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The Diagnosis of Primary Endocardial Fibroelastosis

By FRANK J. SELLERS, M.D., JOHN D. KEITH, M.D., AND JAMES A. MANNING, M.D.
THE term endocardial fibroelastosis was of primary endocardial fibroelastosis with
first used by Weinberg and Himelfarbl other similar conditions.
to describe the condition of infantile cardi-
omegaly in which the pathologic lesion con- Case Material and Criteria for Diagnosis
sisted of varying degrees of fibroelastotic The details of 25 autopsied cases of primary
proliferation within the endocardium. It is endocardial fibroelastosis and 33 cases with simi-
lar clinical findings were reviewed. These infants
now well recognized that there are two forms were seen between the years 1952 and 1960 at
of endocardial fibroelastosis. The first is asso- the Hospital for Sick Children, Toronto, and the
ciated with numerous congenital heart defects Strong Memorial Hospital, Rochester, New York.
and appears to be secondary to them or has The two groups may be defined as follows: group
occurred simultaneously during their devel- I, 25 cases proved at autopsy without valvular
disease and with at least one electrocardiographic
opment. The second is comprised of a group tracing in each case; group II, 33 cases diagnosed
with a marked degree of endocardial thicken- clinically that satisfied the criteria set out below
ing with no obvious explanation for it. The and were observed 2 to 8 years from the onset of
pathologic picture is sufficiently characteristic the illness.
that pediatric pathologists in recent years have The data collected from group-I cases were re-
viewed in detail. It was noted that the diagnosis
recognized it as a distinct entity and re- had been made clinically during life in the cases
ferred to it as primary endocardial fibro- with certain features. A reassessment of this ma-
elastosis.2 terial provided the criteria that were applied to
Vlad et al.3 published the electrocardio- the clinical group II. The criteria established were
onset of congestive heart failure under 2 years of
graphic findings in 23 postmortem cases of age; absence of organic heart murmurs; electro-
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primary endocardial fibroelastosis, and dem- cardiographic evidence of left ventricular over-
onstrated a high incidence of left ventricular loading; and abnormal T waves in leads V3 and
loading patterns. They did not distinguish V6.
between cases with and without valvular in- Congestive heart failure was considered to be
an essential feature of the clinical diagnosis of
volvement. While no attempt was made to endocardial fibroelastosis. All cases proved at au-
define clearly the diagnostic features of this topsy in our series had symptoms and signs of
group clinically, the electrocardiographic pat- congestive heart failure before 21 months of life.
tern was sufficiently suggestive to encourage The absence of organic heart murmurs was a
us to assess the problem from this point of necessary criterion for the diagnosis of primary
view.
endocardial fibroelastosis in order to avoid the
question of valvular abnormality. In no cases of
The purpose of this paper, therefore, is to endocardial fibroelastosis proved at autopsy in
analyze the clinical, electrocardiographic or which the aortic, mitral, pulmonary, or tricuspid
radiologic, and pathologic findings in a group valves were normal was an organic heart murmur
of cases of primary endocardial fibroelastosis heard.
The electrocardiographic pattern associated
so that the clinical entity can be more ac- with left ventricular overload appeared in 85 per
curately identified. Furthermore, we wish to cent of the autopsied cases and was present in a
compare the clinical and laboratory features very similar percentage (78 per cent) in the
group of 23 autopsied cases reported by Vlad
et al.3 Therefore, this electrocardiographic pattern
From the Department of Pediatrics of the Uni- was included in the criteria for diagnosis. Similar-
versity of Toronto, The Research Institute of the Hos- ly, flattening or inversion of the T waves in leads
pital for Sick Children, Toronto, Canada, and the V5 and V6 occurred in 92 per cent of all post-
Department of Pediatrics, University of Rochester, mortem cases. When flattening or inversion of the
Rochester, New York. T wave occurred in lead V5, it was also present
Aided by a grant from the Ontario Heart Founda- in lead V6.
tion. If any of the following criteria (1 to 4) were
Circulation, Volume XXIX, January 1964 49
50 SELLERS, KEITH, MANNING
satisfied, left venitricuilair loadcling
iig was eti(nsile-e(l
to lbe pr-esenit: (1) voltage of S in \V1 of more
thani 20 mm.; (2) vxoltage of 1 in \, of more
thaii 20 mmii.; (:3) Q xwve of more taimi '3 miim.
in V-, a V,;. (4) B/S ratio of V, less thati 0.8
mm. indcler 12 mon-tlis of age aiil 0.2 m-m. be-
tween 1-3 aid 24 montlhs of age; aindcl (5) secoll(l
arvy flatten,inig or in-sversioii of tie TF wavse in) V,-
or V6.
It will be seeni from figuires 1 to 3 that criteria I II 1II aVR aVL aVF

1, 2, anid 3 are more definite thani criterion 4.


Criiteriioni 5 was n1ot always presenit ini the atitopsx-
proved groip l)ut was corsi(lered necessary for
the dliaigniosis on1 clinicall gr-onl-ilds aloie.
All the patienits wer.e treated withi digitailis.4
Those treated early ini the illness siurvivedl loniger.
They were theii kept oni digitalis for- at least 2
yes.irs (fig. 4). -t' I l

Signs and Symptoms


Dyspnea and tachycardia occuirred in all
cases in 1b0th grouips. In eases with severe
congestive heart failure grunting respirations V3R V1 V2 V4 vs V6
and cvanosis were frequient. Rales in the chest Figure 1
were heard only occasionally. Congestive heart Electrocardiogram irn 3- mornth-oldl infanlt sIoIws deep
failure was inade one of the criteria for diag- S in VP tall R,Q, and deeply invertedx T in V6, Stb-
niosis and thus was present in all cases in seq ment altopsy recealed typical pninary, e(lo-
cardial fibro elastosis.
both groups. Gallop rhytlhm was most fre-
(jilent in the cases with continuied conigestive The auscultatorv findings were similar in
lheart failuire. both grotups. The average heart rate of all
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Age 8 months Patient: SED.


. T .
5-t f E s w i

1 I Ill AVL RV3 v# V2 V4 VS V6


Figure 2
Electrocardiogriamis taken on a baby diagnosed cliniically as hlaving enldocardial fibroelasto,si.s.
IIe improved stearlily on digitalis therapy. The electrocardiogramt as well as the heart size was
niormi?al at 6 y?ears of age.
C ir ulaion, Vo/lumc XXIX, January 7964
ENDOCARDIAL FIBROELASTOSIS 51
thoracic ratio was 69 per cent, with a range
Proven Cases % )
1C41byPMClinical of 58 to 75 per cent in the clinical group of
42 (33 Diagnosis-)
cases, and 71 per cent, with a range of 56 to
9 80 per cent in the postmortem group; in the
normal infant the cardiothoracic ratio rarely
No of7
Coses
6
exceeds 55 per cent. Although the average
85 heart size was similar in the two groups, only
4 14 per cent of the clinical group had a ratio
greater than 70 per cent, whereas 64 per
2-
cent of the postmortem group had larger
) 2 5 8 11 14 17 20 23 26 29 32 3 4 6 8 10 12 12+
ratios.
months
Age at Onset
years
On fluoroscopy left atrial enlargement, left
ventricular enlargement, and poor cardiac ac-
Figure 3 tion were noted in both groups. Except dur-
The age of onset of 41 postmortem-proved cases of ing acute congestive heart failure the lung
primary endocardial fibroelastosis and in 33 cases fields appeared normal.
identified clinically: 25 of the postmortem cases are
from our own files, 16 cases are from the report of Electrocardiographic Findings
Kelly and Anderson.5 Rhythm
All cases had sinus rhythm except for the
cases on admission was between 160 and 170 two cases in moribund children. Both these
beats per minute but ranged from 120 to 220 cases had conduction defects including pro-
beats per minute. In moribund infants the longed P-R intervals, intermittent heart block,
heart sounds were of poor quality; tachycardia and wide QRS complexes. On admission, heart
was common, but bradyeardia occurred only rates of all cases ranged from 120 to 220 beats
occasionally. per minute. There was no difference between
Prior to death no murmurs were heard in
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15 of the 25 postmortem cases of primary


endocardial fibroelastosis. In 10 cases func- 12 33di(d79 Cases)
t

tional murmurs were heard: the murmurs in II. El Ca ses


10 *Deaths
three of the cases were obviously functional, 9.
whereas in seven the murmurs could not be
No, ot
so identified until after repeated observations. Cases 7.
In the clinical group of 33 cases, 22 had no 6
5
murmurs on examination at admission, eight 4
had obviously functional murmurs, and three
had probable functional murmurs. At the last
examination, after observation for 2 to 8 years,
0 2 5 8 14 17 2023 26 2932 3 4 6 8 10 12 12+
it was obvious from the quality and variation months years
Age at Onset
of the murmurs that all of them were function- Signs. or Symfotom

al in origin. Figure 4
was in the onset of signs and symptoms. The age of onset of myocarditis in infancy and child-
The one difference between the two groups hood is recorded in 79 cases reported in the litera-
They occurred a little earlier in the autopsied ture 11-13 and from our own files. Epidemics of myo-
group; the age of onset in the two groups carditis such as that reported by Freundlich et al.14
was almost entirely in the first 8 months of with a large number of cases concentrated in a short
life (fig. 3). period of time were not included, since they appear
to be isolated phenomena and do not present any
Roentgenography problem in the differential diagnosis with endocar-
dial fibroelastosis. Furthermore, all the cases reported
Radiologic evidence of cardiac enlargement by Freundlich were 6 months old or more at the
was found in all cases. The average cardio- time of onset.
Circulation, Volume XXIX, January 1964
52( SELLERS, KEITH, MANNING
the heart rates found in the clinical and the the terminal stages of illness, so that the
postmortem groups. electrocardiograms were difficult to interpret
The P-R interval averaged 0.11 second adequately. Two had evidence of right ven-
(range 0.08 to 0.16 second) in the postmortem tricular loading alone and a postmortem find-
group; in the clinical group the average in- ing of endocardial fibroelastosis of the right
terval was 0.12 second (range 0.09 to 0.16 ventricle. Such cases are very difficult or im-
second). In 70 per cent of both groups P-R possible to recognize clinically. There re-
intervals ranged from 0.10 to 0.12 second. mained 20 cases in which there was evidence
The duration of the P waves averaged 0.05 of left ventricular loading in the electrocardio-
second in both groups; the range was from gram, and one of these had evidence implicat-
0.02 to 0.10 second. In 65 per cent the P-wave ing both right and left ventricles. Thus, 19 of
duration ranged from 0.04 to 0.07 second. 22 cases remain (86 per cent) with a left
There appeared to be no relationship between loading pattern in the electrocardiogram.
the P-wave duration or heart rate and the In the autopsied group of cases showing
age of the infant, as is true in normal electro- left ventricular overload and left ventricular
cardiograms.6 involvement at autopsy, 47 per cent had left
The mean amplitude of the P wave in both loading diagnosed on the basis of the R wave
groups was 2 mm. In the autopsied group the in V6 of over 20 mm. as well as an S wave
amplitude varied between 1 and 4.5 mm.; in V, of over 20 mm. Only two cases (10 per
35 per cent (eight cases) had abnormally tall cent) had left loading diagnosed on the basis
P waves. Three of these cases had left atrial of an S wave in V1 alone of 20 mm. or more.
involvement and five had persistent congestive In three cases (17 per cent) left ventricular
heart failure. In the clinical group the am- overloading was diagnosed on the basis of the
plitude of the P wave varied from 1.0 to 3.5 ratio of the R/S in V1 being less than 0.8
mm., and six cases (14 per cent) had large at 12 months of age, or 0.2 between 12 and
P waves of more than 3 mm. In five of these 24 months of age. Similar findings were noted
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cases the P-wave amplitude was abnormal by Vlad et al.3 On electrocardiographic study
following the initiation of therapy. In the of their autopsied cases of endocardial fibro-
sixth case the P wave was still 3 mm. high elastosis 78 per cent of the group had evi-
after 1 year, but it decreased to 1.5 mm. by dence of left ventricular loading; of these, 82
the end of the second year of therapy. per cent had increased voltage in the pertinent
The duration of the QRS interval averaged precordial leads.
0.06 mm. The range was similar in both groups All the clinical cases in the present series
and extended from 0.04 to 0.10 second. The demonstrated evidence of left ventricular load-
average QRS duration in infancy of 0.055 ing either from the beginning of illness or
second6 corresponds closely to the average once congestive heart failure was controlled.
found in our cases with endocardial fibroelas- Three cases (9 per cent) showed right as well
tosis.7 In two cases the QRS interval was 0.10 as left ventricular loading.
second, but there was no other sign of bundle- In a comparison of the clinical and post-
branch block; Zeigler considered this to be mortem groups (table 1) 17 per cent of the
prolonged for infancy. clinical group had electrocardiographic evi-
Patterns of Electrocardiographic Hypertrophy
dence of left ventricular overloading on the
Associated with Endocardial Fibroelastosis basis of the R wave in V6 over 20 mm., 66
Although the age, history, and clinical find- per cent of cases had left ventricular loading
ings are essential for a diagnosis of endo- diagnosed on the basis of the amplitude of the
cardial fibroelastosis, the electrocardiogram is R wave in V6 as well as the depth of the S
of dominant significance. It is characterized in V1 exceeding 20 mm., and only three cases
by a left loading pattern of increased voltage (10 per cent) had left loading diagnosed on
in the left ventricular precordial leads. the bases of the depth of the S wave in V1
Of the 25 autopsied cases, three were in alone. In only two cases (7 per cent) left
Circulation, Volume XXIX, January 1964
ENDOCARDIAL FIBROELASTOSIS 53

Table 1
Incidence of Various Manifestations of Left Ventricular Overloading in Endocardia1
Fibroelastosis and in Myocarditis
Endocardial fibroelastosis Mvocarditis
33 clinical cases 19 postmortem cases 23 cases
Tall RV6 alone 17% 47%1 8%
Tall RV6 and deep SV1 66% 26% 0%
Deep SV1 10% 10% 9%
Ratio R/S V1 alone* 7% 17% 83%
* Abnormally low R/S ratio in V1.
N.B. Vlad et al., 1953, 82 per cent of postmortem group (17), with LVH had increased
voltage.

loading was diagnosed the ratio of R/S


on had a mean electrical axis in a range between
in V1 alone. Thus 93 perhad evidence of
cent plus 20 and plus 800.
left ventricular loading on the basis of in- When it was possible to determine the
creased voltage in the precordial leads. direction of the frontal loop, it was clockwise
T-Wave Direction in V6
in 96 per cent of the postmortem group and
in 85 per cent of the clinical group. A counter-
The T-wave deflection in leads V5 or V6 clockwise loop was found in only six cases.
was characteristically flattened or inverted in
both postmortem and clinical cases initially, History during Pregnancy
prior to the administration of digoxin (table In no case was there any evidence in the
2). The two cases that did not have negative pregnancy history of an etiologic factor that
T waves in V6 died suddenly, and repeated might be related to endocardial fibroelastosis.
electrocardiograms were not taken. One clin- Two mothers had difficulty with the later
ical case had an upright T in V6 initially but stages of pregnancy; one had toxemia and the
it became negative subsequently. baby had respiratory distress for a short time
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In the postmortem group the average depth after delivery, and the other gave birth to a
of the T wave in V6 was 1.5 mm., and in 75 baby who appeared well initially. Kelly and
per cent it was clearly inverted. The clinical Anderson 5 also found no significant history
cases had T waves that were a little deeper; of maternal illness in 17 autopsied cases.
the average depth was 2.5 mm., and in 95 Birth Rank
per cent it was clearly inverted. Data regarding birth order were available
in 51 families. In both groups there was an
Mean Electrical Axis and
Direction of the Frontal Loop increased probability of endocardial fibro-
The mean electrical axis ranged in the post- elastosis with increasing birth rank.8
mortem cases from minus 10 to plus 1100 Birth Weight
and in the clinical cases from minus 10 to plus The average birth weight of the male and
100°. In both groups 77 per cent of the cases female cases was 3,246 and 3,133 Gm., re-
Table 2
T-wave Amplitude in V6
Fibroelastosis Clinical a 1 6 13 4 5 4
groups .

Autopsy -,c
a
1 1 5 5 3 5 2
Myocarditis Z; 1 3 4 1 15 8 3 1
T wave mm. +5 +4 +0.5 0 -0.5 -1 -2 -3 -4 -5
+3 +2 +1
The magnitude of the T wave in precordial lead V6 is compared in the clinical and postmortem groups of
endocardial fibroelastosis with that in myocarditis.
Circulation, Volume XXIX, January 1964
54 SELLERS, KEITH, MANNING
spectively. Eighty per cent of both groups During the course of this study we ob-
of cases had birth weights within the 10- to served a group of cases that responded initial-
90-per cent range. There were four cases that ly to therapy. They were followed for several
were premature by weight (2,180 to 2,450 years. Five of them died during the course of
Gm.). the follow-up, 1 to 3 years after the original
Sex Ratio
clinical diagnosis had been made. All five
In both groups females predominated slight- were found to have the typical endocardial
ly over males. This was only true in the ab-
lesion at autopsy.
sence of associated valvular disease; when the
One case not included in this series had
latter complication was present, males pre- been diagnosed as endocardial fibroelastosis
dominated. in 1953 and responded well to therapy, with
return of the heart size and electrocardiogram
Maternal Age to normal. At the age of 7 years this child de-
In both groups primary endocardial fibro- veloped an unrelated attack of nephritis and
elastosis occurred most often in infants born died. At autopsy pearly white thickening of
to mothers in the age group of 25 to 29 years. the endocardium of the left ventricle was
This age group corresponds to the peak in- readily seen and appeared similar to that
cidence of childbirth in the general popula- seen in infants dying in the first year of life.
tion.9 Analysis of the data, however, suggests The problem in diagnosis involves differen-
that endocardial fibroelastosis did not occur tiation of conditions in which congestive heart
so frequently in the older mothers as in the failure occurs in infancy unaccompanied by
younger, despite the higher frequency of pri- a significant heart murmur, and in which the
mary endocardial fibroelastosis with progres- electrocardiogram indicates a left ventricular
sing birth rank. This suggested that the overload. Idiopathic myocarditis and an anom-
maternal age of mothers of children with alous left coronary artery arising from the
primary endocardial fibroelastosis was signifi- pulmonary artery, calcification of the coronary
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cantly younger than in the general popula- arteries, glycogen-storage disease of the heart,
tion (p = 0.5). medial necrosis of the coronary arteries, co-
Familial Incidence arctation of the aorta, aortic stenosis, and
Data regarding siblings were available in mitral insufficiencv are the chief defects that
80 per cent of families. In six families mul- must be considered. Many of these lesions
tiple cases occurred. Thus, the presence of a may be associated with a mild secondary en-
known case of endocardial fibroelastosis in the docardial fibrotic reaction that is, however,
family increases slightly the possibility of an- relatively insignificant when compared with
other occurrence. One of our cases that de- the endocardium in the classical picture of
veloped congestive heart failure in the new- primary endocardial fibroelastosis.
born period was identified on this basis, de-
Anomalous Left Coronary Artery
spite an electrocardiogram that was not char-
acteristic. Many reports have appeared in the litera-
ture of an anomalous left coronary artery aris-
Discussion ing from the pulmonary artery. A few cases
Over the past 10 years we have been im- survived into adult life but such individuals
pressed with the clinical findings in babies of did not present signs or symptoms during in-
congestive heart failure, a large heart, no fancy. Infants with this anomaly usually have
murmurs, and a distinctive electrocardio- a distinctive picture, the vast majority show
graphic pattern. In such cases we have made signs and symptoms in the first 4 months of
-a diagnosis of endocardial fibroelastosis, and life, rarely before 2 months of age. The onset
in many instances the baby has died in the is that of heart failure, dyspnea, large liver,
next few days and the diagnosis has been and, in a few cases, screaming or crying as if
confirmed. in pain.
Circulation, Volume XXIX, January 1964
ENDOCARDIAL FIBROELASTOSIS 55

The electrocardiogram is very helpful in but occasionally congestive heart failure may
making the differential diagnosis. All of the occur and produce an electrocardiographic
cases of anomalous coronary from the pul- pattern similar to that found in endocardial
monary artery that develop congestive failure fibroelastosis. Thus, the clinical picture, the
in infancy eventually show the ischemic pat- electrocardiographic findings, and the calcifi-
tern of myocardial infarction. This change is cation of the coronary arteries may at times
associated with a left ventricular loading pat- be indistinguishable from primary endocardial
tern usually of the type that produces a deep fibroelastosis. Although this condition must be
S in V1 rather than a tall R in V6. Characteris- considered in the differential diagnosis, it ap-
tically, there is a deep Q wave in leads I, parently does not represent a real problem,
aVL, and in V5 and V6. The S-T segment since it is so rare. It is uniformly fatal and
in V5 and V6 is elevated distinctly in the does not respond to digitalis. X-ray of the
majority of cases, although it may be de- various portions of the body may reveal cal-
pressed. The pattern is that of an anterolateral cification of the arteries and thus lead to the
myocardial infarction. While the electrocardio- correct diagnosis.
gram is almost invariably diagnostic, confirma- Glycogen-Storage Disease of the Heart
tory evidence can be obtained from an aorto- Glycogen-storage disease of the heart is a
gram with the tip of the catheter in the re- uniformly fatal disease in infancy, and death
gion of the coronary arteries. This will reveal usually occurs during the first 8 months of
a large, completely filled right coronary artery
life. The electrocardiogram may show left
arising from the aorta, and will show an ventricular loading with T-wave inversion in
absence of left coronary arising from the V6. The majority of these children have a
aorta, indicating its anomalous presence else- history of generalized muscular weakness
where. from birth, and characteristically have macro-
The cases of anomalous left coronary artery glossia. A histologic section from an involved
arising from the pulmonary artery that de- muscle may reveal the true diagnosis.
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velop heart failure in infancy, almost without


exception are dead by the end of the first Myocarditis
year of life. It is obvious, therefore, that a The problem of differential diagnosis be-
group of 33 clinically diagnosed cases of endo- tween endocardial fibroelastosis and the vari-
cardial fibroelastosis that survived cannot have ous lesions and anomalies that may simulate it
been cases of this anomaly. in infancy is usually clarified by observation
It should be noted that the number of cases for a week or two, and by taking several elec-
of anomalous coronary arising from the pul- trocardiograms. In the present series of 33
monary artery have a mild, pallid degree of cases all were followed for 2 to 8 years, thus
endocardial fibroelastosis of the left ventricle making it virtually certain that the simulating
at postmortem examination, which is obvious- anomalies were ruled out. One problem of
ly a secondary phenomenon and does not myocarditis remains, however. A review of the
rival the dense lesion of primary endocardial clinical findings and especially the electro-
fibroelastosis. cardiogram indicates that the differentiation
between endocardial fibroelastosis and myo-
Calcification of the Coronary Arteries carditis can usually be made during life.
Calcification of the coronary arteries in in- The pattern of age of onset in myocarditis
fancy is associated with widespread calcifica- differs somewhat from that of endocardial
tion of the arteries throughout the body and fibroelastosis. Recent literature demonstrates
may involve the renal and thyroid vessels, and that Coxsackie myocarditis, when it occurs in
the arteries of numerous other vital organs.10 the mother at the end of pregnancy, is likely
In the majority of cases these infants die be- to produce the same infection in the newborn
cause of the general arterial involvement baby and will almost invariably be associated
rather than the specific effect on the heart, with myocarditis with a mortality of approxi-
Circulation, Vo.lume XXIX, January 1964
56 SELLERS, KEITH, MANNING
mately 70 per cent. After the first month of tern, and 93 per cent of these also have an
life the incidence of myocarditis with Cox- increase in voltage in the leads pertaining to
sackie infection falls precipitously, and the the left ventricle. On the other hand, in myo-
mortality becomes very low. After the neo- carditis only 7 per cent of cases showed an
natal period myocarditis appears to be scat- increase in voltage in the same leads, and any
tered irregularly through the pediatric age left loading present is associated with a sim-
group and is not concentrated in any par- ple lowering of the R/S ratio in V,. This
ticular year (fig. 4). On the other hand, in striking difference provides security of diag-
endocardial fibroelastosis the age of onset is in nosis in cases showing the characteristic clin-
the first 8 months of life in 85 per cent of ical and electrocardiographic picture. As a
cases (fig. 3). In myocarditis, on the other result, all of the autopsy-proved cases (20)
hand, if one rules out the Coxsackie virus in- that showed this pattern were diagnosed cor-
fections in the neonatal period, only 30 per rectly during life, and myocarditis was cor-
cent have their onset in the first 8 months rectly ruled out.
of life. One may not always reach the correct
The electrocardiograms in myocarditis and diagnosis, since an occasional case of myo-
endocardial fibroelastosis show differences of carditis may have a left loading pattern with
diagnostic significance. The voltage of the R increased voltage of S in V, or R in V6. This
wave in V6 or the voltage of the S wave in V, is an uncommon finding, and we have not
is abnormally high in most cases of endo- been misled in this manner to date. An oc-
cardial fibroelastosis; it is rarely increased in casional case of endocardial fibroelastosis may
myocarditis (table 1). The R wave in V6 is show a low voltage pattern similar to that seen
abnormally high in most cases of endocardial in myocarditis. This occurrence does not, how-
fibroelastosis; it is rarely increased in myo- ever, invalidate the statement that all cases
carditis. The T wave in V6 is more deeply in- that satisfied the criteria and came to autopsy
verted in endocardial fibroelastosis than in had endocardial fibroelastosis.
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myocarditis in most cases, and it tends to be In the majority of cases with myocarditis
flat or slightly inverted in the myocarditis the diagnosis was correctly identified from the
group (table 2). A pattern of myocardial in- clinical findings and the electrocardiogram.
farction may be seen in 10 per cent of children Confirmation was subsequently obtained at
with myocarditis but is very rare in endo- autopsy. None of our cases of myocarditis was
cardial fibroelastosis. A Q wave in V6 of 1 considered to be endocardial fibroelastosis
mm. or greater is seen in 60 to 70 per cent of during life. We have encountered one case
the cases of endocardial fibroelastosis, but a with endocardial fibroelastosis that was con-
Q wave in V6 is uncommon in myocarditis sidered to be myocarditis because of the low
unless a pattern of myocardial infarction is voltage in the electrocardiogram. An autopsy
present (table 3). revealed the correct diagnosis.
Eighty-five per cent of the cases of endo- Recently Decourt and co-workers reported
cardial fibroelastosis have a left loading pat- on a punch-biopsy study of the heart.15 Five
patients had clinical evidence of endocardial
Table 3 fibroelastosis and t-he presence of this lesion
Incidence of Q waves in Precordial Lead V6 in was confirmed in each case by biopsy of the
Endocardial Fibroelastosis and Myocarditis endocardium. These children are doing well.
Endocardial fibroelastosis Myocarditis
Postmortem Clinical Endocardial Fibroelastosis Associated
0 37% 41% 74% with Valvular Involvement
0.5-1 mm. 4% 5% 12% The cases with valvular involvement were
1+ mm. 59% 54% 14% * excluded from the main body of this study
Three fourths of this figure were q6 due to myo-
* because it is difficult to be certain about the
cardial infarction pattern. type and origin of the valvular pathology.
Circulation, Volume XXIX, January 1964
ENDOCARDIAL FIBROELASTOSIS 57
There may well be an intimate relationship stenosis or large intracardiac left-to-right
between the mural endocardial fibroelastic shunts may at times give similar electrocardio-
reaction and the pearly white thickening of graphic findings.
the mitral valve. This combination was re- We did not encounter any infants who had
garded as primary endocardial fibroelastosis evidence of involvement of the pulmonary or
by Kelly and Anderson.5 In the course of our tricuspid valve associated with the endo-
study we encountered 11 such cases at autop- cardial lesion. Kelly and Anderson 5 had two
sy: 10 had mitral valve involvement as well as cases with an involvement of the tricuspid
the typical endocardial lesion, and six of these valve; some degree of involvement of all four
also had a similar process imposed on the chambers was noted in 15 of their 17 cases.
aortic valve. The eleventh case had aortic At the same time they indicated that the left
valve involvement without the mitral lesion. ventricular or the left atrial lesions were
Seven of the 11 cases showed a left ven- usually more marked and obvious.
tricular overload pattern in the electrocardio- Kelly and Anderson demonstrated that all
gram. Of those cases that did not show left but two of their 17 cases had dilated hearts, an
loading, three had evidence of right ventricu- incidence that was confirmed in our autopsy-
lar overload and one electrocardiogram re- proved material. They referred to these two
corded in a moribund child was difficult to cases as having an absence of dilatation,
assess. One of the cases showing right ven- whereas Edwards used the term "contracted
tricular overload had aortic stenosis, mitral left ventricle." It would seem more suitable
stenosis, and endocardial fibroelastosis with to designate them as nondilated as the former
a nondilated left ventricle. The remaining two authors do, since such hearts are hypertro-
cases showed right ventricular overloading phied and somewhat enlarged. One of our
and were found to have mitral valve involve- cases, as was mentioned above, fell into this
ment at autopsy. category and was associated with aortic and
Among the 11 cases all but one had flat or mitral valve involvement. It is generally recog-
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inverted T waves in V6. The case with the nized that some cases of aortic stenosis may
upright T in V6 was the one with aortic have marked hypertrophy of the left ven-
stenosis as an isolated valvular involvement tricle without significant chamber enlarge-
associated with endocardial fibroelastosis of ment. This type of myocardial response
the left ventricle. would not be expected to give right ventricu-
The seven cases with left ventricular load- lar loading in the electrocardiogram. The
ing had an increased amplitude of R in V6 cause of such loading may be related more to
in two, a tall R in V6 and a deep S in V, the advanced stage of congestive heart failure
in two, and a deep S in V, alone in one. In than has been recognized until now. It has
two cases the only evidence of left ventricular been our experience that the right ventricular
overload was as in inversion of the T wave in loading pattern in such cases changes quickly
V6. Both of these cases were in severe con- to a left loading one if the baby survives un-
gestive heart failure at the time the electro- der treatment. The contracted left ventricle
cardiograms were taken, which may account of aortic or mitral atresia is an entirely differ-
for the absence of increased voltage. ent entity.
One may suspect the presence of endo- Since the present study was begun, Noren
cardial fibroelastosis in a baby with congestive et al.16 and Ainger (quoted by Noren) have
heart failure and a systolic murmur in the first presented preliminary studies on the use of a
year of life with inverted T waves over the mumps antigen skin test in primary endocardi-
left precordium, with or without increased -al fibroelastosis. They have found a high in-
v0oltage of the R in V6 or the S in V,. In the cidence of positive reactions in their clinically
face of the murmurs that go with these diagnosed cases and a very low incidence in
valvular lesions one cannot make the diag- the normal infant. While their emphasis was
nosis with accuracy, since isolated aortic on etiology, to us this appears to offer a test
Circulation, Voilume XXIX, January 1964
58 SELLERS, KEITH, MANNING
of some diagnostic significance and we have, fulfilled and there is some doubt about the
as a result, skin tested 31 cases of primary diagnosis. 3. WVhen an infant under 2 years
endocardial fibroelastosis that satisfied the of age has an organic murmur originating in
diagnostic criteria set forth in this paper. the mitral or aortic valve associated with fail-
Many were children included in this study ure and left ventricular loading in the electro-
and now are available for skin testing up to cardiogram, a positive skin test would provide
9 years after the onset of symptoms. The age strong additional evidence of underlying pri-
at skin testing of these was as follows: under mary fibroelastosis.
1 year, 6; 1 to 2 years, 3; 2 to 5 years, 6; 5
years and over, 16. Summary
Among the total of 31 cases of clinically A comparison has been made of the clinical
diagnosed primary endocardial fibroelastosis, features of a group of autopsy-proved cases
24 had a positive skin test, two were negative, of endocardial fibroelastosis and a clinically
and five were doubtful. The doubtful or nega- diagnosed group with similar findings. It has
tive cases were all in the 5-year-or-over age been possible to make a diagnosis of endo-
group. The blood sera of the patients with cardial fibroelastosis before death in all cases
positive skin tests were uniformly negative in showing a characteristic clinical and electro-
the under-2-year age group. The one positive cardiographic pattern. The characteristic fea-
serum was in an older child. tures are (a) appearance of congestive heart
We skin tested 104 infants and children failure; (b) absence of organic heart mur-
who were in the hospital for a variety of other murs; (c) onset of signs or symptoms in the
conditions (77 had congenital heart disease). first 8 months of life (85 per cent) and rarely
Seven of these were positive and all of them after 1M years; (d) a period of observation
were 5 years of age or older. The sera of most under therapy during which is ruled out the
cases with positive skin tests were tested for conditions that simulate endocardial fibro-
mumps virus antibodies; one was positive. elastosis, such as an anomalous coronary artery
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Thus, the mumps skin test antigen was posi- arising from the pulmonary artery, glycogen-
tive in all cases with clinical primary en- storage disease, coronary artery necrosis, or
docardial fibroelastosis tested under the age myocarditis; (e) an abnormal increase in vol-
of 5 years. These findings are similar to those tage of R in V6, S in V,, or both together; (f )
of Noren and Ainger. a flat or inverted T wave in V6 (85 per cent
The mumps antigen skin test, therefore, ap- have a T wave 1 mm. or deeper); (g) a Q
pears to be a most useful diagnostic procedure wave in V6 (present in 60 per cent).
in the age group under 2, when primary en- All the cases proved at autopsy that fulfilled
docardial fibroelastosis has its characteristic these criteria during life were correctly diag-
onset in the pediatric age group. The reason nosed before death. Approximately 85 per
for this positive reaction in these cases does cent of the total group were thus recognized.
not seem clear at the present time, since it Fifteen per cent were not identified because
appears to be most frequently associated with electrocardiographic tracings showed an
a lack of antibodies in the sera to mumps. atypical right loading pattern. An occasional
Further study of this problem is necessary but case with right loading may be suspected by
it would appear likely that the mumps antigen history of a previous sibling with endocardial
skin test should be considered one of the use- fibroelastosis.
ful criteria for diagnosis in the first 2 years of Since the differential diagnosis between en-
life. docardial fibroelastosis and acute myocarditis
The skin test will prove helpful in three has been considered difficult in the past, a
particular categories: 1. In augmenting our group of infants and children with myocarditis
criteria for the diagnosis of primary endo- were reviewed. The majority were proved at
cardial fibroelastosis. 2. When the criteria for autopsy. Such children were also correctly
diagnosis listed above are not quite adequately diagnosed during life in most instances. The
Circulation, Volume XXIX, January 1964
ENDOCARDIAL FIBROELASTOSIS 59

patients who were diagnosed clinically as hav- cardial fibroelastosis. Bull. Johns Hopkins
ing endocardial fibroelastosis and who sur- Hosp. 72: 299, 1943.
vived had electrocardiographic patterns that 2. ANDERSON, D. H., AND KELLY, J.: Endocardial
fibroelastosis associated with congenital mal-
were similar to those in the autopsy-proved formations of the heart. Pediatrics 18: 513,
group and unlike those in the myocarditis 1956.
group. The chief differences were in voltages 3. VLAD, P., ROWE, R. D., AND KEITH, J. D.: The
of R and S waves in precordial leads V6 or electrocardiogram in primary endocardial fibro-
V,, T waves in V6, and Q waves in V6. elastosis. Brit. Heart J. 2: 189, 1955.
Cases of endocardial fibroelastosis associat- 4. MANNING, J. A., SELLERS, F. J., KEITH, J. D.,
AND BYNUM, R.: Medical management of clini-
ed with mitral or aortic valvular disease usual- cal endocardial fibroelastosis. Circulation 29:
ly had a similar age of onset or a little earlier. 60, 1964.
The electrocardiographic pattern was similar. 5. KELLY, J., AND ANDERSON, D. H.: Congenital
The presence of an aortic or mitral systolic endocardial fibroelastosis. A clinical and patho-
murmur made it difficult to be certain about logical investigation of those cases without as-
the underlying pathology. The left loading sociated malformations including a report of
two familial instances. Pediatrics 18: 539, 1956.
pattern, however, with increased voltage in 6. ZEIGLER, R. F.: Electrocardiographic Studies in
the pertinent precordial leads accompanied by Normal Infants and Children. Springfield, Illi-
a flat or inverted T wave in V6 in a baby with nois, Charles C Thomas, Publisher, 1951.
a large heart or with congestive heart failure, 7. KEITH, J. D., ROWE, R. D., AND VLAD, P.: Heart
provides suggestive evidence of endocardial Disease in Infancy and Childhood. New York,
fibroelastosis. The Macmillan Company, 1958, p. 28.
The contracted type of endocardial fibro- 8. HALDANE, J. B. S., AND SMITH, C. A.: A simple
exact test for birth order effect. Ann. Eugenics
elastosis reported by Edwards is a relatively 14: 114, 1947.
rare finding. When it does occur, it may or 9. Vital Statistics 1957, Canada. Dominion Bureau
may not be associated with a right loading of Statistics, Health and Welfare Division, Au-
pattern in the electrocardiogram. The right gust 1957. (Adapted from Table "D," p. 28.)
Downloaded from http://ahajournals.org by on June 14, 2019

loading pattern in endocardial fibroelastosis is 10. COCHRANE, W. A., AND BOWDEN, D. H.: Calcifi-
more likely to be due to heart failure with cation of the arteries in infancy and childhood.
pulmonary congestion and overloading of the Pediatrics 14: 222, 1954.
right ventricle, which in an infant may then 11. KIBRICH, D.: Viral infections of fetus and new-
born. In Perspectives in Virology. Edited by
overshadow the left. This pattern may revert M. Pollard, Minneapolis, Burgess Publishing
to the more characteristic one of left loading Company, 1961, p. 140.
after digitalization has been completed. 12. WILLIAMS, H., O'REILLY, R. N., AND WILLIAMS,
The mumps antigen skin test is proving to A.: Fourteen cases of idiopathic myocarditis in
be a useful diagnostic tool, since it is found infants and children. Arch. Dis. Childhood
to be positive in primary endocardial fibro- 28: 271, 1953.
elastosis in the first 2 years of life. In our 13. WEBER, M. W., BALDWIN, J. S., AND HALL, J. W.:
Acute isolated myocarditis: Review of the
experience this occurs without a positive literature and a report of a case in a 10 year
serum antibody reaction to mumps virus. old child. Pediatrics 3: 829, 1949.
Normal children, or those with congenital 14. FREUNDLICH, E., BERKOWITZ, M., ELKON, A.,
heart disease in the same age group, rarely AND WILDER, A.: Primary interstitial myocardi-
have a positive skin reaction unless they have tis. Am. J. Dis. Child. 96: 43, 1958.
a recent history of mumps. Further work is 15. DECOURT, L. V., MACRUZ, R., GARCIA, D. P.,
needed to clarify this relationship, but on the AND TORLONI, H.: Endocardial fibroelastosis:
Its study by punch-biopsy of the heart. Fourth
evidence to date its diagnostic value in pri- World Congress of Cardiology, Mexico City,
mary endocardial fibroelastosis shows con- 1962.
siderable promise. 16. NOREN, G. R., ADAMS, P., JR., AND ANDERSON,
R. C.: Positive skin reactivity to mumps virus
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1. WEINBERG, T., AND HIMELFARB, A. J.: Endo- atrics 62: 604, 1963.
Circulation, Volume XXIX, January 1964