Τρέχουσες Κατευθυντήριες Οδηγίες στη Διακαθετηριακή Εμφύτευση Αορτικής

Βαλβίδας: Χρειάζονται αναθεώρηση;

ΠΕΤΡΟΣ Σ. ΔΑΡΔΑΣ, MD, FESC

ΚΛΙΝΙΚΗ ΑΓΙΟΣ ΛΟΥΚΑΣ

7ο IICE, ΘΕΣΣΑΛΟΝΙΚΗ 2014

Aortic stenosis

Management challenges:

• The asymptomatic patient with severe AS

• Low-flow, low gradient severe AS

• Indications for TAVR

class I

Intervention for Severe AS

Indications for TAVR vs surgical AVR:

• Evaluation by a Heart Team

New 2014

Intervention for Severe AS

Indications for TAVR vs surgical AVR:

class I

class I

• Evaluation by a Heart Team

• Surgical AVR for patients at

low or intermediate risk

New 2014

Intervention for Severe AS

Indications for TAVR vs surgical AVR:

• Evaluation by a Heart Team

• Surgical AVR for patients at

low or intermediate risk

• TAVR for patients with

prohibitive surgical risk and

life expectancy >12 months

class I

class I

class INew 2014

Intervention for Severe AS

Indications for TAVR vs surgical AVR:

• Evaluation by a Heart Team

• Surgical AVR for patients at

low or intermediate risk

• TAVR for patients with

class I

class I

class I

class IIa

prohibitive surgical risk and

life expectancy >12 months

• TAVR alternative for patients

at high surgical risk

New 2014

Intervention for Severe AS

Indications for TAVR vs surgical AVR:

• Evaluation by a Heart Team

• Surgical AVR for patients at

low or intermediate risk

• TAVR for patients with

class I

class I

class I

?class

prohibitive surgical risk and

life expectancy >12 months

• TAVR alternative for patients

at MODERATE risk

New 2014

Aortic Stenosis

10%

10 %

25%

60%

Extreme Risk

High Risk

Intermed. Risk

Low Risk

TAVI orSAVR ?

universitätsklinikum giessen

Risk

“unethical”

KERCKHOFF HERZ- UND THORAXZENTRUM

Patients

5%

Outline

• Current status of TAVR

• Defining risk

• Current evidence for intermediate risk

patients

• Future trials

Outline

• Current status of TAVR

• Defining risk

• Current evidence for intermediate risk

patients

• Future trials

All causemortality 20%

10%

0

50%

40%

30%

0 6 12 18 24

TAVR

AVR

Months

24.2%

HR [95% CI] =0.93 [0.71, 1.22]

P (log rank) =

0.6226.8%

40%

20%

0%

100%

80%

60%

0 6 12 18 24

TAVR

Std Tx

30.7%

HR [95% CI] = 0.51 [0.38, 0.68]p (log rank) < 0.001

50.7%

Months

All Cause Mortality (%)

Standard Rx

TAVR

179

179

121

138

85

124

62

110

46

101

27

88

17

70

All Cause Mortality (ITT)Inoperable Cohort (3 years FU)

0%

40%

20%

60%

100%

0 6 12 18 24 30 36

50.8%

Months

Numbers at Risk

HR [95% CI] = 0.53 [0.41, 0.68]p (log rank) < 0.0001

25.0%

80.9%80%

68.0%26.8%

20.1%

30.7%

NNT = 5.0 pts

43.0%

NNT = 4.0 pts

54.1%

NNT = 3.7 pts

Standard Rx

TAVR

TAVR

AVR

348

351

298

252

261

236

239

223

222

202

187

174

149

142

No. at Risk

26.8%

24.3%

34.6%

33.7%

HR [95% CI] =

0.93 [0.74, 1.15]

p (log rank) = 0.483

44.8%

44.2%

TCT 2014 | September 13, 2014

Five-Year Outcomes of TranscatheterAortic Valve Replacement (TAVR) in

“Inoperable” Patients With SevereAortic Stenosis: The PARTNER Trial

Samir R. Kapadia, MDOn behalf of The PARTNER Trial Investigators

All-Cause Mortality (%)

93.6%

All-Cause Mortality (ITT)Crossover Patients Censored at Crossover

Standard Rx (n = 179)

TAVR (n = 179)

50.8%

30.7%

43.0%

68.0%

71.8%

87.5%

64.1%

53.9%

HR [95% CI] = 0.50 [0.39, 0.65]

80.9%

p (log rank) < 0.0001

Months

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

Incidence (%)

Stroke (ITT)

Months

18.2%16.0%

Standard Rx

TAVR

Pivotal Trial Design

TCT 2014 4

TCT 2014 15

All-Cause Mortality or Major Stroke

* Calculated rate for 117 events in 179 patients (65.4%, lower confidence bound of

57.9% by Exact method) (Makkar RR, et al, New Engl J Med, 2012)

Pivotal Trial Design

20Adams NEJM 2014 March 29 (epub ahead of print) Increased Risk RCT

2-Year All-cause Mortality

P < 0.001 for non inferiority

P = 0.04 for superiority

22Adams NEJM 2014 March 29 (epub ahead of print) Increased Risk RCT

All Stroke

23Adams NEJM 2014 March 29 (epub ahead of print) Increased Risk RCT

25Adams NEJM 2014 March 29 (epub ahead of print) Increased Risk RCT

Subgroup Analysis for 1 Year Mortality

The Treatment Effect of

TAVR over SAVR was similar

in patients with STS < 7 and

STS > 7

Outline

• Current status of TAVR

• Defining risk

• Current evidence for intermediate risk

patients

• Future trials

Ospedale Ferrarotto

Università di Catania

The right indication

EACTS/ESC/EAPCI Position statement Eur Heart J 2008

Indication for TAVI is:

Symptomatic severe aortic stenosis and

HIGH-RISK (LES > 20%, STS > 10%) and/or

CONTRAINDICATION for surgical aortic valve replacement

KERCKHOFF HERZ- UND THORAXZENTRUMuniversitätsklinikum giessen

High Risk Intermed.

Risk

Low Risk

EURO > 20 <5

STS > 8 (10) < 4 (3)

What is Intermediate Risk?

?

Beohar, N., et al. Acquired Cardiovascular Disease, 2014.

Existing Risk Scores

Existing risk scores are

poor discriminators of 30

day and 1 yr TAVR

outcome

TAVR-specific risk models

are needed to optimize pt

selection

KERCKHOFF HERZ- UND THORAXZENTRUMuniversitätsklinikum giessen

Frailty

Porcelain aorta

Liver disease

Previous radiation

Hostile chest

Severe concomitant diseases

Not reflected in Scores:

New US Guidelines 2014

Ospedale Ferrarotto

Università di Catania

Coronary artery disease requiring revascularization

Frailty (Katz score + Ambulation Aid + Dementia)

Left ventricular dysfunction (EF <35% by TTE)

Neurological dysfunction (with functional impairment)

Pulmonary disease (GOLD stage II)

Peripheral vascular disease (including porcelain aorta)

Renal disease (KDOQI Stage 3, GFR < 60 mL/min)

Redo cardiac surgery

Pulmonary hypertension (> 60mmHg)

Diabetes

SURTAVI Model Co-Morbidities

Ospedale Ferrarotto

Università di Catania

How can we define the intermediate risk?

SURTAVI model Rationale

Outline

• Current status of TAVR

• Defining risk

• Current evidence for intermediate risk

patients

• Future trials

TAVR in Lower Surgical Risk Patients

Bern1 Munich2

Lower Risk(n=254)

Higher Risk(n=94)

Lower Risk(n=105)

Higher Risk(n=105)

STS (%)

Log EuroSCORE (%)

30 Day Mortality (%)

Total Vascular

Complications (%)

Stroke / TIA (%)

5.1± 1.4

22.1± 11.9

3.9

17.7

5.0

13.3± 7.1

35.1± 15.7

14.9

20.3

3.4

4.8± 2.6

17.8± 12.0

3.8

14.7

1

7.13± 5.4

25.44± 16.0

11.4

28.6

6.7

1Wenaweser,et al., Eur Heart J 2013; 34: 1894-905;2Lange, et al., J Am Coll Cardiol 2012; 59: 280-7

TAVR in Low/Moderate Risk Patients

2 EU centers have directly compared TAVR outcomes

of patients at lower- and higher-risk...

TAVR in Low/Moderate Risk PatientsThe Bern Experience

AUGUST 2007 - OCTOBER 2011 HEART TEAM DECISION

WENAWESER P ET AL. EUR HEART J. 2013

Piazza1 OBSERVANT2 Latib3

TAVI SAVR

p

TAVI SAVR

p

TAVI SAVR

p

STS

(%, mean)

Log EuroSCORE

(%, mean)

(n=255)

3-8

17.3

(n=255)

3-8

17.6

(n=133)

na

8.9

(n=133)

na

9.4

(n=111)

4.6

23.2

(n=111)

4.6

24.4

30 Day Mortality

(%)7.8 7.1 0.74 3.8 3.8 1.000 1.8 1.8 1.00

1Piazza, et al. , J Am Coll Cardiol Intv 2013; 6: 443-51;2D’Errigo,et al., Int J Cardiol 2013; 167: 1945-52;3Latib, et al., Am Heart J 2012; 164: 910-7

TAVR vs. Surgery in “Matched”

Moderate Risk Patients

3 EU studies have compared TAVR vs. Surgery using

propensity-matching in moderate risk patients...

Piazza, et al. , J Am Coll Cardiol Intv 2013; 6: 443-51

• TAVR and SAVR result in similar 30-day (7.8% vs. 7.1%, p=0.74) and 1-yearmortality(16.5% vs. 16.9%, p=0.64)

• Stratified analyses of 1-year all-cause mortality showed women to have agreater benefit from TAVR vs. SAVR compared to men (P interaction = 0.027).

BERMUDA - Clinical Outcomes

OBSERVANT registry propensity-matched analysis from more than 7600 patients

• In PARTNER A and the CoreValve High-Riskstudy, mean logistic EuroScores were 29 and 19, respectively. In OBSERVANT, the mean EuroScore was 9.8

0.00

0.40

Overall mortality (%)

0.30

0.20

0.10

0.00

Overall at risk analysis timemortality

Number

40 515

Mortalità502

180

549 535 525 519569 543 531 517

intervento = AVR intervento = TAVI

10

0

00

390

9270

12360

6

Monthsanalysis time

No. at risk:

650AVR SAVR 625TAVITAVI 625650

549569

535543

525531

519517

HR: 0.99, 95%CI 0.72-1.35; p=0.936

13.1%

20

13.3%

0

SAVR 625TAVI 625

360

495

492

intervento = TAVI25 552 525 intervento = AVR492

25 534

90 180

90

270

534

552502

180 270analysis time

360

515

525 509495

intervento = AVR

30intervento = TAVI

509 AVR

TAVI

1 year OBSERVANT - Marco Barbanti TCT, September 13 2014

Outline

• Current status of TAVR

• Defining risk

• Current evidence for intermediate risk

patients

• Future trials

TF TAVRSAPIEN XT

SurgicalAVR

Primary Endpoint: All-Cause Mortality +

Disabling Stroke at Two Years

(Non-inferiority)

TAVR:TA / TAo

SAPIEN XT

SurgicalAVR

VSVS

Operable(STS ≥4)

ASSESSMENT:

Transfemoral

Access

Transapical (TA) /

TransAortic (TAo)

1:1 Randomization

Transfemoral (TF)

1:1 Randomization

No

n = 2000Randomized

Patients

Yes

The PARTNER IIA TrialStudy Design

Symptomatic Severe Aortic Stenosis

ASSESSMENT by Heart Valve Team

• 2011 patients enrolled

in 22 months!

• Mean STS ~6%

• ~75% TF access

76.2%

18.3%

5.5%

Transfemoral

Transapical

Transaortic

PARTNER IIA - Intermediate RiskVascular Access Sites

> 75% Patients with Trans-femoral Access

0

1

2

3

4

5

6

7

8

PARTNER IIA - Intermediate RiskMean STS Score by Site

Mean STS Score ~ 6

59 enrolling sites

TAVR in MODERATE Risk Patients

SURTAVI UPDATE…

STS risk score

1st 250 2nd 250

5.53±1.305.64±1.40

Up-date 5.08±1.38

Mean 5.42±1.38First patientenrolled withCIP version8

Patient number

8

Screened-Baseline characteristicsSTS risk score

102-Year All-cause Mortality: CoreValve US Pivotal Trial

ACC 2014

11

STS PROM estimateCoreValve US Pivotal Trial

As – Treated Population

STS PROM estimate

Mean estimate - %

< 4% - no. (%)

4 ~ 10% - no. (%)

> 10% - no. (%)

TAVR Group(N = 390)

7.3± 3.0

33 (8.5)

304 (77.9)

53 (13.6)

Surgical Group(N = 357)

7.5± 3.4

40 (11.2)

251 (70.3)

66 (18.5)

Adams DH et al. N Engl J Med 2014;370:1790-1798

12

STS PROM estimateCoreValve US Pivotal Trial

As – Treated Population

STS PROM estimate

Mean estimate - %

< 4% - no. (%)

4 ~ 10% - no. (%)

> 10% - no. (%)

TAVR Group(N = 390)

7.3± 3.0

33 (8.5)

304 (77.9)

53 (13.6)

Surgical Group(N = 357)

7.5± 3.4

40 (11.2)

251 (70.3)

66 (18.5)

Adams DH et al. N Engl J Med 2014;370:1790-1798

13

STS PROM estimateCoreValve US Pivotal Trial

As – Treated Population

STS PROM estimate

Mean estimate - %

< 4% - no. (%)

4 ~ 10% - no. (%)

> 10% - no. (%)

TAVR Group(N = 390)

7.3± 3.0

33 (8.5)

304 (77.9)

53 (13.6)

Surgical Group(N = 357)

7.5± 3.4

40 (11.2)

251 (70.3)

66 (18.5)

Adams DH et al. N Engl J Med 2014;370:1790-1798

14

STS PROM estimateCoreValve US Pivotal Trial

As – Treated Population

STS PROM estimate

Mean estimate - %

< 4% - no. (%)

4 ~ 10% - no. (%)

> 10% - no. (%)

TAVR Group(N = 390)

7.3± 3.0

33 (8.5)

304 (77.9)

53 (13.6)

Surgical Group(N = 357)

7.5± 3.4

40 (11.2)

251 (70.3)

66 (18.5)

Based on STS: > 80% of patients would be considered intermediate risk!Adams DH et al. N Engl J Med 2014;370:1790-1798

• Paravalvular leak

• Stroke

• Vascular complications

• Pacemaker implantation

• Coronary obstruction

TAVR in 2014

Future Directions

• Expanded Clinical Indications - Additional

indications for TAVR are being actively studied

(e.g. bioprosthetic valve failure and moderate risk

patients), and if valve durability can be assured, “less-

invasive” TAVR may offer new clinical treatment

possibilities, even beyond current surgical indications

(e.g. severe asymptomatic AS).

Treating bioprosthetic failure by transcatheter valve-in-

valve implantation has been shown to be feasible.

Current evidence is limited, therefore it cannot be considered

as a valid alternative to surgery except in inoperable or high-

risk patients as assessed by a ‘heartteam’.

A. Vahanian et al, Eur Heart J. 2012 Oct; 33(20):2569-619

ESC guidelines 2012

Valve in valve

Valve in valve

Components of an Ideal Valve•

•

•

•

•

•

•

•

•

Low profileExcellent hemodynamicsPredictable deploymentRetrievable/RepositionableMinimal paravalvular regurgitationMinimal interference with surrounding anatomyLow thrombotic riskDurableCost Effective

The SAPIEN 3 Valve is Designed to Minimize PVL

While Achieving an Ultra-low Delivery Profile

Outer skirt

• Polyethylene terephthalate (PET)

outer skirt designed to minimizeparavalvular leak

Ultra-low delivery profile

• 14F eSheath compatible1

• 18F Certitude sheath compatible2

1. 14FeSheath compatible for 23mmand 26mmSAPIEN3 valves. 16FeSheath compatible for 29mmSAPIEN3 valve. 2. 18FCertitude Sheath compatible for 23mmand 26 mmSAPIEN3valves. 21FCertitude Sheath compatible for 29mm SAPIEN3 valve.

10

• Full annulus range (18 – 29mm)

• True anatomical fit (TruFit™) forannular sealing

CoreValve Evolut R System

Fully Resheathable, Repositionable, Recapturable*

• Delivery system built on next

generation platform (InVia™)

• Includes InLine™ Introducer Sheathfor reduced delivery profile

* Until fully deployed

TAVR in 2014

Accomplishments

• Encouraging Valve Durability - Echocardiogrphy

results with follow-up for at least 5 years are without

evidence of structural valve deterioration and indicate

maintained excellent valve hemodynamics.

CONCLUSION

• three reasons for not extending TAVR beyond high surgical-risk patients are:

– the excellent outcomes with SAVR

– the high cost of TAVR

– the lack of durability data

• We [assume] these [TAVR] valves will last as long as biological surgical valves, but we have to act on evidence-based medicine

CURRENT PRACTICE

• Very old low-risk patients– TF approach – local anaesthesia

– Avoid discomfort of surgery and long term recovery

• Younger – low risk patients– Procedural safety

– Long term durability• In the event of accelerated valve failure, low risk patients would remain

good canditates for SAVR

• In the event of late valve deterioration, valve-in-valve TAVI could always be an option

Intervention for Severe AS

Indications for TAVR vs surgical AVR:

• Evaluation by a Heart Team

• Surgical AVR for patients at

low or intermediate risk

• TAVR for patients with

class I

class I

class I

?class

prohibitive surgical risk and

life expectancy >12 months

• TAVR alternative for patients

at MODERATE risk

New 2014

TAVR: A Medical Breakthrough

Finally, will we see in the future SAVR reserved to patients with

contra-indications to TAVR ?…

In the coming years, with continuous advances in technologies and

simplified techniques, TAVR should expand to a broad population

of lower risk AS patients