Trans-Catheter Therapy for
Valvular Heart Disease Sanjay K. Gandhi
Section on Cardiology
Disclosures
• Investigator – Medtronic
Objectives
• Review clinical challenges in treating high risk patients with aortic stenosis
• Discuss the development of trans-catheter aortic valve replacement(TAVR) and potential indications for its use.
• Review the surgical treatment options for mitral regurgitation
• Discuss the development of trans-catheter treatment for mitral regurgitation
Adult Valvular Heart Disease:
The Scope of the Problem
New York state
Supino PG, et al. Adv Cardiol. 2002;391-6.
Adult Valvular Heart Disease:
The Scope of the Problem
• Mitral Stenosis
• Mitral Regurgitation
• Aortic Stenosis
• Aortic Regurgitation
Adult Valvular Heart Disease:
The Scope of the Problem
• Mitral Stenosis
• Mitral Regurgitation
• Aortic Stenosis
• Aortic Regurgitation
Valvular Heart Disease:
Aortic Stenosis
• Most common cardiac valvular lesion in US
• With progressive narrowing of the valve orifice, adaptive and maladaptive concentric left ventricular hypertophy develops in response to the pressure overload on the ventricle.
• Eventually leads to decreased coronary flow, diastolic dysfunction, and systolic dysfunction
• Symptomatic development of syncope, angina, and heart failure conveys an extremely poor prognosis
• Surgical valve replacement has historically been the only effective therapy
Wake Forest School of Medicine
• Mortality difference for people with
symptomatic AS treated with Aortic
Valve Replacement (AVR) versus
those not undergoing this procedure
is one of the most striking in
medicine
• AVR can be withheld in such
patients only when compelling
contraindications exist
Symptomatic AS
Treatment: Surgical AVR
1Schwartz et al. Circulation 1982; 66: 1105-10.
AVR
No AVR
Standard of care for
Severe AS
Bioprosthetic Valves
Mechanical Valves
Valvular Heart Disease: Aortic Stenosis Surgical valve replacement has been associated with
higher surgical morbidity and mortality in certain high risk
patient subsets
• Elderly patients with comorbidities
• Severely reduced left ventricular systolic function
• Severe COPD
Surgical mortality in general is 2-8%; it may be in excess of
20% in certain high risk populations. (Eltchaninoff H, et al, J
Interven Cardiol 2003;16:515-521. Florath I, et al, Ann Thorac Surg
2003;76:75-83. Connoly H, et al, Circulation 2000;1940-1946)
Almost one-third of patients with severe valvular lesions
who may benefit from interventions are declined for
operative treatment because of high risk status (Iung B, et al,
Eur Heart J 2003;24:1231-43).
Valvular Heart Disease: Aortic Stenosis
Treatment of Elderly Patients
Sundt M, et al, Circulation. 2000;102[suppl III]:III-70-III-74.
Valvular Heart Disease: Aortic Stenosis
Treatment of Elderly Patients
Florath I, et al. Ann Thorac Surg 2003;76:75-78
Valvular Heart Disease: Aortic Stenosis
Severely Reduced Left Ventricular Function
Powell E, et al. Arch Intern Med. 2000;160:1337-1341
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Severe Symptomatic AS: Percent of patients treated
EU US
Untreated
Surgery
Pellikka2 Charlson1 Lung3 Bouma4
59% 68% 70%
40%
41% 32% 30% 60%
Multiple studies quantify the extent of under-treatment
1Charlson E, Legedza AT, Hamel MB. J Heart Valve Dis 2006;15: 312-321.
3Lung B, Baron G, Butchart E, et al. Eur Heart J 2003; 24: 1231-1243.
4Bouma BJ, van den Brink, et al. Heart 1999; 82: 143-48.
2Pellika PA, Sarano ME, et al. Circulation 2005; 111: 3290-95.
Is Surgical AVR Underutilized?
Old age Co-morbidities Frailty Prior cardiac surgery Dementiae
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AS Challenges-Case Study
EF 35%
Valvular Heart Disease: Aortic
Stenosis
• Surgical valve replacement significantly improves long
term outcome and decreases mortality in symptomatic
patients with severe aortic stenosis.
• But what options are available for patients who are
deemed “too high risk” for surgery?
• ? Balloon Valvuloplasty?
36 to 80% restenosis in one year
Inpatient mortality up to 13%
High rate of stroke, vascular complications, and
aortic regurgitation
Aortic Stenosis and Treatment
Options for “Inoperable” Patients • Back to the ground rules for Interventional Cardiology:
Opening blockages is good – stents are even better.
• Why not put a prosthetic valve inside a stent and
deliver it with it a catheter?
Eltchaninoff H et al, J Interven Cardiol 2003;16:515-521
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Percutaneous Treatment of AS
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History of Percutaneous Valve Implants
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Percutaneous Treatment of AS
Percutaneous Heart Valves(PHV) for
Aortic Stenosis
Cribier A et al, J Am Coll Cardiol 2004;43:698-703
PHV for Aortic Stenosis:
The Cribier-Edwards Valve • Series of first six patients(implantation attempted April,
2002 – August, 2003)
• 5 men, 1 women; mean age 75(57-91)
• All had been denied surgical valve repair
• All with severe CHF; 3 with cardiogenic shock
• All with aortic valve area < 0.6 cm2
• Only one had significant concurrent coronary disease
PHV for Aortic Stenosis:
The Cribier-Edwards Valve
Age M/F Comorbidities
57 M Severe PAD, lung CA, silicosis, chronic pancreatitis
80 M Severe AR, CVA, ESRD, asbestosis, prostate CA
91 M Cachexia, bedridden>1 month
63 M Rectal Adenocarcinoma, Severe COPD, ESRD
80 F Metastatic breast CA, COPD, Kyphoscoliosis
77 M Stroke, Porcelain aorta, ESRD
Patients 2 and 6 developed hemodynamic collapse during balloon pre-dilation requiring “transient external massage and adrenalin.”
Cribier A, et al. J Am Coll Cardiol 2004;43:698-703
•PHV for Aortic Stenosis:
The Cribier-Edwards Valve
• 5 of 6 patients survived the procedure.
• In patients who survived the procedure, aortic
valve area increased from 0.49 + 0.08 to 1.66 +
0.13 cm2 (p < 0.04)
• Mean valve gradient decreased from 38 + 11 to
5.6 + 3.4 mmHg
• 3 patients died of non-cardiac causes
• 2 patients stable at 8 week followup
Cribier A, et al. J Am Coll Cardiol 2004;43:698-703
PHV for Aortic Stenosis:
The Cribier-Edwards Valve
• Followup in first 36 patients attempted implant reported
• Mean age 80 + 7 (62-91)
• 28% patients with EF < 0.30
• 76% with CAD
• 38% with ESRD
• 41% with severe lung disease
• 38% with pulmonary hypertension
• 27% with PAD
• 27% with at least moderate regurgitation
Cribier A, et al. J Am Coll Cardiol 2006;47:1214-23.
The Cribier-Edwards Valve • 36 patients enrolled; Implantation attempted in 33; 27 successful
implantations; 21 patients survived to 30 day followup
• 11 patients alive at nine month followup(9-26 months)
Cribier A, et al. 2006;47:1214-23.
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Stent Valve Options for Percutaneous Treatment of AS
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Hemodynamic Characteristics of Stent Valves
Wake Forest School of Medicine Coeytaux R R et al. Ann Intern Med
2010;153:314-324
Percutaneous Treatment of AS: Evidence Base
One large RCT of
TAVR vs AVR
PARTNER
(CoreValve
trial pending)
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Edwards SAPIEN Medtronic CoreValve
CE Mark Nov 2007 April 2007
Aortic Stent Valve Available OUS-Clinical Trials US
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TAVR Worldwide Experience
Over 30,000 implants in 34 countries as of July 2011
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Sapien Stent Valve
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Percutaneous Treatment of AS: PARTNER Trial
AVR mortality
> 10%
AVR mortality
> 50%
Severe symptomatic AS (AVA <0.8cm2; peak AVG >60, mean AVG > 40
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PARTNER Trial: Inoperable Cohort (cohort B)
Leon et al. NEJM 2011; 363:1597-1607.
50% reduction in mortality
at 12 months with TAVR
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PARTNER Trial: Inoperable Cohort (cohort B)
Leon et al. NEJM 2011; 363:1597-1607.
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PARTNER Trial: High Risk Patients (cohort A)
Smith et al. NEJM 2011; 364:2187-98.
TAVR and AVR outcomes
similar at 12 months
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PARTNER Trial: High Risk Patients (cohort A)
Smith et al. NEJM 2011; 364:2187-98.
PARTNER: 2 Year Outcomes:
Surgery vs TAVR
Kodali, S. et al. NEJM, 3/26/21012(epub)
PARTNER: 2 Year Outcomes: Surgery vs TAVR
Kodali, S. et al. NEJM, 3/26/21012(epub)
PARTNER: 2 Year Outcomes: Surgery vs TAVR
Kodali, S. et al. NEJM, 3/26/21012(epub)
PARTNER: 2 Year Outcomes: Surgery vs TAVR
Kodali, S. et al. NEJM, 3/26/21012(epub)
PARTNER: 2 Year Outcomes:
Inoperable Patients
Makkar, R. et al. NEJM, 3/26/21012(epub)
PARTNER: 2 Year Outcomes:
Inoperable Patients
Makkar, R. et al. NEJM, 3/26/21012(epub)
PARTNER: 2 Year Outcomes:
Inoperable Patients
Makkar, R. et al. NEJM, 3/26/21012(epub)
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CoreValve Stent Valve
Wake Forest School of Medicine Piazza et al Eurointervention 2008; 4:242-9
Procedural and 30-day outcomes following transcatheter aortic valve implantation using the
third generation (18 Fr) corevalve revalving system: results from the multicentre, expanded
evaluation registry 1-year following CE mark approval.
Aortic regurgitation
CoreValve post CE Mark Registry
AVGradient
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CoreValve US Pivotal Trial
(Inclusion and exclusion criteria same
as PARTNER Trial)
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CoreValve TAVR Trial
Inclusion Criteria
Severe symptomatic AS - AVA < 0.8mm2 and peak
AVG >60 mmHg or mean AVG > 40 mmHg
High Risk-est. 30 day mortality >15%, <50%
Extreme Risk-not surgical candidate (est. 30 day
mortality >50%)
Both expected to survive at least one year
Vascular access, annulus, sinus of Valsalva,
and ascending aorta size appropriate
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CoreValve TAVR Trial
Principal Exclusion Criteria
Untreated sig CAD
BMS within 30 days; DES within 6 months
EF < 20%
eGFR <20cc /min
GIB within 3 months
CVA within 6 months
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CoreValve-Case Study Balloon Aortic Valvuloplasty (BAV)
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CoreValve-Case Study Final Result
Before TAVI After TAVI
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CoreValve TAVR Trial
Evaluations
Echo
Cardiology, CTS evaluations
PFTs
Cardiac cath within 1 year
Cardiac CT
CTA chest, abdomen, and pelvis
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TAVR Challenges
Durability
Vascular access complications
Stroke risk
Pacemaker (CoreValve)
Aortic regurgitation
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Vancouver Experience of TAVR Durability (SAPIEN)
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Femoral artery 6-9mm (18-27 Fr)
“Percutaneous” treatment AS
Requires very large catheter sizes
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“Percutaneous” treatment AS
Requires very large catheter sizes
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Access site needs to be carefully evaluated
(largest source of peri-procedural complications)
Avulsion of external iliac artery
Dissection of left subclavian artery
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Alternatives to femoral access
Trans-apical (SAPIEN)
Subclavian Iliac conduit
Direct aortic
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Peri-procedural Stroke
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TAVI in lower risk patients-it’s coming
TAVR Summary
Serruys, PW. PCR 2010
Breakthrough technology and treatment
Downsizing delivery systems under development
should reduce complications
Durability to be determined
Training standards; who will implant is an issue
Ultimate role in treatment of all pts with severe
AS remains to be determined
Mitral Regurgitation
• Degenerative/Myxomatous
• Rheumatic
• Infectious
• Ischemic/Functional
Mitral Regurgitation:
Surgical Treatment
Surgical Replacement
Surgical Repair
Mitral Regurgitation:
Surgical Treatment
Surgical Replacement
Surgical Repair
Mitral Regurgitation:
Surgical Treatment
Surgical Replacement
Surgical Repair:
Annuloplasty
Resection with Annuloplasty
Shortening of the Papillary Muscle
Chordal Replacement and Shortening
Papillary Muscle Sling
Surgical Relocation of the Posterior Papillary Muscle
Alfieri Edge-to-Edge Repair
Alfieri Edge-to-Edge Repair for
Mitral Regurgitation
Maisano F, et al. European J of Cardiothorac Surg. 1998;13:240-246
Alfieri Edge-to-Edge Repair
Maisano F, et al. European J of Cardiothorac Surg. 1998;13:240-246
Freedom from reoperation
N = 121 113 had concurrent annuloplasty 33 required additional reconstruction 68% Degenerative 15% Endocarditis 12% Rheumatic 5% Ischemic
Survival
Alfieri Edge-to-Edge Repair
With or Without Annuloplasty
Kherani A, et al. Ann Thorac Surg 2004;78:73-76.
Alfieri Edge-to-Edge Repair
The Basis For a Percutaneous Option?
Feldman T, et al. J Am Coll Cardiol 2005;46:2134-40
Procedure
A catheter is introduced through the patient’s skin in the groin area, and is guided from the femoral vein to the mitral valve.
Then, a smaller delivery catheter that holds the MitraClip device is introduced through the first catheter so that the Clip can be guided into place and attached to the leaflets of the mitral valve.
Then, a smaller delivery catheter that holds the MitraClip device is introduced through the first catheter so that the Clip can be guided into place and attached to the leaflets of the mitral valve.
MitraClip attached to the mitral valve leaflets.
Once the Clip is securely attached and MR is reduced, it is deployed and the catheters are removed.
EVEREST II: Trial Design
Feldman, T, et al. N Enl J Med 2011;364:1395-406.
EVEREST II: Baseline Data
Feldman, T, et al. N Enl J Med 2011;364:1395-406.
EVEREST II: Outcomes
Feldman, T, et al. N Enl J Med 2011;364:1395-406.
EVEREST II: Outcomes
Feldman, T, et al. N Enl J Med 2011;364:1395-406.
EVEREST II: Outcomes
Feldman, T, et al. N Enl J Med 2011;364:1395-406.
Conclusions
• TAVR is an emerging treatment strategy for
patients with critical aortic stenosis who are
deemed “inoperable.”
• Studies are ongoing to determine if TAVR may be
an acceptable alternative treatment strategy for
critical aortic stenosis patients deemed “high risk”
for surgery.
• Trans-catheter strategies are being developed for
treatment of patients with mitral regurgitation.