Valvular Interventional Cardiology in Perspective

Present and Future

Cesar Morís

Profesor Cardiología

Director Área del Corazón

Htal Universitario Central de Asturias

Universidad de Oviedo

OVIEDO -- ESPAÑA

MY DISCLOSURES

• Corevalve Proctor

• I serve on a Medical Advisory Board for Medtronic, Inc.

Hospital Universitario Central de Asturias

Universidad de Oviedo

OVIEDO -- ESPAÑA

Oviedo

World Wide Cardiology Market Trends

Estimated Global TAVR Growth

SOURCE: Credit Suisse TAVI Comment –January 8, 2015. ASP assumption for 2024 and 2025 based on analyst model. Revenue split assumption in 2025 is 45% U.S., 35% EU, 10% Japan, 10% ROW

In the next 10 years, TAVR growth will increase X4!

M.B Leon TVT Chicago 2015

Valvular Interventional Cardiology in Perspective

• Tricuspid

TR is Currently Ignored !! STS Database 2009

TR cases

Annual New TR

Annual MR Surgeries

Annual TR Surgeries

1,600,000

250,000

50,000

5,500

Interventional Cardiology Perspective of Functional Tricuspid Regurgitation. Argarwal et al. Circ Cardiovasc Interv 2009;2:565-573

…and they die! TR Increases Mortality !

Nath. JACC 2004;43:405.

5223 subjects : Mod-Sev TR increased mortality independent of

PASP, LVEF, IVC size, RV size/ function.

OK ! Don‟t ignore TR : How to do it ?

Repair Lessons for Functional TR

Annuloplasty Rings DeVega

DeVega. Rev Esp Cardiol 1972;25:6.

Circ Cardiovasc Interv. 2015;8:e002155. DOI: 10.1161/CIRCINTERVENTIONS.114.002155

17 percutaneous valves were implanted in 16 pts. With TV bioprosthesis dysfunction

Men follow-up: 2.1 years (3 days to 6.3 years). The percutaneous valve was performing well in 15 of 16 patients

First-in-Human Transcatheter Tricuspid Valve Repair in

a Patient With Severely Regurgitant Tricuspid Valve

J Am Coll Cardiol. Published online March 04, 2015. doi:10.1016/j.jacc.2015.01.025

Valvular Interventional Cardiology in Perspective

• Mitral

Prevalence of valvular heart disease by age

Lancet 2006; 368:1005

Complexity of aortic and mitral valve disease

Challenges in the mitral space

• Multitude of pathologies with different etiology, mechanism, prognosis, type of repair and response to repair

Interaction with LV function

It makes harder to predict who will benefit with mitral regurgitation

Percutaneous Treatment of Mitral Valve Disease

Aortic Stenosis

LV dysfunction

Mitral Regurgitation

LV dysfunction

Funcional (IMF)

Degenerativa (IMD)

Robbins et al. Am J Cardiol 2003; 91:360 Grigioni F et al. Circulation 2001 ;103:1759-1764

Bursi F et al. Eur J Heart Fail 2010;12:382-388

Mortality and MR

MR predictor of mortality in those with

less advanced HF HR 1.23

Trichon BH. Am J Cardiol 2003;91:538

¿Que hacer con la IM funcional?

Castleberry AW, Circulation 2014;129:2547

El tratamiento médico está asociado con las

mayores cifras de mortalidad a 20 años

N=4989

Euro Heart Survey

surgery is often denied in the older patients

Isolated MR

(n=877)

Severe MR

(n=546)

No Severe MR

(n=331)

No Symptoms

(n=144)

Symptoms

(n=396)

No Intervention

(n=193) 49%

Intervention

(n=203) 51%

Mirabel et al, European Heart J 2007;28:1358-1365

2/3 of symptomatic MR patients >70 are

denied surgery

Patients with secondary MR

Duke Databank: 1,538 pts with echocardiographic 3+ - 4+ FMR and LVEF ≥20% between

2000 and 2010 not undergoing CABG

11.4% 5.9% 8.4% 11.8% 18.4%

0%

25%

50%

75%

100%

All pts 20%-30% 30%-40% 40%-50% 50%-60%

Conservative management Isolated MV surgery

LVEF

N=1538 N=440 N=298 N=313 N=479

8 other pts had LVEF >60%; none underwent MV surgery

How are Patients with Isolated FMR Treated?

Mirabel M et al. Eur Heart J 2007;28:1358-1365

Euro Heart Survey – Conducted in 2001

Decision to operate according to comorbidity

Muchas dudas beneficio cirugía IMF

No-MVA

MVA

Wu A, J Am Coll Cardiol 2005;45:381–7

n= 419 OP: muerte, asistencia VI, TxC a 1 año FE en CVM 23%

n=301 CABG vs CABG + MVRepair

CABG

CABG + MVR

p

Cualquier evento NRL 3.1 9.6 0.03

Ictus 1.5 5.2 0.1

Smith PK, N Engl J Med 2014, In press

Magne J, Cardiology 2009;112:244

Unmet need in mitral regurgitation

• Similar to aortic stenosis, there are many patients

with severe MR who would benefit from mechanical

correction of the hemodynamic lesion, but are not

receiving this treatment because of high risks (real or

perceived) associated with the required surgical

procedure

Percutaneous Treatment of Mitral Valve Disease

Mitral Valve repair

„Alfieri‟ (edge to edge) repair

Percutaneous Treatment of Mitral Valve Disease

The MitraClip System

Percutaneous Treatment of Mitral Valve Disease

• Take note of the clip itself, and the steering / delivery system that allows three-dimensional alignment

CLÍNICAL EVIDENCE

Feldman T, N Engl J Med 2011; 2011;364:1395

73% Degenerative MR Stringent echo criteria Central valve pathology

Surgery is better for younger patients with degenerative MR and preserved LV function

EFFICACY

n Acute procedural success

EVEREST II 279 77%

Franzen 2010 51 96%

Franzen 2011 50 94%

GRASP registry 117 100%

TRAMI registry 486 94%

TRAMI aged 1064 96%

ACCESS EU 567 99.6%

ESC SENTINEL 628 95.4%

Franzen O, EHJ 2010;31:1373

Franzen O, Eur J Heart Fail 2011;13:569

Grasso C, Am J Cardiol 2013;111:1482e 1487

Baldus S, Eur Jour of Heart Fail 2012; 14: 1050

Schillinger W, EuroIntervention 2013

Maisano F, J Am Coll Cardiol 2013; 62:1051

Nickenig G, J Am Coll Cardiol 2014

MR REDUCTION

ACCESS EU ESC SENTINEL

Maisano F, J Am Coll Cardiol 2013; 62:1051 Nickenig G, Estevez-Loureiro R, J Am Coll Cardiol 2014;64:875

VERSATILITY

IMD resultado “surgical-like” tras 2 clips

IMF resultado bueno para tipo de paciente

Bilge M, CCI 2014;83:137 Grasso C, J Am Coll Cardiol 2014;63:834

Schäfer U, EuroIntervention 2014;In press

VERSATILITY

Estevez-Loureiro R, Arzamendi D, Freixa X, Cardenal R, J Am Coll Cardiol 2015; in press

VERSATILITY

ESC SENTINEL

ACCESS EU

MEJORÍA CLASE NYHA

MEJORÍA 6MWT

Maisano F, J Am Coll Cardiol 2013; 62:1051 Nickenig G, Estevez-Loureiro R, J Am Coll Cardiol 2014;64:875

MEJORÍA CALIDAD DE VIDA EVEREST HIGH RISK

Glower D, J Am Coll Cardiol 2014,64:172

FUNCTIONAL IMPROVEMENT

MitraClip in recent valve disease guidelines

European (2012):

– Clip procedure may be considered in . . . symptomatic severe

secondary MR after optimal medical Rx (including CRT if indicated)

assuming echo criteria met and inoperable or high surgical risk (class

IIb, LOE C)

AHA / ACC (2014):

– Transcatheter MV repair may be considered for severely symptomatic

patients (NYHA class III/IV) with chronic severe primary MR (stage

D) who have . . . . prohibitive surgical risk because of severe

comorbidities (class IIb, LOE B)

Other transcatheter techniques

Estévez-Loureiro R, PanMinerva Medica 2013;55(4):327-37

Trans-apical beating

heart neo chordae

Seeburger J, J Am Coll Cardiol 2014;63:914

≈50% éxito IM ≤2+ a 30 días

Coronary Sinus Approach Cardiac Dimensions Carillon XE 2 Device

AMADEUS Trial. Circulation. 2009;120:326-333 Adapted from Hermiller TCT 2011

Pulling tension

Valtech Cardioband

Transeptal access super-annular implant by TEE/Fluoro guidance

Mitralign – pledgeted annular plication

Spiral nitinol coils – anchoring by atrial ring

and cinching of chordae by ventricular ring

Millipede

Transcatheter mitral annular reduction with a self-

centering, positioning, and attaching device

Ring in mitral valve

Ring expanded

Adapted from Hermiller TCT 2011

Trans-catheter Mitral

Valve Replacement

JACC 2014; 64 , NO.17

Transcatheter Mitral Valve Replacement

Tendyne Valve

Self expanding trileaflet pericardial valve sewn onto a nitinol frame

Transapical

The first 2 cases of human Tendyne valve implantation were

performed in 2013 in patients going to surgical MV replacement at the French Hospital, Asuncion,

Paraguay

JACC 2015; 6 5: 2352-3

Tendyne Valve

TIARA Valve

Self-expanding bioprosthesis with cross-linked bovine pericardial tissue leaflets mounted inside a metal

alloy frame

The first 2 cases of human Tiara valve implantation were

performed in January and February 2014 at St. Paul’s Hospital,

Vancouver, British Columbia, Canada.

Transapical

Tiara Valve

Valvular Interventional Cardiology in Perspective

• Aortic

Dr. Alain Cribier First-in-Man PIONEER

April 16, 2002

It was impossible

to predict the general

application of this

new procedure!

Catheterization and Cardiovascular Interventions 2005; 66:465–469

Bogotá 2015

> 40.000 válvulas implantadas en el mundo

> 200.000 válvulas implantadas en el mundo en 2015

Estimated Global TAVR Procedures

SOURCE: Credit Suisse TAVI Comment –January 8, 2015. Revenue split assumption in 2025 is 45% U.S., 35% EU, 10% Japan, 10% ROW

18,000

M.B Leon TVT Chicago 2015

Estimated Global TAVR Growth

SOURCE: Credit Suisse TAVI Comment –January 8, 2015. ASP assumption for 2024 and 2025 based on analyst model. Revenue split assumption in 2025 is 45% U.S., 35% EU, 10% Japan, 10% ROW

In the next 10 years, TAVR growth will increase X4!

M.B Leon TVT Chicago 2015

TAVR “Underutilization” is Largely Driven by

Variation in Health Policy and Reimbursement

SOURCE: Eurostat, U.S. Census Bureau, Industry estimates

M.B Leon TVT Chicago 2015

How is the Market developing

Source BIBA Data until dec 31 2014

Total

Transfemoral

Transapical

2% 3% 3% 2% 2% 3% 2% 2% 2%

2% 2% 2% 2%

26% 23% 22%

21% 20% 20% 19% 17% 17% 16% 16% 16% 16%

71% 71% 73% 73% 73% 72% 72%

75% 76% 77% 78% 79% 79%

0% 2% 3%

5% 5% 5% 6% 6% 4% 4% 3% 3%

CY11 Q4 CY12 Q1 CY12 Q2 CY12 Q3 CY12 Q4 CY13 Q1 CY13 Q2 CY13 Q3 CY13 Q4 CY14 Q1 CY14 Q2 CY14 Q3 CY14 Q4

Europe Including Germany

TF

TA

SC DA

How is the Market developing

3.2% 4.0% 3.6% 2.8% 2.6% 3.7% 2.7% 2.8% 2.2%

4.1% 3.8% 1.9%

4.0%

19.8% 18.9% 17.3%

15.3% 13.7% 14.5%

11.6% 12.3% 12.3% 10.0% 10.7% 10.5% 10.8%

77.0% 74.2%

75.7% 77.0%

79.3%

75.4% 76.2% 78.1% 78.4%

79.9% 80.3% 83.2% 82.0%

0.0% 2.9% 3.5%

4.9% 4.4% 6.4% 6.8% 7.0% 6.1% 5.1% 4.4% 3.2%

CY11 Q4 CY12 Q1 CY12 Q2 CY12 Q3 CY12 Q4 CY13 Q1 CY13 Q2 CY13 Q3 CY13 Q4 CY14 Q1 CY14 Q2 CY14 Q3 CY14 Q4

Europe Without Germany

TF

TA

SC

DA

TAVI Implants. Access route

1.Introduction

2.Clinical research

3.Expanding indications

4.Issues

5.Adjunctive Pharmacology

6.Ideal Transcatheter Valve

7.Summary

• Randomized clinical trials ( PARTNER and US CoreValve)

and important registries (e.g. TVT, ADVANCE)

Rigorous Clinical Research

8.494 patients included in FDA trials

( 279 ptes in EVEREST II Trial )

PARTNER Manuscripts in NEJM (October, 2010 – May, 2012)

PARTNER B PARTNER A

PARTNER 5-year FU in Lancet (March, 2015)

PARTNER II

High Risk patients at 30 days

Mortality and Stroke Baseline characteristics

PARTNER II

Intermediate Risk patients at 30 days

Mortality and Stroke Baseline characteristics

N Engl J Med on March 29, 2014 JACC on May 20, 2014

Corevalve Trials (March 2014 – May, 2014)

PRIMARY END POINT

4.9 % Absolute risk reduction

P<0.001 for noninferiority;

P = 0.04 for superiority)

The results were similar in the intention-to-treat analysis; the event rate was 13.9% in the TAVR group, as compared with 18.7% in the surgical group (absolute risk reduction, 4.8 %)

2 years All Cause Mortality Corevalve US Pivotal trial

Echocardiographic valve performance Corevalve US Pivotal trial

J Am Coll Cardiol 2015;65:2184–94

Nordic Aortic Valve Intervention (NOTION) Trial

Objective: Compare TAVI vs. SAVR in patients >70 years eligible

for surgery (all-comers population)

Primary outcome: Composite rate of death from any cause, stroke or

myocardial infarction at 1 year (VARC II-defined)

Secondary

outcomes:

Safety and efficacy (NYHA), echocardiographic

outcomes

(VARC II-defined)

J Am Coll Cardiol 2015;65:2184–94

Enrollment Criteria

Main inclusion criteria

•Severe AS

•Age ≥70 years

•Life expectancy ≥ 1 year

•Suitable for TAVR & SAVR

Main exclusion criteria

• Severe CAD

• Severe other valve disease

• Prior heart surgery

• Need for acute treatment

• Recent stroke or MI

• Severe lung disease

• Severe renal failure

J Am Coll Cardiol 2015;65:2184–94

13.1 16.3

ITT

TAVI SAVR

Primary Outcome*

Death from any cause, stroke or myocardial infarction

3.2% absolute difference; p . 0.43 for superiority

Secondary Outcomes at 2 Years

1 Year 2 Years

Outcome, % TAVI SAVR p-value TAVI SAVR p-value

Death, any cause 4.9 7.5 0.38 8.0 9.8 0.54

Death, cardiovascular 4.3 7.5 0.25 6.5 9.1 0.40

Stroke 2.9 4.6 0.44 3.6 5.4 0.46

TIA 2.1 1.6 0.71 6.0 3.3 0.30

Myocardial infarction 3.5 6.0 0.33 5.1 6.0 0.69

Atrial fibrillation 21.2 59.4 <0.001 22.7 60.2 <0.001

Pacemaker 38.0 2.4 <0.001 41.3 4.2 <0.001

Aortic valve re-intervention 0.0 0.0 na 0.0 0.0 na

J Am Coll Cardiol 2015;65:2184–94

Aortic Valve Performance

J Am Coll Cardiol 2015;65:2184–94

David Wood MD, FRCPC, FACC, FESC, FSCAI, FSCCT

Structural & Interventional Cardiology, VGH and SPH

Associate Clinical Professor, UBC

Centre for Heart Valve Innovation

How to TAVR Session II: Procedural Trends

Adoption of the Minimalist Approach

Williford C, Third Floor

June 4th, 2015

16:59 – 17:07

The North American 3M TAVR Study

Multidisciplinary, Multimodality, but Minimalist

To achieve optimal results…

• Safe

• Reproducible (general anesthetic or awake)

• Reduced LOS to not only improve cost effectiveness

but also clinical outcomes

• Glimpse of the future (for both individual Heart

Teams and regional Health Authorities)…

Considered at increased surgical risk by the Heart Team

COMPLETE REVASCULARIZATION Staged PCI of all suitable

non-culprit lesions (< 45 days)

3M TAVR Study Design To evaluate the efficacy, feasibility and safety of next day discharge home in patients undergoing balloon expandable transfemoral TAVR utilizing the Vancouver 3M Clinical Pathway

Patients with severe symptomatic AS undergoing elective transfemoral TAVR

Primary Outcomes: All-cause mortality and major stroke (modified Rankin Scale of 2 or

more) at 30 days AND the proportion of patients who are discharged the next day

Vancouver 3M Clinical Pathway

(n = 400)

Meets all general, anatomical, functional, and

peri-procedural exclusion criteria

Standard TAVR

(n = 800)

All remaining patients at all sites

Standard Care

Secondary Outcomes: each component of the primary endpoint; death or non-fatal stroke at 1 year; 30 day major

vascular complications/life-threatening bleed/hospital readmission/repeat procedure for valve related

dysfunction/stage 3 acute kidney injuries (AKIN classification); periprocedural MI, conversion to

GA/intubation; KCCQ and SF-12 at 2 weeks, 30 days, and 1 year

Methods (Pilot Study)

• From a potential pool of 385 patients considered high risk for surgery, 85

(22%) were selected for the 3M protocol and underwent SAPIEN XT

(Edwards Lifesciences Inc.) valve implantation

• The Vancouver 3M Clinical Pathway was prospectively utilized for

objective anatomical and functional screening, peri-procedural

management, and to determine if next day discharge home was

appropriate

• Thirty day and one year outcomes were reported according to VARC-2

guidelines

J Am Coll Cardiol. 2014;64(11_S):. doi:10.1016/j.jacc.2014.07.773

“Outpatient” Same-Day TAVR Sacre-Coeur Hospital; Montreal, CN

Philippe Genereux

Philippe Demers

Donald Palisaitis

• Overall, 62/85 (73%) were discharged home one day post

TAVR with 2 readmissions (2.4%) within 30 days.

• At 30 days and 1 year, 97% (83/85) and 93% (51/55) were

NYHA class I or II with mild or less paravalvular

regurgitation.

1.Introduction

2.Clinical research

3.Expanding indications

4.Issues

5.Adjunctive Pharmacology

6.Ideal Transcatheter Valve

7.Summary

0%

5%

10%

15%

20%

25%

30%

35%

23 mmn=27

26 mmn=353

29 mmn=549

31 mmn=94

Sizi

ng

Rat

io (

%)

IFU Sizing Window

Mean Sizing Ratio by Valve Size

N=1023

Sizing Ratio and Mod/Severe PVL

17.60%

9.90%

6.30% 4.90%

0%

2%

4%

6%

8%

10%

12%

14%

16%

18%

20%

≤10% n=136

10-15%n=304

15-20%n=269

>20%n=206

[(CoreValve Perimeter – Annulus) / Annulus] x 100

N=1023

% M

od

erat

e/Se

vere

Dis

char

ge P

VL

Permanent Pacemaker Placement

15.1%

21.6% 17.9%

24.6%

0%

5%

10%

15%

20%

25%

30%

≤ 10% n=152

10-15%n=338

15-20%n=291

>20%n=228

[(CoreValve Perimeter – Annulus) / Annulus] x 100

N=1023

Inci

den

ce o

f N

ew P

erm

anen

t Pa

cem

aker

at

30

Day

s

Embolization Compresion Endocarditis

Conclusion: Transcatheter heart valves are susceptible to failure modes typical to those of surgical bioprostheses and unique to their specific design. Transcatheter heart valve compression and late embolization represent complications previously unreported in the surgical literature

http://www.scai.org/TAVRCenter/Presentation.aspx?cid=da88a902-105a-401c-880d-cfae3bf9c2ab#

SCAI TAVI Center

What Happened to the Valve?

1.Introduction

2.Clinical research

3.Expanding indications

4.Issues

5.Adjunctive Pharmacology

6.Ideal Transcatheter Valve

7.Summary

A total of 672 TAVI patients treated: • ASA (N=415) • DAPT (N=257)

Hassell MECJ, et al. Heart 2015;0:1–8

No difference in net adverse clinical and cerebral events was observed

However, ASA was associated with a decreased tendency of life-threatening and major bleeding

TAVR Adjunct Pharmacology

Customized Patient-Based Therapy

New TAVR Pharmacology Trial

PIs: Dangas, G. Windecker, S.

International Multicenter Randomized

TAVR UNLOAD

Trial

Heart Failure LVEF < 50% NYHA ≥ 2

Optimal HF therapy (OHFT)

Moderate AS

R

TAVR + OHFT

OHFT alone

Follow-up: 1 month 6 months

1 year

Clinical endpoints Symptoms

Echo QoL

Primary Endpoint

Hierarchical

occurrence of:

• All-cause death

• Disabling stroke

• Hospitalizations

for HF, aortic

valve disease, or

non-disabling

stroke

• Change in KCCQ

Reduced AFTERLOAD

Improved LV systolic

and diastolic function

1.Introduction

2.Clinical research

3.Expanding indications

4.Issues

5.Adjunctive Pharmacology

6.Ideal Transcatheter Valve

7.Summary

The Ideal Transcatheter Aortic Valve

MDT Evolut R Edwards Sapien 3

Significant technology differences among devices, but no major mortality/stroke

differences between Sapien vs. CV; choice determined by secondary outcomes and

anatomic considerations

TAVR Systems with CE-Approval (2007-15)

SUMMARY

The “IDEAL” Aortic Trans-catheter Valve should be:

• Durable

• Trans Femoral

• Sheath Outer diameter <14 French

• Precise and predictable positioning

• Low complication rates:

• Pacemaker rate < 10%

• Stroke rate lower than surgery

• Moderate or severe aortic regurgitation absent

1.Introduction

2.Clinical research

3.Expanding indications

4.Issues

5.Adjunctive Pharmacology

6.Ideal Transcatheter Valve

7.Summary

• Dominant technology for severe AS, supported by

rigorous clinical research.

• Further technology enhancement (including

adjunctive imaging) and procedural simplification.

• Expanded clinical indications and creative new

applications (TAVI+ PCI, LAAC, Mitraclip, etc.

• Platform extensions to treat all forms of valvular

disease

TAVI future. SUMMARY

¿ Quienes no son buenos candidatos para cirugía?

¿ Quienes son buenos candidatos para TAVI?

Cambio de la pregunta

In Summary

World Wide Cardiology Market Trends

Staged or Single-Stage Procedures are here

• Aortic valve-in-valve

• MitraClip

• LAA closure

• Coronary stent

J. Webb

Agosto 2015 Muchas gracias