Download Transcatheter Aortic Valve Replacement(TAVR)

Transcatheter Aortic Valve
Replacement(TAVR)
NCVH - 2016 Update
Rodney Reeves, MD
• Disclosures: none
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
3
Current FDA Approved Valves
» Edwards Sapien 3 - balloon expandable
» Medtronic Corevalve Evolut R- selfexpanding
» 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
4
Pre TAVR workup
» Meet the patient and family(discuss goals/
expectations)
» CT
» RHC/LHC
» Assess risk(PFTs, frailty index,
comorbidities, STS score, etc.)
» Surgical Consultation
5
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
6
Post-op till Discharge
»
»
»
»
Early ambulation
Lines out quickly
Avoidance of sedatives/narcotics
Aspirin/Plavix
7
TAVR Heart Team Concept
2014
Valvular Disease
Guidelines
Cohesive, Multi-disciplinary Approach Embodies
▪ Optimal patient centric care
▪ Dedication across medical specialties
▪ Collaborative treatment decision
Interventional
Cardiologist
Imaging
Specialists
AHA / ACC
Cardiologist
Surgeon
TAVR Valve Clinic
Coordinator
Heart Team
National Coverage
Determination18
The patient (preoperatively and postoperatively) is under
the care of a heart team
Cardiac
CATH Lab
and
O.R. Staff
Referring
Cardiologist
Anesthe-
siologist
18. National Coverage Determination (NCD) for Transcatheter Aortic Valve Replacement (TAVR). 2012.
8
TAVR Evaluation Pathway
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
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.
9
Characteristics of a TAVR Patient19
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
19. Leon M et al. New England Journal of Medicine 2010 October 21;363(17):1597-1607.
10
Alain Cribier: First Human Transcatheter
Valve Replacement (2002)
11
What Causes Aortic Stenosis in Adults?
Less Common
Congenital
Abnormality
More Common
Rheumatic
Fever
Age-Related
Calcific Aortic
Stenosis
Images courtesy of John Webb, MD at St. Paul’s Hospital and Renu Virmani, MD at the CVPath Institute
12
Population at Risk for Aortic Stenosis is Increasing
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
4.0%
3.1%
▪ Aortic Stenosis is estimated to be
prevalent with 12.4% of the
population over the age of 75.2
2.6%
2.8%
2.4%
▪ 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
2.2%
1.3%
0.0%
1910-1930
1950-1970
1990-2010
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.
13
Symptoms of Aortic Stenosis
▪
▪
▪
▪
▪
Shortness of breath
Angina
Fatigue
Syncope or Presyncope
Other
▪ Rapid or irregular heartbeat
▪ Palpitations
Sandy
Severe Aortic Stenosis
(Actual Patient)
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 to
37% exhibit symptoms.6
5. Das P. European Heart Journal. 2005;26:1309-1313; 6 . Lester SJ et al. CHEST 1998;113(4):1109-1114.
14
Severe Aortic Stenosis is Life Threatening
and Treatment is Critical6
ADULTS AVERAGE COURSE WITH VALVULAR AORTIC STENOSIS
100%
Onset Severe Symptoms
80%
Angina
Survival, %
After the onset of
symptoms, patients
with severe aortic
stenosis have a
survival rate as low
as 50% at
2 years and 20%
at 5 years without
aortic valve
replacement7
60%
40%
Syncope
Latent Period
Failure
(Increasing Obstruction, Myocardial Overload)
0
20%
2
4
6
Average Survival, y
0
0
40
50
Age, Years
60
70
50% of patients died within 1 year without valve replacement
Per the Inoperable Cohort of the PARTNER Trial
6. Lester SJ et al. CHEST 1998;113(4):1109-1114; 7. Otto CM. Heart. 2000:84:211-218.
15
Worse Prognosis than Many Metastatic Cancers
5-YEAR SURVIVAL
8
(Distant Metastasis)
35
30
Survival, %
30
25
28
23
20
15
12
10
4
5
0
Breast Cancer
Lung Cancer
3
Colorectal Cancer
Prostate Cancer
Ovarian Cancer Severe Inoperable AS*
5 year survival of breast cancer, lung cancer, prostate cancer,
ovarian cancer and severe inoperable aortic stenosis
*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.
16
Timely Intervention is Critical for Patients
with Symptoms9
▪ 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:
2014
Valvular Disease
Guidelines
AHA / ACC
▪ 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
9. Nishimura RA et al. JACC. 2014. doi: 10.1016/j.jacc.2014.02.537.
17
Definition of Severe Aortic Stenosis9
Patients with severe aortic stenosis typically
have an aortic valve area ≤ 1.0 cm2
Definition
2014
Valvular Disease
Guidelines
AHA / ACC
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%
Symptoms:
Dyspnea or decreased exercise tolerance, heart failure, angina, syncope and presyncope
9. Nishimura RA et al. JACC. 2014. doi: 10.1016/j.jacc.2014.02.537.
18
Paradoxical Low Flow and/or Low Gradient
Severe Aortic Stenosis10
▪ Dobutamine stress echocardiography can
be 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
Dobutamine stress in low gradient, low ejection fraction
AS Chambers, Heart. 2006 April; 92(4): 554–558
10. Dumesnil et al. European Heart Journal 2010; 31, 281-289.
19
At Least 40% of Patients Who Need Valve
Replacement Do Not Get Treatment11-17
UNDERTREATEMENT OF AORTIC STENOSIS
100%
80%
54%
43%
60%
61%
40%
39%
Patients, %
60%
52%
74%
69%
40%
20%
46%
57%
48%
26%
31%
0%
Bouma 1999
Pellikka 2005
Charison 2006 Varadarajan 2006
January 2009
Aortic Valve Replacement (AVR)
Bach 2009
Freed 2010
No AVR
Studies show that patients with severe aortic
stenosis are under-diagnosed and under-treated
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.
20
Medical Management and BAV are Inadequate
Therapies for Inoperable Patients
T H E PA R T N E R T R I A L
Control Group (Med Rx and BAV) (n
= 179)
80.9%
87.5%
93.6%
All-Cause Mortality (%)
68.0%
50.7%
HR [95% CI] = 0.50 [0.39, 0.65]
p (log rank) < 0.0001
Months
* In an age and gender matched US population without comorbidities, the mortality at 5 years is 40.5%.
▪ 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
21
Options for Aortic Valve Replacement per Guidelines9
Severe Aortic Stenosis is Defined as: Valve Area < 1.0 cm2
Mean Gradient > 40 mmHg OR Jet Velocity > 4.0 m/s
Therapy
Transcatheter Heart Valve
Low- to
Moderate-Risk
High Risk
Greater Risk
Transcatheter Aortic
Valve Replacement
(TAVR)
Open-Heart Surgery
(AVR)
Surgical
Heart Valve
High Risk Patients
Defined by STS Risk
Score > 8%
9. Nishimura RA et al. JACC. 2014. doi: 10.1016/j.jacc.2014.02.537.
22
Edwards SAPIEN 3 Transcatheter Heart Valve
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
Society of Thoracic Surgeons operative risk score
≥ 8% OR at a ≥ 15% risk of mortality (at 30 days)
23
24
25
26
TAVR is Better than Medical Management
for Inoperable Patients
Edwards
SAPIEN Valves
Significantly
Improve
Survival
27
TAVR is Better than Medical Management
for Inoperable Patients
Edwards SAPIEN
is superior to
medical
management in inoperable
patients
TAVR with
Edwards SAPIEN
valves is a
reasonable
alternative to
surgery
Edwards
SAPIEN 3 valve:
Transformational
design
Edwards
SAPIEN Valves
Significantly
Improve
Survival
27
TAVR is Better than Medical Management
for Inoperable Patients
TAVR is superior
Edwards
SAPIEN
is superior
to
medical to
medical
management
for
management Inoperable
in inoperable
Patients
patients
TAVR with
Edwards SAPIEN
valves is a
reasonable
alternative to
surgery
Edwards
SAPIEN 3 valve:
Transformational
design
Edwards
SAPIEN Valves
Significantly
Improve
Survival
27
Standard Therapy is an Ineffective Treatment
for Severe Aortic Stenosis Patients
A L L - C A U S E M O R TA L I T Y
Inoperable Cohort
100%
93.6%
Standard Rx (n = 179)
TAVR (n = 179)
All-Cause Mortality (%)
80%
71.8%
50.7%
60%
21.8% absolute
reduction in
mortality at
5 years
40%
HR [95% CI] = 0.50 [0.39, 0.65]
p (log rank) < 0.0001
30.7%
20%
Without treatment
94% of patients in the standard
therapy group
died within
5 years
0%
0
12
24
36
48
60
Months
Standard therapy includes medical management and BAV
28
Standard Therapy Patients Were Rehospitalized
Twice as Often as TAVR Patients
R E H O S P I TA L I Z AT I O N
Inoperable Cohort
100%
Standard Rx (n = 179)
TAVR (n = 179)
87.3%
Hospitality (%)
80%
60%
47.6%
39.7% absolute
reduction of
rehospitilization
40%
HR [95% CI] = 0.40 [0.29, 0.55]
p (log rank) < 0.0001
20%
87.3% of patients
with standard
therapy were
rehospitalized
for cardiac issues at 5 years
0%
0
12
24
36
48
60
Months
Standard therapy includes medical management and BAV
29
TAVR with Edwards SAPIEN Valves
is Equivalent to Surgery
With the
Benefits of a Less Invasive
Procedure
30
TAVR with Edwards SAPIEN Valves
is Equivalent to Surgery
TAVR is superior
to medical
management for
Inoperable
Patients
Edwards SAPIEN
valve is a
reasonable
alternative to
surgery in highrisk patients
Edwards
SAPIEN 3 valve:
Transformational
design
With the
Benefits of a Less Invasive
Procedure
30
TAVR with Edwards SAPIEN Valves
is Equivalent to Surgery
TAVR is superior
to medical
management for
Inoperable
Patients
TAVR
Edwards
withSAPIEN
Edwards
valve is aSAPIEN
valves
reasonable
is a
reasonable
alternative to
alternative
surgery in to
highsurgery
risk patients
Edwards
SAPIEN 3 valve:
Transformational
design
With the
Benefits of a Less Invasive
Procedure
30
TAVR is Equivalent to Surgery in High-Risk Patients
A L L C A U S E M O R TA L I T Y
A t 5 Ye a r s
100%
SAVR
Error Bars Represent
95% Confidence Limits
TAVR
67.8%
All-Cause Mortality (%)
80%
60%
62.4%
40%
HR [95% CI] = 1.04 [0.86, 1.24]
p (log rank) = 0.76
20%
0%
0
12
No. at Risk
TAVR 348
SAVR 351
24
36
Months Post Randomization
48
60
262
228
191
154
61
236
210
174
131
64
At 5 Years
Patients that had TAVR with the
Edwards SAPIEN
valve showed
survival
equivalent to SAVR
Per ACC / AHA Guidelines, TAVR is a reasonable alternative to surgery in patients
who meet an indication for AVR and who have high surgical risk for surgical AVR9
9. Nishimura RA et al. JACC. 2014. doi: 10.1016/j.jacc.2014.02.537.
31
Patients Continued to Show Improved Symptom
Relief 5 Years After TAVR
NYHA CLASS OVER TIME
100%
I
p = 0.91
p = 0.64
II
III
IV
p = 0.35
13%
15%
p = 0.93
14%
15%
20%
Percent of Evaluable Echoes
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.
19%
80%
60%
94%
94%
40%
20%
0%
TAVR
SAVR
348
349
Baseline
TAVR
SAVR
250
226
1 Year
TAVR
SAVR
165
145
3 Years
TAVR
SAVR
100
97
5 Years
32
Longest Follow-Up in Any TAVR Randomized Study
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 HighRisk Patients
▪ Equivalent mortality benefit
▪ Persistent symptom relief
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
20. Lancet. 2015 Jun 20;385(9986):2477-84. doi: 10.1016/S0140-6736(15)60308-7. Epub 2015 Mar 15.
33
Now Approved: The Edwards SAPIEN 3 Valve
34
Now Approved: The Edwards SAPIEN 3 Valve
TAVR is superior
to medical
management for
inoperable
patients
TAVR is a
reasonable
alternative to
surgery for highrisk patients
Transformational
advance in valve
design: Edwards
SAPIEN 3 Valve
34
Now Approved: The Edwards SAPIEN 3 Valve
TAVR is superior
to medical
management for
inoperable
patients
TAVR is a
reasonable
alternative to
surgery for highrisk patients
Edwards
Transformational
advance3invalve:
SAPIEN
valve
design: Edwards
Transformational
SAPIEN 3 Valve
design
Unprecedented
Clinical
Outcomes
34
Low Mortality at 30 Days
The PARTNER II Trial: SAPIEN 3 Valve High-Risk
MORTALITY
(As Treated Patients)
100%
All-Cause Mortality of
the 491 patients in the
PARTNER II Trial was
1.6% at 30 days
Cardiovascular
Mortality was 1.0%
All-Cause
Cardiovascular
75%
50%
26%
1%
1.60%
1%
High-Risk (TF)
35
All-Cause Mortality Has Decreased Overall
A L L - C A U S E M O R TA L I T Y a t 3 0 D AY S
20%
PARTNER I Trial and PARTNER II Trial
6%
5%
4%
5%
4%
2%
0%
PARTNER I B (TF)
175
PARTNER I A (All)
PARTNER I A (TF)
344
SAPIEN Valve
240
PARTNER II B (TF)
271
PARTNER II B (TF)
PARTNER II HR (TF)
282
491
SAPIEN XT
Valve
SAPIEN 3 Valve
36
Low Stroke at 30 Days
The PARTNER II Trial: SAPIEN 3 Valve HR
DISABLING STROKE
( A s Tr e a t e d P a t i e n t s )
Of the 491
Patients in the
PARTNER II Trial:
Disabling Stroke
was 0.8% at 30
days
100%
Disabling
75%
50%
25%
0%
0.8%
High-Risk (TF)
37
Other Clinical Events at 30 Days (as Treated Patients)*
SAPIEN 3 Valve HR
TF
Events (%)
Major Vascular Comps.
Bleeding – Life Threatening
*PARTNER II Trial high-risk TF SAPIEN 3 valve cohort 30-day results.
(n = 491)
5.3
5.5
Femoral Case Example
39
40
40
41
41
42
42
Transapical Case Example
43
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
47
Case Examples:
48
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%
49
50
50
51
51
52
52
Edwards Sapien 3
» 88 yo WM
» NYHA Class III
» Good functional capacity
53
54
54
55
55
56
56
57