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 Clinical Morphologic Assessment-Part 11
BRUCEF.WALUR,M.D.,*~~
JANEHOWARD,M.D.,tSTEPHENFESS, M.D.,$
*CardiovascularPathology 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 examines the histologic and

morphologic basis for stenotic and purely regurgitant aortic
valves. Part I discussed stenotic aortic valves and Part II discusses causes of purely regurgitant aortic valves. In over 95%
of stenotic aortic valves, the etiology is one of threetypes: congenital (primarily bicuspid), degenerative, and rheumatic. Other
rare causes included active infective endocarditis, homozygous
type 11hyperlipoproteinemia, and systemic lupus erythematosis. The causes of pure aortic regurgitation are multiplebut can
be separated into diseases affectingthe valve (normal aorta) (infective endocarditis, congenital bicuspid, rheumatic, floppy),
diseases affecting the walls of aorta (normal valve) (syphilis,
Marfans, dissection),disease affectingboth aorta and valve (abnormal aorta, abnormal valve) (ankylosingspondylitis),and disease affecting neither aorta nor valve (normal aorta, normal
valve) (ventricularseptal defect, systemic hypertension).Diseases affectingthe aortic valve alone are the most common subgroup of conditions producing purely regurgitant aortic valves.

Key words: aortic regurgitation,aortic endocarditis,bicuspid

aortic valve, ankylosing spondylitis,Marfans syndrome
Introduction
Pure aortic regurgitation ranks fifth in the list of valvular lesions in patients undergoing 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: December 17, 1993

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

pure aortic regurgitation.

Pure Aortic Regurgitation

In marked contrast to the relatively simple 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.Etiologies of pure aortic regurgitation include (Figs. 1-1 1) (Tables
1-w):1-16
1. Congenitalbicuspid (Fig. 1,6)
2. Active or healed mfective endocarditis
3. Rheumatic disease
4. Floppy (prolapsing)
5. Collagen-vasculardisorders
6. Reiters syndrome
7. Ankylosing spondylitis
8. Syphilis
9. Systemichypertension
10. Prolapse secondary to ventricularseptal defect
11. Trauma
12. Aortic dissection
13. Subaorticstenosis
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 cardiac 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 associated re-

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

TABLEI Etiology of purely regurgitant operatively excised aortic

valves

Numberof valves (%)

Etiology

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
Combined withother valve excisions
Rheumatic
Ivlitral stenosis + AR = 34
Other
Mitral regurgitation + AR = 14
Infectiveendocarditis (healed) = 11
Floppy mitral valve &
bicuspid aortic valve = 1
Rheumatic = 2
Subtotal
Total

48 (37%)

34 (26%)
29 (23%)

8 (6%)
5 (4%)
2 (2%)
1(1%)

151

tional dysfunctioning valve. Of isolatedpurely qutgitant valves

excised, the most common etiologies for regqitation were: infective endocaditis (37%),rheumatic disease (26%),andcongenitally abnormal valves (23%).Ofthe48 (37%)infected aortic valves, nearly one-third were active endocarditis and the remaining two-thirdswere healed endocarditis@erforatedcusps,
indented margins of cusps, or both)(Table I). Ofthe infected
aortic valves, over half (54%)involved congenitally bicuspid
aortic valves. Of the 29 (23%) purely regurgitant aortic valves
which were congenitallyabnormal, 28 (97%)were bicuspid and
1 was 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%),syphilis ( 1%), and radiationinjectedinjury (l%).I4
In the remaining 48 operatively excised purely regurgitant
aortic valves, another dysfunctional valve was also replaced (i.e.

l(l%)
128 (100%) (73%)

34(71%)

Normal aortic valve

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 regurgitant 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-

Ventricular diastole

Congenitallybicuspid

Infective endocarditis (active or healed) (tricuspid)

Loss

cusp
tissu

n
t

Infective endocarditis (activeor healed) (bicuspid)

R
1

FIG.2 Diagram showing various causes of pure aortic regqitation

FIG. 1 Diagram showing the frequency and etiology of operatively
excised aortic valves: pure aortic regurgitation.

(see Figs. 3-5). A = anterior,L = left, N = noncoronary,

P = posterior,
~.
R = right.

Clin. Cardiol. Vol. 17, March 1994

152
Rheumatic' (with 01 without cornrnissurai fusion)

Ankylosing spondylitis
Comrnissural fusion

'Diffusely thickened mitral valve also present

Aortic tear or laceration (dissection or trauma)
Swernic hypertension (chronic, sevetd
Taut margins of closure
1

Degenerative
Marfan or Marfan-like

A
FIG. 3 Diagram showing three additionalcauses of pure aortic regurgitation(seeFigs. 1,4,5).

nonisolated aortic regurgitawr)(Table I). Rheumatic disease

(mitral stenosis) was the basis for a purely regurgitantoperatively excised aortic valve in 34 of 48 (7 1%) pahents and for various other acquired (infection = 11, rheumatic = 2) or congenital (1) conditions in the remaining 14 of 48 (29%) patients
(Table I).
Several other s t u d i e ~have
~ - ~ reportedcauses for purely regurgitant aortic valves (Table 11).Of over 600 excised valves,
the most common etiologies were rheumatic diseaseM congenital infective endocarditis,2$ and aortic root disease6 (Table
II). Depending on the study, rheumatic disease,47 infective endocarditis? or disease of aortic mot2were the most common etiology.
The various etiologies of pure aortic regurgitation described
above can be subgroupedinto those conditions primarily affecting the aortic valve cusps, the walls of the aorta, and those
conditions affecting both or neither valve and aorta (Tables
I-Iv) (Figs. 2-12).'-*6
Valve Cusps
Diseases of the aohc valve account for the vast majority
(77-92%) of opratively excised purely regUrgitant aortic valves
(Tables III,IV)(Figs. 6-11). Principal conditionsin this category include active or healed infective endocarditis involving a
bicuspid or tricuspid aortic valve (Fig. 6), a congenital bicuspid

Prolapse from ventricular septai defect

FIG. 4 Diagram showing four additional causes of pure aortic regurgitation(see Figs. 2,3,5).

aortic valve (Fig. 6),rheumatic disease,and floppy aortic valves

(Fig. 10).Most if not all of the diseases in this category can be
detected by echocardiographicimaging techniques.Rheumatic
disease of the aortic valve (generally associated with disease of
the mitral valve) is characterized by diffuse fibrous thickening
of each cusp; retraction of one or more cusps: minimal, if any,
commissural fusion;and minimal, if any, calcific deposits (Fig.
7). Jnfective endocarditis produces aortic regurgitation by cusp
destruction (identation, perforation), cusp prolapse into the left
ventricular outflow tract, by interpositionof vegetations,between the closing margins of the cusps, or various combinations
(Fig, 8). Congenitallybicuspid valves which are inhmtly purely regurgitanthave markedinequalityof cusp size and minima,
if any, calcificdeposits. Floppy aortic valves have been reported as an isolated cause of pure aortic
l4 (Fig.
lo), but others have been in association with cystic medial degeneration of the aorta. In discretesubaortic stenosis, the aortic
valve cusps become thickened from the high-pressurejet of

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

153

TABLE
II Etiology of operativelyexcised purely regurgitant aortic valves in six previously qorted studies
Davies4
1980
Rheumatic
Congenital
(bicuspid)
Aortic root dilation
Aortitis
Marfan's
Syphilis
Idiopathic
Dissection
Aneurysm
Infective endocarditis
Floppy (myxomatous)
Subaorticstenosis
VSD
Radiation
Spontaneous tear
Trauma
SLE
Uncertain
Totals

26
16
(16)

~oberts~

1981

94
13
(13)
26
0

23

Olson6
1984

Allen2
1985

103

11
2
(2)

Lakier7
1985

Tonnemakd
I987

5
1
(1)
3
0

15

0
0
0
21
2
0
0
0
2
0
0
2
I00

0
2
0

43

0
0
21
0
0

0
0
0

3
0

31

47
(45)
48

41
0
2
10
0
0

4
13
13
1
1
0
0
0
0
8
55

4
0
0
0
0
2
225

0
0
I87

3
0

0
0
0
0
0

Totals (%)

2
2
(1)

241 (38)
81 (13)
(78)
118(19)
8
45

4
0

16

43
2

12
6
0
0
0
0
1

15
27

111 (18)
21 (3)
3 (0.5)
15 ( 2 )
0
2 (0.2)
2 (0.2)
I (0.1)
36 (6)
631 (100)

37

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). The fibrous
thickening per se or secondary infective endocarditis may produce severe pure aortic regurgitation. Rarer causes of purely
valvular aortic regurgitation include systemic lupus erythematosis? rheumatoid arthritis,'"mediastinal irradiation,l4 and

metastatic tumor. I I

Rheumatoid arthritis

TABLE Site of disease and etiology of operatively excised purely

regurgitant aortic valves (from Table I)
siteof

Valve
Endocarditis = 48 + 11 = 59
Rheumatic = 34+ 36 = 70
Congenital = 29 + 1 = 30
Floppy = 2
Radiation = 1
Aorta
Aortic dissection + 8
Marfan's = 5
Syphilis = 1
Both
Neither

Number of valves (%)

162 (92)

0
0

1 76(100)

Discrete subaortic stenosis

TABLE
IV Site of disease in known etiology of operatively excised
purely regurgitant aortic valves (fromTable III)
Site of disease
-,/.

Valve

Aorta

Neither valve nor aorta a

Both valve and aorta

FIG.5 Diagram showing two additional causes of pure aortic regurgitation (see Figs. 2-4).

Number of valves (%)

459(77)
llS(20)
18 (3)

0
595 (loo)

Subaortic stenosis = 3, ventricular septal defect = 15.

154

Clin. Cardiol. Vol. 17, March 1994

FIG.6 Composite of nine operatively excised purely regurgitant aomc valves: (A) healed infective endocarditis, (J3) aortic dissection, (C) Marfans
syndrome, (D) systemic hypertension, (E) healed endocarditis, (F) congenital bicuspid, (G) rheumatic, (H) congenital bicuspid, (I) active end@
carditis.

Disesses of the Aorta

Pweaortic regurgitation may be associated with various diseases affectingthe ascending aorta. Diseases of the aorta account
for 8-20% of operatively excised purely regurgitant aortic
valves (Tables III, IV).In this category, the aortic valve is ana-

tomically normal (Fig. 12).Echocardiographic diagnosis of diseases in this category will have major therapeutic implications
since both aorta and aortic valve may need repair or replacement. Three major diseases fall into this category: aortitis (syphilis), Marfans disease, and aortic dissection. Table V compares morphologicfindings in each of these categories which

FIG.7 Radiographs showing three operatively excised purely regurgitant aortic valves. No calcific deposits are present.

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

Active

155

Healed

thickening Perforation

Bicuspid

FIG.8 Diagram showing various mechanisms of pure aortic regurgitation in active and healed infective endocarditis.

FIG.9 Diagram showing quadricuspidaortic valve producing pure

aortic regurgitation. From Ref. 14 withpermission.

may be detected echocardiographically.In Marfan's syndrome,

the disease process is confined to the sinus portion of the aorta
and the m16cwalls are extremely thin due to lass of medialelastic fibers.In syphilis, the tubular portion of the aortais commonly involved and the aortic walls are thickened by fibrosis.The
mechanism of pure aortic regurgitation in this subgroup of diseases is by stretching of the aortic walls and a "central" leak.

ankylosingspondylitis, the proximal portionof the tubular aorta(licesyphilis) and the sinusportion of theaorta (like Marfan's)
are involved, but the diseaseprocess also extendsinto the heart
to involve aortic valve cusps and the anteriorleaflet of the mitralvalve. The aortic valve cusps become thickened and retracted,cauSingpureregUrgitation.In~ntrasttoMarran'ssyn~~
but similar to syphilis,the aortic walls are thickened. To our
knowledge,no operativelyexcised aortic valve from this disorder has been reported.In Marfan's disease,the wall of the aorta (sinus portion) is abnormallythin and the aortic valve may be
purely regurgitant due to prolapse.

Both Aorta and Valve

Ankylosing spondylitis and Marfan's syndrome are the only
diseases producing pure aortic regurgitation by involvement of
both the wall of the aorta and abnormal aortic valve cusps.I2In

Normal aortic valve

Aortic wall

Floppy aortic valve

ff

Neither Aorta Nor Valve

Pureaortic regurgitation from "prolapsing" aortic valve cusps

secondary to ventricular septaldefect2p5s6and systemic hypertension 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,IV).

AV cusp

aorta

Valve

(3%)

Present study (n = 176)

Neither
valve nor
aorta
(2%)

Cuspal circumferenz
X'>>X, y h y , z5>z
FIG.10 Diagram defining morphologic and morphometric criteria
for floppy aortic valves. From Ref. 14 with permission.

Total (n = 771)

FIG.1I Diagram showing sites and frequency of conditions producing purely regurgitant aortic valves.

156

Clin. Cardiol. Vol. 17, March 1994

TABLE
V Certain morphologic characteristicsuseful in distinguishingvarious diseases of the ascending aorta producing pure aortic regurgitation
which can be detected echocardiographically

Aorta
Marked dilation
Limited to sinuses of Valsalva
Thickened aortic walls
Calcific deposits
Aortic valve
Three-cuspid
cuspal thickening
Focal
Diffuse

syphilis

Ankylosing
spondylitis

Marfan's

+/0
0

0
0

+/0

+
+
0

Idiopathic
dilation

Systemic
hypertension

+
+

0
0

O/(+)
0

+/0
0
0
0

+I0

+I0

+I0
0

+/0
0

3. TonnemacherD, Reid C, Kawaniski D, Cummings T,Chandrasoma

P, McKay CR, Rahimtoola SH, Chandrasoma PAN: Frequency of
myxomatous degeneration of the aortic valve as a cause of isolated
aortic regurgitation severe enough to warrant aortic valve replace-

ment.AmJCurdiol60,1194-1196(1987)

Fig. 12 Operatively excised portion of ascending aorta and purely

regurgitant aortic valve from a patient with Marfan's cardiovascular
disease. From Ref. 17 with permission.

Conclusion
Thus, in over 95% of operatively excised stenotic aortic
valves, the etiology falls into one of threemajor categories: congenital, rheumatic, or degenerative. In contrast. the causes of
pure aortic regurgitation are multiple but can be subgroupedinto
those diseases primarily affecting the valve (over 75%),the wall
of the aorta (about 20%),neither valve nor aorta, or both valve
and aorta (about 5%).Of the categories of pure regurgitation,
diseases affecting h e valve account for the vast majority of the
lesions.

References
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assessment of operatively excised cardiac valves. Part I. Clin Curdiol
17,4146 (1994)
2. Allen WM, Matloff JM, Fishbein MC: Myxoid degeneration of the
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4. Davies MJ: Pathology of Cardiac Vulves. Buttenvorths, London

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5. RobertsWC, M m w AG, McIntosh CL, Jones M, Epstein SE Congenitally bicuspid aortic valve causing severe, pure aortic regurgitation without superimposed infective endocarditis: Analysis of 13 patients requiring aortic valve replacement. Am J Cardi0/47,206-209
(1981)
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