(Circulation. 1995;92:2446-2456.)
© 1995 American Heart Association, Inc.
Articles |
Progression and Regression of Coronary Stenosis in the Long-term Follow-up of Vasospastic Angina
From the Catheterization Laboratory, Department of Interventional Cardiology, Thoraxcenter, Erasmus University, Rotterdam, the Netherlands.
Correspondence to Patrick W. Serruys, MD, PhD, FESC, FACC, Professor of Interventional Cardiology, Thoraxcenter, Erasmus University, PO Box 1738, 3000 DR Rotterdam, Netherlands.
 |
Abstract |
|---|
 Top Abstract IntroductionMethods Results Discussion References |
|---|
Background Whether focal vasospasticity plays a pathogenic role in the progression or regression of coronary atherosclerosis is unknown. To determine whether evidence for such a role exists, we studied long-term changes in coronary luminal measurements in patients with vasospastic angina.
Methods and Results Quantitative coronary angiography and
repeated ergonovine provocation tests were performed 45±16 months
apart in 30 patients. All patients had vasospastic anginal symptoms and
coronary spasm on the initial provocation test. Of the 30
patients, 16 had persistent symptoms of vasospastic angina and showed
coronary spasm at the same site on the follow-up angiogram
(group 1), while the remaining 14 whose vasospastic anginal symptoms
disappeared at follow-up demonstrated a negative response to
ergonovine on the follow-up tests (group 2). There was no
significant difference in patients' baseline characteristics between
the two groups. Long-term changes in minimal (MLD) and mean (MEAN)
luminal diameter were measured (in millimeters) after administration of
isosorbide dinitrate in 19 spastic and 93 nonspastic segments in group
1 and in 17 previously spastic and 81 nonspastic segments in group 2.
Both MLD and MEAN were measured in 210 coronary segments of the
30 patients at baseline and after administration of ergonovine and
isosorbide dinitrate by use of a computer-based quantitative
coronary angiography system. Stenosis progression and
regression of individual lesions were defined as a change in MLD of
0.40 mm. In group 1, both the MLD and MEAN of 19 spastic segments
were significantly smaller (progression) at follow-up compared with
the initial angiogram (MLD, 2.21±0.54 initially versus 1.95±0.65
at
follow-up, P<.01; MEAN, 2.80±0.56 initially versus
2.56±0.58 at follow-up, P<.01), whereas the MLD and
MEAN of 93 nonspastic segments in group 1 were not significantly
different between the initial and follow-up angiograms (MLD,
2.47±0.67 initially versus 2.44±0.69 at follow-up,
P=NS; MEAN, 2.96±0.69 initially versus 2.91±0.68
at
follow-up, P=NS). In group 2, the MLD of the 17
previously spastic segments significantly improved (regression) at
follow-up (MLD, 1.99±0.68 initially versus 2.24±0.54 at
follow-up, P<.05); the MLD and MEAN of the 81
nonspastic segments were not significantly different (MLD, 2.36±0.59
initially versus 2.39±0.60 at follow-up, P=NS; MEAN,
2.81±0.58 initially versus 2.81±0.61 at follow-up,
P=NS). In group 1, significant stenosis progression
of individual lesions was observed more frequently at spastic than
nonspastic segments (6 of 19 versus 10 of 93, P<.05),
whereas stenosis regression was observed in no spastic and 3
nonspastic segments (P=NS). In group 2, stenosis
progression was observed at 1 previously spastic segment and 4
nonspastic segments (P=NS), while significant
stenosis regression of individual lesions was seen more
commonly in previously spastic than nonspastic segments (6 of 17 versus
7 of 81, P<.01).
Conclusions These results have demonstrated in patients an association between persistent vasospastic activity and progression of atherosclerosis and an association between cessation of vasospastic activity and regression of atherosclerosis.
Key Words: atherosclerosis • vasospasm • angina • coronary spasm • tests • angiography
|
Introduction |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
Progression or regression of coronary atherosclerosis is of prognostic importance in patients with angina pectoris in the determination of risk of MI and sudden cardiac death.1 2 3 4 5 6 7 8 9 10 The primary role of coronary spasm in vasospastic angina11 12 13 14 15 16 17 18 19 and certain categories of MI20 21 22 23 is established. Although it has been known for decades that coronary spasm frequently occurs at sites of significant atherosclerosis,11 14 15 16 20 21 24 it has not yet been determined whether vasospasm plays a role in the progression or regression of atherosclerosis.
Attempts in previous experimental and clinical studies to indirectly detect a possible link between spasm and acceleration of atherosclerosis have provided conflicting circumstantial evidence. In an animal model, severe coronary spasm was found by Nagasawa et al25 and Kuga et al26 to induce intimal hemorrhage and intimal thickening and eventual rapid progression of fixed stenosis; however, no such results have been found in humans. In a single patient, Marzilli et al27 reported rapid progression of coronary atherosclerosis at a site of previous spasm, while in a study of 10 patients with variant angina, Kaski et al28 found that stenosis progression at the spastic site was rare (only 1 patient) despite the persistence of vasospastic activity in all patients.
To determine whether focal vasospastic activity over several years in human coronary arteries is linked with the progression or regression of local atherosclerosis, we compared the chronological changes in MLD and MEAN of the AHA coronary segment in patients with persistent symptoms of vasospastic angina with those of patients with vasospastic angina whose symptoms resolved over a follow-up period of 45 months. We used a computer-based coronary angiographic analysis system (CAAS II) to make this comparison.
|
Methods |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
Criteria of Vasospastic Angina
The following criteria of vasospastic angina were used: (1) chest pain at rest associated with ST-segment changes of >0.2 mV on ECG, (2) pain relief immediately after the administration of nitroglycerin, (3) no subsequent evidence of MI, and (4) ergonovine-provoked coronary spasm associated with chest pain and ischemic ECG changes. Coronary spasm was defined as a transient total or near-total occlusion reversible with isosorbide dinitrate or as a transient significant (>50%) narrowing reversible with isosorbide dinitrate in normal or nearly normal segments.29 30 31 We used the ergonovine provocation test because it has been found to have high sensitivity and specificity and short-term reproducibility of spontaneous angina attacks in patients with vasospastic angina.32 33 34
Study Population
To determine the relation between long-term
focal
vasospasticity and the progression of atherosclerosis,
we compared the progression of atherosclerosis in 16
patients with persistent vasospasm at a constant coronary
location with that in 14 patients in whom vasospastic angina completely
resolved. The study population was selected from a total of 44 patients
with variant angina who had undergone long-term angiographic and
ergonovine provocation follow-up.
Of the 44 patients who had chest pain at rest with ischemic ST-segment changes at the time of the initial angiographic study, vasospastic anginal symptoms were persistent during the follow-up period in 29, while in the remaining 15 patients, symptoms of vasospastic angina resolved during follow-up. Of the 29 patients, 13 did not demonstrate vasospasticity at the same site on the initial and the follow-up angiograms. In these 13 patients with a change in location in vasospasticity, it was not possible to determine exactly when vasoconstriction started at the new site or when vasospasm ceased at the previous spastic location; therefore, they were excluded from the study. Of the 29 patients, 16 had persistent symptoms of vasospastic angina with ischemic ST-segment changes during the follow-up period, and vasospasm was reproduced at the identical coronary site at the follow-up angiogram (group 1). Of the 15 patients, 1 showed vasoconstriction at the follow-up angiogram despite a complete absence of clinical symptoms. Because this patient did not have anginal pain during follow-up, which had been observed previously at the initial test, it was not possible to determine whether long-term vasospastic activity had persisted throughout the follow-up period or whether the patient had simply retained hypersensitivity to ergonovine; therefore, this patient was excluded from the study. In the remaining 14 patients, symptoms of vasospastic angina disappeared completely, and neither ischemic evidence on ECG monitoring nor positive response to ergonovine was demonstrated during the follow-up period (group 2).
Basal Clinical Characteristics
Tables 1
and
2 give the clinical
characteristics of groups 1 and 2, respectively. Specifically, no
significant differences were found between groups 1 and 2 in age (55±8
versus 55±7 years), sex (women, 1 of 16 versus 1 of 14), follow-up
period (45±15 versus 45±18 months), or coronary risk factors
such as smoking, diabetes, hypertension, total cholesterol
level, or HDL cholesterol level at the time of the initial
angiogram or at follow-up (total cholesterol: group 1,
190±35 and 196±37 mg/dL; group 2, 193±33 and
198±36 mg/dL; HDL
cholesterol: group 1, 51±15 and 50±15 mg/dL; group 2,
53±21 and 50±15 mg/dL, initially and at follow-up,
respectively).
Blood pressure was well controlled throughout the follow-up period
in those patients with a history of hypertension. No patient had
insulin-dependent diabetes mellitus, and 2 patients (1 from each
group) had diet-controlled adult-onset diabetes.
|
|
|
Medication
Medication (Tables 1
and
2) consisted of sustained-release
isosorbide dinitrate and a calcium antagonist (diltiazem).
Two patients were maintained on an additional calcium
antagonist (nicorandil). Four patients took an additional
calcium antagonist (nifedipine) for a short
period only. The average doses of calcium antagonist
(diltiazem 218±30 mg/d) and sustained-release isosorbide dinitrate
(59±5 mg/d) in group 1 were significantly higher than in group 2
(diltiazem 189±18 mg/d, isosorbide dinitrate 53±10 mg/d) because
of
persistent symptoms of vasospastic angina in group 1. The medication
was effective in both groups. In group 1, the medication reduced the
frequency of ischemic attacks; however, vasospastic angina
persisted throughout the follow-up period. Waters et
al35 and Previtali et al36 reported that the
response to the ergonovine provocation test is of value in the
prediction of spontaneous activity of vasospastic angina. Thus, we
performed follow-up angiography and ergonovine provocation testing
to detect the progression and regression of coronary
atherosclerosis, to estimate vasospastic activity, and
to provide information on the necessity for long-term medication.
In patients whose symptoms disappeared (group 2), the dose was tapered
or discontinued after the follow-up angiogram.
Anginal Symptoms During Follow-up
The disease activity of
vasospastic angina was assessed by
anginal symptoms, 12-lead ECG during attacks, and ambulatory
in-hospital ECG monitoring or out-of-hospital Holter
monitoring in all patients. Of the 30 patients studied, 29 had
intermittent chest pain with ST-segment elevation and 1 had
intermittent chest pain with ST-segment depression at the time of the
initial angiographic study (Tables 1 and 2).
These attacks were
observed over a period of a few days to several weeks (the
so-called "hot phases" of the disease28 ). In
group 1, over the follow-up period, 10 of the 16 patients had a
second hot phase, 4 had a second and third hot phase, and the remaining
2 did not require readmission for management of a hot phase but
complained of regular anginal symptoms throughout the follow-up
period (Table 1). During the second and third hot phases, all
14
patients required readmission and had ischemic episodes of
ST-segment changes recorded on ambulatory ECG monitoring and/or
resting 12-lead ECG in hospital. Of the remaining 2 patients who did
not experience a second hot phase but had regular variant anginal
attacks, 1 showed ST-segment elevation during an exercise test in the
morning, and 1 had ST-segment elevation during out-of-hospital
Holter monitoring. Patients 3 and 10 developed a non–Q-wave MI
(maximal creatinine phosphokinase was more than double but
less than triple the upper limit of the normal range), and patient 13
experienced transient complete AV block during an anginal attack during
the follow-up period. While all group 2 patients underwent 12-lead
ECG recording at follow-up, ambulatory in-hospital ECG
monitoring, and out-of-hospital Holter monitoring, none
experienced either chest pain or a cardiac event during follow-up
(Table 2).
Study Protocol
The study was approved by the hospital's
ethics
committee, and written informed consent was obtained from each patient
before examination. All 30 patients studied were admitted to the
coronary care unit before the study. Sublingual
nitroglycerin was administered as required, but calcium
antagonists and oral nitrate were gradually tapered, and
calcium antagonists were discontinued for 36 hours and oral
nitrate was discontinued for 24 hours before the study.
Coronary angiography was performed in the morning (from 8:30 to
11 AM) by the Sones' technique at Anjo Kosei Hospital,
Anjo, Japan. After baseline angiograms suitable for quantitative
analysis of the right and left coronary arteries had
been obtained, 0.2 mg IV ergonovine maleate was administered by a rapid
bolus injection during the initial and follow-up angiograms.
Radiographic projections were identical during the
sequential angiographic studies. Heart rate and aortic pressure were
monitored continuously, and 12-lead ECGs were recorded at 30-second
intervals. Whenever chest pain or significant ST-segment changes were
observed, selective coronary angiograms were immediately
performed. When coronary spasm was not seen, a further rapid
bolus of up to 0.4 mg ergonovine was
given.16 29 30 35 37
Coronary vasospasm was relieved by isosorbide
dinitrate38 39 40 41 42
given as one or two
intracoronary boluses to a total of 5 mg. To exclude the
possibility of pseudoprogression, we gave a dose (5 mg IC) of
isosorbide dinitrate, which was greater than the dose (3 mg) previously
demonstrated to achieve maximal coronary
vasodilatation in patients with vasospastic
angina.38 39 The follow-up angiogram was performed in
the same angiographic projection as the initial angiogram after the
initial angiographic records and cinefilm were viewed. Then, the
severity of fixed stenoses was quantified in matched views
between the initial and follow-up angiograms by use of the
quantitative angiographic analysis system.
QCA Analysis
The new version of CAAS
II43 44 was
used to perform the quantitative analysis in a core
angiographic laboratory (Cardialysis, Rotterdam, the Netherlands). In
the CAAS analysis, which is described
elsewhere,44 45 46 47 the
entire 18x24-mm cineframe is
digitized at a resolution of 1329x1772 pixels. Correction for
pincushion distortion is performed before analysis. Boundaries
of a selected coronary segment are detected automatically. The
absolute diameter of the stenosis (in millimeters) is
determined with the guiding catheter as a scaling device. To
standardize the method of analysis of the initial and
follow-up angiograms, the following measures were
taken.48 49 All study frames selected for analysis
were end-diastolic to minimize motion artifact.
Arterial segments were measured between the same
identifiable branch points at baseline and after the administration of
ergonovine and isosorbide dinitrate.
Coronary Segments Analyzed
The coronary segments were coded
according to the AHA
system.50 The entire lengths of the major AHA segments of
the RCA, LAD, and LCx were analyzed after administration of
isosorbide dinitrate (AHA segments 1, 2, 3, 6, 7, 11, and 13). Tables
1 and 2 show the sites of coronary spasm in both
groups. The
locations of coronary spasm on the initial and follow-up
angiograms in group 1 were 9 RCA, 4 LAD, and 6 LCx segments; the
locations on the initial angiogram in group 2 were 7 RCA, 8 LAD, and 2
LCx segments.
Criteria of Progression or Regression
Only the absolute
luminal diameter obtained after administration
of isosorbide dinitrate was used to assess progression or regression of
atherosclerosis.51 52 We measured the MLD
and MEAN of AHA coronary segments.50 A difference
greater than twice the SD for repeated measurements of the
CAAS system may represent a true change with
>95% confidence. Because both Waters et al53 and our
group54 recently reported that the SD of repeated
quantitative measurements with the CAAS system of serial
clinical coronary angiograms is 0.20 mm, we therefore accepted
a change in MLD of 0.40 mm as a reliable indicator of the presence of
progression or regression of coronary
atherosclerosis.
Statistical Analysis
A paired Student's t test
was used to compare
chronological changes at the same segment in the same patients.
Unpaired Student's t tests were used to compare the two
study groups. Differences between proportions were analyzed by
the 
2 test with correction. A value of
P<.05 was considered significant.
|
Results |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
Patient Groups
Of the 30 patients studied, 16 had persistent symptoms of vasospastic angina with ischemic ST-segment changes during the follow-up period, and vasospasm was reproduced at the same coronary site at the follow-up angiogram (group 1), while vasospastic angina disappeared completely during follow-up in the remaining 14 patients in whom vasospasm was provoked by ergonovine at the initial angiogram and was not provoked at the follow-up angiogram (group 2).
Response to Ergonovine at Spastic Segments
Fig
1 gives the changes in MLD in the spastic
segments in group 1 at baseline and after the administration of
ergonovine and isosorbide dinitrate on the initial and follow-up
angiograms. At follow-up, no significant change in responsiveness
to ergonovine was seen (spastic response, 1.17±0.47 and
1.07±0.46 mm
initially and at follow-up, respectively; P=NS). Fig
2 gives the changes in MLD in the spastic segments in
group 2 at baseline and after the administration of ergonovine
and isosorbide dinitrate on the initial and follow-up angiograms.
At follow-up, the vasospastic responsiveness to ergonovine was lost
in group 2 (1.00±0.39 and 0.32±0.38 mm initially and at
follow-up, respectively; P<.001).
|
|
Stenosis Progression or Regression: Assessment of
Absolute Values
Both the MLD and MEAN of AHA coronary segments after
the
administration of isosorbide dinitrate were compared (Table 3)
between the initial and follow-up angiograms in
group 1 (19 spastic segments and 93 nonspastic segments) and group 2
(17 previously spastic and 81 nonspastic segments). At the initial
angiogram, no significant differences were observed between groups 1
and 2 in MLD and MEAN values in both spastic and nonspastic segments.
In group 1, both the MLD and MEAN of the 19 spastic segments
significantly decreased (progression) (P<.01 for both) at
the follow-up angiogram, whereas the MLD and MEAN of the 93
nonspastic segments in group 1 were not significantly different between
the initial and follow-up angiograms. In group 2, the MLD of the 17
previously spastic segments significantly increased (regression) at
follow-up (P<.05), whereas the MEAN of the 17
previously spastic segments and both the MLD and MEAN of 81
nonspastic segments in group 2 were not significantly
different between the two angiograms.
|
The changes in luminal diameter
at spastic and nonspastic segments
between the initial and follow-up angiograms are displayed
graphically for group 1 in Fig 3 and for group 2 in Fig
4. In both figures, data points below the line of
identity (dashed line) indicate that the luminal diameters at
follow-up were smaller than at the initial angiogram, while
data points above the line of identity indicate that the luminal
diameters at follow-up were larger than at the initial angiogram.
Whereas data points below the dotted line (0.40-mm decrease in MLD)
indicate significant stenosis progression (0.40-mm reduction
in MLD) in Figs 3 and 4, data points above the
dotted line (0.40-mm
increase in MLD) indicate significant stenosis regression
(0.40-mm increase in MLD) in both figures. In group 1 (Table
1),
significant stenosis progression (0.40-mm reduction in MLD)
of individual stenoses was observed in 6 (32%) of the 19
spastic segments and 10 (11%) of the 93 nonspastic segments
(P<.05), while significant regression (0.40-mm increase
in MLD) occurred in no spastic segments and 3 (3%) of the 93
nonspastic segments (P=NS). In group 2 (Table
2),
progression was observed in only 1 previously spastic and 4 nonspastic
segments (P=NS), and regression of individual
stenoses was observed in 6 (35%) of the 17 previously spastic
segments and 7 (9%) of the 81 nonspastic segments (P<.01).
The remaining segments without significant progression or regression
(13 spastic segments and 80 nonspastic segments in group 1 and 10
spastic segments and 70 nonspastic segments in group 2) were regarded
as stabilized. Fig 5 gives an example of angiographic
evidence of regression of a patient in group 2.
|
|
|
Assessment of Relative Values: Percent Diameter
Stenosis
Tables 1 and 2 give the fixed
percent diameter stenosis of
individual spastic segments at the initial and follow-up angiograms
after administration of isosorbide dinitrate. In patients with
significant fixed stenosis (>50% luminal narrowing), the
location of coronary spasm coincided with the site of
significant fixed stenosis (Tables 1 and 2). In
group 1, at the
initial angiogram none of the spastic segments had significant fixed
stenosis, whereas at follow-up 3 spastic segments had
significant fixed stenosis. In group 2, at the initial
angiogram 3 spastic segments had significant fixed stenosis,
whereas at follow-up no segment had significant fixed
stenosis. Table 4 shows the average percent
diameter stenosis of the spastic and nonspastic segments in
both groups. Although percent diameter stenosis of spastic
segments tended to be more severe at follow-up in group 1
(P=NS), percent diameter stenosis of spastic
segments was less severe at follow-up in group 2
(P<.01). No difference was observed in nonspastic segments
in either group.
|
Caution should be applied, however, in the use of percent diameter stenosis in the study of progression and regression of coronary artery disease in view of the risk of "pseudoregression" as described below in the "Discussion."51 52
|
Discussion |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
The novel findings of this study were as follows. First, angiographic follow-up of the average MLD of the patients with persistent vasospastic angina (group 1) revealed significant progression of coronary artery stenoses in the segments, demonstrating persistent vasospasticity, whereas angiographic follow-up of the patients in whom symptoms of vasospastic angina resolved (group 2) showed significant regression of coronary artery disease in the previously spastic segments. Second, MLD and MEAN of nonspastic segments did not change at follow-up in both groups. Third, significant individual stenosis progression was observed more frequently in spastic than nonspastic segments in group 1. Fourth, significant individual stenosis regression was seen more commonly in previously spastic than nonspastic segments in group 2. These results indicate an association between long-term focal vasospastic activity and local progression and regression of fixed coronary stenoses.
Previous Experimental Studies
In 1981, Gertz et
al55 studied the
endothelial response to partial arterial
constriction (by external ligation to achieve 40% to 60% reduction in
transluminal diameter) in a canine coronary model and a rabbit
carotid model. Scanning electron microscopy revealed
endothelial damage as evidenced by
endothelial craters, fragmentation, desquamation, and
platelet attachment to exposed subendothelial
tissues and microthrombi. Endothelial injury and
platelet activation may be an initiating process of the development
of atherosclerosis, which was again proposed by
Ross56 57 in a revision of the
"response-to-injury hypothesis" in 1986. These findings
may suggest a potential pathophysiological role
for coronary spasm in the development of coronary
atherosclerosis.
Recent studies by Nagasawa et al25 and Kuga et al26 in swine models provide further experimental evidence suggesting that vasoconstriction may be causally related to coronary atherosclerosis. They observed that strong coronary spasm caused histological intramural hemorrhage and intimal thickening, which frequently resulted in rapid progression of coronary atherosclerosis. Conversely, in a study of vasospastic responsiveness to serotonin in hypercholesterolemic primates over time, Heistrad and colleagues58 observed that regression of atherosclerotic plaques was associated with a reduction in vasospastic responsiveness.
Although the results of the above25 26 and other58 59 60 61 62 63 experimental studies have almost consistently provided indirect evidence to suggest a causal link between repeated coronary spasm and atherogenesis in a variety of animal models, the results of most clinical studies to date have been conflicting and have not provided hard evidence of an association between vasospastic activity and progression or regression of atherosclerosis in humans.
Previous Clinical Studies
Kaski et al28 recently
reported a lack of
stenosis progression in vasospastic segments in 10 patients
with vasospastic angina despite chronic disease activity over years.
Several differences in methodology may explain the discordance between
the results of the study of Kaski et al and our results. First, the
average follow-up period of their study was 25 months, while in our
study it was 45 months. A longer observation period in their study
might have revealed more frequent occurrence of
progression.3 8 Second, their study included 10
patients
with vasospastic angina, whereas ours is the largest study ever
undertaken on the relation between coronary vasospasticity and
progression of atherosclerosis and is the largest study
in the field of vasospastic angina to perform quantitative angiographic
analysis. Third, their criterion of stenosis
progression was different from ours. They determined progression by the
difference in percent diameter stenosis between the baseline
and follow-up angiograms. We insisted on using absolute changes in
MLD (0.40 mm) as criteria of progression or regression. The
advantages of using an absolute rather than a relative measure of
stenosis progression include the following. If diffuse
segmental progression has occurred and the reference diameter itself
decreases at follow-up, then comparison of percent diameter
stenosis may fail to detect true progression or regression at
the site of the stenosis.51 In our study, both the
MEAN and MLD of AHA coronary segments of group 1 were
significantly smaller at follow-up; thus, percent diameter
stenosis at follow-up failed to detect a significant
progression (increase in percent diameter stenosis) because of
the concomitant diffuse progression in the reference vessel diameter.
Moreover, Stone et al52 recently suggested that changes in
percent diameter stenosis can be misleading in progression or
regression trials because the MLD and adjacent reference segments may
progress independently at different rates at follow-up
(pseudoregression51 ).
In conflict with the above findings, indirect evidence in support of an association between vasospasticity and development of atherosclerosis from other clinical studies has been reported. Nobuyoshi et al64 recently found that a positive response to an ergonovine provocation test was a predictor of subsequent MI and progression of coronary atherosclerosis at angiographic follow-up, although they did not perform repeated ergonovine tests and thus did not examine the relation between focal spastic site and site of progression or perform QCA analysis. Marzilli et al27 reported that a patient with coronary spasm developed a rapid progression of coronary atherosclerosis at the site of coronary spasm and suggested that coronary spasm might be an antecedent to atherosclerosis. Little et al65 observed in a recipient of an orthotopic heart transplant that coronary spasm preceded the development of coronary atherosclerosis. Further indirect evidence of the interaction of coronary spasm and coronary artery disease has been derived from several studies reporting that patients who demonstrate coronary vasospastic activity before or after balloon angioplasty are predisposed to the subsequent development of restenosis.31 66 67 68
Study Limitations
Whereas patients in whom anginal symptoms
resolved (group 2)
underwent 12-lead ECG at follow-up, ambulatory in-hospital ECG
monitoring, and out-of-hospital Holter monitoring, no patient
experienced either chest pain or a cardiac event during follow-up.
Although it was practically impossible to perform Holter monitoring
every day for several years, these patients had symptoms of variant
angina, ischemic ECG changes, and a positive ergonovine test at
the initial angiogram; then these symptoms and ECG changes disappeared
during follow-up. Thus, it is clinically assumed that vasospastic
activity ceased during follow-up.
Bertrand et al15 and Bott-Silverman and Heupler69 reported that coronary spasm involves the RCA more commonly than the LAD or LCx. A similar tendency was shown in our total patient population (16 spastic segments were RCA, 8 were LCx, and 12 were LAD). In group 1 (the progression group), 4 spastic segments were in the LAD of a total of 19 spastic segments; in group 2 (the regression group), 8 spastic segments were in the LAD of a total of 17 spastic segments (not statistically significant). It remains undetermined from the data obtained whether the distribution of the coronary artery location directly relates to the propensity to progression or regression.
We examined changes of absolute luminal diameter over time at the vasospastic site after the administration of intracoronary isosorbide dinitrate using QCA. While recent progress in intracoronary ultrasound techniques may provide us with additional tomographic information on mural morphology, we feel that a number of limitations remain to be resolved in applying intracoronary ultrasound to long-term progression and regression studies. First, in our study the average follow-up period was 4 years, and intracoronary ultrasound itself was not available when our study began. Second, the reported correlation of luminal measurements between intracoronary ultrasound and QCA has ranged from 0.12 to 0.92,70 71 72 and a satisfactory agreement between ultrasound measurement and angiographic measurements has not yet been established. Third, although it is easy with QCA to compare the same coronary sites at the initial and follow-up angiograms to estimate progression and regression,51 73 74 it can be rather difficult during ultrasound examination to ensure that the exact same position of the coronary artery is quantified at follow-up. Finally, many previous and ongoing progression and regression studies have been and still are performed using QCA only, and we think that angiographic information is still the gold standard in this field.2 4 5 7 9 Thus, we feel that widespread adoption of intracoronary ultrasound as an integral or essential component of progression and regression studies with an interval of several years may have to wait until the current rapid development phase of intracoronary ultrasound technology reaches a plateau (as occurred with QCA) and ECG-gaited three-dimensional reconstructed images become more widely available.75
Conclusions
We have demonstrated in patients an association
between persistent
vasospastic activity and progression of atherosclerosis
and between cessation of vasospastic activity and regression of
atherosclerosis. These results indicate that persistent
vasospastic angina is not a benign disease and that patients with
persistent symptoms of vasospastic angina require long-term
follow-up. Further studies will be required to determine the
mechanism of the association between vasospasticity and
atherosclerosis in humans and to determine effective
medical therapy for the prevention of progression of
atherosclerosis in these patients.
|
Selected Abbreviations and Acronyms |
|---|
|
|
|
Acknowledgments |
|---|
Dr Ozaki is a recipient of a grant from Takeda Medical Research (Taisha Ijo) Foundation, Osaka, Japan. Dr Keane is a recipient of a travel grant from the Peel Medical Research Trust, London, UK. We gratefully acknowledge the dedication and contribution of Drs Fumimaro Takatsu, Yukio Shiga, Masahito Watarai, Seiji Shimizu, and Atsusi Nishiyama; Takeshi Suba; and all the staff of the catheterization laboratory at Anjo Kosei Hospital in Japan. In addition, we are grateful to the staff of the core angiographic laboratory at Cardialysis Rotterdam (Netherlands) for their quantitative analysis of the coronary angiograms. We thank Marie-Angèle Morel and Eline Montauban van Swijndregt for preparation of the figures and Eric Boersma for statistical analysis. We are grateful to Dr Ken Lehmann for his helpful advice.
Received November 21, 1994; revision received May 10, 1995; accepted June 8, 1995.
|
References |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
1. Waters DD, Craven TE, Lespérance J. Prognostic significance of progression of coronary atherosclerosis. Circulation. 1993;87:1067-1075.
2. Watts GF, Lewis B, Brunt JNH, Lewis ES, Coltart DJ, Smith LDR, Mann JI, Swan AV. Effects on coronary artery disease of lipid-lowering diet or diet plus cholestyramine in the St Thomas Atherosclerosis Regression Study (STARS). Lancet. 1992;339:563-569. [Medline] [Order article via Infotrieve]
3.
Applegate RJ, Herrington DM, Little WC.
Coronary angiography: more than meets the eye.
Circulation. 1993;87:1399-1401.
4. MAAS Investigators. Effects of simvastatin on coronary atheroma: the Multicentre Anti-Atheroma Study (MAAS). Lancet. 1994;344:633-638. [Medline] [Order article via Infotrieve]
5.
Waters DD, Higginson L, Gladstone P, Kimball B, Le May
M, Boccuzzi SJ, Lespérance J, for the CCAIT study group.
Effects of monotherapy with an HMG-CoA reductase
inhibitor on the progression of coronary
atherosclerosis as assessed by serial quantitative
arteriography: the Canadian Coronary
Atherosclerosis Intervention Trial.
Circulation. 1994;89:959-968.
6. Mancini GBJ, Bourassa MG, Williamson PR, Leclerc G, DeBoe SF, Pitt B, Lespérance J. Prognostic importance of quantitative analysis of coronary cineangiograms. Am J Cardiol. 1992;69:1022-1027. [Medline] [Order article via Infotrieve]
7.
Blankenhorn DH, Azen SP, Kramsch DM, Mack WJ,
Cashin-Hemphill L, Hodis H, Deboer LWV, Mahrer PR, Masteller MJ, Vailas
LI, Alaupovic P, Hirsch LJ, for the MARS Research Group. The
Monitored Atherosclerosis Regression Study (MARS):
coronary angiographic changes with lovastatin
therapy. Ann Intern Med. 1993;119:969-976.
8. Buchwald H, Varco RL, Matts JP, Long JM, Fitch LL, Campbell GS, Pearce MB, Yellin AE, Edmiston WA, Smink RD Jr, Sawin HS Jr, Campos CT, Hansen BJ, Tuna N, Karnegis JN, Sanmarco ME, Amplatz K, Gastaneda-Zuniga WR, Hunter DW, Bissett JK, Weber FJ, Stevenson JW, Leon AS, Chalmers TC, for the POSCH group. Effect of partial ileal bypass on mortality and morbidity from coronary heart disease in patients with hypercholesterolemia. N Engl J Med. 1990;323:946-955. [Abstract]
9. Brown G, Albers JJ, Fisher LD, Schaefer SM, Lin JT, Kaplan C, Zhao XQ, Bisson BD, Fitzpatrick VF, Dodge HT. Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. N Engl J Med. 1990;323:1289-1298. [Abstract]
10.
Lipid Research Clinics Program. Lipid research
clinics coronary primary prevention trial results: reduction in
incidence of coronary heart disease. JAMA. 1984;251:351-364.
11. Maseri A, Pesola A, L'Abbate A, Persola A, Ballestra AM, Marzilli M, Maltinti G, Severi S, De Nes DM, Parodi O, Biagini A. Coronary vasospasm in angina pectoris. Lancet. 1977;1:713-718. [Medline] [Order article via Infotrieve]
12. Oviva RB, Pott DE, Pluss RG. Coronary arterial spasm in Prinzmetal angina: documentation by coronary arteriography. N Engl J Med. 1973;288:745-751.
13.
Chahine RA, Raizner AE, Ishimori T, Luchi RJ, McIntosh
HD. The incidence and clinical implications of coronary
artery spasm. Circulation. 1975;52:972-978.
14. Maseri A, Severi S, Nes MD, L'Abbate A, Chierchia S, Marzilli M, Ballestra AM, Parodi O, Biagini A, Distante A. Variant angina: one aspect of a continuous spectrum of vasospastic myocardial ischemia. Am J Cardiol. 1978;42:1019-1035. [Medline] [Order article via Infotrieve]
15.
Bertrand ME, Lablanche JM, Tilmant PY, Thieuleux FA,
Delforge MR, Carre AG, Asseman P, Berzin B, Libersa C, Laurent JM.
Frequency of provoked coronary arterial
spasm in 1089 consecutive patients undergoing coronary
arteriography. Circulation. 1982;65:1299-1306.
16. Conti CR, Feldman RL, Pepine CJ. Coronary artery spasm: prevalence, clinical significance, and provocative testing. Am Heart J. 1982;103:584-588. [Medline] [Order article via Infotrieve]
17. McFadden EP, Clarke JG, Davies GJ, Kaski JC, Haider AW, Maseri A. Effect of intracoronary serotonin on coronary vessels in patients with stable angina and patients with variant angina. N Engl J Med. 1991;324:648-654. [Abstract]
18. Ozaki Y, Takatsu F, Osugi J, Sugiishi M, Watarai M, Anno T, Toyama J. Long-term study of recurrent vasospastic angina using coronary angiograms during ergonovine provocation tests. Am Heart J. 1992;123:1191-1198. [Medline] [Order article via Infotrieve]
19.
Ozaki Y, Keane D, Haase J, Baptista J, Meneveau N, de
Feyter PJ, Takatsu F, Serruys PW. Temporal variability and
correlation with geometric parameters in vasospastic
angina: a quantitative angiographic study. Eur Heart
J. 1994;15:61-67.
20. Maseri A, L'Abbate A, Baroldi G, Chierchia S, Marzilli M, Ballestra AM, Severi S, Parodi O, Biagini A, Distante A, Perola A. Coronary vasospasm as a possible cause of myocardial infarction: a conclusion derived from the study of `preinfarction' angina. N Engl J Med. 1978;299:1271-1277. [Abstract]
21. Waters DD, Szlacheic J, Miller D, Theroux P. Clinical characteristics of patients with variant angina complicated by myocardial infarction or death within 1 month. Am J Cardiol. 1982;49:658-664. [Medline] [Order article via Infotrieve]
22.
Yasue H, Takizawa A, Nagao M, Nishida S, Horie M,
Kubota J, Omote S, Takaoka K, Okumura K. Long-term prognosis
for patients with variant angina and influential factors.
Circulation. 1988;78:1-9.
23.
Nakamura M, Takeshita A, Nose Y. Clinical
characteristics associated with myocardial infarction,
arrhythmia, and sudden death in patients with vasospastic
angina. Circulation. 1987;75:1110-1116.
24. MacAlpin RN. Relation of coronary arterial spasm to sites of organic stenosis. Am J Cardiol. 1980;46:143-153. [Medline] [Order article via Infotrieve]
25.
Nagasawa K, Tomoike H, Hayashi Y, Yamada A, Yamamoto T,
Nakamura M. Intramural hemorrhage and
endothelial changes in atherosclerotic coronary
artery after repetitive episodes of spasm in x-ray irradiated
hypercholesterolemic pigs.
Circ Res. 1989;65:272-282.
26.
Kuga T, Tagawa H, Tomoike H, Mitsuoka W, Egashira S,
Ohara YI, Takeshita A, Nakamura M. Role of coronary
artery spasm in progression of organic coronary
stenosis and acute myocardial infarction in a swine
model. Circulation. 1993;87:573-582.
27. Marzilli M, Goldstein S, Trivella MG, Palumbo C, Maseri A. Some clinical considerations regarding the relation of coronary vasospasm to coronary atherosclerosis: a hypothetical pathogenesis. Am J Cardiol. 1980;45:882-886. [Medline] [Order article via Infotrieve]
28.
Kaski JC, Tousoulis D, McFadden E, Crea F, Pereira WI,
Maseri A. Variant angina pectoris: role of coronary
spasm in development of fixed coronary obstructions.
Circulation. 1992;85:619-626.
29. Schroeder JS, Bolen JL, Quint RA, Clark DA, Hayden WG, Higgins CB, Wexler L. Provocation of coronary spasm with ergonovine maleate: new test with results in 57 patients undergoing coronary angiography. Am J Cardiol. 1977;40:487-491. [Medline] [Order article via Infotrieve]
30. Heupler FA Jr, Proudfit WL, Razavi M, Shirey EK, Greenstreet R, Sheldon WC. Ergonovine maleate provocative test for coronary arterial spasm. Am J Cardiol. 1978;41:631-640. [Medline] [Order article via Infotrieve]
31. Bertrand ME, Lablanche JM, Fourrier JL, Gommeaux A, Ruel M. Relation to restenosis after percutaneous transluminal coronary angioplasty to vasomotion of the distal coronary artery segment. Am J Cardiol. 1989;63:277-281. [Medline] [Order article via Infotrieve]
32.
Curry RC, Pepine CJ, Sabom MB, Conti CR.
Similarity of ergonovine-induced and spontaneous attacks of
variant angina. Circulation. 1979;59:307-312.
33.
Waters DD, Szlachcic J, Bonan R, Miller DD, Dauwe F,
Theroux P. Comparative sensitivity of exercise, cold pressor,
and ergonovine testing in provoking attacks of variant angina in
patients with active disease. Circulation. 1983;67:310-315.
34.
Kaski JC, Crea F, Meran D, Rodriguez L, Araujo L,
Chierchia S, Davies G, Maseri A. Local coronary
supersensitivity to diverse vasoconstrictive stimuli in
patients with variant angina. Circulation. 1986;74:1255-1265.
35. Waters DD, Szlachcic J, Theroux P, Dauwe F, Mizgala HF. Ergonovine testing to detect spontaneous remission of variant angina during long-term treatment with calcium antagonist drugs. Am J Cardiol. 1981;47:179-184. [Medline] [Order article via Infotrieve]
36. Previtali M, Panciroli C, Ponti RD, Chimienti M, Montemartini C, Salerno JA. Time-related decrease in sensitivity to ergonovine in patients with variant angina. Am Heart J. 1989;117:92-99. [Medline] [Order article via Infotrieve]
37. Conti CR. Coronary artery spasm: provocative testing. Clin Cardiol. 1994;17:353. Editorial. [Medline] [Order article via Infotrieve]
38. Lablanche JM, Leroy F, McFadden EP, Bauter C, Bertrand ME. Dose-response curve of angiographically smooth human epicardial vessel segments to intracoronary injections of isosorbide dinitrate. J Cardiovasc Pharmacol. 1992;20:473-478. [Medline] [Order article via Infotrieve]
39. Lablanche JM, Delforge MR, Tilmant PY, Thieuleux FA, Bertrand ME. Effets hêmodynamiques et coronaires du dinitrate d'isosorbide: comparison entre les voies d'injection intracoronaire et intraveineuse. Arch Mal Coeur Vaiss. 1982;75:303-315. [Medline] [Order article via Infotrieve]
40. Hill JA, Feldman RL, Pepine CJ, Conti CR. Regional coronary artery dilation response in variant angina. Am Heart J. 1982;104:226-233. [Medline] [Order article via Infotrieve]
41. Jost S, Bossaller C, Reil GH, Gulba D, Knop I, Hecker H, Lichtlen P. Reproducible uniform coronary vasomotor tone with nitrocompounds: prerequisite of quantitative coronary angiographic trials. Cathet Cardiovasc Diagn. 1990;20:168-173. [Medline] [Order article via Infotrieve]
42. Ozaki Y, Keane D, Serruys PW. Relationship of basal coronary tone and vasospastic activity in patients with variant angina. Br Heart J. 1996. In press.
43. Gronenschild E, Janssen J, Tijdens F. CAAS II: a second generation system for off-line and on-line quantitative coronary angiography. Cathet Cardiovasc Diagn. 1994;33:61-75. [Medline] [Order article via Infotrieve]
44. Haase J, Escaned J, van Swijndregt EM, Ozaki Y, Gronenschild E, Slager CJ, Serruys PW. Experimental validation of geometric and densitometric coronary measurements on the new generation cardiovascular angiography analysis system (CAAS II). Cathet Cardiovasc Diagn. 1993;30:104-114. [Medline] [Order article via Infotrieve]
45.
Keane D, Haase J, Slager CJ, van Swijndregt EM, Lehmann
K, Ozaki Y, Di Mario C, Kirkeedee R, Serruys PW. Comparative
validation of quantitative coronary angiographic systems:
results and implications from a multicenter study.
Circulation. 1995;91:2174-2183.
46.
Serruys PW, Luyten HE, Beatt KJ, Geuskens R, de Feyter
PJ, Brand M, Reiber JHC, Katen HJ, Es GA, Hugenholtz PG.
Incidence of restenosis after successful
coronary angioplasty: a time-related phenomenon: a
quantitative angiographic study in 342 consecutive patients at 1, 2, 3,
and 4 months. Circulation. 1988;77:361-371.
47. Ozaki Y, Keane D, Herrman JP, Foley D, Haase J, den Boer AD, Di Mario C, Serruys PW. Coronary arteriography for quantitative analysis: an experimental and clinical comparison of cinefilm and video recordings. Am Heart J. 1995;129:471-475. [Medline] [Order article via Infotrieve]
48.
Serruys PW, Rutsch W, Heyndrickx GR, Danchin N, Mast
EG, Wijns W, Rensing BJ, Vos J, Stibbe J, for the Coronary
Artery Restenosis Prevention on Repeated
Thromboxane-Antagonism (CARPORT) Study Group. Prevention
of restenosis after percutaneous
transluminal coronary angioplasty with thromboxane
A2-receptor blockade: a randomized, double-blind,
placebo-controlled trial. Circulation. 1991;84:1568-1580.
49. Ozaki Y, Keane D, Ruygrok P, de Feyter PJ, Stertzer S, Serruys PW. Acute clinical and angiographic results with the new AVE Micro coronary stent in bailout management. Am J Cardiol. 1995;76:112-116. [Medline] [Order article via Infotrieve]
50. American Heart Association Committee Report. A reporting system on patients evaluated for coronary artery disease. Circulation. 1975;51:7-34.
51.
Feyter PJ, Serruys PW, Davies MJ, Richardson P, Lubsen
J, Oliver MF. Quantitative coronary angiography to
measure progression and regression of coronary
atherosclerosis: value, limitation, and implication for
clinical trials. Circulation. 1991;84:412-423.
52. Stone PH, Gibson CM, Pasternak RC, McManus K, Diaz L, Boucher T, Spears R, Shindo T, Rosner B, Sacks FM, for Harvard Atherosclerosis Reversibility Project Study Group. Natural history of coronary atherosclerosis using quantitative angiography in men and implications for clinical trials of coronary regression. Am J Cardiol. 1993;71:766-772. [Medline] [Order article via Infotrieve]
53. Waters DD, Lespérance J, Craven TE, Hudon G, Gillam LD. Advantages and limitations of serial coronary arteriography for assessment of progression and regression of coronary atherosclerosis: implication for clinical trials. Circulation. 1993;87(suppl II):II-38-II-47.
54. Foley DP, Deckers J, van den Bos AA, Heyndrickx GR, Laarman GJ, Suryapranata H, Zijlstra F, Serruys PW. Usefulness of repeat coronary angiography 24 hours after successful balloon angioplasty to evaluate early luminal deterioration and facilitate quantitative analysis. Am J Cardiol. 1993;72:1341-1347. [Medline] [Order article via Infotrieve]
55.
Gertz SD, Uretsky G, Wajnberg RS, Navot N, Gotsman MS.
Endothelial cell damage and thrombus formation
after partial arterial constriction: relevance to the role
of coronary artery spasm in the pathogenesis of myocardial
infarction. Circulation. 1981;63:476-486.
56. Ross R. The pathogenesis of atherosclerosis: an update. N Engl J Med. 1986;314:488-500. [Medline] [Order article via Infotrieve]
57. Ross R. The pathogenesis of atherosclerosis. N Engl J Med. 1976;295:369-377. [Medline] [Order article via Infotrieve]
58.
Heistad DD, Mark AL, Marcus ML, Piegors DJ, Armstrong
ML. Dietary treatment of atherosclerosis
abolishes hyperresponsiveness to serotonin: implications
for vasospasm. Circ Res. 1987;61:346-351.
59. Heistad DD, Armstrong ML, Marcus ML, Piegors DJ, Mark AL. Augmented responses to vasoconstrictor stimuli in hypercholesterolemic and atherosclerotic monkeys. Circ Res. 1984;61:711-718.
60. Ganz P, Alexander W. New insights into the cellular mechanisms of vasospasm. Am J Cardiol. 1985;56:11E-15E. [Medline] [Order article via Infotrieve]
61.
Egashira K, Tomoike H, Yamamoto Y, Yamada A, Hayashi Y,
Nakamura M. Histamine-induced coronary spasm in
region of intimal thickening in miniature pigs: role of serum
cholesterol and spontaneous or induced intimal
thickening. Circulation. 1986;74:826-837.
62.
Vanhoutte PM, Shimokawa H.
Endothelium-derived relaxing factor and
coronary vasospasm. Circulation. 1989;80:1-9.
63.
Shimokawa H, Tomoike H, Nabeyama S, Yamamoto H, Araki
H, Nakamura M. Coronary artery spasm induced in
atherosclerotic miniature swine. Science. 1983;221:560-562.
64. Nobuyoshi M, Tanaka M, Nosaka H, Kimura T, Yokoi H, Hamasaki N, Kim K, Shindo T, Kimura K. Progression of coronary atherosclerosis: is coronary spasm related to progression? J Am Coll Cardiol. 1991;18:904-910. [Abstract]
65. Little T, Macoviak J, Villanueva P, Lawrenson WE, Rao A. Diffuse coronary vasospasm and accelerated atherosclerosis in transplanted human heart. Am J Cardiol. 1989;64:825-827. [Medline] [Order article via Infotrieve]
66.
David PR, Water DD, Scholl JM, Crepeau J, Szlachcic J,
Lespérance J, Hudon G, Bourassa MG.
Percutaneous transluminal coronary
angioplasty in patients with variant angina.
Circulation. 1982;66:695-702.
67. Ardissimo D, Barberis P, De Servi S, Merlini PA, Bramucci E, Falcone C, Specchia G. Abnormal coronary vasomotion as a predictor of restenosis after successful coronary angioplasty in patients with unstable angina pectoris. N Engl J Med. 1991;325:1053-1057. [Abstract]
68.
McFadden EP, Bauters C, Lablanche JM, Quandalle P,
Leroy F, Bertrand ME. Response of human coronary artery
to serotonin after injury by coronary
angioplasty. Circulation. 1993;88:2076-2085.
69. Bott-Silverman C, Heupler FA. Natural history of pure coronary artery spasm in patients treated medically. J Am Coll Cardiol. 1983;2:200-205. [Abstract]
70.
Nissen SE, Gurley JC, Grines CL, Booth DC, McClure R,
Berk M, Fisher C, DeMaria AN. Intravascular ultrasound
assessment of lumen size and wall morphology in normal subjects and
patients with coronary artery disease.
Circulation. 1991;84:1087-1099.
71.
Tobis JM, Mallery J, Mahon D, Lehmann K, Zalesky P,
Griffith J, Gessert J, Moriuchi M, McRae M, Dwyer ML, Greep N, Henry
WL. Intravascular ultrasound imaging of human coronary
arteries in vivo: analysis of tissue characterizations with
comparison to in vitro histological specimens.
Circulation. 1991;83:913-926.
72. Haase J, Ozaki Y, Di Mario C, Escaned J, de Feyter P, Roelandt JRTC, Serruys PW. Can intracoronary ultrasound correctly assess the luminal dimensions of coronary artery lesions? A comparison with quantitative angiography. Eur Heart J. 1995;16:112-119.
73. Hermans WRM, Rensing BJ, Foley DP, Deckers JW, Rutsch W, Emanuelsson H, Danchin N, Wijns W, Chappuis F, Serruys PW. Therapeutic dissection after successful coronary balloon angioplasty: no influence on restenosis or clinical outcome in 693 patients. J Am Coll Cardiol. 1992;20:767-780. [Abstract]
74. Keane D, Serruys PW. Quantitative coronary angiography: an integral component of interventional cardiology. In: Topol EJ, Serruys PW, eds. Current Review of Interventional Cardiology. 2nd ed. Philadelphia, Pa: Current Medicine; 1995:205-233.
75.
Roelandt JRTC, Di Mario C, Pandian N, Wenguang L, Keane
D, Slager C, de Feyter P, Serruys PW. Three-dimensional
reconstruction of intracoronary ultrasound images:
rationale, approaches, problems, and directions.
Circulation. 1994;90:1044-1055.
This article has been cited by other articles:
 |
|
 |
|
  K. Wakabayashi, H. Suzuki, Y. Honda, D. Wakatsuki, K. Kawachi, K. Ota, S. Koba, N. Shimizu, F. Asano, T. Sato, et al. Provoked Coronary Spasm Predicts Adverse Outcome in Patients With Acute Myocardial Infarction: A Novel Predictor of Prognosis After Acute Myocardial Infarction J. Am. Coll. Cardiol., August 12, 2008; 52(7): 518 - 522. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Shinoda, Y. Yui, K. Kodama, A. Hirayama, H. Nonogi, K. Haze, T. Sumiyoshi, S. Hosoda, C. Kawai, and for the Japan Multicenter Investigation for Cardio Quantitative Coronary Angiogram Analysis: Nifedipine Retard Versus Angiotensin-Converting Enzyme Inhibitors (JMIC-B Side Arm Study) Hypertension, June 1, 2005; 45(6): 1153 - 1158. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Sun, M. Mohri, H. Shimokawa, M. Usui, L. Urakami, and A. Takeshita Coronary microvascular spasm causes myocardial ischemia in patients with vasospastic angina J. Am. Coll. Cardiol., March 6, 2002; 39(5): 847 - 851. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O Ueda, K Kohchi, Y Kishi, and F Numano Long lasting spasticity in controlled vasospastic angina Heart, May 1, 1999; 81(5): 528 - 532. [Abstract] [Full Text]
|
|
|
|
|
|
H. Suzuki, S. Kawai, T. Aizawa, K. Kato, S. Sunayama, R. Okada, and H. Yamaguchi Histological evaluation of coronary plaque in patients with variant angina: relationship between vasospasm and neointimal hyperplasia in primary coronary lesions J. Am. Coll. Cardiol., January 1, 1999; 33(1): 198 - 205. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G Y H Lip, K K Ray, and M F Shiu Coronary spasm in acute myocardial infarction Heart, August 1, 1998; 80(2): 197 - 199. [Abstract] [Full Text]
|
|
|
|
 |
|
 Y. Ozaki, A. G. Violaris, T. Kobayashi, D. Keane, E. Camenzind, C. Di Mario, P. de Feyter, J. R. T. C. Roelandt, and P. W. Serruys Comparison of Coronary Luminal Quantification Obtained From Intracoronary Ultrasound and Both Geometric and Videodensitometric Quantitative Angiography Before and After Balloon Angioplasty and Directional Atherectomy Circulation, July 15, 1997; 96(2): 491 - 499. [Abstract] [Full Text]
|
|
|
|
|
|
Y. Ozaki, D. Keane, P. Ruygrok, W. J. van der Giessen, P. de Feyter, and P. W. Serruys Six-Month Clinical and Angiographic Outcome of the New, Less Shortening Wallstent in Native Coronary Arteries Circulation, June 15, 1996; 93(12): 2114 - 2120. [Abstract] [Full Text]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||