Severe Aortic Stenosis and TAVR. Disclosures I will not discuss off label use or investigational use in my presentation. I have no financial relationships

Severe Aortic Stenosis and TAVR

Disclosures

•I will not discuss off label use or investigational use in my presentation.

•I have no financial relationships to disclose.

•Employee of MaineHealth Cardiology

3

Prevalence of Aortic Stenosis16.5 Million People in

USOver the Age of 652

Percentage Diagnosed with Aortic Stenosis

Aortic stenosis is estimated to be prevalent in up to 7% of the population over the age of 651

It is more likely to affect men than women; 80% of adults with symptomatic aortic stenosis are male3

Aortic Stenosis Demographics

Aortic stenosis 2% US population >65yrs old

Aortic sclerosis 29% US population> 65 yrs old

Aortic sclerosis 50% greater risk of mortality and myocardial infarction.

Aortic sclerosis progresses to aortic stenosis in 9% over 5 years

What Causes Aortic Stenosis in Adults?

Aortic stenosis in patients over the age of 65 is usually caused by calcific (calcium) deposits associated with aging

Age-Related Calcific Aortic

Stenosis

Age-Related Calcific Aortic

Stenosis

Congenital AbnormalityCongenital

AbnormalityIn some cases adults may develop aortic stenosis resulting from a congenital abnormality

More Common

Less Common

Rheumatic FeverRheumatic Fever Adults who have had rheumatic fever may also be at risk for aortic stenosis

5

3 Major Etiologies for aortic stenosis

Independent clinical factors

associated with degenerative

aortic valve disease include the

following:4

Increasing age

• Male gender

• Hypertension

• Smoking

Elevated lipoprotein A

Elevated LDL cholesterol

9

Major Risk Factors

Signs and Symptoms

• Heart Failure

• Angina

• Syncope

• Carotid Parvus et Tardus

• Laterally displaced PMI

• Soft A2

• Crescendo-Decrescendo

systolic murmur

• Timing of peak murmur

and NOT intensity

predicts severity

Survival after onset of symptoms is 50% at 2 years and 20% at 5 years1

Surgical intervention for severe aortic stenosis should be performed promptly once even minor

symptoms occur1

Aortic Stenosis Is Life Threatening and Progresses Rapidly

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

inoperable aortic stenosis

12

Sobering Perspective5-Year Survival

8

Surv

ival, %

BreastCancer

LungCancer

ColorectalCancer

ProstateCancer

OvarianCancer

SevereInoperable

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

*

According to the 2014 ACC/AHA guidelines, severe aortic stenosis is

defined as:

Aortic valve area (AVA) less than 1.0 cm2

Mean gradient greater than 40 mmHg or jet velocity greater than 4.0 m/s

Echocardiographic Guidelines are the Gold Standard in Assessing Severe Aortic Stenosis6

*Doppler-Echocardiographic measurements

13

Multiple Modalities May Be Used to Diagnose Severe Aortic Stenosis6

14

Echocardiography:Continuity Equation-Conservation of Mass

Echocardiography:Echocardiography:3D Planimetry3D Planimetry

Not so classic aortic stenosis

1. Low Flow, Low Gradient Severe AS

2. Paradoxical Low Flow, Low Gradient

Severe AS

Low Flow, Low Gradient AS

• Low gradient with a small calculated valve area in the

setting of poor systolic function. This may result in lack

of referral for AVR because of the low gradient.

• Dobutamine Stress Echo:

– By increasing cardiac output, we can determine if the AS is

severe by reassessing the gradient across the aortic valve

(increases) AND the aortic valve area (decreases).

– Assess myocardial contractile reserve

• Does the cardiac output improve by 20% or more.

– Critical for decision making regarding aortic valve

replacement.

• 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

underestimation of the severity of the

disease, so many of these patients do

not undergo surgical aortic valve

replacement

Paradoxical Low Flow and/or Low Gradient Severe Aortic Stenosis1

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

23

Stages of Valvular AS.

ACC/AHA 2104 Valve Guidelines Nishimura R A et al. Circulation. 2014;129:e521-e643

Copyright © American Heart Association, Inc. All rights reserved.

Summary of Recommendations for AS: Timing of Intervention.

Nishimura R A et al. Circulation. 2014;129:e521-e643


Study data demonstrate that early and late outcomes were similarly good in both symptomatic and

asymptomatic patients

It is important to note that among asymptomatic patients with SAS, omission of surgical treatment

was the most important risk factor for late mortality

26

Aortic Valve Replacement Greatly Improves Survival

Patient Survival16

AVR, No Symptoms

AVR, Symptoms

No AVR, No Symptoms

No AVR, Symptoms

Years

27

Options for Aortic Valve Replacement

Transcatheter Aortic

Valve Replacemen

t (TAVR)

Transcatheter Aortic

Valve Replacemen

t (TAVR)

Surgical Aortic Valve Replacemen

t

(sAVR)

Surgical Aortic Valve Replacemen

t

(sAVR)

Minimal Incision Valve

Surgery

(MIVS)

Minimal Incision Valve

Surgery

(MIVS)

Inoperable OR High RiskInoperable OR High Risk Patients Suitable for Open Chest SurgeryPatients Suitable for Open Chest Surgery

Transfemoral Approach

Prosthetic Heart Prosthetic Heart ValvesValves

Tilting Disc ValveTilting Disc Valve

Bio-prosthetic ValveBio-prosthetic Valve

• Studies show at least 40% of patients with severe AS are not treated with an AVR9-15

31

Low Percentage of Aortic Valve Surgery

Aortic Valve ReplacementNo Aortic Valve Replacement

Aortic Valve ReplacementNo Aortic Valve Replacement

Summary of Recommendations for AS: Choice of Surgical or Transcatheter Intervention.

Nishimura R A et al. Circulation. 2014;129:e521-e643


• An aortic valve replacement as

an alternative to traditional

thoracotomy.

• Less invasive than traditional

thoracotomy for patients

considered too high risk for

traditional surgery.

What is TAVR-Transcatheter Aortic Valve Replacement?

33

Two TAVR Options• Edwards Sapien Valve

• Stainless Steel Frame

• More Aortic Regurg, less AV

block/PPM

• Better for severe bulky

calcification.

• Medtronic CoreValve

• Nitinol Frame-self expanding

• Less Aortic Regurg, More heart

block/PPM

35

TAVR Multimodality imaging

N = 179

N = 358Inoperable

Inoperable

StandardTherapyStandardTherapy

ASSESSMENT: Transfemoral

Access


Access

Not In StudyNot In Study

TF TAVR

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 Randomization1:1 Randomization

VS

YesYes NoNo

N = 179

TF TAVRTF TAVR AVRAVR

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


TA TAVR

TA TAVR AVRAVR

VS VS

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

PARTNER Study DesignPARTNER Study Design

Symptomatic Severe Aortic StenosisSymptomatic 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 RiskHigh Risk


Access


Access

Transapical (TA)Transapical (TA)Transfemoral (TF)Transfemoral (TF)

1:1 Randomization1:1 Randomization1:1 Randomization1:1 Randomization

YesYes NoNo

Cohort A Cohort A Cohort BCohort B

PARTNER Trial B• Exclusion Criteria:

– bicuspid or noncalcified aortic valve

– acute myocardial infarction

– substantial coronary artery disease requiring revascularization

– left ventricular ejection fraction of less than 20%

– a diameter of the aortic annulus of less than 18 mm or more

than 25 mm

– severe (>3+) mitral or aortic regurgitation

– a transient ischemic attack or stroke within the previous 6

months

– severe renal insufficiency (creatinine greater than 3 or on

dialysis).

– Iliac-femoral anatomy precluding safe sheath insertion

PARTNER Trial B

Primary End-Points:

– Death from any cause

– Rate of a hierarchical composite of the time

to death from any cause or the time to the

first repeat hospitalization from aortic valve

disease or procedure related complication

PARTNER Trial B

• Secondary End-Points:

– the rate of death from cardiovascular causes

– NYHA functional class

– The distance covered during a 6-minute walk test

– Valve performance (assessed by

echocardiography)

– The rates of myocardial infarction, stroke, acute

kidney injury, vascular complications, and

bleeding

41

Characteristics of an Inoperable Patient Cohort B

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

TAVR patients may present with some of the following:

“Standard Medical Therapy”

• 179 Patients assigned

• Balloon Valvuloplasty perfomed in 114

(63.7%) patients in first 30 days and 36

(20.1%) additional patients 30 days after

randomization.

• 12 (6.7%) underwent AVR!

• 5 (2.8%) LV apex to Aorta conduit

TAVR Group

• 179 Patients

• 6 did not undergo TAVR

– 2 died before implantation

– 2 unsuccessful transfemoral access

– 2 aortic valve annulus was to large

Cohort B Survival

44THE PARTNER TRIAL COHORT B

Edwards SAPIEN THV Improved Cardiac Function

Error bars = ± 1 Std Dev


Cohort B HF Improvement


Complications

Stroke was defined as follows: Neurological deficit lasting ≥ 24 hours or lasting less than 24 hours with a brain imaging study showing an infarction.

Major vascular complications were defined as any thoracic aortic dissection, access site or access-related vascular injury (dissection, stenosis, perforation, rupture, arterio-venous fistula, pseudoaneurysm, or hematoma) leading to either death, need for significant blood transfusion (> 3 units), or percutaneous or surgical intervention, and/or distal embolization (non-cerebral) from a vascular source requiring surgery or resulting in amputation or irreversible end-organ damage.

Bleeding event is defined as ≥ 2 units within the index procedure.


N = 179

N = 358Inoperable

Inoperable

StandardTherapyStandardTherapy


Access


Access

Not In StudyNot In Study

TF TAVR

TF TAVR







1:1 Randomization1:1 Randomization

VS

YesYes NoNo

N = 179

TF TAVRTF TAVR AVRAVR



TA TAVR

TA TAVR AVRAVR

VS VS

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

PARTNER Study DesignPARTNER Study Design

Symptomatic Severe Aortic StenosisSymptomatic Severe Aortic Stenosis





Total = 1,057 patients

2 Parallel Trials: Individually Powered

N = 699 High RiskHigh Risk


Access


Access

Transapical (TA)Transapical (TA)Transfemoral (TF)Transfemoral (TF)

1:1 Randomization1:1 Randomization1:1 Randomization1:1 Randomization

YesYes NoNo

Cohort A Cohort A Cohort BCohort B

TAVR 348 298 261 239 222 187 149

AVR 351 252 236 223 202 174 142

Cohort A: All-Cause Mortality Cohort A: All-Cause Mortality

No. at Risk

HR [95% CI] =0.93 [0.74, 1.15]

p (log rank) = 0.483

26.8%

24.3%

34.6%

33.7%

44.8%

44.2%

348 287 250 228 211 176 139

351 246 230 217 197 169 139

TAVR

AVR

Cohort A: StrokesCohort A: Strokes

No. at Risk

3.2%6.0% 9.3%

8.2%

HR [95% CI] =1.09 [0.62, 1.91]

p (log rank) = 0.763

4.9%

7.7%

Months Post Randomization

Iliofemoral Access > 18 Fr Sheath

NoYes

Randomization 1:1

CoreValveNon-

Iliofemoral

Versus

SAVRCoreValve

N=487 N=147

51

TCT 2013 LBCT Extreme Risk Study | Iliofemoral Pivotal

Study Purpose: To evaluate the safety and efficacy of the CoreValve THV for the treatment of patients with symptomatic severe aortic stenosis in whom the predicted risk of operative mortality or serious, irreversible morbidity was 50% or greater at 30 days

Risk Determined by: Two Clinical Site Cardiac Surgeons and One Interventional Cardiologist

Risk Confirmed by: Two Screening Committee Cardiac Surgeons and One Interventional Cardiologist

Study Purpose

Primary Endpoint: All Cause Mortality or Major Stroke at 12 Months

52


Inclusion Criteria:• Severe aortic stenosis: AVA ≤ 0.8 cm2 or AVAI ≤ 0.5 cm2/m2 AND

mean gradient > 40 mm Hg or peak velocity > 4 m/sec at rest or with dobutamine stress (if LVEF < 50%)

• NYHA functional class II or greater

Exclusion Criteria (selected):• Recent active GI bleed (3 mos), stroke (6 mos), or MI (30 days)

• Creatinine clearance < 20 mL/min

• Significant untreated coronary artery disease

• LVEF < 20%

• Life expectancy < 1 year due to co-morbidities

Inclusion and Exclusion Criteria

53


P < 0.0001

25.5%[21.6,29.4]

All

Cau

se M

ort

alit

y o

r M

ajo

r S

tro

ke

Months Post-Procedure

9.3% [6.7,12.0]

All Cause Mortality or Major Stroke

Primary Endpoint

54

Performance Goal = 43%


NYHA Class SurvivorsP

erce

nta

ge

of

Pat

ien

ts

90% of Patients Improved at Least 1 NYHA Class by 1 Year

60% of Patients Improved at Least 2 NYHA Classes by 1 Year

55


Secondary EndpointsEvents* 1 Month 1 YearAny Stroke, % 3.9 6.7

Major, % 2.4 4.1

Minor, % 1.7 3.1

Myocardial Infarction, % 1.3 2.0

Reintervention, % 1.3 2.0

VARC Bleeding, % 35.1 41.4

Life Threatening or Disabling, % 11.7 16.6

Major, % 24.1 27.6

Major Vascular Complications, % 8.3 8.5

Permanent Pacemaker Implant, % 22.2 27.1

Per ACC Guidelines, % 17.4 19.9* Percentages obtained from Kaplan Meier estimates

56


Core Valve TrialCore Valve Trial

57

Study DispositionStudy Disposition

19.1%

4.5%

Surgical

14.2%

P = 0.04 for superiority

3.3%

Transcatheter

Primary Endpoint: 1 Year All-cause MortalityPrimary Endpoint: 1 Year All-cause Mortality ACC 2014

59

2-Year All-cause Mortality2-Year All-cause Mortality ACC 2014

Major StrokeMajor Stroke

62

Other EndpointsOther EndpointsEvents* 1 Month 1 Year

TAVR

SAVR P Value

TAVR

SAVR P Value

Vascular complications (major), % 5.9 1.7 0.003 6.2 2.0 0.004

Pacemaker implant, % 19.8 7.1 <0.001 22.3 11.3 <0.001Bleeding (life threatening or disabling),% 13.6 35.0 <0.001 16.6 38.4 <0.001

New onset or worsening atrial fibrillation, % 11.7 30.5 <0.001 15.9 32.7 <0.001

Acute kidney injury, % 6.0 15.1 <0.001 6.0 15.1 <0.001

* Percentages reported are Kaplan-Meier estimates and log-rank P values

63

MMC Heart Valve Clinic

Marco Diaz, MD John Lualdi,MDDavid Butzell, MD Merle Kellett, MDReed Quinn, MD Scott Buchanan, MDDavid Burkey, MD

Following Patient Referral, the TAVR Team will Perform Further Evaluation

Confirm the patient is

diagnosed with severe

symptomatic native aortic

stenosis

Confirm the patient has

been independently evaluated by two cardiac

surgeons and meets the

indication for TAVR

Evaluate the aortic valvular complex using echocardiograp

hy

Evaluate the peripheral

vasculature and aortic valvular complex using

MDCT

Evaluate the peripheral

vasculature and aortic valvular complex using catheterization

Note: Evaluation using CT is typically not done unless the Heart Team confirms that patient is a candidate for TAVR

44 553311 22

65

• Aortic Stenosis is prevalent with a high morbidity and

mortality when symptomatic and aortic valve replacement

is the only treatment associated with improved outcomes.

• Asymptomatic low risk patients will benefit from surgical

AVR.

• Low gradient does not necessarily exclude severe aortic

stenosis, even when the ejection fraction is normal!!

• TAVR is an excellent alternative to traditional Aortic Valve

Surgery but increased risk of stroke and vascular injury

and the need for a permanent pacemaker.

• MMC Heart Team has performed over 100 TAVR

procedures in three years with excellent outcomes.

Key Takeaways

66

Thank You!

Documents

Severe Aortic Stenosis and TAVR. Disclosures I will not discuss off label use or investigational use in my presentation. I have no financial relationships