reperfusion injury to various organs (gut, kidneys, brain, etc)

– Risk for adverse cerebral effects (cognitive decline)– Need for higher levels of anticoagulation– Need for cardiac standstill with cardioplegia and hypothermia

• Larger effective orifice area (EOA) with transcatheter vs surgical prostheses:– Less Patient-Prosthesis Mismatch (PPM)– PPM may be more important in low flow, low EF with heightened

afterload sensitivity

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Heart Failure

Leading cause of hospitalizations

Aortic Stenosis

Most frequent valvulopathy

Increased AFTERLOAD

(trans-valvular gradient)

Impaired LV systolic function

Diastolic dysfunction

Increased AFTERLOAD

(sympathetic activity)

Impaired LV systolic function

Diastolic dysfunction

Aortic Valve

Replacement

Beta-blockersACEi/ ARBs/ARNI

MRAsDiuretics

Severe AS

Watchful

Waiting

Moderate AS

Coexistence of Heart Failureand Moderate Aortic Stenosis

High risk population

Early AVR may be beneficial

Blais et al. Circulation 2003;108:983-988

Dataset of 1266 patients - PPM in 38%

Prosthesis Patient Mismatch & EF

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Spitzer et al. AHJ 2016;182:80-88

TAVR UNLOAD Concept

Primary endpoint

Hierarchical occurrence of

All-cause death

Disabling stroke

Hospitalizations related to heart failure, aortic

valve disease or non-disabling stroke

Change in KCCQ*To be analyzed with the Finkelstein-Schoenfeld method, 99% PowerIf FS endpoint is statistically significant, proceed with MACCE endpoint, with sufficient (2-sided α = 0.05) power if 40% endpoints are reached

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InternationalMulticenter

Randomized

TAVR-UNLOAD Trial Design

Heart FailureLVEF < 50%

NYHA ≥ 2Optimal HF

therapy(OHFT)

Moderate AS

TAVR UNLOAD

Trial

R

TAVR + OHFT

OHFT Alone

Follow-up:1 month6 months

1 year

Clinical EndpointsSymptomsEcho QoL

Primary EndpointHierarchical occurrence of:

All-cause death Disabling stroke Hospitalizations for

HF, aortic valve disease, or non-disabling stroke

Change in KCCQ

Reduced AFTERLOADImproved LV systolic and diastolic function

Spitzer et al. AHJ 2016;182:80-88

TAVR UNLOAD Concept

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Fast Track

• Extreme example that demonstrates how far we have come

• Issues for early discharge include:

• 2-night CMS rule

• Transfer penalty

• Unknown late risks of bleeding, conduction abnl

• Role of medication changes, readmission rates

• Utility for later in the day cases, home care

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Fully Percutaneous Access

TAVR access: Annual breakdown of implanted patients

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

2007 2008 2009 2010 2011 2012 2013 2014 2015Year

LSC

TAO

TA

TF

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45

TF Completed with MAC or GA

First Quintile of Analysis (April to July 2014)

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

April '14 May '14 June '14 Jul-14

%MAC %GA

Last Quintile of Analysis (Jan to Mar. 2016)

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

JAN 2016 FEB 2016 MAR 2016

% MAC % GA

Catheterization and Cardiovascular InterventionsVolume 85, Issue 4, pages 648–654, March 2015

Original Studies

Original Studies

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Minimalist Experience at Emory University Hospital: Reduced resource utilization, without compromising outcomes

SOURCE: Babaliaros, V et al. “Comparison of Transfemoral Transcatheter Aortic Valve Replacement Performed in the Catheterization Laboratory (Minimalist Approach) Versus Hybrid Operating Room (Standard Approach)”. JACC 2014.

Standard Approach Minimalist Approach• Hybrid operating room• General anesthesia• Intubation

• Cardiac catheterization lab• Local anesthesia• Minimal conscious sedation

218 Procedure Room Time(Minutes)

150

28 Intensive Care Unit Time(Hours)

22

5 Length of Stay(Days)

3

$55.3k Hospital Costs(Dollars)

$45.5k

96% Procedure Success 100%

6% 30-Day Mortality 0%

Increase in MAC from 2014 to 2015

0

50

100

150

200

250

300

350

400

2014 2015 2016

HUP / PPMC MAC vs. GA 2014-1015

MAC GA GA

49%MAC

76%MAC

90%MAC

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Goal

Identify subgroup of patients who could benefit from:

1. Early extubation

2. Fewer ICU days

3. Early ambulation

Fast Track Criteria

Patient Characteristics

• Easy airway management

• No severe lung disease

• LV EF >40%

• PASP < 50 mmHg

• MR < 2+

• eGFR > 60 ml/min

• STS risk < 8%

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Results: Length of Stay and Direct Costs

TABLE III

Monitored Anesthesia Care

• MAC Anesthetic

• Distinguish from conscious sedation

• MAC is a deeper level of sedation and higher level of care than conscious sedation

• Now, the preferred approach for transfemoral TAVR at Penn

i.e. MAC is first choice for all TF cases; must find reason for exclusion if choosing GA.

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Anesthesia Exclusion Criteria

• Non-transfemoral approach

• Inability to lie flat / cooperate

• Potential difficult airway

• Morbid obesity

• Uncertain valve sizing where intraop TEE may be beneficial

• Any concerns for difficult access

Post-TAVR TTE

• Transthoracic echocardiogram performed after valve deployment (along with angiography)

• Valve position and AR

• Ventricular function

• R/O pericardial effusion

• TTE service provided by trained echo technicians

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Increase in MAC from 2014 to 2015

0

50

100

150

200

250

300

350

400

2014 2015 2016

HUP / PPMC MAC vs. GA 2014-1015

MAC GA GA

49%MAC

76%MAC

90%MAC

• Hybrid OR

• Heart team intact (Anesthesia, CV Surgery, Cardiology)

• MAC predominately (vs CS)

• Peripheral access (no PA catheter, no RIJ line)

• Percutaneous access

• Fast track to floor

• D/C home POD # 2-3

TAVR at Penn Today ≈ 450 Cases Annually

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Estimated Global TAVR Procedure Growth

TAVR procedures volumes will double globally in the next 4 years

Global TAVR Procedures

50,000

100,000

150,000

200,000

250,000

300,000

02012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025

32,00041,000

56,00071,000

83,000103,000

125,000144,000

163,000182,000

202,000223,000

256,000

289,000ROW

U.S.

EU

• Hybrid OR

• Heart team intact (Anesthesia, CV Surgery, Cardiology)

• MAC predominately (vs CS)

• Peripheral access (no PA catheter, no RIJ line)

• Percutaneous access

• Fast track to floor

• D/C home POD # 2-3

TAVR at Penn Today ≈ 450 Cases Annually

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Conversion Rates

Frohlich, et al. BMC Med 2014.Bergmann, et al. Anaesthesia2011

-Vascular injury or need for femoral cutdown

7

-Hemodynamic instability 5

-Ineffective sedation / lack of patient cooperation

4

60

Meredith, et al., presented at PCR London Valves 2014; Adams, et al., N Engl J Med 2014; 370: 1790-8; Leon, et. al. presented at ACC 2013; Lefevre et al., J Am Coll Cardiol 2016; 1:; Popma, et al., J Am Coll Cardiol 2014; 63: 1972-81; Linke, et. al. presented at London Valves 2015; Van Mieghem, et al., presented at EuroPCR 2015; Kodali, et al., presented at ACC 2015; Holmes, et al., JAMA 2015; 313: 1019-28; Meredith, et al., presented at ACC 2015, 1 Williams, et. al. presented at ACC 2016; Thourani, et al, presented at ACC 2016

4.0% 3.9%

5.5%

6.8% 7.0%

0.0%

3.3%

4.1%

2.5%

4.9%

4.3%

1.5%

2.7%

5.5%

0%

1%

2%

3%

4%

5%

6%

7%

8%

CoreValveExtremeRisk

N=489

LOTUSRESPONDN=500

PorticoCE StudyN=103

LOTUSREPRISE II

+ ExtN=249

Direct FlowDISCOVERN=75

Evolut RCE StudyN=60

Evolut RIDE N=241*

SAPIENPARTNER

IIBN=276

SAPIENTVT HRN=12182

CoreValveHigh RiskN=390

SAPIEN XTPARTNER

IIBN=284

SAPIEN 3PARTNER II

HRN=583

SAPIEN 3PARTNER II

S3iN=1078

SAPIEN XTPARTNER

IIAN=1011

% Patients with Strke at 30 Days

Extreme Risk Extreme/High Risk High Risk Intermediate Risk

* Disabling Stroke

Incidence of CVA after TAVI remains clinically significant, particularly in high risk patients

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61

• 68-100% of TAVI patients affected1-11

• Most patients have multiple infarcts• “Silent” infarcts associated with12-14

• 2-4-fold risk of future stroke• >3-fold risk of mortality• >2-fold risk of dementia• Cognitive decline• Dementia

New cerebral lesions are found in the vast majority of patients following TAVI

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Rod

es-C

abau

2011

Gha

nem

201

0

Arn

old

2010

Kah

lert

201

0

Ast

arci

201

1

DE

FLE

CT

III

cont

rol a

rm20

15

Biju

klic

201

5

CLE

AN

-TA

VI

cont

rol a

rm

PR

OT

AV

I-C

Neu

roT

AV

R

MIS

TR

AL-

C

% of TAVI patients with new cerebral lesions on DW-MRI

Ghanem, et. al, JACC 2010

1. Rodes-Cabau, et al., JACC 2011; 57(1):18-282. Ghanem, et al., JACC 2010; 55(14):1427-323. Arnold, et al., JACC:CVI 2010; 3(11):1126 –32

4. Kahlert, et al., Circulation. 2010;121:870-8785. Astarci, et al., EJCTS 2011; 40:475-96. Lansky, et al., EHJ 2015; May 19

7. Bijuklic, et al., JACC: CVI 20158. Linke, et al., TCT 20149. Vahanian, TCT 201410. Lansky, et al. London Valves 2015

11. van Mieghem N, et al. EuroIntervention2016;12:499-507 12. Sacco et al., Stroke 201313. Vermeer et al., Stroke 200314. Vermeer et al., New Engl J Med 2009

• 68-100% of TAVI patients affected1-11

• Most patients have multiple infarcts• “Silent” infarcts associated with12-14

• 2-4-fold risk of future stroke• >3-fold risk of mortality• >2-fold risk of dementia• Cognitive decline• Dementia

0%10%20%30%40%50%60%70%80%90%100%

Rodes‐Cabau

2011

Ghanem 2010

Arnold 2010

Kahlert 2010

Astarci 2011

DEFLECT III control arm

…

Bijuklic 2015

CLEAN‐TAVI control arm

PROTA

VI‐C

Neu

roTA

VR

MISTR

AL‐C

% of TAVI patients with new cerebral lesions on DW‐MRI

New cerebral lesions are found in the vast majority of patients following TAVI

11. van Mieghem N, et al. EuroIntervention 2016;12:499-507 12. Sacco et al., Stroke 201313. Vermeer et al., Stroke 200314. Vermeer et al., New Engl J Med 2009

Ghanem, et. al, JACC 2010

1. Rodes-Cabau, et al., JACC 2011; 57(1):18-282. Ghanem, et al., JACC 2010; 55(14):1427-323. Arnold, et al., JACC:CVI 2010; 3(11):1126 –32

4. Kahlert, et al., Circulation. 2010;121:870-8785. Astarci, et al., EJCTS 2011; 40:475-96. Lansky, et al., EHJ 2015; May 19

7. Bijuklic, et al., JACC: CVI 20158. Linke, et al., TCT 20149. Vahanian, TCT 201410. Lansky, et al. London Valves 2015

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Cerebral Embolic Protection

Embrella deflector

Claret dual filter

Keystone Medical (formerly SMT)

Emboline CAP

Background

• The Claret MontageTM dual-filter Cerebral Protection System was developed to protect the brain from injury caused by embolic debris.

• Randomized controlled trial data showing the efficacy of any embolic protection device in TAVR are missing.

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SENTINAL TRIAL:Primary Efficacy Endpoint

42.2% reduction [95% CI: ‐3.2,67.6)

p = 0.33

New

Lesion Volumes in

Protected Territories (mm

3)

350

300

250

200

150

100

50

0

Control(N=98)

178

Median 95% Confidence Limit

Treatment(N=91)

102.8 0%10%20%30%40%50%60%70%80%90%

100%

Valve Leaflet Abnormalities

Diastole

Systole

Makkar, et al. 2015

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34

TAVR Adjunct PharmacologyCustomized Patient-Based Therapy

New TAVR Pharmacology Trial

PIs: Dangas, G.Windecker, S.

US PI:Herrmann, H.

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35

PowerPoint Timesaver: Charts, tables, diagrams, icons, and more

Date

705/26/2017

Bar charts: Tornado

Notes:Sources:

5.0

4.5

4.0

3.5

3.0

2.5

2.0

1.5

5.0

4.5

4.0

3.5

3.0

2.5

2.0

1.5

6 4 2 0 2 4 6

Left Right

Label on the outside








Chart title runs here (units)

Axis label

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36

Vital Components to a Successful Transcatheter Program

Team Work

HUP Physicians:

Cardiothoracic Surgeons

Interventional Cardiologists

Echocardiologists

CT anesthesiologists

Outside Referring Physicians

Hybrid OR Staff

ICU Nurses

Research Coordinators

Sponsoring Company

Patient Families

“It Takes a Village!”

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