Time Of Percutaneous Transluminal Coronary Angioplasty Research Articles

Decoy oligodeoxynucleotide againstactivator protein-1 reducesneointimal proliferation after coronaryangioplasty in hypercholesterolemic minipigs

ObjectivesWe sought to demonstrate, in an appropriate animal model, that co-medication with a transcription factor-blocking agent limits restenosis after percutaneous transluminal coronary angioplasty (PTCA). BackgroundEnhanced synthesis in the vessel wall of endothelin-1 (ET-1), a powerful co-mitogen for vascular smooth muscle cells, appears to be one mechanism that promotes restenosis after PTCA. Deformation-induced expression of prepro-ET-1 is governed by the transcription factor, activator protein-1 (AP-1). MethodsAn anti-AP-1 decoy oligodeoxynucleotide (dODN) strategy was devised in which the dODN-containing solution (20 nmol) was administered locally through a Dispatch catheter into the coronary arteries of hypercholesterolemic minipigs at the time of PTCA (AVE-GFX stent). ResultsTreatment with an AP-1 dODN, mimicking the consensus binding site of the transcription factor, significantly reduced neointimal formation in the coronary arteries of hypercholesterolemic minipigs (n = 10 to 12), compared with vehicle-treated coronary arteries, after four weeks of follow-up (neointimal area 2.64 ± 0.33 vs. 4.81 ± 1.04 mm2[mean ± SEM]; p < 0.05). This effect was maintained after eight weeks (neointimal area 2.04 ± 0.22 mm2; n = 3) and correlated with a reduction in both nuclear translocation of AP-1 and ET-1 synthesis in the vessel wall 48 h after PTCA (n = 4). In contrast, an AP-1 mutant dODN, to which the transcription factor does not bind, showed no effect on neointimal formation at either time point (n = 3 to 7). Moreover, a consensus dODN directed against CCAAT/enhancer binding protein (C/EBP), another deformation-sensitive transcription factor, did not significantly affect neointimal formation after four weeks (n = 3). ConclusionsThese findings demonstrate the feasibility, efficacy and specificity of the anti-AP-1 dODN approach to the treatment of restenosis, which principally but not exclusively targets deformation-induced ET-1 synthesis in the vessel wall. Provided that these findings can be extrapolated to the situation of patients with coronary artery disease, the observed extent of the inhibitory effect of the AP-1 dODN treatment suggests that this co-medication may greatly reduce the incidence of in-stent restenosis.

Reasons for higher in-hospital mortality >24 hours after percutaneous transluminal coronary angioplasty in women compared with men

Women have a higher in-hospital mortality rate than men after percutaneous transluminal coronary angioplasty (PTCA). To determine reasons for this, we analyzed the outcome of PTCA at our institution from 1989 to 1995 for 5,989 patients (2,101 women). Women were older than men (66.8 ± 10.9 vs 61.0 ± 11.2 years, respectively; p <0.0001) and more likely to have diabetes mellitus, hypertension, or a history of congestive heart failure than men. In-laboratory complications at the time of PTCA were similar for women and men. During the first 24 hours after PTCA, women were more likely than men to become hypotensive (0.33% vs 0.08%, p = 0.04) and had a higher rate of vascular injury than men (1.6% vs 0.6%, p <0.001). More than 24 hours after the procedure, women had a significantly higher mortality rate (1.2% vs 0.52%, p = 0.017), which was no longer significantly different after adjustment for age (odds ratio 0.72, 95% confidence interval 0.39 to 1.32). Multivariate correlates of death >24 hours after PTCA were age, a prior history of congestive heart failure, vascular injury, and use of thrombolytic agents. Of those dying >24 hours after the procedure, 67% of women suffered a noncardiac-related death compared with only 10% of men (p <0.001). The noncardiac death rate was 0.8% for women and 0.05% for men. These deaths were related to renal failure, vascular complications, bleeding, hypotension, and stroke, especially hemorrhagic stroke. In conclusion, immediate procedural complications at PTCA were similar for women and men; however, mortality was higher for women >24 hours after PTCA and before discharge due to a higher rate of noncardiac death.

Cost-effectiveness analysis of abciximab: a Canadian hospital perspective.

To assess the cost-effectiveness of abciximab therapy versus traditional practice in high-risk patients receiving percutaneous transluminal coronary angioplasty (PTCA) from a Canadian hospital perspective. A predictive decision analytic model using published clinical and economic evaluations, as well as costs of medical care in Canada. High-risk PTCA patients as defined by the Evaluation of c7E3 for Prevention of Ischemic Complications trial and the c7E3 Fab Antiplatelet Therapy in Unstable Refractory Angina trial. Two treatment strategies were compared: (1) abciximab 0.25 mg/kg intravenous bolus 10 minutes prior to PTCA followed by abciximab 10 micrograms/min intravenous infusion for 12 hours after the procedure, and (2) no abciximab adjunctive therapy at the time of PTCA. Both treatment strategies were combined with intravenous heparin up to 100 units/kg bolus pre-PTCA followed by bolus doses for 1 hour after PTCA per the protocol. Cumulative outcomes were considered up to 6 months after initial PTCA. At 6 months, 29% of the patients in the abciximab treatment arm compared with 33% in the no abciximab arm achieved one of the primary events. The most common adverse event experienced was major bleeding at 4% in the abciximab treatment arm versus 1.6% in the no abciximab arm. The average cost per patient for each strategy was $3261 Can ($1 Can = $0.686 US) (abciximab arm) versus $2073 Can (no abciximab arm), resulting in an incremental cost-effectiveness ratio of $29,700 Can per event-free patient. In univariate sensitivity analyses, the only controllable factor that changed the results of the cost-effectiveness outcome was the cost of abciximab. Although the use of abciximab as an adjunct to PTCA results in a reduction in event rates in high-risk patients compared with traditional treatment, there is an increased cost associated with this strategy.

Relation of Coronary Angioscopic Findings at Coronary Angioplasty to Angiographic Restenosis

Discordant results have been reported regarding morphological predictors of restenosis after percutaneous transluminal coronary angioplasty (PTCA). These discrepancies may be related to the limitations of angiography in the study of plaque morphology. We studied 117 consecutive patients who underwent successful PTCA and who underwent coronary angioscopy before and immediately after the procedure. Angiographic follow-up was performed in 99 (85%) patients. We analyzed the relationship between angioscopic variables at the time of PTCA and the occurrence of restenosis assessed by quantitative coronary angiography. Plaque shape and color had no effect on late loss in luminal diameter (late loss: smooth lesions, 0.55 +/- 0.68 mm; complex lesions, 0.76 +/- 0.60 mm; white plaques, 0.51 +/- 0.56 mm; yellow plaques, 0.65 +/- 0.72 mm; P = NS). An angioscopic protruding thrombus at the PTCA site was associated with significantly greater loss in luminal diameter (late loss: no thrombus, 0.47 +/- 0.54 mm; lining thrombus, 0.59 +/- 0.67 mm; protruding thrombus, 1.07 +/- 0.77 mm; P < .05). Dissection assessed by angioscopy immediately after PTCA had no effect on late loss in luminal diameter (late loss: no dissection, 0.60 +/- 0.60 mm; simple dissection, 0.82 +/- 0.75 mm; complex dissection, 0.57 +/- 0.80 mm; P = NS). These results show that coronary angioscopy may be helpful in predicting the risk of restenosis after PTCA. The high rate of angiographic recurrence observed when PTCA is performed at thrombus-containing lesions supports a role for thrombus in the process of luminal renarrowing after PTCA.

810-4 Remodeling of the Vascular Endothelium Following PTCA in Rabbit Iliac Arteries with Fibrin Adhesive/Endothelial Cell Matrix

We proposed that a possible cause of acute and chronic complications of Percutaneous Transluminal Coronary Angioplasty (PTCA) is the loss of the endothelial cell lining of the arterial wall. The objective of this study was to reattach endothelial cells to the arterial wall at the time of PTCA. We devised a unique process utilizing a delivery device whereby a fibrin adhesive reattaches endothelial cells to denuded vessel walls at the time of PTCA. Following in vitro definition of optimal conditions required forthe adhesive matrix to successfully reattach endothelial cells to an inert plastic surface and subsequent demonstration of viability of these cells after delivery through the infusion catheter system, studies were carried out on iliac arteries (n = 6/group) of New Zealand White rabbits subjected to balloon angioplasty-induced endothelial cell denudation. The Wolinsky infusion balloon (USCI. C.R. Bard) and double balloon was used to deliver the fibrin adhesive/endothelial cell matrix labelled with red fluorescent dye to denuded areas over a 3-5 min period. Immediately following treatment blood was allowed to perfuse the seeded artery for four hours to expose the iliac segments with newly attached endothelial cells to physiologic shear forces. Histological examination demonstrated the ability of this novel method to circumferentially reattach the adhesive/endothelial cell matrix to 70-90% of the denuded arterial wall segments in comparison with 5-8% reattachment following seeding with endothelial cells alone. We conclude that endothelial cells can be successfully reattached to denuded vessel walls with a fibrin adhesive matrix following PTCA.

Activated clotting times in acute coronary syndromes and percutaneous transluminal coronary angioplasty

A discrete fall in the ACT (activated coagulation time) has been observed in patients with known activation of the coagulation cascade. Injury to the coronary artery resulting in thrombin activation, whether spontaneous as in the case of acute myocardial infarction or planned as with percutaneous transluminal coronary angioplasty (PTCA), may therefore be reflected in a change in ACT values. We reviewed the records of patients undergoing PTCA at St. Luke's Episcopal Hospital/Texas Heart Institute from January 1990 through December 1992 for information regarding ACT values and clinical events. A total of 469 patients, whose record contained adequate information for study inclusion, were divided into four separate groups: acute myocardial infarction (group I, n = 62), unstable angina with heparin therapy that was withdrawn at least 4 hr prior to PTCA (group II, n = 102), unstable angina with heparin therapy continued until the time of PTCA (group III, n = 154), and stable angina undergoing elective PTCA (group IV, n = 151). Heparin was discontinued 12-15 hr after the procedure in all but group I where anticoagulation was often maintained up to 72 hr. ACT values were measured prior to the PTCA procedure (baseline), after the initial heparin bolus of 10,000 U (postheparin) and approximately 12-18 hr after the procedure (heparin withdrawal).(ABSTRACT TRUNCATED AT 250 WORDS)

Percutaneous transluminal coronary angioplasty in patients aged ≥90 years

This report describes the acute and intermediate-term results of percutaneous transluminal coronary angioplasty (PTCA) performed on all patients aged ≥90 years at the time of PTCA over a 6.5-year time frame at 7 high-volume academic institutions.

Endothelium dependent and independent responses in coronary artery disease measured at angioplasty.

OBJECTIVE--To investigate the effects of substance P and papaverine, two drugs that increase coronary blood flow by different mechanisms, on vasomotion in stenotic coronary arteries at percutaneous transluminal coronary angioplasty (PTCA). DESIGN--Coronary blood flow responses to substance P and papaverine were measured in stenotic coronary arteries at the time of PTCA with quantitative angiography and a Doppler flow probe. SETTING--A cardiothoracic referral centre. PATIENTS--15 patients undergoing elective PTCA of a discrete epicardial coronary artery stenosis. INTERVENTIONS--Pharmacological coronary flow reserve was determined with papaverine 5-10 minutes before and after successful PTCA. Endothelium dependent responses to 2 minute infusions of substance P (10-15 pmol.min-1) were assessed immediately before PTCA. MAIN OUTCOME MEASURES--Coronary blood flow responses and changes in epicardial coronary artery area at stenotic, proximal, and distal sites with papaverine and substance P. RESULTS--Stenotic sites dilated with papaverine before PTCA (17.7%(6.9%) (mean (SEM)) area increase, p < 0.05 v baseline). Substance P dilated stenotic sites (16.8%(5.7%) area increase, p < 0.05) and proximal (14.3%(5.4%), p < 0.05) and distal sites (41.7%(9.3%), p < 0.005). Coronary flow reserve increased but did not reach normal values after PTCA (2.3(0.4) before PTCA v 3.0(0.4) after PTCA, p < 0.05) and was associated with an increase in peak flow with papaverine. Angioplasty did not alter baseline flow. After PTCA papaverine caused significant vasoconstriction at the stenotic site (-13.6%(4.3%) area decrease, p < 0.05). There was a negative correlation (r = -0.68, p < 0.05) between the dilator response with papaverine before PTCA and the constrictor response after PTCA. CONCLUSIONS--Substance P causes endothelium dependent dilatation in atheromatous coronary arteries, even at sites of overt atheroma. The cause of the paradoxical constrictor response to papaverine after PTCA is uncertain, but unopposed flow mediated vasoconstriction (the myogenic response) after balloon induced endothelial denudation may be one of several contributory factors.

Aggressive clinical pattern of angina at restenosis following coronary angioplasty in unstable angina

The frequency, clinical pattern, and timing of recurrent angina following successful single-lesion percutaneous transluminal coronary angioplasty (PTCA) was assessed in a consecutive group of 104 patients with stable angina and in 85 with unstable angina. In addition, the relationship between lesion morphology and angiographic features and the pattern of recurrent angina was determined. Restenosis, defined as recurrence of symptoms with >50% stenosis at the site of PTCA, occurred in 25 (24%) of the stable group and in 23 (27%) of the unstable group ( p = NS). The pattern of angina at repeat presentation was aggressive in nature in 8% of the stable group and in 48% of the unstable group ( p = 0.002). The time interval between the recurrence of symptoms and repeat coronary angiogram or PTCA was longer in the nonaggressive group than in the aggressive group, 16 ± 12.1 and 5 ± 6.8 weeks, respectively ( p < 0.003). The key factors predicting the recurrent angina pattern identified by multiple logistic regression analysis were the angina status pre-PTCA ( p = 0.001) and the presence of double-vessel disease ( p = 0.01). An aggressive pattern of angina at the time of restenosis is frequent in patients with unstable angina at the time of PTCA, and close post-PTCA surveillance is necessary in these patients.

Immediate and short-term results of a 1988–1989 coronary angioplasty registry

To determine the relevance of recent refinements in angioplasty technology to our particular practice, the records of 507 consecutive patients undergoing a first percutaneous transluminal coronary angioplasty (PTCA) at our center between October 1988 and May 1989 were reviewed. At the time of PTCA, 41% of these patients had class IV angina and 44% were identified as having multivessel disease. Dilatation was attempted in 734 lesions (mean 1.5 per patient), of which 95 (13%) were chronic total occlusions. Overall, 69% of the 734 lesions were judged anatomically complex, and, in dilating these lesions, a rail-type device was used almost exclusively. Successful dilatation was achieved in 659 of the 734 (90%) attempted lesions. There were tow incidences of the major complications of death (0.4%), myocardial infarction (1.8%) and emergency bypass surgery (1.8%). Acute rethrombosis occurred in 54 patients (11%). In these patients, initial strategy of repeat dilatation was successful in 38 of 47 patients (81%). Overall, primary clinical success at PTCA was achieved in 480 patients (95%). At a mean followup of 7.5 ± 1.5 months in 497 of the study patients, the event-free rate (freedom from cardiac death, myocardial infarction, repeat PTCA or coronary bypass surgery or recurrence of severe [class III to IV] angina) was 71%. In conclusion, despite the often complex coronary disease in patients currently presenting to our center, a high initial success rate and acceptable short-term outcome of PTCA was achieved.

Serum from patients with restenosis after percutaneous transluminal coronary angioplasty stimulates proliferation of bovine vascular smooth muscle cells under low extracellular calcium condition.

We compared the effects on the proliferation of bovine vascular smooth muscle cells (VSMC) of serum from 36 patients without restenosis (group A), and 21 patients with restenosis (group B) after percutaneous transluminal coronary angioplasty (PTCA). Baseline characteristics were similar in both groups, except for the greater number of patients with unstable angina at the time of PTCA (52 vs 22%, p = 0.020) and the shorter interval between PTCA and repeat angiography in group B (106 +/- 30 vs 153 +/- 112 days, p = 0.022). Cultured bovine VSMC were stimulated with patient serum (5%) obtained at repeat angiography in either Ca(2+)-containing or Ca(2+)-free culture medium. DNA synthesis was assessed by [3H]thymidine incorporation. The following indices of VSMC proliferation were used: S(+) = [3H]thymidine uptake stimulated by 5% serum in Ca(2+)-containing medium/[3H]thymidine uptake stimulated by 5% fetal calf serum (FCS) in Ca(2+)-containing medium, S(-) = [3H]thymidine uptake stimulated by 5% serum in Ca(2+)-free medium/[3H]thymidine uptake stimulated by 5% FCS in Ca(2+)-free medium, and D = S(-)-S(+). D represented the preserved DNA synthesis in Ca(2+)-deprived medium. S(-) was lower than S(+) in group A (1.35 +/- 0.56 vs 1.57 +/- 0.58, p less than 0.0001), whereas it was higher than S(+) in group B (1.64 +/- 0.66 vs 1.50 +/- 0.58, p = 0.010). D was significantly higher in group B than in group A (0.14 +/- 0.23 vs -0.22 +/- 0.28, p less than 0.0001), and was not associated with any continuous variables including serum calcium level on univariate regression analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Restenosis after transluminal coronary angioplasty: A risk factor analysis

In order to determine the relationship of restenosis following percutaneous transluminal coronary angioplasty (PTCA) to risk factors such as hypercholesterolemia, hyperglycemia, smoking, and weight, we performed a univariate analysis to test the association of these variables with restenosis in 723 patients who had percutaneous transluminal coronary angioplasty and follow-up catheterization. Cholesterol levels were higher in younger and female subjects (less than 0.0001). Initial cholesterol did not predict restenosis, and follow-up cholesterol levels showed an inverse relationship with restenosis (P less than .02). There was a trend (P less than .09) toward decreased restenosis in those who were active smokers at the time of follow-up catheterization. No differences were seen in diabetics with hyperglycemia, in both treated and untreated groups (P = NS). A stepwise multiple logistic regression was used to simultaneously test the association of the above risk factor variables to restenosis. None of the interactions were found to be significant, except cholesterol at follow-up (P = .001). Therefore, the status of serum cholesterol, blood sugar, smoking, and weight during the time of PTCA and at follow-up catheterization may be unimportant in predicting restenosis. Thus, we conclude 1) that to better determine the effect of these variables on restenosis, they should be estimated at times other than follow-up and 2) that the pathophysiological mechanism of restenosis may have different risk factors than progression of atherosclerotic coronary artery disease.

Identifying patients at high risk for restenosis after percutaneous transluminal coronary angioplasty for unstable angina pectoris

To study the determinants of late restenosis after percutaneous transluminal coronary angioplasty (PTCA) performed in patients with unstable angina pectoris, a prospective study was undertaken in 90 patients. Primary PTCA success was achieved in 84 (93%) patients, dilating 116 of 118 coronary narrowings (1.4/patient), while major complications during PTCA occurred in only 1 patient (1 death). Eighty-two patients (114 dilated arteries) were followed for 25 ± 11 months: 68 (83%) were in New York Heart Association functional class I or II, 11 (13%) in class III, and there were 3 deaths. Late restenosis was found in 16 (25%) of 65 lesions (29% of 49 patients) studied by angiography 9 ± 7 months after PTCA. Restenosis was more frequent in left anterior descending coronary artery lesions (p = 0.07) and in those which at the time of PTCA had multiple irregularities (67 vs 14%, odds ratio 12.5, p = 0.002), decreased coronary perfusion (Thrombolysis in Myocardial Infarction grade <3) (50 vs 15%, odds ratio 5.7, p = 0.02) or intraluminal thrombus (67 vs 19%, odds ratio 8.7, difference not significant). Multiple irregularities (p = 0.003) and decreased flow (p = 0.02) remained independent predictors of restenosis (goodness of fit 0.88) after adjustment for 12 pre- and peri-PTCA clinical and angiographic variables by logistic regression analysis. These data underline the feasibility of early revascularization by PTCA in patients with unstable angina pectoris. Careful follow-up should be instituted in patients with multiple irregular lesions, decreased coronary perfusion or intraluminal thrombus at the time of PTCA. In such patients, late restenosis may be the rule rather than the exception.

Increased frequency of restenosis in patients continuing to smoke cigarettes after percutaneous transluminal coronary angioplasty

The influence of continued cigarette smoking on restenosis after percutaneous transluminal coronary angioplasty (PTCA) was retrospectively determined through a study of 160 patients with primary success who underwent follow-up angiography after a mean of 7 ± 7 months. The average number of narrowings at risk for restenosis was 1.7/patient in the 84 patients who continued to smoke (group 1) and 1.9/patient in the 76 patients who stopped smoking at the time of PTCA (group 2) (difference not significant). The 2 patient groups at baseline were similar with respect to gender, frequency of diabetes mellitus, number of pack/year smoking, angina class and number of diseased coronary arteries. The location of the dilated narrowings, the residual luminal diameter stenosis and the transstenotic gradient after the procedure were similar in both groups. The recurrence of angina ≥ class II was the reason for restudy in 43% and 36% of group 1 and group 2 patients, respectively. Restenosis, defined as the presence of ≥50% narrowing at the site of previous successful dilatation at follow-up angiography, was significantly higher in group 1 compared with group 2 patients (55% vs 38%, p = 0.03). Continued smoking was selected as an independent predictor of restenosis by logistic regression analysis. The incidence of coronary artery disease progression (14% vs 10%) was not significantly different between the 2 groups. In conclusion, continued smoking after successful PTCA is associated with an increased risk of restenosis. The higher restenosis rate in smokers emphasizes the need to strengthen educational programs after PTCA.

Early and late morphologic changes in human coronary arteries after percutaneous transluminal coronary angioplasty.

Certain clinical and morphologic observations are described in 6 men who had percutaneous transluminal coronary angioplasty (PTCA) of the left anterior descending (LAD) or right (R) coronary artery early (4 hours to 7 days) or late (80, 90, and 150 days) before coronary endarterectomy and aortocoronary bypass grafting or death. Histologically, each of the 3 early patients had the site of PTCA narrowed 76-95% in cross-sectional area by atherosclerotic plaque, and each had either coronary dissection or plaque hematoma or both at the site of PTCA. Each of the 3 late patients had a decrease in the mean trans-stenotic coronary gradient (17, 38, and 43 mmHg, respectively) and an angiographic increase in the LAD luminal diameter (55, 60, and 65%, respectively) at the time of PTCA. At necropsy, 80, 90, and 150 days later, the LAD coronary artery in the area of the PTCA in each patient was narrowed 76-95% in cross-sectional area by plaques. No cracks in plaques or other lesions which may have resulted from the PTCA procedure were identified histologically in the LAD coronary artery of any late patient.

Coronary arterial aneurysm formation after balloon angioplasty

The mechanism of coronary stenosis dilatation by percutaneous transluminal coronary angioplasty (PTCA) is incompletely understood. Five men who developed coronary arterial aneurysms at the site of PTCA are described. All patients were in New York Heart Association functional class III or IV at the time of PTCA. In 2 patients acute myocardial infarction was evolving and both had acute coronary occlusion. The other 3 patients had angiographic evidence of intimal disruption or acute coronary reocclusion as a result of PTCA, one of whom had undergone emergency coronary artery bypass grafting. Three patients received intracoronary streptokinase during PTCA. One patient was asymptomatic and 4 were symptomatic when the aneurysms were identified between 11 days and 4 months after PTCA. Other than the complex course and anatomy of these patients before and immediately after PTCA, no other features distinguished them from others undergoing this procedure.