VENTRICULAR
SEPTAL
DEFECT
I. Congestive
Heat±
Failure
n Infancy
Beverly C. Morgan, M.D., Sylvia P. Griffiths, M.D., and Sidney Blumenthal, M.D. Babies Hospital, and Department of Pediatrics, College of Physicians and Surgeons, Columbia University
(Accepted July 27, 1959; submitted June 17.)
Supported in part by a grant from the New York Heart Association. Dr. Morgan is a Research Fellow, New York Heart Association.
ADDRESS: (B.C.M.) 3975 Broadway, New York 32, New York,
PEDIATRICS, January 1960
54
T
HIS STUDY was undertaken to evaluatethe course and prognosis of patients
with a ventricular septal defect who
devel-oped congestive heart failure in the first
year of life. The clinical and pathologic
find-ings of infants with this complication will
be reviewed.
Opinion has varied from the original
con-cept of Roger’ in 1879, which implied the
benign course of patients with this anomaly,
to a recent observation that patients with
ventricular septal .defect rarely survive
childhood.2 The natural history of patients
with this malformation needs further
dan-fication.
PATIENT
MATERIAL
Clinical and pathologic data on 125 patients
with ventricular septal defect up to the age of
14 ears have been collected for the 10-year
period 1948 to 1958. This number includes 95
patients from the Pediatric Cardiac Clinic (21%
of annual enrollment of approximately 450
pa-tients with congenital heart disease) and 30
cases#{176}from the Pediatric Pathology Laboratory
(13% of total of 217 specimens of cardiac
mal-formations obtained at necropsy).
The clinical diagnosis of ventricular septal
defect in 95 patients was supported by cardiac
catheterization in 40, and further confirmed by
open-heart surgery in 7. Associated evidence of
corrected transposition of the great vessels on
angiocardiogram excluded one patient from the
study who had a history of congestive failure
in infancy.
In the 30 cascs reviewed at necnopsy,
yen-a One case is included in which the post-mortem examination was carried out at another institution,
Muhlenberg Hospital, Plainfield, New Jersey.
tricular septal defect was the only significant
cardiac anomaly. Anatomic overriding of the
aorta was invariably associated with large
de-fects in the membranous portion of the
ventricu-lar septum.3 Persistence of the foramen ovale
or patency’ of the ductus arteriosus up to 120
days4 or probe patency beyond that age did not
exclude patients from this study. Three cases
were retained with large ventricular septal
de-fects and patency of the ductus beyond the age
of 4 months (Cases 12, 13, and 14, Table IV);
these patients died of infection without ever
having developed .congestive heart failure.
OBSERVATIONS
A review of 125 patients with ventricular
septal defect indicates that 17 had a history
of congestive heart failure (Table I). The
initial episode of decompensation in eacil
case first occurred between 1 and 6 months
of age. Ten of these patients continued to
manifest signs of heart failure and died in
the first year of life; one of them (Case 6)
underwent thoracotomy for the possibility of
patent ductus arteriosus and expired in the
postoperative period. The seven patients who survived are currently being followed
in the Pediatric Cardiac Clinic.
History and Clinical Findings
Analysis of the clinical course and
find-ings of the 17 patients with congestive heart
failure (Table I) did not reveal any
signifi-cant differences between the survivors and
those who succumbed. The birth weights
of these infants were within’ the normal
range with one exception : Case 7 was
pre-mature as evidenced by weight and
1. B.P. (F) 54 6 3,800 5,000
.
J.s.
(F) S S ,900 4,7003. D (F) I 1. 3,100 ,600
4. V.M. (M) 4 4 3,00 4,900
5. L.D. (M) 1 ,900 ,700
6. D.B. (M) S 10 ,730 5,800
7. A.W. (M) S ,000 6,500
8. D.S. (M) 14 3,400 3,880
9. G.F. (M) S 8 3,00 4,700
10. KS. (M) 8 ,800 3,100
Exploratory thoracotomy for
patent ductus arteriosus.
11. 1).M. (M) 1 3,900 4,950
12. CS. (F) 3 3,100 5,000
13. K.L. (F) 3 3 3,50 4,800
14. CD. (M) 6 4 3,400 5,950
15. V.,J. (F) S 4 3,950
-16. J.H. (M) 5 8 ,500 4,500
17. J.M. (M) 2 11 3,400
-TABLE I
CIINIcAL OBSERVATIONS OF 17 Cs.sr.s OF VENTRICULAR SEPTAL DEFECT WITH A HISTORY OF CONOEST1VE FAILURE
Expired Age Onset of Age Death Birth Weight Final Weight
Case8 (Sex) Failure (mo) (mo) (gm) (gm) Comment.,
Liring Cases Age Onset of Present Age Birth Weight Weight at
(Sex) Failure (mo) (iii) (gm) 6 Months (gm)
weight normally, with the possible
excep-tion of Case 7. Bronchitis or pneumonia
frequently occurred in these patients;
how-ever, rapid respirations were commonly
noted when tile infants were apparently
free of pulmonary infection or cardiac
de-compensation. Transient cyanosis was
oc-casionally observed with the exertion of
feeding or crying.
Examination at the time of
decompensa-tion revealed in each case a systolic heart
murmur, generally loud and harsh and
max-imal at the mid to low left sternal border,
but occasionally the bruit was less intense
and diffusely heard. The pulmonic second
sound was usually accentuated.
Electrocardiographic Findings
Electrocardiograms recorded in 15 of the
17 cases were evaluated for evidence of
ventricular hypertrophy according to the
criteria outlined by Keith et al.5 The
find-ings were variable (Table II). The criteria
for right ventricular hypertrophy were
sat-isfied in three instances. In two there was
suggestive but not diagnostic evidence of
Comments
Open-heart surgery 4 yr. Open-heart surgery 6 yr. Open-heart surgery 10 yr.
left ventricular hypertrophy, and combined
ventricular hypertrophy was noted in two.
The most frequent pattern in the precordial
leads, noted in five patients, consisted of
increased voltage of the R and S deflections
in V3 and V4 with deep
Q waves in
V6. Thisobservation, suggestive of septal
hypertro-phy, occurred without definite evidence of
combined or specific chamber hypertrophy.
Upright T waves were occasionally noted in
the right precordial leads irrespective of
medication with digitalis. An example of
this pattern, described as “abnormal” in
Ta-ble II, is illustrated in Figure 1. Arrhythmias
were present in two cases prior to the
ad-ministration of digitalis, being interpreted
as atnial flutter-fibrillation in one patient
(
Case 8) and frequent premature ventricularcontractions in the other (Case 1 1).
Roentgenographic Findings
Roentgenograms of the chest showed
cardiomegaly and prominent bronchovascu-lar markings in each case. The
roentgeno-grams in postero-anterior and left lateral
Case Age
(ma) Axis
Arrhythmias or
Conduction Defects
Precordial Leads
No. interpretation
1 4 Normal None -
-5 Normal None S CVH**
3 4 Right None 3 RVII
4 4 Normal None 3 Abnormal
5 Normal None ‘3 Normal
6 10 Normal None 3 RVII
7 2 Right None 3 RVH
S 14 Normal Atrial flutter-fibrillation S Possible LVII
9 5 Right None 7 Abnormal
10 8 Normal None 7 Possible LVII
I I 2 Normal Premature ventricular
contractions
7 CVII
H 4 Normal None 6 Abnormal
13 4 Normal None 6 Abnormal
14 6 Normal None ‘3 Normal
16 6 Normal None 3 Abnormal
* In Cases 15 and 17 electrocardiographic observations during infancy are not available.
‘a CVH = Combined ventricular hypertrophy.
RVH = Right ventricular hypertrophy.
LVII = Left ventricular hypertrophy. Abnormal=See text.
and are illustrated in Figure 2. The
distinc-tion between pulmonary congestion due to
increased blood flow, congestive failure, and
infection was not clear.
Manifestations of Congestive Failure
Signs of congestive failure were
pre-dominantly right-sided, with occasional
evi-dence of both right and left ventricular
failure.6 Cardiac decompensation was
mani-fested by tachycardia, tachypnea and
hepa-tomegaly; gallop rhythm was sometimes
noted. Though rales were often present in
the lungs, the findings were not typical
of pulmonary edema. Associated pulmonary
infection was observed in many of these
pa-tients at the time of congestive failure.
Pe-ripheral edema was not noted, except in
three cases in which it appeared terminally.
All of the patients were digitalized during
their initial episode of decompensation, and
the 10 patients who succumbed had been
maintained on digitalis until the time of
death. The patients who survived received
digitalis until at least the age of 1 year and
subsequently showed improvement in
growth. Diminished frequency of
respira-tory infections was noted with advancing
age; prophylactic antibiotics were
admin-istered in several cases. Two patients had
exacerbations of right-sided failure later in
childhood associated with pneumonia.
Hemodynamic Findings
Cardiac catheterization data (Table III)
are available in eight patients, including one
who succumbed with congestive heart
fail-ure and each of the seven survivors. A
left-to-right shunt at the ventricular level was
documented in each case by a significant
increment in oxygen content compared to
that in the right atrium. The systemic
arte-nial oxygen saturation was normal in the
cases in which this determination was
car-ned out, and ruled out the presence of a
right-to-left shunt.
In the two patients in whom
catheteriza-lion was performed during the first year of
life, the study was carried out within 2
months after the onset of cardiac
decom-pensation. Pulmonary hypertension was
marked and of similar magnitude in these
two cases; one infant subsequently
ex-pined (Case 9) and the other has survived
TABLE II
$1
U Ut oVR
aVL
oVF
V2 V3 V4 V5 V6
TT1iTT ‘-Y1 #{149}
. #{149}1#{149}#{149}
ii
rIrtrrr
t Dalnped pressure tracing.
VI
1:1..
:
:j
V
3R
V6 I
flff
Fic. 1. Case 9. Increased amplitude of R and S defiections in leads V and V4; upright T in V1; receiving digitalis. The extremity leads are at full- and the precordial leads at half-standardization. Simultaneous
leads, V3 and V, are recorded at fast paper speed.
TABLE III
ILEMODYNAMIC I)ATA OBTAINED AT CARDIAC CAThETERIZATION
(Eight cases of ventricular sepia! defect with a history of congestire heart failure in infancy.)
Systemic
(‘ase Age
Pressure
-(mm Jig)
----Oxygen Content” (,‘ol %)
---VC RA RI’ PA
.4rterial
Oxygen Saturation
(%)
JIJ’* PA
9 .5 nio 100/7 100/47 7.5 8.2 10.1 9.8 !)‘2
11 3 nio 105/6 105/48 8.1 7.8 10.() 10.3
-1’2 yr 100/4 100/50 10.9 10.4 12.1 14.3
-13 3yr 80/4 ‘24/10 9.6 10.5 1.4 13.5 914
H 3yr 7,’.5 7Q/30 11.3 10.1 13.0 13.0 92
1.5 3yr 4,’5 4’2/.5() 1t.0 10.7 12.0 1’2.7 9’3
16 5yr 80/0 70/45f 11.8 11.9 15.0 13.5 95
17 8yr 72,’5
110/
72/35 1L 12.8 15.3 15.2
-lOyr 67/2 68/27 13.5 14.1 15.4 15.7 94
* RV = Right ventricle; PA = Pulmonary artery ;VC = Venae cavae (average of inferior and superior) ;RA = right
at 1111111.
1
Cardiomegaly and prominent pulmonary vascular markings are illustrated.
Fic. 2. Case 9.
(Case 11). In the remaining six patients,
cardiac catheterization was performed after
the age of 2 years. There was moderate to
marked pulmonary hypertension in all but
one patient; in Case 13 a significant systolic
pressure gradient existed across the
pul-monic valve compatible with infundibular
pulmonic stenosis or hypertrophy of the
right ventricular outflow tract. The second
cardiac catheterization of Case 17 indicated
two distinct pressure levels in the right
ventricle; this observation, consistent with
muscular hypertrophy of the outflow tract,
was confirmed at the time of open-heart
surgery.
Necropsy Data
Review of the necropsy files of Babies
Hospital from 1948 to 1958 disclosed 30
cases of isolated ventricular septal defect;
25 were less than 1 year of age at time of
death (Table IV) while 5 were between 3
and 12 years. The latter group died as a
result of complications occurring after
surgi-cal repair of the defect.
Post-mortem examination of the 10 infants
who expired with congestive heart failure
indicated that the size of the ventricular
septal defect varied from 4 to 15 mm in
maximal diameter. Nine of these defects
were high and involved the membranous
portion of the ventricular septum; one was a
large defect in the muscular portion.
Among the 15 other patients with
ventric-ular septal defect wllO (lied in tile first
year of life, 4 expired because of pulmonary
infection or sepsis; in these the ventricular
defect was large, ranging between 10 and
18 mm in greatest diameter, despite which
heart failure was not a complication. In the
11 patients who died of prematurity or
corn-plications of non-cardiac anomalies, the
size of the defect was significantly smaller
than in the preceding groups of cases, and
measured from 1 to 7 mm. Tile size of the
defect in relation to the age of the patient
and cause of death is illustrated in
Fig-tire 3.
In this series, patients with ventricular
septal defect who survived the first year of
life did not succumb from complications
during childilood. The late deaths occurred
in five patients after open-heart surgery.
Microscopic examination of the lungs of
the infants, with reference to pulmonary
vasculature, was considered inadequate for
significant interpretation. Evaluation of
hy-pertrophy of the smaller arteries and
arte-rioles by inspection of routine histologic
see-tions is subject to error.
0 The state of contraction of the pulmonary yes-sels at the time of fixation affects the relationship
of diameter of lumen to width of media or total
vessel wall. Also, it is difficult to identify vessels
Duct us
Arteriosus Comment
Death Due to Congestive Heart Failure
I (F) 6 9X1 Mid (Muscular) Closed
2 (F) 5 8X9 High Closed
3 (F) 11a 55 High D’=3mnI
4 (M) 4 8X8 High Closed
5 (M) 7X8 High PP.”
6 (M) 10 15X15 High Closed
7 (M) 5 9X9 High Closed
8 (M) 4X4 High P.P.
9 (M) 8 8X8 high Closed
10 (M) 8 6X8 High Closed
Imperforate anus
Omphalocele
t
15 (M) days 1X1 High Patent Prematurity; hyaline membrane disease
16 (M) 1day 1 X 1 High Patent Prematurity; hyaline membrane disease
17 (M) 3 days 3X4 High Patent Prematurity; multiple anomalies
18 (F) days High Patent Prematurity; intracranial hemorrhage
19 (M) 14 days 3X4 High Patent Prematurity; hydrocephalus
0 (F) 3 days 6X6 High Patent Prematurity; tracheo-esophageal fistula
1 (F) 4 days 3X6 High Patent Prematurity; tracheo-esophageal fistula
(F) 7 days High Patent Tracheo-esophageal fistula
3 (F) 7 days X7 High Patent Traeheo-esophageal fistula
24 (F) 6 days 4X7 High Patent Multiple anomalies
25 (F) 5 mo I X Mid Closed Multiple anomalies, biliary atresia
aD = External diameter of patent ductus.
‘a p,p = Probe patent.
t Patent died following exploratory thoracotomy for patent (luetus arteriosus. TABLE IV
PosT-IouTE%I FINDINGS OF 5 INFANTS WITH VENTRICULAR SEPTAL DEFECT
Case Age
(Sex) (mo)
Ventricular Septa.l Defect
Size (mm) Location
Death Due to Infection
11 (M) 2 IOX1O High
1l (M) 4 10X12 High
13(F) 6 14X18 High
14 (F) 4 8X10 High
Closed Bronchopneumonia
D =3 mm Laryngeal stridor Mongolism, bronchopneumonia
D = 6 mm Mongolism, bronchopneumonia
Shigella dysentery
D=lmm Sepsis
Duodenal ulcer
Death Due to Prematurity and/or Non-cardiac Anomalies
DISCUSSION
Ventricular septal defect occurring as an
isolated lesion is a relatively common
car-diac malformation. The incidence of 21%
among clinically diagnosed cases of
con-genital heart disease observed in this series
is similar to that reported by Gasul and
Fell’ and Keith et al. In a review of the
literature reporting on pathologic material,
Wood et al.’ estimate the incidence of
yen-tnicular septal defect to be 15%. This figure
is approximately the same as that obtained
in the necropsy data presented here. Congestive heart failure associated with ventricular septal defect in infancy has been
described by several authors.1#{176}’3 Approxi-mately 14%, or 17 patients, in the present series developed this complication. Our
ob-servation that the onset of congestive failure
occurs within the first 6 months of life
par-allels the experience of other investigators who have reported decornpensation early in
U) ‘C
C 0 E
I
I-.
w
I-4
Ui
4
9
.
8 .
7
6
.
5
.
4- S
3
2- S S 0
S
S
0 0
0 I I - #{149}Congestive Failure
10 - 0 Infection 0
- >c Prematurity or
Anomalies
I I I I I I I I I I I I I I I I I I
I 2 3 4 5 6 7 8 9 $0 II 12 13 14 15 16 17 18
MAXIMAL DIAMETER OF VENTRICULAR DEFECT (mm)
Ftc. 3. Relationship of size of ventricular septal defect to age and cause
of death.
prognosis of infants with ventricular septal
defect who develop congestive failure is
guarded; in this series, over half of these
pa-tients succumbed within the first year of life.
In those who survived this critical period,
exacerbations of failure were rare during
childhood.
The clinical data on the 17 infants with
ventricular septal defect and congestive
failure were nonspecific diagnostically,
ex-cept as they evidenced features of a large
left-to-right shunt with increased pulmonary
blood flow. Laboratory studies utilizing
car-diac catheterization and angiocardiography
are usually necessary in this age group to
differentiate certain other cardiac
malforma-tions, such as patent ductus arteniosus,
trun-cus arteniosus, endocardial cushion defect or
single ventricle, from an isolated
ventricu-lan septal defect.14 There was no
observa-tion of prognostic significance which
distin-guished between those patients with
yen-tricular septal defect who, after developing
cardiac decompensation, adapted to their
disease and survived, and those who
pro-gressed with a fulminating course to death.
The range of birth weight in the patients
with ventricular septal defect who
devel-oped cardiac decompensation was within
normal limits, except for one infant. The
association of prematurity and ventricular
septal defect pointed out by Engle11 is
ap-parent in the present series only among the infants who died because of complications other than the cardiac malformation.
Anatomic studies indicate that the size of
the ventricular septal defect is important in
determining the clinical significance of the
lesion.15’ 16 Minimal hemodynamic changes
occur in the presence of a small defect,
whereas a large defect permits a marked
left-to-right shunt and excessive pulmonary
blood flow. From the necropsy data it is
ap-parent that the majority of cases in the
group with congestive failure had defects of
medium or large size (according to the
classification of Selzerl5). In the four
pa-tients who died with predominant evidence
of infection, large ventricular septal defects
were present; the role played by the defect
and by patency of the ductus arteriosus in
the course of the terminal illness is
un-known. The size of the ventricular septal
\Vllo died of prematurity or of non-cardiac
anomalies.
Tile location of the defect in the majority
of these cases was high in the membranous
portion of the septum. This area, which is
in proximity to the ventricular outflow
tracts, is the most common site of
ventnicu-lar septal defects.’5 The actual position of
tile defect, whether high or predominantly
in the muscular portion, makes little
differ-ence in the clinical implications of this
car-diac malformation. The significance of
over-riding of the aorta is predominantly
physio-logic rather than anatomic. As long as the
systemic resistance exceeds that in the
pul-monary circuit, the aorta will receive little
if any blood from the right ventricle.
The cause of congestive failure in
yen-tricular septal defect is related to the
magni-tude of the left-to-right shunt and the state
of the pulmonary vascular bed. In the
pres-ence of a large left-to-right shunt an
in-crease in cardiac output is necessary to
maintain an adequate systemic blood flow.
Under these circumstances, high-output
myocardial failure may develop.17 Survival
of the infant with cardiac failure depends
upon the development of sufficient
resist-ance in the pulmonary vascular bed or
right ventricle to limit excessive pulmonary
blood flow. In some patients, an increase in
pulmonary resistance occurs as a result of
pulmonary vascular changes or
vasocon-strictive influences.1?l9 From the
catheteri-zation data in this series, it is apparent that
the two youngest infants (Cases 9 and 11)
manifested severe pulmonary hypertension.
This finding probably reflects the “common
ejectile force” or “systemic right ventricle”
described by Edwards2#{176} consequent to a
large ventricular septal defect. The severity
of the clinical condition cannot be
evalu-ated Ijy the degree of pulmonary
ilyper-tension alone, hut must take into account
both blood flow tllrough the lungs and
pul-monary vascular resistance. It is lik&y that
in tile infants who succumbed, the
pulmo-nary vascular evolution outlined by
Dam-mann and Ferencz17 followed a relatively
normal course resulting in a decrease in the
peripheral resistance of the lungs, and hence
an increase in pulmonary blood flow.
Fol-lowing this same reasoning, it is possible
that the successful adaptation in Case 11
was achieved by maintenance of high
pul-monary vascular resistance due to
persist-ence of the fetal state of thick-walled,
small-lumen pulmonary vessels.
In other patients with large ventricular septal defect, pulmonary blood flow may be
limited by the development of infundibular
pulmonic stenosis secondary to hypertrophy
of the right ventricular outflow tract, as
described by Gasul et al.2’ This was noted
in two of our patients (Cases 13 and 17).
The guarded prognosis of infants who
de-velop congestive failure warrants
considera-tion of surgical intervention. The palliative
approach of creating pulmonic stenosis22 to
reduce pulmonary blood flow deserves
at-tention. Closure of a ventricular septal
de-feet under direct vision23 may be
consid-ered the optimal procedure when the
opera-tive risk is reasonable in this age group.
SUMMARY
Seventeen patients had a history of
con-gestive heart failure in infancy out of a total
of 125 cases of ventricular septal defect
re-viewed. The initial episode of cardiac
de-compensation occurred in the first 6 months
of life. Ten of the patients had evidence of
unremitting failure and died in the first year
of life, while seven survived infancy.
Exac-erbations of decompensation after infancy
were rare; patients who survived the first
year of life did not succumb to
complica-tions of the defect in childhood.
Acknowledgment
The authors wish to express their gratitude to Dr. Dorothy H. Andersen for her generous
help in reviewing the pathologic material.
REFERENCES
1. Roger, H. : Recherches cliniques sur la
communication congenitale des deux coeurs, par inocclusion du septum inter-ventriculaire. Bull. Acad. de med., Paris,
2. Lillehei, C. W. : Contributions of open
heart cardiotomy to the correction of
congenital and acquired cardiac disease.
New England
J.
Med., 258:1044, 1958.3. Selzer, A., and Laqueur, C. L. : Eisen-menger complex and its relationship to
the uncomplicated defect of the
ventnic-ular septum. Review of 35 autopsied
cases of Eisenmenger’s complex
includ-ing two new cases. Arch. Int. Med., 87: 218, 1951.
4. Christie, A. : Normal closing time of
fora-men ovale and ductus arteriosus :
ana-tomic and statistical study. Am.
J.
Dis.Child., 40:323, 1930.
5. Keith, T. D., Rowe, R. D., and Vlad, P.:
Heart Disease in Infancy and Childhood.
New York, Macmillan, 1958, (a) p. 38;
(b) p. 219.
6. Blumenthal, S., and Andersen, D. : Conges-five heart failure in children.
J.
ChronicDis.,9:590, 1959.
7. Andersen, D. : Personal communication.
8. Casul, B. M., and Fell, E. : Salient points in the clinical diagnosis of congenital heart
disease. J.A.M.A., 161:39, 1956.
9. Wood, P., Magidson, 0., and Wilson, P. A.
D. : Ventricular septal defect with note
on acyanotic Fallot’s tetralogy. Bnit.
Heart
J.,
16:387, 1954.10. Marquis, R. M. : Ventricular septal defect
in early childhood. Brit. Heart
J.,
12:265, 1950.
1 1. Engle, M. A. : Ventricular septal defect in
infancy. PEDIATRICS, 14: 16, 1954.
12. Harned, H. S., Jr., Crothers, C. H., and
Whittemore, R. : Diagnosis of atrial and
ventricular septal defects. Am.
J.
Dis.Child., 9:211, 1955.
13. Zacharioudakis, S., Terplan, K., and
Lam-bert, E. : Ventricular septal defects in the
infant age group. Circulation, 16:374,
1957.
14. Nadas, A. : Pediatric Cardiology.
Philadel-phia, Saunders, 1957, p. 319.
15. Selzer, A. : Defect of the ventricular
sep-turn. Arch. mt. Med., 84:798, 1949.
16. Becu, L. M., et al.: Anatomic and
patho-logic studies in ventricular septal defect.
Circulation, 14:349, 1956.
17. Darnrnann,
J.
F., Jr., and Ferencz, C. : The significance of the pulmonary vascularbed in congenital heart disease. II.
De-fects between the ventricles of great
yes-sels in which there is a common ejectile
force. Am. Heart
J.,
52:210, 1956.18. Wood, P. : The Eisenmenger syndrome, or
pulmonary hypertension with reversed
central shunt. II. Brit. M.
J.,
2:755,1958.
19. Heath, D., and Edwards,
J.
E. : Thepa-thology of hypertensive pulmonary
vas-cular disease. Circulation, 18:533, 1958.
20. Edwards,
J.
E. : Structural changes of thepulmonary vascular bed and their
func-tional significance in congenital cardiac
disease. Proc. Inst. Med. Chicago, 18:6,
1950.
21. Gasul, B. M., Dillon, R. F., and Vrla, V.:
Ventricular septal defects, their natural
transformation into those with
infundib-ular stenosis or into the cyanotic or
acyanotic type of tetralogy of Fallot.
J.A.M.A., 164:847, 1957.
22. Muller, W. H., Jr., and Dammann,
J.
F.,Jr. : The treatment of certain congenital
malformations of the heart by the
crea-tion of pulmonic stenosis to reduce
pul-monary hypertension and excessive
pul-monary blood flow. Surg. Gynec. &
Obst., 95:213, 1952.
23. Kirklin,
J.
W., Harshbarger, H. G., Donald,D. E., and Edwards,
J.
E. : Surgicalcor-rection of ventricular septal defect:
ana-tomic and technical considerations.
