二葉式主動脈瓣疾病-發(fā)病機理和治療的新感悟英文課件

OverviewWhat

causes

BAV

and

its

complications?BAV

associated

aortopathy:

MechanismsPatterns

of

BAV

associated

aortopathyWhen

should

the

aorta

be

replaced?Bicuspid

Aortic

Valve

Disease1BackgroundBicuspid

Aortic

Valve

(BAV)Most

common

congenital

cardiac

defectOne

in

3

will

develop

complicationsIncidence

1-2%

(~25

million

in

China)Most

common

cause

of

AS/AI

in

patients

under

70Causes

more

morbidity

than

all

other

congenitaldisorders

combinedNot

affected

by

race

or

geographyMale:

Female

ratio

of

3:1Inheritance

unclear

(autosomal

dominant?)2Fedak

P,

Verma

S,

Circulation

2019;106(8):900-4Etiology

and

Development

of

Congenital

BAVp.Abnormal

aortic

cusp

formation.Adjacent

cusps

fail

to

separate,resulting

in

a

single

aberrantcusPhenotypic

continuum

(unicuspid,bicuspid,

tricuspid)Fedak

P,

Verma

S,

Circulation

2019;

106(8)3:900-4Fedak,

David,

Borger,

Verma,

Expert

Rev

Cardiovasc

Ther

2019Sabet

etal,

Mayo

Clin

Proc,

1994;74:14-26Bicuspid

Aortic

Valve

(BAV)

Morphology

Leaflet

Position4Anterior-PosteriorLeft-RightEtiology

and

MechanismsAbnormal

blood

flowthroughaortic

valveduringvalvulogenesis

results

in

afailure

of

cusp

seperationEmbryonic

theory(abnormalities

in

conotruncalseperation)Cono-truncus

divided

by

thespiral

conotruncal

septumRight

&

left

aorticleafletsform

at

the

junctionofventricular

&

arterial

ends

ofconotruncal

channel5Coronary

Anomalies

in

BAV6Present

in

large

proportion

ofpatientsLeft

dominant

system

with

short

leftmain180o

separationLeft

coronary

from

PA(rare)Stenosis

of

left

coronary

ostium

(rare)Anomalies

Associated

With

BAV

Disease8Aortic

dilation

and

aneurysm

formationAortic

dissectionAortic

coarctation

and

interruptionCoronary

anomalies

(dominant

Cx)VSD,

bicuspid

PV

(rare)Williams

syndrome

and

TurnersBAV

and

Aortic

DissectionBAV

is

associated

with

a

9

fold

increase

in

riskBAV

found

inupward

of

15%of

type

A70%

of

cases

have

normal

valvular

functionMost

common

cause

of

aortic

dissection9Molecular

Mechanisms

of

Aortic

Dilatation

inBicuspid

Aortic

Valve

Disease:Fedak,

Verma,

et

al. JTCVS

2019;

126(3):

79170-806Role

of

Matrix

Remodeling50%

of

young

asymptomatic

patientsIndependent

of

valve

functionAssociated

degeneration

of

aortic

mediaEtiology

and

mechanisms

unknownAortic

Dilatation

and

BAV11Aortic

Dilatation

and

BAVPoor

Correlation

Between

Degree

of

AS

and

Aortic

Dilation12Magrad

et

al.

JTCVS2019MediaIntimaAdventitiaHuman

Aorta13Elastic

Lamellae

of

MediaElastin

&CollagenSmoothMuscleCellsFibrillin-1Microfibrils14The

Roleof

Fibrillin-115Developmental

RoleDirects

formation

of

valve

and

aortaFunctional

RoleMaintains

Tissue

ElasticityFbn-1

gene

defect

(Marfan

Syndrome)Altered

fibrillin-1

contentAortic

dilation

and

dissectionPNAS

2019;

96:3891Fibrillin-1DeficientMouse:Progressive

Aortic

Dilation16Verma

S,

Circ

Res

2019;

88(1):

37Fibrillin-1DeficientMouse:Matrix

Disruption

in

Aortic

MediaNormal

MouseFbn-1

Deficient

MouseDisrupted

MatrixAortic

AneurysmNormal

Matrix

No

Aortic

Dilation17Fibrillin-1DeficientMouse:Fibrillin-1

Deficient

Tissues

Release

MMPsFibrillin-1

DeficiencyIncreased

MatrixMetalloproteinases

(MMP)Matrix

DisruptionAortic

Dilation18Matrix

Disruption

in

BAV

PatientsAORTIC

MEDIA19Tricuspid

AV

(TAV)Bicuspid

AV

(BAV)Objective20HypothesisIn

BAV

patients,

fibrillin-1

deficiencyand

increased

MMP

matrix

degradationresult

in

aortic

dilationFibrillin-1

DeficiencyFedak,

Verma,

et

al. JTCVS

2019;

126(3):

79272-806

SDIncreased

MMP-2

Activity24Novel

Mechanism

of

Aortic

Dilation25FBN-1

GeneMutation

(?)Decreased

FBN-1

ProductionFBN-1

DeficiencySMC

Detachment

from

Elastin

LaminaeMMP-2

ReleaseMatrixDegradationApoptosisMedial

DegenerationA

Novel

Mechanism

for

Aortic

DilatationSecondaryEventsAortic

Dilatatio2n6Anatomic

Patterns

of

Aortic

DilationCustom

Tailoring

Required27Patterns

of

Aortic

Dilation

inBicuspid

Aortic

ValvesA:

aortoventricular

jxnB:

Sinuses

of

ValsalvaC:

Sinotubular

jxnD:

Tubular

ascending

aortaE:

Proximal

innominateF:

Distal

innominateG:

Proximal

left

subclavianH:

Distal

left

subclavianI:

Proximal

descendingJ:

Descending

at

diaphragm28Patterns

of

Aortic

Dilation

inBicuspid

Aortic

ValvesAscending+Transverse

Arc(RAA

and

Hemiarch)Ascending

Aorta(Supracoronary

Graft)Root

(Sinuses)

Dilation(Valved

Conduit

or

Repair)2930Aortopathy

in

Bicuspid

Valve31When

Should

the

AscendingAorta

Be

Replaced

in

Patientswith

Bicuspid

Aortic

ValveDisease?Borger,

Fedak,

Verma

etal.

JTCVS32

2019Current

recommendations

forreplacement

of

the

ascending

aorta(RAA):>

5.5

cm

in

diameter>5.0

cmKoiuinchoMukoasrNfTa,

nDo’sugepnias

tDti.eNnEtnsglJ

Med

2019;336:1876-88Optimal

diameter

for

RAA

in

ptsundergoing

aortic

valve

surgery

isunknownHinge

Point

(6cm)

may

be

different

inBAV30

times

higher

risk

ofpost-operativedissection

post

AVR

if

AA

>5.0cmWhen

Should

RAA

be

Done

in

BAV

Patients?33To

determine

incidence

of

long-termascending

aorta

complications(aneurysm,

dissection

or

sudden

death)and

survival

in

BAV

pts

with

mildaorticdilatation

(40

–

50

mm)

versus

nodilatationTo

determine

the

threshold

diameterfor

RAA

in

BAV

patients

undergoingaortic

valve

surgeryPurpose

of

Study34Methods35Retrospective

review

of

201

BAV

ptsundergoing

aortic

valve

replacementDiameter

of

ascending

aorta

determined

bydirect

measurement,

TEE,

or

intaoperativedescription:“normal”

→

less

than

4.0

cm“mildly

dilated”

→

4.0

–

4.4

cm“moderately

dilated”

→

4.5

–

4.9

cmPatients

with

aortic

diameters

>

5.0cmunderwent

RAA

and

were

excludedCauses

of

ReoperationSVD

28Aortic

aneurysm 7

(+11)Endocarditis

3Pannus

formation

2Aortic

dissection

1Mitralregurg

1LVOT

obstruction

1Heart

transplant

1Total

reoperations

=

44(22%)11

of

these

pts

also

had

ascendingaortic

aneurysmsResults38Results39JTCVS

2019Freedom

from

Aortic

ComplicationsResults40JTCVS

2019Long-Term

SurvivalImplications

BAV

disease

is

associated

with

a

moderaterisk of

ascending

aortic

complications

afterAVR

In

BAV

patients

at

the

time

of

AVR,replace

the

ascending

aorta

if

>

4.5

cm

indiameter

to

reduce

aortic

complications

andimprove

long-term

survival

An

approach

to

ascribe

moderate

dilationto“post-stenotic

dilation”

may

be

misleading4142Surgical

Options43Isolated

AS/AI

and

AD

<

4.5AVRAS/AI

and

AD

>

4.5AVR

+RAA(supracoronary)Reduction

aortoplastyBentallValve

RepairNo

valvular

involvement

and

AD

4.5-5Rate

of

growthROOTVALVEComposite

GraftToronto

General

Hospital44SeparateGraftN=89N=50Mechanical(55%)Stented-Tissue(16%)Stentless-Tissue

(29%)Mechanical(36%)Stented-Tissue(60%)Stentless-Tissue

(4%)Aortic

diameter

increased

in

9%

by

4-8

mm

over

the

follow

up46474849SummaryBAV

is

a

common

congenital

cardiac

malformation

that

occurs

during

valvedevelopment,

perhaps

due

to

aberrant

gene

expression.Disrupted

ECM,

endothelial

injury

and

changes

in

cell-death

pathways

have

beenimplicated

in

BAV

associated

aortopathy.BAV

implies

disease

of

entire

aortic

root,and ascending

aorta,

and

predisposesto

valve

dysfunction,

endocarditis,

dilation/dissection.Several

distinct

patterns

of

aortic

dilation

are

pr