Transcript Slide 1

TAVI Education
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Learning Objectives
1. Provide information on pathophysiology, etiology,
prevalence, symptoms, and prognosis for severe aortic
stenosis (AS)
2. Describe methods used to diagnose AS
3. Identify treatments for severe AS and associated clinical
outcomes
4. Provide information on transcatheter aortic valve
implantation (TAVI)
5. Identify potential patients for surgical aortic valve
implantation (SAVR) or TAVI procedures
6. Describe the potential future for TAVI
Agenda
• Aortic Stenosis Overview
• Aortic Stenosis Diagnosis
• Aortic Stenosis Treatment Options and Outcomes
• TAVI:
–
–
–
–
–
–
–
–
Description
Surgical Procedure
CE-Mark Approved Products
Patient Selection
Clinical Outcomes
Future
Patient Case Example
Conclusions
Aortic Stenosis Overview
Healthy Aortic Valve
Stenosed
Aortic Valve
Pathophysiology and Prevalence
• Pathophysiology:
– Progressive, degenerative disease of the native leaflets
– Mechanism of stenosis is similar to atherosclerosis1
Aortic Sclerosis
Aortic Stenosis
• Mild calcification
• No obstruction of
blood flow
• Severe calcification
• Obstruction of
blood flow
• Prevalence2:
– 2% of people over 65
– 3% of people over 75
– 4% of people over 85
– Most prevalent native valve disease
1 Otto
CM. Circulation 1994;90:844-853.
BF. J Am Coll Cardiol 1997;29:630-634.
2 Steward
Disease Etiology
Predominantly a Degenerative Disease
Etiology of Single Native Left-sided Valve Disease
100%
80%
Other
% of Total
Ischemic
60%
Congenital
Inflammatory
Endocarditis
40%
Rheumatic
Degenerative
20%
0%
Aortic Stenosis
Aortic
Regurgitation
Messika-Zeitoun D.. Eur Heart J 2003;24:1244-1253.
Mitral Stenosis
Mitral
Regurgitation
Aortic Stenosis Severity
Indicator
Jet Velocity
(m/s)
Mean Gradient
(mmHg)
Valve Area
(cm2)
Valve Area Index
(cm2/m2)
Mild
Moderate
Severe
< 3.0
3.0 – 4.0
> 4.0
< 25
25 – 40
> 40
> 1.5
1.0 – 1.5
< 1.0
–
–
< 0.6
Bonow RO. ACC/AHA 2006 Guidelines for the Management of Patients with Valvular Heart Disease: A Report of the
American College of Cardiology/American Heart Association on Practice Guidelines. Circulation 2006;114:e84-e231.
Onset of Severe Symptoms
Onset of dyspnea and other heart failure symptoms
foretell the worst outlook for aortic stenosis patients
Classic symptoms
of aortic stenosis:
• Heart Failure
• Syncope
• Angina
Ross J, Braunwald E. Circulation 1968; 38: 61-67.
Carabello BA. Lancet 2009;373:956-966.
Symptoms & Mortality if Valve Not Replaced
• Mortality for untreated severe AS: 38%, 68%, and 82%
at 1, 5, and 10 years, respectively. 1,2,3,4
• Aortic Stenosis combined with:
– Heart Failure has a 50% 2 yr mortality rate2
– Syncope has a 50% 3 yr mortality rate2
– Angina has a 50% 5 yr mortality rate2
1 Vahanian A.
Eur Heart J. 2008;29:1463-1470.
Ross J. Circulation 1968;38:61-67.
3 Bonow RO J Heart Valve Dis. 1998;7:672-707.
4 Varadarajan P. Ann Thorac Surg. 2006;82:2111-2115.
2
Aortic Stenosis Diagnosis
Physical Examination
• Slow rate of rise of the carotid pulse
• Mid to late peak intensity of murmur
• Decreased intensity of the second heart sound
• Peripheral signs include:
– Slow-rising, small volume carotid pulse
– Narrowed pulse pressure
– Sustained, heaving apex beat that is not displaced unless
systolic dysfunction of the left ventricular has developed
Echocardiography and Cardiac Catheterization
• Echocardiography
Purpose: Evaluate certain heart murmurs
Helps:
• Define primary lesion, cause and severity
• Evaluate hemodynamics, secondary lesions
• Evaluate chamber size and function
• Re-evaluate patient after intervention
• Cardiac Catheterization
Purpose: Provide additional information beyond initial
echocardiographic and clinical findings
Helps:
• Provide more information about severity and regurgitation
• Confirm non-invasive disease suspicions
Diagnosis: Evaluating Murmurs
Cardiac Murmur
Systolic Murmur
Midsystolic (grade
2 or less)
Asymptomatic
Diastolic Murmur
• Early systolic
• Midsystolic
(grade 3 or less)
• Late systolic
• Holosystolic
Symptomatic or
other signs of
cardiac disease
Continuous
Murmur
Echocardiography
Catheterization
and/or
Angiography
• Venous hum
• Mammary soufflé
or pregnancy
No further workup
Required
Bonow RO. ACC/AHA 2006 Guidelines for the Management of Patients with Valvular Heart Disease: A Report of the
American College of Cardiology/American Heart Association on Practice Guidelines. Circulation 2006;114:e84-e231.
Severe AS Treatments and Outcomes
Treatments
SAVR
TAVI
Aortic Balloon
Valvuloplasty
• In the absence of serious co-morbid
conditions, SAVR is indicated in virtually all
symptomatic patients with severe AS1
• High risk or contraindications for SAVR
• Bridge to surgery in hemodynamically
unstable adult patients with AS who are at
high risk for AVR1
• For palliation in adult patients with AS in
whom AVR cannot be performed because of
serious comorbid conditions1
Medical Management • Serious comorbid conditions, malignancy,
short life expectancy or patient preference1
1. Adapted from Bonow RO. J Am Coll Cardiol. 2008;52(13):e1-142.
ESC Valvular Heart Disease Guidelines:
Class I Indications for SAVR
1. Patients with severe AS and any symptoms
2. Patients with severe AS undergoing CABG or surgery on
the ascending aorta or other heart valves
3. Asymptomatic patients with severe AS and systolic left
ventricular dysfunction (LVEF < 50%)
4. Asymptomatic patients with severe AS showing symptoms
on exercise
Vahanian A. Eur Heart J 2007;28:230-268.
Severe AS Survival Results:
With and Without AVR
AS=aortic stenosis; AVR=aortic valve replacement.
1. Varadarajan P, et al. Eur J Cardiothorac Surg. 2006;30:722-727.
Aortic Balloon Valvuloplasty
• High restenosis rate: 50% in six years1,2
• Acute improvements: 26% repeat BAV after 30 days3
• Only 21% of patients were in NYHA II or less at one year3
1Otto
CM. Circulation 1994;89:642-650.
SH. J Am Coll Cardiol 1994;23:1076-1078.
3Tuzcu, EM. Clinical Outcomes from “Standard Therapy” in the PARTNER Inoperable Patients. TCT 2010, Washington D.C.
2Rahmitoola
% Severe AS Patients Not Treated with SAVR
No SAVR
SAVR
Charlson1
Pellikka2
U.S.
1 Charlson
E. J Heart Valve Dis 2006;15:312-321.
2 Pellikka PA. Circulation 2005;111:3290-3295.
Iung3
Bouma4
Europe
3 Iung
B. Eur Heart J 2003;24:1231-1243.
BJ. Heart 1999;82:143-148.
4 Bouma
Reasons Severe AS Patients are Not Treated
with SAVR
Meet Medical Guidelines – But Not Treated1,2 :
• Age concerns
• Co-morbidity concerns
• Lack of guideline knowledge
• Patient refusal
Contra-indicated for SAVR:
• Surgery risk too high
1 Charlson
E. J Heart Valve Dis 2006;15:312-321.
2 Iung
B. Eur Heart J 2003;24:1231-1243.
Transcatheter Aortic Valve Implant
(TAVI) Background
TAVI Description
• Provides percutaneous orthotopic placement of a
prosthetic tissue heart valve
• Replaces native aortic heart valve without open-heart
surgery and without concomitant surgical removal of the
failed native valve
• Placed within the annulus of the stenotic valve by
means of a catheter
• Three components:
– Delivery Catheter System
– Aortic Valve Prosthesis
– Crimping/Loading System
TAVI Implantation Approach Options
1. Transfemoral: Catheter advanced to the stenotic aortic
valve via the femoral artery.
2. Subclavian / Axillary: Catheter advanced to the stenotic
aortic valve via a small incision exposing the subclavian /
axillary artery.
3. Direct Aortic: Catheter advanced to the stenotic aortic valve
via minimally invasive thoracotomy (e.g. right anterior minithoracotomy) or sternotomy (e.g. upper partial ministernotomy)
4. Transapical: Catheter is inserted via a small intercostal
incision. The apex of the left ventricle is punctured, and the
valve is positioned within the stenotic aortic valve.
TAVI Implantation Approach Options
Direct Aortic
Subclavian
Transapical
Transfemoral
TAVI Procedure Example:
CoreValve® Transfemoral Approach
1. Balloon catheter
threaded through
sheath and into heart
2. Transcatheter valve
placed into position
over the diseased
aortic valve
3. Transcatheter valve in
place, procedure completed
TAVI Procedure and Recovery
• Local or general anesthesia
• No heart-lung bypass machine required
• Catheter is placed transarterially
• 1 to 3 hour procedure (typical)
• 3 to 5 day hospital stay (typical)
• Approximately 1 week recovery
Note: SAVR patients who undergo open-heart surgery typically have a longer
hospital stay and 6-8 week recovery period.
EACTS, ESC and EAPCI Position Statement
on TAVI Patient Selection
• Calcified pure or predominant AS
• Severe AS with symptoms
• Patients at high-risk or with contraindications for SAVR
• Assessment for TAVI contraindications
Vahanian A. Eur Heart J 2008;29:1463-1470.
EACTS, ESC and EAPCI Position Statement
TAVI Patient Selection – Contraindications
• Aortic annulus < 18 or > 25 mm for balloon-expandable
and < 20 or > 27 for self-expandable devices
• Bicuspid valves because of the risk of incomplete
deployment of the prosthesis
• Presence of asymmetric heavy valvular calcification,
which may compress the coronary arteries during TAVI
• Aortic root dimension > 45 mm at the aorto-tubular
junction for self-expandable prostheses
• Presence of apical LV thrombus
Vahanian A. Eur Heart J 2008;29:1463-1470.
Note: With 31mm valve, CoreValve® annulus ranges is 20-29mm.
CE-Mark Approved TAVI Products for the
Treatment of Severe AS
Company
Medtronic
Edwards Lifesciences
Product
CoreValve®
SAPIEN™
2007
2007
Self-expandable
Balloon-expandable
Nitinol
Stainless Steel / Cobalt
Chromium
Porcine
Bovine
18Fr
22-26Fr and 18-19.5Fr
20 mm–29 mm
(Transfemoral, Subclavian,
& Direct Aortic)
Transfemoral: 18 mm–25
mm
Transapical: 18 mm–27 mm
CE approval
Expansion
Frame
Valve Material
Sheath Size
Aortic
Annulus
Over 20,000 TAVI procedures have been
performed since 2007
TAVI Outcome Results
1. PARTNER (SAPIEN™) Cohort B Clinical Trial Results
2. CoreValve® 18 Fr Safety and Effectiveness (SE)
Study; Australian and European Registry Study
Results
3. CoreValve® Quality of Life Study
4. CoreValve® Safety and Durability Studies
PARTNER Trial Purpose
• Assess the safety and effectiveness
of TAVI (n=179) compared with standard therapy
(n=179) in patients with severe AS and cardiac
symptoms, who can not undergo surgery (“inoperable”)
Leon MB. N Engl J Med 2010;363:1597-1607.
PARTNER: All Cause Mortality
All-cause mortality (%)
100
Standard Rx
TAVI
P < 0.001
Hazard Ratio 0.55
45% reduction in
all cause mortality
with TAVI
80
60
50.7%
40
30.7%
20
0
0
6
12
18
24
Months
Numbers at Risk
TAVI
179
138
122
67
26
Standard Rx
179
121
83
41
12
Leon MB. N Engl J Med 2010;363:1597-1607.
PARTNER: Cardiovascular Mortality
Cardiovascular mortality (%)
100
Standard Rx
TAVI
P < 0.001
Hazard Ratio 0.39
80
60
61% reduction in
all CV mortality
with TAVI
44.6%
40
20
20.5%
0
0
6
12
18
24
Months
Numbers at Risk
TAVI
179
138
122
67
26
Standard Rx
179
121
83
41
12
Leon MB. N Engl J Med 2010;363:1597-1607.
PARTNER: Mortality or Repeat Hospitalization
All-cause mortality or
repeat hospitalization (%)
100
Standard Rx
TAVI
80
60
P < 0.001
Hazard Ratio 0.46
54% reduction in mortality
or repeat hospitalization
with TAVI
70.4%
(44.1% hospitalization only)
42.5%
(22.3% hospitalization only)
40
20
0
0
6
12
18
24
Months
Numbers at Risk
TAVI
179
117
102
56
22
Standard Rx
179
86
49
23
4
Leon MB. N Engl J Med 2010;363:1597-1607.
PARTNER: NYHA Class Over Time
NYHA Class
I
P=0.68
II
III
P<0.001
IV
Dead
P<0.001
P<0.001
100%
Patients (%)
80%
60%
40%
20%
0%
TAVI
Standard
TAVI
Baseline
Leon MB. N Engl J Med 2010;363:1597-1607.
Standard
30 Days
TAVI
Standard
6 Months
TAVI
Standard
1 Year
MedtronicSponsored Studies
CoreValve® System Clinical Experience
Study
Study Size
Number of Centers
Follow-up
Status
Australia-New
Zealand Registry1
362
10
12 months
Enrolling
REDO Study2
18
3
12 months
Complete
1015
44
30 days
Enrollment Complete
Study Size
Number of Centers
Follow-up
Status
Italian Registry4
772
14
3 year
Enrolling
Belgian Registry5
297
9
3 year
Enrolling
Spanish Registry6
108
3
6 months
Enrolling
France II Registry7
785
33
6 months
Enrolling
UK Registry8
452
25
2 years
Enrolling
German Registry9
588
22
30 days
Enrolling
Brazilian Registry10
198
12
Procedural
Enrolling
ADVANCE Study3
Independent
Studies
Study
1. Meredith I.T. 12 Month Results from ANZ CoreValve TAV Study. Presented at: TCT 2011. 2. Müller R. Short- And Long-term Safety & Effectiveness of TAVI in a Failing
Surgical Aortic Bioprosthesis. Presented at: TCT 2011. 3. Medtronic CoreValve® ADVANCE Study. http://clinicaltrials.gov/ct2/results?term=NCT01074658. Accessed
7/13/11. 4. Petronio AS. Italian Registry. Presented at: EuroPCR 2010. 5. Bosmans J. Belgian TAVI Registry. Presented at: London Valves 2011. 6. Avanzas P, et al. Rev
Esp Cardiol. 2010;63:141-148. 7. Cribier A. FRANCE II Multicenter TAVR Registry. Presented at: TCT 2011. 8. Moat N.E., et al. JACC. 2011; 58. 9. Zahn R., et al.
European Heart Journal. 2011; 32:198-204. 10. Brito F.S. Brazilian Registry. Presented at TCT 2011.
Baseline Patient Characteristics
ANZ
Registry1
Italian
Registry2
UK
Registry3
Belgian
Registry4
Brazilian
Registry5
Spanish
Registry6
362
772
452
297
198
108
Age, years
84 ± 6
82 ± 6
81.3 ± 7.4
83 ± 6
82.2
78.6 ± 6.7
Female, %
46
56
48
54
55
54.6
Logistic EuroSCORE,
%
18 ± 11
22.9 ± 13.5
18.1
24 ± 15
21.4
16 ± 13.9
NYHA class III and IV,
%
78
70.6
73.9
80
83.5
58.4
LVEF, %
58 ± 11
51 ± 13
–
57 ± 15
–
–
Mean pressure
gradient, mm Hg
51 ± 15
52 ± 17
–
47 ± 16
–
55 ± 14.3
Aortic valve area, cm2
0.7 ± 0.2
–
–
0.63 ± 0.14
–
0.63 ± 0.2
N
ANZ=Australia-New Zealand; EuroSCORE=European System for Cardiac Operative Risk Evaluation; LVEF=left ventricular ejection fraction; NYHA=New York Heart Association.
1. Meredith I.T. 12 Month Results from ANZ CoreValve TAV Study. Presented at: TCT 2011. 2. Petronio AS. Italian Registry. Presented at: EuroPCR 2010. 3. Moat N.E., et al.
JACC. 2011;58. 4. Bosmans J. Belgian TAVI Registry. Presented at: London Valves 2011. 5. Brito F.S. Brazilian Registry. Presented at TCT 2011. 6. Avanzas P, et al. Rev Esp
Cardiol. 2010;63:141-148.
Meta-analysis of Patient Characteristics
• N=2156 patients analyzed from 7 national registries
– Australia-New Zealand, Belgium, France, Germany, Italy, Spain, and
the United Kingdom
• Mean age of the population: 81.6 years
• Male: 47%
• New York Heart Association class III and IV: 77%
• Mean Logistic EuroSCORE: 21.3% (range, 16.0-24.7)
• Mean aortic valve area: 0.63 cm2
• Mean gradient: 49.7 mm Hg
EuroSCORE=European System for Cardiac Operative Risk Evaluation.
1. Ruiz CE, et al. Weighted meta-analysis of early and late clinical outcomes after CoreValve ® – TAVI in seven national registries. Presented at: EuroPCR;
May 17-20, 2011; Paris, France. Analysis sponsored by Medtronic, Inc.
Procedural Success* in
CoreValve® System Studies
1. Buellesfeld L, et al. J Am Coll Cardiol. 2011;57:1650-1657.
CoreValve® Haemodynamic Improvement
Consistent Improvement Across Studies at 30 Days
1. Meredith I.T. 12 Month Results from ANZ CoreValve TAV Study. Presented at: TCT 2011. 2. Avanzas P, et al. Rev Esp Cardiol. 2010;63:141-148. 3.
Petronio AS. Italian Registry. Presented at: EuroPCR 2010.
CoreValve® Hemodynamic Performance at 2
Years
1. Buellesfeld L, et al. J Am Coll Cardiol. 2011;57:1650-1657.
CoreValve® Functional Improvement at 2
Years
NYHA=New York Heart Association.
1. Gerckens U. Stable durability and effectiveness at 2 years with CoreValve ® transcatheter aortic valve. Presented at: EuroPCR; May 17-20, 2011; Paris, France.
CoreValve® Aortic Regurgitation at 2 Years
1. Gerckens U. Stable durability and effectiveness at 2 years with CoreValve ® transcatheter aortic valve. Presented at: EuroPCR; May 17-20, 2011; Paris, France.
CoreValve® 1-Year Survival Rates Across
Clinical Trials
Survival rates reported are based on Kaplan-Meier analysis.
1. Meredith I.T. 12 Month Results from ANZ CoreValve TAV Study. Presented at: TCT 2011. 2. Moat N.E., et al. JACC. 2011;58. 3. Petronio AS. Italian
Registry. Presented at: EuroPCR 2010. 4. Bosmans J. Belgian TAVI Registry. Presented at: London Valves 2011. 5. Ruiz C.E. Weighted meta-analysis
of CoreValve® Outcomes.Presented at: EuroPCR 2011 (analysis sponsored by Medtronic, Inc.).
CoreValve® 2-Year and 3-Year Survival Rates
Survival rates reported are based on Kaplan-Meier analysis.
1. Bosmans J. Belgian TAVI Registry. Presented at: London Valves 2011. 2. Moat N.E., et al. JACC. 2011;58. 3. Tamburino C. Italian CoreValve Registry.
Presented at TCT 2011,
Prospective TAVI Quality of Life Study
100%
•
87 CoreValve® Patients
80 Years; 80 survived to 6
months follow-up:
–
–
–
>
6 Months after TAVI
90%
80%
70%
Average scores of all 8 health
components significantly
improved after TAVI
60%
Both physical and mental
component scores improved
significantly
30%
Brain natriuretic peptide levels
also improved significantly
Before TAVI
50%
40%
20%
10%
0%
Physical
Functioning
RolePhysical
Bodily
Pain
Vitality
General
Health
RoleSocial
Emotional
Functioning
Short Form 36-Item Health Survey
Bekeredijian R. Am J Cardiol 2010;106(12):1777-1781.
Mental
Health
Potential Complications
Implantation of the transcatheter valve has been associated with
complications.
In TAVI clinical studies, patients experienced additional adverse
events during or after the procedure which included but were not
limited to:
– Death including all cause and cardiovascular mortality
– Myocardial infarction including coronary occlusion
– Stroke including permanent stroke and TIA
– Re-intervention including SAVR and repeat valve placement
– Aortic regurgitation
– Permanent pacemaker placement
– Pericardial tamponade (wire perforations)
– Vascular and bleeding complications
– Valve migration or fracture
Items are listed in order of severity. For complete list of adverse
events, warnings and contraindications reference CoreValve® IFU.
TAVI Future
• Continued Clinical Evaluation in Current Patient Population
– TAVI will continue to be evaluated in prospective trials for
severe symptomatic AS patients at high or extreme risk for
SAVR
• Clinical Evaluations in New Patient Populations
– TAVI will be evaluated in a prospective randomized-controlled
trial for severe symptomatic AS patients compared to SAVR
• Product and Surgery Improvements
– TAVI outcomes could improve as refinements are made to
devices and implantation techniques, and implantation
experience grows
TAVI Patient Selection
Involves multi-disciplinary consultation between cardiologists,
surgeons, imaging specialists, anesthesiologists, and others as
needed.
Steps:
1. Confirm severity of AS
2. Evaluate symptoms
3. Analyze risk of surgery
4. Assess current life expectancy and quality of life
5. Identify exclusion based on TAVI contraindications
Vahanian A. Eur Heart J 2008;29:1463-1470.
Case Study Slide
Case Study Slide
Outcomes At My Center
• Hospital Length of Stay:
• Procedural Success Rate:
Other Complications or Adverse Events:
• (enter here)
Conclusions or Next Steps – From Physician
Presenter
Potential TAVI Patients
Patients to Consider for TAVI Referral
– Patient has severe, symptomatic aortic stenosis
– Patient is high risk for surgical aortic valve replacement or is
inoperable
– Patient was previously rejected for surgical aortic valve
replacement
Patients NOT Recommended for TAVI Referral
–
–
–
–
Severe ventricular dysfunction (LVEF < 20%)
End-stage renal disease requiring chronic dialysis
Life expectancy less than 12 months
Mitral regurgitation greater than grade 2
CoreValve® is a registered trademark of Medtronic CV Luxembourg S.a.r.l.
Edwards SAPIEN™ is a registered trademark of Edwards Lifesciences Corporation.