Transcatheter Aortic Valve Implantation (TAVI): Current ... · Evidence 3. TAVI Learning Curve ....

Transcatheter Aortic Valve Implantation (TAVI):

Current Evidence Davy C. H. Cheng, MD MSc FRCPC FCAHS CCPE

Distinguished University Professor & Chair / Chief

Department of Anesthesia & Perioperative Medicine

Professor, Critical Care Medicine, Department of Medicine

Western University

London, Ontario, Canada

davy.cheng@LHSC.ON.CA

Department of Anesthesia & Perioperative Medicine www.uwoanesthesia.ca

LHSC (UH-VH) $1.1 Billion

SJHC London $500 Millions

42 OR (3-4 Cardiac OR/d,

1,350 cardiac surgery/yr)

68 ICU beds (14 CSRU)

88 Anesthesia Faculty

20 Fellows

47 Residents

DISCLOSURE

No Industries Conflict of Interest

Ministry of Health and Long-Term Care AFP

Innovation Fund (MOHLTC)

Canadian Institutes of Health Research

Co-Chair ISMICS Consensus Conferences

Co-Chair ECTS Consensus Conference

Acknowledgement: Janet Martin

OBJECTIVES

1. Consensus Conference in TAVI

versus SAVR and Medical

Management

2. TAVI Outcomes and Current

Evidence

3. TAVI Learning Curve

AVR in Octogenarians

Author City n 30 day

Mort. %

Journal (2007-8)

Melby SJ St Louis 245 9 Annals Thorac Surg

Roberts WC Dallas 196 10 Am J Cardiol

Bose AK Newcastle 68 13 J Cardiothorac Surg

Urso S San

Sebastian 100 8 J Heart Valve Dis

Kolh P Liege 220 9 Eur J Cardiothor Surg

Mohr FW Leipzig 282 9.2 Eur J Cardiothor Surg, submitted

Conventional SAVR surgery

is the ‘Gold Standard’

Surgery was denied in 33% of elderly

patients with severe, symptomatic AS

Homograft – 1962

Porcine valve, 1965

Pericardial tissue valve, 1969

1950 1960 2002 1970 2004 2005

First CoreValve Transcatheter AVR by

Retrograde Approach

Laborde, Lal, Grube – July 12, 2004

First PVT Transcatheter AVR

by Antegrade Approach

Alain Cribier - 2002

Surgery

Transvascular

Aortic Valve Replacement

2006

First CoreValve Percutaneous AVR

by Retrograde Approach – Oct 12, 2006

Serruys, DeJaegere, Laborde

First Edwards/PVT Transapical

Beating Heart AVR

Webb, Lichtenstein – Nov 29, 2005

2001 2000

First PVT animal

implantation

A. Cribier

First Corevalve

animal implantation

JC. Laborde

2007

PARTNER Trial

First plastic ball

valve - TDA, 1952

Charles Hufnagel

Mechanical aortic valve, 1962

Transcatheter Aortic Valve

Implantation (TAVI)

8

Trans Femoral approach

Trans Apical

Trans Subclavian

Trans Subclavian

Trans Aorta

INTERNATIONAL SOCIETY FOR

MINIMALLY INVASIVE

CARDIOTHORACIC SURGERY

ISMICS 2012 EXPERT CONSENSUS PANEL MEMBERS

Paris – April 20-22, 2012 Gregory Fontana, Chair New York, USA

Davy Cheng, Co-Chair London, Canada

Janet Martin London, Canada

Anson Cheung Vancouver, Canada

Todd Dewey Dallas, USA

Gino Gerosa Padova, Italy

John Knight Adelaide, Australia

Francesco Maisano Milano, Italy

Raj Makkar LA, USA

Ganesh Manoharen Belfast

Alan Menkis Winnipeg, Canada

Nicolo Piazza Montreal, Canada

Carlos Ruiz New York, USA

Vinod Thourani Atlanta, USA

Thomas Walther Bad Nauhaim, Germany

Olaf Wendler London, UK

Mat Williams New York, USA

TAVI vs SAVR CC Objectives

1. TAVI vs SAVR

To assess TAVI (TF and TA) improves

clinical and resource-related outcomes in

AS patients eligible for conventional open

SAVR

2. TAVI vs MM

To assess TAVI (TF) improves clinical and

resource-related outcomes compare with

medical management (MM) in AS patients

ineligible for open SAVR

N = 179

N = 358 (B)

Inoperable

Standard

Therapy

ASSESSMENT:

Transfemoral

Access

Not In Study

TF TAVR

Primary Endpoint: All-Cause Mortality

Over Length of Trial (Superiority)

Co-Primary Endpoint: Composite of All-Cause Mortality

and 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 VS

VS

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

The PARTNER Study Design

Symptomatic Severe Aortic Stenosis

ASSESSMENT: High-Risk AVR Candidate

3,105 Total Patients Screened

Total = 1,057 patients

2 Parallel Trials:

Individually Powered

N = 699 (A)

High Risk

ASSESSMENT:

Transfemoral

Access

Transapical (TA) Transfemoral (TF)

1:1 Randomization 1:1 Randomization

Yes No

N Engl J Med 2010;363:1597-1607.

Partner B Trial

N Engl J Med 2011;364:2187-98.

Partner A Trial

N Engl J Med 2012 May

Partner B Trial Follow up

N Engl J Med 2012 May

Partner A Trial Follow up

Citations Screened:

N = 3630 (up to April 2012)

Potentially Relevant Level A/B

Retrieved:

N = 986 Potentially -relevant Trials

Excluded after Retrieval:

n = 491

Relevant Level A/B studies:

N = 495

Relevant trial Excluded from

after retrieval: n = 335 Included Level A/B studies

N = 44 (3 RCTs, 41 NRCTs)

Non-relevant Trials Excluded

before Retrieval: n = 3136

Meta-Analysis of TAVI: Level A/B

TAVI vs SAVR

Group byComparison

Study name Subgroup within study Comparison Outcome Statistics for each study Odds ratio and 95% CI

Odds Lower Upper ratio limit limit p-Value

N Dallas_Dewey 08 MIXED N death, 30d 1.58 0.13 19.12 0.72

N Paris_Descoutures 08 TF N Death, 30d 9.67 0.89 104.82 0.06

N Malaga_CaballeroBorrego 11 TF N death, 30d 0.47 0.05 4.66 0.52

N Catania-Pedara_Tamburino12 MIXED N Death, 30d 1.48 0.74 2.98 0.27

N Vancouver_Higgins11 unmatched TA N death, 30d 6.61 2.47 17.67 0.00

N Pisa_DeCarlo 10 TF N death, 30d 0.54 0.09 3.15 0.49

N Milan-Pisa_Ranucci 10 MIXED N death, 30d 5.71 3.08 10.60 0.00

N Rotterdam-Cali-Bogota_Nuis 12 TF N death, 30d 1.02 0.22 4.67 0.98

N Cleveland_Kapadia 09 vs SAVR MIXED N death, 30d 3.34 0.13 87.52 0.47

N Salzburg_Motloch 12, all MIXED N death, 30d 5.12 0.59 44.74 0.14

N Bern-Rotterdam_Piazza 09 MIXED N death, 30d 4.57 2.17 9.65 0.00

N Bochum_Strauch 12 TA N Death, 30d 1.65 0.50 5.43 0.41

N Bern_Amonn 12 TA N Death, 30d 1.05 0.29 3.76 0.95

N 2.44 1.46 4.07 0.00

RCT STACCATO_Nielson 12 TA RCT Death, 30d 8.11 0.40 163.12 0.17

RCT PARTNER A_Smith 11, all MIXED RCT Death, 30d 0.53 0.26 1.10 0.09

RCT 1.39 0.11 17.66 0.80

Y Hamburg_Conradi 12 MIXED Y Death, 30d 0.85 0.27 2.63 0.77

Y Monzino Milan_Fusari 12, matched MIXED Y Death, 30d 0.13 0.01 2.61 0.18

Y Frankfurt_Zierer 09 TA Y Death, 30d 1.50 0.27 8.28 0.64

Y Milan-Pisa_Guarracino10 TF Y Death, in-hospital 3.22 0.32 32.89 0.32

Y Aachen_Stohr11 MIXED Y Death, 30d 1.70 0.82 3.51 0.15

Y Leipzig_Holzhey12 TA Y death, in hospital 0.76 0.36 1.58 0.46

Y Vancouver_Higgins11, matched TA Y death, 30d 1.58 0.41 6.00 0.51

Y Nord_Steigen 11 MIXED Y Death, 30d 4.57 0.47 44.17 0.19

Y BERMUDA triangle MIXED Y Death, 30d 1.12 0.58 2.17 0.74

Y 1.17 0.83 1.66 0.37

Overall 1.48 1.11 1.97 0.01

0.01 0.1 1 10 100

Lower with TAVI Lower with SAVR

TAVI vs SAVR: All-Cause Mortality at 30 days

I2=61%

Group byComparison

Study name Subgroup within study Comparison Outcome Statistics for each study Odds ratio and 95% CI

Odds Lower Upper ratio limit limit p-Value

N Dallas_Dewey 08 MIXED N Stroke, 30d 6.24 0.30 130.07 0.24

N Catania-Pedara_Tamburino12 MIXED N CVA 0.83 0.28 2.42 0.73

N Vancouver_Higgins11 unmatched TA N CVA, postop 3.52 0.81 15.31 0.09

N Essen_Kahlert 10, TF TF N stroke/TIA, 30d 0.21 0.01 5.41 0.35

N London SGH_Jahangiri 11 vs SAVR MIXED N stroke/TIA, 30d 4.95 0.54 45.48 0.16

N Salzburg_Motloch 12, all MIXED N stroke, 30d 3.11 0.12 77.37 0.49

N Bochum_Strauch 12 TA N Stroke, 30d 0.28 0.03 2.52 0.25

N Bern_Amonn 12 TA N Stroke, 30d 1.10 0.25 4.80 0.90

N 1.36 0.66 2.80 0.41

RCT STACCATO_Nielson 12 TA RCT stroke, 30d 3.39 0.33 34.27 0.30

RCT PARTNER A_Smith 11, all MIXED RCT Stroke, any, 30d 2.07 0.87 4.89 0.10

RCT 2.19 0.98 4.92 0.06

Y Hamburg_Conradi 12 MIXED Y Stroke, 30d 1.00 0.14 7.27 1.00

Y Leipzig_Holzhey12 TA Y cerebral ischemia, postop 0.56 0.16 1.95 0.36

Y Vancouver_Higgins11, matched TA Y CVA, postop 0.19 0.01 4.10 0.29

Y Nord_Steigen 11 MIXED Y Stroke, 30d 0.32 0.01 8.25 0.49

Y 0.55 0.21 1.43 0.22

Overall 1.28 0.80 2.05 0.30

0.01 0.1 1 10 100

Favours TAVI Favours SAVR

TAVI vs SAVR: Stroke at 30 days

I2=8%

OUTCOMES: TAVI vs SAVR

SIMILAR INCREASED DECREASED

Mortality Stroke A Fibrillation

MI AR Bld Tx

ARF PPM Reexploration

Stroke (TA and TF)

Miller et al. J Thorac Cardio Surg 2012: 143: 832-43

• Major VC were frequent after TF-TAVI in the

PARTNER trial using first-generation devices

and were associated with high mortality.

N Engl J Med 2012;366:1705-15

May 2014

TAVI vs SAVR

TAVI vs SAVR

Outcomes

TAVI vs Medical Management

Senile Aortic Valve Stenosis

Medical managed patients – survival

rate (62% 1-yr, 32% 5-yr, 18% 10-yr).

It is worse in the presence of

advanced age, LV dysfunction, heart

failure, and renal failure

A Tradeoff between Stroke and Death “For every 100 patients treated with TAVI instead of

medical mgt, there will be 20 additional survivors at 1 year, but at a cost of 6 more stroke/TIAs …”

↑ 6 strokes/TIAs ↓ 20 deaths ↑ 33 symptom-free survival

↓ 6 stroke/TIA ↑ 20 deaths ↓ 33 symptom-free survival

MM (+/-BAV)

TAVI

Cost-Effectiveness Analysis at LHSC

Incremental Cost-Effectiveness Ratio of TAVI vs Medical Management?

COST QALY ICER

TAVI $192,639 4.48

$ 38,448 ($32,000 - 44,000)

STD CARE $ 78,837 1.52

ICER = ∆C/ ∆E = ($192,639 - $78,837) = $38,448/QALY

(4.48 – 1.52)

ISMICS Recommendation:

TAVI vs MM

• In severe AS patients who are

ineligible for SAVR, it is

reasonable to perform TAVI. The

choice between TAVI and MM

involves a trade off between the

increased risk of stroke with

TAVI vs improved 1 yr survival,

clinical status and resource

utilization. [Class IIa, level B]

TAVI vs MM

TAVI vs MM

Learning Curve & Death at 30d

Within increasing experience, 30-day all-cause mortality declines

(p=0.00016)

Regression of Experience on Logit event rate

Experience

Lo

git

ev

en

t ra

te

-29.00 9.40 47.80 86.20 124.60 163.00 201.40 239.80 278.20 316.60 355.00

0.80

0.12

-0.56

-1.24

-1.92

-2.60

-3.28

-3.96

-4.64

-5.32

-6.00

Martin J, Chu M, Cheng D, et al 2012

50 75 5 25 100 125 150 125 175 200 225 250 275 300 400

p=0.00016

Take Home Messages

TAVI: LHSC Hybrid Operating Room (with Fluoroscopy )

LHSC: TAVI (Total 168, May 2015)

TransFemoral 92 – Core Valves (Medtronic)

TransApical 55 – Sapiens (Edwards),

Accurate TA valves (Symetis), Engagers

(Medtronic)

Direct Aortic 19 - Core Valves (Medtronic)

TransAxillary 2 – Core Valves (Medtronic)

Total mortality : 8.9%

LOS in Hospital 7.1± 6.2

47

TAVI vs SAVR

TAVI vs SAVR

Outcomes

TAVI vs MM

TAVI vs MM

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