Cardiac hypertrophy and insufficiency of unknown etiology; a clinical and pathologic study of ten cases


Elster, S.K.; Horn, H.; Tuchman, L.R.

American Journal of Medicine 18(6): 900-922

1955


Cardiac
Hypertrophy
and
Insufficiency
of
Unknown
Etiology*
A
Clinical
and
Pathologic
Study
of
Ten
Cases
SAMUEL
K.
ELSTER,
M.D.,
t
HENRY
HORN,
M.D.
and
LESTER
R.
TUCHMAN,
M.D.
New
York,
New
York
I
N
recent
years
interest
has
been
awakened
in
certain
cases
of
cardiac
enlargement
which
cannot
be
ascribed
to
such
common
etiologic
mechanisms
as
hypertension,
coronary
arterio-
sclerosis,
bronchopulmonary
disease,
rheumatic
fever,
syphilis,
congenital
defects
or
a
systemic
affection.
Attention
was
first
directed
to
this
group
by
Josserand
and
Gallavardini
and
subse-
quently,
similar
instances
have
been
de-
scribed.
2-
"
Levy
and
his
co-workers
character-
ized
the
syndrome
as
consisting
of
cardiac
hypertrophy,
scarring
of
the
myocardium
and
focal
myocardial
necrosis
of
unknown
origin.
Rapidly
progressive
heart
failure,
associated
with
disturbances
in
rhythm
and
complicated
by
pulmonary
and
systemic
embolizations,
were
recognized
as
common
features."
It
is
unfortunate
that
many
reports
have
at-
tempted
to
attach
to
this
group
an
unwarranted
variety
of
causative
factors
and,
accordingly,
a
number
of
descriptive
names.
It
has
been
con-
fused
with
beri-beri
heart
disease,
cardio-
vascular
collagenosis,
nutritional
heart
disease,
endocardial
fibrosis
and
familial
cardiomegaly.
The
present
study
is
designed
to
examine
the
fundamental
clinical
and
anatomic
pattern
of
ten
such
cases
and
to
make
such
correlations
as
appear
indicated.
MATERIAL
AND
METHODS
The
material
included
in
this
study
consists
of
ten
instances
of
cardiomegaly
without
con-
ventional
etiology.
The
postmortem
files
of
The
Mount
Sinai
Hospital
for
the
years
1937
to
1952
have
been
examined
and
all
instances
of
enlargement
of
heart
have
been
reviewed.
Those
instances
in
which
congenital
defects,
hyper-
tensive
vascular
disease,
valvular
deformities,
syphilis,
arteriovenous
shunt,
coronary
arterio-
sclerosis,
anemia,
kyphoscoliosis,
hyperthyroid-
ism,
allergic
state,
primary
abnormal
rhythm,
von
Gierke's
disease,
amyloidosis
or
non-specific
myocarditis
could
not
be
incriminated
were
then
subjected
to
further
clinical
and
pathologic
survey.
Ten
cases
remained
that
failed
to
show
cause
for
the
cardiomegaly.
Detailed
analysis
was
made
of
the
necropsy
and
clinical
material.
Sections
of
portions
of
the
left
and
right
sides
of
the
heart
were
examined
carefully.
The
hearts
were
also
studied
in
detail
for
abnormalities
of
the
valves,
endocardium
and
pericardium.
The
aorta
was
especially
examined
for
any
lesion
which
might
compromise
the
coronary
ostia.
The
coronary
artery
tree
was
sectioned
transversely
at
intervals
of
1
to
3
mm.
after
having
been
properly
fixed.
The
other
viscera
were
studied
for
any
possible
causative
relationship.
CLINICAL
DATA
The
sex,
age
and
race
distribution
are
listed
in
Table
I.
Males,
young
to
middle
age,
and
Negro
patients
constituted
the
majority.
All
subjects
had
a
normal
dietary
history;
two
had
a
mild
to
moderate
alcoholic
intake.
Seven
of
the
group
recalled
the
onset
of
their
illness
with
dyspnea
as
evidence
of
congestive
heart
failure;
one
had
had
abdominal
pain.
The
onset
in
one
instance
was
signaled
by
pulmonary
infarction,
while
one
patient
had
been
informed
of
the
presence
of
cardiac
enlargement
during
a
routine
physical
examination.
In
seven
cases
symptoms
were
present
for
less
than
six
months
before
the
patients
sought
*
From
the
Departments
of
Medicine
and
Pathology,
The
Mount
Sinai
Hospital,
New
York,
N.
Y.
Presented
in
part,
before
the
New
York
Pathological
Society,
the
New
York
Academy
of
Medicine,
May
27,
1954.
t
Elsa
and
William
Menke
Fellow
in
Medicine.
900
AMERICAN
JOURNAL
OF
MEDICINE
Pressures
Mm.
Hg
No.
of
Cases
Systolic
Diastolic
Pulse
120-140
100-120
70-80
81-90
91-100
101-110
10-19
20-29
30-39
40-49
3
7
3
2
2
3
1
4
3
2
Cardiac
Hypertrophy
of
Unknown
Etiology—Elster
et
al.
90I
medical
attention.
Eight
patients
succumbed
within
eighteen
months
following
the
onset
of
symptoms.
The
clinical
manifestations
are
detailed
in
Table
it.
The
most
constant
features
consisted
of
an
enlarged
heart
accompanied
by
severe
left-
TABLE
I
SEX,
AGE
AND
RACE
DISTRIBUTIONS
Sex
Male
7
Female
3
Age
20-29
1
30-39
4
40-49
4
50-59
1
Race
White
4
Negro
6
TABLE
II
CLINICAL
MANIFESTATIONS
Incidence
1.
Cardiomegaly
10
2.
Hepatomegaly
10
3.
Dyspnea
9
4.
Edema
of
lower
extremities
7
5.
Hemoptysis
6
6.
Pulmonary
findings:
Basal
rales
6
Right
hydrothorax
5
Pleural
friction
rub
1
Left
hydrothorax
1
7.
Abnormal
cardiac
rhythm:
Gallop
rhythm
6
Ventricular
premature
contractions
4
Pulsus
alternans
3
Auricular
premature
contractions
1
Nodal
tachycardia
1
Auricular
flutter
1
Auricular
fibrillation
1
8.
Abnormal
blood
pressure
5
9.
Distended
neck
veins
5
10.
Cyanosis
4
11.
Thrombophlebitis
4
12.
Significant
cardiac
murmurs
4
13.
Precordial
pain
1
and
right-sided
congestive
heart
failure.
Six
of
the
ten
patients
in
this
group
had
sustained
well
documented
pulmonary
infarctions;
in
only
one
instance
was
this
complication
present
early
in
the
course
of
the
illness.
Of
these
six
cases
four
had
obvious
thrombophlebitis
of
the
lower
extremities.
Tachycardia
was
observed
in
all
patients.
Gallop
rhythm
was
a
frequent
and
prominent
finding.
Major
abnormalities
of
rhythm
(nodal
tachycardia,
auricular
flutter
and
auricular
fibrillation)
occurred
in
three
patients.
In
four
cases
grade
4
systolic
murmurs
were
heard.
A
low
systolic,
slightly
elevated
diastolic
JUNE,
1
9
5
5
and
diminished
pulse
pressure
was
common.
(Table
tn.)
In
no
instance
was
there
a
history
of
hypertension.
The
temperature
course
was
normal
in
one
instance,
usually
normal
with
an
occasional
elevation
in
three
and
generally
elevated
in
six.
TABLE
III
DISTRIBUTION
OF
BLOOD
PRESSURE
READINGS
TABLE
IV
LABORATORY
DATA
Laboratory
Test
No.
of
Cases
No.
Abnormal
Albuminuria
9
9
Abnormal
venous
pressure
and
cir-
culation
time
7
7
Leukocytosis
(12,000-23,000)
9
4
Azotemia:
9
Early
1
Late
4
Elevated
erythrocyte
sedimentation
rate
9
Plasma
protein
changes
9
0
The
laboratory
data
are
detailed
in
Table
iv
and
offer
no
lead
as
to
an
etiologic
factor.
Mild
albuminuria
occurred
consistently
but
no
formed
elements
were
noted
in
the
urine
and
there
was
no
glycosuria.
The
specific
gravity
of
the
urine
indicated
preservation
of
renal-concentrating
capacity.
The
blood
hemoglobin
was
normal
in
all.
For
the
most
part
the
white
blood
counts
were
normal
but
in
four
instances
transient
or
preterminal
leukocytosis
appeared.
Serologic
tests
for
syphilis
were
consistently
negative.
In
eight
of
nine
cases
the
blood
urea
nitrogen
was
normal
during
the
early
period
of
observation,
but
azotemia
appeared
terminally
in
four
cases.
In
three
of
these
patients
this
finding
was
asso-
ciated
with
evidence
of
severe
congestive
heart
902
Cardiac
Hypertrophy
of
Unknown
Etiology—Elster
et
al.
failure
accompanied
by
the
"low-salt
syndrome"
with
hyponatremia
and
hypochloremia.
The
plasma
protein
levels
were
normal
in
all
cases.
In
a
few
instances
special
laboratory
procedures
were
undertaken
in
a
search
for
an
etiologic
factor,
but
without
success.
These
tests
included
TABLE
V
ELECTROCARDIOGRAPHIC
ABNORMALITIES
No.
of
Cases
RST
depressions
and
T
wave
inversions
5
Prolonged
P-R
interval
2
Left
bundle
branch
block
2
Right
bundle
branch
block
1
TABLE
VI
ANTEMORTEM
DIAGNOSES
No.
of
Cases
Idiopathic
myocarditis
4
Idiopathic
cardiac
hypertrophy
1
Unknown
heart
disease
Rheumatic
and
arteriosclerotic
heart
disease
1
Rheumatic
and
hypertensive
heart
disease
Recurrent
pulmonary
embolism
with
cor
pulmonale
1
Glomerulonephritis,
acute
L.E.-cell
phenomenon,
serum
protein-bound
iodine,
blood
cultures,
serum
cholesterol,
histo-
logic
study
of
skin
and
muscle
and
Congo-red
retention
tests.
Symmetric
cardiomegaly
was
noted
fluoro-
scopically
in
those
examined;
in
only
one
in-
stance
was
the
enlargement
thought
to
be
confined
to
the
left
cardiac
chambers.
The
elec-
trocardiographic
patterns,
detailed
in
Table
v,
suggest
no
clue
for
the
identification
of
this
type
of
cardiopathy.
In
all
instances
only
a
very
transient
response
to
therapy
was
obtained.
The
usual
regimen
for
congestive
cardiac
failure
was
employed,
with
salt
restriction,
administration
of
digitalis
and
diuretics.
Antibiotics
were
used
in
most
cases.
Dicumarol
was
administered
to
two
patients
with
pulmonary
infarction.
In
two
patients
with
the
low-salt
syndrome
hypertonic
saline
was
given,
without
notable
response.
In
one
instance
each,
thiamine
in
high
doses
and
cortisone
exerted
no
beneficial
effect.
All
patients
succumbed
with
the
picture
of
intractable
congestive
heart
failure.
Of
these,
two
were
also
in
shock,
while
the
course
of
one
was
terminated
by
a
pulmonary
artery
embolism.
A
review
of
the
final
clinical
diagnoses
of
our
cases
disclosed
the
need
for
greater
awareness
of
the
condition
described
herein.
In
but
one
instance,
and
that
the
last
case
observed,
was
the
precise
diagnosis
made.
(Table
vi.)
However,
diagnoses
of
unknown
heart
disease
(one
case)
and
idiopathic
myocarditis
were
made
in
four
cases.
ANATOMIC
DATA
Macroscopic
Findings.
The
hearts
in
all
ten
cases
in
this
series
were
considerably
hyper-
trophied
and
their
chambers
were
dilated.
The
heart
weights
ranged
between
430
and
800
gm.,
with
an
average
weight
of
575
gm.
The
peri-
cardium
revealed
no
abnormalities
in
five
cases;
in
three,
scattered
agonal
petechial
hemorrhages,
in
one,
pleuropericardial
and
in
another
viscero-
parietal
pericardial
fibrous
bands
were
present.
The
coronary
artery
tree
was
everywhere
normal
in
four
instances;
minimal
patchy
arterio-
sclerosis
was
seen
in
five
others
without,
how-
ever,
any
encroachment
on
the
vessel
lumen.
In
one,
arteriosclerotic
stenosis
of
the
lumen
of
a
secondary
and
superficial
branch
of
the
right
coronary
artery
was
found.
The
lumen
of
the
remaining,
and
the
ostia
of
all,
were
widely
patent
and
the
arterial
walls
revealed
no
note-
worthy
alterations.
The
cardiac
valves
occasionally
were
the
seat
of
tension
thickening
and
edema.
These
changes
were
mild,
focal
and
irregular
in
distribution.
In
one,
the
posterior
leaflet
of
the
mitral
valve
was
slightly
vascularized
probably
the
sequel
of
an
episode
of
rheumatic
fever.
Fine
fibrosis
of
the
mitral
ring
was
observed
in
two
cases.
None
of
these
valvular
lesions,
however,
were
con-
sidered
to
have
been
related
pathogenetically
either
to
the
myocardial
changes
or
to
chamber
enlargement.
The
cardiac
muscle
was
generally
firm,
oc-
casionally
flabby
in
consistency,
brownish
red
on
section,
with
linear
or
broader
yellowish
or
yellowish
grey
zones
and
sporadic
hemorrhagic
foci.
The
pectinate
muscles,
trabeculae
carnae
and
papillary
muscles
were
prominent
but
often
appeared
flattened
in
the
more
dilated
specimens.
The
apical
portions
of
the
muscles
on
section,
and
in
a
few
the
subendocardium,
were
the
seat
of
punctate
hemorrhagic
or
yellowish
foci.
The
endocardium
often
presented
fine
or
broader
foci
of
thickening
and
thrombus
forma-
tion
(vide
infra).
Histologic
Findings.
The
predominant
histo-
logic
finding
was
hypertrophied
muscle
fibers
with
increased
transverse
diameter
and
with
nuclei
which
were
often
granular,
hyperchro-
matic,
distorted
or
blunt-edged.
The
capillary
cross
sections
were
relatively
sparse.
Venous
engorgement
was
frequently
striking.
AMERICAN
JOURNAL
OF
MEDICINE
Cardiac
Hypertrophy
of
Unknown
Etiology—Elster
et
al.
9
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3
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FIG.
1.
Case
vu.
Section
of
posterior
papillary
muscle,
left
ventricle,
showing
nuclear
degeneration;
homo-
genization,
fracture
and
necrosis
of
myofibrils;
hemorrhage;
early
reactive
polymorphonuclear
leukocyte
infiltrate.
Scattered
interstitial
and
perivascular
fibrosis.
FIG.
2.
Case
vitt.
Section
of
subendocardial
zone,
posterior
wall
left
ventricle,
showing
homogenization
and
patchy
necrosis
of
muscle
bundles,
focal
hemorrhage.
Note
uninvolved
hypertrophicmmyofibrils
and
scattered
foci
of
fibrosis.
FIG.
3.
Case
x.
Section
of
ventricular
wall
in
vicinity
of
mural
thrombus
showing
vascularized,
edematous,
pro-
liferating
connective
tissue
enmeshing
lymphocytes,
fibroblasts
and
sparse
polymorphonuclear
leukocytes.
FIG.
4.
Case
ix.
Interventricular
septum
showing
patchy,
broad,
linear
and
disseminated,
isolated
zones
of
myocardial
degeneration,
edema,
replacement
fibrosis.
Reactive
cell
infiltrates
consist
of
lymphocytes,
fibroblasts
and
occasional
polymorphonuclear
leukocytes.
In
addition
to
hypertrophy
the
myocardium
presented
degenerative
changes
and
connective
tissue
proliferation.
The
former
consisted
of
granularity
of
muscle
bundles,
vacuolization,
loss
of
striations
and
sarcoplasm
pallor
and,
in
later
stages,
smudging
and
alterations
in
tinctorial
characteristics
of
fibers
and
nuclear
degenera-
tion.
These
changes
were
observed
within
the
myofibrils
adjacent
to
and
those
at
some
distance
from
areas
of
fibrosis.
In
three
instances
the
subendocardial
musculature
contained
a
con-
siderable
quantity
of
glycogen
while
in
four
others
an
increase
in
sudanophilic
substance
was
noted.
A
more
advanced
type
of
lesion
included
transverse
fracture
of
myofibrils,
interstitial
edema,
engorgement
of
capillaries
and
focal
linear
and
broad
hemorrhages
and,
finally,
homogenization
in
which
nuclei
could
no
longer
be
identified
and
necrosis.
(Figs.
1
and
2.)
Indeed,
these
last
alterations
were
indistin-
guishable
from
those
of
myocardial
infarction.
However,
such
severe
changes
were
focal
and
minute
in
character.
Although
all
these
lesions
were
disseminated
throughout
the
entire
thick-
ness
of
the
ventricular
wall,
including
the
subepicardium,
the
more
extensive
changes
ap-
peared
more
commonly
subendocardially
and
within
the
papillary
muscles
of
the
left
ventricle.
In
one
case
perivascular
foci
of
lymphocytes,
groups
of
deeply
basophilic
giant
cells
and
scat-
JUNE,
1955
904
Cardiac
Hypertrophy
of
Unknown
Etiology—Elster
et
al.
if
1‘0401
0
is
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t
A
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4
4.•
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FIG.
5.
Case
v.
Anterior
wall
of
left
ventricle
adjacent
to
subendocardial
layer
showing
granulation
tissue-like
response
with
atrophy
and
degenerative
changes
of
entrapped
myofibrils.
Other
myocardial
fibers
are
hyper-
trophied.
FIG.
6.
Case
V.
Later
phase
of
healing
than
shown
in
Fig.
5.
Extensively
vascularized
zone
of
fibrosis
with
sparse
remaining
cell
infiltrate.
Vessels
appear
thickened
and
show
intimal
cellular
hyperplasia.
FIG.
7.
Case
in.
Dense,
avascular,
richly
elastified,
fibrotic
zone
with
atrophy
of
adjacent
isolated
myofibrils.
FIG.
8.
Case
I.
Section
of
left
ventricle
disclosing
band-like
zone
of
endocardial
fibrosis,
still
moderately
vascularized;
compression
atrophy
of
subjacent
myofibrils.
tered
leukocytes
were
found.
However,
no
other
histologic
or
macroscopic
stigmata
of
rheumatic
fever
were
observed,
and
it
is
doubted
that
these
cellular
infiltrates
were
a
manifestation
of
that
disease.
Cellular
infiltration
was
not
a
prominent
feature
and
was
seen
mainly
in
the
vicinity
of
recent
or
organizing
mural
thrombi
and
necrotic
myocardial
foci.
(Fig.
3.)
The
early
reactive
infiltrates
consisted
of
polymorphonuclear
leuko-
cytes
admixed
with
erythrocytes;
the
healing
lesions
were
invaded
with
lymphocytes
and
fibroblasts.
Occasionally
interstitial
plasma
cells,
macrophages
and
scant
lymphocytes
were
ob-
served.
These
also
were
principally
adjacent
to
degenerated
myofibrils.
There
were
numerous
areas
of
focal
interstitial
and
perivascular
fibro-
sis.
Although
these
were
scattered
through
the
walls
of
both
the
right
and
left
chambers,
they
were
located
mainly
in
the
endocardial
and
subendocardial
layers.
(Fig.
4.)
Multiple
sections
of
various
portions
of
the
heart,
but
most
espe-
cially
of
the
wall
of
the
left
ventricle,
showed
foci
of
fibrosis
in
various
phases
of
development.
Recent,
organizing
and
densely
fibrotic
zones
were
found,
often
concomitantly.
The
earliest
lesion
consisted
of
relatively
loose
cellular
connective
tissue
containing
occasional
lympho-
cytes,
plasma
cells,
macrophages
and,
rarely,
polymorphonuclear
leukocytes.
(Fig.
5.)
Still
other
zones
were
relatively
densely
fibrotic
and
vascularized
(Fig.
6),
while
the
older
lesions
consisted
of
acellular,
avascular
or
densely
fibrotic
scars,
occasionally
richly
elastified.
(Fig.
7.)
Frequently,
there
was
accompanying
AMERICAN
JOURNAL
OF
MEDICINE
7
.477,
„b.
••••••c."
N,
k
.
.
1.4?
4-
A
%
\
N
'15`
;''''7k
1
,
114.;
Cardiac
Hypertrophy
of
Unknown
Etiology
Elster
et
al.
goy
9
10
FIG.
9.
Case
iv.
Section
of
left
ventricle
showing
dense,
fibrotic
and
elastified
thickening
of
endocardium.
Fin.
10.
Case
in.
Organizing
mural
thrombus
intimately
attached
to
fibrotic
endocardial
plaque.
Linear
subendo-
cardial
fibrosis.
Degenerated
myofibrils
intermingled
with
hypertrophied
fibers.
compression
atrophy
and
replacement
of
adja-
cent
myofibrils,
although
in
a
few
instances,
in
the
midst
of
scarred
areas,
islands
of
myofibrils
appeared
unaffected.
The
endocardial
layer
was
the
site
of
patchy
fibrotic
thickening,
occasionally
plaque-like
in
appearance.
(Figs.
8
and
9.)
Thrombi
of
the
mural
endocardium
were
found
in
seven
instances,
of
which
three
were
situated
in
the
left
ventricle;
in
two,
thrombi
were
found
in
the
right
and
left
ventricles;
in
one,
endocardial
thrombosis
was
noted
in
the
right
auricle
and
ventricle,
while
in
one
case
mural
thrombosis
of
the
right
auricle
and
both
ventricles
was
found.
The
thrombi
showed
varying
degrees
of
organization
and
were
situated
usually
over
zones
of
endocardial
fibrosis.
(Fig.
10.)
Extension
of
mural
thrombosis
by
contiguity
was
seen
along
the
endocardial
layer,
into
the
interstices
of
the
trabeculae
carnae
and
occasionally
involving
the
thebesian
channels.
In
addition,
the
endocardial
and
subendocardial
layers
subjacent
to
the
recent
or
organizing
mural
thrombi
contained
islands
of
polymorphonuclear
leukocytes,
lym-
phocytes
and
occasionally,
plasma
cells.
These
cellular
foci
were
limited
generally
to
such
zones
and
were
judged
merely
to
represent
reactions
to
the
overlying
thrombi
rather
than
to
have
been
due
to
primary
myocardial
inflammation.
The
aorta
was
either
normal
or
showed
but
minimal
arteriosclerosis
consisting
of
scattered
linear
or
plaque-like
foci
of
yellowish
thickening.
The
pulmonary
artery
displayed
no
abnormali-
ties
in
five
cases;
in
five,
mild
to
moderate
arteriosclerosis.
In
three,
embolic
occlusions
of
large
branches
of
the
pulmonary
artery
were
found.
The
lungs
were
the
seat
of
infarction
in
seven
of
the
ten
cases.
The
liver,
spleen,
kidneys
and
other
viscera
revealed
the
usual
character-
istics
of
cardiac
failure.
Focal
pyelonephritic
fibrosis
of
the
kidney
was
found
in
one
case
and
renal
infarction
had
occurred
in
three
cases,
in
two
of
which
splenic
infarcts
also
were
noted.
The
spleen
of
still
another
patient
was
the
site
of
an
infarct.
Thrombi
of
the
periprostatic,
femoral
and
perirectal
veins
were
found,
each
in
one
case.
Neither
renal
nor
systemic
vascular
abnormalities
suggestive
of
antecedent
hyper-
tension
were
found
in
any
of
our
cases,
nor
was
there
any
histologic
stigma
of
any
systemic
affection.
COMMENTS
The
cases
which
form
the
subject
of
this
report
represent
cardiac
hypertrophy
with
pro-
gressive,
unrelenting
myocardial
failure,
without
any
conventional
etiology.
Five
of
the
ten
pa-
tients
in
this
study
were
over
the
age
of
forty
and
the
diagnosis
of
"arteriosclerotic
heart
disease"
in
this
age
group,
despite
the
absence
of
anginal
pain,
is
made
often.
The
insignificant
degree
of
coronary
arteriosclerosis
present
in
our
cases
could
not
be
held
accountable
for
the
cardiac
abnormality.
A
conspicuous
finding
of
slightly
elevated
diastolic
blood
pressure
in
five
of
the
ten
cases,
with
diminished
pulse
pressure,
has
been
recognized
previously
as
a
common
accom-
paniment
of
the
severe
heart
failure
in
this
con-
dition.
5,i2,is
That
this
does
not
represent
essential
JUNE,
1955
go6
Cardiac
Hypertrophy
of
Unknown
Etiology—Elster
et
al.
hypertension
is
confirmed
by
the
absence
of
renal
or
systemic
arteriolar
sclerosis.
In
only
one
instance
was
mild
arteriolar
nephrosclerosis
noted,
and
this
in
the
vicinity
of
a
pyelonephritic
fibrotic
zone.
Various
authors
have
attempted
to
implicate
a
number
of
etiologic
and
pathogenetic
mecha-
nisms
in
cases
of
this
type.
Thiamine
deficiency
has
been
held
accountable
in
some
instances.
6,16
'"
However,
the
absence
of
the
dynamics
of
vitamin
B
1
deficiency
heart
disease,
the
adequate
nutritional
histories,
the
failure
of
administra-
tion
of
thiamine
in
large
quantities
to
alter
the
course
of
the
disease
and
the
absence
of
any
associated
stigma
of
vitamin
B
1
deficiency
com-
pels
us
to
reject
this
possibility
as
a
factor
in
the
morphogenesis
of
this
variety
of
cardiopathy.
Recently
a
number
of
reports
have
emanated
from
Africa"
"
,
"
describing
series
of
cases
of
cardiac
hypertrophy
and
insufficiency.
Davies"
has
reported
10
per
cent
of
all
fatal
cases
of
congestive
heart
failure
in
this
area
to
be
due
to
this
syndrome.
These
cases
appear
to
have
been
clinically
and
pathologically
similar
to
those
reported
herein.
Gillanders"
and
Higginson,
Gillanders
and
Murray"
have
been
the
leading
proponents
of
the
view
that
among
the
Bantus
vitamin
deficiency
or
malnutrition
is
the
basically
responsible
factor.
The
Bantus
are
known
to
subsist,
generally,
on
poor
or
inadequate
diets,
and
on
occasion
some
response
to
diet
and
specific
therapy
has
been
demonstrated.
Never-
theless,
these
investigators
add
that
in
long-
standing
disease
the
changes
have
proved
to
be
irreversible
and
moreover,
that
no
single
food
factor
is
responsible.
In
addition,
similar
cases
has
been
observed
in
very
well
nourished
pa-
tients.
It
is
noteworthy
that
experience
gained
from
clinical
and
necropsy
studies
in
prison
and
concentration
camps
has
shown
that
atrophic,
rather
than
hypertrophic
hearts
were
the
rule."
Significantly,
in
a
study
of
109
men
who
had
previously
suffered
for
forty-four
months
with
chronic
nutritional
deficiency
with
clinical
evidences
of
beri-beri,
Griffith
20
has
shown
that
the
few
instances
of
cardiac
enlargement
ob-
served
were
not
the
sequel
of
the
nutritional
deficiency
but
rather
the
effects
of
the
more
com-
mon
causes
of
heart
disease.
The
possible
relationship
of
our
cases
to
isolated
myocarditis
(so-called
Fiedler's
myo-
carditis,
idiopathic
myocarditis,
productive
myocarditis,
giant
cell
myocarditis,
myocarditis
of
unknown
etiology)
must
be
considered.
2
'
This
group
comprises
those
instances
of
more
or
less
widespread
granulomatous
or
diffuse
inflam-
matory
changes
of
the
myocardium,
later
with
connective
tissue
proliferation.
Although
the
pericardium
and
endocardium
are
not
directly
involved,
mural
thrombosis
is
found
often
and
embolic
phenomena
are
common.
These
cases
form
a
heterogeneous
group,
with
neither
a
distinctive
clinical
nor
a
uniform
pathologic
pattern.
They
have
been
considered
the
sequel
of
acute
respiratory
infections,
scarlet
fever
or
typhoid
fever,
virus
infection,"
or
due
to
arsenicals,
sulfur
or
sulfonamides.
The
cases
which
are
the
subject
of
the
present
study,
in
contradistinction
to
those
of
isolated
myo-
carditis,
presented
only
focal
inflammatory
foci
confined
either
to
necrotic
muscle
bundles
or
to
sites
adjacent
to
organizing
mural
thrombi,
and
constituted
reactive
rather
than
primary
cellular
infiltrates.
Amyloidosis
and
von
Gierke's
disease
with
myocardial
involvement
are
readily
eliminated
from
serious
consideration
since
these
are
identifiable
on
the
basis
of
their
characteristic
histochemical
pictures.
The
observation
of
three
cases
of
cardiomegaly
in
one
family,
and
the
necropsy
demonstration
of
myocardial
fibrosis
in
one
of
these,
led
Evans
to
suggest
a
"familial"
factor."
However,
in
six
other
instances
observed
by
that
author
no
such
familial
association
could
be
established.
Still
another
disease
process
to
be
differentiated
is
congenital
fibroelastosis,
most
often
seen
in
infants
within
the
first
year
of
life.24-27
The
lesions
observed
in
infants
have
included
parietal
giant
muscle
nuclei,
vacuolar
granular
degeneration
of
the
myocardium,
endocardial
sclerosis
and
myocardial
fibrosis.
Although
the
morphologic
resemblance
of
these
abnormalities
to
those
which
we
have
described
is
inescapable,
the
wide
disparity
in
age
inci-
dence
would
seem
to
make
untenable
any
belief
that
there
is
a
common
etiologic
denominator.
If
fibroelastosis
were
a
significant
pathogenetic
factor
one
would
expect
to
find
this
abnormality
among
older
children
and
adolescents
but
they
have
been
conspicuously
absent
from
the
literature.
26
The
cases
which
are
the
subject
of
this
report
cannot
be
correctly
designated
as
"endocardial
fibrosis."
Gray
28
believed
that
some
unknown
factor
produced
endocardial
fibrosis
and
this
in
turn
resulted
in
congestive
heart
failure.
It
is
well
recognized,
however,
that
congestive
heart
failure
of
any
cause
may
lead
ultimately
to
the
AMERICAN
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Cardiac
Hypertrophy
of
Unknown
Etiology—Elster
et
al.
907
development
of
endocardial
fibrosis."'"
Gray
also
suggested
that
the
category
designated
endo-
cardial
fibrosis
may
be
a
member
of
the
"ill-
defined
category
of
collagen
diseases."
More
recently
Becker
et
al."
reported
a
number
of
cases
similar
to
those
described
in
this
report
and
believed
that
they
represented
a
manifestation
of
"diffuse
collagen
disease."
The
collagenous
degeneration
was
primarily
endocardial
in
loca-
tion
and
systemic
involvement
was
not
demon-
strated.
We
do
not
subscribe
to
the
belief
that
this
variety
of
endocardial
and
subendocardial
fibrosis
can
be
grouped
with
the
collagen
dis-
eases,
although
there
may
be
some
superficial
histologic
similarities.
It
is
unwarranted,
obvi-
ously,
to
ascribe
specificity
to
a
lesion
of
the
endocardium
which
is
common
to
a
number
of
dissimilar
cardiopathies.
Endocardial
fibrosis
should
be
viewed
as
the
expression
of
abnormal
pressure
relationships
within
the
cardiac
cham-
bers,
or
as
the
result
of
infection,
a
systemic
toxin
or,
most
frequently
perhaps,
as
the
sequel
of
anoxic
effects
upon
the
subendocardium.
The
collagen
diseases,
on
the
other
hand,
are
char-
acteristically
systemic
in
character
and
associated
with
a
distinctive,
although
protean,
clinical
picture.
It
is
noteworthy
that
our
cases
ex-
hibited
no
significant
systemic
or
anatomic
abnormalities.
Furthermore,
the
cardiac
lesions
bore
no
resemblance
to
those
of
the
classical
descriptions
of
Klemperer
and
his
associates.n
Our
histologic
studies
did
not
uncover
any
alterations
specific
for
any
particular
causative
factor,
and
so
the
mechanism
responsible
for
the
cardiomegaly
remains
unclear.
It
is
believed
that
the
pathogenesis
of
the
myocardial
abnor-
malities
can
be
traced,
in
part,
to
the
degenera-
tive
myofibrillar
alterations,
and
to
successive
cellular
reactions
leading
to
connective
tissue
proliferation.
These
changes
are
not
considered
primary
but
rather
the
anatomic
expression
of
faulty
myofibrillar
nutritional
exchange
inci-
dent
to
the
considerable
hypertrophy
and
dilation.
Although
the
alterations
were
scattered
throughout
the
breadth
of
the ventricular
wall,
the
greater
involvement
of
the
subendocardium
and
endocardium
and
the
progressive
cardio-
pathy
can
be
ascribed
to
anoxia
incident
to
the
intracardiac
circulatory
insufficiency."
The
mural
thrombi,
moreover,
are
believed
to
be
the
result
of
stasis
in
association
with
the
endo-
cardial
degenerative
changes
and
the
ensuing
fibrosis.
Although
there
is
no
satisfactory
explanation
for
initiation
of
the
process,
hypertrophy
once
established
acts
deleteriously
of
itself
upon
the
intracardiac
fluid
and
oxygen
exchange
and
con-
tributes
importantly
to
recurrent
and
progressive
myofibrillar
degeneration.
It
has
been
shown
that
the
cardiac
capillary
network
per
unit
of
myo-
fibril
diminishes
with
expansion
of
the
muscle
mass."
Harrison
and
his
associates
have
demon-
strated,
further,
that
the
thicker
the
cardiac
fiber,
the
longer
the
time
required
for
the
meta-
bolic
exchange,
and
so
the
hypertrophied
fiber
is
not
conducive
to
efficient
oxygen
consumption."
Accordingly,
an
enlarging
muscle
mass
con-
tributes
to
impairment
of
muscle
nutrition,
for
hypertrophy
augments
the
requirements
of
the
blood
supply.
This
additive
demand,
in
the
face
of
a
decreased
cardiac
output
resulting
from
heart
failure,
compounds
the
problem
of
the
fail-
ing
myocardium.
The
preponderance
of
the
lesions
due
to
cardiac
anoxia
within
the
subendocardial
myofibrils
has
been
ascribed
to
the
fact
that
these
areas
are
remote
from
the
source
of
blood
supply."
That
the
epicardial
portion
of
the
left
ventricular
myocardium
is
more
richly
vascular-
ized
than
the
subendocardial
layer
may
also
account
for
such
localization.
It
has
been
shown,
in
addition,
that
the
gradient
of
intramyocardial
pressure
decreases
from
the
deeper
to
the
more
superficial
layers
of
the
cardiac
wall
during
systolic
contraction."
In
the
depth
of
the
myo-
cardium
the
intramural
tension
exceeds
that
of
the
aortic
pressure,
while
in
the
superficial
zones
it
may
be
even
less
than,
or
equal
to,
the
pressure
within
the
aorta
and
coronary
artery
tree.
All
these
mechanisms
conspire
finally
to
make
the
subendocardial
musculature
more
vulnerable
and
therefore
more
sensitive
to
the
effects
of
a
deficient
oxygen
supply.
Once
estab-
lished,
the
endocardial
alterations
in
themselves
contribute
to
the
progression
of
the
anoxic
changes
by
further
compromising
the
thebesian
and
capillary
network.
CASE
REPORTS
CASE
I.
R.
B.
(No.
638433),
a
forty
year
old
Negro
man,
entered
The
Mount
Sinai
Hospital
in
January,
1952.
He
had
no
knowledge
of
rheumatic
fever
or
hypertension.
The
nutritional
history
was
good;
alcoholic
intake
was
minimal.
In
1941
he
was
apprised
of
an
enlarged
heart.
There
were
no
symptoms
until
January,
1951,
when
progressive
exertional
dyspnea
and
orthop-
nea
appeared,
soon
followed
by
paroxysmal
JUNE,
1955
go8
Cardiac
Hypertrophy
of
Unknown
Etiology—Elster
et
al.
Fin.
11.
Case
I.
Marked
cardiac
enlargement,
especially
of
left
ventricle.
Kymographic
studies
revealed
di-
minished
pulsations
and
paradoxic
motion
of
left
ven-
tricular
border
suggestive
of
ventricular
aneurysm.
nocturnal
dyspnea.
Digitalis
and
mercurials
were
administered
with
but
transitory
response.
Symptoms
of
heart
failure
worsened
and
he
was
hospitalized.
Examination
disclosed
a
well
nourished
adult
male
with
moderate
respiratory
distress.
Fundu-
scopic
examination
revealed
normal
vessels
with
few
small
exudates.
The
neck
veins
were
distended;
there
was
a
positive
hepatojugular
reflux.
Fine
moist
inspiratory
rales
were
present
at
both
lung
bases.
The
apical
cardiac
impulse
was
diffuse
but
maximal
in
the
sixth
intercostal
space
at
the
anterior
axillary
line;
gallop
rhythm
was
noted
and
the
heart
sounds
were
poor.
A
harsh,
blowing,
grade
4
systolic
murmur
was
audible
at
the
apex
and
transmitted
both
to
the
axilla
and
to
the
base
of
the
heart.
No
thrill
or
pericardial
rub
was
detected.
The
second
pul-
monic
sound
was
markedly
accentuated
and
louder
than
the
second
aortic
sound.
The
blood
pressure
was
120
systolic
and
100
diastolic.
The
heart
rate
equalled
the
pulse
rate
and
was
140
per
minute.
Pulsus
alternans
was
demonstrated.
The
liver
edge
extended
to
a
point
6
cm.
below
the
right
costal
margin.
Ascites
and
peripheral
edema
were
absent.
Fluoroscopic
and
roent-
genographic
examinations
disclosed
marked
enlargement
of
the
heart,
predominantly
of
left
ventricle.
(Fig.
11.)
Diminished
pulsations
were
seen
roentgenographically,
while
electrokymo-
graphic
studies
demonstrated
paradoxic
motion
of
the
left
ventricular border
suggestive
of
ventricular
aneurysm.
The
electrocardiogram
showed
sinus
tachycardia
and
a
pattern
of
left
ventricular
strain.
The
venous
pressure
was
19.0
cm.
of
water;
the
decholin
circulation
time
was
prolonged
to
forty
seconds.
The
blood
hemoglobin,
white
blood
count
and
erythrocyte
sedimentation
rates
were
normal.
The
blood
urea
nitrogen,
fasting
blood
sugar,
glucose
tolerance
test
and
serum
cholesterol
were
all
within
normal
limits.
The
urine
con-
tained
a
trace
of
albumin
and
concentrated
to
a
specific
gravity
of
1.022.
Although
some
ob-
servers
implicated
either
rheumatic
fever,
hyper-
tension
or
arteriosclerosis
as
the
etiologic
agent,
the
majority
opinion
held
that
this
patient
had
"cardiac
hypertrophy
and
insufficiency
of
un-
known
etiology."
He
was
given
a
200
mg.
sodium
diet,
digitalis
and
intramuscular
mercurials.
There
was
a
weight
loss
of
10
pounds
and
some
improvement
of
his
clinical
status.
Large
amounts
of
the
B
vitamins
were
given
paren-
terally
and
orally.
Signs
of
phlebothrombosis
of
the
lower
extremities
appeared
and,
accordingly,
anticoagulant
therapy
was
instituted.
After
three
weeks
he
had
improved
somewhat,
with
sub-
sidence
of
thrombophlebitis
and
was
discharged.
Despite
rigid
maintenance
of
his
regimen
the
patient's
cardiac
status
deteriorated
progres-
sively;
he
sustained
a
pulmonary
infarction
and
was
readmitted
in
March,
1952,
desperately
ill
with
dyspnea,
orthopnea,
chest
pain,
cough
and
hemoptysis.
The
physical
findings
were
similar
to
those
previously
described
except
that
congestive
heart
failure
was
more
severe.
Al-
though
evidence
of
thrombophlebitis
was
not
apparent,
anticoagulants
and
antibiotics
were
resumed,
in
addition
to
measures
for
the
manage-
ment
of
heart
failure.
His
course
was
complicated
by
the
appearance
of
a
shock-like
state
associated
with
the
"low-salt
syndrome"
and
azotemia.
All
attempts
to
correct
these
conditions
failed.
Heart
failure
worsened
and
hemoptysis
recurred.
The
patient
finally
succumbed,
approximately
fifteen
months
after
the
onset
of
his
symptoms
and
three
months
subsequent
to
his
first
admission
to
the
hospital.
Necropsy
Findings
(PM
15268).
The
heart
was
markedly
enlarged
and
weighed
610
gm.
The
pericardial
surfaces
were
smooth
and
glistening;
the
pericardial
sac
contained
15
cc.
of
clear
serous
fluid.
The
right
auricular
chamber
was
markedly
dilated;
its
endocardial
surface
was
smooth
and
glistening.
The
right
auricular
AMERICAN
JOURNAL
OF
MEDICINE
Cardiac
Hypertrophy
of
Unknown
Etiology—Elster
et
al.
909
appendage
showed
no
abnormalities
and
the
foramen
ovale
was
closed.
The
tricuspid
orifice
was
moderately
dilated;
the
valve
leaflets
thin
and
delicate.
The
chordae
tendineae
inserted
in
a
normal
web-like
fashion.
The
right
ventricle
was
markedly
dilated
and
its
wall
slightly
thickened.
The
right
ventricular
endocardium
was
smooth
and
free
of
thrombi.
The
pulmonic
valve
and
orifice
were
normal.
The
main
pul-
monary
artery
and
its
branches,
and
the
pul-
monary
veins
were
smooth-walled
and
patent.
The
left
auricular
chamber
was
markedly
en-
larged;
its
endocardium
smooth
and
glistening.
The
mitral
orifice
was
moderately
widened
but
the
valve
leaflets
were
thin
and
delicate;
its
chordae
tendineae
normal.
The
left
ventricular
chamber
was
conspicuously
enlarged
and
its
wall
markedly
hypertrophied,
measuring
20
nim.
in
thickness.
The
endocardium
over
the
septal
portion
appeared
slightly
thickened
and
greyish
white.
In
the
recesses
of
the
trabeculae
carnae
along
the
septal
surface
a
dark
red,
0.3
cm.,
slightly
adherent
thrombus
was
noted.
Elsewhere
in
the
left
ventricle
the
endocardium
was
glistening
and
free
of
thrombi.
The
aortic
orifice
was
moderately
enlarged
but
the
valve
leaflets
were
thin
and
delicate.
The
coronary
ostia
and
arteries
were
patent
and
showed
but
a
few
scattered,
minute,
slightly
raised
arterio-
sclerotic
intimal
plaques.
Histologic
sections
of
the
heart
revealed
multiple
areas
in
which
the
myofibrils
appeared
granular;
their
architecture
was
indistinct,
with
nuclear
fragmentation
and
loss.
Associated
with
these
were
scattered
granulation
tissue-like
reactive
foci
with
inter-
spersed
lymphocytes
and
fibroblasts.
Within
these
areas
entrapped
muscle
fibers
appeared
atrophic,
while
others
were
deeply
eosinophilic
and
contained
no
nuclei.
Irregularly
dissemi-
nated
fibrotic
zones
were
noted
which
were
principally
subendocardial
in
location.
The
endocardium
over
the
interventricular
septum
showed
focal
avascular,
dense,
fibrotic
thicken-
ing.
The
predominant
histologic
pattern
was
myofibrillar
hypertrophy.
Additional
significant
pathologic
findings
included
passive
congestion
of
viscera;
multiple
pulmonary
emboli
and
infarcts
with
necrotic
infarct
of
the
left
lower
lobe;
hydrothorax
(200
cc.)
and
fibrous
pleuritis
on
the
left.
Comment.
This
case
illustrates
the
progressive,
fatal
course
of
this
disease.
Congestive
heart
fail-
ure
could
be
mitigated
only
temporarily.
Pulmonary
infarction,
incident
to
peripheral
venous
thrombosis,
and
a
shock-like
state
terminated
the
course.
No
clue
as
to
the
etiology
was
afforded
by
either
the
clinical
or
the
ana-
tomic
findings.
CASE
ii.
A.
C.
(No.
622375),
a
thirty-four
year
old
Negro
man,
was
admitted
to
The
Mount
Sinai
Hospital
for
the
first
time
in
November,
1950.
He
was
in
excellent
health
until
1947
when
he
was
hospitalized
elsewhere
for
six
weeks
because
of
chest
pain,
cough
and
hemoptysis.
Ten
months
prior
to
admission
to
The
Mount
Sinai
Hospital
cardiomegaly
was
revealed
by
a
routine
chest
roentgenogram.
Eight
months
before
entry
the
patient
noted
pain
and
swelling
of
his
left
calf,
and
two
months
later
mild
exertional
dyspnea
first
appeared.
Three
months
before
hospitalization
a
non-productive
cough
ensued
and
worsened
progressively.
For
the
ten
days
prior
to
hospitalization
he
noted
nausea,
increasing
abdominal
enlargement,
facial
edema
and,
for
one
day,
severe
cough
and
dyspnea.
Previous
history
revealed
that
he
had
had
diphtheria
at
the
age
of
four
years
but
there
was
no
knowledge
of
scarlet
fever,
rheumatic
fever
or
hypertension.
His
dietary
intake
was
adequate;
his
alcohol
consumption
minimal.
On
admission
the
patient
appeared
acutely
ill
with
evidence
of
congestive
heart
failure.
The
neck
veins
were
distended;
hepatojugular
reflux
was
present.
The
lungs
were
clear
except
for
the
presence
of
a
right
pleural
effusion.
The
heart
was
enlarged.
The
second
pulmonic
sound
was
accentuated
and
greater
than
the
second
aortic
sound.
Regular
sinus
rhythm
with
a
rate
of
102
per
minute
was
present.
A
grade
2
harsh
systolic
murmur
was
maximal
in
the
third
intercostal
space
to
the
left
of
the
sternum.
A
long
harsh
systolic
murmur,
heard
best
at
the
apex,
was
transmitted
to
the
axilla.
The
blood
pressure
was
120
systolic,
95
diastolic.
The
liver
was
felt
at
a
point
five
fingerbreadths
below
the
right
costal
margin
in
the
mid-clavicular
line.
The
spleen
edge
was
not
felt.
One
to
two
plus
pedal
and
sacral
edema
was
present.
The
cir-
cumference
of
the
left
calf
was
2
cm.
greater
than
that
of
the
right
calf.
Labe__
atory
investiga-
tion
revealed
the
specific
gravity
of
the
urine
to
be
1.021.
The
urine
contained
3.0
gm.
of
albumin
per
liter;
no
formed
elements
were
present
in
the
sediment.
Blood
count,
sedimentation
rate,
Wassermann
and
Kahn
reactions
were
all
normal.
Blood
urea,
sugar
and
cholesterol
were
normal,
as
were
liver
function
studies.
The
serum
bilirubin
was
0.5
to
0.9
mg.
per
cent.
JUNE,
1955
9
t
o
Cardiac
Hypertrophy
of
Unknown
Etiology—Elster
et
al.
Blood
cultures
were
sterile.
Venous
pressure
was
elevated
and
the
decholin
circulation
time
was
prolonged.
The
arterial
oxygen
saturation
was
19.4
volumes
per
cent
(92
per
cent).
X-ray
of
the
chest
demonstrated
cardiac
enlargement
in
all
diameters
and
a
right
hydrothorax.
Electro-
cardiograph
showed
sinus
tachycardia,
left
axis
deviation
and
changes
compatible
with
acute
coronary
insufficiency
and
acute
cor
pulmonale.
The
precise
nature
of
the
patient's
disease
was
not
defined
on
his
admission
to
the
hospital.
He
ran
a
febrile
course,
with
temperatures
vary-
ing
from
100
to
102
°
F.
unaltered
by
penicillin
and
streptomycin.
Blood
pressure
varied
between
95/70
and
128/88
(average
106/80).
Despite
bedrest,
salt
restriction,
the
administration
of
digitalis
and
mercurials,
signs
of
heart
failure
progressed
with
increasing
right
pleural
effusion,
distended
neck
veins,
enlarging
liver
and
periph-
eral
edema.
Thoracentesis
yielded
grossly
bloody
but
sterile
fluid
which
contained
mostly
lympho-
cytes
and
erythrocytes.
After
six
weeks
of
illness
he
was
discharged
from
the
hospital
unimproved.
He
remained
at
home
on
a
similar
regimen,
again
to
no
avail.
Three
weeks
following
dis-
charge
he
developed
pain
and
swelling
of
his
right
calf,
and
one
week
later
re-entered
the
hospital.
His
clinical
findings
were
unchanged
except
that
now
there
was
evidence
of
right
femoral
thrombophlebitis.
Forty-eight
hours
following
readmission
he
died
suddenly.
Necropsy
Findings
(PM
14885).
The
heart
weighed
470
gm.
and
was
uniformly
flabby.
There
were
extensive
adhesions
between
the
parietal
leaflet
of
the
pericardium
and
the
mediastinal
pleurae.
The
pericardial
cavity
was
partially
obliterated
by
fibrous
adhesions
which
pocketed
gelatinous
material.
The
parietal
pericardial
layers
were
thin.
Jugular
veins
and
superior
and
inferior
venae
cavae
were
markedly
distended
and
patent
with
smooth
shiny
surfaces.
Conspicuous
dilation
of
the
right
atrium
to
four
times
the
normal
capacity
was
noted.
The
endocardium
was
pink
and
smooth,
except
posterosuperiorly
where
there
was
a
large
yel-
lowish
grey
plaque
of
firm
adherent
thrombus
which
completely
filled
a
dilated
auricular
ap-
pendage.
The
atrial
wall
was
thickened
and
the
musculi
pectinati
were
prominent.
The
tricuspid
valve
orifice
was
dilated.
There
was
marked
dilation
and
hypertrophy
of
the
right
ventricle;
the
wall
was
thick,
flabby
and
reddish
brown
with
punctate
yellow
speckling
and
fine
yellow
streaks.
The
region
of
the
septum
was
occupied
by
two
1
by
2
cm.
soft,
yellow,
smooth,
partially
liquefied
thrombi.
Posterior
to
the
anterior
leaflet
of
the
tricuspid
valve,
and
in
contact
with
it,
there
was
a
1.5
by
3
cm.
soft,
friable,
yellow
thrombus.
The
anterior
leaf
of
the
tricuspid
valve
was
shortened,
ballooned
out
and
ir-
regularly
thickened.
The
posterior
valve
leaflet
was
slightly
thickened;
its
chordae
and
papillary
muscle
were
conglutinated
to
the
ventricular
wall.
The
septal
cusp
was
thin,
with
discrete,
nor-
mally
webbed
chordae
which
were
interlaced
by
fine
interdigitating
webs.
Posterior
to
the
valve
beneath
its
ring
were
small,
irregular,
grey,
firm,
adherent
thrombi.
The
endocardium
inferior
to
the
valve
was
finely
wrinkled
and
stippled,
and
beneath
the
tricuspid
valve
ring
irregular,
broad,
grey,
subendocardial
fibrotic
streaks
were
seen.
The
papillary
muscles
and
trabeculae
carnae
were
considerably
hyper-
trophied.
The
pulmonic
valve
cusps
were
fore-
shortened,
with
shallow
sinuses.
The
right
cusp
was
almost
completely
adherent
to
the
pul-
monary
artery,
having
obliterated
the
sinus
but
leaving
a
thin,
rolled
edge.
Beneath
the
valve
ring
subendocardial
fibrosis
was
marked.
Just
superior
to
the
valve
fine
linear
wrinkling
of
the
pulmonary
artery
was
noted.
The
left
atrium
was
dilated
and
its
wall
slightly
hypertrophied;
its
endocardium,
normal.
The
left
auricular
ap-
pendage
was
dilated
and
free
of
thrombus.
The
mitral
valve
leaflets
were
thin
and
smooth,
the
chordae
tendineae
discrete
and
tenuous
with
normally
webbed
insertions.
The
left
ventricle
was
dilated
and
its
wall
hypertrophied.
The
endocardium
was
smooth
throughout
with
no
thrombi.
The
myocardium
was
flabby,
dark
red-brown
with
fine
punctate
speckling
and
yellow
streaks.
The
papillary
muscles
and
trabeculae
carnae
were
hypertrophied.
The
aortic
valve
orifice
was
normal.
Minimal
aortic
atherosclerosis
was
seen,
only
at
the
arterial
orifices.
The
ostia
and
branches
of
the
coronary
arteries
were
widely
patent.
Histologic
examina-
tion
of
the
right
ventricle
disclosed
multiple
areas
of
subendocardial
and
endocardial
fibrous
thickening
with
contiguous
organizing
mural
thrombosis.
In
one
section
a
tricuspid
valve
chorda
tendinea
was
incorporated
into
a
fibrosed
endocardial
zone.
The
base
of
the
pulmonary
artery
showed
partial
sinus
obliteration
by
the
endocardial
and
subendocardial
scarring,
while
the
tricuspid
valve
pocket
was
partially
oblit-
erated
by
the
fibrous
endocardial
thickening.
The
right
atrium
was
the
seat
of
scattered
AMERICAN
JOURNAL
OF
MEDICINE
Cardiac
Hypertrophy
of
Unknown
Etiology—Elster
et
al.
911
fibrosed
foci.
The
left
ventricular
wall
revealed
widespread
but
predominantly
subendocardial
fibrosis.
Interstitial
and
perivascular
foci
were
noted
as
well,
accompanied
by
moderate
re-
placement
of
muscle
fibers;
myofibrillar
hyper-
trophy
dominated
the
histologic
picture.
There
were
scattered
zones
of
atrophy,
granularity
and
smudging
of
sarcoplasm,
with
myofibrillar
frac-
ture,
mainly
subendocardially.
Other
significant
necropsy
findings
included
severe
passive
congestion
of
viscera,
mul-
tiple
pulmonary
infarcts,
anasarca,
and
right
hydrothorax.
CASE
in.
M.
G.
(No.
550720)
was
a
twenty-
four
year
old
white
man
whose
history
was
inade-
quate
due
to
mental
deficiency.
Years
prior,
the
patient
had
an
attack
of
paroxysmal
tachycardia
for
which
he
had
received
mercuhydrin®.
On
the
evening
of
admission
cramp-like
peri-
umbilical
pain
appeared
two
hours
post-
prandially,
followed
by
weakness
which
in-
creased
progressively.
The
abdominal
cramps
worsened
and
were
joined
by
watery
stools.
There
was
no
history
of
fat
intolerance.
However,
he
recalled
postprandial
distention,
relieved
by
gaseous
eructations.
Physical
examination
re-
vealed
an
acutely
ill
male
with
a
rectal
tem-
perature
of
102.4°F.
The
cervical
veins
were
not
distended
and
the
chest
was
clear.
The
heart
was
enlarged
with
the
point
of
maximal
in-
tensity
outside
the
mid-clavicular
line
at
the
fifth
intercostal
space.
The
second
pulmonic
sound
was
louder
than
the
second
aortic
sound
and
was
markedly
accentuated.
Sinus
arrhyth-
mia
of
92
per
minute
was
noted.
The
blood
pressure
was
120
systolic,
70
diastolic.
Marked
rigidity
of
the
right
upper
abdominal
quadrant
was
noted,
with
upper
right
rectus
spasm
and
tenderness.
No
masses
were
palpable.
The
urinary
specific
gravity
was
1.030;
2
plus
albuminuria
was
present.
Urinary
glucose
and
bile
were
absent
and
only
rare
leukocytes
were
found
in
the
sediment.
The
blood
hemoglobin
was
normal
but
the
white
blood
count
was
12,450
cells
per
cu.
mm.
with
an
increase
of
polymorphonuclear
leukocytes
to
90
per
cent.
Blood
studies,
includ-
ing
urea
nitrogen,
cholesterol,
sugar,
total
protein,
serum
bilirubin,
erythrocyte
sedimenta-
tion
rate
and
Wassermann
reaction,
were
all
normal.
Blood
cultures
remained
sterile.
Elec-
trocardiograph
revealed
auricular
flutter,
an
auricular
rate
of
300
with
a
4:1
block.
A
left
bundle
branch
block
pattern
was
demonstrated.
The
impression
on
admission
was
that
the
pa-
tient
possibly
had
acute
cholecystitis.
However,
the
electrocardiographic
pattern
of
auricular
flutter
and
the
subsequent
palpation
of
an
en-
larged,
smooth,
tender
liver
suggested
that
the
clinical
picture
rather
might
he
due
either
to
myocarditis
with
cardiac
failure
or,
perhaps,
to
thrombosis
of
the
hepatic
veins
with
associated
myocarditis.
The
arrhythmia
was
treated
with
quinidine,
digitalis
and
atabrine®,
without
effect,
and
his
febrile
course
persisted
despite
penicillin.
The
patient
became
very
disturbed
and
required
sedation
with
paraldehyde.
On
the
third
hos-
pital
day
he
suddenly
became
cyanotic
and
succumbed.
Necropsy
Findings
(PM
13481).
The
heart
weighed
800
gm.
and
was
markedly
enlarged,
particularly
the
left
ventricle.
The
pericardial
surfaces
were
smooth
and
glistening;
the
peri-
cardial
sac
contained
75
cc.
of
blood-stained
fluid.
The
right
auricle
was
slightly
dilated.
The
wall
of
the
right
auricle
was
thickened
and
its
endocardium
greyish
white.
The
right
ventricu-
lar
wall
was
hypertrophied
and
its
chamber
dilated.
The
endocardium
was
greyish
white
and
irregularly
thickened
and
opaque.
The
left
atrium
was
slightly
dilated,
its
endocardium
greyish
white
and
finely
wrinkled.
The
left
auricular
appendage
was
reduced
in
size,
its
orifice
obliterated
but
its
lumen
was
patent
and
the
lining
was
smooth.
The
left
ventricle
was
markedly
hypertrophied
and
dilated;
its
endo-
cardium
was
normal.
A
mural
thrombus
which
measured
1
cm.
in
diameter
occupied
the
apical
segment
and
overlay
a
zone
of
endocardial
fibrosis.
The
anterior
papillary
muscle
was
markedly
hypertrophied.
All
the
cardiac
valves
were
normal.
The
pulmonary
arter),
revealed
no
arteriosclerosis.
The
aorta
was
smooth
and
elastic;
the
coronary
ostia
were
normal.
The
coronary
arteries
were
widely
patent
through-
out,
and
revealed
no
abnormalities.
Histologic
study
of
the
left
ventricle revealed
severe
dis-
seminated,
occasionally
confluent
zones
of
fibrosis,
frequently
with
admixed
elastified
fibers.
These
fibrotic
areas
were
distributed
throughout
the
thickness
of
the
left
ventricular
wall
but
were
more
frequent
and
conspicuous
within
the
inner
half.
Sudanophilic
and
glycogen-contain-
ing
islands
were
scattered
within
several
fibrosed
areas.
Here
and
there
muscle
fibers
trapped
within
areas
of
connective
tissue
proliferation
were
atrophic
and
had
a
ghost-like
appearance.
Striking
myofibrillar
hypertrophy
with
bizarre
hyperchromatic
nuclei
was
widespread.
There
JUNE,
1955
912
Cardiac
Hypertrophy
of
Unknown
Etiology—Elster
et
al.
was
general
sparsity
of
capillaries.
Subendo-
cardial
myocardial
degeneration,
eosinophilic
smudging
and
atrophy
were
noted.
Section
through
the
apex
of
the
left
ventricle,
in
addition
to
the
foregoing
alterations,
disclosed
an
overly-
ing
adherent
thrombus
the
base
of
which
was
extensively
vascularized
and
organized.
Left
auricular
hypertrophy
with
focal
replacement
fibrosis
and
a
connective
tissue
endocardial
excrescence
were
present.
An
occasional
focus
of
fibrosis
was
noted
within
the
wall
of
the
right
ventricle,
associated
with
hypertrophy
and
subendocardial
fatty
change
of
myocardial
fibers.
There
was
no
significant
histologic
valvu-
lar
abnormality.
Additional
pertinent
necropsy
findings
con-
sisted
of
bilateral
hydrothorax
and
severe
passive
visceral
congestion.
There
was
no
evidence
of
cholecystitis
and
no
arteriolosclerosis.
CASE
IV.
S.
L.
(No.
600921),
a
thirty-two
year
old
white
man,
first
became
ill
fifteen
months
prior
to
his
final
admission
to
The
Mount
Sinai
Hospital.
The
patient
had
experienced
exertional
and
paroxysmal
nocturnal
dyspnea
requiring
a
brief
admission
to
another
hospital,
where
severe
left
heart
failure,
a
very
large
heart
and
a
blood
pressure
of
125
systolic
and
105
diastolic
were
recorded.
Three
months
later
he
first
entered
The
Mount
Sinai
Hospital.
He
was
slightly
dyspneic;
blood
pressure
was
120
systolic,
88
diastolic;
pulse
rate
was
112
per
minute.
The
optic
fundi
were
normal.
The
heart
was
enlarged
to
the
left;
diastolic
gallop
rhythm
was
heard.
Neither
edema
nor
cyanosis
was
present.
On
fluoroscopy
the
heart
appeared
markedly
enlarged,
predominantly
to
the
left.
Blood
hemoglobin
was
14.2
gm.,
the
white
blood
cell
count
11,650
per
cu.
mm.
Urinalysis
was
normal
except
for
slight
albuminuria.
The
erythrocyte
sedimentation
rate
was
10
mm.
per
hour
(Westergren).
The
venous
pressure
was
15
cm.
of
blood
with
a
rise
to
19.5
cm.
upon
right
upper
quadrant
pressure.
The
circulation
time
with
decholin
was
25
seconds.
The
blood
urea
nitrogen
was
15
mg.,
and
fasting
blood
sugar,
89
mg.
per
cent.
The
electrocardiogram
showed
regular
sinus
tachycardia;
P
waves
were
wide
and
notched.
Coronary
arteriosclerosis,
diffuse
vascular
disease,
acute
non-specific
myocarditis
and
re-
current
pulmonary
embolism
were
all
considered
as
diagnostic
possibilities.
Hyperthyroidism
was
excluded
by
appropriate
laboratory
studies.
During
the
first
six
hospital
days
he
was
fairly
comfortable
with
but
mild
tachycardia,
low
grade
fever
and
slight
dyspnea.
Following
this
period
he
became
acutely
and
severely
dyspneic,
orthopneic,
expectorated
bright
red
blood
and
then
developed
crepitant
rales
over
the
right
lower
lobe
accompanied
by
suppression
of
breath
sounds.
He
had
obviously
sustained
a
pulmonary
infarct,
confirmed
by
roentgeno-
gram.
Treatment
consisted
of
a
salt-poor
diet,
digitalis,
mercurial
diuretics,
penicillin,
heparin
and
dicumarol.
For
the
ten
ensuing
days
the
patient
remained
critically
ill
and
then
slowly
improved.
When
finally
ambulated,
gallop
rhythm
and
dyspnea
reappeared
and
he
gained
several
pounds,
all
of
which
responded
fairly
well
to
mercurial
diuretics.
After
eight
weeks
in
the
hospital
he
was
discharged
somewhat
im-
proved.
The
patient
remained
on
a
salt-restricted
diet,
received
digitalis
and
mercuhydrin
injec-
tions.
Nevertheless,
exertional
dyspnea,
orthop-
nea,
some
substernal
discomfort,
nausea
and
diaphoresis
remained
throughout
this
period.
Two
days
prior
to
readmission
he
experienced
a
severe
exacerbation
of
substernal
pain
accom-
panied
by
pallor,
sweating,
vomiting
and
dyspnea.
On
readmission
his
rectal
temperature
was
100.2
°
F.
and
pulse
130
per
minute;
blood
pressure
was
110
systolic
and
90
diastolic.
The
optic
fundi
were
normal.
The
left
lobe
of
the
thyroid
gland
was
diffusely
enlarged.
Coarse,
bubbling
rales
at
both
lung
bases
and
rhonchi
throughout
the
pulmonary
fields
were
audible.
The
heart
was
enlarged,
both
to
the
left
and
to
the
right;
a
loud
apical
systolic
murmur
and
diastolic
gallop
rhythm
were
present.
The
liver
edge
was
firm
and
palpable
one
fingerbreadth
below
the
costal
margin.
Laboratory
findings
were
similar
to
those
found
on
the
first
admission.
The
cardiac
failure
which
earlier
seemed
to
have
been
purely
left-sided
now
had
elements
of
right-sided
failure
as
well.
On
several
occasions
the
patient
developed
a
shock-like
state
followed
by
pulmonary
signs,
a
picture
considered
to
be
compatible
with
recurrent
pulmonary
embolism.
Temperature
elevations
accompanied
these
episodes
but
for
the
most
part
the
course
was
afebrile.
Right
pleural
pain
was
marked
and
persistent.
Oxygen
therapy
and
digitalis
seemed
of
only
limited
value.
The
patient's
condition
deteriorated
progressively
and
he
died
on
the
seventieth
hospital
day.
Necropsy
Findings
(PM
14463).
The
heart
weighed
740
gm.
The
pericardium
was
partially
adherent
to
the
pleura
by
fibrous
bands.
The
AMERICAN
JOURNAL
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Cardiac
Hypertrophy
of
Unknown
Etiology—Elster
et
al.
913
visceral
pericardium
was
normal.
The
vena
cavae
showed
slight
dilation
and
slight
intimal
thickening.
The
right
auricle
was
dilated;
its
wall
and
endocardium
were
thickened.
The
tricuspid
valve
was
normal.
An
irregular
grey-
white
mural
thrombus,
about
3
cm.
in
diameter,
was
attached
firmly
to
the
underlying
muscle
of
the
apex
of
the
right
ventricle.
The
right
ven-
tricle
was
markedly
dilated;
its
muscle
measured
0.6
cm.
on
cut
section.
The
myocardium
was
the
seat
of
diffuse
grey
flecks
of
fibrosis.
Beneath
the
thrombus
the
wall
appeared
firm,
grey-white
and
scarred,
except
for
a
thin
subepicardial
brown
muscle
layer.
The
pulmonic
valve,
pul-
monary
artery
and
pulmonary
veins
were
nor-
mal.
The
left
auricle
showed
irregularly
thick-
ened
endocardium
and
was
markedly
dilated
and
hypertrophied;
the
muscle
on
section
aver-
aged
0.5
cm.
in
thickness.
The
mitral
valve
was
normal.
The
left
ventricle
was
markedly
dilated
and
hypertrophied.
The
muscle
appeared
red-
brown,
slightly
firmer
than
usual
and
was
flecked
with
small
grey-white
fibrosed
foci;
the
papillary
muscles
were
rotund
and
firm.
The
interventric-
ular
septum
measured
1.5
cm.
in
width
and
displayed
a
gross
picture
similar
to
that
of
the
papillary
muscle
and
the
wall
of
the
left
ven-
tricle.
A
grey,
laminated,
firmly
adherent
mural
thrombus,
about
4
cm.
in
diameter,
was
situated
on
the
left
ventricular
wall
near
the
apex,
at-
tached
to
opacified
endocardium
over
the
trabeculae
carnae.
The
muscle
beneath
the
thrombus
was
grey-white
throughout
the
ventricular
wall
to
the
pericardium.
The
re-
mainder
of
the
endocardium
in
the
left
ventricle
was
opaque
and
thickened.
The
aortic
valve
was
normal.
The
aorta
showed
but
slight
arterio-
sclerosis
and
was
hypoplastic.
The
coronary
arteries
were
widely
patent
throughout
their
course;
arteriosclerotic
alterations
were
sparse.
Microscopic
examination
of
the
heart
dis-
closed
striking
muscle
fiber
hypertrophy.
Endo-
cardial
and
subendocardial
fibrosis
was
widely
disseminated
and
moderately
severe,
associated
with
granularity,
vacuolization,
smudging
and
fracture
of
adjacent
myocardial
fibers.
The
apical
mural
thrombi
were
extensively
fibrosed,
contained
macrophages
laden
with
iron-pigment
and
were
traversed
by
islands
of
lymphocytes.
Focal
myonecrosis
of
the
posterior
papillary
muscle
of
the
left
ventricle
was
noted,
with
linear
hemorrhage
and
reactive
polymorpho-
nuclear
leukocytes.
A
small
intramuscular
branch
of
a
coronary
artery
within
the
vicinity
of
a
fibrotic
lesion
was
the
site
of
an
organized
occlusion,
and
was
believed
to
have
been
the
sequel
to
the
myocardial
abnormality.
The
aorta
and
cardiac
valves
presented
no
histo-
pathologic
changes.
Associated
necropsy
findings
included
throm-
bophlebitis
of
the
right
posterior
tibial
veins,
organized
and
recent
pulmonary
emboli
with
infarction,
bilateral
organized
pleuritis,
small
left
pleural
effusion
and
organized
and
recent
infarcts
of
kidneys
and
spleen.
CASE
V.
M.
M.
(No.
575111),
a
thirty
year
old
Puerto
Rican
woman
with
no
previous
history
of
hypertension,
renal
disease
or
rheu-
matic
fever,
noted
the
onset
of
exertional
dyspnea
one
month
prior
to
entry.
This
symptom
gradu-
ally
increased
in
severity.
Subsequently,
orthop-
nea
and
ankle
edema
appeared
with
rapid
worsening
in
the
few
days
prior
to
hospitaliza-
tion.
Examination
presented
an
obese,
well
developed
female
in
moderate
congestive
heart
failure
and
respiratory
distress.
Diminution
of
breath
sounds
at
the
right
lung
base
was
noted.
The
heart
was
enlarged,
with
the
point
of
maximal
intensity
in
the
fifth
intercostal
space
to
the
left
of
the
mid-clavicular
line.
The
second
pulmonic
sound
was
equal
to
the
second
aortic
sound;
a
soft
blowing
systolic
murmur
was
heard
best
at
the
apex.
The
pulse
was
regular
and
rapid
with
a
rate
of
120
per
minute.
The
blood
pressure
was
140
systolic
and
100
diastolic.
The
ocular
fundi
were
normal.
The
liver
edge
was
tender
and
palpated
8
cm.
below
the
right
costal
margin.
The
spleen
was
felt
at
the
left
costal
border.
Edema
of
both
lower
extremities
was
present.
The
urine
revealed
a
specific
gravity
of
1.022,
2
plus
albumin,
no
sugar
and
occasional
red
and
white
blood
cells
on
micro-
scopic
examination.
The
blood
count,
sedimen-
tation
rate,
blood
urea
nitrogen,
fasting
blood
sugar,
cholesterol
and
serum
protein
values
were
all
normal.
Serologic
tests
for
syphilis
were
nega-
tive.
Phenolsulfonphthalein
excretory
studies
demonstrated
55
per
cent
excretion
in
two
hours;
the
urea
clearance
was
30 cc.
per
minute
(55
per
cent
of
normal).
Moderate
symmetric
cardiac
enlargement
and
bilateral
pleural
effusions
were
demonstrated
by
teleroentgenogram.
Electro-
cardiogram
revealed
regular
sinus
rhythm
with
T
waves
either
low
or
diphasic
in
all
leads,
indic-
ative
of
myocardial
abnormality.
Venous
pres-
sure
was
elevated
to
17.5
cm.
of
water;
circula-
tion
time
(calcium
gluconate)
was
40
seconds.
A
regimen
of
salt
restriction,
digitalis
and
mer-
JUNE,
1955
914
Cardiac
Hypertrophy
of
Unknown
Etiology—Elster
et
al.
curials
effected
a
loss
of
40
pounds
of
weight
within
the
first
week
of
hospitalization.
During
the
subsequent
four
weeks
however,
no
further
weight
loss
occurred.
Blood
pressure
averaged
approximately
140
systolic
and
100
diastolic.
In
spite
of
an
apparently
initial
satisfactory
re-
sponse,
pulsus
alternans
supervened
on
the
forty-ninth
hospital
day,
she
suddenly
com-
plained
of
dizziness
and
died.
Necropsy
Findings
(PM
13928).
The
heart
weighed
550
gm.
and
was
considerably
en-
larged.
The
pericardial
sac
contained
100
cc.
of
thin
serosanguineous
fluid.
All
chambers
were
dilated
and
their
walls
were
thickened.
The
valves
were
normal
except
for
a
few
minute
nodose
areas
along
the
edges
of
the
mitral
and
tricuspid
leaflets.
A
few
chordae
tendineae
of
the
tricuspid
valve
appeared
shortened
but
the
remaining
chordae
of
the
tricuspid
and
all
of
those
of
the
mitral
valve
appeared
normal.
The
coronary
arteries
and
their
ostia
disclosed
no
ab-
normalities.
The
endocardium
was
smooth
and
the
chambers
contained
no
thrombi.
The
pul-
monary
artery
was
normal;
minimal
arterio-
sclerosis
of
the
aorta
was
noted.
Histologic
study
revealed
widespread
extensive
myocardial
scar-
ring
in
varying
stages.
The
earliest
lesions
were
composed
of
loose,
relatively
cellular
connective
tissue
containing
moderate
numbers
of
lympho-
cytes,
plasma
cells,
macrophages
and
rare
polymorphonuclear
leukocytes.
Other
areas
were
dense,
acellular
but
vascularized,
whereas
the
oldest
lesions
were
avascular,
often
elastified
and
acellular.
Fragmented,
granular
and
occa-
sionally
vacuolated
myocardial
fibers
were
scattered
throughout,
usually
in
association
with
the
more
recent
fibrotic
foci.
Focal
necrosis
of
the
anterior
wall
of
the
left
ventricle
was
seen,
with
associated
fine
linear
hemorrhage.
Hyper-
trophied
muscle
fibers
were
abundant.
Although
interstitial
and
replacement
myofibrillar
fibrosis
was
seen
throughout
the
thickness
of
the
ventric-
ular
wall,
predominant
alterations
were
in
the
subendocardium
and,
to
a
somewhat
lesser
degree,
in
the
endocardium.
The
tricuspid
valve
was
mildly
edematous
and
contained
a
moderate
number
of
loosely-knit
fibroblasts,
as
well
as
a
focal
collection
of
lymphocytes.
Vascularization
was
absent.
In
the
area
of
adherent
chordae
(vide
supra)
sclerosis
of
endocardium
was
mild
and
extended
into
the
subjacent
myocardium.
Significant
associated
postmortem
findings
included
chronic
passive
congestion
of
the
lungs,
liver,
spleen
and
kidneys.
Some
mild
pyelone-
phritic
scarring
was
found
but
evidence
of
ar-
teriosclerosis
of
the
kidneys
and
other
organs
was
absent.
Comment.
This
patient's
course
was
quite
brief
following
the
inception
of
cardiac
failure.
Although
blood
pressure
values
were
persistently
at
levels
of
140
systolic,
100
diastolic,
post-
mortem
studies
failed
to
demonstrate
any
nephrosclerosis
or
other
significant
renal
lesion.
Hence
hypertension
is
not
considered
to
have
been
the
etiologic
factor
in
her
cardiac
disease.
The
outstanding
pathologic
feature
was
the
myocardial
and
interstitial
lesion
which
could
not
be
ascribed
to
vascular
factors.
CASE
VI.
J.
0.
(No.
408197),
a
forty-four
year
old
Puerto
Rican
woman,
was
admitted
in
extremis.
A
detailed
history
was
unobtainable
but
apparently
for
four
months
she
had
had
marked
dyspnea
and
edema
of
the
lower
extremities.
During
this
period
the
respiratory
difficulty
was
almost
intractable,
with
slight
and
but
transitory
relief
following
digitalization.
Physical
examination
disclosed
an
extremely
dyspneic,
orthopneic
woman
with
ashen-grey
cyanosis.
The
pupils
were
miotic
due
to
morphine.
The
lungs
upon
percussion
were
flat
at
both
bases
and
mid-way
up
the
right
hemithorax.
Breath
sounds
were
distant
over
both
lower
lobes,
with
fine
moist
rales
audible
at
both
bases.
The
heart
was
enlarged,
both
to
the
right
and
to
the
left;
the
point
of
maximal
impulse
was
at
the
anterior
axillary
line
at
the
sixth
rib.
The
cardiac
sounds
were
distant
and
the
rate
rapid.
A
systolic
murmur
which
was
not
transmitted
was
audible
at
the
apex.
The
blood
pressure
was
140
systolic
and
100
diastolic.
Moderate
ascites
was
present.
The
liver
was
enlarged,
its
edge
extending
almost
to
the
level
of
the
umbili-
cus.
Vigorous
therapy
consisting
of
phlebotomy,
digitalization,
thoracentesis,
mercurials
and
oxygen
yielded
no
improvement.
Her
pulse
remained
rapid
and
weak,
the
respiratory
rate
decreased,
the
blood
pressure
fell
to
shock
levels
and
the
patient
died
within
several
hours
of
her
admission.
Necropsy
Findings
(PM
10355).
The
heart
weighed
430
gm.
There
were
many
agonal
pin-
head-sized
petechial
hemorrhages
in
the
parietal
pericardium.
The
pericardial
sac
held
a
small
quantity
of
straw-colored
fluid.
The
vena
cavae
and
tributaries
were
greatly
engorged.
The
auricular
endocardial
layer
was
opaque
and
suggestively
rugose.
The
tricuspid
valve
leaflets
were
thin,
with
scalloped
edges;
chordae
AMERICAN
IOURNAL
OF
MEDICINE
Cardiac
Hypertrophy
of
Unknown
Etiology—Elster
et
al.
9
1
5
tendineae
were
delicate.
The
wall
of
the
right
ventricle
was
moderately
hypertrophied,
flabby
and
had
a
grey
cast.
In
the
subendocardium
were
many
greyish
yellow
linear
streaks.
The
sinus
venosus,
pulmonary
conus
and
pulmonary
valve
cusps
presented
no
abnormalities.
The
left
auricular
wall
was
moderately
hypertrophied
and
its
chamber
dilated.
The
mitral
valve
and
its
chordae
tendineae
were
normal.
The
left
ventricle
was
strikingly
dilated
and
its
wall
greatly
hypertrophied.
The
myocardium
was
flabby
and
greyish
red;
the
endocardium
was
irregularly
thickened.
The
aortic
valve
cusps
were
thin
while
the
aorta,
except
for
a
moderate
number
of
small
intimal
plaques,
presented
no
abnormalities.
The
coronary
ostia
and
arteries
were
normal.
Histologic
examination
revealed
a
greatly
and
irregularly
thickened
auricular
endocardium.
Beneath
this
a
layer
of
fat
vacuoles
was
noted.
The
subepicardial
capillaries
were
dilated
and
engorged.
The
mitral
valve
leaflet
was
focally
vascularized,
its
free
margin
slightly
swollen
and
composed
of
loose
connective
tissue.
The
ventricular
endocardium
was
irregularly
thick-
ened
due
to
connective
tissue
proliferation;
marked
perivascular
fibrosis
was
scattered
throughout.
Perivascular
collections
of
lympho-
cytes
were
seen,
intermingled
with
minute
groups
of
deeply
basophilic
giant
cells.
The
latter
contained
large
vesicular
nuclei
with
darkly
staining
nucleoli.
Much
of
the
ventricular
myocardium
exhibited
an
amorphous,
deeply
eosinophilic
stain
with
indistinct
cross-striations.
Other
areas
contained
collections
of
lymphocytes
with
an
occasional
polymorphonuclear
leuko-
cyte
grouped
about
foci
of
necrotic
and
atrophic
myofibrils.
Hypertrophied
muscle
fibers
domi-
nated
the
histologic
picture.
A
fat
stain
dis-
closed
no
increase
in
sudanophilic
material.
Associated
postmortem
findings
consisted
of
ascites,
bilateral
hydrothorax
and
localized
fibrocaseous
tuberculosis
of
the
right
upper
lobe.
CASE
VII.
R.
P.
(No.
633181),
a
forty-one
year
old
white
woman,
was
well
until
three
years
prior
to
her
admission
to
The
Mount
Sinai
Hospital
when
she
first
suffered
the
onset
of
exertional
dyspnea
and
was
found
to
have
a
right
hydrothorax.
She
was
treated
with
digitalis,
mercurials
and
salt-restriction.
In
the
interven-
ing
period
she
had
had
intermittent
but
only
moderate
symptoms
which
were
characterized
by
dyspnea,
cough
and
bouts
of
palpitation.
Her
symptoms
increased
in
severity
and
she
was
JUNE,
1955
therefore
hospitalized.
There
was
no
familial
history
or
previous
personal
knowledge
of
diabetes
mellitus
or
rheumatic
fever.
Physical
examination
revealed
a
chronically
ill
but
well
developed
white
female.
The
fundi
were
normal.
The
thyroid
gland
was
not
en-
larged.
The
neck
veins
were
distended.
Bilateral
pleural
effusion
was
present.
Examination
of
the
heart
revealed
the
point
of
maximal
intensity
in
the
sixth
intercostal
space
at
the
anterior
axillary
line.
Heart
sounds
were
of
poor
quality,
sinus
tachycardia
and
a
gallop
rhythm
were
noted;
heart
rate
averaged
140
heats
per
minute.
The
blood
pressure
was
130
systolic
and
100
diastolic.
The
second
aortic
sound
was
more
intense
than
the
second
pulmonic
sound.
The
liver
edge
was
felt
2
cm.
below
the
right
costal
margin.
One
plus
bilateral
pitting
pretibial
edema
was
present.
The
venous
pressure
was
elevated
and
the
circulation
time
with
decholin
was
prolonged
to
forty
seconds.
Laboratory
studies
disclosed
a
normal
blood
hemoglobin,
the
white
cell
count
varied
from
levels
of
7,000
per
cu.
mm.
to
as
high
as
18,000
per
cu.
mm.
Differential
smear
showed
an
increase
of
poly-
morphonuclear
leukocytes.
The
sedimentation
rate,
however,
was
normal
(Westergren).
Blood
urea
nitrogen,
initially,
was
normal
and
the
fasting
blood
sugar,
150
mg.
per
cent.
Urinary
studies
revealed
a
specific
gravity
of
1.018,
1
plus
albuminuria,
no
glycosuria
and
a
catheter-
ized
urine
specimen
contained
many
leukocytes
which
were
occasionally
clumped.
Blood
culture
studies
were
negative.
A
skin
and
muscle
biopsy
showed
no
evidence
of
systemic
vascular
disease.
Lupus
erythematosus
cells
were
not
found.
Blood
cholesterol,
cholesterol
esters
and
blood
proteins
were
all
normal.
Fluoroscopy
and
teleroentgeno-
gram
demonstrated
moderate
symmetric
cardiac
enlargement
but
no
pulmonary
infiltrations.
Electrocardiogram
presented
regular
sinus
tachy-
cardia
with
occasional
auricular
and
ventricular
premature
contractions.
There
was
left
axis
deviation;
the
P
waves
were
wide
and
notched.
Inversion
of
the
T
waves
in
the
limb
leads
and
the
majority
of
the
precordial
leads
was
present.
On
admission
the
patient's temperature
varied
between
100°
and
101
°
F.
Routine
therapy
for
congestive
heart
failure
effected
a
weight
loss
of
14
pounds.
The
fever
and
urinary
findings
launched
an
extensive
urologic
investigation.
Urine
culture
yielded
E.
coli
and
enterococci.
Cystoscopy
disclosed
only
injection
of
the
vesical
mucosa
but
catheters
placed
in
both
ureters
916
Cardiac
Hypertrophy
of
Unknown
Etiology—Ester
et
al.
showed
the
urinary
efflux
to
contain
numerous
white
cells.
Retrograde
pyelography
nevertheless
revealed
normal
kidneys.
Therapy
of
the
urinary
tract
infection
included
gantrisin®,
chioro-
myce
ti
n
®,
penicillin
and
streptomycin,
in
various
combinations
and
dosages,
all
of
which
failed
to
alter
her
urinary
status.
The
blood
pressure
remained
at
approximately
130/100.
On
the
sixteenth
hospital
day
the
patient
suffered
an
episode
of
headache
and
dizziness
followed
by
numbness
of
the
entire
right
side
of
the
body,
and
by
a
shock-like
picture
with
blood
pressure
falling
to
90/72.
In
view
of
the
possibility
that
diffuse
myocarditis
might
be
responsible
for
these
findings
cortisone
was
administered,
with
subsidence
of
fever
but
no
improvement
in
the
patient's
status.
Cough,
hemoptysis
and
cyanosis
appeared;
shock
persisted.
Suspension
of
the
cortisone
failed
to
change
her
course
and
the
patient
succumbed
two
weeks
after
the
initia-
tion
of
cortisone
therapy,
and
two
months
following
admission.
Necropsy
Findings
(PM
15163).
The
heart
was
enlarged
and
weighed
450
gm.
The
pericardium
was
normal.
The
right
atrium
was
dilated
to
approximately
one
and
one-half
times
the
usual
capacity;
its
wall
was
somewhat
thickened.
The
endocardial
surface
was
smooth.
Two
grey-
pink
thrombi
0.5
cm.
in
diameter
were
conglu-
tinated
to
the
auricular
appendage
between
the
musculi
pectinati.
The
right
ventricular
chamber
was
moderately
dilated
and
its
wall
markedly
thickened.
The
left
atrium
was
dilated
con-
siderably
and
only
slightly
hypertrophied;
its
endocardium
was
smooth,
glistening
and
free
of
thrombi.
The
left
ventricle
was
conspicuously
dilated
and
its
wall
moderately
thickened.
Its
chamber
was
partially
filled
with
a
massive
pink-grey
thrombus
which
occupied
the
apical
portion
of
the
ventricular
cavity.
This
thrombus
was
adherent
to
the
endocardium
of
the
antero-
inferior
segment
of
the
interventricular
septum
and
the
posterior
ventricular
wall,
except
in
the
region
beneath
and
behind
the
posterior
cusp
of
the
mitral
valve.
The
central
portion
of
the
thrombus
was
diffluent
and
grey;
more
periph-
eral
areas
were
friable,
grey-pink
and
trav-
ersed
by
grey-white
bands
in
coral
pattern.
In
several
places
where
the
thrombus
was
adherent
to
the
endocardium,
thin
linear
junctional
fibrosis
appeared
to
course
within
both
endo-
cardium
and
subendocardium.
The
endo-
cardium
uninvolved
by
thrombus
was
smooth
and
translucent.
The
apex
of
the
left
ventricle
was
thinned
for
an
area
of
3
cm.
in
diameter,
averaged
0.5
cm.
in
width,
and
was
brown
on
section.
Cut
surfaces
of
the
myocardium
pre-
sented
many
scattered,
thin,
linear
areas
of
grey-
white
tissue
throughout,
occasionally
mainly
subepicardial,
more
often
principally
subendo-
cardial
in
site.
The
apices
of
the
anterior
and
posterior
papillary
muscles
of
the
left
ventricle
were
streaked
with
mottled
yellow-brown
and
the
seat
of
scattered
petechial
hemorrhages.
The
cor-
onary
arteries,
their
ostia
and
the
cardiac
valves
were
normal.
The
aorta
and
pulmonary
artery
presented
focal
disseminated
intimal
plaques.
Histologic
study
of
the
heart
disclosed
diffusely
scattered
islands
of
connective
tissue,
often
mainly
subendocardial
with
entrapped
myo-
fibrils.
The
endocardium
also
showed
fibrous
tissue
thickening,
both
avascular
and
occa-
sionally
fairly
well
capillarized.
Degeneration
of
muscle
fibers,
fragmentation,
vacuolization,
eosinophilic
smudging
and
loss
of
striations
were
seen
with
occasional
reactive
infiltrates
consist-
ing
of
lymphocytes,
macrophages
and
plasma
cells.
Adjacent
to
the
mural
thrombi,
scattered
linear
and
occasionally
broader
islands
of
poly-
morphonuclear
leukocytes
were
noted.
A
striking
feature
was
the
presence
of
foci
of
necrosis,
hemorrhage
amongst
fractured
myofibrils
and
polymorphonuclear
leukocytes
within
the
poste-
rior
papillary
muscle
of
the
left
ventricle.
Myo-
cardial
hypertrophy
was
the
principal
histo-
pathologic
feature.
A
gram
stain
for
bacteria
was
negative.
Section
of
the
right
atrium
showed
subendocardial
and
endocardial
fibrosis
with
organizing
mural
thrombus.
Associated
significant
postmortem
findings
included
chronic
passive
congestion
of
the
lungs,
liver
and
spleen.
Multiple
pulmonary
infarctions
were
present.
Infarction
of
the
spleen
and
kidneys
was
also
noted.
Left
renal
calculus
with
secondary
hydronephrosis
and
chronic
pyelone-
phritis
was
found.
However,
there
was
no
evidence
of
systemic
or
renal
vascular
disease.
Comment.
This
patient
had
a
three-year
course
of
congestive
heart
failure.
Although
there
was
some
elevation
of
the
diastolic
pressure,
it
was
believed
that
this
degree
of
elevation
could
not
account
for
her
cardiomegaly,
but
rather
that
it
was
an
expression
of
paradoxic
stasis
pressure.
Other
conventional
etiologic
mecha-
nisms
of
heart
disease
were
excluded.
The
patient's
final
course
was
marked
by
fever
and
simulated
that
of
an
active
myocarditis
but
ultimately
was
more
accurately
ascribable
to
the
AMERICAN
JOURNAL
OF
MEDICINE
Cardiac
Hypertrophy
of
Unknown
Etiology
Elster
et
al.
9
1
7
multiple
infarctions
and
to
pyelonephritis.
There
was
no
systemic
vascular
disease.
CASE
VIII.
W.
R.
(No.
49863),
a
forty-one
year
old
white
man,
learned
two
years
before
admission
that
he
had
a
very
slow
pulse.
During
the
course
of
a
physical
examination
two
and
one-half
months
prior
to
hospitalization
he
was
informed
of
the
presence
of
"possible
fibrilla-
tion."
Following
this
he
noted
exertional
dyspnea
for
the
first
time.
He
later
gained
em-
ployment
as
a
hospital
orderly,
at
which
time
an
electrocardiograph
showed
regular
sinus
rhythm.
Nevertheless,
he
was
given
digitalis.
Three
weeks
before
admission
he
noted
progressively
increas-
ing
dyspnea,
soon
joined
by
swelling
of
the
legs
which
then
worsened
rapidly.
Several
nights
before
hospitalization
he
had
had
an
attack
of
paroxysmal
dyspnea
accompanied
by
a
choking
sensation.
There
was
no
previous
history
of
rheumatic
fever,
hypertension
or
diabetes.
The
patient
was
markedly
obese,
dyspneic,
orthopneic
and
cyanotic.
The
cervical
veins
were
distended.
Signs
of
fluid
were
detected
over
the
right
lower
hemithorax;
moist
rales
were
audible
bilaterally.
The
cardiac
apex
was
dis-
placed
to
the
left,
with
the
point
of
maximal
impulse
felt
in
the
fifth
and
sixth
interspace
beyond
the
left
anterior
axillary
line.
The
heart
sounds
were
of
poor
quality
and
a
faint
localized
apical
systolic
murmur
was
heard.
The
second
pulmonic
sound
was
accentuated
and
louder
than
the
second
aortic
sound.
The
rhythm
was
regular
with
rare
extrasystoles.
The
blood
pres-
sure
was
100
systolic
and
80
diastolic.
The
liver
was
markedly
enlarged
and
tender.
Considerable
edema,
extending
to
above
the
iliac
crests
and
involving
the
lower
half
of
the
abdominal
wall,
was
noted.
Laboratory
studies
revealed
a
normal
blood
count,
fasting
blood
sugar,
blood
urea
nitrogen,
plasma
protein
and
icteric
index.
Serologic
tests
for
syphilis
were
negative.
The
electrocardiogram
showed
left
axis
deviation,
regular
sinus
rhythm
with
occasional
premature
ventricular
contractions.
The
QRS
complex
measured
0.12
seconds.
T1
and
T2
were
diphasic,
and
T3
isolectric.
Serial
tracings
failed
to
demonstrate
progressive
changes.
The
pa-
tient's
temperature
varied
irregularly
from
nor-
mal
to
102°F.
His
symptoms
of
dyspnea
and
orthopnea
progressed
despite
therapy
with
salt
restriction,
digitalis,
diuretics,
oxygen,
phlebot-
omy,
thoracentesis
and
large
doses
of
thiamine
chloride.
His
course
was
complicated
by
an
episode
of
left
chest
pain,
following
which
a
JUNE,
1955
pleuropericardial
friction
rub
appeared
to
the
left
of
the
sternum.
The
blood
urea
nitrogen
rose
steadily
from
8
to
66
mg.
per
cent,
and
the
patient
succumbed
on
the
fifteenth
hospital
day
in
intractable
heart
failure
and
uremia.
Among
the
clinical
diagnoses
considered
were:
rheumatic
heart
disease
with
silent
mitral
stenosis,
Fiedler's
isolated
myocarditis,
hypertensive
heart
disease
with
previous
myocardial
infarction,
beri-beri
heart
disease,
heart
failure
due
to
obesity,
myxedema
heart
disease
and
right
heart
failure
due
to
pulmonary
hypertension
of
un-
known
etiology.
Necropsy
Findings
(PM
12360).
The
heart
was
markedly
enlarged
and
weighed
710
gm.
The
pericardium
was
adherent
to
the
pleura
at
the
base
of
the
left
upper
lobe
but
was
easily
detached.
The
epicardium
presented
ill-defined
congested
areas
over
its
anterior
aspect.
The
pericardial
sac
contained
a
few
cubic
centi-
meters
of
clear,
straw-colored
fluid.
The
cardiac
valves
were
normal.
The
myocardium
was
brownish
yellow,
markedly
hypertrophied
and
extremely
flabby.
All
the
chambers,
particularly
those
of
both
ventricles,
were
considerably
dilated
but
contained
no
thrombi.
On
section
a
few
tiny,
irregular,
deep
red
foci,
especially
in
the
anterior
papillary
muscle
and
in
the
anterior
wall
of
the
left
ventricle,
were
observed.
In
the
posterior
wall
of
the
left
ventricle
there
was
an
irregular
endocardial,
slightly
elevated,
yellow-
ish
grey
transverse
streaked
area
measuring
approximately
8
by
2
mm.
The
main
branches
of
the
coronary
arteries,
but
chiefly
the
left
circumflex,
showed
occasional
flat,
small
athero-
matous
plaques;
however,
their
lumina
were
widely
patent
throughout.
The
coronary
ostia
were
normal.
The
aorta
was
elastic
and
showed
scattered
atheromatous
plaques.
Histologically,
the
heart
disclosed
diffuse
and
conspicuous
fibrosis
with
atrophy,
granular-
ity,
loss
of
striations,
occasional
fracture
and
replacement
of
scattered
muscle
bundles,
the
major
alterations
being
within
the
subendo-
cardial
layers.
Fibril
hypertrophy,
nevertheless,
was
the
dominant
cardiac
abnormality.
Focal
hemorrhage
and
necrosis
of
the
anterior
papillary
muscle
of
the
left
ventricle
was
seen.
Slight
scattered
focal
thickening
of
the
left
ventricular
endocardium
was
noted.
The
cardiac
valves
dis-
closed
no
noteworthy
histopathologic
altera-
tions.
Sections
of
the
coronary
artery
tree
revealed
minimal
arteriosclerosis
without
lumen
encroachment.
918
Cardiac
Hypertrophy
of
Unknown
Etiology—Elster
et
al.
Other
significant
necropsy
findings
included
severe
acute
and
chronic
passive
congestion
of
the
liver,
spleen
and
intestines,
bilateral
femoral
and
left
saphenous
vein
thromboses
with
multi-
ple
secondary
pulmonary
infarcts,
subacute
duodenal
ulcer
and
obesity.
CASE
ix.
L.
V.
(No.
630024),
a
thirty-one
year
old
Puerto
Rican
man,
was
admitted
with
the
complaints
of
shortness
of
breath
and
ankle
edema
of
only
a
few
months'
duration.
Prior
to
this
the
patient
stated
that
he
had
been
in
excellent
health.
At
the
age
of
eighteen
years
he
had
passed
an
Army
physical
examination,
at
which
time
his
blood
pressure
and
urine
were
said
to
have
been
normal.
Four
months
before
hospitalization
shortness
of
breath
and
weakness
appeared
abruptly
and
became
progressively
worse
soon
thereafter.
At
another
hospital
he
was
treated
vigorously
with
mercurial
diuretics,
digitalis
and
a
low-salt
diet,
which
had
resulted
in
a
loss
of
30
pounds.
Following
a
brief
con-
valescence
he
returned
to
work
but
was
never
free
of
shortness
of
breath
and
he
continued
to
be
easily
fatigued.
Three
weeks
before
entry
he
again
noted
ankle
edema,
rapid
weight
gain,
increasing
dyspnea
and
abdominal
swelling.
Examination
revealed
a
young
male
in
severe
congestive
failure;
dyspneic,
orthopneic
and
cyanotic.
Temperature
was
100
°
F.;
pulse
120
per
minute;
blood
pressure
108
systolic
and
90
diastolic.
The
neck
veins
were
markedly
dis-
tended
and
filled
from
below.
Fine,
moist,
basal
rales
were
heard
bilaterally.
The
heart
was
markedly
enlarged
to
both
the
right
and
left;
heart
sounds
were
distant.
A
distinct
gallop
rhythm
and
a
soft
apical
non-transmitted
systolic
murmur
were
heard.
The
abdomen
was
dis-
tended
and
its
wall
edematous.
The
liver
was
tender
and
enlarged
to
two
fingerbreadths
below
the
costal
margin.
Two
plus
ankle
edema
and
one
plus
sacral
edema
were
present.
The
urine
revealed
a
specific
gravity
of
1.010,
one
plus
albumin,
an
occasional
red
cell,
two
to
three
white
cells
per
high
power
field,
and
an
occasional
hyaline
cast.
The
hemoglobin,
white
blood
count,
erythrocyte
sedimentation
rate
and
blood
urea,
sugar,
chlorides,
carbon
dioxide
combining
power,
sodium,
potassium
and
pro-
teins
were
normal.
L.
E.
cells
were
not
demon-
strated.
The
antifibrinolysin
titer
was
normal.
Electrocardiogram
showed
a
sinus
tachycardia
with
frequent
premature
ventricular
contrac-
tions.
The
RS-T
interval
was
depressed
and
the
T
wave
inverted
in
leads
i
and
n.
The
RS-T
interval
was
elevated
in
precordial
lead
V
1
to
V3
and
depressed
in
lead
V4
to
V6.
Teleroentgenogram
demonstrated
marked
car-
diac
enlargement,
predominantly
of
the
left
ventricle.
The
patient's
course
was
one
of
intractable
myocardial
insufficiency;
he
was
never
fully
relieved
of
congestive
failure
during
the
seven
weeks
to
exitus.
Venous
pressure
remained
over
200
mm.
of
water,
while
decholin
circulation
time
ranged
between
fifty
and
sixty-five
seconds.
Digoxin
was
at
first
withheld
because
of
the
electrocardiographic
demonstration
of
bigeminal
rhythm
and
varying
A-V
block,
later
given
without
benefit.
Mercurial
diuretics
were
admin-
istered
repeatedly
for
alleviation
of
dyspnea
and
edema.
After
one
month
in
the
hospital
he
com-
plained
of
left
calf
tenderness
and,
despite
dicumarolization,
developed
pleuritic
pain,
fever
and
hemoptysis.
A
friction
rub
appeared
first
at
the
right
base
and
subsequently
on
the
left
side.
Icterus
followed,
with
blood
bilirubin
rising
to
9
mg.
per
cent.
Mercurial
diuretics
were
with-
held
in
view
of
the
fear
of
inducing
a
low-salt
syndrome,
until
pulmonary
edema
finally
supervened.
Following
one
injection
of
mercu-
hydrin
evidences
of
the
low-salt
syndrome
recurred.
The
patient
precipitately
became
severely
dyspneic,
maniacal
and
died
after
seven
weeks
in
the
hospital.
Necropsy
Findings
(PM
75095).
The
heart
weighed
550
gm.
and
was
enlarged
in
all
dimen-
sions.
The
pericardium
was
normal.
The
inferior
vena
cava
was
dilated
and
engorged;
the
left
internal
jugular
vein
was
found
completely
occluded
by
a
dark
greyish
red,
friable
mass.
The
chamber
of
the
right
auricle
was
dilated
and
its
wall
slightly
hypertrophied;
its
endo-
cardium
was
smooth
and
shiny.
The
tricuspid
valve
was
normal.
The
right
ventricle
was
dilated;
its
wall
and
trabeculae
carnae
thickened.
The
myocardium
measured
3
mm.
in
thickness
except
for
one
area
4
cm.
in
diameter
at
the
upper
portion
of
the
anterior
wall,
where
it
was
barely
1
mm.
in
thickness.
Here
it
was
diffusely
grey,
inelastic
and
on
its
pericardial
aspect
had
a
slightly
purplish
hue,
while
the
adjacent
endocardium
was
grey
and
opaque.
The
re-
mainder
of
the
myocardium
showed
a
number
of
diffuse
yellow-grey
patches
of
fibrosis
spreading
from
the
endocardium
toward
but
not
reaching
the
pericardium.
A
2
mm.
round,
red,
firm
thrombus
was
adherent
to
the
endocardium
of
the
lower
anterior
wall
of
the
left
ventricle.
The
AMERICAN
JOURNAL
OF
MEDICINE
Cardiac
Hypertrophy
of
Unknown
Etiology—Elster
et
al.
9
1
9
pulmonic
valve
and
pulmonary
artery
were
normal.
The
left
auricle
was
enlarged
and
its
wall
thickened.
The
mitral
valve
disclosed
no
ab-
normalities.
The
left
ventricle
was
markedly
dilated
and
moderately
thickened;
its
wall
aver-
aged
1.2
cm.
in
thickness.
Several
1
to
2
cm.
laminated
thrombi
were
firmly
attached
to
the
endocardium.
A
number
of
scattered
0.2
to
0.5
cm.
diffuse,
grey-white
areas
were
seen
in
the
endocardium.
The
cut
surface
of
the
myocardium
contained
small,
grey-yellow
subendocardial
areas
similar
to
those
observed
in
the
wall
of
the
right
ventricle.
High
on
the
posterior
aspect
of
the
left
ventricle
near
the
septum,
a
thinned
zone,
2
cm.
in
diameter,
was
located.
The
aortic
valve
was
normal;
the
aorta
elastic.
The
coronary
arteries
and
ostia
were
widely
patent,
although
the
arterial
intima
contained
a
few
flat,
yellow,
atherosclerotic
plaques.
Histologic
examination
of
representative
seg-
ments
of
the
heart
disclosed
predominantly
hypertrophied
muscle
fibers
which,
here
and
there,
had
been
replaced
by
connective
tissue.
Within
these
foci
scattered
myofibrils
appeared
granular
and
vacuolated,
and
their
architecture
indistinct.
In
addition,
fracture
of
smudged
myofibrils,
the
nuclei
of
which
had
undergone
degenerative
changes,
was
present
while
a
number
of
fibrils
showed
complete
loss
of
nuclei.
Reactive
foci
of
lymphocytes
and
scant
poly-
inorphonuclear
leukocytes
were
seen,
especially
in
the
vicinity
of
mural
thrombi.
Fibrosis
was
encountered,
principally
toward
the
endo-
cardium
with
conspicuous
involvement
of
this
layer
with
foci
of
hyalinization.
In
addition,
organizing
and
healed
mural
thrombi
were
noted,
with
elastification
of
the
endocardium
and
subendocardium
adjacent
to
the
thrombotic
masses.
The
posterior
papillary
muscle
of
the
left
ventricle
revealed
widespread
fibrosis;
the
anterior
papillary
muscle
was
the
seat
of
both
focal
and
confluent
scarred
areas.
Minimal
arteriosclerosis
of
the
coronary
arteries
was
found.
However,
in
one
area
of
an
accessory
right
coronary
artery
to
the
upper
anterior
right
ventricle
what
appeared
to
be
an
organized
occlusion
was
found.
Nevertheless,
the
total
myocardial
alterations
could
not
reasonably
be
ascribed
to
this
lesion.
Except
for
mild
edema
of
the
mitral
valve
posteriorly,
there
were
no
histopathologic
valvular
findings.
Other
significant
necropsy
findings
consisted
of
severe
passive
congestion
of
viscera,
multiple
J
UNE,
1955
infarcts
of
lungs,
spleen
and
kidneys,
bilateral
pleural
effusion
and
icterus.
CASE
X.
0.
W.
(No.
406347),
a
fifty-three
year
old
Negro
porter,
became
ill
six
months
prior
to
hospitalization
with
productive
cough
and
right
chest
pain.
Two
months
later
exer-
tional
dyspnea
appeared,
followed
by
orthopnea,
ankle
edema,
episodes
of
nocturnal
dyspnea
and
finally,
hemopytsis.
Previous
history
included
gonorrheal
urethritis
at
the
age
of
sixteen
years,
but
syphilis
was
denied.
He
had
knowledge
neither
of
rheumatic
fever
nor
of
any
other
significant
infectious
disease;
nor
was
there
an
allergic
background,
hypertension
or
coronary
artery
disease.
The
patient
was
fairly
well
developed,
some-
what
undernourished
and
markedly
dyspneic
and
orthopneic.
The
pupils
were
slightly
irregular,
the
left
larger
than
the
right,
but
both
reacted
to
light
and
accommodation.
The
retinal
arteries
were
mildly
narrowed
but
there
were
no
hemorrhages
or
exudates.
The
chest
configura-
tion
was
normal.
Bilateral
pleural
effusions
were
detected
with
many
coarse,
moist
rales
at
both
lung
bases,
more
marked
in
the
left
lung.
A
coarse,
loud
friction-rub
was
audible
over
the
lower
right
mid-axillary
line.
The
cardiac
apical
impulse
was
diffuse
but
palpable
maximally
in
the
mid-axillary
line
in
the
fifth
and
sixth
inter-
costal
spaces.
High-pitched,
loud
apical
systolic
and
soft
systolic
pulmonic
murmurs
were
heard,
neither
transmitted.
The
heart
sounds
were
of
poor
quality;
the
second
pulmonic
sound
was
accentuated.
Gallop
rhythm
with
regular
sinus
tachycardia
was
present.
Radial
pulses
were
equal,
synchronous,
regular
and
of
full
quality;
the
blood
pressure
was
118
systolic
and
108
diastolic.
The
liver
edge
was
percussed
4
cm.
be-
low
the
right
costal
margin.
Slight
pitting
edema
of
the
lower
extremities
was
seen.
There
was
no
evidence
of
peripheral
neuropathy.
Labora-
tory
data
disclosed
the
urinary
specific
gravity
to
be
1.020.
A
faint
trace
of
albumin,
no
gly-
cosuria
and
occasional
white
blood
cell
and
granular
casts
were
detected.
The
blood
count
was
normal.
The
blood
urea
nitrogen
was
35
mg.
per
cent
and
the
fasting
blood
sugar
175
mg.
per
cent.
The
erythrocyte
sedimentation
rate
was
90
mm.
per
hour
(Westergren).
Serologic
tests
for
syphilis
were
negative.
The
electrocardio-
gram
revealed
left
bundle
branch
block.
On
admission
to
the
hospital
his
status
was
extremely
grave.
Despite
salt
restriction,
digitalis,
mercurial
injections,
oxygen
and
phlebotomy,
g2o
Cardiac
Hypertrophy
of
Unknown
Etiology—Elster
et
al.
the
severity
of
heart
failure
was
unabated,
the
febrile
course
persisted
with
preterminal
rise
to
102°F.,
and
he
died
six
days
following
entry.
Necropsy
Findings
(PM
10312).
The
heart
weighed
500
gm.
The
pericardial
cavity
con-
tained
a
small
quantity
of
clear,
straw-colored
fluid.
Numerous
petechial
hemorrhages
were
seen
in
the
epicardium.
Several
epicardial
plaques
(soldier's
patch)
were
present
on
the
anterior
and
posterior
surfaces
of
the
right
ventricle.
The
right
auricular
chamber
was
dilated;
the
foramen
ovale
closed.
The
tricuspid
valve
was
irregularly
thickened
in
the
distal
margins
of
the
anterior
leaflet.
The
cavity
of
the
right
ventricle
was
moderately
dilated
and
its
wall
was
thickened.
Flattened
and
thickened
trabeculae
carnae
were
present.
The
pulmonic
valve
cusps
were
normal.
The
left
auricle
was
dilated
and
its
wall
was
hypertrophied.
The
endocardium
disclosed
several
yellowish
grey
and
yellowish
pink
flat,
firm
elevations
2
to
5
mm.
in
size.
The
anterior
leaflet
of
the
mitral
valve
contained
greyish
yellow
foci
of
thickening
along
its
distal
third.
The
chordae
were
thin
and
showed
normal
web-like
insertions.
The
cavity
of
the
left
ventricle
was
markedly
dilated,
its
wall
thickened.
The
interventricular
septum
bulged
into
the
right
ventricular
chamber.
The
endocardium
of
the
left
ventricle
was
the
seat
of
numerous
mural
thrombi.
These
were
firm,
yellowish
grey
with
reddish
brown
areas;
section
revealed
firm
reddish
brown
laminated
material
near
the
base.
Four
large
mural
thrombi,
aver-
aging
3.5
cm.,
and
many
0.5
to
1.0
cm.
in
diam-
eter
were
located
in
the
interstices
of
the
trabecu-
lae
carnae
over
the
posterior,
anterior
and
apical
segments
of
the
left
ventricle.
The
endocardium
over
the
posterior
papillary
muscle
showed
yellowish
grey,
quadrilateral,
1
by
1.5
cm.
plaque-like
thickening.
The
apex
of
the
posterior
papillary
muscle
was
yellowish
white
and
the
site
of
2
to
3
mm.,
irregularly
shaped,
greyish
yellow
areas.
The
papillary
muscles
were
large
and
rotund.
The
aortic
valve
showed
no
abnor-
malities.
The
myocardium
throughout
was
brown
and
fairly
firm.
The
coronary
ostia
were
normally
patent
and
the
wall
of
the
coronary
vessels
disclosed
no
abnormalities.
The
aorta
was
normal
but
the
site
of
scattered,
slightly
elevated
intimal
plaques,
predominantly
in
the
abdominal
aorta.
Histologic
studies
of
the
auricular
endo-
cardium
in
its
deeper
layers
revealed
swollen,
clear,
smooth
muscle
cells
with
irregular
nuclei.
The
ventricular
endocardium
was
irregularly
thickened
by
fibrous
tissue
proliferation
within
the
elastic
lamina.
Beneath
the
auricular
and
ventricular
endocardium
the
muscle
cells
were
pale,
vacuolated
and
showed
considerable
glycogen
deposits.
Sections
of
many
varied
sites
revealed
numerous
areas
of
interfascicular
fibrosis
with
atrophic
muscle
fibers.
In
scattered
zones
the
fibers
were
separated
by
extensive
bundles
of
connective
tissue.
The
latter
was
generally
very
loose
in
character
and
principally
situated
near
the
endocardial
layer.
Scattered
perivascular
zones
of
fibrosis
were
also
present;
in
other
sites
fine
diffuse
interfascicular
fibrosis
was
the
dominant
feature.
Occasionally
in
the
thickened
septa,
collections
of
a
few
lymphocytes
and
mesenchymal
cells
were
seen.
In
one
area
of
the
left
ventricle
there
was
a
diffuse
inter-
fascicular
infiltrate
of
polymorphonuclear
leuko-
cytes
beneath
the ventricular
endocardium
adjacent
to
a
mural
thrombus
and
extending
for
a
short
distance
toward
the
pericardium.
In
this
same
region
the
fibers
were
considerably
separated
from
each
other
and
from
the
en-
gorged
capillaries.
The
intervening
spaces
contained
a
small
amount
of
fine
connective
tissue
fibers
and
some
"mesenchymal"
cells
and
very
occasional
lymphocytes
and
cells
with
eosinophilic
cytoplasm.
The
small
and
large
blood
vessels
and
the
pericardium
showed
no
abnormalities.
The
mural
thrombi
presented
evidences
of
varying
degrees
of
organization,
especially
at
their
bases.
Myofibrillar
hyper-
trophy
was
the
predominant
histopathologic
feature.
Associated
significant
postmortem
findings
included
chronic
passive
congestion
of
the
liver,
spleen
and
kidneys.
An
organized
renal
infarct
was
present
but
there
was
no
evidence
of
nephrosclerosis.
Multiple
organized
and
recent
pulmonary
infarcts
were
found.
There
was
bronchopneumonia
and
a
fibroadenoma
of
the
prostate
gland.
Comment.
Despite
mild
elevation
of
blood
pressure,
there
was
no
anatomic
evidence
that
this
factor
was
responsible
for
the
patient's
cardiac
disease.
The
absence
of
renal, ocular
or
systemic
vascular
changes
all
militate
against
the
belief
that
hypertensive
cardiovascular
disease
could
account
for
this
picture.
Myo-
cardial
fibrosis
was
conspicuous
despite
the
absence
of
coronary
arteriosclerosis.
The
pa-
tient's
terminal
episode
appeared
to
have
been
AMERICAN
JOURNAL
OF
MEDICINE
Cardiac
Hypertrophy
of
Unknown
Etiology-Elster
et
al.
92
I
precipitated
by
pulmonary
embolism,
in
asso-
ciation
with
heart
failure.
SUMMARY
Ten
cases
of
cardiac
hypertrophy
and
myo-
cardial
failure
of
unknown
origin
are
presented.
Conventional
etiologic
factors,
such
as
rheu-
matic
fever,
hypertension,
syphilis,
arterio-
sclerosis,
bronchopulmonary
disease
and
con-
genital
abnormalities,
were
excluded.
The
clinical
course
of
these
patients
was
rapidly
progressive
and
fatal,
and
frequently
complicated
by
recurrent
pulmonary
and
systemic
thromboembolism.
At
necropsy
the
hearts
showed
striking
hyper-
trophy.
Degenerative
muscular
changes,
focal
necrosis,
patchy
fibrosis
were
found
predomi-
nantly
subendocardially
and
endocardially,
frequently
associated
with
mural
thrombosis.
There
were
no
significant
abnormalities
of
the
pericardium,
coronary
artery
tree,
cardiac
valves
or
aorta.
A
brief
review
of
similar
cases
previously
described
is
presented.
None
of
the
causes
heretofore
suggested
as
primarily
responsible
for
this
syndrome
are
believed
by
us
to
have
been
established.
Myocardial
anoxia,
a
concomitant
of
the
considerable
hypertrophy
and
dilation,
is
be-
lieved
to
be
an
important
factor
in
the
intensifi-
cation
of
the
intracardiac
abnormality.
Attention
is
drawn
to
the
importance
of
con-
sidering
this
entity
in
all
cases
of
cardiac
hyper-
trophy
when
a
conventional
etiology
cannot
be
established.
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