Transcatheter Aortic Valve Implantation · TAVI/TAVR Disruptive Technology Team sport! CS/IC both scrub together Important team members: Two IC Two CS Imaging - X-ray, ECHO, CT OR

Transcatheter Aortic Valve Implantation:

Evolving to Mainstream Therapy?

William D. Anderson, MDDirector, Exempla Structural Heart Program

Thursday, January 31, 13

• None!

Disclosures


• Click to edit Master text styles





Structural Heart DiseaseDiversity of Therapeutic Targets

• Congenital Anomalies:– Atrial septum (ASD, PFO)– Ventricular Septum– Pulmonic Valve

• Acquired Heart Disease:– LAA (Watchman)– Mitral Valve (Mitraclip)– Aortic Valve (TAVI)– Others: paravalvular leaks,

ventricular support


Exempla TAVI Program



Larry



Larry Curly



Larry Curly Moe




Shemp!


ESJH: Hybrid OR


TAVI/TAVRDisruptive Technology

Team sport!CS/IC both scrub togetherImportant team members:

Two ICTwo CSImaging - X-ray, ECHO, CTOR support staffCath lab support staffPerfusion (wet pump)12-15 staff members in room


Calcific Aortic Stenosis• Mechanism of stenosis is similar to atherosclerosis1

– Mainly solid calcium deposits within the valve cusps – Similar risk factors to Coronary Artery Disease (CAD)– High coincidence of CAD and AS in same individual2

– 7th, 8th and 9th decades of life

1Otto CM, Lind BK, et al. Circulation 1994; 90: 844-53. 2Otto CM, Lind BK, et al. New Eng J Med 1999; 341: 142-147.


Aortic Stenosis

Indicator:! ! ! Mild! Moderate! Severe

Jet velocity (m/s)! ! <3.0! 3.0–4.0 ! >4.0Mean gradient (mmHg)* <25! 25–40! >40Valve area (cm2)! ! >1.5! 1.0–.5! <1.0Valve area index ! ! ! ! ! <0.6 (cm2/m2)! ! ! !

2008 Focused Update for the Management of Patients With Valvular Heart Disease: (J Am Coll Cardiol;52:e1–e142)


Aortic Valve ReplacementMarked Mortality Benefit

For patients with symptomatic, severe AS, SAVR offers striking mortality benefit1.

AVR should be withheld in such patients only when compelling contraindications exist.

1 C.M. Otto. Valve Disease: Timing of Aortic Valve Surgery. Heart 2000


ACC/AHA Guidelines

(J Am Coll Cardiol 2008;52:e1-e142)


ACC/AHA Guidelines



ACC/AHA Guidelines



ACC/AHA Guidelines



ACC/AHA Guidelines



Surgical AVR in Octogenarians:Mortality & Logistic Euroscore Risk Stratification (n=282)

Leontyev et al, Ann Thorac Surg 2009;78:1440-1445


Severe Symptomatic AS: Percent of patients treated

EUUS

Untreated

Surgery

Pellikka2Charlson1 Iung3 Bouma4

59%68%70%40%

41%32%30%60%

From David H Adams MD, “Current Standard of Care for Treating Severe Aortic Stenosis: Surgical Treatment”

1Charlson E, Legedza AT, Hamel MB. J Heart Valve Dis 2006;15: 312-3212Pellika PA, Sarano ME, et al. Circulation 2005; 111: 3290-953Iung B, Baron G, Butchart E, et al. Eur Heart J 2003; 24: 1231-12434Bouma BJ, van den Brink, et al. Heart 1999; 82: 143-48

Patients with Severe ASHow many receive therapy?


sAVR for patient with ASWhy is it underutilized?

•Those expecting to live for more than 5 years are likely to derive significant benefit from AVR

•For those who survive 6 months after their operation, life expectancy matches that of age-matched controls

Age

65

70

75

80

85

90

Life expectancy for US population (years)

Hornick et al. Clin Geriatr Med 2006; 22: 499-513.From David H Adams MD, “Current Standard of Care for Treating Severe Aortic Stenosis: Surgical Treatment”


Transcatheter Aortic Valve Implantation(TAVI)

• Alain Cribier - FIM implant in 2002

• Antegrade transseptal approach

• Cardiac standstill• 22-24F Delivery System• Bovine pericardial tissue• Sustained hemodynamic

improvement Edwards SAPIENTM THV

Cribier, Circulation 2002;106:3006


Edwards SAPIEN MDT CoreValve

BSC Lotus

Direct FlowJena Valve

Sorin PercevalATS/3F Enable

ATS/3F Entrata

AorTx PAVR

Heart LeafletABPS PercValve

Lutter Valve

Transcatheter Valves in Development

St Jude Portico


TMVR?

News Release

FOR IMMEDIATE RELEASE

Contact: Ronald Trahan, APR, Ronald Trahan Associates, Inc., +1 508-359-4005, x108

CardiAQ™ Valve Technologies reports cardiovascular medicine

miles tone: f irs t- in-human nonsurgical percutaneous

implantation of a bioprosthetic mitral heart valve

Nearly 50% of patients suffering from a diseased mitral heart valve with

severe, symptomatic regurgitation are denied open-heart surgery because

it is cons idered too risky; in the future, Transcatheter Mitral Valve

Implantation (TMVI) may offer new hope for these patients .

IRVINE, Calif., June 14, 2012—CardiAQ Valve Technologies (CardiAQ), which has developed the

world’s first self-conforming and self-anchoring technology for nonsurgical Transcatheter Mitral

Valve Implantation (TMVI), today announced that the Company has achieved a cardiovascular

medicine milestone: a bioprosthetic mitral heart valve was successfully implanted as a compassionate

treatment into an 86-year-old male suffering from severe mitral regurgitation (MR 4+). The

breakthrough TMVI procedure was performed on June 12, 2012, at The Heart Centre, Rigshospitalet

University Hospital, Copenhagen, Denmark, by interventional cardiologists Lars Søndergaard, M.D.,

and Olaf Franzen, M.D., cardiovascular surgeon Susanne Holme, M.D., anesthesiologist Peter Bo

Hansen, M.D., and echocardiographer Nikolaj Ihlemann, M.D.

“Our TMVI system is designed to make nonsurgical mitral heart valve replacement a future alternative

to open-heart surgical replacement and repair,” said Rob Michiels, CEO of CardiAQ Valve

Technologies. “CardiAQ is currently the only transcatheter-transvessel implantation approach to

treating MR. While several companies have been trying to perfect a percutaneous approach to repair

the mitral valve, we believe that such technologies will have a very difficult time demonstrating

sufficient efficacy in treating such a heterogeneous disease,” added Michiels. “CardiAQ’s nonsurgical

valve implantation approach is designed to become a disruptive technology with a much broader

application.”

“CardiAQ has focused on replacement or implantation—not repair—for three reasons: Replacement of

the diseased mitral valve offers (1) the best chance of eliminating regurgitation, (2) the widest

applicability across patient and disease variations, and (3) can be made into a simple, fast,

straightforward interventional—i.e., nonsurgical—procedure,” said Brent Ratz, co-founder and COO.

“As cardiac surgeons, we are taught that residual mitral regurgitation will only lead to more mitral

regurgitation and progressive symptoms. That is why we have focused our efforts on developing a

replacement technology with the potential to eliminate clinically significant MR, not just reduce it,”

said Arshad Quadri, M.D., chairman, founder/inventor and CMO of CardiAQ. “Moreover, many of

these inoperable patients suffer from functional MR, which is actually a result of ventricular dilatation.

CardiAQ’s chordal-sparing approach, combined with its unique anchoring system, provides what can

best be described as a ‘face-lift for the heart’ that may also help promote positive remodeling of the

ventricle.”


TMVR?

News Release

FOR IMMEDIATE RELEASE

Contact: Ronald Trahan, APR, Ronald Trahan Associates, Inc., +1 508-359-4005, x108

CardiAQ™ Valve Technologies reports cardiovascular medicine

miles tone: f irs t- in-human nonsurgical percutaneous

implantation of a bioprosthetic mitral heart valve

Nearly 50% of patients suffering from a diseased mitral heart valve with

severe, symptomatic regurgitation are denied open-heart surgery because

it is cons idered too risky; in the future, Transcatheter Mitral Valve

Implantation (TMVI) may offer new hope for these patients .

IRVINE, Calif., June 14, 2012—CardiAQ Valve Technologies (CardiAQ), which has developed the

world’s first self-conforming and self-anchoring technology for nonsurgical Transcatheter Mitral

Valve Implantation (TMVI), today announced that the Company has achieved a cardiovascular

medicine milestone: a bioprosthetic mitral heart valve was successfully implanted as a compassionate

treatment into an 86-year-old male suffering from severe mitral regurgitation (MR 4+). The

breakthrough TMVI procedure was performed on June 12, 2012, at The Heart Centre, Rigshospitalet

University Hospital, Copenhagen, Denmark, by interventional cardiologists Lars Søndergaard, M.D.,

and Olaf Franzen, M.D., cardiovascular surgeon Susanne Holme, M.D., anesthesiologist Peter Bo

Hansen, M.D., and echocardiographer Nikolaj Ihlemann, M.D.

“Our TMVI system is designed to make nonsurgical mitral heart valve replacement a future alternative

to open-heart surgical replacement and repair,” said Rob Michiels, CEO of CardiAQ Valve

Technologies. “CardiAQ is currently the only transcatheter-transvessel implantation approach to

treating MR. While several companies have been trying to perfect a percutaneous approach to repair

the mitral valve, we believe that such technologies will have a very difficult time demonstrating

sufficient efficacy in treating such a heterogeneous disease,” added Michiels. “CardiAQ’s nonsurgical

valve implantation approach is designed to become a disruptive technology with a much broader

application.”

“CardiAQ has focused on replacement or implantation—not repair—for three reasons: Replacement of

the diseased mitral valve offers (1) the best chance of eliminating regurgitation, (2) the widest

applicability across patient and disease variations, and (3) can be made into a simple, fast,

straightforward interventional—i.e., nonsurgical—procedure,” said Brent Ratz, co-founder and COO.

“As cardiac surgeons, we are taught that residual mitral regurgitation will only lead to more mitral

regurgitation and progressive symptoms. That is why we have focused our efforts on developing a

replacement technology with the potential to eliminate clinically significant MR, not just reduce it,”

said Arshad Quadri, M.D., chairman, founder/inventor and CMO of CardiAQ. “Moreover, many of

these inoperable patients suffer from functional MR, which is actually a result of ventricular dilatation.

CardiAQ’s chordal-sparing approach, combined with its unique anchoring system, provides what can

best be described as a ‘face-lift for the heart’ that may also help promote positive remodeling of the

ventricle.”


Valve Clinicpreoperative assessment



• weekly clinic and weekly conference



• weekly clinic and weekly conference• 1-2 IC, 1-2 CS, CRNP + clinic staff



• weekly clinic and weekly conference• 1-2 IC, 1-2 CS, CRNP + clinic staff• Clinical assessment

– STS score– non-STS risk





• TTE





• TTE• Cath (preferably RHC and LHC)





• TTE• Cath (preferably RHC and LHC)• CT

– gated cardiac for annular size– runoff for aorta and iliofemoral vessels


CT Imagingexpertise required!






Sheath Insertion


Initial BAV


Valve Advancement




ECHO AssessmentPost Deployment


ECHO AssessmentPost Deployment



0

13

25

38

50

Baseline 30 Day 1 Year 2 Year 3 Year0

0.5

1.0

1.5

2.044.2

10.2 10.9 10.6 10.60.64

1.55 1.61 1.581.68

Mea

n G

radi

ent (

mm

Hg)

EOAMean Gradient

N = 158

N = 162

N = 137

N = 143

N = 84

N = 89

N = 65

N = 65

N = 9

N = 9

AVA (cm²)

ECHO FindingsMean Gradients & Valve Area

Makkar, TCT 2011

PARTNER Cohort B


• Severe AS: Echo-derived AVA <0.8 cm2 (or AVA index <0.5 cm2/m2) and mean AVG >40 mm Hg or peak jet velocity >4.0 m/s

• Cardiac Symptoms: NYHA Functional Class ≥II• Cohort A - High surgical risk: Predicted operative risk ≥15%

(site surgeons x 2 and cardiologist); guideline = STS score ≥10

• Cohort B - Inoperable: risk of death or serious irreversible morbidity >50%

PARTNER Study DesignInclusion Criteria


Patient Characteristics - Inoperable

Characteristic TAVR (n = 179) Standard Rx (n = 179) p value

Age – yr 83.1 ± 8.6 83.2 ± 8.3 0.95

Male sex (%) 45.8 46.9 0.92

STS Score 11.2 ± 5.8 12.1 ± 6.1 0.14NYHA

I or II (%)

III or IV (%)

7.8

92.2

6.1

93.9

0.68

0.68CAD (%) 67.6 74.3 0.20

Prior MI (%) 18.6 26.4 0.10

Prior CABG (%) 37.4 45.6 0.17

Prior PCI (%) 30.5 24.8 0.31

Prior BAV (%) 16.2 24.4 0.09CVD (%) 27.4 27.5 1.00

Makkar, TCT 2011


12

Characteristic TAVR (n = 179) Standard Rx (n = 179)

n = 179

p value

PVD (%) 30.3 25.1 0.29

COPD

Any (%)

O2 dependent (%)

41.3

21.2

52.5

25.7

0.04

0.38Creatinine > 2 mg/dL (%) 5.6 9.6 0.23

Atrial fibrillation (%) 32.9 48.8 0.04

Perm. pacemaker (%) 22.9 19.5 0.49

Pulmonary HTN (%) 42.4 43.8 0.90

Frailty (%) 18.1 28.0 0.09

Porcelain aorta (%) 19.0 11.2 0.05

Chest wall radiation (%) 8.9 8.4 1.00

Chest wall deformity (%) 8.4 5.0 0.29

Liver disease (%) 3.4 3.4 1.00

Patient Characteristics - Inoperable

Makkar, TCT 2011


PARTNER Cohort BAll Cause Mortality

(Smith, TCT 2010)

Numbers at Risk Numbers at Risk TAVI 179 138 122 67 26 Standard Rx 179 121 83 41 12

HR [95% CI] =0.54 [0.38, 0.78]

P (log rank) < 0.0001

All-

caus

e m

orta

lity

(%)

Months

0

20

40

60

80

100

Absolute Risk Reduction 20%NNT = 5

50.7%

30.7%

Standard Rx

TAVI


J Am Coll Cardiol 2012;60:483-92

PARTNER 1B Trial Clinical Outcomes


PARTNER Study Design

Leon, TCT 2010Thursday, January 31, 13

Symptomatic Severe Aortic Stenosis

ASSESSMENT: High Risk AVR Candidate3105 Total Patients Screened






Total = 1058 patients2 Trials: Individually

PoweredHigh Riskn= 700 Inoperable n=358





High Risk TA

ASSESSMENT: Transfemoral Access

TAVITrans

femoralSurgical

AVR

High Risk TF

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

TAVITrans

femoralSurgical

AVR

1:1 Randomization1:1 Randomization

VS VS







High Risk TA


TAVITrans

femoralSurgical

AVR

High Risk TF

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

TAVITrans

femoralSurgical

AVR

1:1 Randomization1:1 Randomization

VS VSStandard Therapy

(usually BAV)


Not In Study

TAVITrans

femoral

Primary Endpoint: All Cause Mortality over length of trial (Superiority)

1:1 Randomization

VS




0

0.1

0.2

0.3

0.4

0.5

0 6 12 18 24

TAVRAVR

Months

348 298 260 147 67

351 252 236 139 65

No. at Risk

TAVR

AVR

Primary Endpoint:All-Cause Mortality at 1 Year


0

0.1

0.2

0.3

0.4

0.5

0 6 12 18 24

TAVRAVR

Months

348 298 260 147 67

351 252 236 139 65

No. at Risk

TAVR

AVR

26.8



0

0.1

0.2

0.3

0.4

0.5

0 6 12 18 24

TAVRAVR

Months

348 298 260 147 67

351 252 236 139 65

No. at Risk

TAVR

AVR

26.8

24.2


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

P (log rank) = 0.62


J Am Coll Cardiol 2012;60:483-92

PARTNER 1A Trial Clinical Outcomes


Cohen, AHA 2010

PARTNER Cohort B: TAVI vs Med Rx


Cost Effectiveness: TAVR vs ControlPARTNER Cohort B

Reynolds, ACC 2011

iCER: incremental cost-effectiveness ratio


TAVI ComplicationsSapien Valve (TF and TA)

Leon, TVT 2010



Leon, TVT 2010



Leon, TVT 2010



Leon, TVT 2010



Leon, TVT 2010


TAVI Complications


TAVI Complications


Figure 2. Survival Curves by Post-Procedural AR

Survival curves for post-procedural AR grade: 0 or 1 (group 1, blue), 2 (group 2, green), and 3 to 4 (group 3, red). Cumulative survival rates were calculated bythe Kaplan-Meier method and compared with the log-rank test. (A) Survival curves by post-procedural AR in the whole cohort. (B) Survival curves in the patientswho received the Edwards valve. (C) Survival curves in the patients who received the CoreValve. (D) Survival curves in the patients who had LVEF !40%. (E) Sur-vival curves in the patients who had LVEF !40%. AR " atrial regurgitation; LVEF " left ventricular ejection fraction.

J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S , V O L . 5 , N O . 1 2 , 2 0 1 2 Hayashida et al.D E C E M B E R 2 0 1 2 : 1 2 4 7 – 5 6 Post-Procedural AR and Mortality After TAVI

1253

Downloaded From: http://interventions.onlinejacc.org/ by William Anderson on 01/29/2013

Figure 2. Survival Curves by Post-Procedural AR

Survival curves for post-procedural AR grade: 0 or 1 (group 1, blue), 2 (group 2, green), and 3 to 4 (group 3, red). Cumulative survival rates were calculated bythe Kaplan-Meier method and compared with the log-rank test. (A) Survival curves by post-procedural AR in the whole cohort. (B) Survival curves in the patientswho received the Edwards valve. (C) Survival curves in the patients who received the CoreValve. (D) Survival curves in the patients who had LVEF !40%. (E) Sur-vival curves in the patients who had LVEF !40%. AR " atrial regurgitation; LVEF " left ventricular ejection fraction.

J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S , V O L . 5 , N O . 1 2 , 2 0 1 2 Hayashida et al.D E C E M B E R 2 0 1 2 : 1 2 4 7 – 5 6 Post-Procedural AR and Mortality After TAVI

1253

Downloaded From: http://interventions.onlinejacc.org/ by William Anderson on 01/29/2013

J Am Coll Cardio Intv 2012;5:1247-‐1256

Aortic RegurgitationImpact on Survival post TAVI


All Cerebrovascular Events (%)Makkar, TCT 2011

≤ 30 Days 31 Days – 1 Year 1 Year – 2 Years

All CVA p = 0.010 p = 0.387 p = 0.028

Ischemic Stroke p = 0.017 p = 0.155 p = 0.083

Hemorrhagic Stroke p = 0.316 p = 0.121 p = 0.415

Eve

nts

Note: Percents are of patients in the trial (n/179).


Sapien Valve Thrombosis

80 yo F s/p Sapien #23mm

- MPG 10mmHg- DAPT started

DOE 10 mos laterTTE: thrombus

- MPG 54mmHgCoumadin x 3 mosSx and thrombus resolved

- MPG 13mmHg

Cota et al, Article in Press, Jan 2013


Severe AS?

• LV dysfunction / low gradients / small AVA– DSE (or cath with Dobutamine)

• Paradoxical Low Flow / Low Gradient– Normal LV systolic fxn, small AVA

• Max symptoms but only moderate AS (AVA 1.0-‐1.2cm2)

• Severe AS and severe MR• Prosthetic valve dysfunction


Conclusions


Conclusions• Catheter-based and ‘minimal access’ therapies will

increasingly be employed in the treatment of structural heart disease.




• TAVI is currently receiving an enthusiastic response, but durability will largely determine the extent of adoption.





• Patient selection will continue to be a challenge: patient preferences are outpacing our data sets!






• Questions: – Who is too sick for TAVI?– What to do with patient profiles excluded from

PARTNER/CoreValve Trials?







PARTNER/CoreValve Trials?• Nature will fight back! Iterative changes in

technology will reduce procedural complications.







PARTNER/CoreValve Trials?• Nature will fight back! Iterative changes in

technology will reduce procedural complications.

Patient selection is KEY!



Severe Aortic Stenosis(n=622)

Pellikka et al, Circulation 2005;111:3290-3295

% ofPatients

Years of Follow-up

1 year: 82%2 years: 67%5 years: 33%

Survival Free of Symptoms

100

80

40

20

0

60

0 1 2 3 4 5 6 7 8 9 10


Severe Aortic Stenosis(n=622)

Pellikka et al, Circulation 2005;111:3290-3295

% ofPatients

Years of Follow-up

1 year: 82%2 years: 67%5 years: 33%

Survival Free of Symptoms

100

80

40

20

0

60

0 1 2 3 4 5 6 7 8 9 10

Markers of poor outcome:1.Advanced age2.Heavy Ca++

3.Velocities >4m/sec


Paravalvular Aortic RegurgitationPARTNER Cohort A

0

20.0000

40.0000

60.0000

80.0000

100.0000

TAVR AVR TAVR AVR TAVR AVR

P < 0.001 P < 0.001 P < 0.001

1 Year6 Months30 Days

% P

atie

nts

None Trace Mild Moderate Severe


Echo FindingsParavalvular Regurgitation

30 Days30 Days30 Days 1 Year1 Year1 Year

Finding – no. (%) TAVR AVR TAVR AVR

None 65 (22.6) 168 (73.7) <.0001 73 (32.9) 123 (77.8) <.0001

Trace/Mild 187 (65.2) 58 (25.4) <.0001 134 (60.4) 32 (20.3) <.0001

Mod/Severe 35 (12.2) 2 (0.9) <.0001 15 (6.8) 3 (1.9) <.0001

p-value p-value

Smith, ACC 2011


Alternatives to sAVRBAV Registry (n=674)

BAV:High recurrence rate: 50% in six months1,2

Absence of mortality benefit1,2

Inability to substantially alter leaflet morphology1Otto CM, Mickel MC, et al. Circulation 1994; 89: 642-502Rahmitoola SH. J Am Coll Cardiol 1994; 23: 1076-78.


Has BAV Improved?PARTNER Cohort B

Standard Rx

All-

caus

e m

orta

lity

(%)

Months

0

20

40

60

80

100

50.7%!

Smith, TCT 2010


Documents

Transcatheter Aortic Valve Implantation · TAVI/TAVR Disruptive Technology Team sport! CS/IC both scrub together Important team members: Two IC Two CS Imaging - X-ray, ECHO, CT OR