THERAPY AND PREVENTION
PTCA
Changes in cross-sectional area of the coronary lumen
in the six months after angioplasty: a quantitative
analysis of the variable response to percutaneous
transluminal angioplasty
MARYL R. JOHNSON, M.D., GAIL P. BRAYDEN, M.D., ELIZABETH E. ERICKSEN, M.S.E.E.,
STEVE M. COLLINS, PH.D., DAVID J. SKORTON, M.D., DAVID G. HARRISON, M.D.,
MELVIN L. MARCUS, M.D., AND CARL W. WHITE, M.D.
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ABSTRACT Although immediate and late changes in coronary stenoses after percutaneous transluminal coronary angioplasty (PTCA) have been reported, most investigators have employed qualitative
or semiquantitative techniques to analyze the angiograms. Such data is not optimal because of considerable interobserver variability and the use of relative instead of absolute changes in lesion geometry.
Analysis is further compounded by the indistinct edges that characterize coronary lesions immediately
after angioplasty. To quantify the changes in minimal cross-sectional area (MCSA) of the coronary
lumen that occur during and after PTCA, we analyzed the angiograms of 23 patients before PTCA,
SD) months follow-up using two computerimmediately after PTCA, and at 7.2 + 3.0 (mean
assisted methods of angiographic analysis quantitative coronary angiography (QCA) and videodensitometry (VID). QCA provides an absolute measure of the area of the lumen; VID is a nongeometric
method that is not dependent on exact border recognition. Based on these quantitative methods, we
found that successful angioplasty is associated with about a three-fold increase in the MCSA of the
lesion (from 1.0 to 3.2 mm2). This area is, however, well below normal and is less than half of the
average MCSA of the inflated dilating balloon. Analysis of follow-up angiograms demonstrated that
eight of 23 patients had a substantial late increase in the MCSA of the lesion (from 2.7 to 4.1 mm2) after
the angioplasty procedure. Clinical, hemodynamic, and angiographic characteristics immediately after
PTCA were not predictive of MCSA of the lumen at follow-up. Because substantial late increases in
MCSA of the lumen occur in about one-third of patients, angiographic and noninvasive analyses
performed immediately after PTCA will not define the ultimate adequacy of coronary dilation in many
patients undergoing PTCA.
Circulation 73, No. 3, 467-475, 1986.
±
PERCUTANEOUS transluminal coronary angioplasty
(PTCA) has gained wide clinical acceptance as a treatment for coronary artery disease.1' 2 Despite widespread use, however, neither the mechanisms responsible for the initial coronary luminal enlargement
From The Cardiovascular Center, The Cardiovascular Image Processing and Ultrasonic Imaging Laboratories, and Departments of Internal Medicine, Electrical and Computer Engineering, and Radiology
University of Iowa and Iowa City Veterans Administration Medical
Center, Iowa City.
Supported by National Institutes of Health grants HL27633,
HL29976, HL00916, HL14388, HL32295 (Specialized Center of Research in Ischemic Heart Disease), and HL01290 (Research Career
Development Award, Dr. Skorton), and the U.S. Veterans Administration grant MRIS 1100.2.
Address for correspondence: Maryl Johnson, M.D., Cardiovascular
Division, Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA 52242.
Received July 1, 1985; revision accepted Oct. 3, 1985.
Vol. 73, No. 3, March 1986
produced by PTCA nor the factors that determine the
duration of the increase in the size of the lumen are
well understood.
Previous angiographic follow-up studies have
shown that restenosis occurs in approximately onethird of initially successful dilations.3 Visual estimates of percent stenosis have also suggested that in
some cases a further increase in size of the lumen may
occur in the 6 months after PTCA.' 6,7 The significance of such observations based on percent stenosis is
uncertain for several reasons. First, estimates of percent stenosis are associated with a high degree of interobserver variability." Second, measurements of percent stenosis correlate poorly with size of the lumen
and physiologic significance of the lesion.'2 '4 Third,
immediately after angioplasty, the dilated coronary
467
JOHNSON et al.
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segment has a shaggy or rough appearancel 15 and luminal borders may be difficult to define. Finally, assessing changes in size of the lumen with the use of
percent stenosis after angioplasty may be especially
difficult since balloon dilation may change the adjacent "tnormal" segment as well the stenotic segment. 16
In this study we used two computer-assisted methods of angiographic analysis - quantitative coronary
angiography and videodensitometry - to quantify the
changes in cross-sectional area of the coronary lumen
that occur during and after angioplasty. Such quantitative studies of dilated lesions may help elucidate the
mechanism of continued symptom relief in most patients after PTCA. In addition, if quantitative angiographic characteristics of the lesion immediately after
angioplasty or changes in size of the lumen from before to immediately after PTCA predict the course of
the patient during follow-up, perhaps the need for follow-up coronary angiography to detect asymptomatic
restenosis could be obviated. Quantitative coronary
angiography was selected since it has low interobserver variability and provides an absolute measure of
the cross-sectional area of the vessel.'17 18 Such absolute measures of luminal area correlate with the physiologic significance of coronary stenoses.'3 Videodensitometric analysis was selected as a nongeometric
approach that is not based on the assumptions inherent
to quantitative coronary angiography. During videodensitometry, x-ray transmission through the contrastfilled coronary artery provides an index of size of the
lumen that is independent of its shape.'9 Therefore, the
videodensitometric method is not directly dependent
on precise operator definition of vessel edges and may
be particularly appropriate for evaluating lesions immediately after PTCA when vessel edges may be indistinct and the shape of the lumen may be irregular.
Videodensitometric analysis of coronary lesions is reproducible, and the results of videodensitometric analysis correlate with size of the coronary lumen and with
the physiologic significance of the lesion.20 21
Methods
Patient population. Between June 1981 and September
1982, 47 patients underwent single-vessel angioplasty at the
University of Iowa. The lesion was successfully dilated in 30 of
the 47 cases (64%). All patients with successful angioplasties
were asked to return for routine follow-up coronary angiography at 6 months. Twenty-five patients (83%) did so. Twentythree of these patients, restudied at 7.2 + 3.0 (mean + SD)
months after angioplasty, had high-quality initial and follow-up
angiograms that were adequate for analysis by quantitative
coronary angiography. Thus, 23 patients form the basis of this
report. The angiograms of 18 of these patients were also technically suitable for videodensitometric analysis.
468
PTCA protocol. The investigational protocol and consent
forms were approved by the institutional review committee of
the University of Iowa and written informed consent was obtained from each patient before angioplasty.
Pharmacologic therapy. For 24 to 48 hr before PTCA, patients were treated with 325 mg aspirin every 8 hr, 75 mg
dipyridamole every 8 hr, and 10 mg nifedipine every 8 hr
(minimum dose). Whenever possible /3-blocker therapy was
tapered over the same period and discontinued at least 6 to 12 hr
before the procedure. During the angioplasty procedure, all
patients received 200 to 500 ml 10% Dextran in normal saline
by infusion and nitroglycerin sublingually and/or by the intracoronary route (average dose 1.0 + 0.1 mg, mean + SEM).
Eighteen of the 23 patients were also treated with sublingual
nifedipine (average dose 14.4 + 1.7 mg). Intravenous nitroglycerin was administered to one patient during the procedure.
Nifedipine, aspirin, and dipyridamole were continued during
the follow-up period. l3-Blocker therapy was resumed at the
time of hospital discharge.
Follow-up angiograms were performed after sublingual and/
or intracoronary nitroglycerin in 22 of the 23 patients (average
dose 0.6 + 0.1 mg). Two patients received sublingual nifedipine and one patient received intravenous nitroglycerin at the
time of follow-up angiography.
Coronary angiography. Coronary angiography was performed by the percutaneous femoral technique described by
Judkins.22 Angiograms were obtained in multiple single-plane
projections with the use of a Siemens angioscope with a 7 inch
cesium iodide image intensifer. The angiograms were recorded
on 35 mm film at 60 frames/sec. Projections were selected so
that orthogonal right anterior oblique (RAO) and left anterior
oblique (LAO) views of the vascular segmpent containing the
lesion were available for analysis. Film processing was carefully controlled.
Measurement of intracoronary pressures and lesion gradients. Arterial pressure measurements were made with a contrast-filled diagnostic or guiding coronary catheter immediately
before contrast injections. The mean pressure gradient across
the stenosis was measured before and after completion of angioplasty with the guiding catheter and the angioplasty catheter,
both of which were filled with contrast.
Angioplasty techniques. All dilations were performed with a
USCI DG or G 20-30 balloon and were done before the availability of steerable catheter systems. An average of four dilations per procedure were used. Dilation pressures ranged from 2
to 9 atmospheres, with the average inflation time being 20 sec.
Quantitative coronary angiography. The Brown-Dodge
system of quantitative coronary angiography'7 18 was used to
define absolute minimal coronary cross-sectional area in the
vicinity of the dilated lesion. Data from two orthogonal midcycle cine frames was entered into the computer and the absolute
minimal cross-sectional area of the vascular segment was determined automatically by the computer program. 17 This analytic
procedure was repeated for each of three consecutive paired
orthogonal angiographic frames of lesion segments before
PTCA, immediately after PTCA, and at follow-up. The average
value of the determinations of minimal cross-sectional area
from the three sets of frames at each angiographic study was
then calculated and reported as the lesion minimal cross-sectional area. The size of the inflated dilating balloon at an average inflation pressure was similarly determined with quantitative coronary angiographic techniques.
The reproducibility of quantitative coronary angiographic
measurements of minimal cross-sectional area of the coronary
lumen in the study population was defined by having two independent observers perform the analysis on each pre-PTCA,
immediate post-PTCA, and follow-up angiogram.
CIRCULATION
THERAPY AND PREVENTION-PTCA
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Videodensitometric analysis. Videodensitometric analysis
was performed as previously described.20 Individual cine
frames were digitized with a Vanguard cine film transport, the
projected image of which was coupled through selectable optical lenses to a high-quality vidicon camera (Cohu model 8000).
Prior to digitizing cine frames, calibration data relating mean
gray level (digitized value) and optical density of the film were
measured using a Kodak gray level step-wedge with 21 optical
density levels. These data were entered into the computer, and a
continuous calibration curve was calculated by use of linear
interpolation between measured data points. Individual cineangiographic frames were then digitized at a magnification of 3.7
into a 512 x 512 pixel matrix with eight-bit (256 levels) graylevel resolution. The digitized images were displayed on a video
monitor and an operator-interactive program was used to perform the videodensitometric analysis. The length of the segment
of the vessel to be analyzed was identified by the operator. The
computer then calculated and displayed a gray-level profile
perpendicular to the axis of the vessel at the defined segment of
interest. Using the plotted profile as an aid, the operator then
identified the vessel borders as well as background regions on
both sides of the vessel. The gray-level profile for each lesion
was converted to an optical density profile with the use of the
previously determined calibration curve. The optical density for
each point on the profile within the vessel was corrected for the
optical density of the corresponding background, and an integrated optical density value for the vascular segment of interest
was obtained by summing the resultant optical densities over all
points within the vessel. This value for integrated optical density was reported in optical density units. Under certain assumptions,23 integrated optical density is proportional to cross-sectional area of the lumen. We have previously found that values
of integrated optical density determined in this way have good
intraobserver (r = .98) and interobserver (r = .87) reproduc-
ibility.21
Statistical methods. Except as otherwise noted, values are
expressed as mean + SEM. Interobserver variability for quantitative coronary angiographic analysis was defined in two ways.
First, we calculated the average percent variability between
values of minimal cross-sectional area determined by the two
observers. Second, we defined the mean absolute variability (in
mm2) for all lesions analyzed by both observers. Interobserver
variability before PTCA, immediately after PTCA, and at follow-up were compared by analysis of variance (ANOVA).
Variability at the different times was also compared by use of
confidence intervals of the calculated sample variance of the
differences. Hemodynamic data for the patient groups before
PTCA, immediately after PTCA, and at follow-up were analyzed by ANOVA and Duncan's multiple-range test. Quantitative coronary angiographic and videodensitometric data from
the pre-PTCA, post-PTCA, and follow-up angiograms were
also analyzed by ANOVA and Duncan's multiple-range test.
Linear regression analysis was used to compare results obtained
with quantitative coronary angiography to those obtained with
videodensitometric analysis.
Results
Patient population. The study group included 16 men
and seven women with a mean age of 53.3 ± 1.9
years. The mean duration of angina before PTCA was
7.6 + 2.7 months. The group included 15 patients
who underwent PTCA of the left anterior descending
coronary artery, six who underwent PTCA of right
coronary artery, and two who underwent PTCA of the
Vol. 73, No. 3, March 1986
circumflex artery. The clinical indication for angioplasty was stable angina in 10 (43%), unstable angina
in six (26%), and severe residual stenosis after myocardial infarction in seven (30%). Thirteen patients
(57%) had recurrent chest pain believed to be compatible with angina before follow-up angiography. This
recurrent pain was mild in three patients and moderate
in 10 patients. At the time of angiographic follow-up,
19 patients were still taking one or more antianginal
drugs (nitrates in 14 patients, calcium-channel
blockers in nine patients, and /3-blockers in nine patients). Other clinical features of the patient population
included diabetes mellitus in one (4%), hypertension
TABLE 1
Minimal cross-sectional areas of coronary lesions before PTCA,
immediately after PTCA, and 6 months after PTCA
MCSA (mm2)
Patient No.
Group A (n 8)
1
2
3
4
5
6
7
8
Mean
+SEM
Group B (n 7)
9
10
11
12
13
14
15
Mean
-+SEM
Group C (n -8)
16
17
18
19
20
21
22
23
Mean
+ SEM
Before
After
Vessel
PTCA
PTCA
Follow-up
LAD
RCA
LCX
LAD
RCA
LAD
RCA
RCA
1.43
1.03
1.28
0.45
1.15
1.53
1.27
0.64
1.08
0.13
1.57
2.29
3.24
2.90
1.92
3.85
3.26
2.85
2.74
0.27
1.87
2.80
4.32
3.93
4.70
4.66
7.07
3.37
LAD
LAD
RCA
LAD
LAD
LCX
LAD
0.78
0.70
0.74
1.83
1.36
0.41
0.59
0.92
0.19
2.43
2.37
4.19
4.11
2.74
3.31
2.36
3.07
0.30
2.64
1.98
3.73
4.72
2.61
3.21
1.98
2.98A
0.37
LAD
LAD
LAD
LAD
LAD
LAD
LAD
RCA
1.57
0.88
0.86
0.58
0.97
1.56
1.41
1.12
1.12
0.13
2.71
5.73
2.63
1.94
3.54
4.65
3.37
5.13
3.71
0.47
2.07
1.05
1.42
0.92
1.49
1.60
1.42
2.98
1.62
0.23
4.09A
0.55
MCSA - minimal cross-sectional area of vessel defined by quantitative coronary angiography; LAD = left anterior descending coronary
artery; RCA = right coronary artery; LCX = left circumflex artery.
Ap < .05 compared with group C at follow-up.
469
JOHNSON et al.
in nine (39%), hypercholesterolemia (greater than 250
mg/dl) in eight (35%), and a history of smoking in 15
(65%).
Quantitative coronary angiography
-
interobserver
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variability. Average interobserver variability was found
to be 41% for the pre-PTCA angiograms and 17% for
the immediate post-PTCA and follow-up angiograms.
The larger percent variability in the pre-PTCA group
reflected the smaller size of the lumen before PTCA
than after PTCA or at follow-up (table 1). When considered in absolute terms, interobserver variability was
similar for the pre-PTCA, post-PTCA, and follow-up
angiograms (0.4, 0.6, and 0.6 mm2, respectively; p =
NS by ANOVA). The confidence intervals for interobserver variability were not different immediately after
PTCA compared with at follow-up.
Patient subgroups. Patients were divided into three
groups based on the change in minimal cross-sectional
area of the coronary lumen from the angiogram obtained immediately after PTCA to the angiogram obtained at follow-up. Changes greater than those due to
our average percent interobserver variability (±+ 17%)
were considered significant for the purpose of defining
the groups. The three groups thus defined were as
follows: group A (n = 8), patients with a significant
increase in minimal cross-sectional area of the coronary lumen during follow-up; group B (n = 7), patients with no significant change in minimal crosssectional area of the coronary lumen during follow-up;
group C (n = 8), patients with a significant decrease in
minimal cross-sectional area of the coronary lumen
(i.e., restenosis) during follow-up.
Groups A, B, and C did not differ with respect to
age, duration of angina before PTCA, history of smoking, or incidence of diabetes mellitus, hypertension, or
hypercholesterolemia. Although there were no significant differences in nitroglycerin or nifedipine therapy
among the groups at the time of angioplasty or at
follow-up, patients in all groups received more vasodilator therapy during the PTCA procedure than at the
follow-up catheterization.
Table 2 lists the hemodynamic measurements made
at the time of PTCA and at the follow-up catheterization. The transstenotic gradient before and immediately after PTCA, as well as the change in gradient from before to immediately after PTCA, did not
differ significantly between the groups. The mean
aortic pressure immediately after PTCA and at followup did not differ between the groups. Similarly,
for groups A, B, and C the mean aortic pressure was
not significantly different immediately after PTCA
than at follow-up. Seventy-five percent of group A
470
TABLE 2
Hemodynamic measurements at PTCA and follow-up
Transstenotic gradient
(mm Hg)
Before PTCA
After PTCA
Mean aortic pressure
(mm Hg)
After PTCA
Follow-up
Ap
=
Group A
Group B
Group C
54.0±6.5
22.2±6.7
49.0±6.5
15.0±5.3
46.0±4.5A
11.1 ±3.0A
70.0±6.5
79.9±4.8
78.8±4.4
81.0±7.0
64.0±4.1A
72.9±2.9A
NS, group A vs group B vs group C.
patients, 38% of group B patients, and 50% of group C
patients had complaints of chest pain before follow-up
angiography.
Characteristics of coronary lesions - quantitative coro-
nary angiography. Table 1 shows the minimal crosssectional areas of the dilated coronary arterial segments before PTCA, immediately after PTCA, and at
follow-up for the groups. Groups A, B, and C did not
differ significantly with respect to mean size of the
lumen before PTCA, mean size immediately after
PTCA, or the change in size from before to immediately after PTCA. Thus, immediate results were comparable in the three patient groups. At follow-up, size of
the coronary lumen was significantly greater in groups
A and B than in group C (p < .05).
Figure 1 shows the individual values for minimal
cross-sectional area of the lumen before PTCA, immediately after PTCA, and at follow-up for group A patients (n = 8), the patients who showed an increase in
minimal cross-sectional area of the lumen during the
follow-up period. Figure 1 also shows the cross-sec-
8
6
Minimal
CrossSectional
Area
4
(mm2)
2
0
Before
PTCA
Follow
Inflated
Balloon
FIGURE 1. Vessel minimal cross-sectional areas for group A patients
before PTICA, immediately after PTCA, and at follow-up. Also shown
for reference is the cross-sectional area of the inflated dilating balloon as
Immediately
After PTCA
up
defined by quantitative coronary angiography.
CIRCULATION
THERAPY AND PREVENTION-PTCA
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tional area of the inflated angioplasty balloon used in
these patients as determined by quantitative coronary
angiography (6.9 mm2). In this patient group, the minimal cross-sectional area of the lesion was 2.74 ± 0.27
mm2 immediately after angioplasty. Minimal crosssectional area of the lesion had increased an average of
49% by the time of the follow-up study (to 4.09 +
0.55 mm2). In three of the patients, the increase in size
of the lumen during follow-up was greater than the
increase in size from before to immediately after angioplasty. In all of the patients, however, size of the
lumen immediately after angioplasty was significantly
less than the cross-sectional area of the inflated dilating
balloon. The mean minimal cross-sectional area of the
dilated segment in group A patients immediately after
PTCA was 40% of the cross-sectional area of the inflated dilating balloon. This increased to 59% of the
cross-sectional area of the inflated dilating balloon
during follow-up. The cross-sectional area of the dilated segment at follow-up was similar to the size of the
inflated dilating balloon in only one patient.
Characteristics of coronary lesions - videodensitometric
analysis. Eighteen of the patients had initial and followup angiograms that were analyzed by videodensitometric analysis. As shown in figure 2, the results of
videodensitometric analysis performed on these angiograms correlated well with results of quantitative coronary angiography (r - .77). The changes in size of the
coronary lumen in patients in group A (figure 3), group
B (figure 4), and group C (figure 5) were similar
whether defined by videodensitometric techniques or
quantitative coronary angiography. Using videodensitometric techniques, we again found no significant
Quantitative Coronary
Angiography
6
Minimal
CrossSectional
Area
(MM2)
4
2
0
Before Immediately Follow
up
PTCA After PTCA
Videodensitometry
20
-*
15
Integrated
Optical 10
Density
5
0
Before Immediately Follow
PTCA After PTCA
up
FIGURE 3. Coronary lumen sizes for group A patients before PTCA,
immediately after PTCA, and at follow-up, defined by quantitative
coronary angiography (top) and videodensitometry (bottom). *p < .05
compared with integrated optical density immediately after PTCA.
8
differences in lumen size before PTCA or immediately
after PTCA between the groups, confirming that the
immediate results of angioplasty were the same in all
groups. At follow-up, integrated optical density, an
index of cross-sectional area of the lumen, was significantly greater in groups A and B than in group C (p <
.05). Two of the five group A patients in whom videodensitometric analysis was performed showed evidence of an increase in area of the lumen during follow-up that was greater than the increase in area from
before to immediately after PTCA. Thus, our data,
obtained by two methods of quantitative angiographic
analysis, illustrate the variable outcome of dilated lesions during follow-up despite similar results immediately after PTCA.
FIGURE 2. The relationship between integrated optical density (defined by videodensitometric analysis and reported in optical density
units) and minimal cross-sectional area of the lesion (defined by quantitative coronary angiography) for pre-PTCA, post-PTCA, and follow-up
angiograms of 18 patients.
Discussion
There is considerable evidence, in addition to subjective angiographic findings, that PTCA represents an
effective treatment for selected coronary stenoses.
This evidence includes decreased transstenotic gradi-
25
20
15
Integrated
Optical
Density 10
A
5
r=0.77
n=54
~
0
l
0
'AI
-
l
l
l
7
4
5
1
2
6
3
Minimal Cross-Sectional Area
(mme
Vol. 73, No. 3, March 1986
471
JOHNSON et al.
6
Quantitative Coronary
Angiography
N=7
Minimal
Cross Sectional
Area
(mm2)
4
~r
2
0
20
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Integrated
Optical
Density
---
1,~~~
1
Before Immediately Follow
PTCA After PTCA
up
Videodensitometry
N=6
15
*1*
10
rt~~~--
5
0
5
a
5
i
Before Immediately Follow
up
PTCA After PTCA
FIGURE 4. Coronary lumen sizes for group B patients before PTCA,
immediately after PTCA, and at follow-up, defined by quantitative
coronary angiography (top) and videodensitometry (bottom). 'p = NS
compared with integrated optical density immediately after PTCA.
ents, ' improved symptomatic and electrocardiographic
response to exercise,24 fewer myocardial perfusion defects on thallium-201 scintigraphy,24 25 improved left
ventricular diastolic filling velocity,26 and normalization of exercise-induced wall motion abnormalities on
the radionuclide ventriculogram.27' 28 This study provides additional objective documentation of the results
of angioplasty by defining in absolute terms, using two
methods of computer-assisted analysis of coronary angiograms (quantitative coronary angiography and videodensitometry), the change in area of the lumen that
occurs during and after angioplasty.
In this study, as in previous studies,3-' we found that
approximately one-third of lesions (35% in our study)
restenose during the follow-up period. Importantly,
however, 35% of our patients (group A) showed a late
increase in area of the lumen over the period of followup. Indeed, the amount of increase in lumen area during follow-up was substantial, in three cases surpassing the change in area from before to immediately after
angioplasty. This late increase in lumen area in onethird of the patients after dilation is particularly intrigu472
ing since studies of the natural history of untreated
atherosclerotic lesions using quantitative coronary angiography have shown that only 4% of lesions spontaneously regress during a similar time period.'8
Although computer-assisted quantitative coronary
angiography is of greater reliability and accuracy than
visual angiographic estimates, this technique nonetheless relies on drawing of vessel borders from an unenhanced cineangiographic image. Casual inspection
suggests that detection of the coronary lesion edge
may be especially problematic immediately after
PTCA when the vessel edge is indistinct." '1 However,
in our study the interobserver variability immediately
after PTCA was the same as that at follow-up, suggesting that edge definition, at least with the high-quality
and greatly magnified angiograms on which we performed quantitative coronary angiography, may not
represent a greater problem immediately after PTCA
than at other times. In the future, the development of
digital image acquisition and newer computer techniques of edge detection and enhancement may minimize any border recognition difficulties that do exist.
Quantitative Coronary
Angiography
6
Minimal
Cross-
Sectional
Area
(mm2)
N=8
4
2
0
m
a
.
I
a
-F
--1ma
Before Immediately Follow
PTCA After PTCA
up
20
Integrated
Optical
Density
Videodensitometry
15
10
5
0
Before Immediately Follow
PTCA After PTCA
up
FIGURE 5. Coronary lumen sizes for group C patients before PTCA,
immediately after PTCA, and at follow-up, defined by quantitative
coronary angiography (top) and videodensitometry (bottom). t p = NS
compared with integrated optical density immediately after PTCA.
CIRCULATION
THERAPY AND PREVENTION-PTCA
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For the present, however, the agreement seen between
results obtained by quantitative coronary angiographic
analysis and those obtained by videodensitometric
analysis, a procedure that depends less on exact definition of vessel edges, strengthens the conclusions of our
study.
We found no differences in hemodynamic, quantitative angiographic, or videodensitometric characteristics of coronary lesions in the three patient subgroups
before or immediately after angioplasty. Specifically,
the transstenotic pressure gradient, the minimal crosssectional area, and the integrated optical density of the
lesion before and immediately after angioplasty did not
significantly differ among the three groups in which
there were markedly disparate late outcomes. The
change in size of the lumen during follow-up also
could not be predicted by the presence or absence of
recognized coronary risk factors. We noted a similar
incidence of recurrent chest pain among patients in all
groups, despite the fact that the average minimal crosssectional area of the lesion at follow-up was significantly greater in groups A and B than in group C. The
reason for recurrent chest pain in group A and B patients despite the preservation of size of the coronary
lumen is unclear, but could relate to the activity level
of the patient, to vasospasm, or to the lack of a suitable
functional assessment of coronary vasodilator reserve.
Of more concern is the absence of angina in 50% of
group C patients despite significant restenosis - restenosis that could be treated with repeat PTCA but
that was not clinically apparent before routine followup angiography. Thus, we found no clinical or quantitative angiographic characteristics that could predict
the late outcome of a patient with a successfully dilated
coronary segment.
Mechanism of dilation in PTCA. Despite evidence of
decreased lesion severity and improved myocardial
perfusion after PTCA, there is not widespread agreement regarding its underlying mechanism. Initially it
was assumed that simple compression of atheroma resulted in an immediate increase in lumen size.29 Subsequent experimental evidence suggested focal intimal
fractures30' 31 and overstretching of elastic fibers in the
vessel wall32 as possible mechanisms. Our finding that
the cross-sectional area of dilated lesions immediately
after PTCA is less than the cross-sectional area of the
inflated balloon suggests that vascular stretching occurs during dilation that is followed by elastic recoil.
However, the fact that one-third of successfully dilated
lesions show a substantial further increase in size of the
lumen during late follow-up without further balloon
inflations shows that vascular stretching is not the only
Vol. 73, No. 3, March 1986
mechanism of improvement after PTCA. If the effects
of angioplasty were related only to vascular stretching
and the magnitude of the lumen area achieved after
balloon removal, we would expect that the area would
remain unchanged during late follow-up (as occurred
in 30% of our patients), or perhaps show evidence of
restenosis (if the atherosclerotic process continued or
were accelerated). Late improvement in size of the
lumen is thus unexpected. We speculate that two
mechanisms may be involved. First, coronary vasospasm may occur in some patients immediately after
dilation, despite the use of vasodilating agents. The
late increase in cross-sectional area of the lumen at
follow-up would then represent resolution of spasm at
the site of dilation. Second, pathologic studies have
indicated that fracture of intimal plaque often occurs at
the time of successful dilation.30' 31 During the followup period, retraction of the intimal flap with fibrosis
and endothelial healing could result in an increased
lumen size33 if excessive platelet deposition or accelerated atherosclerosis did not occur.
Quantitative analysis of coronary stenoses. Serruys et
al.34 have also used quantitative angiographic and videodensitometric techniques to analyze coronary lesions before and after angioplasty. However, these
authors emphasized lesion analysis with the use of
percent stenosis and diameter measurements rather
than absolute cross-sectional area of the lumen. Although of importance in understanding the physiologic
significance of coronary stenoses in general,12' 13 calculation of the minimal cross-sectional area of lesions
after PTCA is especially critical. The relationship between the position of the lesion and the dilating balloon
during angioplasty is often imprecise. Since multiple
dilations in slightly varying positions are usually performed, late changes in percent stenosis may reflect
changes in the dilated lesion, the adjacent dilated "normal" segment, or both. We have previously shown that
significant changes in the cross-sectional area of the
adjacent "normal" segment occur during late followup.16 Therefore, it is likely that only an absolute measurement of coronary cross-sectional area can yield
quantitative information regarding progression or regression of the dilated lesion during follow-up.
Limitations of the study. There are several potential
limitations of this study. First, the sample size was
small and represented our initial experience with angioplasty. Despite the small sample size, however, the
series was consecutive and a high proportion of patients (83%) returned for follow-up angiograms. Although steerable catheter systems have increased the
primary success rate of angioplasty, we have no reason
473
JOHNSON et al.
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to postulate that this would have exerted a major influence on the late outcome after PTCA. Changes in
dilation parameters (either inflation pressure or duration) could influence the results, but these changes
have not influenced the restenosis rate, and thus would
be unlikely to alter our results.
There were major differences in the drugs the patients received at the time of the two catheterizations.
Vasodilators were used more frequently and in larger
doses during the dilation procedure than at the time of
follow-up angiography. This does not, however, preclude the possibility of angioplasty-induced vasospasm immediately after PTCA, with subsequent release of vascular tone over time. Indeed, if vasodilator
therapy had been comparable during PTCA and at follow-up, minimal areas of the lumen at follow-up may
have been even larger, resulting in more patients in
groups A and B and fewer in group C.
Clinical implications. Our findings may be clinically
important in the management of patients after PTCA.
Because stenosis resistance is primarily dependent on
the fourth power of the radius of the lesion at its narrowest point, even a small late change in area of the
lumen may result in a change in coronary flow sufficient to alter a patient's symptomatology or objective
evidence of ischemia. Thus, the adequacy of coronary
dilation should not be judged solely on immediate
changes in the gradient or angiographic appearance, or
even on the minimal cross-sectional area of the dilated
lesion immediately after PTCA. Our results also indicate that noninvasive tests performed soon after PTCA
(e.g., graded exercise testing, myocardial scintigraphy, and exercise-gated radionuclide ventriculography) should be interpreted cautiously with regard to
predicting the long-term success of the dilation. Since
neither the hemodynamic nor the angiographic characteristics of the lesions immediately after PTCA nor the
clinical characteristics of the patients during follow-up
seem to be able to predict restenosis, at the present
time a follow-up angiographic study appears to be
needed in most instances.
Finally, our results confirm a variable late outcome
after initially successful PTCA - an outcome that may
be susceptible to manipulation by improved angioplasty techniques or the use of pharmacologic agents.
Controlled trials of different dilation techniques, as
well as of antiplatelet agents and other therapies that
might minimize restenosis, with quantitative angiographic follow-up are needed to further investigate
these possibilities.
We thank Janice Ripley and Kyle Snowden for technical
assistance and Jill Christy for preparation of the manuscript.
474
Data analysis was performed with "Clinfo" (supported by grant
RR59 from the Clinical Research Centers Branch, NIH).
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475
Changes in cross-sectional area of the coronary lumen in the six months after
angioplasty: a quantitative analysis of the variable response to percutaneous transluminal
angioplasty.
M R Johnson, G P Brayden, E E Ericksen, S M Collins, D J Skorton, D G Harrison, M L
Marcus and C W White
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Circulation. 1986;73:467-475
doi: 10.1161/01.CIR.73.3.467
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