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Magnification Pulmonary Wedge Angiography
in the Evaluation of Children with Congenital
Heart Disease and Pulmonary Hypertension
MICHAEL R. NIHILL, M.D., M.R.C.P. AND DAN G. MCNAMARA, M.D.
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SUMMARY In order to determine the presence and extent of obstructive pulmonary vascular disease in patients with congenital heart disease, magnified cineangiograms were obtained with a catheter in the pulmonary
artery wedge position in 155 infants and children undergoing cardiac catheterization. The wedge angiograms
(WA) were analyzed in groups according to the pulmonary hemodynamics: group A normal pulmonary
blood flow (PBF) and pulmonary artery pressure (PAP) (31 patients; 53 WA); group B increased PBF and
normal PAP (46 patients; 69 WA); group C: increased PBF and PAP but a pulmonary vascular resistance
(PVR) < 6 u/m2 (19 patients; 33 WA); group D increased PAP and PVR > 6 u/M2 (30 patients; 66 WA);
pulmonary venous hypertension (15 patients; 27 WA); and group F: infants < 3 months old with a
group E
variety of congenital heart defects (14 patients; 19 WA).
WA from group A patients defined the microcirculation of the secondary pulmonary lobule with an evenly
tapering, orderly arborization of muscular pulmonary arteries and numerous supernumerary vessels as small
as 100 ,u in diameter with a full, even granular capillary blush surrounding each small, muscular artery. Increased PBF produced dilation of the elastic and muscular vessels with engorgement of the lobule, while increased PAP produced tortuosity of the vessels. An elevated PVR was manifest by dilation and tortuosity of
the elastic vessels and a more abrupt tapering of the muscular arteries. Patients with a PVR > 12 u/M2 and
those with obstructive vascular disease by histological examination (eight patients) showed marked reduction
or absence of supernumerary vessels and decreased arborization of the distal muscular pulmonary arteries as
well as the other hypertensive changes, and the capillary blush was incomplete, patchy and reticular. Obstructive signs were distributed randomly within the lobules and the lung lobes.
Pulmonary venous hypertension was associated with dilation of the paralobular veins with a vein:central
artery ratio of > 1.3: 1. WA in the infants showed no obstructive pattern, and the microvascular morphology
reflected the pulmonary hemodynamics seen in groups A, B and C.
We conclude that the presence of obstructive pulmonary vascular disease can be determined in patients with
pulmonary hypertension and elevated PVR by magnification wedge angiography. The degree and extent of
obstructive vascular lesions can be assessed more readily by this method than by histologic examination or random lung biopsy specimens.
vascular disease, demonstrating a correlation between
the morphological pattern in the wedge angiogram
and the stage of pulmonary vascular disease described
by Heath and Edwards."
This technique, however, has not had wide clinical
application because of technical factors. Until
recently, in order to obtain high resolution pictures, it
was necessary to construct special equipment with fine
focal spot x-ray tubes; large cut films which were used
in previous studies limited the number of exposures,
and magnification for small vessel visualization was
limited."' 5, 8 Lung parenchymal damage frequently
occurred when powered injections were used, and
repeated injections were often necessary to obtain
adequate visualization of all vessels. In recent years,
fine focal spot x-ray tubes and high-resolution cesium
iodide image intensifiers with variable magnification
have become available. These factors, together with
fine grain cine x-ray film, have made good quality
magnification wedge angiography possible in most
modern catheterization laboratories.
This paper describes a simplified technique for obtaining magnified pulmonary wedge angiograms in infants and children with congenital heart disease, both
those with normal vessels and those with various
degrees of PVOD. The purpose of this study was to
compare the angiographic morphology in the
pulmonary microcirculation with hemodynamic data,
THE CLINICAL USE of magnification pulmonary
wedge angiography was first described by Loomis Bell
in 1958, to study the morphology of the small
pulmonary arteries in patients with pulmonary
hypertension.' These studies developed from work of
Evans and Short,2 3 who studied magnified postmortem angiograms of lungs from patients with
various forms of pulmonary hypertension. These
workers compared the angiographic morphology with
histological data and were able to identify specific
angiographic patterns which corresponded with
various stages of pulmonary vascular obstructive disease (PVOD).
Since the first publications of Bell,"1 4there have
been several studies in patients and in experimental
animals'-IO with varying degrees of pulmonary
From the Lillie Frank Abercrombie Section of Cardiology,
Department of Pediatrics, Baylor College of Medicine and Texas
Children's Hospital, Houston, Texas.
Supported in part by Grant HL-5756 from the National Institutes
of Health, US Public Health Service, and by US Public Health Service Grant RR-00l 188 from the General Clinical Research Branch,
National Institutes of Health.
Address for reprints: Michael R. Nihill, M.D., Pediatric Cardiology, Texas Children's Hospital, 6621 Fannin Street, Houston,
Texas 77030.
Received January 27, 1978; revision accepted July 21, 1978.
Circulation 58, No. 6, 1978.
1094
WEDGE ANGIOGRAPHY/Nihill and McNamara
1095
TABLE 1. Hemodynamic Groups
Pulmonary
Group
A
hemodynamics
Normal
B
tFlow
N pressure
T Flow
t Pressure
t Pulmonary
arterial
resistance
Pulmonary
venous
hypertension
<3 mo old
C
D
E
F
No.
pts
31
46
19
30
15
14
Age (years)
range and
mean
2 - 16
m = 7.6
5 mo- 16
m = 7.6
5 mo- 16
m = 4.4
1 - 22
m = 6.8
5 mo - 15
m= 7.7
5 days- 3 mo
m = 1.7 mo
No. of
angios
53
PAP
(mm Hg)
<20
69
Hemodynamic criteria
PRU
Qp/Qs
(u/M2)
Rp/Rs
1:1
<3
<0.2
<20
>1:1
<3
<0.10
33
>20
>1:1
6
<0.4
66
>40
>6
>0.4
27
PAW
>15
19
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Total
155
267
=
Abbreviations: m
mean; PAP = mean pulmonary artery pressure; PRU/m2 = pulmonary resistance
units per meter squared; Qp/Qs = pulmonary-to-systemic flow ratio; Rp/Rs
pulmonary-to-systemic
resistance ratio; PAW = mean pulmonary arterial wedge pressure; T = increased; N = normal.
and histological findings in a few instances, to determine if the pulmonary wedge angiogram is a reliable
indicator of the presence and extent of PVOD.
Material and Methods
There were 267 wedge angiograms performed in 155
infants and children undergoing diagnostic cardiac
catheterization at Texas Children's Hospital (table 1).
Pulmonary blood flow was calculated by the indirect
Fick method, using the oxygen consumption data
from the tables of LaFarge and Miettinen.12
Pulmonary vascular resistance index (PVR-units/m2)
was calculated by subtracting the mean pulmonary
wedge pressure from the mean pulmonary artery
pressure and dividing by the pulmonary blood flow
(1 /min/m2). The ratio of pulmonary-to-systemic
blood flow (Qp/Qs) was calculated using measured
left atrial saturation (assumed to be 95% if not
measured), pulmonary artery saturation, aortic or
femoral artery saturation, and superior vena cava
saturation. The data from these patients were
classified into six groups according to the
hemodynamics of the pulmonary circulation determined at the same catheterization (table 1).
Hemodynamic data for all patient groups are listed
in table 2.
The 31 patients in group A (normal hemodynamics)
included some patients who had repair of tetralogy of
Fallot (11 patients), ventricular septal defect (two patients) or pulmonary valve stenosis (six patients). Each
of these patients was catheterized at least one year
after operation and each had normal pulmonary
artery pressure and no left-to-right shunt. All of the
patients who had ventricular septal defect repair had
normal PVR before surgery. The morphology of the
wedge angiogram in these postoperative patients subsequently was identical to that of the patients with a
normal pulmonary circulation; thus, we felt justified in
including the data from these patients with data from
patients with a normal pulmonary circulation. There
were seven patients with normal cardiac anatomy and
hemodynamics catheterized for electrophysiological
studies.
Group B consisted of patients with ventricular septal defect (18 patients), atrial septal defect (10 patients), transposition, patent ductus anteriosus and
systemic-to-pulmonary shunts (six patients each). The
lesions in group C consisted of ventricular septal
defect (10 patients), systemic-to-pulmonary shunts
(four patients), atrioventricular canal (three patients)
and transposition (two patients).
Increased PVR (group D) was due to transposition
(14 patients), ventricular septal defect (eight patients), atrioventricular canal (six patients) and
anomalous pulmonary venous drainage and truncus
anteriosus (one patient each).
Group E included patients with pulmonary venous
hypertension. These patients were grouped together
because of various congenital or acquired heart
defects which caused pulmonary venous hypertension;
pulmonary hypertension was due to left ventricular
failure secondary to cardiomyopathy or early postoperative noncompliance with high left ventricular
end-diastolic pressures in five patients. Three patients
had congenital mitral regurgitation and one had
prosthetic mitral valve replacement with obstruction.
Three patients had cor triatriatum, two of whom had a
large left-to-right shunt; two patients had unilateral
pulmonary vein obstruction after a Mustard
procedure and one had congenital pulmonary vein
atresia on the right side.
VOL 58, No 6, DECEMBER 1978
CIRCULATION
1096
TABLE 2. Hemodynamics
PAP
(mm Hg)
No.
Range
Group pts Mean SD
PAP:AoP
PAW
(mm Hg)
Range
Mean SD
3-14
8.7 - 3.9
QP/Qs
Range
Mean SD
1:1
PRU/m2
Range
Mean == SD
Rp/Rs
Range
Mean- SD
0.6-3.4
1.4 = 0.71
0.03-0.19
0.08 = 0.05
A
31
8-20
14 i 3.9
Range
Mean SD
0.1-0.3
0.18 - 0.06
B
46
12-20
15.5 - 3.37
NS
0.17-0.3
0.19 - 0.66
NS
5-14
8.0 - 4.83
NS
0.57
P <0.001
0.42-1.24
0.87 - 0.26
P <0.05
0.03-0.09
0.05 i 0.02
NS
30-85
7-28
14.7 = 5.9
P <0.05
0.9-5.1
2.3 = 1.02
NS
1.22-5.98
P <0.001
0.36-0.94
0.6 = 0.18
P <0.001
3.3 = 1.27
P <0.001
0.05-0.4
0.23 - 0.09
P <0.001
40-95
75.0 - 13.9
P <0.001
0.41-1.05
0.88 - 0.13
P <0.001
5-25
11.23
NS
0.35-3.80
1.43 - 0.98
P <0.001
6.0-33.5
0.42-2.36
13.57 - 11.19 0.86 - 0.28
P <0.001
P <0.02
18-105
0.18-1.05
0.52 = 0.35
P <0.001
15-40
23.6 - 8.6
P <0.001
0.74-3.4
1.28 = 0.76
P <0.001
0.22-23.7
5.26 i 6.4
P = 0.01
B:A
C
19
46.0
C:B
D
30
D:C
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E
15
-
14.4
42
26.8
P <0.001
E:A
-
4.48
1.2-3.0
2.05
-
0.02-0.96
0.24 - 0.28
P <0.02
1-4.3
0.46-5.5
0.02-0.24
4-32
9-60
0.35-0.9
0.17 - 0.13
1.77
2.25
11.36 - 4.7
2.98 f 1.83
35.3 - 16.3 0.59 - 0.18
P <0.05
NS
NS
NS
NS
F:C
NS
Abbreviations: B:A C:B, D:C, E:A, F:C = comparison of mean values (P values) between groups; AoP
- mean aortic pressure. Other abbreviations same as in table 1.
F
14
Fourteen patients less than 3 months of age were
grouped separately (group F); this group included
patients with a variety of congenital heart defects and
pulmonary hemodynamics, and we assumed that these
infants were likely to have grade I and were very unlikely to have greater than grade II pulmonary
vascular changes.
The angiograms were performed during cardiac
catheterization in a standard laboratory equipped with
an undertable x-ray tube with an 0.6 mm focal spot
(Siemens) and a 6/10-inch cesium iodide image intensifier which produces a magnification of 1.3 when in
the 6-inch mode, 9 inches from the table top. This was
determined by filming a radiopaque grid of 1 cm2.
When the end- and sidehole catheter (GoodaleLubin) was placed in the desired wedge position, the
image intensifier was raised 21 inches from the table
top, producing a magnification of 2.4 times actual size
in the 6-inch mode. The size of the lung field to be
studied was ascertained from a small test injection of
0.5 ml of contrast medium, sufficient to visualize the
peripheral arteries. The shutters were then closed to
the desired field size to reduce radiation scatter and
enhance definition. We found it desirable to include
some part of the hilus to evaluate pulmonary venous
drainage. The x-ray factors are then set at 60-70 kV
(depending upon the anterior-posterior chest diameter), 10 milliamperes (mA) and 4 msec exposure
for maximum contrast and definition. A fine-grain 35
mm cine film (Ilford Cinegram F Type (CF-718-2))
was exposed at 30 frames/sec to eliminate movement
artifact. If the heart or diaphragmatic shadows were
overlying the catheter tip, a slightly higher kV setting
was used for more penetration (65-75 kV).
The main bolus was delivered by hand injection with
a 3 ml syringe; 0.5-3 ml of contrast medium
(Hypaque-m, 75%) was injected slowly while the lung
field was observed on the fluoroscope while filming.
The speed and force of the injection was estimated by
the operator after the test injection, when some tactile
judgement could be made of the pulmonary resistance.
The contrast medium was injected until most of the
small arteries and some of the paralobular veins were
seen on the video monitor. Using either a three-way
stopcock or by exchanging syringes, 5-10 ml of standard catheter flush solution (5% dextrose and heparin
3,000 u/l) were flushed through the catheter until the
major pulmonary veins were filled and the lobular
capillary blush disappeared.
When the catheter could not be wedged, larger
amounts of contrast (3-5 ml) were injected more
forcefully in the distal small elastic pulmonary arteries
so that several secondary pulmonary lobules were
filled; opacification of more than one lung segment
was satisfactory to obtain magnified angiograms of
several small pulmonary lobules, but overlapping
vessels often obscured fine details.
On four occasions, a wedge-balloon catheter was
manipulated almost to the periphery of the lung and
the injection was made with balloon inflated. This
WEDGE ANGIOGRAPHY/Nihill and McNamara
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technique was necessary when the endhole catheter
could not be wedged because of large dilated elastic
pulmonary arteries. Only well-filled, muscular
pulmonary arteries < 2 mm in diameter were studied.
An angiographic catheter was used on seven occasions, and satisfactory wedge angiograms of several
small pulmonary lobules were obtained, since the dye
extruded from the sideholes into small pulmonary
arteries.
Recordings of phasic and mean pulmonary artery
wedge pressure were made immediately before and
after the wedge angiogram. Any contrast remaining in
the radiographic field after flushing and withdrawing
the catheter was recorded as a stain.
One to five separate wedge angiograms in different
positions were performed in each patient; a greater
number of injections were made in different areas of
the lungs in patients with pulmonary hypertension.
The most easily analyzed angiograms were obtained
from the peripheral or cortical areas of the right lower
lobe, right upper lobe and left upper lobe, in that
order. In the cortical areas of the lung the secondary
pulmonary lobules are aligned horizontally along radii
from the hilus.'3 Angiograms near the hilus were
sometimes difficult to interpret because the orientation of the lobule may be parallel to the direction of
the x-ray beam.
A Tagarno 35 mm projector was used to project the
films onto a matte white wall 6-8 feet away, producing
an average magnification of 7.5 times actual size. The
projected catheter diameter was used as the reference
diameter for calculating the magnification factor and
absolute arterial diameter. Although there was some
degradation in the edge definition at this magnification, projected arterial images of 1.5-2 mm (220-270
,u actual size) could be measured with reproducible accuracy.
Measurements were made of: 1) the catheter
diameter, 2) the diameter of the artery just distal to
the catheter tip, and 3) the paralobular vein at the
same level as the arterial measurement (fig. 1). The
ratio of the vein diameter to the arterial diameter was
then calculated. When the pulmonary artery branched
dichotomously (branching angle less than 900), the
diameter of the branches was measured and compared
to the diameter of the parent artery. Branches of the
small pulmonary arteries which subtended a 90° angle
(monopedial branching) were also measured and this
diameter was compared to the parent branch. A note
was made about the uniformity and completeness of
the background capillary blush and graded a) sparse,
b) patchy, c) incomplete, d) full. Reflux of contrast
around the catheter back into the pulmonary arteries
was graded from none (0) to minimal (+) to gross
Biopsies were taken at cardiac surgery from the
same lung as the angiogram in 19 patients within one
week of catheterization. Lung histology was obtained
in three of the patients who died after open heart surgery. Pulmonary vascular pathology was examined by
Dr. Harvey Rosenberg, who reported the findings in
1097
relation to Heath and Edwards' grading of pulmonary
vascular disease.1'
Results
Two hundred sixty-seven wedge angiograms were
obtained in 155 patients without serious side effects or
complications. Seventeen (6%) were unsatisfactory for
analysis because of poor exposure. Extravasation of
contrast (stain) occurred in two infants under 3
months of age and in 10 of 66 patients with pulmonary
hypertension. Any residual contrast remaining in the
lung field after flushing and withdrawing the catheter
from the wedge position disappeared within 5 minutes.
One or two coughs occurred in 23 patients (14.8%)
during the injection (30 of 267 angiograms, 11.2%),
but paroxysmal coughing occurred only twice and no
patient had hemoptysis, pneumothorax or pulmonary
infarction. There was no change in the phasic or mean
wedge pressure after the angiogram. Respiratory
movement did not alter the angiographic morphology
of the vessels, which became more crowded in expiration, but measurement of vessel size could still be
made.
Group A - Normal Hemodynamics
Fifty-three angiograms were obtained in 31 patients, and 51 were suitable for analysis.
In the normal lung, a catheter with an outside
diameter of 1.7-2 mm (#5-6 French gauge) in the
wedge position, produces an angiogram which
represents the vascular anatomy of the secondary
pulmonary lobule. The centrally placed muscular or
transitional pulmonary artery was 1-2 mm in
diameter (average 1.64 + 0.48 mm), which branched
dichotomously in a uniform, evenly tapering arborization. (fig. IA) The diameter of the branches was
68-79% (mean 72 + 3.4%) of the parent artery, while
more numerous monopedial or supernumerary
branches arose at right angles to the parent branch,
and their diameter was 20-60% (mean 42.1 ± 12%) of
the parent branch. The dichotomous branches follow
the respiratory bronchiolar branching, while the
monopedial branches represent the supernumerary
and terminal branches which give off precapillary
arterioles at right angles and supply the alveolar
capillary network.15 16 The monopedial branches were
also seen to arise from the larger muscular, transitional and elastic arteries along the course of the
major bronchi where respiratory alveoli occur."7 18
With a film speed of 30 frames/sec, we could see
sequential filling of all arterial branches followed by a
dense, granular, uniform blush which represented the
capillary phase (fig. 1B). With continued injection of
contrast, the peripheral veins of the secondary
pulmonary lobule started to fill and usually coalesced
to a single vein which ran in the septa of the lobules,
parallel to the central artery. Sometimes several small
veins were filled and drained to other lobar veins. It
was possible to measure accurately vessels 250-400 ,u
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VOL 58, No 6, DECEMBER 1978
CIRCULATION
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D
FIGURE 1. Wedge angiogram from the right lower lobe. Group A morphology, normal hemodynamics. A) A rterialphase with
early filling of the paralobular vein. B) Mid-flush phase showing a complete capillary blush surrounding all of the small arteries
and better filling of the pulmonary veins. C) Venous phase showing clearing of the capillary blush and complete filling of the
paralobular
B
=
draining to the left
of artery measured distal
veins
diameter
atrium.
to
eter, D = capillary background blush; E
D)
A
line
the catheter tip; C
=
drawing of the flush phase (B).
diameter
paralobular vein; F
-
of the
A
vein measured at
catheter diameter (2 mm);
same
level
as
the arterial diam-
monopedial muscular artery 600 M in diameter.
WEDGE ANGIOGRAPHY/Nihill and McNamara
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FIGURE 2. Right lower lobe angiogram (left) with inflated balloon catheter; group B morphology, increased flow with low resistance. This is a 10-month-old infant with transposition of the great arteries and
patent ductus arteriosus. Pulmonary artery pressure = 25/15 (mean 19 mm Hg); Qp/Qs 4:1; pulmonary
resistance 0.43 u/mt. Catheter diameter 1.7 mm. (right) A - inflated balloon catheter with filling of
secondary lobule directly distal to the tip in the right lower lobe; the muscular arteries are dilated with normal branching and capillary blush. B = incomplete filling of adjacent elastic artery.
=
=
in diameter, and vessels of 100 l were clearly seen in
most angiograms.
The flush phase of the angiogram produces even
greater filling of the small pulmonary arteries and a
more uniform capillary blush and greater filling of the
pulmonary veins (fig. lC). Incomplete filling of the
small pulmonary vessels during the initial injection of
contrast was probably due to the high viscosity of the
contrast medium, and the flush phase is an important
step in the complete evaluation of the vascular
morphology.
Group B
Pressure
Increased Pulmonary Blood Flow and Normal
The 69 wedge angiograms were almost identical to
the normal group, except that the proximal arteries
and veins were larger (1.9 ± 0.5 mm; P < 0.02) and
there was a more dense and diffuse capillary blush
(fig. 2).
Group C
smaller because of the parent artery dilation.
The capillary blush remained full when there was a
direct injection into the lobular artery (fig. 3B), but
reflux of contrast was more common (27.3% of the
angiograms), and more extensive in this group, and
there was often incomplete filling of adjacent lobular
arteries.
The effect of increased blood flow on the wedge
angiogram morphology is to produce generalized dilation of all vessels and an engorged lobule; an increase
in pulmonary artery pressure leads to further dilation
of the elastic and transitional vessels together with tortuosity and dilation of all vessels, including the
muscular arteries.
Seven patients with group C hemodynamics had a
lung biopsy at the time of corrective surgery, and each
showed medial hypertrophy in the small muscular
arteries (grade I); three patients had isolated areas of
intimal fibrosis in a few larger muscular arteries (early
grade III).
Increased Pulmonary Flow and Pressure
Although the mean Qp/Qs ratio for this group was
not significantly different from that in group B, the
added component of increased pulmonary artery
pressure was associated with an increased arterial tortuosity (fig. 3A). The degree of tortuosity was more
pronounced in patients with the highest pulmonary
artery pressures. The mean proximal pulmonary
artery diameter was 1.93 mm (range 0.99-3.97 mm),
similar to group B; the proximal vein to arterial ratio
was smaller because of the larger size of the artery
rather than a small venous size. For this same reason,
small arteries arising at right angles appeared to be
Group D - Increased Pulmonary Arterial Resistance
These 30 patients were grouped together because
they had pulmonary hypertension with an increase in
pulmonary resistance of greater than 6 u/M2, with an
average pulmonary-to-systemic resistance ratio
(Rp/Rs) of 0.86 ± 0.28 (range 0.42-2.36). Nine of the
66 angiograms (13.6%) were unsuitable for analysis
because of poor x-ray exposure. The appearance of the
wedge angiograms ranged from very similar to group
C angiograms to the classical "pruned tree"
appearance of PVOD.
There was a more abrupt termination of dilated tor-
CIRCULATION
1100
VOL 58, No 6, DECEMBER 1978
FIGURE 3. Group C morphology. A S-year-old patient
with transposition of the great arteries, pulmonary stenosis,
and ascending aorta-to-right pulmonary artery shunt.
Pulmonary artery pressure 60/40 (mean 50 mm Hg);
Qp/Qs 1.4: 1; pulmonary resistance = 4.2 u/mt. Catheter
diameter 2 mm. A) shows dilated elastic arteries and tortuous muscular arteries. B) shows almost a complete
capillary blush surrounding all the arteries.
-
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tuous arteries and the number of supernumerary
(monopedial) branches was markedly decreased or absent. The capillary blush was incomplete or patchy in
random areas of the lobule and absent around many
well filled larger vessels during the flush phase. There
was a reticular consistency rather than the granular
blush seen in normal lungs (fig. 4). There was an increased resistance to injection and contrast refluxed
back around the catheter in 63.6% of the angiograms,
especially during the flush phase, rather than passing
through the high-resistance lobule.
Beading and irregularity of the lumen of the arteries
less than 600 j in diameter was seen in patients whose
pulmonary vascular resistance was greater than 12
u/m2. Lower lobe arteries showed a greater degree of
pathology than upper lobe arteries in five patients
whose pulmonary resistance was equal to or greater
than systemic resistance and with right-to-left shunting (Eisenmenger's syndrome). There was the typical
"pruned tree" appearance in the lower lobe, while the
upper lobe in the same patient showed changes consistent with group C hemodynamics.
It was impossible to wedge the catheter in six patients and pre-wedge angiograms were obtained; these
were not as satisfactory as the wedge angiograms,
since more contrast material was required to adequately fill the smaller vessels, and we could not be
sure that the lack of filling was due to high resistance
and vascular disease or to inadequate opacification
with contrast material. If a Goodale-Lubin catheter
could not be wedged, better filling of the smaller
vessels was obtained when a pre-wedge angiogram was
performed with an inflated balloon catheter.
The five patients with Eisenmenger's syndrome had
severe pruning of the peripheral vessels and only an
occasional vessel less than 500 A was seen (fig. 5).
There was delayed filling of the pulmonary veins and
some contrast material would linger in abruptly terminating tortuous vessels, producing a streaked
residual picture quite different from an iatrogenic
stain.
Group E - Pulmonary Venous Hypertension
If pulmonary hypertension was entirely due to
pulmonary venous obstruction, the wedge angiogram
demonstrated the typical vasoconstrictive pattern in
the lower lobes as described by Evans and Short3 with
long, slowly tapering proximal arteries and a
decreased number of monopedial branches (figs. 6A
and B). There was a faint but uniform capillary blush
with no gaps, but the concentration of contrast was
decreased with a rather weblike reticular pattern to
the small arteries. The paralobular veins were normal,
but the vein running parallel to the proximal injected
artery was dilated; when the vein and artery were
measured at the same level, the average ratio was
significantly greater than normal (1.43 vs 1.04,
P < 0.001).
When angiograms were taken in both the upper and
the lower lobes in the same patient, a distinctly
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FIGURE 4. Group D morphology. Right lower lobe injection in a 3-year-old boy with transposition of the great
arteries, tricuspid atresia and ventricular septal defect.
Pulmonary artery pressure 100/60 (mean 75 mm Hg);
12 u/mt,
1.6:1; pulmonary resistance
Qp/Qs
Rp/Rs 0.65: 1. Catheter diameter 2 mm. A) mid-arterial
and B) flush phase. There is dilation of the elastic arteries
and tortuosity of the distal muscular vessels. There is patchy
filling of the capillaries with an incomplete background
blush. Histological section showed generalized grade II
changes with patchy early and late grade III changes.
=
different pattern was seen in the morphology of the
microvasculature: the upper lobes showed dilated
arteries and a full capillary blush, while the bases
showed generalized vasoconstriction and oligemia as
described by Doyle et al.'8 Using wedge angiography,
in two patients we found pulmonary varices which
were not observed by conventional main pulmonary
artery angiograms. Both patients had anomalies of
pulmonary venous return, one with cor triatriatum
1 101
FIGURE 5. Group D morphology. A) Mid-arterial and B)
flush phases of a 9-year-old patient with Eisenmenger's syndrome with ventricular septal defect. Pulmonary artery
pressure 110/70 (mean 85 mm Hg), Qp/Qs 0.5:1.
Rp/Rs 2:1; PR U 46.4 u/m'. Catheter diameter is 2
mm. There is severe pruning of the upper lobe vessels and
very few supernumerary vessels and very sparse capillary
=
=
filling.
and the other with single ventricle with partial
anomalous pulmonary venous return with obstruction.
Group F - Less Than 3 Months of Age
These 14 patients were all less than 3 months of age,
with a variety of congenital heart defects; only three
had no left-to-right shunt and all but three had
elevated pulmonary artery pressure. It is assumed that
VOL 58, No 6, DECEMBER 1978
CIRCULATION
1102
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FIGURE 6. Group E morphology. Pulmonary venous obstruction. A) Arterial and B)flush phases of a right
lower lobe injection in a 25-year-old patient with cardiomyopathy and mitral valve replacement. Pulmonary
90/40 (mean 60 mm Hg); pulmonary artery wedge
30 mm Hg; pulmonary
artery pressure
resistance 13.7 u/m2. Catheter diameter 2 mm. There is severe vasoconstriction of the arteries, with only
occasional filling of the muscular arteries in the lower lobe, while there is preservation of a more normal
architecture in the proximal vessels. C) and D) A rterial and venous phases with an inflated balloon catheter
in the right lower lobe of a 5-month-old infant with cor triatriatum and complete atrioventricular canal.
85/40 (mean 65 mm Hg); pulmonary artery wedge = 32 mm Hg;
Pulmonary artery pressure
Qp/Qs 3: 1; pulmonary resistance 2.5 u/m2. Catheter diameter 2 mm. The arterial phase resembles
that of group B morphology, with dilated vessels and a complete capillary blush. Venous phase shows very
distended veins and the ratio of the vein-to-the-artery diameter is 1.5:1.
=
=
=
there was medial hypertrophy (grade I changes) in
those patients who had some degree of pulmonary
hypertension.
The morphology of the microcirculation in each patient corresponded to the hemodynamics of the con-
genital heart lesion; no patient had pulmonary
resistance of greater than 5.5 u/M2 or an
Rp/Rs > 0.22. Some dilation and mild tortuosity was
seen in the patient with the highest pulmonary artery
pressure and highest resistance (group C
1103
WEDGE ANGIOGRAPHY/Nihill and McNamara
TABLE 3. Histological-Angiographic Correlations
PVR
Muse
Histological Age
arteries
Diagnosis
Group PAP:AoP Qp/Qs (u/m2) Reflux
grade
(years)
0.12
1.1
Dilated
B
0.5
1-4 TGA, VSD, PS
Normal
0.83
1.7
5.5
Dilated
C
+
0.9 VSD, coarct.
Dilated
0.55
3.4
1.3
0.25 VSD, PDA
E
I
F
0.8
5.4
1.4
Constricted
0.2
AV canal
Normal
0.66
1.2
3.8
6
C
TGA
II
III
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Late III
IV
1
1.4
Cor Triat.
TGA, VSD
E
C
1.3
1.0
1.0
2.3
11.9
3.5
-
Constricted
Tortuous,
constricted
Dilated
Dilated,
tortuous
Constricted
Dilated,
tortuous
Constricted,
tortuous
Dilated,
tortuous
Constricted
Dilated,
C
C
0.6
0.38
4.0
0.6
2.2
3.3
-
2
2.5
VSD
Pseudotrunc.
shunt
VSD
C
VSD
D
0.68
1.0
1.8
2.0
4.3
6.3
+
0.33
VSD, ASD
D
0.9
3.0
5.5
++
1
TGA, VSD
D
0.9
5.0
5.7
-
2
2
C
D
0.7
0.74
1.4
0.6
5.6
8.9
++
13
TGA, VSD
TGA, VSD,
Band
PO VSD
D
0.78
1.0
11.5
++
14
10
VSD
TGA, VSD
D
D
0.93
0.88
2.9
0.7
8.5
17
++
Dilated,
straight
Constricted
Dilated,
15
VSD, Band
D
0.37
0.9
12
++
tortuous
Dilated
5
3
-
-
Monopedial Capillary
vessels
Numerous
Numerous
Numerous
Reduced
Numerous
Numerous
Reduced
blush
Full
Full
Full
Full
Patchy,
mottled
Full
Full
Reduced
Numerous
Full
Full
Numerous
Reduced
Full
Incomplete
Reduced
Patchy
Numerous
Full
Reduced
Reduced
Full
Patchy
Rare
Patchy,
reticular
Rare
Rare
Sparse
Sparse
Pruned,
rare
Reduced
Sparse
tortuous
-
Patchy
Dilated,
tortuous
Patchy
D
++ + Constricted Reduced
0.86
2.8
8.3
7
VSD, PDA
Sparse
++
Constricted, Rare
1.0
1.0
13.1
TGA, VSD
D
14
tortuous
Abbreviations: TGA = transposition of the great arteries; VSD ventricular septal defect; PS = pulmonary stenosis; PDA
= patent ductus arteriosus; AV canal = artioventricular canal; Cor Triat. = Cor Triatriatum; ASD = atrial septal defect;
PO VSD = postoperative VSD closure; Band = main pulmonary artery banding; PO Truncus = postoperative Rastelli repair
of truncus arteriosus; Pseudotrunc. = pseudotruncus arteriosus. Other abbreviations same as in table 1.
2.5
PO Truncus
D
0.8
morphology); the wedge angiograms obtained in the
other 13 patients were indistinguishable from those of
groups A and B.
Histological Correlations
Lung histology was available from autopsy material
in three patients and from lung biopsies taken at
operation in 19 patients (table 3).
PVR was .6.7 u/M2 (range 6.7-17 u/M2) in those
with late grade III PVOD or greater, but the level of
PVR was not a good indicator of the degree or extent
of PVOD, either angiographically or histologically.
With lesser degrees of PVOD histologically, there was
a wide range of values for PVR. One patient with a
ventricular septal defect and coarctation had normal
vessels histologically and angiographically and had a
PVR of 5.5 u/M2, while another with cor triatriatum
had a PVR of 11.9 u/M2 and only grade II changes
histologically.
Intimal fibrosis was observed histologically in 10
1.1
6.7
patients ranging from slight fibrosis in the hyperplastic intima (early grade III) to diffuse, irregular,
dense fibrous plaques, almost occluding the vessel
lumen in some of the vessels. Four patients had extensive grade III changes, short of occlusion, and were
labelled "late grade III" changes. There were three
patients with early grade IV changes, with occlusive
intimal lesions and one with an isolated angiomatoid
lesion (grade V).
Patients with either normal, grade I or grade II
changes were from hemodynamic groups B, C, E and
F. All patients with grade III changes or greater were
from groups C and D. The patients with late grade III
changes or obstructive vascular disease were from the
group with elevated PVR (group D).
The angiograms of patients with late grade III
changes were almost identical to those of patients with
grade IV or greater pulmonary vascular disease. The
common feature in those patients with advanced
obstructive vascular disease was incomplete filling of
the capillary background blush; when there was fill-
1104
VOL 58, No 6, DECEMBER 1978
CIRCULATION
TABLE 4. Wedge
Angiographic Features and Hemodynamics
Angiographic
features
Resistance to hand
Group A
Normal
hemodynamics
Low
Group B
I Flow
Normal pressure
Low
Low
Rare
Straight
Rare
Dilated
Group C
Group D
I Flow
I Pressure
to moderate
I PVR
Increased
Group E
Pulmonary venous
hypertension
Variable
injection
Reflux of contrast
Proximal muscular
arteries
Frequent 27Q,o
Dilated
Usual 63%o
Dilated, tortuous
tortuous
Occasional 10%o
Dilated or
constricted
(1-2 mm)
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Tapering of muscular Even, gradual
arteries
Supernumerary vessels Numerous from
(monopedial
elastic and
branching)
muscular arteries
Capillary blush
Full, granular
blush around
each artery
Small veins (1-2 mm) Narrow, orderly
vein artery
aborisation
Diameter ratio
Mean - SD
V/A = 1.04
-0.28
Histology grade"
Normal to I
Even, rapid
Uneven, rapid
Full, granular
arteries
Full reticulargranular (18%,o)
Sparse, patchy
Dilated
Dilated
Normal
Dilated
V/A - 0.99
0.23
+
V/A
V/A
V/A = 1.43
Uneven, rapid,
Even, rapid
(lower lobes)
Beading
Numerous, dilated Reduced, especially Reduced to sparse Reduced, constricted
or absent
from elastic
Normal to II
(22 patients)
=
0.87
=0.18
Normal to early
III
94%,
0.93
= 0.22
=
Sparse-full coarse,
reticular (18%)
0.33
(P <0.001)
Early III, late III II to early III
IV and V
Abbreviations: t - increased; PVR = pulmonary vascular resistance.
ing, there tended to be a coarse, reticular pattern
rather than a fine, granular blush as seen in unobstructed vessels. The degree of filling varied from
lobe to lobe and was random in distribution in the
lobules; pulmonary hypertension and obstructive
vascular disease (Eisenmenger's syndrome) had a
more pruned appearance to the lobules, especially in
the lower lobes.
There were nine patients with less than complete
capillary filling, and each of these had a pulmonary
resistance > 6 u/mi. Only one of the nine patients had
early grade III vascular disease and the others had late
grade III or greater.
All grades of severity of pulmonary vascular disease
by histology were associated with a wide range of
pulmonary artery pressures, resistance ratios and flow
ratios, so these factors were not predictive of the
degree of histological pulmonary vascular disease.
When the vascular disease was obstructive by
histological findings (late grade III to grade IV
changes) the most consistent and specific angiographic
finding was a patchy or incomplete capillary blush in
one or more lobular angiograms. If a patient had a
PVR > 6 u/M2 or greater and an incomplete capillary
blush, then there was an 89% chance that he had
diffuse, late grade III changes or better.
The hemodynamic, angiographic and histological
findings are compared in table 4.
Discussion
The difficulties in evaluating the state of the
pulmonary vascular bed in children with congenital
heart disease have been analyzed in great detail by
Hoffman.'9
The measurement of pulmonary blood flow and
calculations of PVR are only approximations, at best,
using standard techniques,20 22 and the finding of an
elevated PVR poses the question of interpretation of
this value. There have been some empirical correlations between pulmonary resistance calculations
and the degree of pulmonary vascular disease and its
reversibility,23 but in any patient, one cannot rely too
heavily on the calculated resistance value because of
the many sources of possible error in the
calculations.22 Even if reactivity of the pulmonary
vascular bed is demonstrated by administering
vasodilator drugs, it is still possible that 50% of the
small vessels have occlusive pulmonary vascular disease.'9 Conventional examination of lung biopsies
may not present an accurate picture of the extent of
the vessel pathology, since vascular lesions are not
uniformly distributed over the whole lung or even
along the length of a single vessel.3' 10, 11
Studying the morphology of the intact pulmonary
lobular circulation allows a better overall evaluation
of the degree and extent of pulmonary vascular
changes in a patient with pulmonary hypertension.
Detailed studies of the normal peripheral pulmonary
vascular bed have clearly defined the size, structure
and morphology of the vessels of the primary and
secondary pulmonary lobules,'3- ' and it is at this level
that the early stage of obstructive pulmonary vascular
disease occurs. 1 24 21 Since Bell's first report of the
clinical use of magnification pulmonary wedge
angiography,' many investigators have been able to
WEDGE ANGIOGRAPHY/Nihill and McNamara
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reproduce detailed angiograms of the secondary pulmonary lobule and of vessels as small as 100-300 , in
diameter.5-9 Previous studies in animals,9 patients with
mitral stenosis7 and children with congenital heart disease' 6 10 have shown a correlation between changes
in the magnified wedge angiogram or postmortem
magnification angiograms with histological changes in
the pulmonary arteries.
Increased tortuosity, dilation and abrupt tapering
of muscular arteries was noted to be associated with
an increase in PVR4' 6, 8 in children with congenital
heart defects. These changes were also noted by Friedman9 in serial studies of experimental animals with
left-to-right shunts and pulmonary hypertension.
Reduced small vessel arborization and a patchy
capillary blush were associated with intimal fibrosis
and luminal occlusion in histological specimens from
these studies4 8, 9 (grades III-IV of Heath and Edwards).
Using a quantitative structural analysis of necropsy
and lung biopsy specimens, Reid and colleagues24' 25
described changes in the pulmonary microcirculation
associated with pulmonary hypertension. They found
abnormal extension of medial musculature into
arteries less than 250 ,, together with abnormal
thickening in the larger muscular arteries. There was
also a decrease in the number and size of smaller
intra-acinar arteries which was indicated by reduction
in the background blush in the postmortem
angiograms and a decrease in the number of small
arteries per unit area of the lung histologically. This
latter observation corresponds with our finding of a
decreased number of supernumerary vessels and the
incomplete or patchy capillary blush in the magnified
wedge angiograms.
Until recently, however, the equipment necessary to
obtain high-quality, high-definition angiograms was
not available in all catheterization laboratories; the introduction of very high resolution cesium iodide image
intensifiers, coupled with fine-grain 35 mm
cineangiographic film and fine focal spot x-ray tubes,
has made it possible to obtain high-quality magnification wedge angiograms in any patient undergoing
routine cardiac catheterization. Manual injection of
contrast, with video monitoring, allows the operator
to evaluate the technical quality of the image as it is
formed, and a complete study of all phases of the
microcirculation is obtained without excessive use of
contrast material or force. With a little experience,
this technique can be performed without serious complication. Repeated wedge angiograms should be performed in several areas of the lung, since the distribution of vascular disease is not uniform.
The findings in this study are in general agreement
with previously published reports in that there are
identifiable angiographic features of the peripheral
pulmonary vasculature with different degrees of
PVOD. There is a distinct difference in the wedge
angiogram of the patient with elevated pulmonary
artery pressure and low vascular resistance compared
with that of the patient with high resistance and
PVOD. The primary features of pulmonary hyperten-
1105
sion with increased pulmonary blood flow are dilation
and tortuosity of the elastic pulmonary arteries, with
rapid tapering of arteries less than 1 mm in diameter
to the peripheral vasculature of the secondary
pulmonary lobule. The diameter of the monopedial
branches which arise at right angles remains constant,
but the ratio of the branch to the parent artery
becomes smaller because of proximal dilation. With
high pulmonary artery pressure and flow, tortuosity
increases and the morphology of the secondary lobule
becomes distorted; there is still a complete granular
background blush and supernumerary vessels are
reduced in number, but still present on the elastic
arteries if there is no obstructive vascular disease or
late grade III changes.
As pulmonary resistance rises with intimal fibrosis
and occlusion, tortuosity of the elastic and muscular
arteries becomes more prominent and there is an increased resistance to manual injection while the
amount of reflux increases; there is also slower filling
of pulmonary veins and slower clearing of the
capillary bed and small muscular arteries due to
reduction in the lumen.
When intimal fibrosis encroaches upon the lumen of
the vessel and becomes occlusive, particularly at the
right angle on supernumerary branches, fewer small
vessels are filled, together there is a lack of filling of
the surrounding capillary bed. Supernumerary vessels
are among the first vessels affected by occlusive
pulmonary vascular disease, and these become sparse
and finally are not seen on the angiogram. Failure to
demonstrate any of these vessels suggests late grade
III or grade IV changes. Vascular occlusion occurs in
a random fashion, and not all vessels are affected
simultaneously or to the same degree. The capillary
blush will look patchy and incomplete until
progressive occlusive vascular disease obstructs all
capillary filling and the bare, pruned "tree-in-winter"
appearance is seen. This morphology is seen in the
lower lobes more frequently, but may be seen in other
lobes next to lobules with less severe changes.
Clinical examination, chest radiography and
routine ventriculography will easily identify the
patients with pulmonary hypertension who have increased pulmonary blood flow and a low PVR and
those who have a high fixed resistance or Eisenmenger
syndrome. If, however, a patient has pulmonary
hypertension with a moderate-to-high pulmonary
resistance (6-10 u/m2) and a modest left-to-right
shunt (Qp/Qs < 2:1), pulmonary wedge angiography
will identify the presence of irreversible intimal
sclerosis by the presence of abrupt tapering of the 1-2
mm muscular arteries and a reduction in the small
vessel arborization, together with an incomplete
capillary blush. The extent of this obstructive vascular
disease can be determined by wedge angiograms in
several areas of the lung. If these changes are not present, then it can be assumed that there may be up to
grade II changes or, at most, scattered, slight intimal
sclerosis in larger elastic arteries, and that these
changes are reversible after corrective surgery. The
angiographic signs of diffuse intimal obstructive dis-
CIRCULATION
1106
ease means that pulmonary resistance will not fall
even after successful corrective surgery, and
progressive vascular disease may continue in these
patients.
It may be useful to observe directly any changes in
vascular caliber and capillary filling by repeating the
wedge angiogram after administering vasodilator
drugs directly into the peripheral vascular bed.
Magnification wedge angiography of the pulmonary
lobular vascular bed from several areas of the lung
provides a comprehensive and accurate assessment of
the presence and degree of pulmonary vascular disease
in children with congenital heart disease.
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M R Nihill and D G McNamara
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Circulation. 1978;58:1094-1106
doi: 10.1161/01.CIR.58.6.1094
Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 1978 American Heart Association, Inc. All rights reserved.
Print ISSN: 0009-7322. Online ISSN: 1524-4539
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