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Circulation. 1995;91:2140-2150

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(Circulation. 1995;91:2140-2150.)
© 1995 American Heart Association, Inc.

Articles

Long-term Luminal Renarrowing After Successful Elective Coronary Angioplasty of Total Occlusions

A Quantitative Angiographic Analysis

Presented in part at the 66th Scientific Sessions of the American Heart Association, Atlanta, Ga, November 8-11, 1993.

Andonis G. Violaris, MD, MRCP (UK); Rein Melkert, MD, MS; Patrick W. Serruys, MD, PhD

From the Catheterisation Laboratory, Thoraxcenter, Erasmus University, and the Department of Epidemiology and Biostatistics, Cardialysis (R.M.), Rotterdam, The Netherlands.

Correspondence to Prof P.W. Serruys, MD, PhD, FACC, FESC, Catheterisation Laboratory, Thoraxcenter, Erasmus University Rotterdam, Postbus 1738, 3000 DR, Rotterdam, The Netherlands.


*    Abstract
up arrowTop
 *Abstract
down arrowIntroduction
 down arrowMethods
down arrowResults
down arrowDiscussion
down arrowReferences
 
Background The long-term angiographic outcome after successful dilatation of coronary occlusions remains unclear. The objective of this study was to examine long-term restenosis after successful balloon dilatation of coronary occlusions at a predetermined time interval with quantitative angiography and compare this with a control population of stenoses.

Methods and Results The study population comprised 2950 patients (3583 lesions) prospectively enrolled in and successfully completing four major restenosis trials (86% quantitative angiographic follow-up). Cineangiographic films were processed and analyzed at a central core laboratory with the use of an automated interpolated edge detection technique. The study population comprised 266 occlusions (7%) defined as total when there was absent anterograde filling beyond the lesion (109 lesions) and functional (157 lesions) when faint, late anterograde opacification of the distal segment was seen in the absence of a discernible luminal continuity; 3317 lesions were defined as stenoses (93%). Restenosis was significantly higher after successful dilatation of occlusions than of stenoses. With the categorical (>50% diameter stenosis at follow-up) approach, the restenosis rate was 44.7% in occlusions compared with 34.0% in stenoses (P<.001; relative risk, 1.575; CI, 1.224 to 2.027). Similarly, the absolute loss (defined as the change in minimal lumen diameter between post coronary angioplasty and follow-up; in millimeters, mean±SD) (0.43±0.68) in occlusions was significantly higher than in stenoses (0.31±0.51, P<.001), as was the relative loss, defined as the change in minimal lumen diameter between postangioplasty and follow-up, adjusted for the vessel size (0.17±0.28 versus 0.12±0.20, P<.001). The higher restenosis rate in the occlusions group was due predominantly to an increased number of occlusions at follow-up angiography in this group (19.2% compared with 5.0% for stenoses, P<.001). Within the occlusions group, there were no significant differences in long-term outcome between total and functional occlusions (restenosis rate, 45.0% versus 44.6%; reocclusion rate, 23.9% versus 15.9%; absolute loss, 0.53±0.69 versus 0.36±0.67; relative loss, 0.21±0.28 versus 0.15±0.28; P=NS).

Conclusions These results indicate that successfully dilated coronary occlusions, both total and functional, have a higher rate of angiographic restenosis at 6 months than stenoses. This is due chiefly to a higher rate of occlusion at follow-up angiography in this group of lesions. Measures aimed at reducing restenosis after successful dilatation of coronary occlusion should be focused in this direction.


Key Words: angioplasty • occlusions • angiography


*    Introduction
up arrowTop
 up arrowAbstract
 *Introduction
down arrowMethods
down arrowResults
down arrowDiscussion
down arrowReferences
 
After the introduction of coronary angioplasty by Grüntzig et al in 1979,1 the indication for its use were at first tentatively and subsequently more strikingly expanded to include patients with total occlusions.2 3 4 5 6 Although a number of factors are known to influence the acute success rate,4 7 8 9 relatively little is known regarding long-term luminal renarrowing after successful dilatation of total occlusions. A number of studies have investigated this, but uncertainty continues with restenosis rates in the literature varying from 20% to 65%.2 3 5 6 10 11 12 13 14 15 16 17 This variation has three primary sources. First, most studies have been retrospective analyses that use small patient numbers and no control group.2 3 11 12 15 16 Second, the angiographic follow-up rates have been low and performed for the recurrence of symptoms rather than at a predetermined time interval, thus introducing important selection bias.5 6 17 Finally, some have used visual assessment to estimate angiographic severity, which is subject to wide interobserver and intraobserver variability.18 This study attempted to overcome these limitations by using a validated automated edge detection technique to evaluate restenosis prospectively in a large series of patients undergoing successful balloon angioplasty and routine follow-up angiographic assessment at a predetermined time interval. Furthermore, a control cohort of patients with stenoses was used to directly compare the long-term results.


*    Methods
up arrowTop
 up arrowAbstract
 up arrowIntroduction
 *Methods
down arrowResults
down arrowDiscussion
down arrowReferences
 
Patients
The study population comprised 3582 patients with significant primary stenoses in native coronary arteries who were prospectively enrolled in four major restenosis trials19 20 21 22 and who underwent successful coronary angioplasty (postprocedural stenosis <50%). These trials demonstrated that active therapy had no effect on restenosis or clinical outcome in the first 6 months after balloon angioplasty, so for the purposes of this study, the data for the active and placebo groups were pooled. Men or women were eligible for study entry if they were symptomatic or asymptomatic with stable or unstable angina pectoris and proven angiographically significant narrowing in one or more major coronary arteries. Informed consent was obtained in all cases before the coronary angioplasty procedure. Patients with evolving myocardial infarction and significant left main disease were excluded from the study.

Angioplasty Procedure and Follow-up Angiography
Coronary angioplasty was performed with a steerable, moveable guide wire system by the femoral route. Standard balloon catheters were used. The choice of balloon type and brand, inflation duration, and inflation pressure was left to the discretion of the operator. Patients were followed up for 6 months; then a follow-up study was performed. If symptoms recurred within 6 months, coronary angiography was performed earlier. If no definite restenosis was present and the follow-up time was less than 4 months, the patient was asked to undergo further coronary arteriography at 6 months.

Quantitative Angiography
In total, three coronary angiograms were obtained for each patient—before and after percutaneous transluminal coronary angioplasty (PTCA) and at angiographic follow-up. To standardize the method of data acquisition and to ensure exact reproducibility of the angiographic studies, measures were taken as previously described, and all angiograms were processed in a central angiographic core laboratory.19 20 22 The angiograms were recorded in such a manner that they were suitable for quantitative analysis by the computer-assisted CORONARY ANGIOGRAPHY ANALYSIS SYSTEM, which was described and validated earlier.23 24 Because the computer algorithm cannot measure total occlusions, a value of 0 mm was substituted for the minimal lumen diameter and a value of 100% for the pre-PTCA percent diameter stenosis. In these cases, the post-PTCA reference diameter was substituted for vessel size.

Definitions
Total Occlusion
As in previous studies, total occlusions were divided into absolute occlusions (Thrombolysis in Myocardial Infarction [TIMI] flow grade 0) where no anterograde filling beyond the lesion was visible and functional occlusions (TIMI grade 1) where faint, late anterograde opacification of the distal segment was present in the absence of a discernible luminal continuity.17 25

Occlusion at Follow-up Angiography
Occlusion at follow-up angiography was defined as the presence of an absolute or functional occlusion at the previously dilated angioplasty site on angiographic follow-up.

Angiographic Parameters Assessed
Vessel size refers to the reference diameter of the relevant coronary segment and is represented by the interpolated reference diameter pre-PTCA because this is the closest and most objective approximation of the disease-free vessel wall.

Minimum luminal diameter (MLD) is the point of maximal luminal narrowing in the analyzed segment.

Many criteria have been proposed for the assessment of restenosis.26 27 28 For the purposes of this study, two approaches were used: the categorical approach with the traditional cutoff point of >50% diameter stenosis at follow-up and a continuous approach that used absolute and relative loss, which reflect the behavior of the lesion during and after angioplasty and may be more representative of the pathological process involved during follow-up.28 29

Absolute gain and absolute loss represent the improvement in MLD achieved at intervention and the absolute change during follow-up respectively, measured in millimeters. Absolute gain is post-PTCA MLD minus pre-PTCA MLD. Absolute loss is post-PTCA MLD minus MLD at follow-up.

Relative gain and relative loss depict the improvement in MLD achieved at intervention and the change during follow-up respectively, normalized for vessel size. Relative gain is (post-PTCA MLD minus pre-PTCA MLD) divided by vessel size. Relative loss is (post-PTCA MLD minus MLD at follow-up) divided by vessel size.

The absolute net gain is the MLD at follow-up minus pre-PTCA MLD. The net gain index is the net gain normalized for the vessel size. The net gain index is (MLD at follow-up minus pre-PTCA MLD) divided by vessel size.

The loss index is the relation of late loss to acute gain: loss index is (MLD at follow-up minus post-PTCA MLD) divided by (post-PTCA MLD minus pre-PTCA MLD).

Statistical Analysis
Data were analyzed with the SAS statistical software package. Categorical variables are presented as absolute numbers (%). Continuous variables are expressed as mean value±SD. Differences between groups were evaluated with adjusted {chi}2 tests for categorical variables and Student's t tests for continuous variables. The contributions of clinical, angiographic, and procedural variables to the categorical outcome parameters were evaluated with logistic regression analysis. For the continuous outcome parameter (absolute loss), multiple linear regression analysis was used. Categorical variables were dichotomized and entered into the analysis as indicator variables with values of 0 and 1. Selection of variables was achieved in a stepwise fashion. The adjusted R2 was used as the criterion for model selection. Probability values <.05 were considered significant.


*    Results
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 up arrowAbstract
 up arrowIntroduction
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*Results
down arrowDiscussion
down arrowReferences
 
Patient Characteristics and Clinical Follow-up
The study population comprised 2950 patients (3583 lesions, 1.21 lesions per patient) who successfully completed the study and had follow-up quantitative angiography. The overall angiographic restudy rate was 86% of all patients undergoing successful PTCA. We found that 266 lesions in 249 patients out of 3583 lesions in 2950 patients complied with the angiographic definition of total occlusion. Of these, 109 were absolute and 157 were functional total occlusions.

Tables 1Down and 2Down summarize the clinical and angiographic characteristics of the 249 patients with occlusions compared with the 2701 with stenoses. Patients with total occlusions were younger and had a significantly higher rate of previous myocardial infarction than patients with stenoses. Furthermore, the duration of angina in this group was significantly shorter than in stenoses. Additionally, the presence of thrombus either before or after PTCA was significantly higher in occlusions. Of the procedural characteristics, the nominal size of the largest balloon was significantly higher in stenoses, while the total number of balloon inflations required, total duration, and maximum inflation pressure were higher in occlusions. Within the occlusions group, there were no significant differences between lesions with total and functional occlusions.


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  		Table 1. Baseline Clinical Characteristics of Patients With Occlusions and Stenoses Before Coronary Angioplasty


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  		Table 2. Baseline Angiographic and Procedural Data of Patients With Occlusions and Stenoses Before Coronary Angioplasty

Seventy-one (28.5%) of the patients with successfully dilated total occlusions and 598 (22.1%) of the patients with stenoses had clinical end points (additional PTCA, coronary artery bypass graft [CABG] surgery, acute myocardial infarction, or death) during follow-up. The difference was statistically significant (P=.026). The individual components of death, myocardial infarction, CABG, and re-PTCA were 0%, 3.6%, 3.6%, and 21.3%, respectively, for occlusions and 0.2%, 2.8%, 2.4%, and 16.7%, respectively, for stenoses. The differences in the individual clinical end points between the two groups were also statistically significant (P=.022). Fig 1Down summarizes the time course of clinical end points. Although the mean time to clinical follow-up was similar in the two groups, when we compared the pattern of occurrence of clinical end points by way of the log-rank test, clinical end points in the occlusions group were found to occur earlier than in stenoses (P=.022).



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  		Figure 1. Graph showing cumulative distribution curves of clinical end points over time for total occlusions and stenoses. Numbers given are mean±SD (days). *P<.05.

Interestingly, when lesions that went on to occlude at follow-up angiography were excluded from the analysis, 50 patients (25.1%) with occlusions and 541 patients (21.1%) with stenoses reached a clinical end point, and the difference was no longer statistically significant (P=.217). The individual clinical end points and the time to a clinical end point were also no longer significantly different (P=.238 and .214, respectively).

Quantitative Angiographic Analysis
A mean of 2.12 matched angiographic projections per lesion had satisfactory quantitative analysis performed at the central Angiographic Core Laboratory before and after PTCA and at follow-up (Table 3Down). The reference diameter was significantly lower in occlusions than in stenoses, and this difference remained at follow-up. As expected, the MLD increased substantially more after dilatation of occlusions than of stenoses, which was reflected in the substantially greater relative gain. Nevertheless, the post-PTCA MLD was significantly lower in occlusions, perhaps reflecting the smaller vessel diameter in this group (Fig 2aDown). When this was taken into account, the percent stenosis after PTCA was similar in both groups (Fig 2bDown). At follow-up, previously occluded lesions deteriorated significantly more in terms of both absolute and relative loss (Fig 3Down, Table 3Down), resulting in a smaller follow-up MLD and higher percent stenosis (Fig 2aDown and 2bDown, Table 3Down). Thus, in addition to restenosis being higher when the continuous, absolute, and relative loss approach was used, the restenosis rate when the categorical approach was used was also significantly higher (44.74% in occlusions compared with 33.95% in stenoses; P<.001; relative risk, 1.575; CI, 1.224 to 2.027).


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  		Table 3. Quantitative Analyses of 266 Lesions in 249 Patients With Occlusions and 3317 Stenoses in 2701 Patients Included in the Analysis



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  		Figure 2. Graphs showing (a) cumulative distribution curves of mean luminal diameter (MLD) after percutaneous transluminal coronary angioplasty (PTCA) and at follow-up for total occlusions and stenoses and (b) cumulative distribution curves of percentage stenosis after PTCA and at follow-up for total occlusions and stenoses. Numbers given are mean±SD. *P<.001.



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  		Figure 3. Graphs showing (a) cumulative distribution curves of absolute loss (Abs) (change in mean luminal diameter [MLD] from before percutaneous angioplasty to follow-up) for total occlusions and stenoses and (b) cumulative distribution curves of relative (rel) loss (change in MLD from before percutaneous angioplasty to follow-up corrected for vessel size) for total occlusions and stenoses. Numbers given are mean±SD. *P<.001.

Although angiographic restenosis was higher in occlusions than stenoses, there were no significant differences in the presentation of restenosis between the two groups. Of recanalized total occlusions with angiographic restenosis, 40% were symptom-free, while 18.5% complained of angina and 41.5% had a clinical end point. This compares with 39.9%, 18.7%, and 41.4%, respectively, for stenoses with angiographic restenosis.

The higher restenosis rate in the occlusions was due predominantly to an increased number of occlusions at follow-up angiography in this group (19.2% versus 5.0% for stenoses, P<.001). Thus, recanalized occlusions accounted for 23.5% of all occlusions at follow-up angiography even though they formed only 7% of the total study population. The relative risk for occlusion at follow-up angiography was 4.503 (95% CI, 3.196 to 6.344).

Subgroup Analysis of Occlusions Group
Subgroup analysis of the occlusions group revealed 109 absolute and 157 functional occlusions (Table 4Down). The reference diameter after angioplasty was significantly higher in absolute than in functional occlusions, but this difference did not persist to follow-up angiography. There were no significant differences in the MLD or percent stenosis after PTCA or at follow-up (Table 4Down) between the two groups. The categorical restenosis rate (>50% diameter stenosis at follow-up) was almost identical (44.95% versus 44.59%) in the two groups. Although the reocclusion rate in absolute occlusions tended to be higher than in functional occlusions (23.9% versus 15.9%), this did not reach statistical significance (P=.06). By use of the continuous measurements of restenosis, the absolute and relative loss tended to be lower in functional occlusions (Table 4Down), resulting in a significantly higher net gain index and a significantly lower loss index.


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  		Table 4. Quantitative Angiographic Analysis of 109 Total and 157 Functional Occlusions Included in the Analysis

Univariate and Multivariate Analyses of Restenosis in Total Occlusions
Univariate analysis of the available clinical-, procedural-, and lesion-related characteristics was performed to assess whether any of these variables were associated with an increased categorical restenosis rate (Table 5Down). The only significant associations were with a shorter duration of angina, a longer balloon total inflation time, higher residual stenosis after PTCA, and a lower relative gain. Stepwise logistic regression analysis was used to further evaluate the relation between this dichotomous definition of restenosis and the above variables, as well as all other clinical, lesion, and procedural characteristics. The number of diseased vessels and the percent stenosis after PTCA were positively related; duration of angina (in days) was negatively related to the probability of restenosis at follow-up (Table 6Down).


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  		Table 5. Univariate Analysis of Patient-, Lesion-, and Procedure-Related Characteristics Relevant to Long-term Restenosis1 in 266 Occlusions


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  		Table 6. Regression Analyses to Evaluate the Respective Contributions of Clinical, Angiographic, and Procedural Variables on the Categorical Restenosis Rate,1 Absolute Loss, and Reocclusion During Follow-up

Univariate analysis of clinical, procedural, and lesion characteristics related to absolute loss showed the only significant associations to be with total inflation time (P=.0004), presence of thrombus (P=.0039), post-PTCA MLD (P=.0144), duration of angina (P=.0262), left anterior descending coronary artery location (P=.0418), and lesion calcification (P=.0443). Multiple linear regression analysis was used to further evaluate absolute loss. Of the variables assessed, total inflation time (in seconds) and the presence of thrombus were both positively related to absolute loss (Table 6Up).

Univariate and Multivariate Analysis of Occlusions at Follow-up Angiography
The finding that the higher restenosis rate after dilatation of occlusions was due predominantly to an increased number of reocclusions at follow-up angiography in this group prompted us to examine a number of variables predictive of reocclusion (Table 7Down). The clinical characteristics of the two groups were similar, although lesions that went on to reocclude had a shorter duration of angina (27±52 versus 74±132 weeks). Procedural characteristics were also similar, although lesions that went on to reocclude required a longer balloon inflation (537±478 versus 373±294 seconds). Logistic regression analysis was performed for the above and for all other clinical, angiographic, and procedural parameters thought to be associated with the occlusion at follow-up. Of these variables, the total inflation time (in seconds) was positively related and the post-PTCA reference diameter (in millimeters) was negatively related to reocclusion at follow-up angiography (Table 6Up).


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  		Table 7. Univariate Analysis of Patient, Lesion, and Procedural Characteristics Relevant to Reocclusion During Follow-up in 266 Occlusions


*    Discussion
up arrowTop
 up arrowAbstract
 up arrowIntroduction
 up arrowMethods
up arrowResults
*Discussion
down arrowReferences
 
Our study specifically addressed the problem of long-term luminal renarrowing after dilatation of total coronary occlusions in a large patient population with a control group, a high angiographic follow-up rate, and quantitative angiography at a predetermined time interval. We demonstrated using both a categorical and a continuous approach that restenosis is significantly greater after balloon dilatation of occlusions than of stenoses. Furthermore, we also showed that this is mainly the result of an increased rate of occlusion at follow-up angiography, which is specifically related to total inflation time and reference diameter after intervention. We also demonstrated that restenosis and reocclusion occur to an equal extent in both absolute and functional occlusions. These findings support and expand our current understanding of the long-term angiographic outcome after successful angioplasty of coronary occlusions.

Our overall restenosis rate of 44.7% with the categorical (>50% diameter stenosis) approach compares with the previously reported recurrence rate of 65% from our center3 and is within the 20% to 65% range described previously.2 3 5 6 10 11 12 13 14 15 16 Our restenosis rate, however, is significantly lower than those of the two largest studies published to date,5 6 perhaps as a result of our high angiographic follow-up rate. With univariate analysis, a number of risk factors have been postulated for the higher restenosis rate after dilatation of chronic occlusions. These include anatomic factors such as lesion location (left anterior descending and circumflex)6 14 and absence of functional occlusion,6 procedural factors such as multivessel dilatations6 and increased balloon inflations at higher pressures,10 and residual stenosis after intervention.6 12 14 15 A final risk factor is thought to be the presence of collateral vessels, which may exert competitive pressure even after they are no longer visibly functional30 and thus lead to an increased restenosis rate.

Univariate analysis in our study confirmed significant associations between the categorical definition of restenosis (>50% diameter stenosis at follow-up) and a shorter duration of angina, a longer balloon total inflation time, higher residual stenosis after PTCA, and a greater relative gain. Multivariate analysis, however, suggested that the only significant positive relations were with the number of diseased vessels and the percent stenosis after PTCA, while duration of angina was negatively related to the probability of restenosis at follow-up. The positive relation between the number of diseased vessels and the percent stenosis after PTCA with a categorical definition of restenosis is in keeping with previous studies in both occlusions6 and stenoses.31 The negative relation with duration of angina is also in keeping with previous studies suggesting a positive relation between recent onset of symptoms and a higher risk of restenosis.32 33 34

Interestingly, when we looked at the absolute loss as a marker of restenosis, an outcome measure that may better indicate the underlying pathological process involved, the above variables were no longer significant. The only significant relations were found to be with total inflation time and the presence of thrombus. Both of these were positively related to the subsequent absolute loss. The duration of balloon inflation as a positive risk factor may represent the sum total of the lesion characteristics and a more difficult, more complex procedure with a consequently higher risk of occlusion, thereby markedly influencing the absolute loss. In keeping with this is the fact that we also demonstrated total inflation time to be positively related to the subsequent risk of occlusion at follow-up angiography. The positive relation between the presence of thrombus and the subsequent absolute loss may also reflect a greater likelihood of subsequent occlusion, although we were unable to demonstrate this in our study. Previous studies, however, showed thrombus to be a risk factor for subsequent occlusion,35 36 perhaps acting as a nidus for further platelet deposition.

The main reason for the significantly higher rate of angiographic restenosis in recanalized occlusions in our study was the high rate of occlusion at follow-up angiography in this group (19.2% versus 5.0% after dilatation of stenoses). A number of reasons may account for this. First, this group may represent a subset of the total population that has an intrinsic hematological propensity to thrombosis. Although our laboratory data did not confirm this, there are other hematologic factors such as fibrinogen levels that we did not measure that may influence reocclusion covertly.35

Second, there are substantial morphological differences between lesions,37 which may have considerable influence on the subsequent risk of occlusion. Angiography provides little information on this or on the pathway of subsequent recanalization, which may vary from subintimal to periatheromatous and transatheromatous.38 What effect these variables may have on the subsequent reocclusion and indeed restenosis rates is unknown. Differences in these lesion characteristics may be reflected in the total inflation time, which was significantly higher in lesions more likely to reocclude.

Third, the coronary vasomotor responses after balloon angioplasty of chronic total occlusions may be abnormal. Distal vasoconstriction occurs frequently after angioplasty and correlates well with coronary perfusion pressure, suggesting that chronic hypoperfusion resets epicardial coronary autoregulation and that restoration of normal perfusion pressure after PTCA may provoke reflex vasoconstriction,39 thus precipitating early reocclusion.

Finally, the increased reocclusion rate may relate to local flow dynamics. The reference diameters before and after PTCA and at follow-up were significantly lower in occlusions than in stenoses. Furthermore, within the occlusions group multivariate analysis suggested that there is a negative relation between vessel size and subsequent risk of reocclusion. Thus, successfully dilated occlusions in larger vessels were less likely to reocclude than those in smaller vessels. This is in keeping with experimental work that suggested that smaller vessel diameters and hence higher shear rates favor local platelet activation and deposition,40 41 resulting in a greater likelihood of occlusion.

In addition to being responsible for the higher rate of angiographic restenosis, the high reocclusion rate in recanalized occlusions also seems to have been responsible for the higher rate of clinical events in this group of patients. Patients with recanalized occlusions had a significantly higher proportion of clinical events, mainly in terms of myocardial infarction, CABG, and repeated PTCA. Furthermore, these occurred earlier in occlusions than in stenoses. When patients with occlusions that went on to occlude at the time of follow-up angiography were removed from the analysis, the differences between the two groups were no longer significant, suggesting that the excess risk relates to the higher rate of occlusion at follow-up angiography. Interestingly, despite the higher rate of reocclusion in recanalized occlusions, there were no significant differences in the presentation of restenosis between the two groups, with approximately 40% of patients with angiographic restenosis in both groups being symptom-free.

Although studies of total occlusions suggest that there are important differences in the acute success rates between total and functional occlusions,7 8 our data suggest that in terms of restenosis and reocclusion, there is little difference between the two groups. Although reocclusion after successful dilatation of total occlusions was higher than in functional occlusions (23.9% versus 15.9%), this did not reach statistical significance. However, there was a tendency for functional occlusions to mount less of a fibroproliferative response, which was reflected in the significantly greater net gain index and lower loss index. The cause for this is unclear but is likely to reflect differences in the underlying pathological substrate.

Clinical Implications
Up to 20% of patients undergoing diagnostic catheterization have one or more total occlusions; thus, they make up 10% to 20% of the total angioplasty population.42 Furthermore, in multivessel disease, they may make the difference in referring the patient for angioplasty or for CABG surgery. Although great attention has been paid to increasing the acute success rate with the use of sophisticated new devices such as the low-speed rotational angioplasty43 and the Excimer laser,44 relatively little attention has been paid to long-term restenosis and its amelioration. Our results suggest that the higher restenosis in these lesions is likely to relate in part to the very high rate of occlusion at follow-up angiography in this group. Thus, it suggests that if we can identify these lesions and stop reocclusion, then the angiographic and clinical courses of recanalized total occlusions are likely to be similar to those of stenoses. The question of how we do this, however, is a vexing one. The clinical course in our patient population and previous studies would suggest that reocclusions tend to occur early.45 A number of pharmacological and mechanical approaches have been tried. Ellis and colleagues17 demonstrated that drug therapy with aspirin, dipyridamole, or warfarin did not influence the overall restenosis rate. In a prospective study, Di Sciascio and colleagues46 demonstrated that restenosis is not modified by a longer balloon inflation time. A more recent study assessed the value of coronary stenting for dissection with threatened closure following recanalization of total occlusions.47 The restenosis rate at follow-up was high at 57%, as was the recurrent occlusion rate (20%). When stenting was used routinely after recanalization of chronic total occlusions and hence when vigorous anticoagulation was used, the restenosis rate was low at 24% in a small patient population (65 patients) with an 80% angiographic follow-up rate.48 Thus, whether the reocclusion rate can be ameliorated by additional (eg, stenting) or alternative percutaneous revascularization techniques (high-speed rotational atherectomy or laser angioplasty) with or without concomitant pharmacological therapy remains to be established.

Study Limitations
A number of limitations of the present study are to be acknowledged. First, the study was a retrospective analysis of prospectively gathered data and hence is subject to the limitations inherent in any retrospective study.

Second, there were minor variations in the entry criteria of the studies. In CARPORT and PARK, for example, patients were randomized before PTCA, whereas in MERCATOR and MARCATOR, patients were entered into the trial only after a successful angioplasty procedure.19 20 21 22 Thus, we are unable to comment on clinical, angiographic, or procedural factors influencing the acute success rate of the procedure. Furthermore, patients taking part in large multicenter studies like these are selected in certain ways; therefore, care needs to be taken in extrapolating our results to the broader angioplasty population.

Third, for obvious reasons, the reference diameter in the occlusions group before PTCA could not be reliably measured, so we took the reference diameter after dilatation as the reference diameter before dilatation. The statistical analyses remain valid, however, because even if we substitute the post-PTCA reference diameter for the pre-PTCA reference diameter in the stenoses group, the significant differences between the two groups remain.

Fourth, because of the nature of the data, we unfortunately are unable to comment on whether certain previously documented risk factors for restenosis such as the degree of collateral supply11 or the measured coronary wedge pressure49 50 may relate to reocclusion rather than to long-term restenosis.

Finally, data from the active therapy group and the placebo group were amalgamated. Although the drugs did not seem to influence the overall restenosis rate, the Ketanserin in the PARK study and the thromboxane A2-receptor blocker in the CARPORT studies may have had a covert influence on the reocclusion rate after dilatation of occlusions that we were unable to detect.

Nonetheless, we believe that the merging of the data is justified because the data amalgamated were common to all studies and the angiographic criteria were standardized, with one central laboratory performing the quantitative angiographic analysis in all studies. Furthermore, the resulting large study population provides a unique opportunity to obtain accurate quantitative angiographic data at a predetermined time interval in a field where such few data currently exist.

Conclusions
These results indicate that successfully dilated coronary occlusions, both total and functional, have a higher rate of angiographic restenosis at 6 months than stenoses. This is due chiefly to a higher rate of occlusion at follow-up angiography in this group of lesions. Measures aimed at reducing restenosis after successful dilatation of coronary occlusions should therefore be focused in this direction.


*    Acknowledgments
 
Dr Violaris is the recipient of a 1992-1994 Wellcome Trust International Research fellowship. We gratefully acknowledge the continually high-quality quantitative angiographic analysis from the staff of the Angiographic Core Laboratory at Cardialysis, Rotterdam, and the sponsorship of Glaxo Group Research Ltd, Middlesex, United Kingdom; F Hoffmann-La Roche Ltd, Basel, Switzerland; and Janssen Research Foundation, Beerse, Belgium. We would also like to acknowledge the work of the 31 European, 40 American, and 7 Canadian centers that participated in the CARPORT, MERCATOR, MARCATOR, and PARK studies, without whose assistance this study would not have been possible. A full list of participating centers can be found in References 19 through 22.

Received October 5, 1994; revision received November 21, 1994; accepted December 3, 1994.


*    References
up arrowTop
 up arrowAbstract
 up arrowIntroduction
 up arrowMethods
up arrowResults
up arrowDiscussion
*References
 

  1. Grüntzig AR, Senning A, Siegenthaler WE. Nonoperative dilatation of coronary artery stenosis: percutaneous transluminal coronary angioplasty. N Engl J Med. 1979;301:61-68. [Abstract]
  2. Holmes DR Jr, Vlietstra RE, Reeder GS, Bresnahan JF, Smith HC, Bove AA, Schaff HV. Angioplasty in total coronary artery occlusion. J Am Coll Cardiol. 1984;3:845-849. [Abstract]
  3. Serruys PW, Umans V, Heyndrickx GR, van den Brand M, de Feyter PJ, Wijns W, Jaski B, Hugenholtz PG. Elective PTCA of totally occluded coronary arteries not associated with acute myocardial infarction; short-term and long-term results. Eur Heart J. 1985;6:2-12. [Abstract/Free Full Text]
  4. Stone GW, Rutherford BD, McConahay DR, Johnson WL Jr, Giorgi LV, Ligon RW, Hartzler GO. Procedural outcome of angioplasty for total coronary artery occlusion: an analysis of 971 lesions in 905 patients. J Am Coll Cardiol. 1990;15:849-856. [Abstract]
  5. Bell MR, Berger PB, Bresnahan JF, Reeder GS, Bailey KR, Holmes DR Jr. Initial and long-term outcome of 354 patients after coronary balloon angioplasty of total coronary artery occlusions. Circulation. 1992;85:1003-1011. [Abstract/Free Full Text]
  6. Ivanhoe RJ, Weintraub WS, Douglas JS Jr, Lembo NJ, Furman M, Gershony G, Cohen CL, King SB. Percutaneous transluminal coronary angioplasty of chronic total occlusions: primary success, restenosis, and long-term clinical follow-up. Circulation. 1992;85:106-115. [Abstract/Free Full Text]
  7. LaVeau PJ, Remetz MS, Cabin HS, Hennecken JP, McConnell SH, Rosen RE, Cleman MW. Predictors of success in percutaneous transluminal coronary angioplasty of chronic total occlusions. Am J Cardiol. 1989;64:1264-1269. [Medline] [Order article via Infotrieve]
  8. Stewart JT, Denne L, Bowker TJ, Mulcahy DA, Williams MG, Buller NG, Sigwart U, Rickards AF. Percutaneous transluminal coronary angioplasty in chronic coronary artery occlusion. J Am Coll Cardiol. 1993;21:1371-1376. [Abstract]
  9. Tan KH, Sulke AN, Taub NA, Watts E, Sowton E. Coronary angioplasty of chronic total occlusions: determinants of procedural success. J Am Coll Cardiol. 1993;21:76A. Abstract.
  10. Clark DA, Wexman MP, Murphy MC, Fishman-Rosen J, Shaw RE, Stertzer SH, Myler RK. Factors predicting recurrence in patients who have had angioplasty (PTCA) for total occluded vessels. J Am Coll Cardiol. 1986;7(suppl):20A. Abstract.
  11. Libow MA, Leimgruber PP, Roubin GS, Grüntzig AR. Restenosis after angioplasty (PTCA) in chronic total coronary artery occlusion. J Am Coll Cardiol. 1985;5(suppl):445. Abstract.
  12. DiSciascio G, Vetrovec GW, Cowley MJ, Wolfgang TC. Early and late outcome of percutaneous transluminal coronary angioplasty for subacute and chronic total coronary occlusion. Am Heart J. 1986;111:833-839. [Medline] [Order article via Infotrieve]
  13. Melchior JP, Meier B, Urban P, Finci L, Steffenino G, Noble J, Rutishauser W. Percutaneous transluminal coronary angioplasty for chronic total coronary arterial occlusion. Am J Cardiol. 1987;59:535-538. [Medline] [Order article via Infotrieve]
  14. Ellis SG, Shaw RE, King SB, Myler RK, Topol EJ. Restenosis after excellent angiographic angioplasty result for chronic total coronary artery occlusion: implications for newer percutaneous revascularization devices. Am J Cardiol. 1989;64:667-668. [Medline] [Order article via Infotrieve]
  15. Warren RJ, Black AJ, Valentine PA, Manolas EG, Hunt D. Coronary angioplasty for chronic total occlusion reduces the need for subsequent coronary bypass surgery. Am Heart J. 1990;120:270-274. [Medline] [Order article via Infotrieve]
  16. Finci L, Meier B, Favre J, Righetti A, Rutishauser W. Long-term results of successful and failed angioplasty for chronic total coronary arterial occlusion. Am J Cardiol. 1990;66:660-662. [Medline] [Order article via Infotrieve]
  17. Ellis SG, Shaw RE, Gershony G, Thomas R, Roubin GS, Douglas JS Jr, Topol EJ, Startzer SH, Myler RK, King SB. Risk factors, time course and treatment effect for restenosis after successful percutaneous transluminal coronary angioplasty of chronic total occlusion. Am J Cardiol. 1989;63:897-901. [Medline] [Order article via Infotrieve]
  18. Haase J, Keane D, di Mario C, Escaned J, Slager CJ, Serruys PW. How reliable are geometric coronary measurements? In vitro and in vivo validation of digital and cinefilm-based quantitative coronary analysis systems. In: Serruys PW, Foley DP, de Feyter PJ, eds. Quantitative Coronary Angiography in Clinical Practice. Norwell, Mass: Kluwer Academic Publishers; 1994:27-49.
  19. Serruys PW, Rutsch W, Heyndrickx GR, Danchin N, Mast EG, Wijns W, Rensig BJ, Vos J, Stibbe J. Prevention of restenosis after percutaneous transluminal coronary angioplasty with thromboxane A2-receptor blockade: a randomized, double-blind, placebo-controlled trial: Coronary Artery Restenosis Prevention on Repeated Thromboxane-Antagonism Study (CARPORT). Circulation. 1991;84:1568-1580. [Abstract/Free Full Text]
  20. MERCATOR Study Group. Does the new angiotensin converting enzyme inhibitor Cilazapril prevent restenosis after percutaneous transluminal coronary angioplasty? Results of the MERCATOR study: a multicenter, randomized, double-blind, placebo-controlled trial. Circulation. 1992;86:100-110. [Abstract/Free Full Text]
  21. Faxon DP, for the MARCATOR Study Group. Effect of high dose angiotensin-converting enzyme inhibition on restenosis: final results of the MARCATOR study, a multicenter, double-blind, placebo-controlled trial of Cilazapril. J Am Coll Cardiol. 1995;25:362-369. [Abstract]
  22. Serruys PW, Klein W, Tijssen JGP, Rutsch W, Heyndrickx GR, Emanuelsson H, Ball SG, Decoster O, Schroeder E, Leibermann H, Eichhorn E, Willerson JT, Anderson HV, Khaja F, Alexander RW, Baim D, Melkert R, van Oene JC, van Gool R. Evaluation of ketanserin in the prevention of restenosis after percutaneous transluminal coronary angioplasty: a multicenter randomized double blind placebo controlled trial: the Post-Angioplasty Restenosis Ketanserin (PARK) trial. Circulation. 1993;88:1588-1601. [Abstract/Free Full Text]
  23. Di Mario C, Haase J, den Boer A, Reiber JH, Serruys PW. Edge detection versus densitometry in the quantitative assessment of stenosis phantoms: an in vivo comparison in porcine coronary arteries. Am Heart J. 1992;124:1181-1189. [Medline] [Order article via Infotrieve]
  24. Haase J, Di Mario C, Slager CJ, van der Giessen WJ, den Boer A, de Peyter PJ, Reiber JH, Verdouw PD, Serruys PW. In-vivo validation of on-line and off-line geometric coronary measurements using insertion of stenosis phantoms in porcine coronary arteries. Cathet Cardiovasc Diagn. 1992;27:16-27. [Medline] [Order article via Infotrieve]
  25. TIMI Study Group. The thrombolysis and myocardial infarction (TIMI) trial: phase I findings. N Engl J Med. 1985;312:932-936. [Medline] [Order article via Infotrieve]
  26. Beatt KJ, Serruys PW, Hugenholtz PG. Restenosis after coronary angioplasty: new standards for clinical studies. J Am Coll Cardiol. 1990;15:491-498. [Abstract]
  27. Kuntz RE, Baim DS. Defining coronary restenosis: newer clinical and angiographic paradigms. Circulation. 1993;88:1310-1323. [Free Full Text]
  28. Serruys PW, Foley DP, de Feyter PJ. Restenosis after coronary angioplasty: a proposal of new comparative approaches based on quantitative angiography. Br Heart J. 1992;68:417-424.
  29. Serruys PW, Foley DP, Kirkeeide RL, King SB III. Restenosis revisited: insights provided by quantitative coronary angiography. Am Heart J. 1993;126:1243-1267. [Medline] [Order article via Infotrieve]
  30. Meier B. Total coronary occlusion: a different animal? J Am Coll Cardiol. 1991;17:50B-57B.
  31. Guiteras Val P, Bourassa MG, David PR, Bonan R, Crepeau J, Dyrda I, Lesperance J. Restenosis after successful percutaneous transluminal coronary angioplasty: the Montreal Heart Institute experience. Am J Cardiol. 1987;60:50B-55B. [Medline] [Order article via Infotrieve]
  32. Holmes DR Jr, Vlietstra RE, Smith HC, Vetrovec GW, Kent KM, Cowley MJ, Faxon DP, Grüntzig AR, Kelsey SF, Detre KM, van Raden MJ, Mock MB. Restenosis after percutaneous transluminal coronary angioplasty (PTCA): a report from the PTCA Registry of the National Heart, Lung and Blood Institute. Am J Cardiol. 1984;53:77C-81C. [Medline] [Order article via Infotrieve]
  33. Leimgruber PP, Roubin GS, Hollman J, Cotsonis GA, Meier B, Douglas JS, King SB III, Grüntzig AR. Restenosis after successful coronary angioplasty in patients with single-vessel disease. Circulation. 1986;73:710-717. [Abstract/Free Full Text]
  34. Myler RK, Topol EJ, Shaw RE, Stertzer SH, Clark DA, Fishman J, Murphy MC. Multiple vessel coronary angioplasty: classification, results, and patterns of restenosis in 494 consecutive patients. Cathet Cardiovasc Diagn. 1987;13:1-15. [Medline] [Order article via Infotrieve]
  35. Harker LA. Role of platelets and thrombosis in mechanisms of acute occlusion and restenosis after angioplasty. Am J Cardiol. 1987;60:20B-28B. [Medline] [Order article via Infotrieve]
  36. Arora RR, Platko WP, Bhadwar K, Simpfendorfer C. Role of intracoronary thrombus in acute complications during percutaneous transluminal coronary angioplasty. Cathet Cardiovasc Diagn. 1989;16:226-229. [Medline] [Order article via Infotrieve]
  37. Katsuragawa M, Fujiwara H, Miyamae M, Sasayama S. Histologic studies in percutaneous transluminal coronary angioplasty for chronic total occlusion: comparison of tapering and abrupt types of occlusion and short and long occluded segments. J Am Coll Cardiol. 1993;21:604-611.[Abstract]
  38. Sanborn TA. Recanalization of arterial occlusions: pathologic basis and contributing factors. J Am Coll Cardiol. 1989;13:1558-1560. [Medline] [Order article via Infotrieve]
  39. Leung W-H. Coronary vasomotor response after angioplasty of chronic total occlusions: relation to change in coronary perfusion pressure. Circulation. 1993;88(suppl I):I-505. Abstract.
  40. Goldsmith HL, Turritto VT. Rheologic aspects of thrombosis and haemostasis: basic principles and applications. Thromb Haemost. 1986;56:415-435.
  41. Badimon L, Badimon JJ. Mechanisms of arterial thrombosis in non parallel streamlines: platelet thrombi grow on the apex of stenotic severely injured vessel wall: experimental study in a pig model. J Clin Invest. 1989;84:1134-1144.
  42. Baim DS, Safian RD. Coronary angioplasty for total occlusion: ongoing problems despite improving results. J Am Coll Cardiol. 1990;15:857-858. [Medline] [Order article via Infotrieve]
  43. Kaltenbach M, Hartmann A, Vallbracht C. Procedural results and patient selection in recanalization of chronic coronary occlusions by low speed rotational angioplasty. Eur Heart J. 1993;14:826-830. [Abstract/Free Full Text]
  44. Holmes DR Jr, Forrester JS, Litvack F, Reeder GS, Leon MB, Rothbaum DA, Cummins FE, Goldenberg T, Bresnahan JF. Chronic total obstruction and short-term outcome: the Excimer Laser Coronary Angioplasty Registry experience. Mayo Clin Proc. 1993;68:5-10. [Medline] [Order article via Infotrieve]
  45. Meier B. `Occlusion angioplasty': light at the end of the tunnel or dead end? Circulation. 1992;85:1214-1216. [Free Full Text]
  46. Di Sciascio G, Vetrovec GW, Lewis SA, Nath A, Cole SK, Edwards VL. Clinical and angiographic recurrence following PTCA for nonacute total occlusions: comparison of one- versus five-minute inflations. Am Heart J. 1990;120:529-532. [Medline] [Order article via Infotrieve]
  47. Bilodeau L, Iyer SS, Cannon AD, Agrawal SK, Dean LS, Hearn JA, Liu MW, Baxley WA, Roubin GS. Stenting as an adjunct to balloon angioplasty for recanalization of totally occluded coronary arteries: clinical and angiographic follow-up. J Am Coll Cardiol. 1993;21:292A. Abstract.
  48. Almagor Y, Borrione M, Maiello L, Khlat B, Finci L, Colombo A. Coronary stenting after recanalization of chronic total coronary occlusions. Circulation. 1993;88(suppl I):I-504. Abstract.
  49. Probst P, Baumgartner C, Gottsauner Wolf M. The influence of the presence of collaterals on restenoses after PTCA. Clin Cardiol. 1991;14:803-807. [Medline] [Order article via Infotrieve]
  50. Probst P, Zangl W, Pachinger O. Relation of coronary arterial occlusion pressure during percutaneous transluminal coronary angioplasty to presence of collaterals. Am J Cardiol. 1985;55:1264-1269. [Medline] [Order article via Infotrieve]



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