Ionic or non-ionic contrast media during coronary intervention: does it make a difference?
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Biomedical subjects
Publications and source records attributed to V Legrand.
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AIMS: To prospectively evaluate the influence of stent length on 6 month clinical and angiographic outcome, in patients with native coronary lesions up to 45 mm in length, undergoing elective Magic Wallstent implantation. METHODS AND RESULTS: On the basis of pre-procedural angiography, 276 patients (aged 61.3+/-10.2 years; 78.6% male; 41.7% unstable angina) with a total of 302 lesions were prospectively assigned to one of five different length categories of Magic Wallstent. Angiography in multiple matched projections before and after implantation and at 6 months follow-up was analysed at the core laboratory. Primary end-points for the efficacy analysis were cumulative incidence of major adverse cardiac events and quantitative coronary angiography analysis 6 months after stent implantation. Magic Wallstent implantation was successful in 301 of 302 lesions and in 98.6% a residual stenosis <20% by online quantitative coronary angiography was achieved. At 30 days, 6.2% (1.8% subacute occlusion) of patients had experienced major adverse cardiac events, 27.5% at 6 months and 30.4% at 9 months. Angiographic restenosis occurred in 37%. Restenosis rates for the mini, extra-short, short, medium and long Wallstent groups were 25.9%, 25%, 22.6%, 36.2% and 67.5%, respectively. Multivariate analysis revealed stent length to be independently associated with greater angiographic restenosis and major adverse cardiac events. CONCLUSIONS: While shorter Magic Wallstents provided late outcomes comparable with short balloon-expandable stents, excessive restenosis with longer Wallstents should obviate their use in elective percutaneous intervention. Long coronary lesions provide a challenging substrate for emerging antirestenosis therapies, such as stent coatings and brachytherapy.
We examined the immediate and long-term outcome after stenting of the left main coronary artery (LMCA) in 41 consecutive patients who had been considered unsuitable for coronary artery bypass graft surgery (CABG). The procedure was elective in thirty-two patients (78%) with a protected LMCA in 24 patients and non-protected LMCA in 8 patients; the procedure was acute in the setting of myocardial infarction or complication of a diagnostic angiography in 9 patients (22%). The mean follow-up duration was 19 +/- 13 months. There were 5 in-hospital and 3 late deaths; repeat angioplasty was performed in 5 cases, but only one for LMCA restenosis. Results varied considerably depending on the clinical presentation. For acute patients, technical success was achieved in 89%, survival at hospital discharge was 44% and there was no cardiac event at the late follow-up. For elective patients, technical success was achieved in 100%, survival at hospital discharge was 96% and 90% at follow-up. The results of our study suggest that when patients have surgical risks, elective LMCA stenting either protected or unprotected may be undertaken with a high procedural success rate and a favourable clinical late follow-up.
Unstable angina generally is a serious condition which often requires hospital treatment. In this review article, we shall describe our therapeutic approach to unstable angina. It is almost identical worldwide. This attitude is based on the evidence provided by well controlled clinical trials. It is therefore a good example of Evidence-Based Medicine.
Stable angina is one of the manifestations of coronary artery disease. In this review, we shall define the clinical criteria for the diagnosis of angina. The different techniques of evaluation will be discussed with a particular emphasis on the international recommendations for the use of coronary arteriography. The different therapeutic modalities will be outlined based on the results of large controlled clinical trials. Finally, the guidelines proposed for the use of coronary by-pass surgery and PTCA will be reviewed.
Adenovirus (Ad) tropism is mediated in part through the fibre protein. The common coxsackie B virus and Ad receptor (CAR) was recently identified as the major receptor for subgroup C Ad serotype 5 (Ad5) and serotype 2 (Ad2) fibres. Effects of mutations in the Ad5 fibre gene were studied to assess domains of the fibre capsomer that could alter virus tropism without altering virus assembly and replication. All mutants that accumulated as fibre monomers failed to assemble with a penton base and proved lethal for Ad5 which suggests that the absence of infectious virions resulted in part from a defect in fibre penton base assembly. Cell binding capacity of all fibre mutants was investigated in cell binding competition experiments with adenovirions using CHO-CAR cells (CHO cells that have been transfected with CAR cDNA and express functional CAR). The results suggest that the R-sheet of the Ad5 fibre knob monomer contains binding motifs for CAR and that beta-strands E and F, or a region close to them, may also be involved in receptor recognition.
In vivo targeting of therapeutic genes to specific tissues has become a major issue in gene therapy, in particular when recombinant adenovirus vectors are used. Restriction of the viral tropism to selected cell types requires the abrogation of the interaction between the viral fiber and its natural cellular receptors and the introduction of a new binding specificity into the virion. In this context, fiberless adenoviruses are attractive vectors, since they may be used as substrates for the insertion of a new ligand in other capsid proteins. In this study, we confirm by using cloned full-length adenovirus genomes with the fiber gene deleted that efficient virus particle formation can occur in the absence of fiber. As expected, the infectivity of such fiberless viruses was severely reduced, but it could be only partially restored when the viruses were produced in cells stably providing the fiber in trans. Although incorporation of penton base into the fiberless particles was normal and binding of the particles to the cellular integrins was functional, several pieces of experimental evidence suggest that later steps in the cell entry process are impaired in correlation with an incorrect maturation of several structural proteins of the fiberless particles. These observations support the hypothesis that the fiber protein may have additional biological functions besides its role in cell binding. Together with the fiber complementation cells, such fiberless vectors constitute unique tools to investigate the role of the fiber in virus assembly, maturation, and cell entry and to explore the possibility of deriving gene transfer vectors with novel target specificities.
Cardiovascular diseases represent the major cause of death in women. If women are early in life relatively protected by their hormones, after the menopause heart disease and stroke become their greatest health threat. Altogether one in three women will die of cardiovascular disease whereas only one in twenty-two will die of breast cancer. The risk factors for cardiovascular diseases are similar in both sexes. It should be noted however that the impact of diabetes on the development of coronary artery disease is markedly higher in woman than in man. In woman the first presenting symptom of coronary artery disease frequently is angina pectoris. In man it is more often an acute myocardial infarction whether it be symptomatic or silent. The various non invasive techniques used for the diagnosis of coronary artery disease may yield results that pose very difficult problems of differential diagnosis in women. Several studies indicate that in the past, probably because of the ignorance by the public and, perhaps, the medical profession of the high prevalence of cardiovascular and coronary artery diseases in women, the latter have not always received an optimal treatment when they suffered an acute ischemic attack. But, in this decade, they have been dramatic changes in the patents of clinical practice related to coronary heart disease in women. Statistical investigations however indicate that thrombolytic therapy appears less efficacious in women than in men whereas beta-blockers administered early in acute MI are of remarkable efficacy in women. It seems generally agreed that the results of revascularization by coronary artery bypass surgery are poorer in women than in men both in terms of operative mortality and morbidity. Initially, the same pessimism was reported for PTCA. However, recent results allow a much more optimistic view.
Revascularization techniques such as coronary angioplasty or coronary artery bypass surgery play a growing role in the management of coronary artery disease. Angioplasty is the treatment of choice for single coronary lesions while surgery remains the best approach for the revascularization of multivessel disease. There are some exceptions to this rule, however. Bypass surgery may be recommended for the revascularisation of proximal left anterior descending lesions and, of course, for isolated left main stenosis. On the opposite, coronary angioplasty and stenting is used more frequently in the treatment of multivessel lesions amenable to this technique. Choice of either method of revascularization is pragmatic, based on clinical, anatomical and physiological considerations and organized in the setting of a medicosurgical collaboration.
The present study has documented changes in the in situ distribution of viral DNA and capsid proteins in 293 cells infected with fiber gene-deleted adenoviruses. It shows that infection results in the intense production of progeny viruses which appear morphologically intact although they are devoid of fiber-coding sequence in their genome and hence of fiber protein in their capsid. The data confirm, therefore, that fiber protein is not essential for the assembly of progeny viruses. The main contribution of our observations concerns specific intranuclear structures induced by infection with either wild-type or fiber gene-deleted viruses. These clear amorphous inclusions contain two cellular proteins, PML and Sp100, which in non-infected cells co-localize to a special type of nuclear bodies. PML and Sp100 nuclear bodies appear to directly modulate or to be altered in a wide variety of situations including viral infections, cell death and transformation. In cells infected with fiber gene-deleted viruses, the clear amorphous inclusions now accumulate non-used hexon and penton base proteins, whereas the absence of fiber protein prevents the assembly of capsid proteins in crystallin arrays. Taken together, the data suggest that the clear amorphous inclusions may correspond to storage sites of structural and regulatory proteins. Consequently, these virus-induced structures may promote the productive cycle of adenoviruses by regulating the amount of over-produced viral proteins and the shutoff of the host cell metabolism.
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BACKGROUND: Dual therapy with ticlopidine and aspirin has been shown to be as effective as or more effective than conventional anticoagulation in patients with an optimal result after implantation of intracoronary metallic stents. However, the safety and efficacy of antiplatelet therapy alone in an unselected population has not been evaluated. METHODS: Patients were randomized to conventional anticoagulation or to treatment with antiplatelet therapy alone. Indications for stenting were classified as elective (decided before the procedure) or unplanned (to salvage failed angioplasty or to optimize the results of balloon angioplasty). After stenting, patients received aspirin and either ticlopidine or conventional anticoagulation (heparin or oral anticoagulant). The primary end point was the occurrence of bleeding or peripheral vascular complications; secondary end points were cardiac events (death, infarction, or stent occlusion) and duration of hospitalization. RESULTS: In 13 centers, 236 patients were randomized to anticoagulation and 249 to antiplatelet therapy. Stenting was elective in 58% of patients and unplanned in 42%. Stent implantation was successfully achieved in 99% of patients. A primary end point occurred in 33 patients (13.5%) in the antiplatelet group and 48 patients (21%) in the anticoagulation group (odds ratio=0.6 [95% CI 0.36 to 0.98], P=0.03). Major cardiac-related events in electively stented patients were less common (odds ratio=0.23 [95% CI 0.05 to 0.91], P=0.01) in the antiplatelet group (3 of 123, 2.4%) than the anticoagulation group (11 of 111, 9.9%). Hospital stay was significantly shorter in the antiplatelet group (4.3+/-3.6 versus 6. 4+/-3.7 days, P=0.0001). CONCLUSIONS: Antiplatelet therapy after coronary stenting significantly reduced rates of bleeding and subacute stent occlusion compared with conventional anticoagulation.
BACKGROUND: The multicentre, randomised Benestent-II study investigated a strategy of implantation of a heparin-coated Palmar-Schatz stent plus antiplatelet drugs compared with the use of balloon angioplasty in selected patients with stable or stabilised unstable angina, with one or more de-novo lesions, less than 18 mm long, in vessels of diameter 3 mm or more. METHODS: 827 patients were randomly assigned stent implantation (414 patients) or standard balloon angioplasty (413 patients). The primary clinical endpoint was event-free survival at 6 months, including death, myocardial infarction, and the need for revascularisation. The secondary endpoints were the restenosis rate at 6 months and the cost-effectiveness at 12 months. There was also one-to-one subrandomisation to either clinical and angiographic follow-up or clinical follow-up alone. Analyses were by intention to treat. FINDINGS: Four patients (one stent group, three angioplasty group) were excluded from analysis since no lesion was found. At 6 months, a primary clinical endpoint had occurred in 53 (12.8%) of 413 patients in the stent group and 79 (19.3%) of 410 in the angioplasty group (p=0.013). This significant difference in clinical outcome was maintained at 12 months. In the subgroup assigned angiographic follow-up, the mean minimum lumen diameter was greater in the stent group than in the balloon-angioplasty group, (1.89 [SD 0.65] vs 1.66 [0.57] mm, p=0.0002), which corresponds to restenosis rates (diameter stenosis > or =50%) of 16% and 31% (p=0.0008). In the group assigned clinical follow-up alone, event-free survival rate at 12 months was higher in the stent group than the balloon-angioplasty group (0.89 vs 0.79, p=0.004) at a cost of an additional 2085 Dutch guilders (US$1020) per patient. INTERPRETATION: Over 12-month follow-up, a strategy of elective stenting with heparin-coated stents is more effective but also more costly than balloon angioplasty.
OBJECTIVES: This study reports the first multicenter experience with the Wiktor coil stent for treatment of chronic total coronary artery occlusions (CTOs). BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) of CTO is associated with very high restenosis and reocclusion rates. Coronary stenting has been proposed as a means of improving outcome. However, the Wiktor device for CTOs has never been tested in a large patient sample. METHODS: From January 1993 to December 1996, 89 patients with 91 CTOs underwent Wiktor stent implantation after successful PTCA. The post-stenting regimen consisted of warfarin (Coumadin) plus aspirin in the initial 49 patients (55%) and aspirin plus ticlopidine in 40 patients (45%). RESULTS: Stenting was successful in 87 patients (98%). At 1 month, 6% of patients had subacute stent thrombosis, 3% had a major bleeding event, and 1% had access-site complications. Subacute stent thrombosis showed univariate association with warfarin therapy (p = 0.009). Angiographic follow-up was obtained in 76 (93%) of 82 eligible patients. The restenosis rate was 32%, including 4% reocclusions. By multiple logistic regression analysis, restenosis was independently associated with multiple stents (adjusted odds ratio [OR] 27.67, 95% confidence interval [CI] 4.25 to 79.95, p = 0.0008) and increasing values of occlusion length (adjusted OR 1.23, 95% CI 1.09 to 1.39, p = 0.001). Freedom from death, myocardial infarction or stented vessel revascularization was 87% and 72% at 1 and 3 years, respectively. CONCLUSIONS: Short- and long-term clinical and angiographic outcomes are favorable in patients undergoing Wiktor stent implantation in CTO. Further technical improvement is needed to reduce the restenosis rate in patients with long lesions and multiple stents.
BACKGROUND: Experimental studies suggest that the antiproliferative effect of heparin after arterial injury is maximized by pretreatment. No previous studies of restenosis have used a pretreatment strategy. We designed this study to determine whether treatment with nadroparin, a low-molecular-weight heparin, started 3 days before the procedure and continued for 3 months, affected angiographic restenosis or clinical outcome after coronary angioplasty. METHODS AND RESULTS: In a prospective multicenter, double-blind, randomized trial, elective coronary angioplasty was performed on 354 patients who were treated with daily subcutaneous nadroparin (0.6 mL of 10,250 anti-Xa IU/mL) or placebo injections started 3 days before angioplasty and continued for 3 months. Angiography was performed just before and immediately after angioplasty and at follow-up. The primary study end point was angiographic restenosis, assessed by quantitative coronary angiography 3 months after balloon angioplasty. Clinical follow-up was continued up to 6 months. Clinical and procedural variables and the occurrence of periprocedural complications did not differ between groups. At angiographic follow-up, the mean minimal lumen diameter and the mean residual stenosis in the nadroparin group (1.37+/-0.66 mm, 51.9+/-21.0%) did not differ from the corresponding values in the control group (1.48+/-0.59 mm, 48.8+/-18.9%). Combined major cardiac-related clinical events (death, myocardial infarction, target lesion revascularization) did not differ between groups (30.3% versus 29.6%). CONCLUSIONS: Pretreatment with the low-molecular-weight heparin nadroparin continued for 3 months after balloon angioplasty had no beneficial effect on angiographic restenosis or on adverse clinical outcomes.
To determine whether metallic stent implantation within a coronary artery modifies the accuracy of angina or exercise test results in predicting stenosis, we studied 172 patients assigned to stent implantation and 153 patients assigned to balloon angioplasty enrolled in the Benestent trial comparing de novo stenting with conventional balloon angioplasty. Sensitivity and specificity curves were constructed for the prediction of percentage diameter stenosis and minimal lumen diameter. Receiver-operator curves were constructed for comparison of diagnostic accuracy. Identical exercise load and duration were achieved in the two groups, despite a better angiographic result in patients treated with a stent. Similarly, the diagnostic accuracy of clinical symptoms or exercise test results as a function of the angiographic results were similar in patients with and patients without a stent. The intersection points of the sensitivity and specificity curves for recurrent angina or ST-segment depression were 72% to 77%. The corresponding cut-off points for percentage diameter stenosis were, respectively, 52% and 50% for patients with and without a stent (1.35 and 1.50 mm for minimal lumen diameter). We conclude that the presence of an intracoronary stent does not affect the diagnostic accuracy of recurrent angina or exercise-induced ST depression in predicting residual stenosis. We also conclude that exercise tolerance is similar after balloon angioplasty, with or without stenting, despite a better angiographic outcome in the group receiving a stent, suggesting a minimal threshold beyond which the patient is no longer at risk for ischemia during exercise.
AIMS: Angiographic studies on the natural course of both focal and diffuse coronary atherosclerosis have not been performed before, but can both be assessed by quantitative coronary angiography. The objective of this study was to describe the natural course of focal and diffuse coronary atherosclerosis over time. METHODS AND RESULTS: In 129 patients with mild coronary artery disease, but not on lipid-lowering medication, three coronary angiograms were made each 2 years apart. Nine hundred and sixty five angiographically diseased and non-diseased segments were analysed by quantitative coronary angiography. Mean lumen diameter and minimal lumen diameter were used as measures of diffuse and focal coronary atherosclerosis. Mean lumen diameter and minimum lumen diameter decreased by 0.02 and 0.03 mm per year. The rate of progression was similar in the angiographically non-diseased, as in the mildly and moderately diseased segments. Progression of diffuse coronary atherosclerosis was largest in severely stenosed lesions (percentage diameter stenosis > or = 50%) and in the right coronary artery with a loss of 0.19 mm and 0.16 mm in mean lumen diameter. Progression of focal disease was most prominent in new and mild lesions and the right coronary artery, with a decrease in minimum lumen diameter of 0.34 mm and 0.22 mm. In most subgroups, progression occurred gradually over time. On a per segment level, progression and the occurrence of new lesions occurred in 4.4% and 4.2%. Regression and disappearance of a lesions was found in 2.3% and 1.9%. On a per patient level, 36% were progressors, 12% had a mixed response, 36% were stable, and 16% were regressors. CONCLUSION: Diffuse and focal coronary atherosclerosis progressed at the same rate in the first and second 2 years in stenosed and non-stenosed segments. The rate of coronary atherosclerosis progression was small, but was higher for focal than for diffuse disease. A minority of lesions progressed and spontaneous regression was rare.
In case of failed angioplasty, coronary stenting has gradually emerged as a non-surgical method to restore vessel patency and optimize coronary blood flow. There is still little clinical and angiographic information on the use of radiopaque single loose interdigitating wire stents in angioplasty complicated by threatened or acute closure. Seventy-one patients received Wiktor stents after threatened vessel closure in 53 cases and acute closure in 18 cases. Stent delivery was successful in 98%. In-hospital death occurred in 1 case (1.4%). Stents occlusion were faced in 10 cases (14%), of which 6 presented early and 4 late after the procedure. Urgent bypass surgery was needed in 9 cases (12%) and 7 patients (10%) developed acute myocardial infarction. Serious bleeding complications occurred in 7 cases (10%) and vascular repair was performed in 4 patients (5%). During a follow-up of 20 +/- 10 months, 2 patients died, no myocardial infarction was observed and recurrence of angina was noted in 17 patients (24%). Angiographic analysis showed an acute gain in minimal lumen diameter of 1.71 +/- 0.22 mm and a late loss of 0.63 +/- 0.17 mm. Angiographic restenosis (diameter stenosis > 50%) presented in 20% of patients. Therefore, Wiktor stenting yields similar results than currently used stents in acute closure and strictly defined threatened vessel closure following angioplasty.