Kevin J. Beatt

Incidence of restenosis after successful coronary angioplasty: a time-related phenomenon. A quantitative angiographic study in 342 consecutive patients at 1, 2, 3, and 4 months.

Data from experimental, clinical, and pathologic studies have suggested that the process of restenosis begins very early after coronary angioplasty. The present study was performed to determine prospectively the incidence of restenosis with use of the four National Heart, Lung, and Blood Institute and the 50% or greater diameter stenosis criteria, as well as a criterion based on a decrease of 0.72 mm or more in minimal luminal diameter. Patients were recatheterized at 30, 60, 90, or 120 days after successful percutaneous transluminal coronary angioplasty (PTCA). After PTCA all patients received 10 mg nifedipine three to six times a day and aspirin once a day until repeat angiography. Of 400 consecutive patients in whom PTCA was successful (less than 50% diameter stenosis), 342 underwent quantitative angiographic follow-up (86%) by use of an automated edge-detection technique. A wide variation in the incidence of restenosis was found dependent on the criterion applied. The incidence of restenosis proved to be progressive to at least the third month for all except NHLBI criterion II. At 4 months a further increase in the incidence of restenosis was observed when defined as a decrease of 0.72 mm or more in minimal luminal diameter, whereas the criteria based on percentage diameter stenosis showed a variable response. The lack of overlap between the different restenosis criteria applied affirms the arbitrary nature of angiographic definitions currently in use. Restenosis should be assessed by repeat angiography, and preferably ascertained according to the change in absolute quantitative measurements of the luminal diameter.

Angiographic follow-up after placement of a self-expanding coronary artery stent

BACKGROUND The placement of stents in coronary arteries after coronary angioplasty has been investigated as a way of treating abrupt coronary-artery occlusion related to the angioplasty and of reducing the late intimal hyperplasia responsible for gradual restenosis of the dilated lesion. METHODS From March 1986 to January 1988, we implanted 117 self-expanding, stainless-steel endovascular stents (Wallstent) in the native coronary arteries (94 stents) or saphenous-vein bypass grafts (23 stents) of 105 patients. Angiograms were obtained immediately before and after placement of the stent and at follow-up at least one month later (unless symptoms required angiography sooner). The mortality after one year was 7.6 percent (8 patients). Follow-up angiograms (after a mean [+/- SD] of 5.7 +/- 4.4 months) were obtained in 95 patients with 105 stents and were analyzed quantitatively by a computer-assisted system of cardiovascular angiographic analysis. The 10 patients without follow-up angiograms included 4 who died. RESULTS Complete occlusion occurred in 27 stents in 25 patients (24 percent); 21 occlusions were documented within the first 14 days after implantation. Overall, immediately after placement of the stent there was a significant increase in the minimal luminal diameter and a significant decrease in the percentage of the diameter with stenosis (changing from a mean [+/- SD] of 1.88 +/- 0.43 to 2.48 +/- 0.51 mm and from 37 +/- 12 to 21 +/- 10 percent, respectively; P less than 0.0001). Later, however, there was a significant decrease in the minimal luminal diameter and a significant increase in the stenosis of the segment with the stent (1.68 +/- 1.78 mm and 48 +/- 34 percent at follow-up). Significant restenosis, as indicated by a reduction of 0.72 mm in the minimal luminal diameter or by an increase in the percentage of stenosis to greater than or equal to 50 percent, occurred in 32 percent and 14 percent of patent stents, respectively. CONCLUSIONS Early occlusion remains an important limitation of this coronary-artery stent. Even when the early effects are beneficial, there are frequently late occlusions or restenosis. The place of this form of treatment for coronary artery disease remains to be determined.

Randomized Comparison of Percutaneous Coronary Intervention With Coronary Artery Bypass Grafting in Diabetic Patients: 1-Year Results of the CARDia (Coronary Artery Revascularization in Diabetes) Trial

OBJECTIVES The purpose of this study was to compare the safety and efficacy of percutaneous coronary intervention (PCI) with stenting against coronary artery bypass grafting (CABG) in patients with diabetes and symptomatic multivessel coronary artery disease. BACKGROUND CABG is the established method of revascularization in patients with diabetes and multivessel coronary disease, but with advances in PCI, there is uncertainty whether CABG remains the preferred method of revascularization. METHODS The primary outcome was a composite of all-cause mortality, myocardial infarction (MI), and stroke, and the main secondary outcome included the addition of repeat revascularization to the primary outcome events. A total of 510 diabetic patients with multivessel or complex single-vessel coronary disease from 24 centers were randomized to PCI plus stenting (and routine abciximab) or CABG. The primary comparison used a noninferiority method with the upper boundary of the 95% confidence interval (CI) not to exceed 1.3 to declare PCI noninferior. Bare-metal stents were used initially, but a switch to Cypher (sirolimus drug-eluting) stents (Cordis, Johnson & Johnson, Bridgewater, New Jersey) was made when these became available. RESULTS At 1 year of follow-up, the composite rate of death, MI, and stroke was 10.5% in the CABG group and 13.0% in the PCI group (hazard ratio [HR]: 1.25, 95% CI: 0.75 to 2.09; p=0.39), all-cause mortality rates were 3.2% and 3.2%, and the rates of death, MI, stroke, or repeat revascularization were 11.3% and 19.3% (HR: 1.77, 95% CI: 1.11 to 2.82; p=0.02), respectively. When the patients who underwent CABG were compared with the subset of patients who received drug-eluting stents (69% of patients), the primary outcome rates were 12.4% and 11.6% (HR: 0.93, 95% CI: 0.51 to 1.71; p=0.82), respectively. CONCLUSIONS The CARDia (Coronary Artery Revascularization in Diabetes) trial is the first randomized trial of coronary revascularization in diabetic patients, but the 1-year results did not show that PCI is noninferior to CABG. However, the CARDia trial did show that multivessel PCI is feasible in patients with diabetes, but longer-term follow-up and data from other trials will be needed to provide a more precise comparison of the efficacy of these 2 revascularization strategies. (The Coronary Artery Revascularisation in Diabetes trial; ISRCTN19872154).

Quantitative angiographic assessment of elastic recoil after percutaneous transluminal coronary angioplasty

Little is known about the elastic behavior of the coronary vessel wall directly after percutaneous transluminal coronary angioplasty (PTCA). Minimal luminal cross-sectional areas of 151 successfully dilated lesions were studied in 136 patients during balloon inflation and directly after withdrawal of the balloon. The circumvent geometric assumptions about the shape of the stenosis after PTCA, a videodensitometric analysis technique was used for the assessment of vascular cross-sectional areas. Elastic recoil was defined as the difference between balloon cross-sectional area of the largest balloon used at the highest pressure and minimal luminal cross-sectional area after PTCA. Mean balloon cross-sectional area was 5.2 +/- 1.6 mm2 with a mean minimal cross-sectional area of 2.8 +/- 1.4 mm2 immediately after inflation. Oversizing of the balloon (balloon artery ratio greater than 1) led to more recoil (0.8 +/- 0.3 vs 0.6 +/- 0.3 mm, p less than 0.001), suggestive of an elastic phenomenon. A difference in recoil of the 3 main coronary branches was observed: left anterior descending artery 2.7 +/- 1.3 mm2, circumflex artery 2.3 +/- 1.2 mm2 and right coronary artery 1.9 +/- 1.5 mm2 (p less than 0.025). The difference was still statistically significant if adjusted for reference area. Thus, nearly 50% of the theoretically achievable cross-sectional area (i.e., balloon cross-sectional area) is lost shortly after balloon deflation.

Restenosis After Coronary Angioplasty: New Standards for Clinical Studies

With the high initial success rates for coronary angioplasty that are reported regularly, it has become increasingly difficult to demonstrate methods or techniques that are able to provide more beneficial early results than can be achieved by conventional angioplasty. On the other hand, the incidence of late restenosis has remained much the same over the 10 years that angioplasty has been part of clinical practice, and there is still no proved intervention that modifies the restenosis process. Therefore, the problem of restenosis has assumed increasing relevance in determining the clinical value of coronary angioplasty and, accordingly, studies that address the problem of restenosis need to become more exacting. Although numerous articles have addressed the problem of restenosis in the clinical setting, many defining certain factors associated with restenosis and possible interventions to reduce the incidence of restenosis, there is surprisingly little consensus. Most of the discrepancies can be attributed to three factors: 1) the selection of patients, 2) the method of analysis, and 3) the definition of restenosis employed. This review shows how these three factors influence the outcome and conclusions of restenosis studies.

Long-term Effects of Angiopeptin Treatment in Coronary Angioplasty Reduction of Clinical Events but Not Angiographic Restenosis

Background Angiopeptin is a cyclic octapeptide analogue of somatostatin that has been shown to limit myointimal thickening of arteries in balloon injury models and to restore the vasodilating response to acetylcholine. A randomized, double-blind placebo controlled trial was conducted to assess the effect of angiopeptin in restenosis prevention after percutaneous transluminal coronary angioplasty (PTCA). Methods and Results Patients received a continuous infusion of either placebo or angiopeptin subcutaneously 6 to 24 hours before PTCA and for 4 days after PTCA (3 mg per 24 hours before PTCA followed by 6 mg per 24 hours after PTCA and for the remaining period). A 1.5-mg bolus dose of placebo or angiopeptin was given at PTCA. Aspirin (acetylsalicylic acid, 150 mg/d) was administered throughout the study period. Coronary angiograms obtained before and after PTCA and at 6-month follow-up were subjected to computerized quantification. Clinical follow-up was performed after 12 months. Primary clinical end points were death, myocardial infarction, coronary artery bypass surgery, or repeat PTCA. In total, 553 patients with 742 lesions were randomized. Clinical follow-up was available for all 553 patients. Angiopeptin decreased the clinical events during 12 months of follow-up from 36.4% in the placebo-treated group to 28.4% in the angiopeptin-treated patients ( P =.046). Quantitative angiography after PTCA and at follow-up was available in 423 of 455 patients who underwent successful PTCA. The minimal lumen diameter at follow-up was 1.52±0.64 mm in the angiopeptin-treated group compared with 1.52±0.64 mm in the placebo-treated patients ( P =.96). The late losses were 0.31±0.59 and 0.30±0.62 mm ( P =.81) and the restenosis rates (>50% diameter stenosis at follow-up) were 36% and 37% ( P =.85) in the angiopeptin- and placebo-treated groups, respectively. Conclusions In this study, angiopeptin significantly decreased the incidence of clinical events, principally the rate of revascularization procedures. In contrast, no significant effect was seen on angiographic variables.

Percutaneous transluminal angioplasty of a totally occluded venous bypass graft: A challenge that should be resisted

Abstract Percutaneous transluminal angioplasty is an accepted treatment for stenoses of bypass grafts1,2 and for total coronary artery occlusions.3,5 It follows that the same treatment would also be appropriate for total occlusions of saphenous aortocoronary bypass grafts. This report describes our clinical experience with attempted dilatation of totally occluded saphenous bypass grafts.

Change in diameter of coronary artery segments adjacent to stenosis after percutaneous transluminal coronary angioplasty: failure of percent diameter stenosis measurement to reflect morphologic changes induced by balloon dilation

To determine the changes in stenotic and nonstenotic segments of a dilated coronary artery, detailed quantitative angiographic measurements were performed in 342 patients (398 lesions) immediately after angioplasty and at a predetermined follow-up time of 30, 60, 90 or 120 days after the dilation. Measurements of the stenotic segments were expressed as minimal luminal diameter, and the adjacent nonstenotic segments were expressed as interpolated reference diameter (both in millimeters). A follow-up rate of 86% was achieved. In the patients followed up at 30 and 60 days, there was no significant change in either the mean minimal luminal diameter or the mean reference diameter. However, at 90 and 120 days, there was significant deterioration in both the mean minimal luminal diameter (-0.37 and -0.42 mm, respectively) and the mean reference diameter (-0.17 and -0.26 mm, respectively), all of the changes being highly significant (p less than 0.00001). The reference diameter is involved in the dilation process and may be subject to the same restenosis process that takes place in initially stenotic segments. Percent diameter stenosis measurements, which are conventionally used to express the change in the severity of a stenosis after angioplasty, will tend to underestimate the change when there is a simultaneous reduction in the reference diameter.

Stenting of venous bypass grafts: A new treatment modality for patients who are poor candidates for reintervention

Abstract During a 2-year period, 136 self-expanding Wall-stents were implanted in saphenous vein bypass grafts in 69 patients with end-stage coronary artery disease. All patients had severe symptoms and the majority were poor candidates for either repeat surgery or conventional bypass coronary angioplasty because of unfavorable native anatomy, impaired left ventricular function, or a high-risk bypass lesion anatomy for coronary angioplasty. All procedures were technically successful without major complications and a need for emergency bypass surgery. However, during the hospital stay acute thrombotic complications occurred in seven patients (10%) resulting in one death and acute myocardial infarction in five patients and necessitating emergency repeat PTCA in two patients and repeat CABG in four. Twenty-three patients had serious hemorrhagic complications directly related to the rigorous anticoagulation schedule. Two patients died of fatal cerebral bleeding. During follow-up, another five patients died accounting for a total mortality rate of 12%. At late angiographic follow-up (4.9 ± 3.4 months, n = 53), 25 patients (47%) had a restenosis (≥50% DS) within or immediately adjacent to the stent, necessitating reintervention in 19 patients (PTCA, n = 12; repeat CABG, n = 7). In the group without stent-related restenosis (n = 28), 15 patients had progression of disease in either the native or bypass vessels leading to recurrence of major anginal symptoms within 1 to 24 months. Ten of these patients required further intervention (stent, n = 6; PTCA, n = 3; repeat CABG, n = 1). Stenting in saphenous coronary bypass grafts can be performed safely with excellent immediate angiographic and clinical results. Early occlusion, late restenosis, and bleeding complications associated with the aggressive anticoagulant treatment remain significant limitations. Reintervention as a result of restenosis or progression of disease in other lesions is common. Stenting of diseased bypass grafts in symptomatic patients with end-stage coronary artery disease (who are at high risk for conventional angioplasty or surgical reintervention) may be useful as palliative therapy.

Coronary blood flow velocity during percutaneous transluminal coronary angioplasty as a guide for assessment of the functional result

To investigate the clinical usefulness of intracoronary Doppler recordings during percutaneous transluminal coronary angioplasty (PTCA), the changes of intracoronary blood flow velocity during PTCA were assessed in 20 patients with single proximal coronary stenosis, using a Doppler probe end-mounted on the tip of a PTCA catheter. A mean of 4 inflations was performed in each patient. Intracoronary velocities were measured before and after each inflation and during peak reactive hyperemia after each transluminal occlusion. Quantitative analysis of the coronary stenosis was assessed before and after PTCA, and the dilatation resulted in an increase in minimal luminal cross-sectional area from 1.1 +/- 0.8 to 2.7 +/- 1.2 mm2. A gradual and significant improvement in velocities was observed after the first 3 dilatations, but in 15 of the 20 patients the resting and hyperemic velocities were not affected by the fourth dilatation. Coronary flow reserve measured during reactive hyperemia after the last dilatation with the PTCA catheter across the lesion was 1.9. This value of coronary flow reserve is compatible with the residual stenosis measured after PTCA when corrected for the presence of the Doppler balloon catheter (0.68 mm2). This application of the Doppler technique may provide a new method of on-line functional monitoring of the PTCA procedure in individual patients, but does not yet allow an accurate prediction of the change in coronary geometry brought about by PTCA.