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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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