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J Am Coll Cardiol, 1999; 34:476-485
© 1999 by the American College of Cardiology Foundation
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CLINICAL STUDIES

Restenosis, late vessel occlusion and left ventricular function six months after balloon angioplasty in diabetic patients

Eric Van Belle, MD, PhDa, Kaveh Abolmaali, MDa, Christophe Bauters, MD, FACCa, Eugène P. McFadden, MRCPI, FACCa, Jean-Marc Lablanche, MD, FACCa and Michel E. Bertrand, MD, FACCa

a Department of Cardiology, University of Lille, Lille, France

Manuscript received November 17, 1998; revised manuscript received March 6, 1999, accepted April 19, 1999.

Reprint requests and correspondence: Dr. Michel E. Bertrand, Service de Cardiologie B, Hôpital Cardiologique, Boulevard du Professeur J. Leclercq, 59037 Lille Cedex, France
bertrandme{at}aol.com


   Abstract
Top
 Abstract
Methods
 Results
 Discussion
 References
 
OBJECTIVES

We studied angiographic outcome and its predictors after traditional coronary balloon angioplasty in diabetics. We further examined whether changes in ejection fraction were influenced by the status of the dilated site(s) at follow-up.

BACKGROUND

Recent studies have suggested that diabetics have a particularly poor outcome after balloon angioplasty. The reasons for this observation are not known.

METHODS

We investigated procedural and six-month angiographic outcome, analyzed by quantitative coronary angiography, and left ventricular function in 485 consecutive diabetics (627 lesions) treated by balloon angioplasty without stent implantation.

RESULTS

The procedure was successful in 455 (94%) patients; angiographic follow-up was available in 377 patients (83%). At follow-up, the rates of restenosis and total occlusion were 62% and 13%, respectively. Five independent predictors of restenosis were identified: the presence of organ damage, a saphenous vein graft (SVG) angioplasty, a bifurcation lesion, a Thrombolysis in Myocardial Infarction (TIMI) flow <3 preprocedure and the degree of residual stenosis. Four independent predictors of vessel occlusion were identified: treatment with insulin, a SVG angioplasty, a TIMI flow <3 preprocedure and the degree of residual stenosis after angioplasty. Late vessel occlusion at angioplasty site(s) was observed in 15% of patients, ranging from 11% for a one-site procedure to 37% for a three-site procedure. This complication was associated with a decrease in ejection fraction at follow-up (–6.2 ± 9.9%, p = 0.0001), whereas no significant change was observed in patients without occlusion.

CONCLUSIONS

This study shows that late vessel occlusion is a frequent mode of restenosis in diabetic patients and is associated with a significant decrease in ejection fraction. This could partly explain the poor long-term clinical outcome reported in such patients after traditional balloon angioplasty.

Abbreviations and Acronyms
  CI = confidence interval
  LVEDVI = left ventricular end-diastolic volume index
  LVEF = left ventricular ejection fraction
  MLD = minimal lumen diameter
  QCA = quantitative coronary angiography
  PTCA = percutaneous transluminal coronary angioplasty
  SVG = saphenous vein graft
  TIMI = Thrombolysis in Myocardial Infarction

Coronary artery disease is frequently encountered in diabetic patients (1). Revascularization may be accomplished in such patients either by coronary artery bypass grafting or by percutaneous transluminal coronary angioplasty (PTCA). Diabetes has previously been associated with high restenosis rates after balloon angioplasty (2–6) and a poor long-term clinical outcome (7–10). The results of these studies have recently called into question the use of balloon angioplasty in this subset of patients. However, the actual rate of restenosis after balloon angioplasty in diabetics is still not clearly known, varying from 35% to 71%, these figures being drawn from studies that included only small numbers of diabetic patients (3–6,11–17). It is still not clear whether diabetics may be considered as a homogeneous population regarding their angiographic outcome or whether some additional risk factors may influence outcome. In addition the BARI and CABRI studies (9,10), by showing that clinical outcome of diabetic patients treated by balloon angioplasty was worse than after bypass surgery, may suggest a specific deleterious interaction between diabetes and vascular healing after angioplasty. However, the link between angiographic and clinical outcome is not known.

We thus studied the procedural and six-month angiographic outcome, assessed by quantitative coronary angiography (QCA), in 485 consecutive diabetics (627 lesions) who underwent traditional coronary balloon angioplasty without adjunctive stent implantation in our institution, where we recommend angiographic follow-up to all patients who undergo a successful procedure. We further determined the predictors of angiographic outcome in that population and examined whether changes in left ventricular function between PTCA and follow-up were influenced by the status of the dilated sites at follow-up angiography.


   Methods
Top
 Abstract
 Methods
Results
 Discussion
 References
 
Study population.   From the records of our catheterization laboratory, we identified 485 diabetics (358 men and 127 women) out of 2,670 (18%) patients treated by traditional balloon angioplasty without adjunctive stent implantation between January 1993 and December 1995. Patients undergoing primary or rescue balloon angioplasty for acute myocardial infarction were not included.

At the time of the initial procedure patients were classified as diabetic if they were treated by oral hypoglycemic drugs or insulin or if they had a previous history, documented on their medical chart, of elevated (≥140 mg/dl) fasting blood glucose on at least two separate occasions in conjunction with ongoing dietary measures. They were classified in three categories depending on antidiabetic management at the time of the initial procedure: 1) diet alone, 2) oral hypoglycemic drugs (diet and oral hypoglycemic drugs but no insulin) and 3) insulin (irrespective of other therapy).

Baseline blood glucose and creatinine levels as well as the presence of other organ damage (retinopathy, nephropathy, neuropathy), as documented in the medical charts, were recorded.

Angioplasty procedure.   Balloon angioplasty was performed according to the standard technique in our laboratory (18). All patients received aspirin (100 to 300 mg/day) started at least 24 h before the procedure and continued indefinitely. A bolus dose of heparin (10,000 IU) was administered just before PTCA. When the procedure was performed in the morning, no heparin was administered after the procedure, and the introducer sheath was removed when the effects of heparin had worn off. When the procedure was performed in the afternoon, 1,000 IU of heparin per hour were infused until 6 AM the next day, and the sheath was removed later that morning (18). A vascular segment was considered successfully treated when the residual luminal narrowing in the dilated segment, immediately after angioplasty, was <50%. The procedure was considered successful when at least one vascular segment was successfully treated and when no major complication (electrocardiographic or enzymatic evidence of myocardial infarction, the need for bypass surgery during hospitalization or in-hospital death) occurred.

Angiography was performed in at least two projections, after intracoronary injection of isosorbide dinitrate (2 mg) and just before and immediately after angioplasty. These projections were recorded in our database, and the follow-up angiogram was performed after the intracoronary injection of isosorbide dinitrate in the same projections.

Angiographic and clinical follow-up.   During the study period we routinely attempted to obtain a follow-up angiogram six months after successful angioplasty, regardless of symptomatic status; angiography was performed earlier if there was a clinical indication. Patients with a failed procedure or patients who underwent surgical revascularization without a new coronary angiogram within six months or patients who died without a new coronary angiogram within six months were considered noneligible for the angiographic follow-up. Angiographic follow-up was actually performed at a mean of 6.9 ± 2.7 months in 377 patients (84% of eligible patients) and 476 lesions. Clinical follow-up was obtained at six months.

Angiographic analyses.   The qualitative analyses were performed independently by two experienced interventional cardiologists. Disagreements were resolved by a further joint reading. Lesions were classified in accordance with the American Heart Association/American College of Cardiology classification as modified by Ellis et al. (19). The anterograde blood flow was graded using the classification of the Thrombolysis in Myocardial Infarction (TIMI) study group (20).

Quantitative computer-assisted angiographic measurements were performed on end-diastolic frames with use of the CAESAR (Computer-Assisted Evaluation of Stenosis and Restenosis) system. A detailed description of this system has been reported previously (21). We routinely perform angiography in at least two projections after the intracoronary injection of isosorbide dinitrate (2 mg). These projections were recorded in our database, and the follow-up angiogram was performed, after injection of isosorbide dinitrate, in the same projections. The following definitions were used: the acute gain associated with the procedure was defined as the difference between the minimal lumen diameter (MLD) immediately after the procedure and the MLD before the procedure; the late loss during the follow-up period was defined as the difference between the MLD immediately after the procedure and the MLD at follow-up; the net gain was defined as the difference between the acute gain and the late loss; restenosis was defined as a >50% diameter stenosis at follow-up, and finally, complete vessel occlusion was defined as a TIMI grade flow = 0 or 1.

Quantitative evaluation of global left ventricular function.   Ventricular function was evaluated on single-plane right anterior oblique projection (30°) obtained before angioplasty and at follow-up. The left ventricular contours on end-systolic and end-diastolic frames were manually traced by a single observer who was unaware of the study protocol. The tracings were then digitized with a writing tablet and light pen into a PC 486 microcomputer. The left ventricular end-diastolic volume index (LVEDVI) (ml/m2) and left ventricular ejection fraction (LVEF) (percent shortening) were calculated according to the area length method, with use of the formula described by Kennedy et al. (22).

Statistical analysis.   Data are presented as mean ± SD. For the univariate analysis, continuous variables were divided into tertiles. Differences between proportions were assessed by chi-square analysis. Comparisons between groups for continuous data were made with paired Student t test or analysis of variance followed by the Scheffé F test as appropriate. A value of p < 0.05 was considered to indicate statistical significance.

To study the relation between a binary outcome parameter and multiple categorical and continuous determinants, a multiple logistic regression analysis was performed. Categorical independent variables were encoded as 0 (absent) or 1 (present). Continuous independent variables were incorporated without any change. The analysis was performed using the logistic procedure of the SAS software (version 6.11, SAS Institute, Cary, North Carolina) with a stepwise selection of the independent variables. Significance levels for entry and removal were 0.05 in both cases.


   Results
Top
 Abstract
 Methods
 Results
Discussion
 References
 
Baseline characteristics.   The baseline characteristics of the study population are shown in Table 1. Most of the 485 diabetics were male (74%), with a mean age of 62 ± 9 years. Thirty-one percent had documented complication of diabetes other than atherosclerosis (nephropathy, neuropathy or retinopathy). Twenty-four percent of the patients had unstable angina, and 29% had experienced a recent (<1 month) myocardial infarction. The numbers of diseased vessels and treated lesions were 1.78 ± 0.76 and 1.29 ± 0.51, respectively.


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  		Table 1 Baseline Clinical Characteristics of the 485 Diabetic Patients According to Their Antidiabetic Management

 
Twenty-two percent of patients were treated with diet alone, 66% were treated with oral hypoglycemic drugs and 12% with insulin. Patients treated with insulin were younger, more often women, smoked less and had more frequently documented complications of diabetes than the two other subgroups. Clinical presentation and severity of coronary artery disease was similar among the three subgroups.

The baseline lesion characteristics are shown in Table 2. Balloon angioplasty was performed at a recent infarct-related lesion in 21% of cases and for restenosis in 22% of cases. The dilated lesion was most often (47%) located in the left anterior descending artery, and less frequently in the right coronary artery (27%), the left circumflex artery (23%) or a saphenous vein graft (SVG) (4%). Eighteen percent of the lesions had TIMI grade flow <3.


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  		Table 2 Baseline Lesion Characteristics

 
Immediate outcome.   Procedural success was obtained in 455 patients (94%, Table 3). There were 15 major in-hospital complications: three patients had nonfatal myocardial infarction, four had re-PTCA, two had emergent coronary bypass grafting and six died during hospitalization. Uncomplicated failure (residual stenosis ≥50% by QCA) occurred in 15 additional patients. No significant difference was observed among the patients when classified according to their antidiabetic regimen.


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  		Table 3 Procedural Outcome of the 485 Diabetic Patients According to Their Antidiabetic Management

 
Six-month angiographic outcome.   Five patients died and two had coronary bypass surgery after discharge without recurrent angiography. Three hundred seventy-seven of the 448 remaining patients (84%) underwent angiographic follow-up. No significant difference in angiographic outcome was observed among the patients when classified according to their antidiabetic regimen.

The 71 patients without angiographic follow-up were slightly older than the 377 patients with angiographic follow-up (65 ± 9 years vs. 61 ± 9 years, p < 0.05), with a higher proportion of patients with hypertension (76% vs. 63%, p < 0.05) and a lower proportion of patients with hypercholesterolemia (51% vs. 67%, p < 0.05). No difference was observed between patients with or without follow-up in the other major baseline characteristics described in Tables 1 and 2.

Table 4 summarizes the quantitative angiographic data in the 476 lesions with angiographic follow-up. Restenosis, defined as the presence of >50% stenosis in the dilated segment at follow-up, was present in 297 (62%) of the 476 lesions. Of these lesions, 60 (13% of the 476 lesions) were totally occluded at follow-up and 237 (49% of the 476 lesions) had nonocclusive restenosis. Target lesion revascularization was performed at 165 lesions (35% of the 476 lesions).


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  		Table 4 Quantitative Angiography in the 476 Lesions With Angiographic Follow-up

 
Two hundred fifty-six of the 377 patients (68%) had at least one lesion with restenosis at follow-up. Of these patients, 55 (15% of the 377 patients) had at least one dilated lesion occluded at follow-up. For a patient, the risk that ≥1 lesion would be occluded at follow-up increased with the number of sites dilated during the initial procedure: 11% for a one-site procedure, 25% for a two-site procedure and 37% for a three-site procedure (p = 0.002). The risk of occlusion at a lesion was not modified by the number of lesions treated during the procedure (p = NS). At follow-up, 20 patients with late vessel occlusion had no angina (36%), 18 had stable angina (33%) and 17 had unstable angina or clinical evidence of recent myocardial infarction (31%).

Predictors of restenosis.   We analyzed predictors of restenosis in the 476 lesions with angiographic follow-up. All baseline characteristics as described in Tables 1 and 2, as well as the results of QCA performed before and immediately after the procedure were included in the analysis. Table 5 shows the univariate predictors of restenosis (>50% diameter stenosis at follow-up) in the 476 lesions with angiographic follow-up. Among the clinical parameters, the level of creatinine and the presence of organ damage were associated with a higher rate of restenosis. Among the lesion-related parameters, angioplasty at a de novo rather than a restenotic lesion, a SVG lesion, a complex lesion, an eccentric lesion, a lesion containing thrombus, a long lesion, a lesion with a TIMI grade flow <3 preprocedure, smaller MLD or a higher percent stenosis before PTCA as well as smaller MLD or a higher percent stenosis after PTCA were univariate predictors of restenosis.


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  		Table 5 Univariate Predictors of Restenosis in the 476 Lesions With Follow-up

 
By multivariate analysis, five independent predictors of restenosis were identified: the presence of organ damage, angioplasty at a SVG, a bifurcation lesion, a lesion with TIMI grade flow <3 preprocedure and the degree of residual stenosis after angioplasty (Table 6).


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  		Table 6 Multiple Logistic Regression Analysis for the Dependent Variable of Restenosis

 
Predictors of late vessel occlusion.   Table 7 shows the univariate predictors of late vessel occlusion. Among the clinical parameters, the requirement for insulin therapy and the presence of unstable angina or recent myocardial infarction were associated with a higher rate of late vessel occlusion. Among the lesion-related parameters, angioplasty at an infarct-related lesion, a SVG, a complex lesion, a lesion containing thrombus, a long lesion, a lesion with a TIMI grade flow <3 preprocedure as well as smaller MLD or a higher percent stenosis before PTCA were univariate predictors of late vessel occlusion.


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  		Table 7 Univariate Predictors of Late Vessel Occlusion in the 476 Lesions With Follow-up

 
By multivariate analysis, four independent predictors of late vessel occlusion were identified: requirement for insulin therapy, angioplasty at a SVG, a lesion with TIMI grade flow <3 preprocedure and the degree of residual stenosis after angioplasty (Table 8).


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  		Table 8 Multiple Logistic Regression Analysis for the Dependent Variable of Late Vessel Occlusion

 
Changes in left ventricular function.   Among the 377 patients with angiographic follow-up, 344 (91%) had ventriculograms before PTCA and at follow-up that were suitable for determination of left ventricular function. In the group as a whole, there was a small but statistically significant (p = 0.01) decrease in LVEF from 59.1 ± 15.0% before the PTCA to 57.9 ± 15.1% at follow-up. The LVEDVI at follow-up (74.1 ± 21.8 ml/m2) was similar to the LVEDVI before PTCA (74.7 ± 21.4 ml/m2). Patients were classified into three subgroups based on the patency of the dilated sites at follow-up: 1) patients with (at least one) occlusion at follow-up, 2) patients without occlusion but with (at least one) restenosis and 3) patients without occlusion or restenosis. There were no differences in LVEF and LVEDVI among subgroups before PTCA. During the follow-up period, however, there was a decrease in LVEF in patients with occlusion at follow-up (–6.2 ± 9.9%, p = 0.0001), whereas no significant change was observed in the two other subgroups (+0.5 ± 9.9% and –1.5 ± 9.5%, p = NS). Similarly a trend for an increase in LVEDVI was also noted in patients with vessel occlusion (+2.6 ± 10.2 ml/m2, p = 0.06), whereas no change was observed in the two other groups (–0.8 ± 11.3 ml/m2 and –1.7 ± 12.1 ml/m2, p = NS). These changes resulted in a significantly (p = 0.0005) lower LVEF in the group of patients with occlusion at follow-up (50.8 ± 12.4%) compared with the two other groups without occlusion (59.1 ± 15.2% and 59.6 ± 15.2%). Left ventricular end-diastolic volume index at follow-up was not statistically different among the three groups.


   Discussion
Top
 Abstract
 Methods
 Results
 Discussion
References
 
This study confirms that in diabetic patients, balloon angioplasty without stent implantation is associated with a poor angiographic outcome. More importantly, by virtue of the large number of patients included and the objective assessment of the results of angioplasty by QCA, it extends the results of previous studies by providing a more accurate estimate of the rate of restenosis in diabetics (62%). This study shows in addition that late vessel occlusion, 13% of lesions and 15% of patients, is a frequent mode of restenosis in diabetics and that this specific complication has a notable deleterious effect on left ventricular function. Finally, predictors of late vessel occlusion and restenosis were identified. These findings, especially the high rate of late vessel occlusion, could explain the poor long-term clinical outcome previously reported in diabetic patients after balloon angioplasty.

Procedural outcome.   The overall results of the angioplasty procedure were satisfactory, with a 94% procedural success rate. This is in agreement with a previous study by Stein et al. (8), including over 10,000 patients, in which the procedural success rate was similar in diabetic and nondiabetic patients (87% vs. 88%) and with the results of the BARI and EPILOG studies (9,23), in which in-hospital outcome after PTCA did not differ between diabetics and nondiabetics.

Restenosis rates in diabetic patients after balloon angioplasty.   Several studies have suggested that diabetes was a risk factor for restenosis after balloon angioplasty (2–6,12–17,24,25) (Table 9). In those studies the restenosis rate ranged from 35% to 71%. Each of these studies, however, had at least one of the following limitations; small numbers of diabetics (n < 100) (3,5,6,13–17,24,25), low rates of angiographic follow-up (<70%) (4,6,12,13,15,16,24) or assessment of the degree of stenosis without QCA (3–6,12–14,16). The present study has none of these limitations and may provide a more accurate estimate of the restenosis rate (62%, 95% confidence interval [CI]: 58% to 66%). This rate is significantly higher than that usually reported in the general population (30% to 35%) (2,26,27) and the restenosis rate we previously reported in a consecutive series of 243 nondiabetic patients treated in our institution with the same technique during the same time frame (36%, 95% CI: 30% to 42%) (25).


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  		Table 9 Results of Prior Studies on Angiographic Outcome in Diabetic Patients

 
Mechanisms of lesion recurrence after balloon angioplasty in diabetics.   Our study also demonstrates that late vessel occlusion, which occurs in 13% (95% CI: 10% to 16%) of all treated lesions and in 15% of patients (95% CI: 11% to 19%), is a frequent mode of restenosis in that population; nonocclusive restenosis is observed in 49% (95% CI: 45% to 53%) of lesions. The rate of late vessel occlusion in the present study (13%) is higher than that observed in the general population (3% to 6%) (2,26–28) and higher than the rate we previously reported in a contemporary series of 243 nondiabetic patients treated with the same technique (3%, 95% CI: 1% to 5%) (25). This rate compares with the high rates of late vessel occlusion that are found in patients undergoing angioplasty for total occlusion (19%) (27) or for angioplasty after myocardial infarction (13% to 21%) (29,30). A critical role for late vessel occlusion after balloon angioplasty in diabetics was already suggested by one of our previous studies (25) and Rensing et al.’s (2) report. These results therefore suggest that two distinct phenomena are involved in lesion recurrence after balloon angioplasty in diabetic patients: nonocclusive restenosis and late vessel occlusion.

The prothrombotic milieu present in diabetic patients is likely to explain the increased rate of late vessel occlusion observed in that population (31,32). Previous studies demonstrating that thrombus is both more frequently associated with coronary lesions in diabetics (33) and a predictor of late vessel occlusion after angioplasty (34) are consistent with this suggestion.

The respective roles of intimal hyperplasia and vascular remodeling in non-occlusive restenosis after balloon angioplasty in diabetics are not known. Kornowski et al.’s (35) study using intravascular ultrasound, suggests that intimal tissue growth is increased in diabetic patients after angioplasty; Moreno et al.’s (36) preliminary report suggests that the specific feature of atherectomy specimens from restenotic lesions retrieved in diabetics is not an enhanced smooth muscle proliferation but rather a greater fibrotic response that may lead to vessel constriction.

Risk factors for lesion recurrence after balloon angioplasty in diabetic patients.   To the best of our knowledge there is no information on risk factors of six-month angiographic outcome in the diabetic population. Most of the parameters we identified as risk factors for restenosis or late vessel occlusion are not specific to the diabetic population and were previously described in unselected populations (degree of baseline stenosis, unstable angina, totally occluded lesions and visible thrombus) (2). Similarly angioplasty at SVGs or recent infarct-related lesions were previously shown to be associated with high rates of restenosis or occlusion at follow-up (29,37,38).

Four points deserve specific comment. First, some risk factors identified were associated with unacceptable risks of occlusion (20% to 50%) and restenosis (70% to 94%) (angiographically visible thrombus, TIMI grade flow <3, infarct-related lesions or SVG). Second, even in the absence of known risk factors such as angioplasty at infarct-related lesions or at SVGs the risks of late vessel occlusion or restenosis in diabetics (11% and 60%, respectively) were still higher than those observed in the general population (2,26–28). Third, diabetics treated with insulin had higher rates of late vessel occlusion (23%) than patients treated with oral hypoglycemic drugs or hypoglycemic diet (12%). The reason for this observation is unclear, but may relate to an increased production of plasminogen activator inhibitor-1 in the vessel wall resulting in impaired local fibrinolysis (32). This observation is consistent with previous reports, in which insulin-requiring diabetics had a worse late clinical outcome after angioplasty than non–insulin-requiring diabetics (8,39). Finally, because advanced glycosylation is considered as the common mechanism implicated in the initiation and acceleration of multiple organ damage (nephropathy, neuropathy, retinopathy) (40), the increased rate of restenosis observed in the presence of organ damage may support a role of advanced protein glycosylation in the restenotic process in diabetics (31).

Occlusive restenosis and midterm outcome.   The propensity of diabetic patients to develop ischemia without, or with only limited symptoms is well known (41,42). In the present study, 36% of late vessel occlusions were asymptomatic. However, vessel occlusion was associated with a significant decrease in ejection fraction (–6.0%). Furthermore, due to the large proportion of patients with such occlusion (15%), a significant decrease in ejection fraction (–1.3%) was detected in the population as a whole. Vessel occlusion was also associated with a trend for an increase in left ventricular diastolic volumes. Nonocclusive restenosis, on the other hand, had no effect on left ventricular function. This observation underlines the shortcoming of clinical follow-up in detecting late vessel occlusion. The threshold for the performance of follow-up angiography should perhaps be more liberal in this population.

These results may also provide some insights into some of the findings of the BARI study (9). By showing that 5-year survival of diabetic patients with two- or three-vessel disease treated by balloon angioplasty was worse than after bypass surgery, the BARI study suggested a specific interaction between diabetes, vascular healing after angioplasty and survival. The 25% occlusion rate per diabetic patient treated at two or more sites, as reported in the present study, combined with the effect of these occlusions on left ventricular function may constitute an attractive explanation for the BARI findings.

Study limitations.   This was a retrospective single-center study; thus, complete information on the degree of diabetic control was not available and the technique of PTCA and medical management at our institution may have influenced the results. However, the patients were a consecutive group that underwent the angioplasty procedure in an institution where the probability that a patient undergoes follow-up angiography is less dependent on the symptomatic status after angioplasty. The high rate of angiographic follow-up coupled with the use of quantitative coronary angiography to assess angiographic outcome in a large cohort of patients, allowed an objective assessment of the angiographic probability of restenosis and late vessel occlusion. Finally this study is focused on the six-month follow-up and does not provide information on late clinical outcome.

Clinical implications.   This study demonstrates that despite a satisfactory procedural outcome, traditional balloon angioplasty in diabetics is associated with prohibitive rates of angiographic restenosis and target lesion revascularization. Furthermore, late vessel occlusion is a frequent mode of restenosis and is associated with a negative effect on left ventricular function. This emphasizes the need for new strategies designed to prevent late vessel occlusion in this setting. The results of recent studies suggest that the use of glycoprotein IIb/IIIa blockade or intracoronary stents might be useful to achieve this goal. In the EPILOG study, subgroup analysis demonstrated that the combination of glycoprotein IIb/IIIa blockade and balloon angioplasty was associated with a reduction in ischemic events (death and myocardial infarction) at six months in diabetic patients (23). Similarly, we previously reported that intracoronary stent implantation was associated with acceptable rates of restenosis and late vessel occlusion (<30% and <5%, respectively) in a series of diabetic patients (n = 88) treated in our institution in a period contemporary to the present study (25,43). Some of the risk factors identified in the present study (thrombus, TIMI grade flow <3 before procedure, SVG, degree of residual stenosis) are consistent with a possible benefit of these two strategies. These observations should encourage prospective studies to evaluate strategies designed to prevent late vessel occlusion. Our results suggest also that, due to its negative impact on left ventricular function, the high rate of occlusive restenosis may partly explain the poor late clinical outcome previously reported in this population (7–10). Whether a therapeutic strategy leading to a decrease of late vessel occlusion after angioplasty in diabetics improves late cardiac survival will also require prospective investigation.


   Footnotes
 
This work was supported in part by the Fondation de France.


   References
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 Abstract
 Methods
 Results
 Discussion
 References
 

  1. Frein FS, Scheuer J. Heart disease in diabetes. Rifkin H, Porte D Jr. Ellenberg and Rifkin’s Diabetes Mellitus Theory and Practice. New York: Elsevier Science Publishing; 1990. p. 812–823
  2. Rensing BJ, Hermans WRM, Vos J, et al. Luminal narrowing after percutaneous transluminal coronary angioplasty. A study of clinical, procedural, and lesional factors related to long-term angiographic outcome. Circulation. 1993;88:975–985[Abstract/Free Full Text]
  3. Holmes DR Jr, Vlietstra RE, Smith HC, et al. 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[CrossRef][Medline]
  4. Weintraub WS, Kosinski AS, Brown CL, King SB. Can restenosis after coronary angioplasty be predicted from clinical variables. J Am Coll Cardiol. 1993;21:6–14[Abstract]
  5. Quigley PJ, Hlatky MA, Hinohara T, et al. Repeat percutaneous transluminal coronary angioplasty and predictors of recurrent restenosis. Am J Cardiol. 1989;63:409–413[CrossRef][Medline]
  6. Lambert M, Bonan R, Côté G, et al. Multiple coronary angioplsaty: a model to discriminate systemic and procedural factors related to restenosis. J Am Coll Cardiol. 1988;12:310–314[Abstract]
  7. Kip KE, Faxon DP, Detre KM, et al. Coronary angioplsaty in diabetic patients. The National Heart, Lung, and Blood Institute percutaneous transluminal coronary angioplasty registry. Circulation. 1996;94:1818–1825[Abstract/Free Full Text]
  8. Stein B, Weintraub WS, Gebhart SSP, et al. Influence of diabetes mellitus on early and late outcome after percutaneous transluminal coronary angioplasty. Circulation. 1995;91:979–989[Abstract/Free Full Text]
  9. BARI Investigators. Influences of diabetes on 5-year mortality and morbidity in a randomized trial comparing CABG and PTCA in patients with multivessel disease. Circulation. 1997;96:1761–1769[Abstract/Free Full Text]
  10. CABRI Trial Participants. First-year results of CABRI (Coronary Angioplasty versus Bypass Revascularization Investigation). Lancet. 1995;346:1179–1184[CrossRef][Medline]
  11. Leimgruber PP, Roubin GS, Hollman J, et al. Restenosis after successful coronary angioplasty in patients with single-vessel disease. Circulation. 1986;73:710–717[Abstract/Free Full Text]
  12. Vandormael MG, Deligonul U, Kern MJ, et al. Multilesion coronary angioplasty: clinical and angiographic follow-up. J Am Coll Cardiol. 1987;10:246–252[Abstract]
  13. Ellis SG, Roubin GS, King SB, Douglas JS, Cox WR. Importance of stenosis morphology in the estimation of restenosis risk after elective percutaneous transluminal coronary angioplasty. Am J Cardiol. 1989;63:30–34[CrossRef][Medline]
  14. Macdonald RG, Henderson MA, Hirshfeld JW, et al. Patient-related variables and restenosis after percutaneous transluminal coronary angioplasty—a report from the M-Heart Group. Am J Cardiol. 1990;66:926–931[CrossRef][Medline]
  15. Bourassa MG, Lespérance J, Eastwood C, et al. Clinical, physiologic, anatomic and procedural factors predictive of restenosis after percutaneous transluminal coronary angioplasty. J Am Coll Cardiol. 1991;18:368–376[Abstract]
  16. Rabbani LE, Edelman ER, Ganz P, Selwyn AP, Loscalzo J, Bittl JA. Relation of restenosis after excimer laser angioplasty to fasting insulin levels. Am J Cardiol. 1994;73:323–327[CrossRef][Medline]
  17. Levine GN, Jacobs AK, Keeler GP, et al. Impact of diabetes mellitus on percutaneous revascularization (CAVEAT-1). Am J Cardiol. 1997;79:748–755[CrossRef][Medline]
  18. Lablanche JM, McFadden EP, Bonnet JL, et al. Combined antiplatelet therapy with ticlopidine and aspirin. A simplified approach to intracoronary stent management. Eur Heart J. 1996;17:1373–1380[Abstract/Free Full Text]
  19. Ellis SG, Vandormael MG, Cowley MJ, et al. Coronary morphologic and clinical determinants of procedural outcome with multivessel coronary artery disease. Implications for patient selection. Circulation. 1990;82:1193–1202[Abstract/Free Full Text]
  20. Thrombolysis in Myocardial Infarction (TIMI) Study Group. The Thrombolysis in Myocardial Infarction (TIMI) Trial. N Engl J Med. 1985;312:932–936[Medline]
  21. Bertrand ME, Lablanche JM, Bauters C, Leroy F, McFadden EP. Discordant results of visual and quantitative estimates of stenosis severity before and after coronary angioplasty. Cathet Cardiovasc Diagn. 1993;28:1–6[Medline]
  22. Kennedy JW, Trenholme SE, Kasser IS. Left ventricular volume and mass from single-plane cineangiocardiogram: comparison of anteroposterior or right anterior oblique methods. Am Heart J. 1970;80:343–352[CrossRef][Medline]
  23. Kleiman NS, Lincoff AM, Kereiakes DJ, et al. Diabetes mellitus, glycoprotein IIb/IIIa blockade, and heparin. Evidence for a complex interaction from a multicenter trial. Circulation. 1998;97:1912–1920[Abstract/Free Full Text]
  24. Le Feuvre C, Bonan R, Lespérance J, Gosselin G, Joyal M, Crépeau J. Predictive factors of restenosis after multivessel percutaneous transluminal coronary angioplasty. Am J Cardiol. 1994;73:840–844[CrossRef][Medline]
  25. Van Belle E, Bauters C, Hubert E, et al. Restenosis rates in diabetic patients: a comparison of coronary stenting and balloon angioplasty in native coronary vessels. Circulation. 1997;96:1454–1460[Abstract/Free Full Text]
  26. Rensing BJ, Hermans WRM, Deckers JW, de Feyter PJ, Tijssen JGP, Serruys PW. Lumen narrowing after percutaneous transluminal coronary balloon angioplasty follows a near Gaussian distribution: a quantitative angiographic study in 1,445 successfully dilated lesions. J Am Coll Cardiol. 1992;19:939–945[Abstract]
  27. Violaris AG, Melkert R, Serruys PW. Long-term luminal renarrowing after successful elective coronary angioplasty of total occlusion. A quantitative angiographic analysis. Circulation. 1995;91:2140–2150[Abstract/Free Full Text]
  28. Rozenman Y, Gilon D, Welber S, et al. Total coronary artery occlusion late after successful coronary angioplasty of moderately severe lesions: incidence and clinical manifestations. Cardiology. 1994;85:222–228[Medline]
  29. Bauters C, Khanoyan P, McFadden EP, Quandalle P, Lablanche JM, Bertrand ME. Restenosis after delayed coronary angioplasty of the culprit vessel in patients with a recent myocardial infarction treated by thrombolysis. Circulation. 1995;91:1410–1418[Abstract/Free Full Text]
  30. Brodie BR, Grines CL, Ivanhoe R, et al. Six-month clinical and angiographic follow-up after direct angioplasty for acute myocardial infarction: final results from the Primary Angioplasty Registry. Circulation. 1994;90:156–162[Abstract/Free Full Text]
  31. Aronson D, Bloomgarden Z, Rayfield EJ. Potential mechanisms promoting restenosis in diabetic patients. J Am Coll Cardiol. 1996;27:528–535[Abstract]
  32. Sobel BE. Potentiation of vasculopathy by insulin. Implications from an NHLBI clinical alert. Circulation. 1996;93:1613–1615[Free Full Text]
  33. Silva JA, Escobar A, Collins TJ, Ramee SR, White CJ. Unstable angina. A comparison of angioscopic findings between diabetic and nondiabetic patients. Circulation. 1995;92:1731–1736[Abstract/Free Full Text]
  34. Bauters C, Lablanche JM, McFadden EP, Hamon M, Bertrand ME. Relation of coronary angioscopic findings at coronary angioplasty to angiographic restenosis. Circulation. 1995;92:2473–2479[Abstract/Free Full Text]
  35. Kornowski R, Mintz GS, Kent KM, et al. Increased restenosis in diabetes mellitus after coronary interventions is due to exaggerated intimal hyperplasia. A serial intravascular ultrasound study. Circulation. 1997;95:1366–1369[Abstract/Free Full Text]
  36. Moreno PR, Murcia AM, Fallon JT, Fuster V. Smooth muscle cell proliferation does not account for restenosis in diabetic patients (abstr). Circulation. 1996;94:I-619
  37. Savage MP, Douglas JS, Fischman DL, et al. Stent placement compared with balloon angioplasty for obstructed coronary bypass grafts. N Engl J Med. 1997;337:740–747[Abstract/Free Full Text]
  38. Strauss BH, Natarajan MK, Batchelor WB, et al. Early and late quantitative angiographic results of vein graft lesions treated by excimer laser with adjunctive balloon angioplasty. Circulation. 1995;92:348–356[Abstract/Free Full Text]
  39. Weintraub WS, Stein B, Kosinski A, et al. Outcome of coronary bypass surgery versus coronary angioplasty in diabetic patients with multivessel coronary artery disease. J Am Coll Cardiol. 1998;31:10–19[Abstract/Free Full Text]
  40. Brownlee M. Glycation and diabetic complications. Diabetes. 1994;43:836–841[Medline]
  41. Margolis JR, Kannel WS, Feinleib M, Dawber TR, McNamara PM. Clinical features of unrecognized myocardial infarction—silent and asymptomatic. Eighteen-year follow-up: The Framingham Study. Am J Cardiol. 1973;32:1–7[CrossRef][Medline]
  42. Nesto RW, Phillips RT, Kett KG, et al. Angina and exertional myocardial ischemia in diabetic and non diabetic patients: assessment by exercise thallium scintigraphy. Ann Intern Med. 1998;108:170–175
  43. Bauters C, Hubert E, Prat A, et al. Predictors of restenosis after coronary stent implantation. J Am Coll Cardiol. 1998;31:1291–1298[Abstract/Free Full Text]



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