transcatheter aortic valve replacement(tavr) reeves...dyspnea or decreased exercise tolerance, heart...

Transcatheter Aortic Valve Replacement(TAVR)

NCVH - 2016 Update

Rodney Reeves, MD

• Disclosures: none

3

Current State of TAVR - 2016

» ~350 US Centers performing TAVR » WKHS currently only local institution

performing TAVR(2 ICs, 2 cardiac surgeons) » 2 valve options are currently FDA

approved(Edwards, Medtronic) » Numerous other valves in pipeline/

approval process

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Current FDA Approved Valves

» Edwards Sapien 3 - balloon expandable » Medtronic Corevalve Evolut R- self-

expanding » Both are excellent valves!!! Both are

reasonable options for the majority of patients.

» Advantages and disadvantages to each….we are still learning best way to individualize choice for each patient

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» Meet the patient and family(discuss goals/expectations)

» CT » RHC/LHC » Assess risk(PFTs, frailty index,

comorbidities, STS score, etc.) » Surgical Consultation

Pre TAVR workup

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Day of TAVR

» Team Approach - heart surgeon and interventional cardiologist work together on procedure, both scrubbed

» Lots of help and support!!!(cath lab RNs, rad techs, OR staff, perfusionist on standby, etc.)

» Typically ~ 1 hr, most still general anesthesia, extubate in OR

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Post-op till Discharge

» Early ambulation » Lines out quickly » Avoidance of sedatives/narcotics » Aspirin/Plavix

Cohesive, Multi-disciplinary Approach Embodies ▪ Optimal patient centric care ▪ Dedication across medical specialties ▪ Collaborative treatment decision

TAVR Heart Team Concept

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InterventionalCardiologist

CardiologistSurgeon

Valve Clinic Coordinator

CardiacCATH Lab

and O.R. Staff

Anesthe-siologist

ReferringCardiologist

Imaging Specialists TAVR

Heart Team

National Coverage Determination18

The patient (preoperatively and postoperatively) is under

the care of a heart team

2014 Valvular Disease

Guidelines

AHA / ACC

18. National Coverage Determination (NCD) for Transcatheter Aortic Valve Replacement (TAVR). 2012.

Pre-screening Review of Records

Clinical Evaluation

Gated CTA (Chest / Abdomen / Pelvis)

RHC / LHC Coronary Angiography

Functional Status Assessment (Cognitive Function, Frailty, etc.)

STS Score Calculation

Treatment Plan

TAVR Evaluation Pathway

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Note: The above is a suggested flow for the patient screening process, however, the order in which screening tests are conducted varies depending on the patient’s profile and should be at the discretion of the Heart Team.

TAVR Patients May Present with Some of the Following

Characteristics of a TAVR Patient19

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Old age

Reduced EF

Prior CABG

History of stroke/CVA

History of AFib

Prior chest radiation

Prior open chest surgery

Heavily calcified aorta

History of CAD

History of COPD

History of renal insufficiency

Frailty

History of syncope

Fatigue, slow gait

Peripheral vascular disease Diabetes and hypertension

Severe, Symptomatic Native Aortic Valve Stenosis

19. Leon M et al. New England Journal of Medicine 2010 October 21;363(17):1597-1607.

11

Alain Cribier: First Human TranscatheterValve Replacement (2002)

What Causes Aortic Stenosis in Adults?

More CommonLess Common

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Images courtesy of John Webb, MD at St. Paul’s Hospital and Renu Virmani, MD at the CVPath Institute

Age-Related Calcific Aortic

StenosisCongenital

AbnormalityRheumatic

Fever

Population at Risk for Aortic Stenosis is Increasing

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▪ Aortic Stenosis is estimated to be prevalent with 12.4% of the population over the age of 75.2

▪ The elderly population will more than double between now and the year 2050, to 80 million.3

▪ 80% of adults with symptomatic aortic stenosis are male4

Approx. 2.5 Million People in the U.S. Over the Age of 75 suffer from this

disease.1

ELDERLY AVERAGE ANNUAL GROWTH RATE: 1910 to 2030

0.0%

4.0%

1910-1930 1950-1970 1990-2010

2.8%

1.3%

2.2%2.4%

3.1%

2.6%

1. U.S. Census Bureau, Population Division. June 2015; 2. Ruben L.J.et al. Heart. 2000;84:211-21; 3. U.S. Census Bureau Statistical Brief. May 1995; 4. Ramaraj R, Sorrell VL. Br Med J 2008;336: 550–5.

▪ Shortness of breath ▪ Angina ▪ Fatigue ▪ Syncope or Presyncope ▪ Other ▪ Rapid or irregular heartbeat ▪ Palpitations

Symptoms of Aortic Stenosis

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The symptoms of aortic disease are commonly misunderstood by patients as ‘normal’ signs of aging.5 Many patients initially appear asymptomatic, but on closer examination up to37% exhibit symptoms.6

Sandy Severe Aortic Stenosis

(Actual Patient)

5. Das P. European Heart Journal. 2005;26:1309-1313; 6 . Lester SJ et al. CHEST 1998;113(4):1109-1114.

After the onset of symptoms, patients with severe aortic stenosis have a survival rate as low as 50% at2 years and 20%at 5 years without aortic valve replacement7

Severe Aortic Stenosis is Life Threateningand Treatment is Critical6

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50% of patients died within 1 year without valve replacementPer the Inoperable Cohort of the PARTNER Trial

100%

80%

60%

40%

20%

00 40 50 60 70

Age, Years

Sur

viva

l, %

Onset Severe Symptoms

Average Survival, y

Angina

Syncope

Failure

0 2 4 6

Latent Period(Increasing Obstruction, Myocardial Overload)

ADULTS AVERAGE COURSE WITH VALVULAR AORTIC STENOSIS

6. Lester SJ et al. CHEST 1998;113(4):1109-1114; 7. Otto CM. Heart. 2000:84:211-218.

5-YEAR SURVIVAL(Distant Metastasis)8

Sur

viva

l, %

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Worse Prognosis than Many Metastatic Cancers

5 year survival of breast cancer, lung cancer, prostate cancer, ovarian cancer and severe inoperable aortic stenosis

0

5

10

15

20

25

30

35

Breast Cancer Lung Cancer Colorectal Cancer Prostate Cancer Ovarian Cancer Severe Inoperable AS*

3

2830

12

4

23

*Using constant hazard ratio. Data on file, Edwards Lifesciences LLC. Analysis courtesy of Murat Tuczu, MD, Cleveland Clinic

8. National Institutes of Health. http://seer.cancer.gov/statfacts/. Accessed Nov. 2010.

▪ In the absence of serious comorbid conditions, aortic valve replacement (AVR) is indicated in the majority of symptomatic patients with severe aortic stenosis

▪ Consultation with or referral to a Heart Valve Center of Excellence is reasonable when discussing treatment options for: ▪ Asymptomatic patients with severe valvular heart disease ▪ Patients with multiple comorbidities for whom valve intervention

is considered ▪ Because of the risk of sudden death, replacing the aortic

valve should be performed promptly after the onset of symptoms

▪ Age is not a contraindication to surgery

Timely Intervention is Critical for Patients with Symptoms9

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Guidelines

AHA / ACC

9. Nishimura RA et al. JACC. 2014. doi: 10.1016/j.jacc.2014.02.537.

Definition Valve Hemodynamics

High-gradient severe aortic stenosis

▪ Aortic jet velocity ≥ 4 m/s or mean gradient ≥ 40 mmHg ▪ Or aortic valve area index ≤ 0.6 cm2/m2

Low-flow/low-gradient with reduced left ventricular ejection fraction

▪ Resting aortic jet velocity < 4m/s or mean gradient < 40 mmHg ▪ Dobutamine stress echocardiography shows aortic valve area ≤ 1.0

cm2 with aortic jet velocity ≥ 4m/s at any flow rate ▪ Left ventricular ejection fraction < 50%

Low-gradient with normal left ventricular ejection fraction or paradoxical low-flow

▪ Aortic jet velocity < 4m/s or mean gradient < 40 mmHg ▪ Indexed aortic valve area ≤ 0.6 cm2/m2

▪ Stroke volume index < 35 mL/m2 measured when patient is normotensive (systolic blood pressure < 140 mmHg)

▪ Left ventricular ejection fraction ≥ 50%

Patients with severe aortic stenosis typicallyhave an aortic valve area ≤ 1.0 cm2

Symptoms: Dyspnea or decreased exercise tolerance, heart failure, angina, syncope and presyncope

Definition of Severe Aortic Stenosis9

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Guidelines

AHA / ACC


▪ Dobutamine stress echocardiography canbe used to differentiate between true and pseudo severe aortic stenosis ▪ Better define the severity of the aortic stenosis ▪ Accurately assess contractile / pump reserve

▪ Some patients with severe aortic stenosis based on valve area have a lower than expected gradient (e.g. mean gradient < 30 mmHg) despite preserved LV ejection fraction (e.g. EF > 50%) ▪ Up to 35% of patients with severe aortic

stenosis present with low flow, low gradient ▪ These low gradients often lead to an under

estimation of the severity of the disease,so many of these patients do not undergo surgical aortic valve replacement

Paradoxical Low Flow and/or Low GradientSevere Aortic Stenosis10

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Dobutamine stress in low gradient, low ejection fractionAS Chambers, Heart. 2006 April; 92(4): 554–558

10. Dumesnil et al. European Heart Journal 2010; 31, 281-289.

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UNDERTREATEMENT OF AORTIC STENOSIS

Pat

ient

s, %

Studies show that patients with severe aortic stenosis are under-diagnosed and under-treated

0%

20%

40%

60%

80%

100%

Bouma 1999 Pellikka 2005 Charison 2006 Varadarajan 2006 January 2009 Bach 2009 Freed 2010

69%52%

74%61%60%43%54%

31%48%

26%39%40%57%46%

Aortic Valve Replacement (AVR) No AVR

At Least 40% of Patients Who Need Valve Replacement Do Not Get Treatment11-17

11. Bouma BJ et al. Heart. 1999;82:143-148; 12. Pellikka PA et al. Circulation. 2005;111:3290-3295; 13. Charlson E et al. J Heart Valve Dis. 2006;15:312-321; 14. Varadarajan P et al. Ann Thorac Surg. 2006;82:2111-2115; 15. Jan F et al. Circulation. 2009;120;S753; 16. Bach DS et al. Circ Cardiovasc Qual Outcomes. 2009;2:533-539; 17. Freed BH et al. Am J Cardiol. 2010;105:1339-1342.

▪ Despite frequent BAV, standard therapy did not alter the dismal course of disease for inoperable patients in the PARTNER Trial ▪ 51% died within 1 year ▪ 94% died within 5 years

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T H E P A R T N E R T R I A L

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

All-

Cau

se M

orta

lity

(%)

Months

HR [95% CI] = 0.50 [0.39, 0.65] p (log rank) < 0.0001

Control Group (Med Rx and BAV) (n = 179)

50.7%

68.0%

87.5%80.9%

93.6%

Medical Management and BAV are Inadequate Therapies for Inoperable Patients

Therapy

Low- to Moderate-Risk

High Risk

Greater Risk

Transcatheter Aortic Valve Replacement

(TAVR)

Open-Heart Surgery (AVR)

Options for Aortic Valve Replacement per Guidelines9

Transcatheter Heart Valve

Surgical Heart Valve

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Severe Aortic Stenosis is Defined as: Valve Area < 1.0 cm2

Mean Gradient > 40 mmHg OR Jet Velocity > 4.0 m/s

High Risk Patients Defined by STS Risk

Score > 8%


Society of Thoracic Surgeons operative risk score≥ 8% OR at a ≥ 15% risk of mortality (at 30 days)

For relief of aortic stenosis in patients with ▪ Symptomatic heart disease due to severe native calcific aortic stenosis ▪ Have native anatomy appropriate for the valve delivery system ▪ Evaluated by a Heart Team, including a cardiac surgeon, to be at high or

greater risk for open surgical therapy

Edwards SAPIEN 3 Transcatheter Heart Valve

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TAVR is Better than Medical Managementfor Inoperable Patients

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Edwards SAPIEN Valves

Significantly Improve Survival

Edwards SAPIEN is superior to medical management in inoperable patients


27

TAVR with Edwards SAPIEN valves is a reasonable alternative to surgery

Edwards SAPIEN 3 valve: Transformational design



Edwards SAPIEN is superior to medical management in inoperable patients


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TAVR is superior to medical management for Inoperable Patients



Without treatment 94% of patients in the standard therapy groupdied within

5 years

21.8% absolute reduction in mortality at

5 years

Standard Therapy is an Ineffective Treatmentfor Severe Aortic Stenosis Patients

71.8%

Months

HR [95% CI] = 0.50 [0.39, 0.65] p (log rank) < 0.0001

93.6%

Standard therapy includes medical management and BAV

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All-

Cau

se M

orta

lity

(%)

0 12 24 36 48 60

100%

80%

60%

40%

20%

0%

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

50.7%

30.7%

A L L - C A U S E M O R T A L I T Y I n o p e r a b l e C o h o r t

87.3% of patients

with standard therapy were rehospitalized

for cardiac issues

39.7% absolute reduction of

rehospitilizationat 5 years

Standard Therapy Patients Were RehospitalizedTwice as Often as TAVR Patients

Standard therapy includes medical management and BAV

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Months

100%

80%

60%

40%

20%

0%

87.3%

47.6%

Standard Rx (n = 179)

HR [95% CI] = 0.40 [0.29, 0.55] p (log rank) < 0.0001

0 12 24 36 48 60

TAVR (n = 179)

Hos

pita

lity

(%)

R E H O S P I T A L I Z A T I O N I n o p e r a b l e C o h o r t

TAVR with Edwards SAPIEN Valvesis Equivalent to Surgery

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With the Benefits of a Less Invasive

Procedure



30

Edwards SAPIEN valve is a reasonable alternative to surgery in high-risk patients



Procedure



30

Edwards SAPIEN valve is a reasonable alternative to surgery in high-risk patients




Procedure

At 5 Years

Patients that had TAVR with the Edwards SAPIEN

valve showed survival

equivalent to SAVR

TAVR is Equivalent to Surgery in High-Risk Patients

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Per ACC / AHA Guidelines, TAVR is a reasonable alternative to surgery in patientswho meet an indication for AVR and who have high surgical risk for surgical AVR9

Error Bars Represent95% Confidence Limits

All-

Cau

se M

orta

lity

(%)

Months Post Randomization0 12 24 36 48 60

100%

80%

60%

40%

20%

0%

SAVRTAVR

HR [95% CI] = 1.04 [0.86, 1.24] p (log rank) = 0.76

67.8%

62.4%

No. at Risk

TAVR 348 262 228 191 154 61SAVR 351 236 210 174 131 64

A L L C A U S E M O R T A L I T Y A t 5 Y e a r s


At both 1 year and 5 year follow up, 85% of Patients treated with the Edwards SAPIEN valve were in NYHA Class I or II compared to only 6% at baseline.

TAVR SAVR TAVR SAVR TAVR SAVR TAVR SAVR348 349 250 226 165 145 100 97

Baseline 1 Year 3 Years 5 Years

p = 0.64 p = 0.91 p = 0.35 p = 0.9313%15% 14%100%

80%

60%

40%

20%

0%

19%15%

94%94%

20%P

erce

nt o

f Eva

luab

le E

choe

s

I II III IV

Patients Continued to Show Improved Symptom Relief 5 Years After TAVR

32

NYHA CLASS OVER T IME

Longest Follow-Up in Any TAVR Randomized Study

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5 YEARS of PROVEN VALVE DURABILITY ▪ Sustained hemodynamic performance ▪ No incidence of structural valve deterioration requiring surgical valve

replacement20 ▪ Significant and sustained improvement in functional heart class

The PARTNER Trial 5-Year Results

TAVR vs. Standard Therapy in Inoperable Patients

▪ Significant mortality benefit ▪ Statistically significant reduction in

hospitalization ▪ NNT is 5 patients to save a life

TAVR vs. Surgical AVR in High-Risk Patients

▪ Equivalent mortality benefit ▪ Persistent symptom relief

20. Lancet. 2015 Jun 20;385(9986):2477-84. doi: 10.1016/S0140-6736(15)60308-7. Epub 2015 Mar 15.

Now Approved: The Edwards SAPIEN 3 Valve

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TAVR is superior to medical management for inoperable patients

TAVR is a reasonable alternative to surgery for high-risk patients

Transformational advance in valve design: Edwards SAPIEN 3 Valve


34

TAVR is superior to medical management for inoperable patients

TAVR is a reasonable alternative to surgery for high-risk patients

Transformational advance in valve design: Edwards SAPIEN 3 Valve



34

Unprecedented Clinical

Outcomes

All-Cause Mortality of the 491 patients in the PARTNER II Trial was 1.6% at 30 days

Cardiovascular Mortality was 1.0%

Low Mortality at 30 DaysThe PARTNER II Trial: SAPIEN 3 Valve High-Risk

1%

26%

50%

75%

100%

High-Risk (TF)

1%1.60%

All-Cause Cardiovascular

35

MORTALITY (As Treated Patients)

0%

20%

PARTNER I B (TF) PARTNER I A (All) PARTNER I A (TF) PARTNER II B (TF) PARTNER II B (TF) PARTNER II HR (TF)

2%

4%5%

4%5%

6%

ALL-CAUSE MORTALITY a t 30 DAYS PARTNER I Trial and PARTNER II Trial

All-Cause Mortality Has Decreased Overall

175 344 240 271 282 491

SAPIEN Valve SAPIEN XT Valve SAPIEN 3 Valve

36

Low Stroke at 30 DaysThe PARTNER II Trial: SAPIEN 3 Valve HR

0%

25%

50%

75%

100%

High-Risk (TF)

0.8%

Disabling

37

DISABLING STROKE (As Trea ted Pa t ien ts )

Of the 491 Patients in the PARTNER II Trial: Disabling Stroke was 0.8% at 30 days

Other Clinical Events at 30 Days (as Treated Patients)*

SAPIEN 3 Valve HR TF

Events (%) (n = 491)Major Vascular Comps. 5.3Bleeding – Life Threatening 5.5

*PARTNER II Trial high-risk TF SAPIEN 3 valve cohort 30-day results.

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Femoral Case Example

43

Transapical Case Example

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Where is all this going?

» Number and indication for procedure is growing

» Moving towards a “minimalist” approach » Eventually, the great, great majority of

these Aortic Stenosis cases will be done via TAVR(as opposed to traditional surgery)

» Therapies for Mitral and Tricuspid Valves is evolving quickly

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Case Examples:

49

Valve in Valve with Corevalve Evolut R

» 86 yo male » History of 23mm Medtronic Mosaic Valve ~

15 years ago » Now with bioprosthetic valve stenosis » 3 recent CHF admits » Mean gradient ~35, EF 15%

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Edwards Sapien 3

» 88 yo WM » NYHA Class III » Good functional capacity

transcatheter aortic valve replacement(tavr) reeves...dyspnea or decreased exercise tolerance, heart...

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