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Clin. Cardiol. 17, 150-156 (1994)

Clinical Pathologic Correlations

7his

section

edited

by

Bruce

F

Wallel;M.D.

Pathology

of

Aortic Valve Stenosis

and

Pure Aortic Regurgitation:

A ClinicalMorphologic Assessment-Part 11

BRUCEF.WALUR,M.D. ,*~~ANEHOWARD,M.D.,tSTEPHENFESS, M.D.,$

*Cardiovascular Pathology Registry, St. Vincent Hospital; tNasser, Smith

&

Pinkerton Cardiology, Inc.; tshumacker, Isch, Jolly

Cardiovascular Surgery; Indiana Heart Institute, Indianapolis, Indiana, USA

Summary:

This two-part article exam ines the h istologic and

morphologic basis for steno tic and purely regurgitant aortic

valves. Part I discussed stenotic aortic valves and Part II

dis-

cusses causes of purely regurgitant aortic valves. In over 95%

of stenotic aortic valves, the etiology is one of threetypes: con-

genital (primarily bicuspid), degenerative, and rheumatic. Other

rare causes included active infective endocarditis, homozygous

type11

hyperlipoproteinemia, and systemic lupus erythemato-

sis. The causes of pure aortic regurgitation are multiple but can

be separated into diseasesaffecti ngthe valve (normal aorta) (in-

fective endocarditis, congenital bicuspid, rheumatic, floppy),

diseases affecting the walls of aorta (normal valve) (syphilis,

Marfans, dissection), diseaseaffectingboth aorta and valve (ab-

normal aorta, abnormal valve) (ankylosing spondylitis), and

dis-

ease affecting neither aorta nor valve (normal aorta, normal

valve) (ven tricular septal defect, systemic hypertension). Dis-

easesaffecti ngthe aortic valve alone are he most common sub-

group of conditions producing purely regurgitant aortic valves.

Key

words: aortic regurgitation,aortic endocarditis, bicuspid

aortic valve, ankylosing spondylitis,Marfans syndrom e

Introduction

Pure aortic regurgitation ranks fifth

in

the list of valvular le-

sions in patients undergo ing valve replacement procedures.

Address for reprints:

Bruce F. Waller,

M.D.

8402 Harcourt Road

Suite

400

Indianapolis,

IN

46260, USA

Received: December 16,

1993

Accepted: Decem ber 17,

1993

Part TI of this two-part article discusses various etiologies for

pure aortic regurgitation.

PureAortic Regurgitation

In marked contrast to the relatively sim ple approach to the

etiology of stenotic aortic valves in which 98% of the lesions are

related to congenital, rheumatic, or degenerative conditions, the

etiology of pure (no element of stenosis) aortic regurgitation is

multiple and the approach to etiology is more complex . Etiol-

ogies of pure aortic regurgitation include (Figs. 1-1 1) (Tables

1-w :

-16

1. Congenital bicuspid (Fig. 1 ,6 )

2. Active or healed mfective endocarditis

3. Rheum atic disease

4. Floppy (prolapsing)

5.

Collagen-vasculardisorders

6. Reiters syndrome

7. Ankylosing spondylitis

8.

Syphilis

9. Systemic hypertension

10.

Prolapse secondary to ventricular septal defect

11. Trauma

12. Aortic dissection

13. Subaortic stenosis

14.

Marims

disease

15.

Rheumatoid arthritis

Aortic Regurgitation Severe Enough to Warrant Valve

Replacement

In a recent survey of operatively excised native cardiac

valves, the aortic valve was the most frequently excised card i-

ac valve. Of 2,980 excised valves (2,566 patients), 1,973 (66%)

were aortic valves. Of the 1,973 excised aortic valves, 1,797

(19%) were classified as stenotic (with or without associatedre-

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B. F. Waller

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al.: Aortic valve stenosis and regurgitation

151

TABLE Etiology of purely regurgitant operatively excised aortic

valves

Etiology umber

of

valves

( )

Isolated pure aortic regurgitation AR)

Infective endocarditis

Active=

15 (31%)

Healed = 33 (69%)

Bicuspid valves

=

26 (54%)

Tricuspid

valves

=22 (46%)

Rheumatic

Congenital

Bicuspid=28 (97%)

Quadricuspid = 1

(3%)

Aortic

dissection

Marfans's syndrome

HOPPY (polapse)

Syphilis

Radiation

Subtotal

Combinedwt

other

valveexcisions

Ivlitral stenosis

+

AR

=

34

Mitral regurgitation +AR = 14

Rheumatic

Other

Infective endocarditis (healed)= 11

Floppy

mitralvalve

&

Rheumatic=

2

bicuspid

aortic valve

= 1

Subtotal

Total

48

(37%)

34 (26%)

29 (23%)

8 (6%)

5 (4%)

2

(2%)

1(1%)

l ( l % )

128

(100 )

(73%)

34(71%)

14

(29%)

48

(100 )

(27%)

176

(100 )

gurgitation) and 176(90 )were purely regurgitant no element

of stenosis) (Table I) (Figs. 1-5). Of the 176 excised purely re-

gurgitant aortic valves, 128 (73%) were replaced for isolated

(unassociated with dysfunction

of

another cardiac valve) pure

aortic regurgitation and

48

27%)were replaced with one addi-

FIG.

1 Diagram showing the frequency and etiology of operatively

tionaldysfunctioning valve.

Of

isolatedpurely qu tg it an t valves

excised, the most common etiologies for regqitation were:

in-

fective endo cadit is (37%), heumatic disease (26 ),andcon-

genitally abnormal valves

(23%).

Ofthe48 (37%)infectedaor-

tic valves, nearly one-third were active endocarditis and the re-

maining

two-thirds

were healed endocarditis

@erforated

cusps,

indented margins of cusps, or both) Table I).Of th e infected

aortic valves, over half

(54 )

nvolved congenitally bicuspid

aortic valves. Of the 29 (23 ) purely regurgitantaorticvalves

which w ere congenitally abnormal, 28 (97%)were bicuspid and

1was a quadricuspid aortic valve.I4Less fresuent causes for the

isolated pure aortic regurgitation included aortic dissection

(spontaneous,muma or

both) 6 ),

Marfan's syndrome

(4 ),

floppy or prolapsed cusps

(2 ),

yphilis(1 ), and radiation-

injectedinjury

(l%).I4

In the remaining

48

operatively excised purely regurgitant

aortic valves, another dysfunctional valve was also replaced (i.e.

Normal aortic valve

,

Ventricular diastole

Congenitally bicuspid

Infective endocarditis (activeor healed) (tricuspid)

t

Loss

cusp

tissu

Infective endocarditis (active or healed) (bicuspid)

R

1

FIG. Diagram

showing

various causes of pure aortic regqitat ion

(see Figs.

3-5). A

=anterior,

L =

eft,N

=

noncoronary, P = posterior,

excised aorticvalves:

pure

aorticregurgitation.

R = right.

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B. F. Waller

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153

TABLEI

Etiologyof operatively excised purely regurgitant aortic valves in sixpreviouslyqorted studies

Davies4 ~ober t s~ Olson6 Allen2 Lakier7 Tonnemakd

1980 1981 1984 1985 1985 I987 Totals ( )

Rheumatic

26 94 103

11

5

2

241 (38)

Congenital 16 13

47 2

1

2 81

(13)

(bicuspid)

(16) (13)

(45) (2)

(1) (1) (78)

Aortic root dilation

31 26 48 6

3 4 118(19)

Aortitis 8 0

0 0 0 8

Marfan's

23 15

4 2 0

I 45

Syphilis

0 9

1 0 3 3 16

Idiopathic

0 0

43 0

0 43

Dissection

0

2

0 0

0 0 2

Aneurysm

0

0

0 4 0 0 4

Infective endocarditis 21 41

21 13

3 12 111 (18)

Floppy (myxomatous) 2

0

0 13

6

21 (3)

Subaortic stenosis 0 2

0 1

0

3(0.5)

VSD 0 10

4 1

0 0

15( 2 )

Radiation

0 0 0

0

0

0

0

Spontaneous tear 2

0

0 0

0 2 (0.2)

Trauma

0

1

0

0 0 1

2

(0.2)

SLE

0

0 1 I (0.1)

Uncertain

2 0

2

8

15

9

36 (6)

Totals I00 I87

225 55

27 37 631 (100)

Abbreviurbm:

VSD =ventricular septal defect,SLE

=

systemic lupus erythematosis.

blood passing through the subvalvuiar obstruction

and

hitting

the ventricular aspect of the aortic cusps (Fig.

5).

Th e fibrous

thickeningper se or secondary infective endocarditismay

pro-

duce severe pure aortic regurgitation. Rarer causes

of

purely

valvular aortic regurgitation include syste mic lupus erythe- Valve 162 (92)

matosis? rheumatoid arthritis,' mediastinal

rradiation,

4 and

TABLE

regurgitant aortic valves (from Table

I)

site

f

Siteof

disease

and etiology

of

operatively excised purely

Number

of

valves

( )

Endocarditis=48+ 11 =59

metastatic tumor. I

Rheumatoid arthritis

Discrete subaortic stenosis

Rheumatic

=

34+ 36 =70

Congenital

=

29+

=

30

Floppy =2

Radiation =

Aortic dissection+

8

Aorta

Marfan's =5

Syphilis

=

1

Both

Neither

0

1

76 100)

TABLEV Site of disease in known etiology of operatively excised

purely regurgitant aortic valves (from Table III

Siteof disease

Number of valves ( )

Valve

Neither valve nor aorta

a

Both valve and aorta 0

459 77)

llS(20)

18 (3)

/ I Aorta

595

loo)

FIG.

Diagram showing two additional causesof pure aortic regur-

gitation

see

Figs. 2-4).

Subaorticstenosis=3, ventricular septal defect = 15.

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154

Clin . Cardiol.

Vol. 17,

March 1994

FIG. Composite of nine operatively excised purely regurgitant aom c valves:

(A)

healed infective endocarditis,

(J3)

aortic dissection,

(C)

Marfans

syndrome,

(D)

systemic hypertension,

(E)

healed endocarditis,

(F)

congenital bicuspid,

(G)

rheumatic, (H) congen ital bicuspid,

(I)

active end@

carditis.

Disesses

of

the Aorta

tomically normal (Fig. 12). Echocardiographic diagnosis

of

dis-

eases in

this

category will have major therapeutic implications

since both aorta and aortic valve may need repair

or

replace-

ment.Threemajor diseases fall into this category: aortitis (sy-

philis), Marfans disease, and aortic dissection . Table

V

com-

pares

morphologic findings

in

each

of

these categories which

weaortic regurgitation may be associated with various dis-

eases affecting he ascending aorta. Diseases of the aorta account

for 8-20% of operatively excised purely regurgitant aortic

valves (Tables III,

IV).

n

this

category, the aortic valve is ana-

~

FIG.

Radiog raphs showing three operatively excised purely regu rgitant aortic valves.

No

calcific deposits are present.

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B. F. Waller et al.: Aortic valve stenosis and regurgitation

155

Active

Healed

thickening Perforation

Bicuspid

FIG. Diagram showing

various

mechanisms of pure aortic

regur-

gitation in active and healed infectiveendocarditis.

may bedetected echocardiographically. n Marfan's syndrome,

the diseaseprocess is confined to the sinusportionof the aorta

and them16cwallsareextremely thindue to ass of

medial

elas-

tic fibers.

n

syphilis, the tubular portion of the

aorta s common-

ly involved and the aortic walls

are

thickened by fibrosis. The

mechanism of pure aortic regurgitation in this subgroup

of

dis-

eases is by stretching of the aorticwalls and a central leak.

BothAorta and Valve

Ankylosing spondylitis

and

Marfan's

syndrome

are

he only

diseases producing pure aortic regurgitation by involvement of

both he wall of the

aorta

and abnormal aortic valve cusps.I2 n

Normal aortic valve

Aortic wall

AV

cusp

Floppy

aortic valve

Cuspal circumferen z

X'>>X,

y h y ,

5>z

FIG.10 Diagram defining morphologic and morphometric criteria

for

floppy aortic valves. From Ref. 14

wt

permission.

FIG. Diagram showing quadricusp id aortic valve producing pure

aorticregurgitation.From

Ref. 14

wt permission.

ankylosingspondylitis, theproximal portionof the tubular

aor-

ta

(licesyphilis) and the

sinusportionof

the

aorta (like Marfan's)

are involved, but the diseaseprocess also extends nto the

heart

to involve aortic valve cusps and the anterior eaflet of the mi-

tra valve. The aortic valve cusps become thickened and retract-

ed,cauSingpureregUrgitation.In~ntrasttoMarran'ssyn~~

but similar to syphilis, the aortic walls are thickened. To our

knowledge , no operatively excisedaorticvalve from t h i s dis-

order

has

been

reported. In

Marfan's di sease, he wall of the aor-

ta (sinus portion) is abnormallythnand the aortic valve

may

be

purely regurgitant due to prolapse.

Neither Aorta Nor Valve

Pureaortic regurgitation from prolapsing aortic valve cusps

secondary to ventricular septal defect2p5s6 nd systemic hyper-

tension fall into this category. The aortic valves in each case are

focally thickened but are otherwise anatomically n0r1nal.l~

About

3%

of operatively excised purely regurgitant aortic

valves fall into this category(Table

HI

V).

aorta

(3%)

Valve

Present study (n =

176)

Neither

valve nor

aorta

(2 )

Total n= 771)

FIG.1 Diagram s howing sites and frequen cy of conditions pro-

ducing purely

regurgitant

aortic

valves.

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