transcatheter aortic valve therapies mark russo assistant professor of surgery co-director, center...
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Transcatheter Aortic Valve Therapies
Mark RussoAssistant Professor of Surgery
Co-Director, Center for Aortic Diseases
SUMMARY POINTS
• This is NOT experimental therapy– 45,000 implants worldwide– In Germany, 20-25% of isolated AVRs are TAVI
• Indications– Symptomatic, severe AS deemed inoperable
• Shown to be clinically effective in a well-selected patients– RCT demonstrated an absolute 20% survival benefit– 40%+ of OMM pts are dead at 6 months
ADVANCES IN THE RX OF STRUCTURAL HEART DISEASE
1951 - Cardiopulmonary Bypass
1977- Percutaneous Coronary Intervention
2011 - Transcatheter Valves
CHANGING TREATMENT PARADIGM
• Treatment options: Significant unmet need
• Delivery of care: “Heart team” concept
• Tools available: Catalyze other percutaneous technologies for treatment of structure heart disease
The Problem of Aortic Stenosis
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 AS] should be performed promptly once even…minor symptoms occur”1
1 Lester SJ, Heilbron B, Gin K, Dodek A, Jue J. The natural history and rate of progression of aortic stenosis. Chest. 1998;113:1109-1114.
Helping to Solve a Grave Problem
Latent Period(Increasing Obstruction,Myocardial Overload)
Surv
ival
, %
100
80
60
40
20
0 40 50 60 70 80Age, y
Onset Severe Symptoms
AnginaSyncope
Average Survival, y
Failure
0 2 4 6
THE BURDEN OF AORTIC STENOSIS
• In the US:– AS: 1,500,000– Severe AS: 500,000– Severe, symptomatic AS: 250,000– AVRs performed annually: 85,000
>150,000 untreated AS patients
At least 43-74% of patients with severe aortic stenosis (AS) do not have an AVR
Addressing a Serious Unmet Need
1999 2006 2006 20092005 2010
Pat
ient
s, %
Aortic Valve Replacement (AVR) No AVR
2009
Dismal Outcomes with Severe Inoperable AS
5-Year Survival
Surv
ival
, %
* National Institutes of Health. National Cancer Institute. Surveillance Epidemiology and End Results. Cancer Stat Fact Sheets. http://seer.cancer.gov/statfacts/. Accessed November 16, 2010.
† Using constant hazard ratio. Data on file, Edwards Lifesciences LLC. Analysis courtesy of Murat Tuczu.
†**
* * *
Dismal Outcomes with Severe Inoperable AS
5-Year Survival
Surv
ival
, %
* National Institutes of Health. National Cancer Institute. Surveillance Epidemiology and End Results. Cancer Stat Fact Sheets. http://seer.cancer.gov/statfacts/. Accessed November 16, 2010.
† Using constant hazard ratio. Data on file, Edwards Lifesciences LLC. Analysis courtesy of Murat Tuczu.
†**
* * *
The predicted survival of inoperable patients with severe AS who are treated with standard non-surgical therapy is lower than with certain metastatic cancers.
– Survival after onset of symptoms is 50% at 2 years and 20% at 5 years1
1 Lester SJ, Heilbron B, Gin K, Dodek A, Jue J. The natural history and rate of progression of aortic stenosis. Chest. 1998;113:1109-1114.
Latent Period(Increasing Obstruction,Myocardial Overload)
Surv
ival
, %
100
80
60
40
20
0 40 50 60 70 80
Age, y
Onset Severe Symptoms
Angina
Syncope
Average Survival, y
Failure
0 2 4 6
TAVI for Who?
What is the Data to Support Use?
INDICATIONS
• Severe Symptomatic AS– Aortic Velocity > 40 m/sec– Mean Gradient > 4 mmHg– Valve Area < 1.0 cm2
• Inoperable – determined by a surgeon– Mortality > 15%– Death or serious, irreversible morbidity > 50%– STS score > 8-10
The PARTNER Trial Protocol
Not in Study
AssessmentTransfemoral Access
Yes No
Primary Endpoint: All-Cause Mortality OverLength of Trial (Superiority)
Co-Primary Endpoint: Composite of All-Cause Mortality and Repeat Hospitalization (Superiority)
TFTAVR
(n = 179)
Standard Therapy(Control)(n = 179)
vs
1:1 Randomization
AssessmentTransfemoral Access
TF(n = 492)
TA(n = 207)
Yes No
Primary Endpoint: All-Cause Mortality (1 yr)(Non-inferiority)
TFTAVR
(n = 244)
AVR(Control)(n = 248)
vs
1:1 Randomization
TATAVR
(n = 104)
AVR(Control)(n = 103)
vs
1:1 Randomization
Cohort ACohort A(n = 699)
Cohort B(n = 358)
2 CohortsIndividually Powered
(N = 1,057)
TA, transapical; TF, transfemoral.
AssessmentOperability
NoYes
Severe Symptomatic Native Aortic Valve Stenosis
PARTNER COHORT B
Source: NEJM, 2001
• Mean Age: early 80s• Mean STS Score: 11• Mean EuroScore: 12• NYSA III/IV - 90%• s/p CABG - 40%• COPD - 45%
– O2 - 20%
• PHTN - 40%• Radiation - 10%
• Porcelain Aorta
PARTNER COHORT B
Source: NEJM, 2001
PARTNER TRIAL – COHORT B20% Reduction in Mortality
0 6 12 18 24
∆ at 1 yr = 20.0%NNT = 5.0 pts
All-C
ause
Mor
talit
y, %
50.7%
30.7%HR [95% CI] =
0.51 [0.38, 0.68]P (log rank) < .0001
Numbers at Risk
Edwards SAPIEN THV 179 138 124 103 60
Standard Therapy 179 121 85 56 24
Months
0
20
40
60
80
100 Edwards SAPIEN THV
Standard Therapy
Source: NEJM, 2001
PARTNER TRIAL – COHORT B20% Reduction in Mortality
0 6 12 18 24
∆ at 1 yr = 20.0%NNT = 5.0 pts
All-C
ause
Mor
talit
y, %
50.7%
30.7%HR [95% CI] =
0.51 [0.38, 0.68]P (log rank) < .0001
Numbers at Risk
Edwards SAPIEN THV 179 138 124 103 60
Standard Therapy 179 121 85 56 24
Months
0
20
40
60
80
100 Edwards SAPIEN THV
Standard Therapy
20% absolute reduction in mortality at
1 year
Source: NEJM, 2001
Paravalvular Leaks Over Time
PARTNER TRIAL – COHORT B
NEJM, 2011Source: NEJM, 2001
PARTNER TRIAL– COHORT BQuality of Life Benefits
60
40
20
0
80
100
0 4 6 8 10 122
Standard Therapy
Edwards SAPIEN THV
∆ = 13.9P < .001
∆ = 24.5P < .001
KCCQ
Sco
re (M
ean)
MCID, minimum clinically important difference.
MCID = 5 points
Months
Improvement in quality of life
CONCLUSIONS – PARTNER B
• Standard therapy (including BAV in 83.8% of pts) did not alter the dismal natural history of AS; all-cause and cardiovascular mortality at 1 year was 50.7% and 44.6% respectively
• Transfemoral balloon-expandable TAVI, despite limited operator experience and an early version of the system, was associated with acceptable 30-day survival (5% after randomization in the intention-to-treat population)
Inoperability
• Operative mortality > 15% • Operative severe morbidity or death > 50%• STS score > 8• Previous cardiac surgery – multiple, s/p CABG• Home O2• PHTN• Radiation• Porcelain Aorta• Frailty
Fried Frailty IndexFried Phenotype of Frailty
Weight Loss (unintentional) > 10 lb in previous year
Grip strength Lowest 20% by sex/BMI
Exhaustion Self-report (CES-D depression scale)
Walk time, 15 feet Lowest 20% by sex/height
Low activity Males < 383 kcal/weekFemales < 270 kcal/week
Frailty: ≥ 3 criteriaIntermediate/prefrail: 1 or 2 criteria
Fried LP, et al. J Gerontol A Biol Sci Med Sci. 2001;56:M146-M156.
Approaches
Approaches
• Transfemoral• Illiac Conduit• Transapical• Subclavian• Transaortic
TAVI - Transfemoral
TAVI - Transapical
Anterior Thoracotomy
TAVI - Transapical
Source: theheart.org
TAVI – LEFT SUBCLAVIAN APPROACH
TAVI-Transaortic