מחלות המסתם האאורטלי
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23.10.2013
3 – D Aortic Valve
Aortic StenosisIncidence
• Most frequent valvular heart disease in Europe and the U.S.
• Most frequent heart disease after hypertension and CAD (calcific AS)
• Incidence in the population of advanced age about 2 - 9%
• Aortic valve surgery is the only established treatment
Single Native Valve Disease
Euro Heart Survey on Valvular Heart Disease
0%
20%
40%
60%
80%
100%
Total Northern Eastern Western Medit.
MS
MR
AR
AS
Courtesy of Alec Vahanian
Courtesy of Alec Vahanian
Leonardo Da Vinci; 15th Leonardo Da Vinci; 15th centurycentury
Aortic ValveHistory
Otto CM, O‘Brien K. Heart 2001;85:601-2
CalcificationCalcification
Mohler ER et al. Circulation 2001;103:1522-8
OssificationOssification
BackgroundMedical Therapy for Aortic Stenosis
• Mineralization close to areas of inflammation• Formation of mature lamellar bone
Aortic Stenosis Common features with atherosclerosis
Newby, D E et al. Heart 2006;92:729-734
Rajamannan, N. M. et al. N Engl J Med 2003;349:717-718
Aortic Stenosis Cardiovascular Features of a Patient With
Familial Hypercholesterolemia
Atheromatous plaques
Clotted Circumflex artery
Morbidity associated with Aortic Sclerosis
and Stenosis
Agmon Y et al. J Am Coll Cardiol 2001;38:827-34
Aortic SclerosisIncidence
1.0
0.8
0.6
0.4
0.2
0.0
50 60 70 80 90
Age (yrs)
Men
Women
Pro
bab
ilit
y o
f aort
ic v
alv
e s
cle
rosis
Aortic SclerosisAssociation with Mortality
Patients presenting to the Emergency Room with Chest pain
Chandra HR et al. J Am Coll Cardiol 2004;43:169-175
Moderate-severe Aortic sclerosis (n=54)
Mild Aortic sclerosis (n=149)
No Aortic sclerosis (n=212)
0 40 80 120 160 200 240 280 320 360
100
80
60
40
20
0P < 0.002
Even
t-fr
ee s
urv
ival (%
)
Days
Aortic SclerosisAssociation with Morbidity
Chandra HR et al. J Am Coll Cardiol;43:169-175
0 1 2 3 4
Aortic Sclerosis 1.37 (0.98-1.78) 0.139
Age (years) 1.03 (1.001-1.06) 0.04
Heart Failure 2.15 (1.48-2.82) 0.025
CRP tertiles 2.20 (1.71-2.20) 0.001
MI at admission 2.77 (2.0-3.53) 0.008
CAD 3.23 (2.47-3.99) 0.003
Hazard Ratio (95% CI) p-value
years
increase of both, cardiac and non-cardiac mortality
Surv
ival (%
)
general population
P < 0.005
Rosenhek et al. Eur Heart J 2004;25:199-205
Mortality - Comparison with normal population Mild-to-Moderate AS
100
90
80
70
60
50
40
30
20
10
0
0 1 2 3 4 5 6 7
patients with mild-to-moderate AS
80% increase in mortality!
Aortic Stenosis
Aortic Stenosis a Progressive Disease
Severity of DiseaseMild AS Moderate AS Severe AS
2.5 - 3.0 m/s 2.5 - 3.0 m/s
< 25 mmHg< 25 mmHg
> 1.5 cm2> 1.5 cm2
3.0 - 4.0 m/s3.0 - 4.0 m/s
25 - 50 25 - 50
1.5 - 0.8 cm21.5 - 0.8 cm2
> 4.0 m/s> 4.0 m/s
> 50 mmHg> 50 mmHg
< 0.8 cm2< 0.8 cm2
mean *Gradient
peak *Velocity
ValveArea
* In the presence of normal flow conditions
100
80
60
40
20
0 40 50 60 63 70 80
Surv
ival (%
)
Age (yrs)
Latent period(increasing obstruction,Myocardial overload)
Onset of severe symptoms
angina
Average age of death
2 3 5Average survival (yrs)
Ross, BraunwaldCirculation 1968
syncope
failure
Prognosis of Symptomatic Patients Severe Aortic Stenosis
Cu
mu
lati
ve s
urv
ival (%
)
Time (yrs)2 4 6 8 10
100
80
60
40
20
0P<0.0001
Horstkotte, Loogen. Eur Heart J 1988;9:57-64
Surgery vs. ConservativeSevere Symptomatic Aortic Stenosis
Patients having undergone AVRbecause of severe AS (n=314)
Patients with severe AS who refused surgery (n=35)
Asymptomatic Aortic Stenosis
AV-Vel > 4 m/s
AV-Vel 3-4 m/s
AV-Vel < 3 m/s
Otto CM, et al. Circulation 95:2262, 1997
Even
t-fr
ee S
urv
ival (%
)
0 12 24 36 48 60 months
Rosenhek, R. et al. N Engl J Med 2000;343:611-617
Overall Survival among 126 Patients with Asymptomatic but Severe Aortic Stenosis, as Compared with Age- and Sex-Matched Persons in the General Population
0 1 2 3 4 5
100
90
80
70
60
50
40
30
20
10
0
Patients with Aortic Stenosis
General Population
Wait for Symptoms Strategy
Asymptomatic Severe Aortic Stenosis
P = n.s.
Study
n Mean FU (mths)
Severity of AS
Sudden death (n)
Kelly 1988
51 18 PV 3.5 0
Pellika 1990
113 20 PV 4.0 2
Faggiano 1992
37 24 AVA .85 ± .15
0
Otto 1997
114 30 PV 3.6 ± 0.6
0
Rosenhek 2000
104 27 PV 4.0 1
Incidence of Sudden Death
Asymptomatic Severe Aortic Stenosis
Pellikka 270 65 PV ≥ 4.0 112005
0
1
2
3
4
5
6
7
NYHA INYHA I INYHA I I INYHA IV
NYHA Class
N = 9095
Mortality 3.6%
1997 Preoperative Risk Variables Aortic Valve Replacement
STS Cardiac Surgery Database
OperativeMortality
(%)
0
2
4
6
8
10
12
14
16
ElectiveUrgentEmergent
OperativeMortality
(%)
Urgency
N = 9095
STS U.S. Cardiac Surgery Database
1997 Preoperative Risk Variables Aortic Valve Replacement
Risk of Death on the Waiting ListSevere Aortic Stenosis
• 135 patients• 2 patients had a sudden death before catheterization• 16 deaths (12 of these sudden) on the waiting list (up to 8 mths). Matthews, AW et al. Br Heart J
1974;36:101-103
• 99 patients consecutive prospectively enrolled patients.• Average waiting time: 6 months• 7 deaths on the waiting list
Lund, O et al. Thorac Cardiovasc Surgeon 1996;44:289-295
Mortality on the waiting list 18%/yr
Mortality on the waiting list 14%/yr
Necessity for Risk Stratification
Wait for Symptoms Strategy
Asymptomatic Severe Aortic Stenosis
Aortic Stenosis - etiology
AS: CLINICAL MANIFESTATIONS
• Angina• Syncope• Exertional Dyspnea /
CHF
– GI Bleeding– Atrial Fibrillation– SBE
DIFFERENTIAL DIAGNOSIS OF AORTIC STENOSIS: PHYSICAL FINDINGS
TYPE OF STENOSIS
MAXIMUM MURMUR AND THRILL
AORTIC EJECTION SOUND
AORTIC COMPONENT OF SECOND SOUND
REGURGITANT DIASTOLIC MURMUR ARTERIAL PULSE
Acquired nonrheumatic or rheumatic
Second right sternal border to neck; may be at apex in the aged
Uncommon Decreased or absent Common Delayed upstroke; anacrotic notch; ± small amplitude
Hypertrophic subaortic
Fourth left sternal border to apex (± regurgitant systolic murmur at apex)
Rare Normal or decreased Very rare Brisk upstroke, sometimes bisferiens
Congenital valvular
Second right sternal border to neck (along left sternal border in some infants)
Very common in children, disappearing with decrease in valve mobility with age
Normal or increased in children; decreased with decrease in valve mobility with age
Uncommon in children; not uncommon in adults
Delayed upstroke; anacrotic notch; ± small amplitude
Congenital subvalvular
Discrete: like valvular; tunnel: left sternal border
Rare Not helpful (normal, increased, decreased, or absent)
Almost all
Congenital supravalvular
First right sternal border to neck and sometimes to medial aspect of right arm; occasionally greater in neck than in chest
Rare Normal or decreased Uncommon Rapid upstroke in right carotid, delayed in left carotid; right arm pulse pressure greater than left
From Levinson GE: Aortic stenosis. In Dalen JE, Alpert JS (eds): Valvular Heart Disease. 2nd ed. Boston, Little, Brown and Co, 1987, p 202.
EFFECT OF VARIOUS INTERVENTIONS ON SYSTOLIC MURMURS
INTERVENTIONHYPERTROPHIC OBSTRUCTIVE CARDIOMYOPATHY
AORTIC STENOSIS
MITRAL REGURGITATION
MITRAL VALVE PROLAPSE
Valsalva or
Standing or unchanged
Handgrip or squatting or unchanged
Supine position with legs elevated
or unchanged
Unchanged
Exercise or unchanged
Amyl nitrite
Isoproterenol
= Markedly increased.
Modified from Paraskos JA: Combined valvular disease. In Dalen JE, Alpert JS (eds): Valvular Heart Disease. 2nd ed. Boston, Little, Brown and Co, 1987, p 365.
AS: ECG
AS: CXR
AS: ECHOCARDIOGRAPHY
AS: Pressure measurements
AS: Catheterization
Calcified AOV
LCC
RCC
NCCAOV
LA
LV
R
RV LV
LA
In the middle of calcification
Transission AML to annulus
AO rootLVOT
AS: MANAGEMENT
• Medical
• Surgical
• Valvuloplasty
• PCI
Therapy for AS: previous trials• The association between
TC and progression of native AS (assessed by Doppler) in a community-based study of 156 patients (age 77 ± 12 years; 90 men).
• Thirty-eight patients received statin treatment during follow-up
• Progression of AS is not correlated with TC. Statins are associated with slower progression.
• (Bellamy et al. JACC 2002).
AVR: Surgical Risk
• Operative Mortality:– AVR 4.3%– AVR+CABG 8%– AVR+additional valve 7.4%– AVR+aortic aneurism repair 9.7%
• Risk factors:– NYHA class– LVF– Age– IHD– Arrhythmia– AR
• Cummulative 10 year survival 85%
AS: BALLOON VALVULOPLASTY
• Mortality (Critically ill patients):– Procedure: 3%– 30 day: 14%– 1 year: 45 %
• Serious complications (AR, MI, Perf): 6%
• Restenosis at 6 m: 50%
But could we do better with a percutaneous stented-valve?
Diamond cell configuration
Nitinol: memory shaped/no recoil
Multi-level design incorporates three different areas of radial and hoop strength•Low radial force area orients the system
•Constrained area avoids coronaries and features supra-annular valve leaflets
•High radial force provides secure anchoring and constant force mitigates paravalvular leak
Radiopaque
Self-Expanding Multi-level Support Frame
• Specifically designed for transcatheter delivery
• Single layer porcine pericardium
• Tri-leaflet configuration
• Tissue valve sutured to frame
• Standard tissue fixation techniques
• 200M cycle AWT testing completed
• Supra-annular valve function
• Intra-annular implantation and sealing skirt
Porcine Pericardial Tissue Valve
Percutaneous Heart Valve (PHV) Delivery
PHV Deployment
PHV Post-deployment
18F Registry (N=536)18F Registry (N=536)
AgeAge (years)(years) 80.980.9 ±±6.7 6.7 [46-95][46-95]
FemaleFemale 280280 (52%) (52%) Logistic EuroSCORELogistic EuroSCORE (%)(%) 23.123.1 ±13.7 [3-85] ±13.7 [3-85]
High Risk Co-morbiditiesHigh Risk Co-morbiditiesHypertensionHypertension 57%57%DiabetesDiabetes 28% 28% CADCAD 56% 56% Prior MIPrior MI 13% 13% Prior PCIPrior PCI 30% 30% Prior CABGPrior CABG 21% 21% AFibAFib 32% 32% Prior CVAPrior CVA 7% 7%
PVDPVD 23%23% 3+ Mitral regurgitation 3+ Mitral regurgitation 2% 2%AI ≥ +3AI ≥ +3 4% 4%Porcelain AortaPorcelain Aorta 6% 6%Radiation HistoryRadiation History 3% 3%
Patient Patient Demographics
18F Registry 18F Registry (N=536)
Procedural Success 520 (97%)
Mean Procedure Time 128 ±47 Min±47 Min
Discharged alive & well with CoreValve 504 (94%)
Procedural Results Procedural Results
18F Registry18F Registry Pre-procedure Post-procedure Pre-procedure Post-procedure(N=536)(N=536)
AVA AVA (cm(cm22)) 0.640.64 ±±0.20 [0.2-1.7]0.20 [0.2-1.7] 1.901.90 ±±0.40 [1.3-2.6]0.40 [1.3-2.6]
Mean Gradient Mean Gradient (mm Hg)(mm Hg) 49.7049.70 ±±17.63 [12-114]17.63 [12-114] 2.712.71 ±4±4.73 [0-27]*.73 [0-27]*
Peak Gradient Peak Gradient (mm Hg)(mm Hg) 77.6177.61 ±±26.66 [10-169]26.66 [10-169] 4.474.47 ±8±8.19 [0-60]*.19 [0-60]*
% in NYHA Class III/IV% in NYHA Class III/IV 86%86% 8%**8%**
LVEFLVEF 51%51% ±±14 [10-85]14 [10-85] not availablenot available
Procedural Procedural Results Results (continued)
*Post-procedure gradients by catheterization*Post-procedure gradients by catheterization** At 30 days** At 30 days
18F Registry (N=536)18F Registry (N=536)
Procedural Failures 16 (3%)
Inability to access vessel 0 (0%) Inability to navigate vasculature 0 (0%)Inability to cross native valve 0 (0%)Malplacement 2 (<1%) Aortic Root Perforation 2 (<1%)Aortic Dissection 3 (<1%)Access Vessel Bleeding 3 (<1%)LV Perforation 2 (<1%)RV Perforation, pacemaker wire 2 (<1%)Difficulty with BAV 1 (<1%)Conversion to Surgery 2 (<1%)
Procedural Procedural Results Results (continued)
multiple events in same patients = data not cumulativemultiple events in same patients = data not cumulative
18F Registry (N=536)18F Registry (N=536)
Complications (0–30 Days)*Complications (0–30 Days)*
MI 4 (<1%)
Aortic dissection 2 (<1%)
Coronary impairment 0 (0%)
Acute Vascular complications 7 (1%)
Stroke/TIA 10 (3%)
Pacemaker 48 (9%)
Re-op for non-structural dysfunction 8 (1%)
Procedural Procedural Results Results (continued)
* * multiple events in same patients = data not cumulativemultiple events in same patients = data not cumulative
Regurgitation at DischargePost CE Registry
N=536
Procedural Procedural Results Results (continued)
43210
100
90
80
70
60
50
40
30
20
10
0
Regurgitation at Discharge
Perc
ent
of Patients
0%0%
14%
56%
30%
Clinically Acceptable
18F Registry (N=536)18F Registry (N=536)
All 30-Day Mortality:All 30-Day Mortality: 8% (44)8% (44)
Procedure RelatedProcedure Related 22 (4%)22 (4%)
Non-Procedure/Non-valve RelatedNon-Procedure/Non-valve Related 20 (<4%)20 (<4%)
UnknownUnknown 2 (<1%) 2 (<1%)
30 Day Outcomes30 Day Outcomes
No structural deterioration or migrationNo structural deterioration or migration
Short Axis Post
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