Franz-Josef Neumann

Predictive Factors of Restenosis After Coronary Stent Placement

OBJECTIVESnThe objective of this study was to identify clinical, lesional and procedural factors that can predict restenosis after coronary stent placement.nnnBACKGROUNDnCoronary stent placement reduces the restenosis rate compared with that after percutaneous transluminal coronary angioplasty (PTCA). However, restenosis remains an unresolved issue, and identification of its predictive factors may allow further insight into the underlying process.nnnMETHODSnAll patients with successful coronary stent placement were eligible for this study unless they had had a major adverse cardiac event during the 1st 30 days after the procedure. Of the 1,349 eligible patients (1,753 lesions), follow-up angiography at 6 months was performed in 80.4% (1,084 patients, 1,399 lesions). Demographic, clinical, lesional and procedural data were prospectively recorded and analyzed for any predictive power for the occurrence of late restenosis after stenting. Restenosis was evaluated by using three outcomes at follow-up: binary restenosis as a diameter stenosis > or =50%, late lumen loss as lumen diameter reduction and target lesion revascularization (TLR) as any repeat PTCA or coronary artery bypass surgery involving the stented lesion.nnnRESULTSnMultivariate analysis demonstrated that diabetes mellitus, placement of multiple stents and minimal lumen diameter (MLD) immediately after stenting were the strongest predictors of restenosis. Diabetes increased the risk of binary restenosis with an odds ratio (OR) [95% confidence interval] of 1.86 [1.56 to 2.16] and the risk of TLR with an OR of 1.45 [1.11 to 1.80]. Multiple stents increased the risk of binary restenosis with an OR of 1.81 [1.55 to 2.06] and that of TLR with an OR of 1.94 [1.66 to 2.22]. An MLD <3 mm at the end of the procedure augmented the risk of binary restenosis with an OR of 1.81 [1.55 to 2.06] and that of TLR with an OR of 2.05 [1.77 to 2.34]. Classification and regression tree analysis demonstrated that the incidence of restenosis may be as low as 16% for a lesion without any of these risk factors and as high as 59% for a lesion with a combination of these risk factors.nnnCONCLUSIONSnDiabetes, multiple stents and smaller final MLD are strong predictors of restenosis after coronary stent placement. Achieving an optimal result with a minimal number of stents during the procedure may significantly reduce this risk even in patients with adverse clinical characteristics such as diabetes.

Diabetes mellitus and the clinical and angiographic outcome after coronary stent placement

OBJECTIVESnThe objectives of this study were to analyze the clinical and angiographic outcome of diabetic patients with successful coronary stent placement and to compare these results with those achieved after stenting in nondiabetic patients.nnnBACKGROUNDnThe outcome of diabetic patients treated with stent placement due to coronary artery disease has not been assessed comprehensively.nnnMETHODSnThis study analyzes a consecutive series of patients with successful stent placement comprising 715 patients with diabetes and 2,839 patients without diabetes. Clinical one year follow-up and angiographic control at 6 months were part of the protocol. Death, myocardial infarction and target lesion revascularization were considered as adverse events. An automated edge detection system was used for the angiographic assessment. The primary clinical endpoint was event-free survival at one year. The primary angiographic endpoint was restenosis rate at 6 months (> or = 50% diameter stenosis).nnnRESULTSnEvent-free survival was significantly lower in diabetic than in nondiabetic patients (73.1 vs. 78.5%, p < 0.001). Survival free of myocardial infarction was also significantly reduced in the diabetic group (89.9 vs. 94.4% in nondiabetics, p < 0.001). The incidence of both restenosis (37.5 vs. 28.3%, p < 0.001) and stent vessel occlusion (5.3 vs. 3.4%, p = 0.037) was significantly higher in diabetic patients. Diabetes was identified as an independent risk factor for adverse clinical events and restenosis in multivariate analyses.nnnCONCLUSIONSnPatients with diabetes mellitus have a less favorable clinical outcome at one year after successful stent placement as compared to the nondiabetic patients. The clinical follow-up was characterized by a higher incidence of death, myocardial infarction and reinterventions. Diabetic patients also demonstrated an increased risk for restenosis.

Vessel Size and Long-Term Outcome After Coronary Stent Placement

BACKGROUNDnThe role of coronary stenting in the treatment of patients with small vessels is not well defined. The purpose of this study was to investigate the influence of vessel size on long-term clinical and angiographic outcome after coronary stent placement.nnnMETHODS AND RESULTSnThe study comprised 2602 patients with successful stent implantation for symptomatic coronary artery disease. Patients were subdivided into 3 equally sized groups (tertiles) according to vessel size, with respective ranges of <2.8, 2.8 to 3.2, and >3.2 mm. Event-free survival at 1 year was 69.5% in the group with smaller vessels, 77.5% in the second group, and 81% in the group with larger vessels (P<0.001). Late lumen loss was similar between the 3 groups (1.12+/-0.73, 1.12+/-0.79, and 1.09+/-0. 88 mm, respectively). Angiographic restenosis rate was significantly higher in the small-vessel group (38.6%, 28.4%, and 20.4% in groups 1, 2, and 3, respectively; P<0.001). The analysis identified subgroups with different risk for restenosis even among patients with small vessels. Within this group, the restenosis rate may be as low as 29.6% in patients without additional risk factors and as high as 53.5% in patients with diabetes and complex lesions.nnnCONCLUSIONSnPatients with small vessels present a higher risk for an adverse outcome after coronary stent placement because of a higher incidence of restenosis. However, the unusually high risk for restenosis is confined to those patients with small vessels who have concomitant risk factors such as diabetes and complex lesions.

Influence of lesion length on restenosis after coronary stent placement

The length of a coronary lesion is a significant predictor of restenosis after balloon angioplasty. The influence of lesion length has not comprehensively been assessed after coronary stent placement. This study includes 2,736 consecutive patients with coronary stent placement. Only patients with recent or chronic occlusions before the intervention were excluded. Patients were divided in 2 groups: 573 patients with long lesions (> or = 15 mm) and 2,163 patients with short lesions (< 15 mm). There were no significant differences between the groups with respect to the procedural success rate and incidence of subacute thrombosis. One-year event-free survival was lower in patients with long lesions (73.3% vs 80.0%, p = 0.001). Six-month angiography was performed in 82.5% of the eligible patients. The incidence of binary restenosis (> or = 50% diameter stenosis) was higher in patients with long lesions (36.9% vs 27.9%, p <0.001). Similarly, patients with long lesions presented more late lumen loss than those with short lesions (1.29 +/- 0.89 vs 1.07 +/- 0.77 mm, p <0.001). Multivariate models for both binary restenosis and late lumen loss demonstrated that lesion length was an independent risk factor for restenosis. The risk was further increased by multiple stent placement and overlapping stents that were also independent risk factors of restenosis. Stented segment length did not show any independent effect. Therefore, long lesions represent an independent risk factor for restenosis after coronary stent placement. The results of this study suggest that a possible way to reduce the risk is to cover the lesion with a minimal number of nonoverlapping stents.

Platelets induce alterations of chemotactic and adhesive properties of endothelial cells mediated through an interleukin-1-dependent mechanism. Implications for atherogenesis

Platelets and alterations of chemotactic and adhesive properties of endothelium play an important role in the pathophysiology of atherosclerosis. We investigated the effect of platelets on secretion of monocyte chemotactic protein-1 (MCP-1) and on surface expression of intercellular adhesion molecule-1 (ICAM-1) of cultured endothelium. Pretreatment of cultured monolayers of endothelial cells with alpha-thrombin-activated platelets significantly enhanced secretion of MCP-1 and ICAM-1 surface expression (P<0.01) that could be inhibited by interleukin-1 (IL-1) antagonists by approximately 40%. Activation of transcription factor nuclear factor-kappaB (NF-kappaB) which regulates transcription of early inflammatory response genes such as MCP-1, was significantly increased in endothelial cells treated with activated platelets via an IL-1 mediated mechanism as determined by electrophoretic mobility shift assay (EMSA) and kappaB-dependent transcriptional activity. In trans-well experiments, alpha-thrombin-activated platelets enhanced IL-1-dependent surface expression of vitronectin receptor (alpha(v)beta(3)) on the luminal aspect of endothelial monolayers and promoted alpha(v)beta(3)-mediated platelet/endothelium adhesion that could be inhibited by the antiadhesive peptides GRGDSP and c(RGDfV). We conclude that activated platelets induce significant changes in chemotactic (secretion of MCP-1) and adhesive (surface expression of ICAM-1 and alpha(v)beta(3)) properties of cultured endothelium. These findings imply a potential pathophysiological mechanism of platelets in an early stage of atherogenesis.

Neutrophil and platelet activation at balloon-injured coronary artery plaque in patients undergoing angioplasty☆

OBJECTIVESnThis study sought to investigate changes in the expression of activation-dependent adhesion receptors on neutrophils and platelets after exposure to the balloon-injured coronary artery plaque.nnnBACKGROUNDnActivation of blood cells at the balloon-injured coronary artery plaque may contribute to abrupt vessel closure and late restenosis after percutaneous transluminal coronary angioplasty.nnnMETHODSnIn 30 patients undergoing elective coronary angioplasty, blood specimens were obtained through the balloon catheter proximal to the plaque before dilation and distal to the plaque after dilation. Simultaneous blood samples obtained through the guiding catheter served as control samples. Total surface expression of the inducible fibrinogen receptor (CD41) and surface expression of the activated fibrinogen receptor (LIBS1) on platelets as well as Mac-1 (CD11b) and L-selectin (CD62L) surface expression on neutrophils were assessed by flow cytometry.nnnRESULTSnAfter exposure to the dilated coronary artery plaque, surface expression of LIBS1 on platelets increased by 40.5 +/- 11.0 mean (+/-SE) fluorescence (p=0.001) and that of CD11b on neutrophils increased by 20.1 +/- 4.4 mean fluorescence (p=0.018). Concomitantly, anti-CD62L binding on neutrophils decreased by 6.6 +/- 2.4 mean fluorescence (p=0.022). In contrast, surface expression of the adhesion receptors did not change significantly between the coronary ostium and the prestenotic coronary segment.nnnCONCLUSIONSnThe results of this study demonstrate neutrophil and platelet activation at the balloon-injured coronary artery plaque. This cellular activation may serve as a target for pharmacologic interventions to improve the outcome of coronary angioplasty.

Optimal timing of coronary angiography and potential intervention in non-ST-elevation acute coronary syndromes

AIMSnAn invasive approach is superior to medical management for the treatment of patients with acute coronary syndromes without ST-segment elevation (NSTE-ACS), but the optimal timing of coronary angiography and subsequent intervention, if indicated, has not been settled.nnnMETHODS AND RESULTSnWe conducted a meta-analysis of randomized trials addressing the optimal timing (early vs. delayed) of coronary angiography in NSTE-ACS. Four trials with 4013 patients were eligible (ABOARD, ELISA, ISAR-COOL, TIMACS), and data for longer follow-up periods than those published became available for this meta-analysis by the ELISA and ISAR-COOL investigators. The median time from admission or randomization to coronary angiography ranged from 1.16 to 14 h in the early and 20.8-86 h in the delayed strategy group. No statistically significant difference of risk of death [random effects risk ratio (RR) 0.85, 95% confidence interval (CI) 0.64-1.11] or myocardial infarction (MI) (RR 0.94, 95% CI 0.61-1.45) was detected between the two strategies. Early intervention significantly reduced the risk for recurrent ischaemia (RR 0.59, 95% CI 0.38-0.92, P = 0.02) and the duration of hospital stay (by 28%, 95% CI 22-35%, P < 0.001). Furthermore, decreased major bleeding events (RR 0.78, 95% CI 0.57-1.07, P = 0.13), and less major events (death, MI, or stroke) (RR 0.91, 95% CI 0.82-1.01, P = 0.09) were observed with the early strategy but these differences were not nominally significant.nnnCONCLUSIONnEarly coronary angiography and potential intervention reduces the risk of recurrent ischaemia, and shortens hospital stay in patients with NSTE-ACS.

Coronary stent placement in patients with acute myocardial infarction : Comparison of clinical and angiographic outcome after randomization to antiplatelet or anticoagulant therapy

OBJECTIVESnThe Intracoronary Stenting and Antithrombotic Regimen (ISAR) trial is a randomized comparison of combined antiplatelet with anticoagulant therapy after coronary Palmaz-Schatz stent placement. The objective of this study was to compare early and late clinical and angiographic outcome in a subgroup of patients with stent placement for acute myocardial infarction.nnnBACKGROUNDnStenting has become a treatment option for acute myocardial infarction, but it is not known which antithrombotic regimen is more adequate after stent implantation.nnnMETHODSnOne hundred twenty-three patients with successful stenting after acute myocardial infarction were randomized to receive aspirin plus ticlopidine (n = 61) or intense anticoagulant therapy (n = 62). Six-month repeat angiography was performed in 101 (86.3%) eligible patients.nnnRESULTSnDuring the first 30 days after stenting, patients with antiplatelet therapy had a significantly lower clinical event rate (3.3% vs. 21.0%, p = 0.005) and stent vessel occlusion rate (0% vs. 9.7%, p = 0.03) and a trend to fewer cardiac events (1.6% vs. 9.7%, p = 0.12). After 6 months, the survival rate free of recurrent myocardial infarction was higher in patients with antiplatelet therapy (100% vs. 90.3%, p = 0.03), and the rate of stent vessel occlusion was lower (1.6% vs. 14.5%, p = 0.02). Both groups had comparable restenosis rates (26.5% vs. 26.9%, p = 0.87).nnnCONCLUSIONSnThis study demonstrates that combined antiplatelet therapy after stent placement in patients with acute myocardial infarction is associated with an overall better clinical and angiographic outcome than anticoagulant therapy.

Time course of restenosis during the first year after emergency coronary stenting.

BackgroundPrevention of abrupt vessel closure after percutaneous transluminal coronary angioplasty (PTCA) represents one of the current indications for intracoronary stent implantation. After the procedure, the stented segment undergoes luminal changes that may lead to late restenosis. This study was undertaken to assess the time course of luminal changes during the first year after emergency placement f coronary stents. Methods and ResultsCoronary stenting was indicated in patients with present or threatened vessel closure secondary to large dissections after PTCA. From June 1989 to May 1991, 82 patients who received Palmaz-Schatz stents and did not have early vessel occlusion after stenting were enrolled into a serial angiographic follow-up study. Coronary normal reference diameter and minimal luminal diameter were measured with an automated edge detection technique. Patients who underwent repeat PTCA for restenosis were excluded from further serial angiography. The restudy rate at 3, 6, and 12 months was 96% 81% and 90% of the eligible patients, respectively. The incidence of restenosis (defined as a diameter stenosis .50%) was 22.0% at 3 months, 31.9% at 6 months, and 33.2% at 12 months. Minimal luminal diameter was increased from 0.66±0.32 mm before to 2.85±0.43 mm immediately after stenting. It was 0.46±0.31 mm smaller than the diameter of the maximally inflated balloon during the procedure. The reduction in minimal luminal diameter was 0.80±0.69 mm (p =0.0001) for the first 3 months, 0.29 ± 0.52mm (p=0.0001) between 3 and 6 months, and 0.13±0.32 mm (p=0.01) for the last 6 months. The percentage of patients who presented a significant change in minimal luminal diameter (defined as >0.60 mm) declined from 50.6% during the first 3 months and 18.9% between 3 and 6 months to 6.5% for the period between 6 and 12 months. ConclusionsThe incidence and the time course of restenosis after emergency coronary stenting are similar to that reported for conventional PTCA. Coronary lumen dimensions demonstrated a peak change at 3 months and remained mostly stable after the first 6 months.

Induction of Cytokine Expression in Leukocytes in Acute Myocardial Infarction

OBJECTIVESnThis study sought to investigate whether cytokine expression in leukocytes may be induced by plasma from the reperfused heart of patients with an acute myocardial infarction (MI).nnnBACKGROUNDnReperfusion in acute MI is associated with deleterious local and systemic inflammatory responses that are regulated by cytokines. Induction of cytokine expression in resident leukocytes could contribute to inflammatory responses of the ischemic and reperfused heart.nnnMETHODSnBlood samples of 10 patients with an acute MI were obtained simultaneously from the coronary sinus and the aorta before and 5 min after recanalization of the coronary occlusion. Ten patients with elective percutaneous transluminal coronary angioplasty served as a control group. We incubated leukocytes from healthy donors with plasma samples and analyzed mRNA expression of interleukin (IL)-1 beta, IL-6, IL-8 and tumor necrosis factor-alpha (TNF-alpha) by Northern blot analysis.nnnRESULTSnIn patients with an acute MI, plasma obtained from the coronary sinus after recanalization increased the mRNA expression of IL-1 beta and IL-8 compared with that of plasma before recanalization (median [quartiles] difference before vs. after recanalization: 34.5 [4, 137], p = 0.017, for IL-1 beta; 18.5 [4, 35], p = 0.032, for IL-8) and simultaneously obtained aortic plasma (median [quartiles] coronary sinus-aortic differences after recanalization: 45.5 [-3, 115], p = 0.021, for IL-1 beta; 16 [4, 52], p = 0.005, for IL-8). No induction of IL-6 and TNF-alpha expression could be observed. No changes found in the study patients were detectable in the control group.nnnCONCLUSIONSnPlasma from the ischemic and reperfused heart stimulates the expression of IL-1 beta and IL-8 in leukocytes. Therefore, leukocyte-derived cytokines may contribute to the regulation of cardiac inflammatory responses in patients with an acute MI.