Abstract: BACKGROUND: The oral direct thrombin inhibitor ximelagatran, and its active form, melagatran, have been tested in various clinical conditions as a promising alternative to conventional anticoagulant therapy (CAT), despite some concerns over potentially serious liver injury. OBJECTIVES: To assess its risk/benefit profile, a systematic review and meta-analysis of all randomised controlled trials (RCTs) comparing xi-/melagatran to CAT was performed. METHODS: Leading medical databases were searched. The rates of major adverse events (MAE: all cause death, nonfatal myocardial infarction, nonfatal thromboembolic stroke, nonfatal pulmonary embolism), major bleeds (MB), and hepatotoxicity were compared. Out of 140 potentially relevant citations, 13 RCTs enrolling 22,639 patients were included. Indications for treatment were: 1) perioperative prophylaxis of deep vein thrombosis (DVT); 2) management of DVT; and 3) stroke prevention in atrial fibrillation. RESULTS: Overall, the risk of MAE (OR 0.98 [0.83-1.17]) and MB (OR 1.01 [0.69-1.47]) did not differ significantly between xi-/melagatran and CAT. There was a clear trend towards an increased risk of hepatotoxicity (OR 1.74 [0.50-6.01]), with an incidence of 5.8% with xi-/melagatran versus 2.3% with CAT (p<0.001); more specifically, the rate of hepatotoxicity was markedly augmented in the management of DVT (OR 5.16 [3.38-7.89]), for treatment durations > or = 3 months (OR 6.73 [5.01-9.05]), and in the prevention of atrial fibrillation-related stroke (OR 8.31 [5.65-12.23]). Two fatal cases of liver injury occurred with xi-/melagatran. CONCLUSIONS: Although comparable to CAT in terms of MAE and MB, xi-/melagatran carries a prohibitive risk of hepatotoxicity that cannot be ignored. Newer long-term alternatives are urgently needed.

Abstract: Overlapping homogenous drug-eluting stents (DESs) may be used instead of overlapping bare metal stents (BMSs) to treat coronary lesions longer than available stents. Yet, no data are available on patients treated with overlapping heterogenous DESs or DESs and BMSs. We prospectively assessed 9-month clinical outcome and 6-month angiographic late loss (evaluated at 5 different lesion segments) in a consecutive series of 40 patients who received overlapping homogenous DESs (sirolimus-eluting stent [SES] or paclitaxel-eluting stent [PES]), heterogenous DESs (SES + PES), or overlapping DESs and BMSs. In 8 patients (7 with angiographic follow-up) with overlapping heterogenous DESs, no angiographic or clinical adverse event was observed. Moreover, in-segment late loss was similar to that of patients who received homogenous DESs. In 8 patients (7 with angiographic follow-up) with overlapping DESs and BMSs, there was a higher incidence of major adverse events (3 repeat percutaneous coronary interventions and 1 death, 50% adverse event rate) and worse in-segment binary restenosis rate compared with patients treated with homogenous or heterogenous DESs (p = 0.02 and 0.012, respectively). Late lumen loss at the site of stent overlap showed significant differences according to type of overlapped stent (1.00 +/- 0.76 mm in DES-BMS overlap, 0.32 +/- 0.55 mm in PES-PES overlap, 0.13 +/- 0.11 in SES-PES overlap, and 0.08 +/- 0.10 mm in SES-SES overlap, p = 0.005). In conclusion, the present study suggests that overlap of DESs and BMSs should be avoided because the antirestenotic effect of DESs is skewed by contiguous BMS implantation. Overlap between SESs and PESs in this very preliminary report was associated with no specific adverse event.

Abstract: BACKGROUND: Stent thrombosis (ST) is a recognized complication limiting the clinical efficacy of percutaneous coronary interventions (PCI). Because of the increasing number of stent-based PCI, the absolute number of patients experiencing ST is expected to expand. Re-PCI is the commonly adopted treatment for patients with ST; however, the prognostic variables as well as the angiographic and clinical results have not been systematically assessed. Moreover, the possible benefit associated with the use of adjunctive devices (AD) with theoretical antiembolic property has not been systematically analyzed in this high-risk population. METHODS: We present the design of a prospective and retrospective multicenter registry to assess the contemporary angiographic and clinical outcome of PCI in patients with ST. Moreover, we sought to assess if the use of thrombectomy or distal protection AD is associated with any improvement in the PCI's angiographic results. All patients with angiographically confirmed ST undergoing attempt of PCI in the enrolling centers during a fixed 2-year study period will enter the study. Clinical outcome during hospitalization, at 30 days and 6 months will be assessed. Percutaneous coronary intervention with or without AD will be performed according to physician's discretion. All PCI cine-film will undergo blind core laboratory analysis to assess a series of key angiographic data (TIMI flow, TIMI frame count, thrombus score, myocardial blush grade, distal embolization). CONCLUSIONS: The OPTIMIST study is designed to provide a detailed description of the angiographic and clinical outcome achieved in the real world with contemporary PCI for ST. Moreover, it will provide observational data regarding the role of AD in this high-risk scenario.

Abstract: The present review aims to describe the pharmacological aspects as well as the available clinical data supporting the choice of intracoronary route of administration for abciximab, an antiplatelet drug used in patients with acute coronary syndromes undergoing percutaneous coronary interventions (PCI). Abciximab is a glycoprotein (GP) IIb/IIIa receptor antagonist which determines a potent inhibition of platelet aggregation and thrombus formation. These properties seem to prevent not only thrombus formation but also to promote (at higher drug concentration) lysis of fresh thrombus. Moreover, differently from the other GP IIb/IIIa inhibitors, abciximab also binds to the vitronectin receptor on endothelial, smooth muscle, and inflammatory cells and to an activated conformation of the aMb2 receptor on leukocytes. Such cross-reactivity raises the possibility that clinical benefits derived from its use may not be exclusively due to its anti-thrombotic effect, but may also be related to the suppression of inflammatory pathways involving platelets, white blood cells, and the vascular endothelium. On such basis, the local administration of abciximab at the site of coronary thrombosis may enhance, by increasing its local concentration, the binding to both platelet and endothelium receptors. The results of several angiographic studies assessing the effect of intracoronary abciximab administration support on clinical grounds its adoption in patients with fresh coronary thrombosis. Indeed, better post-angioplasty coronary flow, greater degree of myocardial salvage and a better left ventricular function recovery have been achieved as compared to the intravenous, systemic, administration of drug's bolus. Condensed Abstract Several studies have highlighted the benefits of abciximab, a potent antiplatelet agent, in patients with acute coronary syndromes undergoing percutaneous coronary interventions. Moreover, differently from the other glycoprotein IIb/IIIa receptor antagonists, abciximab also has non-IIb/IIIa-related properties raising the possibility that clinical benefits derived from its use may not be exclusively due to its anti-thrombotic effect, but may also be related to the suppression of inflammatory pathways. Several angiographic studies in patients with fresh coronary thrombosis and recent clinical studies in patients with acute coronary syndromes undergoing mechanical revascularization support the hypothesis that local administration of abciximab at the site of the culprit coronary artery may facilitate both the de-thrombotic and the non-GP IIb/IIIa-dependent properties of the drug. On such basis, the present review aims to describe the pharmacological aspects as well as the available clinical data supporting the choice of intracoronary route of administration for abciximab.

Abstract: Background: Percutaneous coronary intervention (PCI) of coronary bifurcation lesions remains a subject of debate. Many studies have been published in this setting. They are often small scale and display methodological flaws and other shortcomings such as inaccurate designation of lesions, heterogeneity, and inadequate description of techniques implemented. Methods: The aim is to propose a consensus established by the European Bifurcation Club (EBC), on the definition and classification of bifurcation lesions and treatments implemented with the purpose of allowing comparisons between techniques in various anatomical and clinical settings. Results: A bifurcation lesion is a coronary artery narrowing occurring adjacent to, and/or involving, the origin of a significant side branch. The simple lesion classification proposed by Medina has been adopted. To analyze the outcomes of different techniques by intention to treat, it is necessary to clearly define which vessel is the distal main branch and which is (are) the side branche(s) and give each branch a distinct name. Each segment of the bifurcation has been named following the same pattern as the Medina classification. The classification of the techniques (MADS: Main, Across, Distal, Side) is based on the manner in which the first stent has been implanted. A visual presentation of PCI techniques and devices used should allow the development of a software describing quickly and accurately the procedure performed. Conclusion: The EBC proposes a new classification of bifurcation lesions and their treatments to permit accurate comparisons of well described techniques in homogeneous lesion groups. (c) 2007 Wiley-Liss, Inc.

Abstract: There is ongoing debate to identify the most effective, safe and cost-beneficial drug-eluting stent, between the two currently approved and used devices, i.e. sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES). To date, head-to-head comparison studies of SES vs PES have been however limited by relatively small sample sizes and the low number of events typically associated with these highly effective coronary devices. To overcome the drawbacks of single trials, direct and indirect comparison meta-analyses have been designed and conducted to thoroughly compare sirolimus- vs paclitaxel eluting-stents. This article provides results of a pooled analysis of such indirect and direct comparisons, definitively demonstrating across 5854 patients the superiority of SES in comparison to PES (odds ratio 0.62 [95% confidence interval 0.50-0.75], p<0.0001 for binary angiographic restenosis, and odds ratio 0.66 [0.52-0.84], p=0.0008 for target lesion revascularization). Indeed, such combination of direct and indirect comparisons should also be envisaged to soundly and timely appraise the next generation of drug-eluting stents.

Abstract: BACKGROUND: Systemic inflammation is involved in several pathological cardiovascular processes. However, whether it plays a role in the no-reflow phenomenon occurring in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI) is unknown. METHODS: We studies 60 consecutive patients (59.5+/-12 years, 82% males) with a first ST-segment elevation AMI, treated by primary or rescue PCI within 6 h of symptom onset. Angiographic indexes of no-reflow, evaluated at the end of the procedure, included coronary TIMI flow grading, corrected TIMI frame count (c-TFC) and myocardial blush grade (MBG). ECG indexes of no-reflow included the lack of ST segment resolution (defined as a reduction <50% of the measured ST-segment elevation at 90 min, compared to the admission ECG), as analyzed both in the single lead with the maximal ST elevation and in all leads showing ST elevation on admission. Patients were divided into two groups according to baseline high-sensitivity C-reactive protein (CRP) serum levels measured on admission: high CRP group (CRP>5 mg/L) and low CRP group (CRP<5 mg/L). RESULTS: A similar prevalence of final TIMI flow<3 and MBG<3 was observed in patients with high and low CRP serum levels (30% vs. 12%, p=0.1, and 50% vs. 53%, p=1.0, respectively), and c-TFC was also similar in the two groups (26+/-4.5 vs. 24+/-6, p=0.5). Accordingly, the prevalence of lack of ST-segment resolution in the two groups was similar, both by the single-lead method (25% vs. 25%, p=1.0) and the multiple-lead method (29% vs. 19%, p=0.4). CONCLUSION: In this study we failed to demonstrate any significant association between CRP serum levels on admission and coronary no-reflow, as assessed by both angiographic and ECG parameters in AMI patients treated by successful primary or rescue PCI within 6 h of chest pain onset.

Abstract: OBJECTIVES: To overview and summarize the results emerging from the studies on adjunctive devices (AD) with theoretical anti-embolic properties in patients with ST-elevation acute myocardial infarction (STEMI) undergoing percutaneous coronary interventions (PCI). BACKGROUND: A series of small-to-medium size randomized studies have compared different AD with standard PCI (SP) in the setting of STEMI. The reported results are conflicting. METHODS: Eighteen prospective randomized studies on 3180 STEMI patients comparing AD with SP were identified and entered the meta-analysis. Pre-specified angiographic, electrocardiographic (absence of ST-segment resolution, STR) and early (up to 30 days) clinical end-points were assessed. RESULTS: AD were associated with lower rates of angiographically evident distal embolization: OR (95% CI): 0.54 (0.37-0.81). Analyses of angiographic and electrocardiographic reperfusion showed striking heterogeneity among studies and an overall trend toward better results with AD: OR (95% CI) 0.76 (95% CI 0.51-1.12) for TIMI<3, 0.53 (0.37-0.76) for myocardial blush grade (MBG)<3, 0.60 (0.45-0.78) for absence of STR. Subgroup analysis according to the type of AD for the end-point of no STR showed concordant absence of benefit in studies testing distal protection devices, positive results being confined to the studies using thrombectomy devices (OR 0.46, 95% CI 0.32-0.66). However, the possibility of a "small study" bias within thrombectomy studies cannot be discharged (significant heterogeneity and positive Egger's test). Early major adverse cardiac events were not different between AD and SP. CONCLUSIONS: AD use may be associated with reduced rate of angiographic distal embolization, and improved MBG 3 and STR rates. However, efficacy might vary with the type of device employed. Moreover, early clinical outcome is not modified suggesting that further, larger, studies are needed to assess the clinical impact of AD. CONDENSED ABSTRACT: We conducted a meta-analysis of 18 prospective randomized trials comparing adjunctive devices (AD) with standard PCI in the setting of STEMI. The use of AD was associated with lower rates of (angiographically evident) distal embolization. Analyses of angiographic and electrocardiographic reperfusion showed striking heterogeneity and an overall trend toward better results with AD. Subgroup analysis suggested that different types of device may have different effects. Early major adverse cardiac events were similar between AD and SP.

Abstract:

Abstract: BACKGROUND: A series of thrombectomy and distal filter devices have been developed to limit distal embolization during percutaneous coronary interventions (PCI). OBJECTIVE: To evaluate the feasibility of the combined use of thrombus-aspirating catheters and distal filter devices in patients at high risk of no-reflow. METHODS: Thrombus aspiration (TA) and distal filter protection (DFP) were sequentially used in a series of patients undergoing urgent PCI within 48 hours of acute myocardial infarction (MI). Inclusion criteria were: (1) occlusion of the infarct-related artery; (2) at least 2 out of the 6 Yip's classification features of high thrombus burden. Coronary angiograms were evaluated off-line to assess thrombus score, coronary flow and distal embolization in different phases of the procedure. RESULTS: TA followed by DFP prior to balloon dilatation or stent implantation was successfully performed in 20 patients with acute MI due to occlusion of de novo lesions (80%) or in-stent thrombosis (20%) located in a native coronary artery (90%) or a saphenous vein graft (10%). TA was associated with a significant acute reduction of TS and improvement of coronary flow (TIMI grade from 0.7 +/- 0.8 to 1.6 +/- 1.1; p = 0.004 and CTFC from 83 +/- 29 to 52 +/- 36; p = 0.006). This facilitated the deployment of DFP, which did not induce significant flow modification (TIMI grade: 2.3 +/- 0.9 pre-DFP placement vs. 2.2 +/- 1.0 post-DFP placement; p = 0.20; CTFC: 32 +/- 28 pre-DFP placement vs. 35 +/- 28 post-DFP placement; p = 0.47). Post-PCI angiography revealed a 90% TIMI 3 flow rate and 47% MBG 3 rate with only 1 case of angiographically evident distal embolization. CONCLUSIONS: Sequential use of TA and DFP may be successfully used during PCI in patients at very high risk of distal embolization. However, the possible benefits of such an approach should be weighted with the increased complexity of the procedure. Further evaluations of the clinical efficacy of this approach are needed.

Abstract: BACKGROUND: Preprocedural C-reactive protein (CRP) serum levels have been shown to predict the recurrence of angina or major adverse cardiac events after percutaneous coronary intervention. Directional coronary atherectomy (DCA), by reducing residual plaque burden and restenosis, has been shown to improve clinical outcome after coronary stenting. Thus, we assessed the influence of preprocedural CRP serum levels on the recurrence of cardiac events after DCA followed by bare metal stent implantation. METHODS: We enrolled 40 consecutive patients (34 males; 61+/-10 years old) with single-vessel disease who were undergoing DCA. In all patients, preprocedural CRP serum levels were measured by an ultrasensitive nephelometric method. The endpoint of the study was defined as the composite incidence of death, myocardial infarction, and recurrence of angina requiring repeat revascularization at 6-month follow-up. RESULTS: CRP serum levels were a significant independent predictor of the composite endpoint at multiple regression analysis [odds ratio=1.69; 95% confidence interval (95% CI)=1.04-2.75; P=.033]. Patients with recurrence of cardiac events had CRP serum levels higher than those of patients not having events on follow-up [3.95 (2.2-5.7) vs. 2 (1.3-3.3); P=.05]. CONCLUSION: In conclusion, our study shows that baseline CRP serum levels predict cardiac events after coronary bare metal stenting despite plaque debulking with directional atherectomy.

Abstract: OBJECTIVE: Cystatin C (Cys-C) is an accurate marker of renal function. Recent studies have shown that serum Cys-C levels predict the risk of cardiovascular events. The causes of this association, however, are largely unknown. METHODS AND RESULTS: Seventy consecutive patients (age 62+/-12, male sex 87%) undergoing coronary angiography because of typical chest pain and found to have coronary artery disease were included in the present study. Patients with abnormal creatinine-derived glomerular filtration rate (<90ml/min/1.73m(2)) were excluded in order to avoid the well-known effect of overt renal insufficiency on coronary atherosclerosis. Coronary angiography was evaluated by two expert angiographers who assessed disease severity and extent according to the Sullivan's score and lesion morphology. In all patients, Cys-C and C-Reactive Protein (CRP) serum levels were measured on admission. Multivariable analysis was performed to assess independent predictors of angiographic measures. Diabetes was the only predictor of disease severity (p=0.005), while male sex (p=0.03), hypercholesterolemia (p=0.04), diabetes (p<0.0001) and Cys-C (p<0.0001) were independent predictors of disease extent. Independent predictors of smooth lesions were diabetes (p<0.001) and Cys-C (p=0.005). No correlation was found between Cys-C and CRP serum levels (p=0.6). CONCLUSION: Cys-C is associated with coronary atherosclerosis extent and a smooth lesion morphology. The long-term prognostic role of Cys-C might be accounted for by a greater atherosclerotic burden, a necessary substrate for plaque destabilization.

Abstract: OBJECTIVE: The role of oxidised low-density lipoprotein (ox-LDL) in plaque destabilisation is controversial; therefore we aimed at comparing plaque and plasma ox-LDL content in stable and unstable ischaemic syndromes. We also assessed the correlation between plaque or plasma ox-LDL and angiographic complex stenosis morphology. METHODS: Ten consecutive patients with chronic stable angina (SA) and 10 consecutive patients with unstable angina (UA) were studied. Plaque sections obtained by directional coronary atherectomy were immunostained with the monoclonal antibody mAb-4E6, which recognises several oxidation epitopes on LDL (mAb-4E6 ox-LDL), and with the monoclonal antibody mAb-1H11 (mAb-1H11 ox-LDL), which recognises malondialdehyde-modified LDL. An mAb-4E6-based competition ELISA was used for quantification of ox-LDL in plasma. C-reactive protein serum levels were measured by a high-sensitivity nephelometric assay. An angiographic analysis was performed to assess severity and extent of coronary atherosclerotic disease and stenosis morphology. RESULTS: Percent plaque area occupied by mAb-4E6 ox-LDL or mAb-1H11 ox-LDL was similar in patients with SA or UA (22.4 +/- 13.1 vs. 21.1 +/- 19.7%, P = 0.8 and 19.3 +/- 10.4 vs. 16.8 +/- 16.9%, P = 0.6, respectively), whereas ox-LDL plasma levels were significantly higher in patients with UA than in patients with SA (2.4 +/- 1.1 vs. 0.9 +/- 0.6 mg/dl; P = 0.03). Furthermore, a significant correlation was found between plasma levels of ox-LDL and the number of angiographically complex lesions (P = 0.03) or C-reactive protein serum levels (P = 0.04). CONCLUSIONS: Neither plaque mAb-4E6 ox-LDL nor plaque mAb-1H11 ox-LDL seem to be a major trigger of coronary plaque instability. However, circulating ox-LDL might be involved in plaque vulnerability and coronary artery disease activity.

Abstract: Intracoronary injection of bone marrow stem cells seems to improve left ventricular (LV) function after acute myocardial infarction (AMI). Granulocyte colony-stimulating factor (G-CSF) could improve myocardial function and perfusion noninvasively through mobilization of stem cells into peripheral blood, although previous clinical trials have produced controversial results. Forty-one patients with large anterior wall AMI at high risk of unfavorable remodeling were randomized 1:2 to G-CSF (10 microg/kg/day for 5 days) or to conventional therapy. All patients underwent successful primary or rescue percutaneous coronary intervention. LV function was assessed by echocardiography before G-CSF administration, > or =5 days after AMI, and at follow-up. Only patients with a LV ejection fraction <50% at baseline were enrolled in the study. After a median follow-up of 5 months (range 4 to 6) patients treated with G-CSF exhibited improvement in LV ejection fraction, from 40 +/- 6% to 45 +/- 6% (p = 0.068) in the absence of LV dilation (LV end-diastolic volume from 147 +/- 33 to 144 +/- 46 ml at follow-up, p = 0.77). In contrast, patients treated conventionally exhibited significant LV dilation (LV end-diastolic volume from 141 +/- 35 to 168 +/- 41 ml, p = 0.002) in the absence of change in LV ejection fraction (from 38 +/- 6% to 38 +/- 8%, p = 0.95). However, when comparing patients treated with G-CSF with controls, variations in these parameters were significantly different at 2-way analysis of variance (p = 0.04 for LV end-diastolic volume, p = 0.02 for LV ejection fraction). In conclusion, G-CSF prevents unfavorable LV remodeling and improves LV function in patients with large anterior wall AMI and decreased LV ejection fraction after successful percutaneous coronary intervention.

Abstract: BACKGROUND AND OBJECTIVE: Cerebral microembolism detected by transcranial Doppler (TCD) occurs systematically during cardiac catheterization, but its clinical relevance, remains unknown. Studies suggest that asymptomatic embolic cerebral infarction detectable by diffusion-weighted (DW) MRI might exist after percutaneous cardiac interventions with a frequency as high as 15 to 22% of cases. We have set up, for the first time, a prospective multicenter trial to assess the rate of silent cerebral infarction after cardiac catheterization and to compare the impact of the arterial access site, comparing radial and femoral access, on this phenomenon. STUDY DESIGN: This prospective study will be performed in patients with severe aortic valve stenosis. To assess the occurrence of cerebral infarction, all patients will undergo cerebral DW-MRI and neurological assessment within 24 hours before, and 48 hours after cardiac catheterization and retrograde catheterization of the aortic valve. Randomization for the access site will be performed before coronary angiography. A subgroup will be monitored by transcranial power M-mode Doppler during cardiac catheterization to observe cerebral blood flow and track emboli. Neuropsychological tests will also be recorded in a subgroup of patients before and after the interventional procedures to assess the impact of silent brain injury on potential cognitive decline. The primary end-point of the study is a direct comparison of ischemic cerebral lesions as detected by serial cerebral DW-MRI between patients explored by radial access and patients explored by femoral access. Secondary end-points include comparison of neuropsychological test performance and number of microembolism signals observed in the two groups. IMPLICATIONS: Using serial DW-MRI, silent cerebral infarction rate will be defined and the potential influence of vascular access site will be evaluated. Silent cerebral infarction might be a major concern during cardiac catheterization and its potential relationship to cognitive decline needs to be assessed. STUDY REGISTRATION: The SCIPION study is registered through National Institutes of Health-sponsored clinical trials registry and has been assigned the Identifier: NCT 00329979.

Abstract: OBJECTIVES: To describe a novel modification of the T-stenting technique and to report the bench test as well as the first clinical results obtained. BACKGROUND: The best technique to treat bifurcated coronary lesions has not been defined. METHODS: This novel modification of the T-stenting technique is based, after stenting of the main vessel (MV) and kissing balloon, on the intentional minimal protrusion of the side-branch (SB) stent within the MV. Final kissing balloon is performed using the balloon kept uninflated into the MV before SB stenting. The technique was tested in vitro and applied in two independent series of patients undergoing elective drug-eluting stent implantation on one bifurcated lesion. Bifurcated lesions were classified according to the Medina classification. Patients' outcome up to 9 month was prospectively assessed. RESULTS: The bench test showed perfect coverage of the bifurcation with minimal stent's struts overlap at the proximal part of SB ostium and a small, single layer stent struts, neo-carina not affecting the MV patency. Seventy-three complex patients (67% of Medina 1,1,1 lesions; 44% of unprotected distal left main lesions) were treated with sirolimus-, paclitaxel-, or zotarolimus-eluting stents using the TAP technique. Procedural success was achieved in all cases and the clinical outcome up to 9 month was characterized by a low rate of clinically-driven target vessel revascularization (6.8%). CONCLUSIONS: The TAP-stenting is a modification of the T-stenting technique which allows full coverage of bifurcated lesions and facilitates final kissing balloon. The first clinical experience suggests that this technique may be practical, thus calling for further evaluations of the technique.

Abstract: Angiographic myocardial blush grade (MBG) is a potent predictor of long-term outcome after percutaneous treatment of myocardial infarction, yet little is known regarding the underlying pathophysiologic features. The relation between MBG and cardiovascular magnetic resonance (CMR)-defined amounts of necrosis and microvascular obstruction was examined in 27 patients. Another powerful prognostic indicator, ST-segment resolution>70%, was correlated with other predictors. Increasing MBG was associated (p=0.001) in a linear fashion (p<0.001) with less microvascular obstruction using CMR, whereas the inverse relation with amount of necrosis, although significant (p=0.043), was nonlinear (p=0.36). ST resolution was not correlated with either MBG or CMR parameters. In conclusion, MBG is mainly influenced by microvascular patency and is less dependent on the amount of muscle necrosis, and the common practice of including MBG 2 and 3 into a single "patent microcirculation" category might not be justified. Moreover, the mechanisms of ST resolution should be searched for at the cellular level.

Abstract: OBJECTIVE: To appraise multiple systematic reviews on the same clinical topic, focusing on predictors and correlates of quality of reporting of meta-analysis (QUOROM) scores. DESIGN: Case study. SETTING: Reviews providing at least individual quantitative estimates on role of acetylcysteine in the prevention of contrast associated nephropathy. DATA SOURCES: PubMed, the database of abstracts of reviews of effects, and the Cochrane database of systematic reviews (updated March 2005). MAIN OUTCOME MEASURES: Funding, compliance with the QUOROM checklist, scores on the Oxman and Guyatt quality index, and authors' recommendations. RESULTS: 10 systematic reviews, published August 2003 to March 2005, were included. Nine pooled events despite heterogeneity and five recommended routine use of acetylcysteine, whereas the remaining studies called for further research. Compliance with the 18 items on the QUOROM checklist was relatively high (median 16, range 11 to 17), although shorter manuscripts had significantly lower scores (R = 0.73; P = 0.016). Reviewers who reported previous not for profit funding were more likely to score higher on the Oxman and Guyatt quality index. No association was found between QUOROM and Oxman and Guyatt scores (R = -0.06; P = 0.86), mainly because of greater emphasis of the Oxman and Guyatt scores on the appraisal of bias in selection and validity assessment (inadequate in five reviews). CONCLUSIONS: Multiple systematic reviews on the same clinical topic varied in quality of reporting and recommendations. Longer manuscripts and previous not for profit funding were associated with higher quality.

Abstract:

Abstract: Plaque debulking before stenting is still controversial. We performed a meta-analysis of 12 randomized and non-randomized trials comparing directional coronary atherectomy (DCA) before stenting versus stenting alone. Angiographic end points were acute gain, late loss and angiographic restenosis rate. Clinical end points were early major adverse cardiac events [MACEs: death, Q-wave myocardial infarction (MI), non-Q-wave MI], late MACEs (death, Q-wave MI) and target lesion revascularization (TLR). Data are expressed as odds ratio (OR) with 95% confidence intervals (CI) or weighted mean difference (WMD) with 95% CI, as appropriate. A total of 1216 patients undergoing DCA before stent and 1484 patients undergoing stent alone have been included. DCA before stent was associated to a better acute gain compared to stenting alone (WMD 0.23, [0.18-0.28]; p<0.0001), to a striking reduction of angiographic restenosis rate (OR of 0.67, [0.54-0.84], p=0.0003) and to a significantly lower rate of late TLR (OR 0.73 [0.59-0.91], p=0.006). Late loss did not differ between the two groups (WMD 0.00 [-0.08 and 0.08], p=0.98). We found a higher rate of early MACEs for the combined approach (OR 1.87 [1.16-3.02], p=0.01), with similar prevalence of late MACEs (OR 0.83 [0.65-1.06], p=0.13). In conclusion, this meta-analysis demonstrates that DCA before stenting is superior to stenting alone with regard to acute angiographic results and TLR with a similar prevalence of late MACEs. The higher prevalence of early MACEs with DCA before stenting, however, is disturbing and probably related to distal embolization.

Abstract: BACKGROUND: Distal protection devices are increasingly used to prevent embolization during percutaneous coronary interventions (PCI) in saphenous vein grafts (SVG) and native coronary arteries (NV). During interventions with the Filterwire device we have observed reduced flow that is reversible following removal of the filter (filter no reflow, FNR), which might be erroneously interpreted as true no reflow and might be associated with reduced capture efficiency of the basket. METHODS: We analyzed the incidence of FNR in 58 patients (60 lesions) at high risk of embolization undergoing PCI of either a SVG or a NV using the Filterwire (Boston Scientific, Natick, MA). Qualitative and quantitative angiographic analysis was performed, and the volume of collected debris was estimated using a photographic technique. RESULTS: In our population, about 1/3 of the cases showed FNR, which was associated with angiographically visible filling defects within the basket, indicating macroembolism. However some patients (especially those undergoing vein graft interventions) showed filling defects without FNR, and some others FNR without filling defects. Thus we tried to understand the predictors of FNR: FNR was associated with higher amount of collected debris (36.97 +/- 42.98 mm(3) vs. 11.31 +/- 18.47 mm(3), p = 0.005), was neither prevented by abciximab, nor predicted by high thrombotic burden, increasing stent volume or need for predilatation. When patient with and without angiographically evident macroembolisation were separately analyzed, a linear correlation of FNR with the quantity of debris was only apparent in the macroembolization group. CONCLUSIONS: Interventionalists should be aware of the "Filter No Reflow", a common but reversible angiographic complication when the Filterwire device is used. Reduced flow seen during these procedures should be treated conservatively. Mechanical obstruction of the filter, but also other mechanisms (pharmacologically active debris? platelet aggregates?) play a role in this phenomenon.

Abstract: AIMS: The role of aspirin in patients with coronary artery disease (CAD) is well established, yet patients happen to discontinue aspirin according to physician's advice or unsupervised. We thus undertook a systematic review to appraise the hazards inherent to aspirin withdrawal or non-compliance in subjects at risk for or with CAD. METHODS AND RESULTS: Electronic databases were systematically searched (updated January 2006). Study designs, patient characteristics, and outcomes were abstracted. Pooled estimates for odds ratios (OR) were computed according to random-effect methods. From the 612 screened studies, six were selected (50,279 patients). One study (31,750 patients) focused on adherence to aspirin therapy in the secondary prevention of CAD, two studies (2594) on aspirin discontinuation in acute CAD, two studies (13,706) on adherence to aspirin therapy before or shortly after coronary artery bypass grafting, and another (2229) on aspirin discontinuation among patients undergoing drug-eluting stenting. Overall, aspirin non-adherence/withdrawal was associated with three-fold higher risk of major adverse cardiac events (OR=3.14 [1.75-5.61], P=0.0001). This risk was magnified in patients with intracoronary stents, as discontinuation of antiplatelet treatment was associated with an even higher risk of adverse events (OR=89.78 [29.90-269.60]). CONCLUSION: Non-compliance or withdrawal of aspirin treatment has ominous prognostic implication in subjects with or at moderate-to-high risk for CAD. Aspirin discontinuation in such patients should be advocated only when bleeding risk clearly overwhelms that of atherothrombotic events.

Abstract: BACKGROUND: In patients with acute coronary syndromes (ACS), distal embolization of thrombotic material is more likely to play a key role in the pathogenesis of myocardial no-reflow during percutaneous coronary intervention (PCI). Thus, interventional techniques able to reduce thrombus burden at the culprit vessel might improve final myocardial reperfusion. OBJECTIVE: To evaluate a new rapid-exchange thrombus-aspirating catheter, the Diver C.E., in patients with thrombotic coronary lesions undergoing PCI. METHODS: Fifty patients with acute myocardial infarction (n = 44) or with non-ST-elevation ACS and angiographic evidence of coronary thrombus (n = 6) undergoing urgent PCI were prospectively enrolled. The Diver C.E. was used to aspirate coronary thrombus from the culprit lesion after placement of the guidewire. Adjunctive balloon inflations and stent implantation were used to achieve good angiographic result. Angiographic coronary flow (by means of TIMI score and corrected TIMI frame count, cTFC), thrombus score (TS), and myocardial perfusion (by means of postintervention myocardial blush grade, MBG) were assessed in all patients. RESULTS: The device could be successfully employed in 96% of the cases (48/50) and yielded significant (P < 0.0001) acute reduction in thrombus burden (TS: predevice 3.5 +/- 0.8, postdevice 2.5 +/- 0.9) and improvement in coronary flow (TIMI grade: predevice 1.0 +/- 0.9, postdevice 2.0 +/- 0.9; CTFC predevice 71 +/- 31, postdevice 39 +/- 26). Final TIMI grade 0-1 was observed in one patient only (2%). A significant (P = 0.02) correlation was found between preintervention TS and efficacy of thrombus aspiration. A more pronounced acute reduction of thrombus burden after thrombus aspiration (TS reduction > or = 2) was associated with a better postintervention angiographic myocardial perfusion (MBG 2.3 +/- 0.9 vs 1.7 +/- 0.8; P = 0.05). CONCLUSIONS: This new, easy-to-use, device is able to reduce thrombus burden and to improve coronary flow in patients with thrombus-containing lesions. The improvement in myocardial perfusion associated to greater thrombus removal highlights the importance of thrombus aspiration in the management of thrombus-burdened coronary lesions.

Abstract: OBJECTIVES: The aim of this study was to clarify the role of microembolization in the genesis of microvascular obstruction (MO) after percutaneous coronary intervention (PCI). BACKGROUND: Fifty consecutive patients entered the myocardial contrast echocardiography (MCE) substudy of the REMEDIA (Randomized Evaluation of the Effect of Mechanical Reduction of Distal Embolization by Thrombus Aspiration in Primary and Rescue Angioplasty) trial, which defined the role of a new thrombus-aspirating device in preventing distal microembolization after PCI. METHODS: A total of 25 patients were randomized to be pretreated with thrombus aspiration before PCI of the culprit lesion and 25 received standard PCI. At 24 h, 1 week, and 6 months after PCI, MCE was performed by Sonovue, and real-time imaging was performed by contrast pulse sequencing technology. Regional wall motion score index (WMSI), contrast score index (CSI), endocardial length of wall motion abnormality (WML) and contrast defect (CDL), end-diastolic and end-systolic left ventricular (LV) volumes, and ejection fraction were calculated. RESULTS: At each time point, in patients treated with a thrombus-aspiration filter device, WMSI, CSI, WML, and CDL were significantly lower and ejection fraction higher (p < 0.05 vs. control patients), whereas LV volumes were slightly but not significantly smaller compared with control patients. In the overall study population, the extent of MO significantly correlated with temporal changes in LV volumes. CONCLUSIONS: Thrombus aspiration used at the time of PCI significantly reduces the extent of MO and myocardial dysfunction, although it does not have a significant favorable effect in preventing LV remodeling. Thus, the beneficial effect of thrombus aspiration occurs at the microvascular level, but additional mechanisms may play a role in influencing the final extent of MO, which strictly correlates with post-infarct LV remodeling.

Abstract: BACKGROUND: This study was designed to evaluate if patients in whom in-stent restenosis developed had an higher risk of early venous graft failure compared with normal patients. METHODS: The study cohort comprised 120 patients (60 with previous in-stent restenosis and 60 controls) who received a total of 165 complementary venous grafts on the circumflex or right coronary artery system (84 in the restenosis group and 81 in the control group). All patients were prospectively followed-up and underwent reangiography at 5-years follow-up. RESULTS: In the restenosis group, 28 venous grafts (33.%) were perfectly patent, 10 showed major irregularities, and 46 were occluded. In the control patients, 50 grafts (61.7%) were perfectly patent (p < 0.001 compared with the restenosis series), 12 showed major irregularities (p = .74), and 19 were occluded (p < 0.0001). In contrast, the 5-year outcome of internal thoracic artery grafts was not affected by history of in-stent restenosis. CONCLUSIONS: Patients who developed in-stent restenosis have an higher risk of early venous graft failure compared with the control patients. Arterial grafts should probably be preferred in these patients.

Abstract: AIMS: No-reflow after a primary percutaneous coronary intervention (PCI) is associated with a high incidence of left ventricular (LV) failure and a poor prognosis. Endothelin-1 (ET-1) is a potent endothelium-derived vasoconstrictor peptide and an important modulator of neutrophil function. Elevated systemic ET-1 levels have recently been reported to predict a poor prognosis in patients with acute myocardial infarction (AMI) treated by primary PCI. We aimed to investigate the relationship between systemic ET-1 plasma levels and no-reflow in a group of AMI patients treated by primary PCI. METHODS AND RESULTS: A group of 51 patients (age 59+/-9.9 years, 44 males) with a first AMI, undergoing successful primary or rescue PCI, were included in the study. Angiographic no-reflow was defined as coronary TIMI flow grade < or =2 or TIMI flow 3 with a final myocardial blush grade < or =2. Blood samples were obtained from all patients on admission for ET-1 levels measurement. No reflow was observed in 31 patients (61%). Variables associated with no-reflow at univariate analysis included culprit lesion of the left anterior coronary descending artery (LAD) (67 vs. 29%, P=0.006) and ET-1 plasma levels (3.95+/-0.7 vs. 3.3+/-0.8 pg/mL, P=0.004). At multivariable logistic regression analysis, ET-1 was the only significant predictor of no-reflow (P=0.03) together with LAD as the culprit vessel (P=0.04). CONCLUSION: ET-1 plasma levels predict angiographic no-reflow after successful primary or rescue PCI. These findings suggest that ET-1 antagonists might be beneficial in the management of no-reflow.

Abstract: BACKGROUND: Although recent data support an early invasive management in acute coronary syndromes (ACS), overall evidence appears conflicting. We performed a metaregression to explore the impact of intracoronary stenting and aggressive antiplatelet treatment on the risk/benefit ratio of an early invasive approach. METHODS: We searched several databases up to March 2004 for randomized trials comparing an early invasive versus delayed invasive or conservative management in ACS. Random-effects odds ratios were computed for death and/or myocardial infarction at the longest follow-up. Log (odds ratios) were tested for interaction with stenting and aggressive antiplatelet treatment (ie, glycoprotein IIb/IIIa inhibitors or thienopyridines in addition to aspirin). RESULTS: Ten trials (9990 patients, median follow-up 12 months) were pooled. Overall, an early invasive management was associated with significantly reduced rates of death or myocardial infarction (P = .01). Metaregression analysis showed that the 2 most significant predictors of the benefits of an early invasive strategy in patients with ACS on event-free survival were the use, in subjects managed invasively, of aggressive antiplatelet treatment (P = .005) and stenting (P = .011). Moreover, both stenting and aggressive antiplatelet treatment were significantly associated with reduced mortality (respectively, P = .014 and P = .009) and correlated to each other (r = 0.76, P = .010). CONCLUSIONS: This study shows that the benefits of an early invasive approach in patients with ACS are significantly associated with concomitant aggressive antiplatelet treatment and stenting. These findings thus suggest the overall superiority of an early invasive approach in ACS, as long as state-of-the-art therapies are implemented.

Abstract: The buddy wire technique, i.e. the use of a second 0.014 inch guide wire placed alongside the one employed to advance balloons and stents inside the coronary artery during percutaneous coronary intervention (PCI), may help in a series of procedural challenges during PCI. Indeed, by improving both the stability of the guiding catheter and the support for balloon and stent, a buddy wire use is sometimes the simplest way to accomplish a successful procedure. In this paper, we discuss technical aspects of some specific circumstances frequently encountered during PCI, in which a buddy wire may be helpful. These include: 1) The reduction of balloon slippage during angioplasty for in-stent restenosis; 2) insufficient back-up of the guiding catheter; 3) stenting of lesions located in vessels with proximal tortuosities/angulations; 4) stenting of lesions distally located in the vessel; 5) facilitation in the positioning of distal protection devices; 6) stenting of a lesion distally located from a previously implanted stent or from a coronary segment with both calcification and sharp bend; 7) PCI on coronary arteries with anomalous origin. Because of its simplicity, low cost, and availability, the use of a buddy wire should be considered when dealing with the aforementioned conditions during PCI procedures.

Abstract: Reversible vascular obstructive lesions, i.e. pseudostenoses, may pose significant threats to interventional cardiologists as they can be mistaken for obstructive lesions and prompt inappropriate revascularization procedures. We hereby report for the first time in the literature a case of external iliac artery pseudostenosis due to catheter straightening of significant underlying vessel tortuosities. Despite the initial angiographic image obtained from retrograde catheterization of the right external iliac artery which was strongly suggestive for significant stenosis, a thorough review of clinical history, physical examination and a second-look angiography by means of contralateral catheterization and contrast injection showed the absence of any significant lesion in the tortuous left external iliac artery, thus avoiding an unnecessary and potentially harmful vascular intervention. This clinical vignette emphasizes the importance of a thorough clinical examination and angiographic assessment for the appropriate diagnosis and management of reversible stenoses.

Abstract: We present a case of left main spasm which was associated with spasm of a saphenous vein graft. This case emphasizes the importance of excluding an excessive vasoconstrictory response in patients treated with percutaneous coronary interventions.

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Abstract: AIMS: Drug-eluting stents (DES) have been recently investigated, with favorable data for many devices, but comparative data are lacking. We thus performed an adjusted indirect comparison metaanalysis of DES. METHODS: Randomized trials comparing DES vs. bare-metal stents (BMS) were systematically searched, and random effect odds ratios (OR) were computed for target lesion revascularization (TLR) and binary in-stent restenosis rate (BRR) at 6-12 months. We then generated interaction OR for the comparison of different DES. RESULTS: We pooled data from 17 studies (allocating 3048 patients to BMS and 3392 to nine different DES). Indirect head-to-head comparison of sirolimus-eluting Cypher (N=1007) vs. polymeric paclitaxel-eluting Taxus (N=959) showed nonsignificant differences in TLR [OR=0.8 (0.5-1.4), p=0.45] but significant reductions in BRR favoring Cypher [OR=0.3 (0.1-0.6), p<0.001]. Everolimus-eluting stents appeared noninferior to Cypher or Taxus (p>0.50 for both TLR and BRR). Actinomycin-, mycophenolate-, and apolymeric paclitaxel-eluting stents (PES) all proved significantly worse than Cypher or Taxus for TLR or BRR. CONCLUSION: Notwithstanding its inherent limitations, the present metaanalysis confirms the effectiveness of both Cypher and Taxus, supports the promising role of everolimus-eluting stents, and suggests the significant inferiority of most other devices. These post hoc findings, albeit intriguing, await prospective confirmation.

Abstract: Coronary artery anomalies (CAA) often render technically difficult the completion of coronary angiography and intervention. Their presence in patients undergoing emergency angiography for acute myocardial infarction (AMI) is particularly challenging for interventional cardiologists. In this article, we report, for the first time in the literature, a case of rescue percutaneous coronary intervention for failed thrombolysis in a patient with AMI due to occlusion of a left circumflex coronary artery with anomalous origin from right sinus of Valsalva (in an anomalous left coronary system also including an anomalous origin of the left anterior descending artery from the right sinus). In particular, the present clinical vignette emphasizes the importance of a thorough search for the culprit vessel during cardiac catheterization. Especially in the emergency setting, non-invasive methods of ischemia localization, such as ST-segment elevation at the ECG and wall motion abnormalities at echocardiography, are of pivotal usefulness to guide the interventional cardiologist in identifying and treating the diseased coronary vessel in a timely and effective fashion.

Abstract: BACKGROUND: Recent data suggest that the intracoronary (i.c.) administration of a systemic bolus dose of abciximab during PCI may increase the efficacy of this antiplatelet drug. However, the effect of i.c. abciximab on coronary angiographic flow has been not clarified. METHODS: We studied 37 consecutive patients with acute coronary syndromes (ACS) who underwent successful urgent PCI on the target vessel and were treated by an i.c. abciximab bolus (0.25 mg/kg) prior to the first balloon inflation (Group IC), and 37 matched controls who were treated by intravenous (i.v.) abciximab bolus at the same dose (Group IV). Corrected TIMI frame count (CTFC) in the culprit and in a non-culprit coronary artery branch was assessed before treatment, immediately after intracoronary administration of abciximab bolus and at the end of the procedure. RESULTS: After administration of abciximab, CTFC significantly decreased from 48+37 to 33+30 (P=0.001) in the culprit vessel while in the non-culprit vessel it remained unchanged (16+7 pre-treatment and 16+7 post-treatment, P=0.68). Final CTFC was 12+4 in Group IC and 14+5 in Group IV (P=0.069). Post-treatment mean peak of the cardiac enzymes showed a trend toward reduction in Group IC compared with Group IV. CONCLUSIONS: The i.c. administration of abciximab bolus acutely decreases CTFC through culprit vessels of patients with ACS undergoing urgent PCI. Further studies evaluating the potential clinical benefits associated with i.c. abciximab administration are warranted.

Abstract: Gadolinium chelates have been recently proposed and preliminarily tested as contrast agents for diagnostic and interventional angiography in alternative to iodinated media. However, in most studies low-osmolarity agents were employed and digital subtraction was required for satisfactory images. In this article, we report for the first time in the literature two cases of successful percutaneous renal artery stenting in which gadobutrol, a high-osmolar (1 mmol/ml) gadolinium chelate, was employed as contrast agent because of chronic renal failure and substantial risk for iodinated contrast-associated nephrotoxicity. In both patients gadobutrol yielded high-quality images without digital subtraction and was well tolerated with no ensuing renal dysfunction.

Abstract: BACKGROUND: In patients who develop in-stent restenosis, successful revascularization can be difficult to achieve using percutaneous methods. This study was designed to verify the surgical results in this setting and to evaluate the potential beneficial role of arterial bypass conduits. METHODS AND RESULTS: Sixty consecutive coronary artery bypass patients with previous in-stent restenosis and 60 control cases were randomly assigned to receive an arterial conduit (either right internal thoracic or radial artery; study group) or a great saphenous vein graft (control group) on the first obtuse marginal artery to complete the surgical revascularization procedure. At a mean follow-up of 52+/-11 months, patients were reassessed clinically and by angiography. Freedom from clinical and instrumental evidence of ischemia recurrence was found in 19 of 60 subjects in the study group versus 45 of 60 in the control series (P=0.01). The results of the arterial grafts were excellent in both the study and control groups (right internal thoracic artery patency rate, 19 of 20 for both, and radial artery patency rate, 20 of 20 versus 19 of 20; P=0.99). Saphenous vein grafts showed lower patency rate than arterial grafts in both series and had extremely high failure rate in the study group (patency rate, 10 of 20 in the study group versus 18 of 20 in the control group; P=0.001). Use of venous graft was an independent predictor of failure in the study group, whereas hypercholesterolemia was associated with graft failure in both series. CONCLUSIONS: Venous grafts have an high incidence of failure among cases who previously developed in-stent restenosis, whereas the use of arterial conduits can improve the angiographic and clinical results. Arterial grafts should probably be the first surgical choice in this patient population.

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Abstract: BACKGROUND: The purpose of this research was to investigate the in vivo morphofunctional changes induced in the radial artery (RA) by its use as coronary artery bypass conduit by comparing the morphological features and vasoreactivity of the native RA versus the coronary RA graft in the same patient. METHODS AND RESULTS: Ten years after surgery, 10 patients were submitted to intravascular ultrasound examination of the RA graft of the controlateral (in situ) RA and of the internal thoracic artery (ITA) graft and to vasoactive challenges with acetylcholine and serotonin. Quantitative angiographic assessment showed that the mean diameter of the RA coronary grafts was significantly larger than that of the in situ RA and of the ITA (2.89+/-0.40 mm RA grafts, 2.14+/-0.52 mm in situ RA, 2.25+/-0.53 mm ITA grafts; P<0.001). The in situ RA demonstrated a typical muscular architecture, whereas RA coronary grafts showed a clear reduction of the thickness of the medial layer and had a less well-defined muscular component of the media with interposition of elastic tissue. Serotonin endovascular infusion elicited a strong spastic reaction in in situ RAs; the same challenge induced only moderate constriction in RA and ITA coronary grafts. CONCLUSIONS: Implantation in the coronary circulation leads to major anatomic and vasoreactive modifications of the RAs that tend to lose the morphofunctional features of a muscular conduit and assume those of an elastomuscular artery, such as the ITA.

Abstract: OBJECTIVES: The aim of this study was to evaluate the use of a new manual thrombus-aspirating device in unselected patients with ST-segment elevation acute myocardial infarction (STEMI) undergoing urgent percutaneous coronary intervention (PCI). BACKGROUND: Failure to achieve myocardial reperfusion often occurs during PCI in patients with STEMI. The use of thrombus-aspirating devices might improve myocardial reperfusion by reducing distal embolization. METHODS: We prospectively randomized before coronary angiography 100 consecutive patients with STEMI to either standard PCI or PCI with manual thrombus-aspiration. Primary end points of the study were post-procedural rates of myocardial blush grade (MBG) > or =2 and ST-segment resolution (STR) > or =70%. Analyses were planned by intention to treat. RESULTS: Ninety-nine patients entered the analyses. The rates of post-procedural MBG > or =2 and STR > or =70% were, respectively, 68.0% and 44.9% in the thrombus-aspiration group compared with 58.0% and 36.7% in the standard PCI group: odds ratio (OR) 2.6 (95% confidence interval [CI] 1.2 to 5.9), p = 0.020, and 2.4 (95% CI 1.1 to 5.3), p = 0.034, respectively. Moreover, the rate of patients achieving both the angiographic and electrocardiographic (ECG) criteria of optimal reperfusion was significantly higher in the thrombus-aspiration group compared with standard PCI: 46.0% versus 24.5%, OR 2.6 (95% CI 1.1 to 6.2), p = 0.025. In multivariate analysis, randomization to thrombus-aspiration was a significant independent predictor of achievement of MBG > or =2 and STR > or =70% (p = 0.013). CONCLUSIONS: This prospective randomized study shows that manual thrombus-aspiration in unselected patients with STEMI undergoing primary or rescue PCI is clinically feasible and results in better angiographic and ECG myocardial reperfusion rates compared with those achieved by standard PCI.

Abstract: BACKGROUND: The angiographic patency of composite Y internal thoracic artery-saphenous vein grafts has not been investigated in detail. METHODS: Twenty-five patients who received composite Y internal thoracic artery-saphenous vein grafts had control angiography and vasoactive challenges with serotonin, acetylcholine, and isosorbide dinitrate at a mean of 2.5 +/- 1.2 years after surgery. RESULTS: The perfect patency rate of composite Y internal thoracic artery-saphenous vein grafts was 72% (18/25). The distal portion of the internal thoracic artery was stringed in 4 patients and occluded in 2. The saphenous branch of the composite Y internal thoracic artery-saphenous vein grafts was found patent in all patients except 1. No failures were reported in the proximal tract of the internal thoracic artery. The distal tract of the internal thoracic artery showed reduced capacity of endothelium-mediated relaxation. CONCLUSION: The short-term patency of composite Y internal thoracic artery-saphenous vein grafts is suboptimal and markedly influenced by distal runoff and native flow competition.

Abstract: Coronary artery aneurysms are rare findings usually diagnosed incidentally at necropsy or at angiography in patients with symptoms of myocardial ischaemia. Even if atherosclerosis is a common cause of coronary aneurysms in the adult, other acquired diseases with inflammatory pathogenesis are associated with coronary artery aneurysms. We present three cases of patients with low probability of coronary artery atherosclerotic disease, due to their age, risk factors profile and history, complaining of chest pain suggestive of myocardial ischaemia and angiographic documentation of one or more coronary aneurysms. In all cases, although no patient had had a previous diagnosis of Kawasaki disease (KD), an unexplained febrile syndrome had occurred in childhood, which is compatible with misdiagnosed episode of KD causing the aneurysmatic lesions. The present reports highlight the potential clinical relevance of previously misdiagnosed KD in patients with ischaemic chest pain, low probability of atherosclerosis and coronary aneurysms.

Abstract: OBJECTIVE: To investigate the possible link between the G20210A prothrombin gene variant and different forms of ischaemic heart disease. DESIGN: Phenotype-specific meta-analysis of 19 studies published within March 2002, globally including 4944 patients and 7090 controls. Sample size, inclusion criteria, geographical location, clinical presentation, age, cardiovascular risk factors, and angiographic extent of disease were extracted from each study. Analyses were done according to Mantel-Haenszel. RESULTS: Overall, the odds ratio (OR) for unspecified ischaemic heart disease associated with the 20210A allele was 1.21 (95% confidence interval (CI) 0.99 to 1.59, n = 12 034). Similar findings were seen for acute coronary syndromes (unstable angina and myocardial infarction) and for myocardial infarction without age limits (OR 1.24, 95% CI 0.98 to 1.63, n = 10 240; and OR 1.19, 95% CI 0.93 to 1.58, n = 9765). The effects were similar in male and female subjects. In the 1931 subjects < 55 years of age, the OR for myocardial infarction increased to 1.77 (95% CI 1.16 to 3.42) and in the 1359 subjects < 45 years to 2.30 (95% CI 1.27 to 4.59). No significant association was found between the 20210A allele and the presence of angiographically documented coronary disease (OR 1.08, 95% CI 0.70 to 1.64, n = 3444). However, patients with 0/1 vessel disease at angiography showed a greater prevalence of the A allele than those with multivessel disease (relative risk 2.0, 95% CI 1.2 to 3.1, n = 2376). CONCLUSIONS: G20210A prothrombin gene polymorphism may represent a modest but significant risk factor for myocardial infarction at young ages and favour the expression of ischaemic heart disease among individuals who have a limited extent of coronary atherosclerosis at angiography.

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Abstract: We report a complex case of percutaneous intervention on a right coronary artery with calcific stenoses and a large coronary aneurysm with long longitudinal diameter, which was successfully performed using a polytetrafluoroethylene-covered self-expandable stent (Symbiot; Boston Scientific; Natick, MA). The use of this new device may enhance the anatomic indications for percutaneous interventions on coronary aneurysms.

Abstract: BACKGROUND AND OBJECTIVES: The prognostic value of the G20210A prothrombin gene polymorphism in patients with a first acute coronary syndrome has not been previously assessed. We conducted a prospective study to investigate this issue. DESIGN AND METHODS: Genotyping at the 20210 prothrombin gene locus was performed in 162 patients with a first episode of myocardial infarction (MI) or unstable angina (UA) occurring before 65 years of age. Patients were stratified according to cardiovascular risk factors and to treatment strategy. The subsequent two-year relative risk (RR) of adverse events (death, MI and UA) was adjusted for possible confounders and analyzed according to genotype, risk factor category, and treatment allocation. RESULTS: In the entire study population, the prothrombin variant did not significantly increase the two-year risk of events: the adjusted RR for GA vs GG carriers was 1.82 (95% CI 0.68-4.89). However, in the absence of traditional cardiovascular risk factors the risk of events was consistently higher: among the 46 patients without hypertension, diabetes and hypercholesterolemia, GA vs GG carriership was associated with an adjusted RR at two years of 5.64 (95% CI 1.07-29.84). The gene variant also enhanced the risk of events among the 98 patients who did not undergo myocardial revascularization procedures (RR for GA vs GG: 2.89, 95% CI 1.04-8.00), but not among those who did. INTERPRETATION AND CONCLUSIONS: The present prospective study suggests that heterozygosity for the G20210A prothrombin polymorphism adversely affects prognosis after a first acute coronary syndrome in the subgroup of patients without metabolic risk factors and in those not treated by revascularization procedures.

Abstract: Direct stent implantation using radial approach represents to date the less invasive, less traumatic strategy to perform a percutaneous coronary intervention, rendering its adoption an attraction for many interventional cardiologists. A growing series of reports suggests the feasibility of transradial direct stenting in a variety of clinical situations. Here we discuss the main advantages of the adoption of this technique. Moreover, a detailed analysis of the technical issues specifically related with each phase of transradial direct stenting procedures is reported.

Abstract: AIM: Clopidogrel is an established alternative to ticlopidine in addition to aspirin after coronary stenting because of its hematologic safety, but its efficacy in comparison to ticlopidine is debated. We thus systematically reviewed randomized trials comparing clopidogrel vs ticlopidine after coronary stenting. METHODS: Medline (1/1986-10/2003), BioMed Central, Central, Current Contents, LILACS and mRCT were searched. Fixed-effect relative risks (RR [95% CI]) were computed, and the primary end-point was death. Heterogeneity tests and subgroup analyses were performed according to loading vs non-loading clopidogrel scheme. RESULTS: Five trials were retrieved (2 962 patients, average follow-up 7.4 months). In 3 studies both clopidogrel and ticlopidine were started with a loading dose, in 1 trial clopidogrel was administered without loading, and in 1 trial clopidogrel could be administered with or without loading. Overall analysis (p for heterogeneity=0.12) showed a non-significant trend toward increased mortality in patients treated with clopidogrel (38/1 649 [2.3%]) vs ticlopidine (22/1 313 [1.7%], RR=1.64 [0.94-2.86], p=0.080). After stratification, clopidogrel with loading was associated with non-significantly lower mortality rates than ticlopidine (9/959 [0.9%] vs 13/798 [1.6%], RR=0.68 [0.29-1.63], p=0.39). Instead, clopidogrel without any loading yielded a highly significantly 3-fold increased risk of death than ticlopidine (29/690 [4.2%] vs 9/515 [1.7%], RR=2.9 [1.45-6.1], p=0.0029). Similar results were obtained for the rate of death or non-fatal myocardial infarction. CONCLUSION: This meta-analysis suggests that clopidogrel treatment including a loading regimen is equivalent or may even be superior to ticlopidine after coronary stenting. However, current evidence shows conversely that clopidogrel therapy in the absence of a loading dose is associated with a significantly higher risk of death or myocardial infarction.

Abstract: BACKGROUND: Multiple complex stenoses, plaque fissures, and widespread coronary inflammation are common in acute coronary syndromes. A systemic cause of atherosclerotic plaque instability is also suggested by studies of ischemic cerebrovascular disease. We investigated the association between coronary and carotid plaque instability and the potential common causal role of inflammation. METHODS AND RESULTS: The ultrasound characteristics of carotid plaques were evaluated retrospectively in patients scheduled for coronary bypass surgery, 181 with unstable and 92 with stable angina, and prospectively in a similar group of patients, 67 with unstable and 25 with stable angina, in whom serum C-reactive protein levels were also measured. The prevalence of carotid plaques was similar in the retrospective and prospective studies and >64% in both unstable and stable coronary patients. The prevalence of complex, presumably unstable carotid plaques was 23.2% in unstable versus 3.2% in stable patients (P<0.001) in the retrospective study and 41.8% versus 8.0% (P=0.002) in the prospective study. C-reactive protein levels were higher in patients with complex (7.55 mg/L) than in those with simple (3.94 mg/L; P<0.05) plaques or without plaques (2.45 mg/L; P<0.05). On multivariate analysis, unstable angina and C-reactive protein levels >3 mg/L were independently associated with complex carotid plaques (OR, 6.09; 95% CI, 1.01 to 33.72; P=0.039, and OR, 5.80; 95% CI, 1.55 to 21.69; P=0.009, respectively). CONCLUSIONS: In unstable angina, plaque instability may not be confined to coronary arteries, and inflammation may be the common link with carotid plaque instability. These observations may have relevant implications for understanding the mechanisms of acute widespread atherothrombotic plaque inflammation.

Abstract: BACKGROUND: It has been suggested that inflammation can have a role in the development of atrial arrhythmias after cardiac surgery and that a genetic predisposition to develop postoperative complications exists. This study was conceived to verify if a potential genetic modulator of the systemic inflammatory reaction to cardiopulmonary bypass (the -174 G/C polymorphism of the promoter of the Interleukin-6 gene) has a role in the pathogenesis of postoperative atrial fibrillation (AF).Patients and Results- In 110 primary isolated coronary artery bypass patients the -174G/C Interleukin-6 promoter gene variant was determined. Interleukin-6, fibrinogen and C-reactive protein plasma levels were determined preoperatively, 24, 48, and 72 hours after surgery and at discharge. Heart rate and rhythm were continuously monitored for the first 36 to 48 hours; daily 12-lead electrocardiograms were performed thereafter until discharge. GG, CT, and CC genotypes were found in 62, 38, and 10 patients, respectively. Multivariate analysis (which included genotype, age, sex, and classical risk factors for AF) identified the GG genotype as the only independent predictor of postoperative AF. The latter occurred in 33.9% of GG versus 10.4% of non-GG patients (hazard ratio 3.25, 95%CI 1.23 to 8.62). AF patients had higher blood levels of Interleukin-6 and fibrinogen after surgery (P<0.001 for difference between the area under the curve). CONCLUSIONS: The -174G/C Interleukin-6 promoter gene variant appears to modulate the inflammatory response to surgery and to influence the development of postoperative AF. These data suggest an inflammatory component of postoperative atrial arrhythmias and a genetic predisposition to this complication.

Abstract: BACKGROUND: Although some data suggest that the individual genetic predisposition for developing major or minor degrees of postoperative systemic inflammatory reaction may influence postoperative morbidity, this hypothesis has not been clinically tested to date.Methods and results The -174 G/C polymorphism of the promoter of the interleukin 6 gene was determined preoperatively in 111 consecutive patients submitted to primary isolated coronary artery bypass. The results of the genetic analysis were then correlated with the postoperative interleukin 6 levels and the development of postoperative renal and pulmonary complications. G homozygotes had significantly higher interleukin 6 levels postoperatively (P <.0001 for the difference between areas under the curve). These patients also had worse postoperative pulmonary and renal function. The mean perioperative difference in serum creatinine, potassium, and nitrogen was 0.82 +/- 0.34, 0.99 +/- 0.44, and 10.1 +/- 7.8 mg/dL versus 0.18 +/- 0.14, 0.15 +/- 0.48, and 2.6 +/- 4.1 mg/dL for GG versus non-GG carriers (P <.0001), respectively. The mean respiratory index at 6 and 12 hours was 2.9 +/- 0.8 and 2.8 +/- 0.3 versus 2.1 +/- 0.5 and 1.3 +/- 0.1, respectively (P <.0001). The mean duration of mechanical ventilation was 22.5 +/- 2.1 versus 12.7 +/- 6.7 hours (P <.01). A correlation was found between postoperative interleukin 6 levels and renal and pulmonary complications. CONCLUSION: The interleukin 6 -174 G/C polymorphism modulates postoperative interleukin 6 levels and is associated with the degree of postoperative renal and pulmonary dysfunction and in-hospital stay after coronary surgery.

Abstract: Although direct stenting (DS) is increasingly used in clinical practice instead of stent implantation after predilatation (conventional stenting [CS]), its impact has not been scientifically proved. We therefore performed, using Mantel-Haenszel analysis, a meta-analysis of the published randomized studies comparing DS with CS. Furthermore, all the key procedural data were systematically sought out and pooled. Ten trials (2,650 coronary lesions, 2,576 patients) were identified and entered into the analysis. Adopted angiographic exclusion criteria were homogeneous. DS, compared with CS, was found to have a similar success rate (98.7% vs 98.9%) and no specific complications. Across the studies, the mean rate of crossover to predilatation in the DS arm was 5.9%. Overall, DS was associated with a 17% procedural time (95% confidence interval [CI] 14% to 20%), a 18% fluoroscopic time (95% CI 15% to 21%), a 11% contrast volume (95% CI 9% to 14%), and a 22% cost reduction (95% CI 16% to 28%). In the early postintervention period, DS was associated with a trend toward reduction of each of the major adverse events (MACEs) and with a significant reduction of myocardial infarction (MI) + death (odds ratio [OR] 0.57, 95% CI 0.35 to 0.95). However, at 6 months, the OR (95% CI) for death, MI, target lesion revascularization, and MACEs were 0.47 (0.19 to 1.27), 0.72 (0.45 to 1.25), 1.07 (0.77 to 1.46), and 0.82 (0.63 to 1.08), respectively. In the subgroup of studies providing quantitative angiographic data, all the parameters were found to be similar between the CS and DS groups. In conclusion, the present meta-analysis shows that DS compared with CS, in selected coronary lesions, is safe, optimizes equipment use, and may enhance the early results of coronary interventions while warranting similar late clinical outcomes.

Abstract: BACKGROUND: Intravascular ultrasound (IVUS) studies have shown that a mechanism of plaque compression/embolization contributes toward the poststenting increase in lumen area. The aim of this IVUS study was to compare the mechanisms of lumen enlargement after coronary stenting in 54 consecutive patients with unstable angina (UA) (group 1) and 56 with stable angina (group 2) to verify whether plaque embolization plays a major role in the former. METHODS AND RESULTS: Both groups underwent the IVUS assessment (speed, 0.5 mm/sec) before the intervention and after stent implantation. The lumen area, the external elastic membrane area, and the plaque+media area (PA) were measured at 0.5-mm intervals. PA reduction in the lesion site was significantly greater in group 1 (-2.50+/-1.97 versus -0.53+/-1.43 mm2, P<0.001). After stenting, 47% of the lumen area increase in group 1 was obtained by means of PA reduction, and 53% was attributable to external elastic membrane area increase; the corresponding figures in group 2 were 13% and 87% (P<0.05). Decrease in PA after stenting was the only significant predictor of the MB fraction of creatinine kinase (CK-MB) release in a multiple regression model (P=0.047). CONCLUSIONS: Serial volumetric IVUS assessment revealed in UA lesions a marked poststenting reduction in plaque volume, which is significantly greater than in stable angina and is associated with postprocedural CK-MB release. The decrease in PA during the procedure predicts CK-MB release in a multiple regression model. These findings suggest that stent deployment is often associated with plaque embolization in patients with UA.

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Abstract: BACKGROUND AND OBJECTIVE: The 4G/5G plasminogen activator inhibitor-1 (PAI-1) promoter polymorphism has been associated with basal PAI-1 levels, with ischemic heart disease, and with adverse prognosis in critically ill patients. We hypothesized it might also influence the acute-phase levels of PAI-1 following coronary bypass surgery. METHODS: In 111 consecutive patients undergoing elective coronary bypass surgery, 4G/5G genotyping and serial plasma PAI-1 activity and antigen levels were prospectively measured before surgery, daily up to 72 h, and at discharge. The inflammatory reaction was additionally assessed by white cell count, fibrinogen, interleukin-6, and C-reactive protein levels. RESULTS: PAI-1 activity and antigen concentrations increased approximately two-fold after surgery, peaking at 48 hours. Carriers of the 4G-allele, compared with 5G/5G homozygotes, showed approximately 20% higher PAI-1 activity and antigen both preoperatively ( P = 0.007 and P = 0.035) and after surgery. White cell count, fibrinogen, interleukin-6, and C-reactive protein values did not differ significantly according to genotypic groups. In multivariate analysis, the 4G/5G genotype was the only significant modulator of postoperative PAI-1 activity (P = 0.003) and the main significant modulator of postoperative PAI-1 antigen (P = 0.013). No significant interaction was found between the effects of time and genotype on postoperative PAI-1. This indicates that the association between 4G/5G and acute-phase PAI-1 levels is secondary to the genotype-related difference of baseline PAI-1. CONCLUSIONS: Postoperative PAI-1 concentrations of patients undergoing elective coronary bypass surgery are higher in carriers of the 4G-allele than in 5G/5G homozygotes as a result of higher baseline values. Knowledge of 4G/5G status may be useful to predict acute-phase PAI-1 concentrations.

Abstract: Vasopressin is currently recommended in the management of patients with cardiac arrest, but its efficacy is still incompletely established. We systematically reviewed randomized trials comparing vasopressin to control treatment in the management of cardiac arrest in humans and animals. Two human and 33 animal studies were retrieved. At pooled analysis vasopressin appeared equivalent to adrenaline (epinephrine) in the management of human cardiac arrest (N=240), with, respectively 63 (78/124) vs 59% (68/116) ROSC (P=0.43), and 16 (20/124) vs 14% (16/116) survival to hospital discharge (P=0.52). In animal trials (N=669) vasopressin appeared instead significantly superior to both placebo (ROSC, respectively 93 [98/105] vs 19% [14/72], P<0.001) or adrenaline (ROSC, respectively 84 [225/268] vs 52% [117/224], P<0.001). In conclusion, vasopressin is superior to both placebo or adrenaline in animal models of cardiopulmonary resuscitation. Evidence in humans is still limited and confidence intervals estimates too wide to reliably confirm or disprove results obtained in experimental animal settings.

Abstract: AIMS: To investigate the prevalence of the G20210A prothrombin and G1691A factor V gene variants in patients with acute coronary syndrome stratified according to risk factor profile and to extent of coronary disease, in comparison with matched healthy controls. METHODS AND RESULTS: The 20210 prothrombin and the 1691 factor V loci were genotyped in 247 patients < or =65 years of age (190 myocardial infarction and 57 unstable angina as first presentation of disease) and in 247 healthy age- and sex-matched controls. The prevalence of the 1691A factor V allele was similar in cases and controls. The frequency of heterozygotes for the 20210A prothrombin allele was 6.5% among patients and 2.8% among controls (OR 2.4, 95% CI 1.0-5.9), increasing to 8.7% in patients with a family history of myocardial infarction (OR 3.3, 95% CI 1.2-9.1), to 9.9% in patients (n=81) with < or =1 vessel disease (OR 3.8, 95% CI 1.3-10.8), and to 13.0% in patients who were normocholesterolaemic, non-diabetic, normotensive and non-smokers (OR 5.1, 95% CI 1.2-21.4). CONCLUSIONS: These findings suggest that the 20210A prothrombin allele represents an inherited risk factor for acute coronary syndrome among patients who have limited extent of coronary disease at angiography or who lack major metabolic and acquired risk factors.

Abstract: BACKGROUND: Despite its common acceptance in clinical practice, the effective benefits of normothermic systemic perfusion during coronary artery bypass operations are far from established. METHODS: A total of 113 patients undergoing primary isolated coronary artery bypass were randomly assigned to normothermic (37 degrees C) or hypothermic (26 degrees C) systemic perfusion. The clinical course of the patients was prospectively recorded, and several inflammatory and fibrinolytic markers (C-reactive protein, fibrinogen, interleukin 6, plasminogen activator inhibitor 1, prothrombin time, activated partial thromboplastin time, platelets, and white blood cell counts) were determined before surgical intervention; 24, 48, and 72 hours thereafter; and at hospital discharge. RESULTS: Postoperatively, 2 in-hospital deaths occurred in the normothermic series and none in the hypothermic series. Four patients had a myocardial infarction, 1 had respiratory insufficiency, 1 had to be reoperated on for graft malfunction, and none had renal insufficiency in the hypothermic group versus 1 patient with each of these complications in the normothermic series. Mean blood loss in the first 24 hours was 766 +/- 223 mL in the normothermic group and 740 +/- 220 mL in the hypothermic group. None of these differences was statistically significant. Similarly, no significant difference in the postoperative level of any of the measured variables at any time point was evident between the patients in the normothermic and hypothermic groups. CONCLUSION: Normothermic systemic perfusion does not influence the clinical course or the extent of inflammatory and hemostatic activation in patients undergoing primary isolated coronary artery bypass.

Abstract: BACKGROUND: The aim of this study was to determine the course of the main inflammatory and fibrinolytic markers in patients undergoing primary elective coronary artery bypass graft with extracorporeal circulation. METHODS: One hundred and thirteen patients (105 males, 8 females) undergoing primary isolated coronary artery bypass with normo- (37 degrees C) or hypothermic (26 degrees C) systemic perfusion were prospectively studied. The clinical course of the patients was recorded and inflammatory and fibrinolytic markers (C-reactive protein, fibrinogen, interleukin-6, plasminogen activator inhibitor-1, prothrombin time, activated partial thromboplastin time, platelets and white blood cell counts) were determined before surgery, 24, 48 and 72 hours thereafter, and at hospital discharge. RESULTS: Two patients died (mortality 1.7%) and 6 had a major complication (event free survival > 94%). Interleukin-6, lymphocyte, neutrophil and monocyte levels increased after surgery but returned to normal at hospital discharge. C-reactive protein levels increased after 24 hours and remained high at hospital discharge. Plasminogen activator inhibitor-1, prothrombin time, and activated partial thromboplastin time increased from few hours postoperatively and returned to normal before discharge. Platelets decreased immediately after surgery and normalized only at hospital discharge. Fibrinogen decreased in the first 24 postoperative hours, raised later and remained elevated at hospital discharge. CONCLUSIONS: Cardiopulmonary bypass activates inflammatory response and hemostatic/fibrinolytic balance in patients undergoing primary isolated coronary artery bypass.

Abstract: OBJECTIVES: Recently, direct stenting has been shown in retrospective and randomized studies to be feasible and safe in highly selected patients, with a potential interest to reduce the cost of the procedure and the rate of no-reflow. This randomized pilot study was designed to compare the incidence of no-reflow after direct stenting or conventional stenting after balloon predilation in acute coronary syndrome-related lesions. METHODS AND RESULTS: Between December 1998 and October 1999, 130 patients in our center with acute coronary syndromes were included in this study and randomized in 2 groups. In group A (n = 65), direct stent implantation was performed without balloon predilation. In group B (n = 65), conventional balloon predilation was carried out before stent implantation. Baseline clinical and angiographic characteristics before the procedure were similar in the 2 groups of patients. No-reflow was observed in 7.7% after direct stenting and in 6.1% after conventional stent implantation (P = not significant). The immediate clinical success rate was similar in the 2 groups. Among the procedural data, only duration of the procedure (shorter in the direct stenting group), the number of balloons used, and the quantity of contrast agent (lower in the direct stenting group) were significantly different between the 2 groups (P <.05). The 6-month clinical outcome was similar in the 2 groups. CONCLUSION: This randomized study confirms the promising results of previous studies that show the feasibility and the safety of direct coronary stenting in highly selected acute coronary syndrome-related lesions. The major impact of this strategy is the improvement of the cost-benefit ratio, with no major influence on the acute complications and especially on the occurrence of no-reflow in this high-risk population.

Abstract: Four cases of young patients with acute myocardial infarction are discussed in which urgent angiography showed large intracoronary thrombus and TIMI (thrombolysis in myocardial infarction) flow > or = 2 in the infarct related artery. The rest of the coronary tree appeared to be free of detectable atherosclerosis. Percutaneous transluminal coronary angioplasty was not performed and an aggressive antiplatelet/anticoagulant treatment was administered (acetylsalicylic acid, clopidogrel, abciximab, and heparin). In all cases early angiographic control (1-12 days after AMI) showed disappearance of thrombus, no significant residual stenosis, and normal flow. No deterioration of left ventricular function was observed and the clinical course both in hospital and at five months' follow up was uneventful.

Abstract: Membrane glycoprotein (GP) Ia/IIa mediates platelet adhesion to collagen. The linked C807T/G873A polymorphisms in the GP Ia gene are correlated with a variable expression of the platelet surface receptor, the 807 TT/873 AA genotype being associated with a higher receptor density. Our study aimed to evaluate the possible role of the GP Ia C807T/G873A polymorphism as a risk factor for acute coronary syndrome in the Italian population. We investigated 157 patients with acute coronary syndrome (117 with myocardial infarction and 40 with severe unstable angina) as the first manifestation of coronary disease occurring before 65 years of age, compared with 312 healthy controls. All individuals were of Italian ancestry and were genotyped for the GP Ia C807T/G873A polymorphism. Complete linkage between the 807 and 873 sites was found in all samples. The 807 TT genotype was present in 12.7% of cases and in 4.8% of controls; the odds ratio for acute coronary syndrome was 2.9 (95% CI 1.4--5.8) for the 807 TT genotype compared with C-allele carriers and 0.6 (95% CI 0.4--0.9) for the 807 CC genotype compared with T-allele carriers. For the TT genotype, compared with CC homozygotes, the increase in risk was 3.4-fold in patients with at least one risk factor (smoking, hypercholesterolaemia, diabetes, systemic hypertension) and 4.1-fold in patients with angiographically diagnosed two- or three-vessel disease. We conclude that the GP Ia 807 TT (873 AA) genotype is associated with an increased risk of acute coronary syndrome in the Italian population; conversely, the GP Ia 807 CC (873 GG) genotype seems to represent a protective factor.

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Abstract: Interleukin (IL)-6 plasma levels are predictive of major cardiovascular events. The -174 G/C promoter polymorphism of the IL-6 gene affects basal levels in vivo and transcription rates in vitro, but its association with IL-6 acute phase levels among patients with coronary artery disease has not been investigated. In 111 patients with multivessel coronary artery disease undergoing elective coronary artery bypass graft surgery, we prospectively assessed genotype at position -174 and serial blood levels of IL-6 and other inflammatory indexes. Clinical and surgical characteristics did not differ among genotypic groups. IL-6 levels--measured daily up to 72 hours before surgery, after surgery, and at discharge--showed a mean 17-fold increase, peaking at 24 hours (p <0.0001). IL-6 levels (but not fibrinogen, white-blood cell count, and C-reactive protein values) differed significantly according to the -174 genotype (p = 0.042 for difference between areas under the curve), the 62 GG homozygotes exhibiting higher concentrations than the 49 carriers of the C allele (widest difference at 48 hours, p = 0.015 in multivariate analysis). GG homozygosity was associated with longer stays in the intensive care unit (2.5 +/- 3.4 vs 1.4 +/- 0.9 days, p = 0.02) and in the hospital (6.7 +/- 4.0 vs 5.3 +/- 1.4 days, p = 0.02) than C carriership. Rates of postoperative death, myocardial infarction, and stroke were 8% in GG homozygotes and 2% in C-carriers (p = 0.16). The IL-6-174 GG genotype is associated with higher acute phase levels of IL-6 and with longer stays in the hospital and in the intensive care unit than C allele carriership after surgical coronary revascularization.

Abstract: This pictorial introduction to homocysteine illustrates at a glance the nature of homocysteine and its role in cardiovascular disease by means of eight simple figures and an essential bibliography. Homocysteine is a sulfur-containing metabolite of methionine. Conversion back to methionine or transsulfuration to cysteine are the two major metabolic pathways that reduce total homocysteine (tHcy) concentrations in cells and blood. B vitamins are essential cofactors in homocysteine metabolism. Median fasting total homocysteine levels in adult males are approximately 10 micromol/L. Increased plasma tHcy concentrations are found with methionine-rich diets, low vitamin B intake, male gender, age, impaired renal function, and genetically determined defects of the enzymes involved in homocysteine metabolism. An inverse relation exists between plasma tHcy and circulating folate or vitamin B(6) concentrations, and folic acid supplements of 0.5 mg/d can reduce tHcy levels by approximately 25%. Homocystinuric patients, who have severe hyperhomocysteinemia, die prematurely of atherothrombotic disease. Many (but not all) cross-sectional and prospective studies indicate, on average, that plasma tHcy levels <.10 micromol/L are associated with, or predict the development of, coronary, cerebral, and peripheral vascular disease. The risk conferred by hyperhomocysteinemia is graded and is independent of traditional risk factors, with an estimated odds ratio for ischemic heart disease of 1.4 for every 5 micromol/L increase in plasma tHcy. In vitro and in vivo, tHcy has been found to impair endothelial function. It is now well established that tHcy represents a marker of current or subsequent ischemic vascular disease. However, irrefutable proof that hyperhomocysteinemia actually causes atherothrombosis will come only if interventions to lower plasma tHcy will produce concomitant reductions in cardiovascular events.

Abstract: The authors report a case of percutaneous transluminal coronary angioplasty of the circumflex artery complicated by occlusion of the non-diseased left anterior descending artery by spasm. During advanced cardiac life support, required for the subsequent cardiac arrest, intra-coronary nitrates and calcium antagonists were administered. After 45 minutes, the spasm resolved, but N probably as a result of prolonged blood stasis N a thrombus appeared in the left main artery. While attempting to stent the left main, the thrombus was mechanically dislodged, leaving the epicardial coronary tree free, with a good flow.

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Abstract: Many cross-sectional and prospective studies have shown that raised serum/plasma levels of total homocysteine increase the risk of coronary, cerebral, and peripheral artery disease. The risk associated with hyperhomocysteinemia appears to be concentration-dependent and not attributable to traditional risk factors. The odds ratio for ischemic heart disease has been estimated to be 1.4 for every 5 mumol/l increase of total plasma homocysteine. Median fasting total plasma homocysteine in adult males is approximately 10 mumol/l. Mild hyperhomocysteinemia is estimated to occur in 5-10% of the general population. Plasma concentrations are increased as a result of age, male gender, impaired renal function, low vitamin B intake, and genetically-determined defects of the enzymes involved in homocysteine metabolism. Folate supplements can reduce total homocysteine levels by approximately 25%. Studies in vitro and in vivo indicate that homocysteine can impair endothelial function. Despite increasing recognition of hyperhomocysteinemia as a risk factor for arterial occlusive disease, irrefutable proof that mild hyperhomocysteinemia contributes directly to the pathogenesis of atherothrombosis will come if interventions to lower total homocysteine reduce cardiovascular events. Family studies may also provide evidence of causality if genetic causes of hyperhomocysteinemia are found to segregate with disease.

Abstract: The PAI-1 gene promoter 4G/5G polymorphism was found to be associated with plasma PAI-1 activity in Northern and Central Europe populations, but no data are available on the association between this polymorphism and PAI-1 levels in Southern Europe countries (such as Italy) where the incidence of ischemic disorders is lower. This study shows that among populations with different incidence of atherothrombotic disorders the 4G/5G PAI-1 gene promoter polymorphism has the same importance in the regulation of plasma PAI-1 activity. Moreover, we have analysed some gene-environmental interactions: the correlation between PAI-1 and cholesterol in non dyslipidemic subjects and the correlation between PAI-1 activity and tryglicerides in dyslipidemic subjects differed according to the 4G/5G genotype class. Thus, our findings suggest that, among subjects with or without metabolic disorders such as dyslipidemia, completely different gene-environment interactions may occur.

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Abstract: Previous studies have suggested that a decreased fibrinolytic potential can play a role as risk factor for thrombotic events. Blood levels of factors of the fibrinolytic system are highly heritable, supporting the importance of the genetic background. To better understand the impact of two common polymorphisms of the tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) genes on the in vivo regulation of fibrinolysis, we have studied this genetic variables together with other clinical and metabolic factors in a sample of the Italian population. Two hundred-eighteen subjects without history of atherothrombosis or mayor diseases entered the study. A detailed clinical history was collected and evaluations of blood levels of cholesterol, triglycerides, PAI-1 activity, PAI-1 antigen, t-PA activity, t-PA antigen were performed on standard conditions. Genotypes at the locus of the 4G/5G polymorphism of PAI-1 gene promoter and at locus of the insertion/deletion Alu-repeat polymorphism of t-PA gene intron h were studied. No detectable effect was found for the t-PA gene polymorphism in our population. On the other hand, the 4G/5G polymorphism was found to modulate plasma PAI-1 activity levels and the interaction between PAI-1 plasma activity levels and blood lipids. Moreover, such regulation by genotype was found to be affected by the presence or absence of dyslipidemia. In conclusion, our findings suggest that, among subjects with or without metabolic disorders such as dyslipidemia, completely different gene-environment interactions may occur, and could affect the individual risk of thrombosis.

Abstract: A low heart rate variability (HRV) has been shown to be a powerful predictor of cardiac events in patients surviving an acute myocardial infarction (MI), but it is not clear yet which among the HRV parameters has the best predictive value. Time domain and frequency domain HRV was assessed on 24-hour predischarge Holter recording of 239 patients with a recent MI. Patients were followed up for 6 to 54 months (median 28), during which 26 deaths (11%) occurred, 19 of which were cardiac in origin and 12 were sudden. Most HRVs did not show any difference between patients with or without mortality end points, but the average low-frequency and low-frequency/high-frequency ratio was lower in patients with events. However, when dichotomized according to cut points that maximized the risk of sudden death, several HRVs were significantly predictive of clinical end points. Overall, the mean of the standard deviations of all RR intervals for all 5-minute segments and the standard deviation of the mean RR intervals for all 5-minute segments were the time domain variables most significantly associated with mortality end points, whereas very low frequency was the most predictive frequency domain variable. Compared with the best time domain variables, very low frequency showed a better sensitivity (0.27 to 0.42 vs 0.19 to 0.33) for end points with only a small loss in specificity (0.92 vs 0.96). On multivariate Cox proportional analysis, a left ventricular ejection fraction <40% and a number of ventricular premature beats > or = 10/hour were the most powerful independent predictors for all end points, whereas no HRV was independently associated with the events. A low frequency/high frequency ratio < 1.05 only had a borderline association with sudden death (RR = 2.86, p = 0.076). Our data show a strong association between HRV and mortality in patients surviving a recent MI, with a slight better sensitivity of frequency domain analysis. In our study, however, HRV did not add independent prognostic information to more classic prognostic variables (e.g., left ventricular function and ventricular arrhythmias).

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