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ENDOCARDIAL SCLEROSIS IN INFANTS AND CHILDREN*
G. E. COSGROVE, JR., M.D., AND D. H. KAUMP, M.D.
From the Departments of Pathology, Providence Hospital and Wayne University
College of Medicine, Detroit, Michigan
We wish to report six cases of endocardial sclerosis in infants or young children
and to review briefly the pathology and pathogenesis of the disease.
DESCRIPTION OF ENDOCARDIAL SCLEROSIS
Endocardial sclerosis was reported in 1818 by Kreysig (cited by Krstulovic17)
under the term "fetal endocarditis." At that early date intrauterine inflammation was considered as the most likely cause of fetal endocarditis and by the end
of the 19th century this explanation was widely accepted for most congenital
cardiac anomalies. Studies were reported which included gross changes but no
adequate microscopic descriptions. The gross features which were emphasized
were endocardial opacities, valvular contractures, smooth or warty thickenings
of the valve leaflets and occasional adhesion of the leaflets. The resemblance to
rheumatic carditis of the healed type was often mentioned.
The next period apparently started with Fischer8 who was one of the first to
stress the microscopic changes found. Fischer discarded most of the cases reported previous to his time because of the lack of histologic descriptions. The
microscopic criteria accentuated since then have included the presence of extensive necrosis of the myocardium, lymphocytes in the involved areas, dilated
capillaries, connective tissue scars, giant nuclei in the myocardial fibers, and
aggregations of leucocytes in the lumens of the capillaries.
A second series of case reports deals with "idiopathic cardiac hypertrophy"
in infants and children. In a review of this entity by Kugel and Stoloff18, and
in later reports by Mahon21 and by Weissman37 there are many cases in which the
gross description of the heart parallels that of the so-called "fetal endocarditis."
Thirteen of the cases reported by Kugel and Stoloff and two of Mahon's cases
have similar descriptions. These two groups of cases have lesions with similar
features and seem to represent the same disease, but some authors emphasize
the cardiac hypertrophy while others emphasize the valvular lesions.
The gross pathologic findings in endocardial sclerosis are quite variable. The
simplest form consists of thickening and opacity of the endocardium and the extreme form has severely distorted valves. The heart is almost always enlarged
due to fibrosis of the myocardium and to dilatation of the chambers, chiefly of the
ventricles. Occasionally bland mural thrombi may be attached to the thickened
endocardium. Brownish and grayish streaks, representing focal degenerative
changes, may be found in the myocardium, most frequently in the papillary
muscles. The coronary arteries are normal.
The microscopic changes include both vacuolar and fatty degeneration, focal
* Received for publication, February 19, 1946.
322
ENDOCARDIAL SCLEROSIS IN INFANTS
323
myocardial necrosis or atrophy, giant myocardial nuclei, adventitial thickening in
the myocardial vessels, thickened endocardium with large amounts of collagenous and small amounts of elastic tissue in fibrils arranged parallel to the surface with extensions into the myocardium, and occasionally lymphocytic infiltrations, dilated or excessive formation of new capillaries in the abnormal valvular and endocardial tissue, or foci of myocardial calcification.
THEORY OP INTRAUTERINE INFLAMMATION
The likelihood of congenital syphilis has been ruled out in most cases. Recently evidence has been presented that 100 per cent of mothers who contract
rubella in the first two months of pregnancy and approximately 50 per cent of
expectant mothers who contract this disease during the third month of pregnancy,
give birth to infants with congenital anomalies, the most frequent of which are
cataracts, cardiac septal defects, patent ductus arteriosus, deaf mutism and
microcephaly3'10. The mode by which this type of infection may produce
congenital anomalies in the fetus is not known. Similarly the mode of transmission of infection from mother to fetus is not adequately explained by those
authors who regard endocardial sclerosis as an inflammatory lesion. The most
authentic evidence presented has been the microscopic findings. Monckeberg23
regarded the microscopic changes as inflammatory in nature because he had not
seen such changes even in the most severe malformations. Abbott 1,2 demonstrated inflammatory changes in the myocardium in most cases of atresia of the
valvular orifices.
Stohr34 found in two cases microscopic changes which she interpreted as inflammatory. These included round cell infiltration, necrosis, calcification,
fibrosis and connective tissue scars. Other changes which have been regarded as
inflammatory are complete or partial occlusion of the blood vessels, atrophy
associated with hyaline or fatty degeneration of muscle fibers, fibroblastic proliferation, thickening of the endocardium, and cicatrization near the atretic
valves7,28. Farber and Hubbard suggested that the gross valvular distortion
and thickened endocardium are end results of inflammatory changes.
Antagonists of the inflammatory thory have used various arguments. Some
authors 26'29 have not found any changes which they could regard as inflammatory. Mahon considered the history of antecedant acute infection as insufficient
to explain the cardiac changes in his two cases; and when infection was present,
that it precipitated decompensation rather than produced hypertrophy or cardiac changes. Gross11 believed that it was unusual for so destructive a lesion,
if inflammatory, to remain sharply localized in a papillary muscle or in the endocardium. To him the myocardial lesions resembled bland infarcts because there
were not endarteritic vascular changes present in the scar, and similar changes
were found in non-inflammatory cardiac defects. Ribbert 27 believed that the
cardiac ostia, deformed through maldevelopment, may show microscopic changes
similar to those in endocardial sclerosis. Keith15 stated that such lesions are
not inflammatory because it was impossible to conceive of endocarditis giving
rise to the great majority of the lesions described. He failed to find scar tissue
324
G. E. COSGROVE, JR. AND D. H. KAXJMP
in the neighborhood of the lesions except in those cases where superimposed
postnatal infection occurred. Furthermore he found malformations present
in other parts of the body in some cases.
THEORY OF PRIMARY DEFECT IN THE EMBRYO
Congenital heart lesions generally are considered to be due to one of the two
following factors, or to a combination of the two: (1) primary defects or arrest in
development of the embryo, probably due to germ cell deficiency or environmental factors in utero, and (2) infection in the mother which may be transmitted
through the placental barrier to the fetus. The changes due to this latter factor
are believed to occur in the fetus after the third month in utero, and consists of
stenotic or atretic valves with associated myocardial lesions, the relationships
of the septa and great vessels remaining normal.
Weinberg and Himmelfarb86 found endocardial sclerosis in two siblings. Since
there was no infection in the mother during either pregnancy, they believed that
the endocardial sclerosis represented an inherent developmental defect. Rossman29 concluded that these defects arise as developmental errors. Other
authors 11,26 regarded endocardial sclerosis as a primary developmental defect
or as a simple hyperplasia of the nbro-elastic tissue, possibly secondary to a
circulatory change. The hyperplastic endocardium constricts the orifices of
the small vessels communicating with the cavities of the heart, producing stasis
and some degree of myocardial anoxia. The myocardial changes can then be
regarded as secondary to obliteration of the lumens of the arteries and of the
capillaries and Thebesian vessels.
CLINICAL PICTURE
The clinical picture presented by patients with endocardial sclerosis is quite
constant and is characterized by cyanosis, dyspnea, and sudden death. In an
analysis of 36 cases, the following symptoms were encountered in the indicated
number of cases:
cyanosis, 29
dyspnea, 33
edema, 7
irritability and convulsions, 6
vomiting, 4
anorexia, 3
fever, 3
cough, 3
loss of weight, 1
HISTORY OF MATERNAL HEALTH
Although obstetrical histories are often incomplete regarding illnesses of the
mother during the months of pregnancy, the state of the mother's health was
mentioned in 33 cases. Of the 33 mothers, 21 were normal and healthy during
the period of pregnancy. The remaining 12 had illnesses or a history of associated abnormality of some type, as follows: bronchitis, 2 months antepartum;
diarrhea, 8 months antepartum; influenza, 6 weeks antepartum; influenza several
weeks antepartum; abscess of Bartholin's gland incised during pregnancy;
rhinitis at delivery; cardiac disease of undetermined type; cardiac disease of
ENDOCARDIAL SCLEROSIS IN INFANTS
325
unstated type; "cold" for two weeks antepartum; infant born 1 month prematurely; family history of allergy; two relatives of mother together lost 4 children
under similar circumstances. It is suggested that there may be some increase
in the frequency of significant diseases in the mother, and especially in diseases
which occur early in, or are continued throughout, the course of pregnancy.
REPORT OF CASES
Case 1. A3 month old white female was born 2 months prematurely and at birth weighed
3 | pounds. Growth and development were normal. The mother's history was non-contributory. The day before admittance the child cried a good deal but seemed otherwise
normal. On the day of hospitalization she became cyanotic and had generalized tremors.
There was no elevation of temperature. Tachycardia and dyspnea developed and multiple
cutaneous hemangiomata were noted. Oxygen therapy was given because of rapid, shallow,
respirations. Shortly after receiving a small transfusion she became cyanotic and expired
5 hours after admittance. At necropsy she was 56 cm. in length and weighed 3500 grams.
Multiple cutaneous hemangiomata were noted, but there was no edema, ascites, or jaundice.
On opening the thorax the pericardium measured 7.5 cm. transversely. The thymus
weighed 15 grams and appeared normal. Both lungs together weighed 90 grams and each
showed patchy areas of consolidation in the lower lobe. The heart occupied most of the
thoracic cavity. It weighed 54.5 grams (normal 23 grams). There were numerous subepicardial ecchymoses. The foramen ovale was barely patent. The valves appeared normal and had the following measurements: aortic 2.5 cm., mitral 4 cm., tricuspid 5 cm., pulmonic 2 cm. The left ventricular wall was markedly dilated and hypertrophied. The
endocardial surface, especially over the septum and below the aortic valve, was opaque and
very thick. The myocardium and the coronary arteries appeared grossly normal. The
abdominal organs were essentially normal: The final diagnoses were: endocardial sclerosis
of the left ventricle with cardiac hypertrophy and left ventricular hypertrophy; localized
fibrous pericarditis; bilateral pulmonary atelectasis; multiple sessile cutaneous hemangiomata; ovarian retention cysts.
Case 2. A 5J month old white female infant was normal at birth. The prenatal history
was negative. There was a history of "something in the chest" of the child since birth.
For approximately one week previous to hospitalization there had been dyspnea and tachypnea which were regarded as possibly due to bronchopneumonia. On entering the hospital
her temperature was 103°F. and the skin was hot and dry. There was slight rhinitis and the
pharynx was injected. Marked dyspnea and retraction of the intercostal spaces were present. The respiratory rate was 34 per minute and there were crackling rales in both lung
fields. Oxygen was administered but the child grew rapidly worse, the temperature rose to
107°F., and she expired two hours after admittance. At necropsy she was 63 cm. in length
and weighed 6050 grams. External inspection revealed no gross changes. On opening the
thorax the pericardium measured 7.6 cm. transversely and the thymus appeared normal.
Both lungs together weighed 150 grams and revealed mottled areas of discoloration, diminished crepitation with atelectasis, and patchy areas of frothing and edema. The heart
weighed 78 grams (normal 31 grams). Both atria were dilated, the endocardium of the left
ventricle was thickened and grayish-white and the same change was present to a lesser degree in the right ventricle. The valves and their measurements were normal. The abdominal organs were normal. The final diagnoses were: endocardial sclerosis with involvement
of both ventricles; dilatation and hypertrophy of all chambers of the heart, and particularly
of the left ventricle; bilateral pulmonary atelectasis with areas of pulmonary edema and
bronchopneumonia.
Case 3. A newborn white male infant weighed 7 pounds 6 ounces following a normal
spontaneous delivery. The mother's past history and present pregnancy were uneventful.
Male
Male
Female
5 mo.
3 mo.
6iyr.
Kugel-Stoloff,
Case 5
Kugel-Stoloff,
Case 6
Kugel-Stoloff,
Case 7
Cardiomegaly with thick, grayish-white endocardium a b o u t mitral valve; dilatation a n d
h y p e r t r o p h y of ventricles with mural t h r o m b i
in both ventricles.
Cardiomegaly with dilatation and h y p e r t r o p h y
of left auricle and right and left ventricles;
general endocardial thickening.
Marked cardiomegaly involving all chambers;
grayish s t r e a k s between myocardial fasciculi;
thickening of endocardium of left auricle a n d
b o t h ventricles.
M a r k e d cardiomegaly; p a t e n t foramen ovale;
h y p e r t r o p h y of both ventricles.
15 mo.
Kugel-Stoloff,
Case 4
Male
Cardiomegaly; heart flabby and globular; dilat a t i o n of all chambers; endocardium of left
ventricle and auricle thickened.
3 mo.
Cardiomegaly, subepicardial hemorrhages; h y p e r t r o p h y and dilatation of both sides; slight
edema of mitral and tricuspid leaflets.
GROSS CARDIAC FINDINGS
Kugel-Stoloff,
Case 3
SEX
6 mo.
AGE
Kugel-Stoloff,
Case 2
AUTHOR
TABLE 1
R E P O R T S OF C A S E S FROM T H E L I T E R A T U R E
Thickening of endocardium of left ventricle
with organizing t h r o m b i ; interlacing zones
of hypertrophic and atrophic muscle fibers;
areas of fibrosis in degenerating muscle.
Areas of well formed myocardium interspersed
with atrophic muscle and fibroblastic replacement; m a r k e d periarterial
fibro-elastic
proliferation; thickening of media and some
intimal proliferation.
M a n y hypertrophic myocardial fibers; thickening of small coronary arteries with perivascular fibrosis and mild lymphocytic
infiltration; areas of degenerated muscle
fibers with fibrosis; marked
fibro-elastic
thickening of endocardium.
Areas of degeneration of myocardium with
occasional replacement b y loose fibrous tissue ; some hypertrophic muscle fibers; diffuse
lymphocytic infiltration; thick layer of proliferating endocardium.
Areas of myocardial a t r o p h y between areas of
h y p e r t r o p h y ; interfascicular fibrosis; fibroelastic thickening of endocardium; thickening of muscular media of coronary arteries
with elliptical perivascular fibrosis.
H y p e r t r o p h y of muscle fibers with interfascicular fibrosis; atrophic fibers between hypertrophied fibers; beneath endocardium of left
ventricle, swelling and perivascular fibrosis
with a few mononuclear cells,
fibro-elastic
thickening of vessels with medial thickening,
slight proliferation and desquamation of
intima.
MICROSCOPIC CARDIAC FINDINGS
d
SJ
o
DO
o
SJ
o
<
O
H
p
OS
CO
M a r k e d thickening of endocardium of b o t h ventricles; slight aneurysmal dilatation of conus.
Cardiomegaly; flattening of walls of left ventricle with thickening of endocardium.
M a r k e d cardiomegaly; h y p e r t r o p h y of left ventricle with diffuse thickening of endocardium.
D i l a t a t i o n and h y p e r t r o p h y of b o t h ventricles;
thickening of endocardium of left ventricle.
Cardiomegaly; dilatation and h y p e r t r o p h y of
b o t h ventricles; marked thickening of endocardium of all chambers.
Cardiomegaly; moderate dilatation with hypert r o p h y of ventricles; marked thickening of
endocardium of all chambers.
14 mo.
14 mo.
4§ mo.
9
3 | mo.
4 wk.
6 wk.
Oberndorffer
Weinberg a n d
Himmelfarb
Krstulovic
Weinberg and
Himmelfarb
Weisman
Weisman
Female
Male
Female
C o a r c t a t i o n of a o r t a ; cardiomegaly; hypert r o p h y and dilatation of left ventricle; thickening of endocardium of left ventricle.
Cardiomegaly; h y p e r t r o p h y of left ventricle;
thickening of endocardium; weight of t h y m u s ,
42 grams.
Hauser
Male
3 mo.
Steiner a n d Bogin
myocardium;
Fibro-elastic thickening of endocardium.
Moderate thickening of endocardium; perivascular and some interstitial fibrosis; occasional areas of a t r o p h y and degeneration of
myocardial fibers.
Foci of fibro-elastic thickening of endocardium
of right h e a r t ; uniform thickening of endocardium of left ventricle.
H y p e r t r o p h y of muscle fibers.
Fibro-elastic hyperplasia of endocardium;
numerous dilated thin-walled venous channels in myocardium.
H y p e r t r o p h y of muscle cells.
Edema a n d h y p e r t r o p h y of muscles; some
hydropic degeneration.
Fibrosis of endocardium and
vascular sclerosis.
Cardiomegaly; thickening of endocardium of
left auricle and ventricle.
14 wk.
and
Crawford
Weiss
H y p e r t r o p h y of muscle fibers.
Cardiomegaly with dilatation and h y p e r t r o p h y
of b o t h ventricles; thickening of endocardium
of left ventricle; slight thickening of edge of
m i t r a l valve.
3yr.
Michaud
H y p e r t r o p h y of muscle fibers.
Cardiomegaly; diffuse thickening of endocardium of left ventricle.
14 mo.
Hedinger
Calcific deposits in myocardium.
Myocardium vacuolization and fibrosis.
MICROSCOPIC CARDIAC FINDINGS
Mitral insufficiency.
Aortic and mitral involvement; hypertrophy of
ventricles, thickening of endocardium of left
ventricle.
Aortic atresia; hypoplasia of left ventricle and
aorta; hypertrophy of right ventricle; thickening of endocardium.
Pulmonary atresia; tricuspid stenosis; hypertrophy of right ventricle.
Aortic atresia; hypoplasia of left side of heart.
Cardiomegaly; aortic stenosis with fusion of leaf- Thickening of endocardium of left ventricle;
capillary congestion; calcification; necrosis
lets; defect of mitral cusps; patent foramen
in and near capillary muscles; small aggreovale; shortening of papillary muscles of right
gates of erythrocytes; thick hyaline vascular
ventricle; endocardium of left ventricle, thick
sheaths; localized necrosis and thickened
and white.
blood vessels in right ventricle; thickening
of endocardium with irregular myocardial
fibers; myocardial
vacuolization
and
atrophy.
1| hours
5 wk.
40 hr.
2 days
12 hr.
2 days
Ganeff
Fischer
Loesser
von Zalka
Bellet and
Gouley
Stohr
Myocardial scarring.
Myocardial fibrosis.
Thickening of endocardium.
Acute and chronic myocarditis; scarring and
calcification.
Verrucous endocarditis; myocardial fibrosis.
Endocardial fibrosis, myocardial degeneration
and calcification.
Aortic and mitral stenosis; thickening of endocardium of left ventricle.
4 hours
Endocardial and myocardial fibrosis.
Kockel
Aortic stenosis; thickening of endocardium of
left ventricle.
Hypoplasia of left ventricle; thickening of aortic Myocardial fibrosis.
valve; thickening of endocardium of left ventricle.
Calcification of papillary muscles of right ventricle.
Aortic stenosis; thickening of endocardium of
left ventricle.
GROSS CARDIAC FINDINGS
4 days
Male
SEX
Monckeberg
Premature
3 wk.
Jacobsthal
Ruge
4 days
AGE
Stiassny
AUTHOR
TABLE 1—Continued
a
p
>
o
<
©
CO
o
o
H
a
CO
w
Thickening of endocardium, especially near
atretic valves.
Replacement of the myocardium by dense
fibrous connective tissue in region of atretic
aortic valve.
Aortic and mitral atresia; thickening of endocardium of left ventricle; patent foramen
ovale; hypoplasia of aorta and left side of
heart.
Cardiomegaly; marked hypertrophy of right
ventricle; aortic atresia with stenosis of ascending aorta; patent foramen ovale; patent
ductus arteriosus; rudimentary left ventricle.
Male
Male
Female
Male
Male
62 hr.
60 hr.
13 mo.
2|yr.
9 days
Philpott
Wesson
Beaver
Mahon
Mahon
Stohr
Marked fibro-elastic hyperplasia of endocardium with extensions into myocardium;
massive and irregular fibrosis of mitral
valve; some areas of moderate interstitial
round cell infiltration; occasional interstitial
hemorrhage; swelling and proliferation of
endothelium of capillaries.
Elastic connective tissue thickening of endocardium of left ventricle and left auricle;
calcific myocardial deposits in necrotic areas;
hyperemia with engorged capillaries; small
area of calcification on tricuspid valve;
round cell infiltration in aortic adventitia.
Cardiomegaly with dilatation of both ventricles;
entire endocardium thickened and opaque,
especially in left chambers; thickening of leaflets with nodular fibrosis of mitral and tricuspid valves; patent foramen ovale; translucent
plaque on left auricular wall.
Cardiomegaly; distension of right side of heart;
mitral stenosis with only one free leaflet; aortic stenosis with triangular valve flaps;
aneurysmal dilatation of pulmonary artery
with large ductus arteriosus; endocardium of
left ventricle thickened and opaque.
Cardiomegaly with dilatation of all chambers; Marked fibro-elastic thickening of endocardium, predominently elastic at base, more
endocardium of left auricle and ventricle thickcollagenous near surface; irregular extenened and grayish-white; chordae tendineae
sions into myocardium; marked periarterial
and papillary muscles thickened and shortened;
fibrosis; many areas of thinning and of
slight to moderate fibrosis of all valves.
granular degeneration of myocardium and
disappearance of muscle; dense collections
of large and small round cells along veins.
Myocardial calcification of right ventricle and
both auricles; marked thickening of endocardium.
Extensive calcification of myocardium of right
auricle with thickening of endocardium.
Female
30 min.
Diamond
and
Fibro-elastic tissue hyperplasia of endocardium with extension into myocardium.
One insufficient mitral cusp; thickening of endocardium of left auricle and ventricle; absence
of papillary muscles of left ventricle with very
short chordae tendineae.
5 | mo.
Sano and Anderson
Male
Male
Male
Male
20 hr.
4 days
36 hr.
15 days
2\ mo.
5 mo.
3 days
Roberts
Rossman
Farber and
Hubbard
MacGregor and
McKendry
Farber and'
Hubbard
Farber and
Hubbard
Farber and
Hubbard
Male
Female
SEX
AGE
AUTHOR
Endocardial fibrosis; myocardial fibrosis and
calcification.
Fibro-elastic thickening of endocardium of
left ventricle and auricle; small patches of
scarring and calcification in subendocardial
muscle.
Fibrosis and calcification of myocardium with
cellular infiltration.
Old healed endocarditis with superimposed
acute endocarditis and myocarditis.
Thickening of endocardium.
Aortic stenosis with hypertrophy of both ventricles; hypoplasia of aorta; thickening of endocardium of left ventricle; patent ductus
arteriosus; nodular fibrous thickening of aortic valve; adherent thrombi about aortic cusps
and apex of left ventricle.
Aortic stenosis; thickening of endocardium of
left auricle and ventricle.
Pulmonary stenosis with secondary acute terminal streptococcal endocarditis.
Aortic and mitral stenosis; hypoplasia of left
auricle and ventricle; thickening of endocardium of left auricle and ventricle.
Collagenous and moderate elastic thickening
of endocardium of left ventricle.
Thickening of endocardium, especially of left
ventricle with partial or complete obliteration of blood vessels; myocardial fibrosis
with fibroblastic proliferation; hyaline and
fatty degeneration and atrophy of muscle
fibers; calcification and scarring near atretic
valve.
MICROSCOPIC CARDIAC FINDINGS
Aortic atresia with hypoplasia of left auricle and
ventricle; hypoplasia of ascending aorta; thickening of endocardium of left ventricle.
Aortic atresia; mitral stenosis; hypoplasia of
aorta, left auricle and ventricle; patent foramen ovale and ductus arteriosus; hypertrophy
of right ventricle; thickening of endocardium
of left heart.
Mitral stenosis; aortic atresia; hypoplasia of
left ventricle; stenosis of arch and ascending
aorta; patent foramen ovale; hypertrophy of
right ventricle; dilatation of pulmonary artery; patent ductus arteriosus.
GROSS CARDIAC FINDINGS
TABLE 1—Continued
19 m o .
3 days
7 days
Cosgrove and
K a u m p , Case
4
Cosgrove a n d
K a u m p , Case
5
Cosgrove a n d
K a u m p , Case
6
Male
Male
Female
Male
3i mo.
Cosgrove a n d
K a u m p , Case
2
29 h r .
Female
3 mo.
Cosgrove and
K a u m p , Case
1
Cosgrove and
K a u m p , Case
3
Female
5 yr.
Peale and Lucchesi
Female
4 days
Gross
Cardiomegaly with hypoplasia of left ventricle;
m i t r a l stenosis; endocardium of left ventricle
thickened a n d opaque; bicuspid aortic valve
with stenosis; dilatation and h y p e r t r o p h y of
t h e right ventricle; dilatation of both auricles;
p a t e n t ductus arteriosus. •
Cardiomegaly with h y p e r t r o p h y of b o t h ventricles; endocardium of all chambers thickened
and opaque with leaflets of mitral a n d aortic
valves thickened and rolled.
Cardiomegaly; dilatation a n d h y p e r t r o p h y of
left ventricle; moderate h y p e r t r o p h y of right
ventricle; leaflets of mitral valve thickened
and rolled.
Cardiomegaly; dilatation a n d h y p e r t r o p h y of
left ventricle; fibrosis a n d stenosis of aortic
and mitral valves; minimal thickening of leaflets of tricuspid and pulmonary valves.
Cardiomegaly; thickening of endocardium of
left and right ventricles.
Cardiomegaly with subepicardial ecchymoses;
minimal p a t e n c y of foramen ovale; dilatation
and h y p e r t r o p h y of left ventricle; marked
thickening a n d opacity of endocardium of left
ventricle.
H y p e r t r o p h y of myocardium; thickening of endocardium.
Aortic and mitral stenosis with hypoplasia of
root of a o r t a a n d rudimentary development of
left ventricle; p a t e n t ductus arteriosus; diffuse parietal endocardial sclerosis of left ventricle.
Hyperplasia of elastic tissue of endocardium of
left side of h e a r t .
Dense collagenous endocardial sclerosis with
a b u n d a n t elastic fibrils arranged parallel t o
free surface; projection of coarse endocardial
trabeculations into myocardium; extensive
fibrosis of r u d i m e n t a r y papillary muscles
with collagenous formation.
332
G. E. COSGROVE, JR. AND D. H. KAUMP
After delivery the child had intermittent attacks of cyanosis with a weak grunting cry and
weak respirations. The temperature was 99.4°F. The roentgenograms revealed an enlarged heart. On physical examination there were cyanosis and dyspnea, but no cardiac
murmurs were heard. The respirations became more labored and cyanosis more marked, in
spite of the inhalation of oxygen and of carbon dioxide intermittently. He expired 29 hours
after delivery. At necropsy there was no edema. On opening the thorax the pericardium
measured 7.5 cm. transversely, the heart occupied most of the anterior portion of the
thoracic cavity, and had displaced both lungs backward. The thymus weighed 18 grams
and was grossly normal. The combined weight of the lungs was 55 grams and there was
massive fetal atelectasis. The heart weighed 57 grams (normal 25 grams) and there was
marked dilatation and hypertrophy, especially of the left ventricle and left auricle. The
aortic valve measured 1.4 cm. in circumference. The leaflets were rolled, glistening, thickened and edematous. The mitral valve measured 3 cm. in circumference and was similarly
involved but to a lesser degree. The tricuspid valve measured 5 cm. in circumference and
the pulmonic valve 2.9 cm. and both showed minimal thickening and rolling of the leaflets.
The myocardium and the coronary arteries were normal. There were multiple small super-,
ficial mucosal ulcerations of the stomach but no gross abnormalities were noted in the other
organs. The final diagnoses were: endocardial sclerosis with aortic and mitral endocarditis
and minimal involvement of the tricuspid and pulmonic valves; hypertrophy of the heart;
dilatation and hypertrophy of the left auricle and ventricle (grade 3); uric acid infarcts of
both kidneys; bilateral fetal pulmonary atelectasis.
Case 4- A 19 month old white female was admitted to the hospital with a history of two
weeks' duration of upper respiratory infection, general malaise and fever. For the last day
she had refused food. The child had previously been healthy. Examination revealed nasal
discharge, a reddened pharynx, increased tactile fremitus and increased breath sounds over
both lung fields, and rales on the right side. There was a marked tachycardia and a to-andfro murmur over the precordium. The heart was enlarged and there was a right bronchopneumonia. The child became rapidly worse and expired two hours after admittance. At
necropsy no external gross pathologic changes were noted. Both lungs together weighed
226 grams. All the lobes had an increased consistency, diminished crepitation and purplish-red color with frothing and edema (grade 2). The heart weighed 110 grams (normal 54
grams) and was globular in shape. All valves were normal except the mitral whose leaflets
had thick rolled edges. The chordae tendineae were short and thick. The left ventricle
was dilated and hypertrophied (grade 2). The right ventricle was hypertrophied (grade 2).
The left auricle was dilated. The myocardium and coronary arteries were normal. The
abdominal organs were grossly normal. The final diagnoses were: endocardial sclerosis
with involvement of the mitral valve; dilatation of the left auricle and ventricle (grade 2);
hypertrophy of the heart with hypertrophy of the right auricle (grade 1), and of the right
ventricle (grade 2); right confluent bronchopneumonia; toxic swelling of the liver, spleen
and kidneys; patent foramen ovale (anatomical); generalized lymphadenopathy (grade 2).
Case 5. A newborn white male infant was born normally at term to a 31 year old mother,
whose present and past health was good. She had one previous pregnancy which resulted
in a living male child. Her physical examination and history revealed no disease. On the
day after birth the baby became cyanotic, had rapid respirations, and was given inhalations
of oxygen. Roentgenograms showed gross cardiac enlargement. On the following day he
was extremely cyanotic and tachypneic, and on the third day of life he expired. At necropsy
he was 56 cm. in length and weighed 4270 grams. No edema or external abnormalities were
noted. The lungs showed bilateral patchy fetal atelectasis, the thymus appeared normal,
and the heart weighed 42 grams (normal 25 grams). The foramen ovale was widely patent.
The aortic and mitral valves were markedly altered and the leaflets were nodular, opalescent
and pinkish-gray. The endocardium of all chambers was thick and grayish-white in color.
Both ventricles were hypertrophied, the right slightly more than the left. The myocardium
ENDOCARDIAL SCLEROSIS IN INFANTS
333
and the coronary arteries appeared grossly normal. The abdominal organs were grossly
normal. The final diagnoses were: endocardial sclerosis of all chambers with involvement
of the aortic and mitral valves; hypertrophy of the heart with hypertrophy of the left ventricle (grade 2), and dilatation and hypertrophy of the right ventricle (grade 3); patent ductus arteriosus and patent foramen ovale; bilateral partial fetal pulmonary atelectasis.
Case 6. The patient was a full term, normal white male infant, born by a normal spontaneous delivery. The mother was an eighteen year old primipara. She had gained thirtyfour pounds during the pregnancy and developed a dependent pitting edema. Her blood
pressure was 140 systolic and 110 diastolic, and her past health had been good. The infant
was considered to be normal until the third day of life when cyanosis and labored respirations appeared. Roentgenograms revealed a heart of normal appearance. With oxygen
therapy the infant showed no improvement and death occurred on the seventh day of life.
At necropsy there was generalized cyanosis. The body was 55 cm. in length and weighed
3250 grams. On opening the thorax the pericardium measured 6 cm. transversely, the thymus was normal, and the pleural surfaces showed numerous petechiae. The heart weighed
41 grams. Both atria and the right ventricle were dilated. The ductus arteriosus and the
foramen ovale were anatomically patent. The aortic valve was stenosed and bicuspid.
The mitral valve was stenosed with a thick opaque, rolled valvular endocardium. The
left ventricle was hypoplastic and the endocardium was composed of a thick yellowish
fibrous layer. The abdominal organs were grossly normal. The final diagnoses were:
endocardial sclerosis with aortic and mitral involvement and stenosis; bicuspid aortic valve;
hypoplastic left ventricle; patent ductus arteriosus and patent foramen ovale; hypertrophy
of the heart (weight 41 grams, normal 20 grams); chronic passive congestion of the liver,
lungs, kidneys and spleen; bilateral partial fetal pulmonary atelectasis.
Microscopic Findings
In the six cases here reported, it was found that when the valves were involved
in addition to the mural endocardium, the myocardial lesions were more extensive
and severe than when the mural endocardium alone was involved.
The microscopic changes in the hearts of our six patients were all similar
and varied only in extent of involvement. In those hearts which were apparently
least involved there was a simple thickening of the endocardium, which was
composed mostly of collagenous connective tissue with some apparent increase
of elastic tissue. In many areas the thickened connective tissue extended as
finger-like projections between the myocardial fibers. In some areas the thickening assumed a distinctly nodular appearance and resembled myxomatous tissue.
Sometimes there was a suggestion of a cartilaginous component at the base of
the valves, particularly of the aortic valve, although no definite lacunae were
seen. Aschoff nodules were not found. In hearts with valvular lesions there
was an increased vascularity of the central stroma. The covering endocardium
was considerably thickened and the tissue was myxomatous. Occasionally small
vessels showed much narrowing of their lumens, due apparently to the endothelial
fibrosis. The myocardium was often extremely vascular and there were numerous areas of degeneration, varying from beginning loss of striation of the
fibers and distortion of the nuclei to fibers in which there were only small fibrillary
remains. In some areas the necrosis was extensive with calcification. In no
case was there any definite evidence of an inflammatory change such as the presence of myocardial giant cells or lymphocytic or polymorphonuclear infiltration.
334
G. E. COSGROVE, JR. AND D. H. KAUMP
FIG. 1
(CASEI).-
ENDOCARDIAL SCLEROSIS OF THE L E F T VENTRICLE
There is some distortion of the leaflets of the aortic valve
J?IG. 2 ( C A S E 1).
M A R K E D SUBENDOCARDIAL F I B R O S I S OF ENDOCARDIUM OF L E F T VENTRICLE
AND E X T E N S I O N OF F I B R O S I S INTO MYOCARDIUM.
X125
ENDOCARDIAL SCLEROSIS IN INFANTS
F I G . 3 ( C A S E 3).
335
ROENTGENOGRAM OF C H E S T T A K E N W I T H PORTABLE A P P A R A T U S , D E M O N STRATING CARDIAC H Y P E R T R O P H Y
F I G . 4 ( C A S E 3). H E A R T SHOWING H Y P E R T R O P H Y AND D I L A T A T I O N O F L E F T V E N T R I C L E
ENDOCARDIAL SCLEROSIS AND MALFORMATION OF AORTIC VALVE
G. E. COSGHOVE, JR. AND D. H. KAUMP
iMb*
FIG. 5
(CASK •>•.
F I G . 6 ( C A S E 3).
SI.ITHIN
<>F- Nnnri.Mt I-'IHIIIM s M A S VENTRICLE.
X125
FHOM
I-AIHH-AKIHUM OF L E F T
SECTION OF L E A F L E T OF AORTIC V A L V E , SHOWING INCREASED T H I C K N E S S ,
E D E M A AND D I S T O R T I O N OF V A L V E .
X45
ENDOCARDIAL SCLEROSIS IN INFANTS
F I G . 7 ( C A S E 3).
SECTION OF L E A F L E T OF AORTIC VALVE SHOWING M A R K E D E D E M A OF
STROMA.
X200
F I G . 8 ( C A S E 3).
SECTION FROM SUBENDOCARDIUM OF R I G H T VENTRICLE SHOWING F I B B O S I S
AND SMALL VASCULAR C H A N N E L W I T H I N A R E A OF SCLEROSIS.
X200
338
G. E. COSGROVE, JR. AND D. H. KATJMP
F I G . 9 ( C A S E 5).
F I G . 10
( C A S E 5).
ROENTGENOGRAM OF C H E S T T A K E N W I T H P O R T A B L E A P P A R A T U S , D E M O N STRATING CARDIAC E N L A R G E M E N T
H E A R T SHOWING ENDOCARDIAL SCLEROSIS OF L E F T VENTRICLE AND
MALFORMATION OF AORTIC VALVE
ENDOCARDIAL SCLEROSIS IN INFANTS
339
There were occasional zones with slight increase in "myocytes". Areas of myocardial necrosis and degeneration were particularly prominent in the papillary
muscles and were less frequent in the interventricular septum. Except for the
Thebesian vessels, the veins in the myocardium were generally normal, and no
thrombosis was found. There were occasional areas in the larger and medium
sized coronary arteries in which there was a slight medial degeneration and malalignment of the inner muscular cells of the media. There was also some increased perivascular connective tissue. The pericardium, except for an occasional petechial hemorrhage in the subpericardial tissue, was essentially normal
in all instances. There were no abnormal findings in the nerves.
COMMENT
In the cases herein reported or reviewed, there were few evidences of inflammation in the production of the endocardial sclerosis. The extent of myocardial
involvement seems to be related to the extent of endocardial involvement.
If only the mural endocardium was involved, the myocardial changes were scant
but if endocardial involvement was extensive and included the valves, then
myocardial involvement was more extensive. When myocardial lesions occurred, they resembled infarctions rather than inflammatory lesions. This
appearance together with the relative or complete occlusion of the smaller mural
arterial and venous channels emphasizes the probability of the congenital nature
of primary endocardial sclerosis. The microscopic appearance of the valve
rings with its myxomatous stroma and absence of lymphocytes and polymorphonuclears, calls to mind that of "congenital rests" of tissue such as fibroma of
the medulla of the kidney. The marked edema, the absence of advancing proliferation of connective tissue, the relatively young connective tissue and the
apparent minimal tendency toward vascularization all seem to us to indicate
the congenital character of this lesion.
CONCLUSIONS
It is suggested that illness of the mother during pregnancy may be a factor
in the production of endocardial sclerosis in the infant. We believe that because
of the gross as well as of the microscopic characteristics of the lesion, endocardial
sclerosis should be considered as a form of congenital heart disease.
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