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
 Prevalence of Aortic Stenosis
16.5 Million People in US
Over the Age of 652
Aortic stenosis is estimated to
be prevalent in up to 7% of the
population over the age of 651 Percentage
Diagnosed with
Aortic Stenosis

It is more likely to affect men

than women; 80% of adults
with symptomatic aortic
stenosis are male3

3
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?
More Common

Aortic stenosis in patients over the age of 65 is

Age-Related Calcific
usually caused by calcific (calcium) deposits
Aortic Stenosis associated with aging

Adults who have had rheumatic fever may also be

Rheumatic Fever
at risk for aortic stenosis

Congenital In some cases adults may develop aortic stenosis

Abnormality resulting from a congenital abnormality

Less Common

5
3 Major Etiologies for aortic stenosis
 Major Risk Factors
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
 Signs and Symptoms
Heart Failure Carotid Parvus et Tardus

Angina Laterally displaced PMI

Syncope Soft A2
Crescendo-Decrescendo
systolic murmur
Timing of peak murmur and
NOT intensity predicts
severity
 Aortic Stenosis Is Life Threatening
and Progresses Rapidly

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 occur 1
 Sobering Perspective
35 8
5-Year Survival
30
30
28
25

23
Survival, %

20

15

10 12

5
4 3
0
Breast Lung Colorectal Prostate Ovarian Severe
Cancer Cancer Cancer Cancer Cancer Inoperable AS*
*Using constant hazard ratio. Data on file, Edwards Lifesciences LLC. Analysis courtesy of Murat Tuczu, MD, Cleveland Clinic

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

12
Echocardiographic Guidelines are the Gold Standard
in Assessing Severe Aortic Stenosis6
*

*Doppler-Echocardiographic measurements

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

13
Multiple Modalities May Be Used to
6
Diagnose Severe Aortic Stenosis

Trans-thoracic
Auscultation Echo (TTE)

Cardiac Chest
Cath. X-ray

Electro-
cardiogram

14
 Echocardiography:
Continuity Equation-Conservation of Mass
Echocardiography:
3D 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.

 Paradoxical Low Flow and/or
Low Gradient Severe Aortic Stenosis1

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

Dobutamine stress in low gradient, low ejection fraction AS
underestimation of the severity of the disease, Chambers, Heart. 2006 April; 92(4): 554558

so many of these patients do not undergo

surgical aortic valve replacement

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

Copyright American Heart Association, Inc. All rights reserved.

 Aortic Valve Replacement Greatly Improves
Survival
16
Patient Survival AVR, noSymptoms
AVR, No Sx
100 AVR, Sx
AVR, Symptoms
90 No AVR,Nono
No AVR, Sx
Symptoms
80 No AVR,
No AVR,Symptoms
Sx
70
Survival, %

60
50
40
30
20
10
0
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Years

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
Options for Aortic Valve Replacement

Inoperable OR High Risk Patients Suitable for Open Chest Surgery

Transcatheter Surgical Aortic Minimal

Aortic Valve Valve Incision Valve
Replacement Replacement Surgery
(TAVR) (sAVR) (MIVS)

Transfemoral Approach

27
Prosthetic Heart Valves
Tilting Disc Valve
Bio-prosthetic Valve
 Low Percentage of Aortic Valve Surgery

Aortic Valve Replacement

No Aortic Valve Replacement

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

31
Summary of Recommendations for AS: Choice of Surgical or Transcatheter Intervention.

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

Copyright American Heart Association, Inc. All rights reserved.

 What is TAVR-Transcatheter Aortic
Valve Replacement?
An aortic valve replacement as an
alternative to traditional
thoracotomy.

Less invasive than traditional

thoracotomy for patients considered
too high risk for traditional surgery.

33
 Two TAVR Options
Edwards Sapien Valve Medtronic CoreValve
Stainless Steel Frame Nitinol Frame-self expanding
More Aortic Regurg, less AV Less Aortic Regurg, More heart
block/PPM block/PPM
Better for severe bulky calcification.
35
TAVR Multimodality imaging
 PARTNER Study Design
Symptomatic Severe Aortic Stenosis
ASSESSMENT: High-Risk AVR Candidate
Cohort A 3,105 Total Patients Screened Cohort B
Total = 1,057 patients
N = 699 High Risk 2 Parallel Trials: Inoperable N = 358
Individually Powered
ASSESSMENT: ASSESSMENT:
Yes Transfemoral No Transfemoral
Access Access

Transfemoral (TF) Transapical (TA) Yes No

1:1 Randomization 1:1 Randomization 1:1 Randomization Not In Study

N = 244 N = 248 N = 104 N = 103 N = 179 N = 179

Standard
TF TAVR AVR TA TAVR AVR TF TAVR
Therapy
VS VS VS

Primary Endpoint: All-Cause Mortality at 1 yr Primary Endpoint: All-Cause Mortality

(Non-inferiority) Over Length of Trial (Superiority)
Co-Primary Endpoint: Composite of All-Cause Mortality
and Repeat Hospitalization (Superiority)
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 E nd-Points :
the rate of death from cardiovas cular caus es

NYHA functional clas s

The distance covered during a 6-minute walk test

Valve performance (as s es s ed by echocardiography)

The rates of myocardial infarction, stroke, acute

kidney injury, vas cular complications , and bleeding
 Characteristics of an Inoperable Patient
Cohort B
TAVR patients may present with some of the following:
Severe, symptomatic native aortic valve stenosis
Old age Frailty
History of stroke/CVA History of syncope
Reduced EF Heavily calcified aorta
Prior CABG Prior chest radiation
History of AFib History of CAD
Prior open chest surgery History of COPD
Fatigue, slow gait History of renal insufficiency
Peripheral vascular disease Diabetes and hypertension

41
 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

THE PARTNER TRIAL COHORT B 44

 Edwards SAPIEN THV Improved
Cardiac Function

Error bars = 1 Std Dev

THE PARTNER TRIAL COHORT B 45

 Cohort B HF Improvement

THE PARTNER TRIAL COHORT B 46

 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.

THE PARTNER TRIAL COHORT B 47

 PARTNER Study Design
Symptomatic Severe Aortic Stenosis
ASSESSMENT: High-Risk AVR Candidate
Cohort A 3,105 Total Patients Screened Cohort B
Total = 1,057 patients
N = 699 High Risk 2 Parallel Trials: Inoperable N = 358
Individually Powered
ASSESSMENT: ASSESSMENT:
Yes Transfemoral No Transfemoral
Access Access

Transfemoral (TF) Transapical (TA) Yes No

1:1 Randomization 1:1 Randomization 1:1 Randomization Not In Study

N = 244 N = 248 N = 104 N = 103 N = 179 N = 179

Standard
TF TAVR AVR TA TAVR AVR TF TAVR
Therapy
VS VS VS

Primary Endpoint: All-Cause Mortality at 1 yr Primary Endpoint: All-Cause Mortality

(Non-inferiority) Over Length of Trial (Superiority)
Co-Primary Endpoint: Composite of All-Cause Mortality
and Repeat Hospitalization (Superiority)
 Cohort A: All-Cause Mortality

HR [95% CI] =
0.93 [0.74, 1.15]
p (log rank) = 0.483
44.8%

34.6% 44.2%

26.8% 33.7%

24.3%

No. at Risk
TAVR 348 298 261 239 222 187 149

AVR 351 252 236 223 202 174 142

 Cohort A: Strokes

HR [95% CI] =
1.09 [0.62, 1.91]
p (log rank) = 0.763

6.0% 7.7% 9.3%

3.2% 4.9% 8.2%

Months Post Randomization

No. at Risk
TAVR 348 287 250 228 211 176 139

AVR 351 246 230 217 197 169 139

 CoreValve US Pivotal
Trials

Extreme Risk High Risk

Iliofemoral Access >

Randomization 1:1
18 Fr Sheath

Yes No Versus

CoreValve
CoreValve
Non- CoreValve SAVR
Iliofemoral
Iliofemoral

N=487 N=147

5
TCT 2013 LBCT Extreme Risk Study | Iliofemoral Pivotal 1
 Study Purpose
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

Primary Endpoint: All Cause Mortality or Major Stroke at 12

Months

5
TCT 2013 LBCT Extreme Risk Study | Iliofemoral Pivotal 2
 Inclusion and Exclusion Criteria
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

5
TCT 2013 LBCT Extreme Risk Study | Iliofemoral Pivotal 3
 Primary Endpoint
All Cause Mortality or Major Stroke
All Cause Mortality or Major Stroke

P < 0.0001
Performance Goal = 43%

9.3%
[6.7,12.0] 25.5%
[21.6,29.4]

Months Post-Procedure

TCT 2013 LBCT Extreme Risk Study | Iliofemoral Pivotal 54

 NYHA Class Survivors
90% of Patients Improved at Least 1 NYHA Class by 1 Year
60% of Patients Improved at Least 2 NYHA Classes by 1 Year
Percentage of Patients

TCT 2013 LBCT Extreme Risk Study | Iliofemoral Pivotal 55

 Secondary Endpoints
Events* 1 Month 1 Year
Any 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

TCT 2013 LBCT Extreme Risk Study | Iliofemoral Pivotal 56

Core Valve Trial

57
Study Disposition
Primary Endpoint: 1 Year All-cause Mortality ACC 2014

Surgical
Transcatheter

19.1%

14.2%

4.5% P = 0.04 for superiority

3.3%

59
2-Year All-cause Mortality ACC 2014
Major Stroke

62
 Other Endpoints
Events* 1 Month 1 Year
TAV
R 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 <0.001

Bleeding
(life threatening or
disabling),% 13.6 35.0 <0.001 16.6 38.4 <0.001
New onset or
worsening atrial fibrillation,
% 11.7
* Percentages reported are Kaplan-Meier 30.5and log-rank
estimates <0.001P values
15.9 32.7 <0.001

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

63
MMC Heart Valve Clinic
Marco Diaz, MD John Lualdi,MD
David Butzell, MD Merle Kellett, MD
Reed Quinn, MD Scott Buchanan, MD
David Burkey, MD
 Following Patient Referral, the TAVR Team
will Perform Further Evaluation

1 2 3 4 5

Confirm the patient is Confirm the patient Evaluate the Evaluate the Evaluate the peripheral
diagnosed with severe has been aortic valvular peripheral vasculature and aortic
symptomatic native independently complex using vasculature and aortic valvular complex using
aortic stenosis evaluated by two echocardiography valvular complex catheterization
cardiac surgeons and using MDCT
meets the indication
for TAVR

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

65
 Key Takeaways
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.
66
Thank You!