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MORPHOLOGICAL EVALUATION
OF THE SURGICALLY REMOVED AORTIC
AND MITRAL VALVES
Doina Butcovan*, Catalina Arsenescu**,
GIM Geeorgescu**
Cleopatra Borza, G.Tinica**, E Sandica**,
V. Diaconescu**,
University of Medicine and Pharmacy
Faculty of Medicine
*Department of Pathology
**Iasi Center of Cardiology
MORPHOLOGICAL EVALUATION OF THE SURGICALLY EXCISED AORTIC AND MITRAL
VALVES (Abstact): In 2001, of the 114 valves surgically excised at the
Iasi Center of Car1diology from 59 men and 54 women (mean age 51 years;
age range: 25 to 78 years), half were aortic and the other half mitral
valves. The 57 aortic valves, from 20 women and 37 men (mean age 51.1;
age range 25 to 78 years), had been surgically replaced. Functionally,
57.63 percent (30) were stenotic, 21.05 percent (12) were incompetent,
and 26.31 percent (15) were both stenotic and incompetent (aortic disease).
Pure stenosis was related to calcification of degenerative
(73.3 percent), bicuspid (3.33 percent), post-inflammatory (20 percent),
and undetermined (3.33 percent) causes. Pure regurgitation was not related
to calcification and causes included infective endocarditis (50 percent),
bicuspid valve (16.66 percent), postinflammatory (16.66 percent), aortic
root dilatation (8.33 percent), and undetermined (8.33 percent). Aortic
disease was secondary to postinflammatory etiologies (40 percent), degenerative
calcification (33.33 percent), bicuspid and undetermined (13.33 percent
each) causes. The reminder of 57 mitral valves, from 35 women and 24 men
(mean age 45.5 years; age range 28 to 71 years), were surgically replaced.
Functionally, 40.35 percent (23) were purely stenotic, 19.29 percent (11)
were purely regurgitant, and 40.35 percent (23) both stenotic and regurgitant
(mitral disease). The causes of pure stenosis were postinflammatory (presumably
rheumatic) disease in 91.3 percent (21 cases) and degenerative disease
in 8.7 percent (3 cases). Pure regurgitation etiology involved floppy
valves in 45.45 percent (5 cases), degenerative disease in 27.27 percent
(3 cases), postinflammatory disease in 18.18 percent (2 cases) and
infective endocarditis 9.1 percent (1 case). Key words: AORTIC VALVE, MITRAL
VALVE, VALVE DISEASE
INTRODUCTION
The valvular dysfunction may
result from a variety of mechanisms including calcification, fibrosis,
scar retraction, perforation, and congenital malformation (1, 2). Previous
studies of the valves removed surgically at different centers have shown
substantial changes in the relative frequency of the various etiologic
categories by evaluating the pathologic features of surgically excised
aortic and mitral valves (3-6). In general, conclusions regarding the underlying
etiology have been based on gross inspection of the entire valve, removed
during valve replacement procedures (7, 8).
Thus, the current investigation
was undertaken in view of determining an accurate etiologic diagnosis,
and for assessing the etiological trend of valve disease in further investigations,
having this paper as a reference.
MATERIALS AND METHODS
All aortic and mitral valves
excised at the Iasi Center of Cardiology (CCI) during 2001 were assessed
by gross and histological means, as recommended by Davies and Roberts.
Based on morphological criteria each valve was classified as degenerative,
post-inflammatory (presumably rheumatic), congenitally bicuspid, associated
with aortic root dilatation, or involved by active or healing endocarditis.
Valves that could not be confidently classified under one of the above
categories were considered to be of undetermined etiology. For each
specimen the patient's chart was reviewed and the following information
was recorded: age, gender, pertinent clinical diagnosis, valvular functional
state (assessed by electrocardiography and at operation), the surgeon's
description of the valve and aortic root, and the results of the histological
examination of the excised tissue. In assessing the functional state of
the valves, mild degrees of either stenosis or incompetence were not taken
into account. Thus, the functional state was recorded as pure stenosis
when the valve was moderately or severely stenotic, and pure regurgitant
when the valve was moderately or severely regurgitant. Although the incidence
of aortic and mitral disease (combined valvular disease) etiology is a
little different from isolated valvular disease etiology, the etiological
chart of aortic and mitral disease is relatively similar with that of pure
aortic and mitral regurgitation.
RESULTS AND DISCUSSIONS
AORTIC STENOSIS (AS)
Age and gender distribution:
The mean age for the entire group with aortic stenosis was 62.5 years (50
to 75 years) with little variation in mean age for patients in the major
etiologic categories. Sex distribution revealed a male predominance (17
to 13). Males also predominated for degenerative disease (13 to 10).
Morphology and etiological classification:
Obstruction of the aortic valve orifice generally results from fibrocalcific
processes that produce cusp thickening or commissural fusion impeding cusp
excursion. In our study, according to Waller (9), the three most common
causes of aortic stenosis in surgical specimens were, in decreasing order,
degenerative calcification, calcification of congenital bicuspid valve,
and calcification of postinflammatory valves.
1. We found the degenerative calcification as the most
common cause of aortic stenosis, accounting for 73.3 percent (22 of 30)
of the cases. Such a calcification in a tricuspid aortic valve is best
known as "senile" or tricuspid aortic valve stenosis. According to
Waller's description (9), our studied degenerative aortic valves showed,
as common features, fibrosis and calcification. The calcified lesions were
arranged as nodular arch-like ridges along the aortic aspect of each cusp,
that is anchored to the annulus. As a result, degenerative lesions gave
rigidity to the cusps and favored the development of stenosis. Commissural
fusion was minimal or absent. Waller (9) considers that this feature
serves to differentiate the degenerative forms of aortic valve disease
from other causes, particularly the post-inflammatory state. Waller reported,
in his institution, from 980 surgically excised aortic valves, 9.5 percent
were involved by degenerative calcification and 55 percent of them occurred
in men.
2. The frequency of post-inflammatory disease in our surgical
population was of 20 percent (6 patients). Morphologically, two pathological
processes characterize chronic rheumatic aortic valve stenosis: cusp fibrosis
and fusion of the commissures. In our cases, cusp fibrosis was diffuse
rather than focal, leading to cusp thickening and rigidity; secondary calcification,
produced as diffuse and nodular pattern, involving either cusps or commissures,
was responsible of valve stenosis. In some of our cases, the calcific mass
underwent ulceration permitting the secondary development of superimposed
surface small thrombi. The post-inflammatory form of aortic valve disease
was a chronic, apparently non-infectious fibrosing process that produced
valvular distortions, resembling with chronic rheumatic valvulitis (fig.
1) . Davies
(10) considers that this entity should not be designated as rheumatic unless
there is a clinical history of previous acute rheumatic fever, because
nonrheumatic disorders (such as rheumatoid arthritis, systemic lupus erythematosus),
or possibly even viral valvulitis may produce similar lesions. Waller (9)
reported that of 980 surgically excised aortic valves 48 percent were involved
by post-inflammatory disease; of these, 35 percent were purely stenotic.
In agreement with Virmani and Burke (11), we concluded that the present
lower rheumatic incidence might be related to several factors including
the decreasing incidence of acute rheumatic fever in many Western countries.
Waller (9) also noticed that post-inflammatory involvement tended to occur
in patients less than 70 years, with 57 percent in men.
3. We found in our study only one case of congenital aortic
stenosis (CAS) (fig. 2) .
Generally, CAS is the result of valvular dysplasia and hypoplasia, regardless
of the number of cusps (3). The congenital bicuspid state was the single
anomaly of the aortic valve encountered in our study. Davies (10) appreciated
that the term CAS should be used only when the obstruction is present at
or soon after birth. In rest, only 1 percent of the population could present
a risk of developing aortic valve stenosis, at 40 to 50 years of age, by
producing secondary dystrophic calcification of a congenital bicuspid valve.
Burke (11) showed there must be a considerable variation in the susceptibility
of individuals to develop cusp calcification, the causes of which are unknown
yet.
The morphological study of the
bicuspid aortic valve (BAV) revealed that one cusp was larger than the
other, the larger cusp containing a shallow ridge or raphe; this could
represent the line of congenital fusion of the two cusps. Like Waller (1),
we noticed in our case the calcification occurring on the raphe and along
the aortic aspect of the nonconjoined cusp contributing to cusp rigidity.
Waller (9) reported that among his 980 surgically excised aortic valves
33 percent were congenitally bicuspid and 75 percent of them occurred in
men. Burke (11) observed that CAS affect men three to four times more frequently
that women, and also tend to occur in patients less than 70 years old.
4. In 33.3 percent of our cases the etiology was undetermined,
being considered as unspecific cause.
AORTIC INCOMPETENCE OR AORTIC REGURGITATION
Age and gender distribution:
The mean age was 49.5 years (25 to 66), with little variation between the
major etiologic categories. Sex distribution showed male predominance (10
to 2). Males also predominated in the categories of infective endocarditis
(5 to 1). We found this degenerative aortic stenosis at a mean age of 67
years, while Davies (10) observed this senile entity was rare under the
age of 70 years, generally occurring in older patients.
Morphology and etiological classification:
It is well known that in aortic regurgitation (AR) the aortic orifice exceeds
in total area the root of the aorta. The both recognized causes of the
AR were present in our study: the aortic valve disease (A) and the ascending
aortic disease (B).
A1. In our study the most common cause of AR was infective
endocarditis, encountered in 50 percent of the cases (6 patients), and
represented healed forms of endocarditis and not active ones. Morphologically,
the valvular lesions included fibrous thickening, cusp erosions, and scar
retractions corresponding with the areas of previously treated infection.
We had in all cases a clinical history of infective endocarditis. These
cases suggest that an aortic infective endocarditis is not always fatal
if the patient has been treated with antibiotics. Waller (9) reported that
among 980 aortic valves surgically excised in his institution 3.2 were
involved by endocarditis, and 93 percent of these occurred in men.
A2. The second identified cause of AR in our surgical
specimens was post-inflammatory disease, which accounted for 16.66 percent
(2 patients) of the cases (fig.3) .
Grossly, the aortic valves showed cusp fibrosis producing scar retraction
of the cusps; there was no commissural fusion, thereby resulting a valvular
incompetence. In his work, Davies (10) revealed the formation of small
rigid cusps is characteristic for chronic rheumatic disease, and Waller
(9) registered purely AR in 25% of post-inflammatory aortic valve disease.
A3. According to Davies (10), the patients with bicuspid
aortic valves usually develop stenosis, but only a small proportion develops
pure regurgitation. In our study, the two cases (16.66 percent) were characterized
by a marked disproportion in cusp size, containing a small amount of calcium
salts. Among his 319 congenital bicuspid aortic valve, Waller (9) identified
that 17 percent were purely regurgitant.
A4. Of the regurgitant aortic disease cases, only one
case, accounting for 33,33 percent of all cases, was without specific etiology.
B. In our study we found only one case of surgically
excised aortic valve with pure AR, caused by aortic root dilatation in
a patient with Marfan syndrome. The patient was a 45 years old male, having
a clinical history of dilated ascending aorta. In this case aortic valve
incompetence was secondary to the dilatation of the aortic wall at the
commissural level, so that the cusps could not converge during systole.
AORTIC DISEASE
Age and gender distribution:
The mean age for patients with degenerative disease was of 66,5 years (ranges
55 to 78), for those with bicuspid valves of 45 years (34 to 56), and of
58,5 years (49 to 68) for post-inflammatory disease. Males predominated
for post-inflammatory disease (4 to 2) and for degenerative disease (3
to 2).
Morphology and etiological classification: For the 15
cases displaying both stenosis and regurgitation the most common etiology
was post-inflammatory disease – 40 percent (6 patients) followed by degenerative
disease - 33,33 percent (5 patients). Other frequently observed causes
included bicuspid valves 13,3 percent (2 patients) and undetermined etiology
- 13,3 percent (2 patients).
MITRAL STENOSIS (MS)
Age and gender distribution:
The mean age for the entire group of mitral stenosis was 49.5 (28 to 71
years) with little variation between the major etiologic categories. There
was a female predominance (24 to 35) in the entire mitral stenosis group,
women also predominating in the post-inflammatory disease category.
Morphology and etiological classification:
1. According to Waller (9), who appreciated that rheumatic
disease accounted for more than 99% of all etiologies and this had been
considered synonymous with mitral stenosis, we found among 23 operatively
excised stenotic mitral valves 21 cases (91.3 percent) with rheumatic etiology.
Morphologically, the rheumatic
mitral valve involvement (fig. 4)
was characterized by diffuse fibrous thickening, affecting the margins
of closure, the entire posterior and anterior leaflets; one or both commissures
were fused, reducing the size of the valve orifice. In older patients we
also found the association of a variable calcification contributing significantly
to obstruction. The calcification located in the cusps and commissures
developed both as nodules and as a more diffuse form along the closure
line. Virmani (11) theorized that persons with heavy calcific deposits
had higher levels of total serum cholesterol than did persons without calcific
deposits.
Histologically, the leaflet
tissue was composed of dense collagen with varying amounts of calcific
deposits producing major distortion of the normal leaflet layers. Like
Pomerance (12), we consider that the pathology of chronic rheumatic mitral
disease is not specific, being also encountered in nonrheumatic inflammatory
fibrosis. On one side, the Aschoff nodule, which is pathognomonic for acute
rheumatic heart disease, is rarely found within valves. On the other side,
in the chronic phase of the disease the life cycle of the Aschoff nodule
continues with a gradual decrease in cellular content and an increase in
collagen. So, establishing the etiology of "end stage" valve disease is
impossible in individual cases. We agree with Pomerance (12) and Olsen
(13) to call the chronically inflammatory fibrotic mitral valves as rheumatic
only in the presence of a clinical history of previous acute rheumatic
fever. Another point of view supporting this etiology refers to the concomitant
involvement of two valves in inflammatory process, such as mitral and aortic
valves.
In some cases we observed a
significant valvular deformation. Referring to this, Waller (9) appreciated
that the fibrous thickening and distortion of the leaflet could be a sequel
of any severe valvulitis. Pomerance (12) also postulated that the progression
of valve deformation is independent of continued inflammatory activity,
and is secondary only to continued trauma and repeated surface thrombus
deposition and its transformation to fibrous tissue resulting a continuing
valvular thickening. In our opinion, both factors are very important in
the progression of the lesion.
Of 759 surgically excised stenotic
mitral valves studied by Waller (9), all cases (100 percent) were classified
as rheumatic in etiology, while among 452 mitral valve stenoses diagnosed
by Olsen (13), the great majority, meaning 99 %, were rheumatic in etiology.
2. In our study, the etiology in the reminder of 2 mitral
stenosis cases (8,7 percent) was a degenerative disease. In these
two cases the mitral stenosis was produced by massive deposits of calcium
in the mitral annulus and the mitral leaflets having only focal areas of
fibrous thickening.
MITRAL INCOMPETENCE OR MITRAL REGURGITATION (MR)
Age and gender distribution:
The mean age for entire group with mitral regurgitation was 49.5 years
with appropriate variation between different etiologic groups, and with
relatively equal proportions between the two sexes.
Morphology and etiological classification:
Our study showed that in contrast to mitral stenosis, in which rheumatic
disease accounts for more than 90 percent of surgically excised valves,
the causes of pure mitral regurgitation were multiple, being represented
in decreasing order by floppy mitral valve (FMV), degenerative lesions,
rheumatic disease, and infective endocarditis.
FMV is used generally synonymously
with mitral valve prolapse (MVP) and myxomatous degeneration. Several morphologic
definitions use strictly histological criteria, others use morphometric
criteria, and still others use a combination of both criteria for separating
floppy and non-floppy etiology of pure MR, considering MVP: floppy as hereditary
disease or primary MVP and non-floppy, as aging disease, or secondary MVP.
MVP (fig. 5)
was recognized pathologically and clinically by its dome or ballooned shape
due to the expansion of the cusp area and elongated thin chordae, which
may prolapse into the left atrium during systole and sometimes may spontaneously
rupture.
At the histological examination
of these valves we found a large portion of the central mitral valve containing
a mucopolysaccharide material, appearing as myxoid degeneration resulting
in a valvular disorganized structure. But, the amount of mucopolysaccharide
material is increasing with advancing age. So, for differentiating floppy
from non-floppy valves, Waller (9) proposed a morphological and morphometric
analysis, the mucopolysaccharide material being graded from 1+ to 3+. According
to Waller’s (9) indications and using only histological evaluation, we
diagnosed the FMV etiology of MR in the presence of large myxoid areas
(3+) with valvular architecture disorganization due to an increase in the
spongiosa component and by replacing of the valvular fibrosa with mixoid
material. We considered as non-FMV etiology of MR when the myxoid degeneration
was focal (1+) and the spongiosa never invaded the fibrosa layer, as was
the case in the floppy mitral valves.
Taking in consideration these
morphological features we diagnosed the floppy mitral valves in 5 cases
(45.45 percent), and degenerative disease (non-floppy mitral valves) in
3 cases (27.27 percent), the gross appearance being similarly due to secondary
changes, including fibrosis of the surfaces of the leaflets and of the
chordae tendinae. For both these etiologies the chordal rupture may be
a factor in the worsening of pure MR. Davies (10) reported that the majority
of patients with chordal rupture had floppy mitral valves and myxoid changes
in both cusps and chordae. In his study, Olsen (13) found the FMV etiology
of pure MR in 29 percent of the cases. In contrast with him, Waller (9)
accounted for only 3 percent of FMV from purely surgically excised regurgitant
mitral valves.
Regarding FMV, Davies (10) has
another point of view, considering FMV as an unique pathoclinical entity
with various pathogenesis, such as: persistence of a fetal type valve
structure, an age-related degeneration of collagen, a partial failure of
collagen synthesis; this last concept is supported by an association of
FMV with all of known genetic defects in collagen synthesis, particularly
Marfan syndrome.
According to Davies (10), the
majority of the patients with chordal rupture had FMV. In our study, we
also found other causes of chordal rupture, including ischemic disease
(1 case of atherosclerotic coronary disease with systemic hypertension)
and healed infective endocarditis (1 case).
3. In only 2 (13.13 percent) of our cases we found the
involvement of the rheumatic disease in MR.
Morphologically, we noticed
that the structural alterations of the purely regurgitant valve were different
from those of the stenotic mitral valve. Purely regurgitant
rheumatic (fig. 6)
mitral valve showed diffuse fibrous thickening of the margins of closure
and focal areas of fibrous thickening on the remaining portions of the
leaflets; these mitral valves had minimal, if any, calcific deposits, and
the commissures were not fused. The question is why some mitral valves
become stenotic and others purely regurgitant even though the cause of
damage, represented by acute rheumatic fever, is the same? The answer is
unknown yet.
Of 97 patients studied by Waller
(9), only 3 percent had surgically excised valves that were rheumatic in
etiology. In 46 patients studied by Olsen (13), rheumatic etiology was
an infrequent cause of pure MR.
4. In our study, infective endocarditis producing pure
MR was found in 1 patient (9.1 percent of the cases).
Morphologically, we described
only one surgically excised mitral valve with chronic pure MR resulting
from healed infective endocarditis, presenting thickened valves by fibrous
tissue in the areas of previous infection. In healed mitral infective endocarditis,
erosion of the cusp edges and ruptured chordae, as in active endocarditis,
were sequels of valvular fibrous tissue destruction. The patient had a
history of previous active infective endocarditis.
Among 97 patients with surgically
excised purely regurgitant mitral valves studied by Waller, healed infective
endocarditis was the third most frequent etiology occurring in 5 percent
(5 patients) of the cases. In 260 patients with surgically excised mitral
valves, studied by Olsen (13), infective endocarditis was the fourth most
common etiology, representing 6 percent of his cases.
MITRAL DISEASE
Age and gender distribution:
The mean age was 44 years (ranges 39 to 49 years) with a minimal variation
between the different etiologic categories, and with similar proportions
between men and women.
Morphology and etiological classification:
in the 23 cases displaying both stenosis and regurgitation the most common
cause was, in decreasing order, the inflammatory disease 69.56 percent
(16 patients), degenerative disease 17.39 percent (4 cases), and in equal
proportion of 4.34 percent (1 case each) by floppy mitral valve, infective
endocarditis, and undetermined cause.
CONCLUSIONS:
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Degenerative (senile) disease is the most common cause
of aortic stenosis
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Mitral and aortic post-inflammatory (presumably rheumatic)
disease is a relatively common cause in all the three functional categories:
stenotic, regurgitant, and a combination of both
-
Floppy valves is the most common cause of pure mitral
regurgitation
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