Gilles Côté

Effects of Probucol on Vascular Remodeling After Coronary Angioplasty

BACKGROUNDnWe have shown that probucol reduces restenosis after balloon angioplasty. Whether probucol acted via prevention of neointimal formation or improvement in vascular remodeling could not be addressed by angiography and required the use of intravascular ultrasound (IVUS).nnnMETHODS AND RESULTSnBeginning 30 days before angioplasty, 317 patients were randomly assigned to receive probucol, multivitamins, combined treatment, or placebo. Patients were then treated for 6 months after angioplasty. IVUS examination was performed immediately after angioplasty and at follow-up in 94 patients (111 segments). The cross section selected for serial analysis was the one at the angioplasty site with the smallest lumen area at follow-up. In the placebo group, lumen area decreased by -1. 21+/-1.88 mm2 at follow-up, and wall area and external elastic membrane (EEM) area increased by 1.50+/-2.50 and 0.29+/-2.93 mm2, respectively. Change in lumen area, however, correlated more strongly with the change in EEM area (r=0.53, P=0.002) than with the change in wall area (r=-0.13, P=0.49). Lumen loss was -1.21+/-1.88 mm2 for placebo, -0.83+/-1.22 mm2 for vitamins, -0.25+/-1.17 mm2 for combined treatment, and -0.15+/-1.70 mm2 for probucol alone (P=0.002 for probucol, P=0.84 for vitamins). Change in wall area was similar for all groups. EEM area increased by 0.29+/-2.93 mm2 for placebo, 0. 09+/-2.33 mm2 for vitamins only, 1.17+/-1.61 mm2 for combined treatment, and 1.74+/-1.80 mm2 for probucol only (P=0.005 for probucol).nnnCONCLUSIONSnLumen loss after balloon angioplasty is due to inadequate vessel remodeling in response to neointimal formation. Probucol exerts its antirestenotic effects by improving vascular remodeling after angioplasty.

Multiple coronary angioplasty: A model to discriminate systemic and procedural factors related to restenosis

To assess the interrelation of clinical and procedural factors responsible for restenosis, 119 patients undergoing coronary arteriography were studied a mean of 5.8 +/- 3 months after successful multiple percutaneous transluminal coronary angioplasty. In all clinical, angiographic and procedural variables, the 119 patients undergoing repeat catheterization were similar to the 87 patients that did not. Overall, restenosis occurred in 74 (34%) of 215 lesions. Sixty-three patients had no restenosis, 44 had at least one restenosis and 12 had restenosis at all angioplasty sites. The statistical distribution of restenoses did not follow a binomial model, suggesting that restenosis is more than a lesion-specific phenomenon. Of all the clinical and procedural variables assessed by multivariate logistic regression analysis, only percent stenosis before angioplasty (p less than 0.01), diabetes mellitus (p less than 0.01) and percent stenosis after angioplasty (p less than 0.05) were predictive of restenosis in the entire group. Patients with no restenosis and patients with restenosis at all sites were not different with respect to procedural variables; however, patients with restenosis at all sites more often (p less than 0.05) had diabetes and recent onset angina. In contrast, patients with no restenosis differed from patients with isolated restenosis with respect to procedural variables: severity of stenosis before and after angioplasty, balloon/artery lumen ratio and maximal inflation pressure. Thus, procedural factors may be more related to isolated restenosis, but patient-related factors such as diabetes and recent onset angina may play a more important role in patients with multiple restenoses.

Prevention of Restenosis After Angioplasty in Small Coronary Arteries With Probucol

BACKGROUNDnRestenosis remains the major limitation of coronary angioplasty. Coronary stents have reduced the incidence of restenosis in selected patients with relatively large vessels. No strategies to date have demonstrated a beneficial effect in vessels < 3.0 mm in diameter. We have shown in the MultiVitamins and Probucol (MVP) Trial that probucol, a potent antioxidant, reduces restenosis after balloon angioplasty. The purpose of this study was to determine whether the benefit of probucol therapy is maintained in the subgroup of patients with smaller coronary vessels.nnnMETHODS AND RESULTSnWe studied a subgroup of 189 patients included in the MVP trial who underwent successful balloon angioplasty of at least one coronary segment with a reference diameter < 3.0 mm. One month before angioplasty, patients were randomly assigned to one of four treatments: placebo, probucol (500 mg), multivitamins (beta-carotene 30000 IU, vitamin C 500 mg, and vitamin E 700 IU), or probucol plus multivitamins twice daily. The treatment was maintained until follow-up angiography was performed at 6 months. The mean reference diameter of this study population was 2.49+/-0.34 mm. Lumen loss was 0.12+/-0.34 mm for probucol, 0.25+/-0.43 mm for the combined treatment, 0.35+/-0.56 mm for vitamins, and 0.38+/-0.51 mm for placebo (P=.005 for probucol). Restenosis rates per segment were 20.0% for probucol, 28.6% for the combined treatment, 45.1% for vitamins, and 37.3% for placebo (P=.006 for probucol).nnnCONCLUSIONSnProbucol reduces lumen loss and restenosis rate after balloon angioplasty in small coronary arteries.

Quantitative angiographic assessment of coronary anastomoses performed without cardiopulmonary bypass

BACKGROUNDnThe quality of the anastomosis performed during coronary artery bypass grafting without cardiopulmonary bypass is a current concern, and myocardial wall restraining devices have been designed to optimize results. A quantitative angiographic analysis was performed to assess coronary anastomoses performed on beating hearts.nnnMETHODSnWe studied 34 patients who underwent coronary artery bypass grafting without cardiopulmonary bypass between February 1996 and April 1997. The left internal thoracic artery was anastomosed to the left anterior descending coronary artery in all patients. Coronary angiograms were performed 4 +/- 2 days after the operation. The diameter of the anastomoses was quantified by computer-assisted analysis of grafts and native coronary arteries at the toe and heel of the anastomosis.nnnRESULTSnFive of the patients who underwent coronary artery bypass without a stabilizer (n = 20) had stenoses of the internal thoracic artery grafted to the left anterior descending coronary artery of more than 50% at the level of the anastomosis proper, 3 had stenoses at the heel of the coronary anastomosis, and 5 had stenoses at the toe. One of the patients in whom a stabilizer was used (n = 14) had a stenosis of more than 50% at the anastomosis, and 1 had stenosis at the heel. Eight patients in whom the anastomoses were performed without stabilization (8/20, 40%) had stenoses of more than 50%, whereas there was only 1 stenosis of more than 50% of coronary luminal diameter among the patients in whom the operation was performed with a stabilizer (P =.02).nnnCONCLUSIONnThe quantitative angiographic evaluation suggests that left internal thoracic artery graft to left anterior descending coronary artery anastomoses have a lesser degree of intraluminal stenosis when performed with the use of a myocardial wall stabilizer.

Long-term angiographic follow-up after angioplasty of venous coronary bypass grafts

From April 1981 to June 1987, 57 patients underwent venous coronary bypass graft percutaneous angioplasty and had a minimal follow-up of 18 months. The procedure was elective for 28 patients, urgent for 19, and was considered as an emergency for 10. A total of 64 grafts were dilated that had been bypassed 58 +/- 48 months previously (range 2 to 184 months); lesions were located on the aortic anastomosis in 12 grafts, on the body in 38, and on the coronary anastomosis in 14. Technical success was 95.3% (61 of 64) per lesion; clinical success was 84.4% (54 of 64) per lesion and 82.5% (47 of 57) per patient. Thrombotic complications with images of a lacunar defect occurred in 11 grafts (17.2%). Predictive factors for these complications were: age of grafts 38.5% for greater than 60 month grafts versus 2.6% for less than 60 month grafts (p less than 0.01); site of lesion, body lesion 28.9% versus anastomosis none (p less than 0.01); type of lesion, concentric and short 6% versus other 29% (p less than 0.05); and recent fibrinolysis in 66% versus 10.6% (p less than 0.05). Long-term follow-up is available in the 47 successful patients and the three limited non-Q wave myocardial infarction patients. Two patients died at 13 and 17 months. Long-term angiographic follow-up is available in 45 of 48 patients or 94%. At the end of the study, 35 of 57 (61.4%) venous bypass grafts in 32 patients (64%) were patent after one or more percutaneous transluminal angioplasties.(ABSTRACT TRUNCATED AT 250 WORDS)

Restenosis and progression of coronary atherosclerosis after coronary angioplasty

The relation between restenosis and progression of atherosclerosis in other coronary segments after angioplasty was studied in 98 consecutive patients with 110 coronary stenoses successfully treated with angioplasty. At early angiographic restudy (5 +/- 2 months after angioplasty) 37 patients (38%) had restenosis (defined as a stenosis greater than or equal to 50% of the luminal diameter or loss of greater than or equal to 50% of the gain achieved by angioplasty); progression of atherosclerosis was observed in 4 patients with and 7 without restenosis (13 versus 11%, p = NS). Ninety of the 98 patients underwent a late angiographic restudy a mean of 34 +/- 11 months after angioplasty. Late restenosis was found in one patient. Progression of coronary artery disease (defined as a greater than or equal to 20% decrease in the diameter of a vessel initially narrowed by greater than or equal to 50% or a greater than or equal to 30% decrease when the initial stenosis was less than 50%) was examined in relation to restenosis in 85 of the 90 patients. It occurred in 9 of 27 patients with and 22 of 58 patients without restenosis (33 versus 38%, p = NS). Restenosis developed more rapidly than did progression of disease. Diameter stenosis increased from 35 +/- 8 to 73 +/- 11% at the early restudy in lesions with restenosis; in lesions with disease progression it increased from 9 +/- 18 to 20 +/- 28% (p less than 0.001) at the early restudy to 53 +/- 21% (p less than 0.001) at the late restudy.(ABSTRACT TRUNCATED AT 250 WORDS)

Early results, complications and restenosis rates after multilesion and multivessel percutaneous transluminal coronary angioplasty

Initial results, complications, restenosis rates and clinical outcomes were compared in 78 patients undergoing multilesion and 128 patients undergoing multivessel percutaneous transluminal coronary angioplasty (PTCA). Multilesion PTCA was defined as a procedure in which a proximal PTCA site had to be crossed to dilate a distal severe narrowing and multivessel PTCA as multiple dilatations without having to cross 1 severe narrowing to dilate another. The clinical and angiographic features of the 2 groups were similar. More sites per patient were attempted among those who underwent multilesion PTCA. Primary success rate per lesion was 86% (236 of 274) among those who underwent multivessel and 73% (155 of 211) among those who underwent multilesion PTCA (p less than 0.001). A success rate of 81% (101 of 124) for proximal lesions among those with multilesion PTCA was not significantly worse than that for those with multivessel PTCA; however, lesions distal to proximal sites had a success rate of only 62% (54 of 87), worse than either those with proximal stenoses or multivessel PTCA (p less than 0.005). Arterial diameter, severity of stenosis or procedural variables did not account for this difference. Complication rates were similar in the 2 groups. Despite a poorer success rate among patients with multilesion PTCA, clinical improvement to functional class 0 or 1 occurred in more than 70% of patients in both groups and was equal in patients with and without successful distal dilatations. Restenosis rates per lesion in patients with multivessel (31%) and multilesion (30%) PTCA were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Value of exercise electrocardiography in the detection of restenosis after coronary angioplasty in patients with one-vessel disease.

Exercise treadmill testing (ETT) is considered an unreliable method for detection of restenosis after percutaneous transluminal coronary angioplasty (PTCA). The studies on which this belief is based have used quantitative coronary angiography (QCA) as a reference. The inherent limitations of angiography have been demonstrated by intravascular ultrasound (IVUS). To determine the value of ETT for detecting restenosis when IVUS criteria are used to define restenosis, we studied 29 patients with angiographically documented 1-vessel coronary disease (<35% stenosis in all nondilated segments) who underwent angioplasty. ETT was performed < or =2 weeks before follow-up angiography and IVUS imaging. Only patients without any abnormalities precluding an accurate reading of the ST segment during ETT were included. Restenosis was defined as a > or =50% diameter stenosis by QCA criteria and as a cross-sectional area narrowing of > or =75% by IVUS. The ETT was positive in 12 patients and restenosis was documented by QCA and IVUS in 38% and 48% of cases, respectively. Sensitivity, specificity, and positive and negative predictive values of ETT when QCA was used as a reference were 55%, 67%, 50%, and 71%, respectively. This corresponded to an accuracy of 62% when compared with QCA. Sensitivity, specificity, and positive and negative predictive values were 79%, 93%, 92%, and 82% when ETT was compared with IVUS, with an accuracy of 86% (p = 0.002). Thus, ETT is a reliable noninvasive method for detecting the presence of restenosis after PTCA in patients with 1-vessel coronary artery disease. The presence of > or =75% cross-sectional narrowing shown by IVUS is well correlated with > or =1-mm ST-segment depression at follow-up ETT after PTCA.

Management of resistant coronary lesions by the cutting balloon catheter: initial experience.

Resistant coronary lesions remain a challenge for modern angioplasty. Classical approaches include high-pressure inflations, prolonged inflations, or balloon oversizing. More recently, new technologies like rotablator, atherectomy, or laser have been proposed as adjunct to balloon angioplasty for the treatment of these specific lesions. However, all these technologies remain more difficult to handle, costly, and they do not offer long-term benefit over conventional methods. Therefore, a simple device such as the cutting balloon catheter which has been developed from a standard over the wire balloon catheter, may prove to be useful in resistant coronary lesions. We present our single center experience using the new cutting balloon catheter in six resistant lesions.

Randomized Trial Comparing Intravenous Nitroglycerin and Heparin for Treatment of Unstable Angina Secondary to Restenosis After Coronary Artery Angioplasty

BACKGROUNDnThe treatment of unstable angina targets the specific pathophysiological thrombotic process at the site of the active culprit lesion. In unstable angina due to a restenotic lesion, smooth muscle cell proliferation and increased vasoreactivity may play a more important role than thrombus formation. Therefore, the relative benefits of nitroglycerin and heparin might differ in unstable angina associated with restenosis compared with classic unstable angina.nnnMETHODS AND RESULTSnWe randomized 200 patients hospitalized for unstable angina within 6 months after angioplasty (excluding those with intracoronary stents) to double-blind administration of intravenous nitroglycerin, heparin, their combination, or placebo for 63+/-30 hours. Recurrent angina occurred in 75% of patients in the placebo and heparin-alone groups, compared with 42.6% of patients in the nitroglycerin-alone group and 41.7% of patients in the nitroglycerin-plus-heparin group (P<0.003). Refractory angina requiring angiography occurred in 22.9%, 29.2%, 4. 3%, and 4.2% of patients, respectively (P<0.002). The odds ratios for being event free were 0.24 (95% CI, -0.13 to 0.45, P=0.0001) for nitroglycerin versus no nitroglycerin and 0.98 (95% CI, -0.55 to 1. 73, P=NS) for heparin versus no heparin. No patient died or suffered myocardial infarction.nnnCONCLUSIONSnIntravenous nitroglycerin is highly effective in preventing adverse ischemic events (recurrent or refractory angina) in patients with unstable angina secondary to restenosis, whereas heparin has no effect.