Transcript Severe Aortic Stenosis and TAVR

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
Age-Related Calcific
Aortic Stenosis
Aortic stenosis in patients over the age of 65 is
usually caused by calcific (calcium) deposits
associated with aging
Rheumatic Fever
Adults who have had rheumatic fever may also be
at risk for aortic stenosis
Congenital
Abnormality
In some cases adults may develop aortic stenosis
resulting from a congenital abnormality
Less Common
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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
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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
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5-Year Survival
8
30
30
28
Survival, %
25
20
23
15
12
10
5
4
3
0
Breast
Cancer
Lung
Cancer
Colorectal
Cancer
Prostate
Cancer
Ovarian
Cancer
Severe
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
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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
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Multiple Modalities May Be Used to
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Diagnose Severe Aortic Stenosis
Auscultation
Trans-thoracic
Echo (TTE)
Chest
Cardiac
Cath.
X-ray
Electrocardiogram
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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
underestimation of the severity of the disease,
Dobutamine stress in low gradient, low ejection fraction AS
Chambers, Heart. 2006 April; 92(4): 554–558
so many of these patients do not undergo
surgical aortic valve replacement
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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
Survival, %
Patient Survival
100
90
80
70
60
50
40
30
20
10
0
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AVR,
noSymptoms
Sx
AVR, No
AVR,
Sx
AVR, Symptoms
No AVR,
Symptoms
No
AVR,Nono
Sx
No AVR,
No
AVR,Symptoms
Sx
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
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Options for Aortic Valve Replacement
Inoperable OR High Risk
Transcatheter
Aortic Valve
Replacement
(TAVR)
Patients Suitable for Open Chest Surgery
Surgical Aortic
Valve
Replacement
(sAVR)
Minimal
Incision Valve
Surgery
(MIVS)
Transfemoral Approach
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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
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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.
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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
•
Better for severe bulky calcification.
block/PPM
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TAVR Multimodality imaging
PARTNER Study Design
Symptomatic Severe Aortic Stenosis
ASSESSMENT: High-Risk AVR Candidate
3,105 Total Patients Screened
Cohort A
Cohort B
Total = 1,057 patients
N = 699
High Risk
ASSESSMENT:
Yes
1:1 Randomization
Transfemoral
Access
Transapical (TA)
1:1 Randomization
Yes
No
1:1 Randomization
N = 244
N = 248
N = 104
N = 103
N = 179
N = 179
TF TAVR
AVR
TA TAVR
AVR
TF TAVR
Standard
Therapy
VS
VS
Primary Endpoint: All-Cause Mortality at 1 yr
(Non-inferiority)
N = 358
ASSESSMENT:
No
Transfemoral
Access
Transfemoral (TF)
Inoperable
2 Parallel Trials:
Individually Powered
VS
Not In Study
Primary Endpoint: All-Cause Mortality
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 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
Characteristics of an Inoperable Patient
Cohort B
TAVR patients may present with some of the following:
Severe, symptomatic native aortic valve stenosis
Old age
History of stroke/CVA
Frailty
History of syncope
Reduced EF
Heavily calcified aorta
Prior CABG
Prior chest radiation
History of AFib
Prior open chest surgery
Fatigue, slow gait
Peripheral vascular disease
History of CAD
History of COPD
History of renal insufficiency
Diabetes and hypertension
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“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
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Edwards SAPIEN THV Improved
Cardiac Function
Error bars = ± 1 Std Dev
THE PARTNER TRIAL COHORT B
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Cohort B HF Improvement
THE PARTNER TRIAL COHORT B
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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
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PARTNER Study Design
Symptomatic Severe Aortic Stenosis
ASSESSMENT: High-Risk AVR Candidate
3,105 Total Patients Screened
Cohort A
Cohort B
Total = 1,057 patients
N = 699
High Risk
ASSESSMENT:
Yes
1:1 Randomization
Transfemoral
Access
Transapical (TA)
1:1 Randomization
Yes
No
1:1 Randomization
N = 244
N = 248
N = 104
N = 103
N = 179
N = 179
TF TAVR
AVR
TA TAVR
AVR
TF TAVR
Standard
Therapy
VS
VS
Primary Endpoint: All-Cause Mortality at 1 yr
(Non-inferiority)
N = 358
ASSESSMENT:
No
Transfemoral
Access
Transfemoral (TF)
Inoperable
2 Parallel Trials:
Individually Powered
VS
Not In Study
Primary Endpoint: All-Cause Mortality
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%
44.2%
34.6%
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
9.3%
8.2%
7.7%
4.9%
6.0%
3.2%
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 >
18 Fr Sheath
Randomization 1:1
Yes
No
CoreValve
Iliofemoral
CoreValve
NonIliofemoral
N=487
N=147
TCT 2013 LBCT
Versus
CoreValve
SAVR
Extreme Risk Study | Iliofemoral Pivotal
5
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
TCT 2013 LBCT
Extreme Risk Study | Iliofemoral Pivotal
5
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
TCT 2013 LBCT
Extreme Risk Study | Iliofemoral Pivotal
5
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
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NYHA Class Survivors
90% of Patients Improved at Least 1 NYHA Class by 1 Year
Percentage of Patients
60% of Patients Improved at Least 2 NYHA Classes by 1 Year
TCT 2013 LBCT
Extreme Risk Study | Iliofemoral Pivotal
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Secondary Endpoints
Events*
Any Stroke, %
1 Month
3.9
1 Year
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
17.4
19.9
Per ACC Guidelines, %
* Percentages obtained from Kaplan Meier estimates
TCT 2013 LBCT
Extreme Risk Study | Iliofemoral Pivotal
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Core Valve Trial
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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%
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2-Year All-cause Mortality
ACC 2014
Major Stroke
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Other Endpoints
Events*
1 Month
TAV
R
Vascular complications
(major), %
5.9
1 Year
SAVR P Value TAVR SAVR P Value
6.2
2.0
0.004
Pacemaker implant, %
19.8
7.1
<0.001 22.3
Bleeding
(life threatening or
13.6 35.0 <0.001 16.6
disabling),%
New onset or
worsening atrial fibrillation,
%
11.7
30.5and log-rank
<0.001P values
15.9
* Percentages reported are Kaplan-Meier
estimates
11.3
<0.001
38.4
<0.001
32.7
<0.001
Acute kidney injury, %
15.1
<0.001
6.0
1.7
15.1
0.003
<0.001
6.0
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MMC Heart Valve Clinic
Marco Diaz, MD
David Butzell, MD
Reed Quinn, MD
David Burkey, MD
John Lualdi,MD
Merle Kellett, MD
Scott Buchanan, MD
Following Patient Referral, the TAVR Team
will Perform Further Evaluation
1
2
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
3
4
Evaluate the
aortic valvular
complex using
echocardiography
Evaluate the
peripheral
vasculature and aortic
valvular complex
using MDCT
5
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
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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.
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Thank You!