Update on Transcatheter Aortic Valve Replacement Jonathan J. - - PDF document

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Update on Transcatheter Aortic Valve Replacement

Jonathan J. Passeri, M.D.

Assistant Professor of Medicine, Harvard Medical School Co-Director, Heart Valve Program and Director of Interventional Echocardiography, Massachusetts General Hospital December 2, 2017

Disclosures

• None

Alexander Fleming (1881-1955) The Changing Face of Valve Disease

• Shift from rheumatic to “degenerative” etiologies
• Moderate to severe valve disease occurs in*:

§ 1.9% people 55 to 64 years-old § 8.5% people 65 to 74 years-old § 13.2% people 75 years and older

• Prevalence of valve disease increase as the elderly

population continues to grow

• Elderly have an inherent increase in risks associated with

surgery and complexity of medical management

*Nkomo et al. Lancet. 2006; 368: 1005-11.

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Prevalence of Valve Disease by Age

Nkomo et al. Lancet. 2006; 368: 1005-11.

Distribution of Native Heart Valve Disease

Iung et al. Nat. Rev. Cardiol. 2011;8: 162-172

Calcific Aortic Stenosis: Mechanisms

• Calcific aortic stenosis is a biologically

active process

• Lipid accumulation

– LDL accumulation and oxidation

• Inflammation

– T-cells, monocytes, inflammatory

mediators, cytokines

• Calcification

– Osteoblast expression, bone formation

Calcific Aortic Stenosis: Mechanisms

Rajamannan et al. Nature Clinic Prac CV Med 2007;5:254

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Pathophysiology Aortic Stenosis

Aortic Stenosis LV outflow obstruction LVSP LVET LVDP Aortic Pressure LV Mass LV dysfunction Myocardial O2 consumption Diastolic time Myocardial O2 supply Myocardial ischemia LV failure

Natural History of Aortic Stenosis

Ross J Jr, Braunwald E. Circulation 1968; 38: 61–67

Aortic Valve Replacement Surgery Surgery in Elderly Patients with Severe AS

Iung et al. Eur Heart J. 2005; 26: 2714 Aortic Stenosis >75 years N=408 No severe AS N=124 Severe AS N=284 No symptoms N=68 Severe symptoms N=216 No intervention N=72 (33%) Intervention N=144 (67%)

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Transcatheter Aortic Valve Replacement Henning Rud Andersen

Antegrade Transcatheter Aortic Valve Replacement: First Human Case Reported

Cribier A, et al. Circulation 2002;106:3006-8

N = 179

N = 358 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

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 High Risk

ASSESSMENT: Transfemoral Access Transapical (TA) Transfemoral (TF) 1:1 Randomization 1:1 Randomization Yes No

PARTNER: Placement of AoRTic TraNscathetER Valves Trial

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All Cause Mortality (ITT)

Torsten P. Vahl et al. JACC 2016;67:1472-1487

PARTNER Trial (1A): 5-Year Outcomes

Mack et al. Lancet 2015; 385:2477-2484

CoreValve US Pivotal Trials CoreValve Pivotal Trial: Extreme Risk

All Cause Mortality

Cumulative Event Curve for All-Cause Mortality or Major Stroke Event rates were calculated with Kaplan-Meier methods. Brackets indicate 95% confidence interval.

Figure Legend:

J Am Coll Cardiol. 2014;63(19):1972-1981.

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CoreValve Pivotal Trial: High-Risk

Two-year outcomes

Reardon et al. J Am Coll Cardiol. 2015;66(2):113-121.

Primary Endpoint: All-Cause Mortality or Disabling Stroke at Two Years

Randomized Patients n = 2032 Symptomatic Severe Aortic Stenosis ASSESSMENT by Heart Valve Team Operable (STS ≥ 4%)

The PARTNER 2A Trial Study Design

TF TAVR (n = 775) Surgical AVR (n = 775) VS. VS.

ASSESSMENT: Transfemoral Access Transapical (TA) / TransAortic (TAo) Transfemoral (TF) 1:1 Randomization (n = 482) 1:1 Randomization (n = 1550)

TA/TAo TAVR (n = 236) Surgical AVR (n = 246)

Yes No

PARTNER 2: Time-to-event curves

Leon et al. NEJM. 2016;374(17):1609-1620.

PARTNER 2: Time-to-event curves

Leon et al. NEJM. 2016;374(17):1609-1620.

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Events (%) 30 Days 2 Years

TAVR (n = 1011) Surgery (n = 1021) p-value* TAVR (n = 1011) Surgery (n = 1021) p-value* Death (all-cause) and Stroke (disabling) 6.1 8.0 0.11 19.3 21.1 0.33

Death

All-cause 3.9 4.1 0.78 16.7 18.0 0.45 Cardiovascular 3.3 3.2 0.92 10.1 11.3 0.38

Neurological Events

All Stroke 5.5 6.1 0.57 9.5 8.9 0.67 Disabling Stroke 3.2 4.3 0.20 6.2 6.4 0.83 TIA 0.9 0.4 0.17 3.7 2.3 0.09

Primary Endpoint Events (ITT) At 30 Days and 2 Years

Leon et al. NEJM. 2016;374(17):1609-1620.

Events (%) 30 Days 2 Years

TAVR (n = 1011) Surgery (n = 1021) p-value* TAVR (n = 1011) Surgery (n = 1021) p-value* Rehospitalization 6.5 6.5 0.99 19.6 17.3 0.22 MI 1.2 1.9 0.22 3.6 4.1 0.56 Major Vascular Complications 7.9 5.0 0.008 8.6 5.5 0.006 Life-Threatening / Disabling Bleeding 10.4 43.4 <0.001 17.3 47.0 <0.001 AKI (Stage III) 1.3 3.1 0.006 3.8 6.2 0.02 New Atrial Fibrillation 9.1 26.4 <0.001 11.3 27.3 <0.001 New Permanent Pacemaker 8.5 6.9 0.17 11.8 10.3 0.29 Re-intervention 0.4 0.0 0.05 1.4 0.6 0.09 Endocarditis 0.0 0.0 NA 1.2 0.7 0.22

Other Clinical Endpoints (ITT) At 30 Days and 2 Years

Leon et al. NEJM. 2016;374(17):1609-1620.

Sapien 3 THV: Intermediate Risk Registry

Unadjusted Time-to-Event Analysis All-Cause Mortality and All Stroke (AT)

1077 1012 987 962 930 944 805 786 757 743 10 20 30 40 3 6 9 12 3.7% 9.7% 10.8% 18.8%

All-Cause Mortality / Stroke Rate (%)

SAPIEN 3 TAVR P2A Surgery

Months from Procedure

Number at risk: S3 TAVR P2A Surgery

Thourani et al. 2016 ACC

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Unadjusted Time-to-Event Analysis All Stroke (AT)

All Stroke (%)

1077 1012 987 962 930 944 805 786 757 743 4.6% 8.2% 2.7% 6.1% 10 20 30 40 3 6 9 12 Number at risk: S3 TAVR P2A Surgery

Months from Procedure

SAPIEN 3 TAVR P2A Surgery

Thourani et al. 2016 ACC

• 10
• 8
• 6
• 4
• 2

2 4 6 8 10

Favors TAVR Favors Surgery

Superiority Analysis Components of Primary Endpoint (VI)

• 10
• 8
• 6
• 4
• 2

2 4 6 8 10

• 10
• 8
• 6
• 4
• 2

2 4 6 8 10

Stroke Mortality AR > Moderate

Weighted Difference -5.2% Upper 2-sided 95% CI -2.4% Superiority Testing p-value < 0.001 Weighted Difference +1.2% Lower 2-sided 95% CI +0.2% Superiority Testing p-value = 0.0149 Weighted Difference -3.5% Upper 2-sided 95% CI -1.1% Superiority Testing p-value = 0.004

CoreValve Evolution

CoreValve 2014 Evolut-R 2015 Evolut-Pro 2017

Reardon MJ et al. N Engl J Med 2017;376:1321-1331.

SURTAVI: Noninferiority Analysis and Time-to-Event Curves for the Primary End Point.

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Torsten P. Vahl et al. JACC 2016;67:1472-1487

Improving outcomes with TAVR TAVR within Failed Bioprosthesis Self-expanding TAVR within Failed Surgical Bioprosthesis

Deeb et al. JACC Cardiovasc Interv 2017;10(10):1034-1044

Balloon-expandable TAVR within Failed Surgical Bioprosthesis

Webb et al. JACC 2017;69(18):2253-2262

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What’s next?

• Low surgical risk
• Bicuspid aortic valve
• Asymptomatic severe aortic stenosis
• Moderate aortic stenosis with low ejection fraction
• New transcatheter heart valves

So where are we at now? SAVR versus TAVR

• Estimated surgical risk

– STS risk scores – Frailty – Other risk factors

• Concomitant cardiac pathology
• Anatomic and technical considerations
• Other factors

Multidisciplinary Heart Valve Team

Appropriate Use Criteria

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Looking ahead What’s going to happen to centers?

• Expansion of “TAVR centers”
• Impact on cardiac surgical programs
• Centers of excellence

TAVR Centers in United States

John D. Carroll et al. JACC 2017;70:29-41

2017 American College of Cardiology Foundation

TAVR Experience and Outcomes

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Torsten P. Vahl et al. JACC 2016;67:1472-1487

Proliferation of transcatheter heart valves Conclusion

• TAVR has become an established therapy for aortic

stenosis

• TAVR is no longer excluded to “high surgical risk” patients
• Choosing TAVR or SAVR is complex decision that

requires the integration of multiple factors

• Multidisciplinary Heart Team concept is becoming

increasingly important

• We are likely to see significant shifts on how centers and

programs function in the era of TAVR

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THANK YOU!