Author + information
- Received February 4, 2000
- Revision received May 8, 2000
- Accepted July 10, 2000
- Published online November 15, 2000.
- Paul Wexberg, MDa,* (, )
- Mariann Gyöngyösi, MD, PhDa,
- Wolfgang Sperker, BSa,
- Katharina Kiss, MDa,
- Paul Yang, BSa,
- Ali Hassan, MDa,
- Gerard Pasterkamp, MD, PhD∗ and
- Dietmar Glogar, MD, FESCa
- ↵*Reprint requests and correspondence: Dr. Paul Wexberg, Division of Cardiology, Department for Internal Medicine II, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria.
The goal of this study was to investigate the association between the atherosclerotic arterial remodeling and the incidence of cardiac events after coronary interventions in patients with stable angina.
The local mode of de novo atherosclerotic remodeling is associated with plaque vulnerability and clinical symptoms. It may, therefore, reflect plaque morphology influencing the long-term outcome after coronary interventions.
Quantitative angiography and intravascular ultrasound were obtained in 244 patients with stable angina before and after single-vessel revascularization. On the basis of the lesion and the reference segment vessel size, patients were categorized into three groups (adaptive [AR], constrictive [CR] and intermediate [IR] remodeling). The lesion was analyzed for lumen, total vessel and plaque areas. Clinical follow-up was obtained at a mean period of 7.7 ± 3.7 months.
Patients with CR had a higher rate of in-hospital complications (10.9% vs. 2.9% and 2.7% in group CR vs. AR and IR, p = 0.035). In contrast, patients with AR had the highest rate of major adverse cardiac events (MACE) (44.3% vs. 25.5% in IR and 28.1% in CR, p = 0.024) with a predominance of revascularization at follow-up. Both target lesion restenosis (p = 0.036) and nontarget lesion de novo stenosis (p = 0.007) occurred more frequently in this group. Adaptive remodeling was a significant predictor of MACE in multivariate analysis.
Adaptive remodeling is associated with a higher rate of MACE, target lesion restenosis and nontarget de novo stenosis. This finding may be due to differential responses of the adaptively remodeled vessel to revascularization and a generally accelerated course of systemic atherosclerosis.
Arterial remodeling is the geometric alteration of the arterial vessel wall in response to the progression of atherosclerosis; it can be observed in both de novo and restenotic lesions. This phenomenon involves either a large arterial lumen despite a substantial atherosclerotic plaque size, (adaptive remodeling [AR]) (1), or a smaller arterial lumen than expected from the plaque size alone (constrictive remodeling [CR]) (2). Constrictive remodeling has also been found to contribute predominantly to the development of restenosis after coronary interventions (3,4). The pathomechanism of the bidirectional pattern of vascular remodeling is not yet completely understood, but it is considered to be, at least in part, related to adventitial processes (5).
Some reports have already reported the importance of preexisting arterial remodeling as concerns the immediate success and short- and long-term clinical outcomes of coronary revascularization. However, the possible impacts of different remodeling modes on the development of target lesion restenosis in connection with or without acute myocardial infarction (AMI) and cardiac death are still subject to investigation. On the basis of the nature of the different remodeling modes, a better clinical outcome for AR and worse follow-up results for CR could be expected. However, it has been shown that the mode of remodeling did not influence the magnitude of the acute lumen gain after balloon angioplasty (6). Moreover, the AR in coronary arteries presenting in an unselected group of patients with either stable or unstable angina was associated with a significantly higher incidence of target lesion revascularization (7–9). Preexisting adaptive remodeling proved to be a prognostic factor for the occurrence of major adverse cardiac events (MACE) in patients with unstable coronary heart disease (10). The reason for the paradoxical worse clinical outcome of patients with preexisting AR is thought to be the biologically active unstable plaque (11).
The differentiation between stable and unstable angina is based merely on the clinical symptoms (12) and does not necessarily characterize the pathomorphology of the coronary lesion. However, we, as well as other researchers, have shown that unstable clinical symptoms are associated with the mode of de novo atherosclerotic arterial remodeling (13,14). The aim of the present prospective clinical intravascular ultrasound (IVUS) study, therefore, was to investigate the influence of the local remodeling modes on the short- and long-term clinical outcomes of patients presenting only with stable angina pectoris.
The clinical, angiographic and IVUS data on 491 consecutively enrolled patients (IVUS guided coronary intervention between September 1995 and March 1999) at the Division of Cardiology, Department of Internal Medicine II, University of Vienna, were prospectively selected and analyzed. All patients had given written informed consent to cardiac catheterization and IVUS in accordance with the institutional guidelines. Inclusion criteria were symptomatic coronary artery disease, single-vessel coronary intervention in a nonostial de novo lesion, IVUS before and after coronary revascularization, available qualitative and quantitative IVUS assessments and clinical follow-up. Patients after heart transplantation (n = 69) and patients with unstable angina pectoris (n = 95) were then excluded. The results of the patients with unstable angina have previously been published elsewhere (10,13,15). We then excluded 83 patients with missing baseline or follow-up clinical data. The data on the remaining 244 patients presenting with stable angina were included in the further analyses.
Angina pectoris was considered to be stable when it was brought on by exertion, resolved under nitrate-therapy and had not changed in its characteristics (frequency, severity, duration, time of appearance and precipitating factors) for the previous 60 days (16). All patients were requested to undergo follow-up angiography after six months and were clinically followed up for 12 months. If patients developed recurrent angina, angiography was performed at the occurrence of symptoms.
Demographic data (age and gender) and coronary risk factors (family history of coronary artery disease, smoking, medication-dependent diabetes mellitus, medication-dependent hypertension and medication-dependent hypercholesterolemia) were obtained from the patient’s chart. A positive family history was defined as the existence of a male first-degree relative with documented coronary artery disease at <55 years of age or a female first-degree relative with documented coronary artery disease at <65 years of age. Patients who had been smoking within the last three years were classified as smokers.
Coronary angiography, IVUS and coronary intervention
Biplane coronary angiography was performed in a routine manner, the Judkin’s technique being used. After the intracoronary administration of 150 to 200 μg nitroglycerine, baseline angiograms were recorded in at least two projections on either cine film or CD-ROM. After the completion of coronary angiography, the culprit lesions were identified, and IVUS imaging of these lesions was performed, the description of which has been previously published (13). Stenoses <50% were only revascularized if the patient had symptoms showing evidence of lesion-related ischemia.
Before each IVUS procedure, 100 to 200 μg nitroglycerine was administered, intracoronary, to prevent vasospasm, and an IVUS imaging catheter was advanced at least 1.0 cm distal to the stenosis. The catheters used in this study were 2.6, 2.9 or 3.2F mechanical imaging catheters (Boston Scientific Corp., Sunnyvale, California) and 3.0F electronic imaging catheter (EndoSonics, Rancho Cordova, California). The catheter was then pulled back manually or automatically at a constant velocity of 0.5 mm/s, and the images were recorded on s-VHS videotapes for subsequent off-line analysis. Immediately before the intervention, the patients received 250 mg aspirin and 10,000 IU heparin intravenously. During the procedure the activated clotting time was measured and was maintained at >300 s by repeated intravenous heparin application. The interventional device (balloon, stent, and directional atherectomy) was chosen according to the angiographic and ultrasonographic appearance of the lesion. Optimizing interventions and IVUS guidance were performed at the interventionist’s discretion. After finalization IVUS was performed as described above. After the intervention patients were treated with aspirin (100 mg); in the case of stenting, they took aspirin (100 mg) for at least one year, and they took ticlopidine (500 mg) for 30 days.
Angiograms were analyzed in two different sessions by two experienced observers blinded to the ultrasonographic results. Consensus was achieved between the two observers with regard to the qualitative angiographic parameters. Qualitative analysis was performed according to clinical standards (17). Special emphasis was placed on proximal lesions and stenoses with type C morphology, which have previously been found to have a worse outcome. Quantitative angiographic measurements were performed with a computer-assisted quantitative coronary arteriographic edge-detection algorithm (for cineangiograms: Cardiovascular Measurement System, Medis, the Netherlands; for CD-ROM: ACOMPC, Siemens, Germany), and the mean values of the two observer’s measurements were calculated. End-diastolic frames were chosen for assessment of the minimal lumen diameter and reference diameter, lengths of stenoses and percent diameter stenoses. In the projection with the least amount of foreshortening, the lesion length (in millimeters) was measured from the proximal to the distal shoulder of the stenosis (18).
Intravascular ultrasound images obtained via mechanical catheters were analyzed in off-line mode by two experienced observers with a computer-assisted IVUS analysis system (TapeMeasure, Indec Systems Inc., Capitola, California). Those images obtained by electronic catheters were analyzed on the EndoSonics Oracle Imaging System (EndoSonics, Rancho Cordova, California).
The qualitative features of the culprit lesion were independently determined by the two observers; in cases of disagreement the final decision was obtained in a consensus reading. We have previously published the underlying definitions for plaque composition (soft, fibrocalcific, calcification) and plaque eccentricity elsewhere (13). The plaque was suspicious for containing thrombus when it had a scintillating or sparkling appearance, with a finer tissue structure and brighter individual speckles than soft plaque, which was not affected by a contrast injection through the guiding catheter. Plaque rupture was defined as an abrupt, focal, superficial break in the linear continuity of the plaque that extended in a radial direction only. When irregularities within the surface of the diseased vessel wall were observed without actual rupture, the surface was classified as ulcerated (19). The site of the minimum lumen cross-sectional area, that is, the lesion site, was identified by carefully scrolling the tape forward and back and by orientation on anatomic landmarks. At the lesion site and in adjacent proximal and distal reference segments, quantitative measurements were performed by two independent observers as described below, and the average value of the two measurements was then calculated. For each segment the lumen area (mm2) and the total vessel area (mm2) were measured in diastolic frames by manually tracing the leading edge of the intima and the external elastic membrane (EEM), respectively. The plaque area, defined as intima + media area, was calculated from the difference between the lumen and the total vessel areas (mm2). The plaque burden (%) on each cross-section was calculated as (plaque area/total vessel area) × 100. The proximal and distal reference segments were defined as the segments closest to the lesion site (with no major side-branch originating between the lesion site and the reference site) with a plaque burden of <50%.
Major adverse cardiac events were considered to be death, nonfatal AMI and revascularization. Target lesion restenosis was defined as a lesion with ≥50% diameter stenosis at the originally treated lesion site at follow-up. Nontarget de novo stenosis was considered to be a significant stenosis (percent diameter stenosis ≥50%) at any lesion in any coronary artery except at the target site, which was not present at the first angiography.
Intervention complications were defined as complications during the coronary intervention. An acute complication was defined as a complication within 24 h after the intervention. In-hospital complications occurred after the intervention and before hospital discharge. Intervention, acute and in-hospital complications were AMI, life-threatening cardiac arrhythmias with a need for resuscitation or pacemaker implantation, rest angina with electrocardiogram changes, repeat acute revascularization and death from any cause.
Adaptive remodeling was assumed when the EEM cross-sectional area at the lesion site was larger than the proximal reference EEM cross-sectional area, whereas a lesion EEM cross-sectional area smaller than that at the distal reference site was defined as CR. Intermediate remodeling (IR) was present when the EEM cross-sectional areas of the lesion was smaller than that of the proximal and larger than that of the distal reference segment (Fig. 1).
All data are expressed as means ± standard deviation for continuous variables. Categoric variables are presented as frequencies. Comparisons between groups were made with analysis of variance (ANOVA) for differences in means or with the chi-square test for categorical variables, respectively. Differences were considered to be significant when p < 0.05.
Additionally, uni- and multivariate analyses were performed in order to determine the confounding variables effecting the results and to define the significant predictors of in-hospital complications, composite MACE, target lesion restenosis and nontarget lesion de novo stenosis as dependent variables. First, all clinical, angiographic and IVUS parameters were tested in univariate analyses; then the significant parameters were entered into the multivariate analyses. Odds ratios (OR) with 95% confidence intervals (CI) were calculated for all significant predictors in multivariate analyses.
The follow-up events (MACE, target lesion restenosis and nontarget de novo stenosis)—free survival functions (Kaplan-Meier curve)—were estimated and supplemented with the log-rank test.
Data on reproducibility in our IVUS laboratory have been published elsewhere (13). In brief, measurements on single arterial segments were performed by two observers, and regression analysis was used to assess the interobserver variability. The coefficient of correlation of the interobserver variability was r = 0.956 (p < 0.001). One-way ANOVA with repeated measurements was used to determine the intraobserver variability and the reproducibility of IVUS measurements. The standard error of the estimate of the ANOVA was used to derive the methodological error. The coefficient of variation of the repeated measurements of the lumen and EEM diameter was 3%, whereas that of the lumen and EEM cross-sectional area was 1.7%. The methodological error of the measurement of the lumen and EEM diameter was 0.19 mm and for the lumen and EEM cross-sectional areas was 0.38 mm2.
The clinical, angiographic and IVUS data on 244 patients presenting stable angina, comprising 196 men and 48 women (average age 59.1 ± 10.9 years) were analyzed. Control angiography within the first 12 months was obtained in 196 patients (80.3%). Seventy (28.7%) patients exhibited AR (group AR), 110 (45.1%) were classified as IR (group IR), and 64 patients (26.2%) presented with CR (group CR).
Overall, a positive family history was present in 16.0%, smoking in 52.1%, diabetes mellitus in 15.6%, hypertension in 36.5% and hypercholesterolemia in 74.2%. In 132 patients (54.1%) lesions were revascularized by stenting; in 70 (28.7%) balloon dilatation was performed as a stand-alone procedure, and in 42 patients (17.2%) other procedures (atherectomy, laser) were applied. The distribution of the intervention types did not differ between the groups nor did the demographic and clinical baseline data (Table 1). Six patients (5.5%) required treatment with glycoprotein IIb/IIIa antagonists after intervention.
Qualitative and quantitative coronary angiography results
The patients in group IR suffered from multivessel disease significantly less frequently than the other patients did, with an overall frequency of 52.0%. The distribution of analyzed arteries was as follows: 125 left anterior descending (51.2%), 24 circumflex (9.8%) and 95 right coronary (39.0%). The lesion was located in a proximal vessel segment in 60.7%, and 22.5% were type C lesions. The mean length of the stenoses was 7.91 ± 4.45 mm. Before intervention the mean minimal lumen diameter was 1.44 ± 0.62 mm, which increased to 2.70 ± 0.59 mm after the coronary intervention. The pre- and postinterventional reference diameter was 3.02 ± 0.75 and 3.38 ± 0.67 mm, while the percentage of diameter stenosis decreased from 54.4 ± 19.3% to 19.7 ± 9.1%. The differences between the groups in arterial dimensions as measured by quantitative coronary angiography were not significant (Table 2).
Soft plaque was found in 37.3% of all lesions; 23.4% displayed thrombotic components, and 40.2% presented calcification. The plaque was concentric in 65.2% of the lesions. Spontaneous plaque dissection/rupture and ulceration were found in 16.8% and 14.8%. The qualitative IVUS data did not differ significantly between the groups although there was a trend toward a higher frequency of thrombotic plaque components in the patients with AR (28.6% vs. 20.3% in CR and 18.2% in IR, p = 0.074; Table 3). For all patients the minimal lumen, plaque and vessel areas and plaque burdens were: 4.24 ± 2.40, 11.17 ± 4.97 and 15.45 ± 5.47 mm2 and 70.7 ± 14.2% before the intervention and 8.06 ± 2.87, 7.46 ± 3.87 and 15.59 ± 5.34 mm2 and 47.1 ± 12.5% after the intervention.
Before the coronary intervention, the plaque and vessel areas were significantly larger in the patients with AR than they were in those without (p < 0.001 and p = 0.001, respectively), whereas the minimal lumen area and plaque burden did not differ between the three groups. After the coronary intervention, the residual plaque area was significantly larger in group AR than it was in groups CR and IR (p = 0.044; Table 3).
Short- and long-term outcomes
Neither the coronary intervention complications nor the occurrence of acute complications differed significantly between the three groups, with overall rates of 2.9% and 2.1%, respectively. However, there was a trend towards a higher rate of postinterventional dissections for patients with CR (10.9% vs. 1.4% in group AR and 7.3% in group IR; p = 0.078). These patients also had the highest rate of in-hospital complications after the interventions (10.9% vs. 2.9% and 2.7% in group CR vs. groups AR and IR, p = 0.035). The distribution of in-hospital complications was as follows: three urgent percutaneous transluminal coronary angioplasties (PTCA), one death, one ventricular fibrillation with successful resuscitation, two rest angina pectoris with electrocardiogram changes in group CR, two non-Q wave AMIs in group AR and two non-Q wave AMIs and one death in group IR.
Clinical follow-up was performed in all patients at a mean period of 7.7 ± 3.7 months. Follow-up angiography was performed in 196 patients (80.7%). Major adverse cardiac events occurred in 31.6% (77 patients) of all patients: 44.3% in group AR but in only 28.1% of the CR patients and 25.5% of the group IR patients (p = 0.024; Table 4A).
The predominant event was revascularization in any lesion with an overall frequency of 28.3% (69 patients). Repeated angioplasty was performed significantly more frequently for patients with AR (28 PTCA and 2 coronary artery bypass grafting [CABG], 42.9%) than for patients in groups CR (13 PTCA and 2 CABG, 23.4%) and IR (21 PTCA and 3 CABG, 21.8%; p = 0.006). During the follow-up period seven patients (2.9%) died, and six patients (2.5%) suffered a nonfatal AMI (Table 4A). Target lesion restenosis occurred significantly more frequently in patients with AR (p = 0.036) and so did nontarget lesion de novo stenosis (p = 0.007; Table 4B).
Predictors for in-hospital complications, MACE, target lesion restenosis and nontarget lesion de novo stenosis
The in-hospital complications correlated only with the presence of preexisting CR in the univariate analysis (p = 0.042).
Major adverse cardiac events were significantly associated with AR (p = 0.018) and male gender (p = 0.045) in the univariate analysis. Multivariate analysis revealed only AR as a significant predictor (p = 0.036) for the occurrence of MACE with an OR of 1.882 and a 95% CI of 1.864 to 2.530.
Target lesion restenosis showed a significant positive correlation with AR (p = 0.017), preintervention percent diameter stenosis (p = 0.049), plaque area (p = 0.042), EEM area (p = 0.033) and postinterventional plaque area (p = 0.044). Multivariate analysis revealed AR (p = 0.044, OR: 1.239 with 95% CI of 1.156 to 1.511) as a significant predictor for target lesion restenosis.
For nontarget lesion de novo stenosis univariate analysis revealed a relation with AR (p = 0.023), pre- and postinterventional EEM area (p = 0.006 and p = 0.003, respectively) and multivessel disease (p = 0.007) as significant parameters. Multivariate analysis showed AR (p = 0.047, OR: 3.022, 95% CI: 2.944 to 4.226) as significant and multivessel disease as borderline significant (p = 0.067) predictors for nontarget lesion de novo stenosis.
The survival curves exhibited a significantly worse clinical outcome in the patients with AR with regard to the composite MACE (Fig. 2A), target lesion restenosis (Fig. 2B) and nontarget lesion de novo stenosis (Fig. 2C). However, when the observation period was restricted to the first six months, the event-free survival function revealed only a trend towards a worse outcome in patients with AR, without reaching the level of significance.
This study demonstrates the different clinical and angiographic outcomes of preexisting AR, CR and IR for patients with stable angina pectoris. As expected, these patients present predominantly with nonadaptive remodeling (IR and CR) (14). Constrictive remodeling is associated with a higher rate of in-hospital complications after coronary interventions, which do not transform into a worse late clinical outcome. Adaptive remodeling is predictive of a higher rate of composite MACE and both target lesion restenosis and nontarget de novo stenosis. On the basis of the significantly higher frequency of multivessel disease and follow-up nontarget de novo stenosis, we may assume a more progressive systemic atherosclerosis for patients presenting with coronary artery AR.
CR and in-hospital complications
The coronary lesions exhibiting CR features presented the smallest plaque area, obviously as a consequence of the decreased vessel area, while the lumen area was similar in all groups. The degree of lumen narrowing in CR lesions is, therefore, primarily independent of the size of plaque area and is merely the result of a geometric compromise. The high proportion of in-hospital complications in these patients leads to the speculation of an only modest short-term interventional success in terms of vessel stretch, plaque compression and debulking, as suggested by the higher frequency of postinterventional dissections in this group.
AR and MACE
The results of our study indicate that AR is associated with a higher frequency of MACE in patients with stable angina. The plaque and vessel areas in the AR group were significantly higher before the interventions, which corresponds well to the first description of vascular remodeling (1). We have previously shown that a higher incidence of thrombus, as detected by IVUS, was associated with AR in patients with unstable angina (13). In this study we observed a similar trend, and we may suppose that the presence of thrombotic components in clinically stable patients might have an additional, although not sole, effect on the development of adaptive vessel remodeling and on the proliferative potential of the vessel wall. Generally, AR seems to be associated with a worse outcome of coronary interventions because patients with unstable angina, with their known higher risk of MACE, had a higher occurrence of AR than patients with stable angina (36.7% vs. 28.7%) at the expense of IR (40.8% vs. 45.1%), but they had a comparable distribution of CR (26.2% vs. 23.3% ). Considering the higher biological activity of AR lesions (11), we may, thus, speculate on an enhanced development of a hemodynamically significant lumen encroachment, especially in large plaque areas, as expected in lesions featuring AR. Moreover, we found a strikingly higher incidence of eccentric (63%), soft (58%), thrombotic (78%), ruptured (43%) plaques and smaller lumen cross-sectional area for patients with unstable angina (10). It, therefore, seems that there are morphological differences between the lesions in stable and unstable angina. However, the term “unstable angina” is characterized solely by clinical features and does not necessarily correlate fully with the histological features of plaque stability or instability.
Nontarget lesion de novo stenosis
Overall, we found a high rate of de novo nontarget lesions in all patients within one year of follow-up (20.3%). This may be related to the distribution of risk factors, especially the high prevalence of hypercholesterolemia (74.2%) and smoking history (52.1%). Furthermore, the Kaplan-Meier event-free survival curves of the three groups are comparable within the first six months and are also comparable with other published data. The mean follow-up period in our study was 7.7 ± 3.7 months; however, we followed our patients for up to one year. Since almost 50% presented multivessel disease, we think that the occurrence of significant de novo lesions in 20% is not surprising. Interestingly, patients featuring AR in the target lesion were more likely to develop nontarget lesion de novo stenosis, despite similar risk profiles. Thus, AR may not only be a peculiarity of the culprit lesion but may represent a generally higher severity of atherosclerosis. This hypothesis appears to be supported by the increased frequency of multivessel disease in the AR group. Considering that the clinical characteristics and qualitative morphologic data on lesions were similar in all three remodeling groups, it seems that additional factors may exist that lead to an overall progression of coronary artery disease for patients presenting with AR in a coronary lesion. Since the degree of vessel enlargement is often individually determined (20) and associated with pathohistological markers for inflammation and plaque vulnerability (11), the observation of AR might reflect some state of vascular inflammation throughout the coronary tract of such patients. These individually determined inflammatory processes may not only accelerate the progression of atherosclerosis but may also induce plaque rupture.
The survival curve revealed a significantly worse clinical outcome for patients with AR during the one-year follow-up period, while during the first six months there was only a nonsignificant trend toward a higher incidence of MACE and restenosis in these patients. Since we have previously reported that AR is a significant predictor of MACE during the first six months in patients with unstable angina (10), it seems that the atherosclerotic progression in patients with stable angina is slower as compared with that in unstable clinical conditions.
Comparison with previous studies
Our results are partially concordant with the recently published reports on preinterventional AR as a predictor of target lesion revascularization (7,9). However, there are important differences in study design between our study and those reports, which exclude a direct comparison. First, in the studies by Dangas et al. (7) and Ahmed et al. (9), CR and IR were taken as one group of lesions featuring “intermediate/negative remodeling.” Second, the patients were included regardless of their anginal status, and, thus, a high rate of unstable patients in these two studies may have biased the results. Moreover, the postinterventional plaque burden reported for all of the patient groups of Dangas et al. (7) was surprisingly high (64.1 ± 10.53% and 66.6 ± 10.99%), and this might also strongly influence the follow-up results (21). However, in that study nonstent interventions were assessed, and the predictive role of AR in the target lesion revascularization after stent implantation was evaluated separately (9). It is well known that the mechanisms of restenosis differ after specific interventions (22). Whereas the major pathomechanism of in-stent restenosis is neointimal hyperplasia (23), CR is primarily responsible for restenosis after balloon angioplasty (24) and directional coronary atherectomy (4,25). In our cohort more than one-half of the patients were treated with stents. Interestingly, there is no general accordance on a standardized therapy for the variations in remodeling in the present clinical practice. Although the distribution of revascularization techniques was similar in all three groups, further studies to assess the effects of specific interventional techniques on different remodeling modes in separate patient groups (stable or unstable angina) are needed.
Our study is based exclusively on observations in nonostial de novo stenoses, so the results may not be applicable to restenotic and ostial lesions.
Furthermore, there were different types of interventions performed in the included patients (mainly stenting). It is conceivable that the predominant mechanism of a single revascularization technique (debulking, plaque compression, etc.) may be of different value in the various modes of remodeling. However, the percentage of intervention techniques did not differ significantly between the three groups.
For the determination of vascular remodeling, only a single IVUS image in the culprit lesion was assessed (“snapshot view”). The lesion may feature various geometric differences along its length, so that the chosen frame may not be characteristic of certain biological properties of the entire stenosis. However, in view of the international practice of defining vascular remodeling by comparison of single segments (4,7,21,26), and in consequence of the standardized methods of image selection within our IVUS laboratory, our study presents a uniform and reproducible data set with regard to quantitative description.
Soft plaque and slowly flowing blood with a speckled echo might lead to thrombus misinterpretation. Although several IVUS studies have reported data on thrombotic plaque, the identification of thrombus is still one of the less specific and sensitive aspects of IVUS imaging.
The observations on vessel geometry may be distorted by either a vasospasm caused by the catheter, mimicking CR or vasodilation as a response to nitroglycerine, mimicking AR. Since all patients received the same antianginal therapy before and during the procedure, the differences between individual patients are reduced to a minimum. However, if a vasospasm did occur during the IVUS procedure, the catheter was removed immediately, and the procedure was repeated after an intracoronary injection of nitroglycerine. The final recording was then used for quantitative analysis.
Our study has shown that AR is associated with an increased frequency of composite MACE, with a predominance of revascularization and both target lesion restenosis and nontarget de novo stenosis in patients with stable angina. Whereas the high rate of in-hospital complications in patients featuring CR may be related to the vessel injury caused by the intervention, the enhanced development of restenoses and de novo stenoses in patients with AR may be due to a generally accelerated course of systemic atherosclerosis.
- acute myocardial infarction
- adaptive remodeling
- analysis of variance
- coronary artery bypass grafting
- confidence interval
- constrictive remodeling
- external elastic membrane
- intermediate remodeling
- intravascular ultrasound
- major adverse cardiac events
- odds ratio
- percutaneous transluminal coronary angioplasty
- Received February 4, 2000.
- Revision received May 8, 2000.
- Accepted July 10, 2000.
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