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Supplemental Digital Content is available in the text., Background: Thrombotic events are reduced with cangrelor, an intravenous P2Y12 inhibitor. We sought to characterize the timing, number, and type of early events (within 2 hours of randomization) in CHAMPION PHOENIX (A Clinical Trial Comparing Cangrelor to Clopidogrel Standard of Care Therapy in Subjects Who Require Percutaneous Coronary Intervention). Methods: CHAMPION PHOENIX was a double-blind, placebo-controlled trial that randomized patients undergoing percutaneous coronary intervention to cangrelor or clopidogrel. For this analysis, we evaluated the efficacy of cangrelor in the first 2 hours postrandomization with regards to the primary end point (death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis). Sensitivity analyses were performed evaluating a secondary, post hoc end point (death, Society of Coronary Angiography and Intervention myocardial infarction, ischemia-driven revascularization, or Academic Research Consortium definite stent thrombosis). Results: The majority of events (63%) that occurred in the trial occurred within 2 hours of randomization. The most common early event was myocardial infarction; next were stent thrombosis, ischemia driven revascularization, and death. In the first 2 hours after randomization, cangrelor significantly decreased the primary composite end point compared with clopidogrel (4.1% versus 5.4%; hazard ratio, 0.76 [95% CI, 0.64–0.90], P=0.002). Similar findings were seen for the composite end point of death, Society of Coronary Angiography and Intervention myocardial infarction, ischemia-driven revascularization, or Academic Research Consortium stent thrombosis at 2 hours (0.9% versus 1.6%; hazard ratio, 0.57 [95% CI, 0.40–0.80], P=0.001). Between 2 and 48 hours, there was no difference in the primary composite end point (0.6% versus 0.5%; odds ratio, 1.17 [95% CI, 0.71–1.93]; P=0.53). Early (≤2 hours of randomization) GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) moderate or severe bleeding events were infrequent, and there was no significant difference with cangrelor compared with clopidogrel (0.2% [n=10] versus 0.1% [n=4]; adjusted odds ratio, 1.41 [95% CI, 0.37–5.40]; P=0.62). Conclusions: The reductions in ischemic events and overall efficacy seen with cangrelor in CHAMPION PHOENIX occurred early and during the period of time in which patients were being actively treated with cangrelor. These findings provide evidence that supports the importance of potent platelet inhibition during percutaneous coronary intervention. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01156571.

Background It remains unclear whether radial access (RA), compared with femoral access (FA), mitigates the risk of acute kidney injury (AKI). Objectives The authors assessed the incidence of AKI in patients with acute coronary syndrome (ACS) enrolled in the MATRIX-Access (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) trial. Methods Among 8,404 patients, 194 (2.3%) were excluded due to missing creatinine values, no or an incomplete coronary angiogram, or previous dialysis. The primary AKI-MATRIX endpoint was AKI, defined as an absolute (>0.5 mg/dl) or a relative (>25%) increase in serum creatinine (sCr). Results AKI occurred in 634 patients (15.4%) with RA and 712 patients (17.4%) with FA (odds ratio [OR]: 0.87; 95% confidence interval [CI]: 0.77 to 0.98; p = 0.0181). A >25% sCr increase was noted in 633 patients (15.4%) with RA and 710 patients (17.3%) with FA (OR: 0.87; 95% CI: 0.77 to 0.98; p = 0.0195), whereas a >0.5 mg/dl absolute sCr increase occurred in 175 patients (4.3%) with RA versus 223 patients (5.4%) with FA (OR: 0.77; 95% CI: 0.63 to 0.95; p = 0.0131). By implementing the Kidney Disease Improving Global Outcomes criteria, AKI was 3-fold less prevalent and trended lower with RA (OR: 0.85; 95% CI: 0.70 to 1.03; p = 0.090), with stage 3 AKI occurring in 28 patients (0.68%) with RA versus 46 patients (1.12%) with FA (p = 0.0367). Post-intervention dialysis was needed in 6 patients (0.15%) with RA and 14 patients (0.34%) with FA (p = 0.0814). Stratified analyses suggested greater benefit with RA than FA in patients at greater risk for AKI. Conclusions In ACS patients who underwent invasive management, RA was associated with a reduced risk of AKI compared with FA. (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX [MATRIX]; NCT01433627 )

Background Cangrelor, an intravenous, reversible P2Y12 antagonist, is approved for use in patients undergoing percutaneous coronary intervention (PCI). Objectives This study sought to evaluate the efficacy and safety of cangrelor compared with clopidogrel in subgroups that did and did not receive glycoprotein IIb/IIIa inhibitors (GPIs). Methods This pooled, patient-level analysis of the 3 CHAMPION (Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition) trials analyzed all randomized patients who underwent PCI and received the study drug (n = 24,902). Only bailout/rescue GPI use was permitted, except in CHAMPION PCI, in which routine or bailout/rescue GPI use was at the site investigator’s discretion. The primary efficacy endpoint was the composite of all-cause mortality, myocardial infarction, ischemia-driven revascularization, or stent thrombosis at 48 h after randomization. Results Overall, 3,173 patients (12.7%) received a GPI, most commonly eptifibatide (69.4%). Despite variation in indications for GPIs, baseline characteristics were well balanced between the cangrelor and clopidogrel arms in subsets receiving and not receiving GPIs. Rates of the primary composite endpoint were lower with cangrelor compared with clopidogrel in patients who did (4.9% vs. 6.5%; odds ratio [OR]: 0.74; 95% confidence interval [CI]: 0.55 to 1.01) or did not receive a GPI (3.6% vs. 4.4%; OR: 0.82; 95% CI: 0.72 to 0.94; Pint = 0.55). Cangrelor did not increase the primary safety endpoint, GUSTO-defined severe/life-threatening bleeding, in patients who did (0.4% vs. 0.5%; OR: 0.71; 95% CI: 0.25 to 1.99) or did not receive GPIs (0.2% vs. 0.1%; OR: 1.56; 95% CI: 0.80 to 3.04; Pint = 0.21). GPI use was associated with increased risk of bleeding in both treatment arms. Conclusions Cangrelor’s efficacy in reducing ischemic complications in patients undergoing PCI was maintained irrespective of GPI administration. GPI use was associated with substantially higher bleeding rates, regardless of the randomization to cangrelor or clopidogrel. (A Clinical Trial to Demonstrate the Efficacy of Cangrelor [PCI]: NCT00305162 ; Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition [PLATFORM]: NCT00385138 ; A Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention [PCI] [CHAMPION PHOENIX] [CHAMPION]: NCT01156571 )

Summary Background The Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox (MATRIX) programme was designed to assess the comparative safety and effectiveness of radial versus femoral access and of bivalirudin versus unfractionated heparin with optional glycoprotein IIb/IIIa inhibitors in patients with the whole spectrum of acute coronary syndrome undergoing invasive management. Here we describe the prespecified final 1-year outcomes of the entire programme. Methods MATRIX was a programme of three nested, randomised, multicentre, open-label, superiority trials in patients with acute coronary syndrome in 78 hospitals in Italy, the Netherlands, Spain, and Sweden. Patients with ST-elevation myocardial infarction were simultaneously randomly assigned (1:1) before coronary angiography to radial or femoral access and to bivalirudin, with or without post-percutaneous coronary intervention infusion or unfractionated heparin (one-step inclusion). Patients with non-ST-elevation acute coronary syndrome were randomly assigned (1:1) before coronary angiography to radial or femoral access and, only if deemed eligible to percutaneous coronary intervention after angiography (two-step inclusion), entered the antithrombin type and treatment duration programmes. Randomisation sequences were computer generated, blocked, and stratified by intended new or current use of P2Y12 inhibitor (clopidogrel vs ticagrelor or prasugrel), and acute coronary syndrome type (ST-elevation myocardial infarction, troponin-positive, or troponin-negative non-ST-elevation acute coronary syndrome). Bivalirudin was given as a bolus of 0·75 mg/kg, followed immediately by an infusion of 1·75 mg/kg per h until completion of percutaneous coronary intervention. Heparin was given at 70–100 units per kg in patients not receiving glycoprotein IIb/IIIa inhibitors, and at 50–70 units per kg in patients receiving glycoprotein IIb/IIIa inhibitors. Clinical follow-up was done at 30 days and 1 year. Co-primary outcomes for MATRIX access and MATRIX antithrombin type were major adverse cardiovascular events, defined as the composite of all-cause mortality, myocardial infarction, or stroke up to 30 days; and net adverse clinical events, defined as the composite of non-coronary artery bypass graft-related major bleeding, or major adverse cardiovascular events up to 30 days. The primary outcome for MATRIX treatment duration was the composite of urgent target vessel revascularisation, definite stent thrombosis, or net adverse clinical events up to 30 days. Analyses were done according to the intention-to-treat principle. This trial is registered with ClinicalTrials.gov, number NCT01433627. Findings Between Oct 11, 2011, and Nov 7, 2014, we randomly assigned 8404 patients to receive radial (4197 patients) or femoral (4207 patients) access. Of these 8404 patients, 7213 were included in the MATRIX antithrombin type study and were randomly assigned to bivalirudin (3610 patients) or heparin (3603 patients). Patients assigned to bivalirudin were included in the MATRIX treatment duration study, and were randomly assigned to post-procedure infusion (1799 patients) or no post-procedure infusion (1811 patients). At 1 year, major adverse cardiovascular events did not differ between patients assigned to radial access compared with those assigned to femoral access (14·2% vs 15·7%; rate ratio 0·89, 95% CI 0·80–1·00; p=0·0526), but net adverse clinical events were fewer with radial than with femoral access (15·2% vs 17·2%; 0·87, 0·78–0·97; p=0·0128). Compared with heparin, bivalirudin was not associated with fewer major adverse cardiovascular (15·8% vs 16·8%; 0·94, 0·83–1·05; p=0·28) or net adverse clinical events (17·0% vs 18·4%; 0·91, 0·81–1·02; p=0·10). The composite of urgent target vessel revascularisation, stent thrombosis, or net adverse clinical events did not differ with or without post-procedure bivalirudin infusion (17·4% vs 17·4%; 0·99, 0·84–1·16; p=0·90). Interpretation In patients with acute coronary syndrome, radial access was associated with lower rates of net adverse clinical events compared with femoral access, but not major adverse cardiovascular events at 1 year. Bivalirudin with or without post-procedure infusion was not associated with lower rates of major adverse cardiovascular events or net adverse clinical events. Radial access should become the default approach in acute coronary syndrome patients undergoing invasive management. Funding Italian Society of Invasive Cardiology, The Medicines Company, Terumo, amd Canada Research Chairs Programme.

Clopidogrel has been widely investigated, even if resistance limits its efficacy. Prasugrel and ticagrelor obtain a greater and homogeneous inhibition of platelet aggregation, but a delay onset of action in patients with stent thrombosis elevation myocardial infarction and an increased bleeding risk in case of surgical revascularization have been reported. Cangrelor is an intravenous reversible P2Y12 inhibitor with an immediate onset and a quick offset of action. Based on its pharmacokinetic and pharmacodynamic profile, and on clinical data, cangrelor could become the antiplatelet of choice in case of elective percutaneous coronary intervention without clopidogrel pretreatment and in acute coronary syndrome requiring urgent coronary angiography. However, in acute setting, data of comparison with prasugrel and ticagrelor are needed.

Background/objectives Long term safety of DES, particularly regarding thrombosis is of concern. The hypothesized underlying mechanisms (stent underexpansion, malapposition) could be prevented by IVUS guidance. Aim of this meta-analysis of randomized controlled clinical trials (RCT) and high quality observational cohort studies (HQ-OBS) is to quantify the potential clinical benefit of intravascular ultrasound (IVUS) guidance in drug-eluting stents (DES) implantation. Methods We performed an extensive literature search for full-text articles published in 2003–2013. The primary outcome was the rate of major adverse cardiac events (MACE) in RCT and HQ-OBS; secondary outcomes were death, myocardial infarction (MI), revascularization, thrombosis and post-procedural minimum lumen diameter (MLD). Fixed/random effect relative risks (RRs) or standardized mean difference (SMD) and 95% confidence interval (95% CI) were computed for the meta-analysis. Results Thirty-four articles were retrieved from 268 found; of these 3 were RCT and 9 were HQ-OBS; 18,707 patients were enrolled, 1037 in RCT and 17,670 in OBS. Median follow-up was 20months. IVUS guidance was associated with a significantly lower rate of MACE (RR=0.80, 95% CI 0.71–0.89, p Conclusions In this meta-analysis, IVUS guidance in DES implantation appears to reduce MACE, mortality and MI, possibly by reducing thrombosis rather than restenosis rate. Patients at high risk for thrombosis might be identified as the best candidate for IVUS guidance.

Remote ischemic postconditioning as a strategy to reduce acute kidney injury during primary PCI: A post-hoc analysis of a randomized trial☆ Gabriele Crimi ⁎, Marco Ferlini , Fabio Gallo , Maria Pia Sormani , Claudia Raineri , Ezio Bramucci , Gaetano M. De Ferrari , Silvia Pica , Barbara Marinoni , Alessandra Repetto , Arturo Raisaro , Sergio Leonardi , Paolo Rubartelli , Luigi Oltrona Visconti , Maurizio Ferrario a

Objectives The purpose of this study was to compare sulfur hexafluoride microbubble (SonoVue)-enhanced myocardial contrast echocardiography (MCE) with single-photon emission computed tomography (SPECT) relative to coronary angiography (CA) for assessment of coronary artery disease (CAD). Background Small-scale studies have shown that myocardial perfusion assessed by SonoVue-enhanced MCE is a viable alternative to SPECT for CAD assessment. However, large multicenter studies are lacking. Methods Patients referred for myocardial ischemia testing at 34 centers underwent rest/vasodilator SonoVue-enhanced flash-replenishment MCE, standard Tc-99m-labeled electrocardiography-gated SPECT, and quantitative CA within 1 month. Myocardial ischemia assessments by 3 independent, blinded readers for MCE and 3 readers for SPECT were collapsed into 1 diagnosis per patient per technique and were compared to CA (reference standard) read by 1 independent blinded reader. Results Of 628 enrolled patients who received SonoVue (71% males; mean age: 64 years; >1 cardiovascular [CV] risk factor in 99% of patients) 516 patients underwent all 3 examinations, of whom 161 (31.2%) had >= 70% stenosis ( 131 had single-vessel disease [SVD]; 30 had multivessel disease), and 310 (60.1%) had >= 50% stenosis. Higher sensitivity was obtained with MCE than with SPECT (75.2% vs. 49.1%, respectively; p < 0.0001), although specificity was lower (52.4% vs. 80.6%, respectively; p < 0.0001) for >= 70% stenosis. Similar findings were obtained for patients with >= 50% stenosis. Sensitivity levels for detection of SVD and proximal disease for >= 70% stenosis were higher for MCE (72.5% vs. 42.7%, respectively; p < 0.0001; 80% vs. 58%, respectively; p = 0.005, respectively). Conclusions SonoVue-enhanced MCE demonstrated superior sensitivity but lower specificity for detection of CAD compared to SPECT in a population with a high incidence of CV risk factors and intermediate-high prevalence of CAD. (A phase III study to compare SonoVue (R) enhanced myocardial echocardiography [MCE] to single photon emission computerized tomography [ECG-GATED SPECT], at rest and at peak of low-dose Dipyridamole stress test, in the assessment of significant coronary artery disease [CAD] in patients with suspect or known CAD using Coronary Angiography as Gold Standard-SonoVue MCE vs SPECT; EUCTR2007-003492-39-GR) (c) 2013 by the American College of Cardiology Foundation

Mechanical debulking of coronary plaques with rotational atherectomy (RA) has been used for more than 20 years during percutaneous coronary interventions (PCI). Modification of plaque characteristics may be accomplished with selective ablation of inelastic fibrocalcific tissue. The use of RA, though reduced with the development of bare-metal stents (BMS) and even more with drug-eluting stents (DES), has never been completely abandoned. The present review will analyze reasons for conflicting results obtained in large series and randomized trials on this topic in the past, and will identify criteria for an appropriate use in current times.

Background Percutaneous coronary intervention (PCI) has been shown to be the best reperfusion therapy for acute myocardial infarction with ST-elevation (STEMI), but data from registries show differences in patient populations and outcomes between randomized trials and real life. Objectives We sought to provide information about the current status of this treatment with a registry collecting data in Lombardy, the most densely populated region in Italy, with widespread availability of cathlabs and a well-established network for the treatment of STEMI. Methods and results Patient enrollment was performed by 32 hub centres recruiting 3901 STEMI patients who underwent PCI procedures within 12 h of the onset of symptoms, of whom 3317 patients underwent primary PCI, 376 'facilitated' PCI, and 208 rescue PCI in cathlabs located, in 77% of cases, in the same hospital of admission. In-hospital and 30-day total death were 4.4 and 6.6%, respectively. At multivariate analysis independent negative predictors of 30-day mortality were Killip class 3-4, number of involved ECG leads, chronic renal failure and age, whereas positive predictors were ST resolution more than 50% and postprocedural grade 3 thrombolysis in myocardial infarction flow. Conclusions LombardIMA PCI registry enrolled STEMI patients representing a real-world population treated with PCI. Findings presented in this study may provide a benchmark for similar registries undertaken in other Italian regions and may be helpful to assess future possible developments of care for STEMI patients.

A 51-year-old man was hospitalized for recurrence of acute coronary syndrome after few months. Coronary angiography during first hospitalization showed no significant coronary stenosis, while the second time, right coronary artery presented an expansion at the proximal segment. Optical coherence tomography documented a long fibroatheroma with an ulceration and residual white thrombus.

Background— Myocardial salvage is often suboptimal after percutaneous coronary intervention in ST-segment elevation myocardial infarction. Posthoc subgroup analysis from a previous trial (AMIHOT I) suggested that intracoronary delivery of supersaturated oxygen (SSO 2 ) may reduce infarct size in patients with large ST-segment elevation myocardial infarction treated early. Methods and Results— A prospective, multicenter trial was performed in which 301 patients with anterior ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention within 6 hours of symptom onset were randomized to a 90-minute intracoronary SSO 2 infusion in the left anterior descending artery infarct territory (n=222) or control (n=79). The primary efficacy measure was infarct size in the intention-to-treat population (powered for superiority), and the primary safety measure was composite major adverse cardiovascular events at 30 days in the intention-to-treat and per-protocol populations (powered for noninferiority), with Bayesian hierarchical modeling used to allow partial pooling of evidence from AMIHOT I. Among 281 randomized patients with tc-99m-sestamibi single-photon emission computed tomography data in AMIHOT II, median (interquartile range) infarct size was 26.5% (8.5%, 44%) with control compared with 20% (6%, 37%) after SSO 2 . The pooled adjusted infarct size was 25% (7%, 42%) with control compared with 18.5% (3.5%, 34.5%) after SSO 2 ( P Wilcoxon =0.02; Bayesian posterior probability of superiority, 96.9%). The Bayesian pooled 30-day mean (�SE) rates of major adverse cardiovascular events were 5.0�1.4% for control and 5.9�1.4% for SSO 2 by intention-to-treat, and 5.1�1.5% for control and 4.7�1.5% for SSO 2 by per-protocol analysis (posterior probability of noninferiority, 99.5% and 99.9%, respectively). Conclusions— Among patients with anterior ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention within 6 hours of symptom onset, infusion of SSO 2 into the left anterior descending artery infarct territory results in a significant reduction in infarct size with noninferior rates of major adverse cardiovascular events at 30 days. Clinical Trial Registration— clinicaltrials.gov Identifier: NCT00175058

Background— Prasugrel is a novel thienopyridine that reduces new or recurrent myocardial infarctions (MIs) compared with clopidogrel in patients with acute coronary syndrome undergoing percutaneous coronary intervention. This effect must be balanced against an increased bleeding risk. We aimed to characterize the effect of prasugrel with respect to the type, size, and timing of MI using the universal classification of MI. Methods and Results— We studied 13 608 patients with acute coronary syndrome undergoing percutaneous coronary intervention randomized to prasugrel or clopidogrel and treated for 6 to 15 months in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel–Thrombolysis in Myocardial Infarction (TRITON-TIMI 38). Each MI underwent supplemental classification as spontaneous, secondary, or sudden cardiac death (types 1, 2, and 3) or procedure related (Types 4 and 5) and examined events occurring early and after 30 days. Prasugrel significantly reduced the overall risk of MI (7.4% versus 9.7%; hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.67 to 0.85; P P =0.0002) and nonprocedural (type 1, 2, or 3) MIs (2.8% versus 3.7%; HR, 0.72; 95% CI, 0.59 to 0.88; P =0.0013) and consistently across MI size, including MIs with a biomarker peak ≥5 times the reference limit (HR. 0.74; 95% CI, 0.64 to 0.86; P =0.0001). In landmark analyses starting at 30 days, patients treated with prasugrel had a lower risk of any MI (2.9% versus 3.7%; HR, 0.77; P =0.014), including nonprocedural MI (2.3% versus 3.1%; HR, 0.74; 95% CI, 0.60 to 0.92; P =0.0069). Conclusion— Treatment with prasugrel compared with clopidogrel for up to 15 months in patients with acute coronary syndrome undergoing percutaneous coronary intervention significantly reduces the risk of MIs that are procedure related and spontaneous and those that are small and large, including new MIs occurring during maintenance therapy.

The PROMUS™ Element™ European Post-Approval Surveillance Study (PE-Prove) is a prospective, open-label, multicentre observational study designed to assess outcomes following PROMUS Element everolimus-eluting stent implantation in an unselected patient population.A total of 1,010 patients were enrolled at 40 clinical sites in Europe, including 24.9% with medically treated diabetes, 50.0% with Type B2/C lesions, 6.1% with chronic total occlusion, 17.8% with acute myocardial infarction (MI ≤24 hours pre-procedure), and 20.1% with unstable angina. The target lesion was the culprit for ST-segment elevation MI in 7.3% of patients. The one-year, per patient target vessel failure rate was 6.2% (60/975), 3.4% (33) being related to the PROMUS Element stent. Rates of cardiac death, MI, and Academic Research Consortium (ARC) definite/probable stent thrombosis were 1.7%, 3.5%, and 0.6%, respectively. The target vessel revascularisation rate was 3.2% (31/975), 2.1% (20) being related to the PROMUS Element stent.In a large and relatively complex group of "real-world" patients, coronary artery revascularisation with the PROMUS Element everolimus-eluting stent provides favourable results with low event rates consistent with those reported for other contemporary drug-eluting stents.

Sirolimus-eluting stents reduce rates of restenosis and reintervention, as compared with uncoated stents. Data are limited regarding the safety and efficacy of such stents in primary percutaneous coronary intervention (PCI) for acute myocardial infarction with ST-segment elevation.We performed a single-blind, multicenter, prospectively randomized trial to compare sirolimus-eluting stents with uncoated stents in primary PCI for acute myocardial infarction with ST-segment elevation. The trial included 712 patients at 48 medical centers. The primary end point was target-vessel failure at 1 year after the procedure, defined as target-vessel-related death, recurrent myocardial infarction, or target-vessel revascularization. A follow-up angiographic substudy was performed at 8 months among 174 patients from selected centers.The rate of the primary end point was significantly lower in the sirolimus-stent group than in the uncoated-stent group (7.3% vs. 14.3%, P=0.004). This reduction was driven by a decrease in the rate of target-vessel revascularization (5.6% and 13.4%, respectively; P0.001). There was no significant difference between the two groups in the rate of death (2.3% and 2.2%, respectively; P=1.00), reinfarction (1.1% and 1.4%, respectively; P=1.00), or stent thrombosis (3.4% and 3.6%, respectively; P=1.00). The degree of neointimal proliferation, as assessed by the mean (+/-SD) in-stent late luminal loss, was significantly lower in the sirolimus-stent group (0.14+/-0.49 mm, vs. 0.83+/-0.52 mm in the uncoated stent group; P0.001).Among selected patients with acute myocardial infarction, the use of sirolimus-eluting stents significantly reduced the rate of target-vessel revascularization at 1 year. (ClinicalTrials.gov number, NCT00232830 [ClinicalTrials.gov].).

The aim of this study was to compare the short- (< 30 days) and long-term (≥ 30 days) clinical outcomes of left internal mammary artery bypass grafting (LIMA-LAD) and directional coronary atherectomy plus stent implantation (DCA + stent) in the treatment of isolated proximal left anterior descending coronary (LAD) lesions. One hundred and twenty-six patients underwent LIMA-LAD and 132 consecutive patients underwent DCA + stenting. The primary endpoint was the incidence of short- and long-term major adverse cardiac events (MACE); the secondary endpoints included any periprocedural events and long-term target vessel revascularization (TVR). We found no significant between-treatment difference in the occurrence of short-term MACE, and the long-term MACE rate per 100 person-years was 3.0 in the LIMA-LAD group and 4.6 in the DCA + stent group. After 5-year follow-up, 79% of the patients in the DCA + stent group and 89% of those in the LIMA-LAD group were still MACE-free. The risk of any periprocedural events was six times lower in the DCA + stent group, and the risk of TVR was six times higher. We conclude that both procedures lead to good short- and long-term follow-up results in isolated proximal LAD disease. As fewer periprocedural events and more TVRs occur after DCA + stenting than after LIMA-LAD, they can be considered valuable alternatives to each other. Catheter Cardiovasc Interv 2005;64:45–52. © 2004 Wiley-Liss, Inc.

We conducted a prospective observational study to evaluate the indications, technique, in-hospital and 9-month results of consecutive patients treated with rotational atherectomy (RA) in 12 centers during 1 year, as well as their relationship with volume of RA activity. The study included 345 lesions in 289 patients treated (4.4% +/- 2.6% of procedures at the participating centers). The lesions were mostly calcified (63%) and type B2 or C (74%). Procedural success was obtained in 94% of patients, with a major adverse cardiac event (MACE) rate of 4.5%. At 9 months, MACE occurred in 17.3%. Multivariate analysis identified multivessel disease and slow flow as negative predictors of procedural success, whereas balloon pressure

Current guidelines for the management of patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) recommend the administration of dual antiplatelet therapy with aspirin and an ADP receptor blocker "as early as possible" before angiography (upstream), though this suggestion is not based on the results of randomized clinical trials designed to investigate pre-hospital rather than in-hospital drug administration. The present review analyzed randomized clinical trials, registries and observational studies that assessed clopidogrel, prasugrel and ticagrelor administration in STEMI patients undergoing primary PCI to evaluate if their upstream use may be justified in clinical practice. A significant difference favoring early clopidogrel administration has been demonstrated in observational studies. No evidence is available for prasugrel and ticagrelor; however, the initial delay of their antiplatelet effect in STEMI patients could support an upstream strategy to obtain complete platelet inhibition in the first hours after PCI and prevent major adverse events (e.g., stent thrombosis) despite an increased risk of major bleeding, particularly in case of urgent bypass surgery. Data from specifically designed randomized clinical trials are warranted to establish whether early administration of prasugrel and ticagrelor may favor reperfusion and improve clinical outcome with an acceptable risk-benefit ratio.

Long term safety of DES, particularly regarding thrombosis is of concern. The hypothesized underlying mechanisms (stent under expansion, malapposition) could be prevented by IVUS guidance. Aim of this meta-analysis of randomized controlled clinical trials (RCT) and high quality observational cohort studies (HQ-OBS) is to quantify the potential clinical benefit of intravascular ultrasound (IVUS) guidance in drug-eluting stents (DES) implantation.We performed an extensive literature search for full-text articles published in 2003–2013. The primary outcome was the rate of major adverse cardiac events (MACE) in RCT and HQ-OBS; secondary outcomes were death, myocardial infarction (MI), revascularization, thrombosis and post-procedural minimum lumen diameter (MLD). Fixed/random effect relative risks (RRs) or standardized mean difference (SMD) and 95% confidence interval (95% CI) were computed for the meta-analysis.Thirty-four articles were retrieved from 268 found; of these 3 were RCT and 9 were HQ-OBS; 18,707 patients were enrolled, 1037 in RCT and 17,670 in OBS. Median follow-up was 20 months. IVUS guidance was associated with a significantly lower rate of MACE (RR=0.80, 95% CI 0.71–0.89, p b 0.001), death (RR=0.60, 95% CI 0.48–0.74, p b 0.001), MI (RR=0.59, 95% CI 0.44–0.80, p=0.001) and thrombosis (RR=0.50, 95% CI 0.32–0.80, p=0.007) and larger MLD (SMD=0.15, 95% CI 0.03 to 0.27, p=0.014), but not of revascularization (RR=0.95, 95% CI 0.82–1.09, p=0.75).In this meta-analysis, IVUS guidance in DES implantation appears to reduce MACE, mortality and MI, possibly by reducing thrombosis rather than restenosis rate. Patients at high risk for thrombosis might be identified as the best candidate for IVUS guidance.

Optimal perioperative antiplatelet therapy in patients with coronary stents undergoing surgery still remains poorly defined and a matter of debate among cardiologists, surgeons and anaesthesiologists. Surgery represents one of the most common reasons for premature antiplatelet therapy discontinuation, which is associated with a significant increase in mortality and major adverse cardiac events, in particular stent thrombosis. Clinical practice guidelines provide little support with regard to managing antiplatelet therapy in the perioperative phase in the case of patients with non-deferrable surgical interventions and/or high haemorrhagic risk. Moreover, a standard definition of ischaemic and haemorrhagic risk has never been determined. Finally, recommendations shared by cardiologists, surgeons and anaesthesiologists are lacking. The present consensus document provides practical recommendations on the perioperative management of antiplatelet therapy in patients with coronary stents undergoing surgery. Cardiologists, surgeons and anaesthesiologists have contributed equally to its creation. On the basis of clinical and angiographic data, the individual thrombotic risk has been defined. All surgical interventions have been classified according to their inherent haemorrhagic risk. A consensus on the optimal antiplatelet regimen in the perioperative phase has been reached on the basis of the ischaemic and haemorrhagic risk. Aspirin should be continued perioperatively in the majority of surgical operations, whereas dual antiplatelet therapy should not be withdrawn for surgery in the case of low bleeding risk. In selected patients at high risk for both bleeding and ischaemic events, when oral antiplatelet therapy withdrawal is required, perioperative treatment with short-acting intravenous glycoprotein IIb/IIIa inhibitors (tirofiban or eptifibatide) should be taken into consideration.

Higher levels of tissue factor (the initiator of blood coagulation) have been found in coronary atherosclerotic plaques of patients with unstable coronary artery disease, but it is not established whether they are associated with a different thrombotic response to in vivo plaque rupture. In 40 patients undergoing directional coronary atherectomy, prothrombin fragment 1 + 2, a marker of thrombin generation, was measured in intracoronary blood samples obtained proximally and distally to the coronary atherosclerotic plaque before and after the procedure. Before the procedure, plasma prothrombin fragment 1 + 2 levels were significantly increased across the lesion in patients with unstable, but not in those with stable, coronary disease (unstable, median increase, 0.37 nM; range, −0.35-1.16 nM) (stable, median increase, −0.065 nM; range, −0.58-1.06 nM) ( P = .0021). After plaque removal, an increase in prothrombin fragment 1 + 2 across the lesion was observed only in patients with unstable coronary disease (unstable, median increase, 0.25 nM; range, −1.04-4.9 nM) (stable, 0.01 nM; range, −0.48-3.59 nM) ( P = .036)]. There was a correlation between the tissue factor content of the plaque and the increase in thrombin generation across the lesion (ρ = 0.33; P = .038). The higher tissue factor content found in plaques obtained from patients with unstable coronary disease was associated with a local increase in thrombin generation, thus suggesting a link with the in vivo thrombogenicity of the plaque.

Unstable angina and non-Q-wave myocardial infarction still represent an unsolved problem for clinicians, owing to their unpredictable evolution and high incidence of coronary events in the follow-up. Traditional antithrombotic agents, unfractionated heparin and aspirin, have been proved to be highly effective, but show some important limitations. New potent antithrombotic therapy have been studied to improve their efficacy, with encouraging results. Among these drugs, low molecular weight heparins (for subcutaneous administration) and inhibitors of platelet glycoprotein receptor IIb/IIIa (for intravenous, and possibly oral, administration) are the most promising and are now under extensive investigation.

OBJECTIVE--To determine whether the increasing use of percutaneous transluminal angioplasty in patients with unstable angina has reduced the need for bypass surgery and whether this change in the choice of treatment affected the outcome at one year in patients with unstable angina who were admitted to hospital in two different periods of time. DESIGN--Retrospective analysis of consecutive patients with unstable angina (angina at rest with ST-T changes during pain) who underwent coronary arteriography in two different periods of time. PATIENTS--158 patients were admitted to hospital between January 1988 and June 1989 (group 1) and 140 patients admitted between January 1992 and June 1993 (group 2). RESULTS--Coronary angioplasty procedures nearly doubled from 29% in group 1 to 56% in group 2 whereas bypass surgery decreased from 36% in group 1 to 23% in group 2 (P < 0.01). Coronary angioplasty increased and bypass surgery decreased in patients with one vessel disease (P < 0.01), two vessel disease (P < 0.05), and three vessel disease (P < 0.01). Coronary angioplasty also increased and bypass surgery decreased in refractory angina and in patients with ejection fraction < 0.50 (both P < 0.05). At 1-year follow up, 14 patients in group 1 (9%) and 10 in group 2 (7%) either died or had myocardial infarction (P = NS). Revascularisation procedures were needed in 16 group 1 patients (10%) and 27 group 2 patients (19%, P < 0.05). CONCLUSIONS--Coronary angioplasty became more widely used in patients with unstable angina. This reduced the need for bypass surgery in patients with multivessel disease, refractory angina, and depressed left ventricular function. This change in treatment did not affect 1-year mortality or the myocardial infarction rate. More patients in the more recent group in which angioplasty was the preferred treatment required a further revascularisation procedure than in the earlier group in which bypass grafting was more often used as the initial treatment.

The management of antiplatelet therapy in patients with coronary stents undergoing surgery is a growing clinical problem and often represents a matter of debate between cardiologists and surgeons. It has been estimated that about 4-8% of patients undergoing coronary stenting need to undergo surgery within the next year. Surgery represents one of the most common reasons for premature antiplatelet therapy discontinuation, which is associated with a significant increase in mortality and major adverse cardiac events, in particular stent thrombosis. In addition, surgery confers an additional risk of perioperative cardiac ischemic events, being high in these patients because of the pro-inflammatory and pro-thrombotic effects of surgery. Current international guidelines recommend to postpone non-urgent surgery for at least 6 weeks after bare metal stent implantation and for 6-12 months after drug-eluting stent implantation. However, these recommendations provide little support with regard to managing antiplatelet therapy in the perioperative phase in case of urgent operations and/or high hemorrhagic risk. Furthermore, ischemic and hemorrhagic risk is not defined in detail on the basis of clinical and procedural characteristics. Finally, guidelines shared with cardiologists and surgeons are lacking. The present consensus document provides practical recommendations on the management of antiplatelet therapy in the perioperative period in patients with coronary stents undergoing surgery. Cardiologists and surgeons contributed equally to its creation. An ischemic risk stratification has been provided on the basis of clinical and procedural data. All surgical interventions have been defined on the basis of the hemorrhagic risk. A consensus on the most appropriate antiplatelet regimen in the perioperative phase has been reached on the basis of the ischemic and hemorrhagic risk. Dual antiplatelet therapy should not be withdrawn for surgery at low bleeding risk, whereas aspirin should be continued perioperatively in the majority of surgical operations. In the event of interventions at high risk for both bleeding and ischemic events, when oral antiplatelet therapy withdrawal is required, perioperative treatment with short-acting intravenous glycoprotein IIb/IIIa inhibitors (tirofiban or eptifibatide) should be considered.

We assessed the relation between female sex and sirolimus-eluting stent (SES) use on long-term outcomes in acute myocardial infarction.There are no data on sex-specific differences in long-term benefit of SES use compared with bare-metal stent (BMS) use among patients undergoing primary percutaneous coronary interventions.We performed a post hoc analysis of the MULTISTRATEGY trial. Hazard ratios (HRs) of events with 95% CI for sex and stent type were computed using Cox proportional regression with adjustment for confounders.A total of 744 patients, 64 years old (55-73 years old), 179 (24.1%) women, were enrolled. After a follow-up of 1,080 days, SES use was associated with a significant reduction of major adverse cardiovascular events, that is, the composite of all-cause death, reinfarction, or clinically driven target vessel revascularization (TVR) (13.9% vs 23.6%, adjusted HR 0.62, 95% CI 0.41-0.94, P = .026) and of TVR (6.1% vs 15.1%, adjusted HR 0.35, 95% CI 0.19-0.63, P.001) in men. Conversely, SES use was not associated to a better outcome among women (major adverse cardiovascular events 21.9% in SES vs 18.2% in the BMS group, adjusted HR 1.27, 95% CI 0.53-3.02, P = .59; TVR 6.6% vs 9.1%, adjusted HR 0.62, 95% CI 0.17-2.21, P = .46).In this analysis, the clinical benefit of SES use, over BMS, at 3-year follow-up was restricted to men and was not observed among women.

AIMS: Percutaneous coronary stenting is synonymous with dual antiplatelet therapy, ranging from four weeks to lifelong. However, even short-term (four weeks) therapy with aspirin and thienopyridines is occasionally contraindicated. No study has ever appraised very short-term dual antiplatelet therapy after stenting. We thus aimed to exploit the pro-healing features of the Genous™ Bio-engineered R stent™ (Genous) (OrbusNeich Medical Technologies, Hong Kong, People's Republic of China) and evaluate the safety of a 10-day dual antiplatelet regimen after its implantation in up to 50 patients. METHODS AND RESULTS: Forty-nine consecutive patients with de novo lesions located in vessels able to receive a 2.5 mm Genous stent were included. After stenting, they received lifelong aspirin plus clopidogrel for 10 days. The primary endpoint of the study was sudden cardiac death, myocardial infarction or angiographic evidence of stent thrombosis ascribable to the study stent. Almost 70% of patients effectively discontinued clopidogrel nine to 11 days after stenting. At three-month clinical follow-up, no patient had died or reached the primary endpoint (95%; confidence interval 0-7.3%). Repeat revascularisation occurred instead in three (6.1%[2.1-16.5%]), with target lesion revascularisation in two (4.1%[1.1-13.7%]). CONCLUSIONS: Even very short-term dual antiplatelet therapy seems safe after coronary stenting with Genous in de novo coronary artery lesions located in secondary branch vessels. This preliminary exploratory study gives some support to planning a large trial to test the hypothesis of short dual antiplatelet therapy following Genous stent implantation.

To compare the antiischemic effects of intracoronary administration of a beta blocker, atenolol, and of a calcium antagonist, nifedipine, on the clinical and electrocardiographic signs of myocardial ischemia induced by balloon occlusion of the coronary artery, we studied 32 consecutive patients undergoing routine PTCA. In each patient at least three balloon inflations were performed: the first served to verify the occurrence of ischemia (ST segment depression/elevation >1.5 mm); the second was used as a control occlusion; the third was performed after the patients were assigned to receive either atenolol 1.0 mg IC (group 1, N=16) or nifedipine V=0.2 mg IC (group 2, N=16). In a control population of 10 patients, the time to return to baseline of the ECG tended to be progressively shorter during the three consecutive inflations, but the other clinical and ECG parameters did not change significantly. In group 1 and group 2, two patients did not show ECG signs of ischemia at the third inflation; the time to ischemia increased in group 1 (+76%, p < .001) and group 2 (+85%, p < .01; NS group 1 versus group 2); ST segment displacement at 30 seconds decreased in group 1 (-38%, p < .01) and group 2 (-36%, p < .01; NS group 1 versus group 2). In group 1, 2/16 patients were symptom free, and the time to chest pain was significantly delayed (+47%, p < .01) at the third inflation; in group 2 no patient became asymptomatic at the third inflation, and the time to chest pain did not change (+5%, NS; NS group 1 versus group 2). In conclusion, the regional cardioplegia obtained through the blockade of the slow calcium channels with IC nifedipine or of the beta receptors with IC atenolol reduced myocardial ischemia to a similar extent during ballon occlusion of the coronary artery. Atenolol was also very effective on chest pain, though not significantly more than nifedipine.

We thank Dr Movahed for his interest in our study1 and for raising the issue of the classification of coronary bifurcations. The problem of finding a suitable classification of coronary bifurcations is highlighted by the fact that …

Background Mortality and morbidity after acute myocardial infarction (AMI) remain high even when myocardial reperfusion is successful. Erythropoietin (EPO) protects against experimental MI. Methods The aim of this single-centre study was to investigate the effects of short-term high-dose erythropoietin on peripheral blood cells (PBCs) and infarct size in 30 patients with a first uncomplicated AMI undergoing percutaneous coronary intervention (PCI) who were randomly assigned to treatment with EPO (33×10 3 IU before PCI, and 24 and 48h after admission), or placebo. We considered short-term CD34+ cell mobilisation, quantitative PBC gene expression in the apoptotic, angiogenic and inflammatory pathways, and enzymatically estimated infarct size. Echocardiographic and cardiac magnetic resonance studies were performed in the acute phase and six months later. Results CD34+ cell mobilisation 72h after admission was greater in the EPO-treated patient group (93cells/μl [36–217] vs 22cells/μl [6–51]; p =0.002), who also showed higher expression of the anti-apoptotic AKT and NFkB , the pro-angiogenic VEGFR-2 , and the EPO-R genes, and lower expression of the pro-apoptotic CASP3 and TP53 and pro-inflammatory IL12a genes. Moreover, they showed smaller infarct size (30% reduction in CK-MB release; p =0.025), and a favourable pattern of left ventricular remodelling. Conclusions Short-term high-dose EPO administration in patients with AMI treated by PCI and standard anti-platelet therapy increases the levels of circulating CD34+ cells, shifts PBC gene expression towards anti-apoptotic, pro-angiogenic and anti-inflammatory pathways, and decreases infarct size. The clinical relevance of these results needs to be confirmed in specifically tailored trials.

High rates of restenosis after coronary angioplasty have been reported in patients with vasospastic angina. This study was designed to determine whether the occurrence of abnormal coronary vasoconstriction, detected by means of hyperventilation testing before angioplasty, influences the risk of restenosis after successful dilation.Hyperventilation testing was performed 0 to 4 days before coronary angioplasty in 106 consecutive patients with unstable angina and single-vessel coronary artery disease. Abnormal coronary vasoconstriction was considered present if hyperventilation-induced myocardial ischemia occurred during the recovery phase of the test. All patients had follow-up angiography 8 to 12 months after angioplasty.Abnormal coronary vasoconstriction was observed in 48 patients (group 1), whereas 58 patients (group 2) had either a negative response throughout the test or a positive response only during the overbreathing phase of the hyperventilation test. Angioplasty was successful in 40 patients in group 1 and 51 in group 2. Restenosis was documented in 29 patients (73 percent) in group 1 and 13 (25 percent) in group 2 (relative risk of restenosis, 2.84; 95 percent confidence interval, 1.69 to 4.28; P less than 0.001). In a multivariate analysis, the following three characteristics were independently related to the risk of restenosis (in descending order of importance): ST-segment elevation during spontaneous ischemic attacks (P less than 0.001), hyperventilation-induced abnormal coronary vasoconstriction (P less than 0.001), and the presence of a lesion more than 10 mm long in the left anterior descending coronary artery (P less than 0.05).In patients with unstable angina and single-vessel coronary artery disease who have been selected for coronary angioplasty, the presence of hyperventilation-induced abnormal coronary vasoconstriction identifies a subgroup at high risk for restenosis.

Leukotriene C4is a potent constrictor of smooth muscle in vitro and may induce coronary vasoconstriction in vivo. To study leukotriene C4release by neutrophils in patients with coronary artery disease, neutrophils were separated from blood samples taken from the coronary sinus and aorta in 20 patients with stable exertional angina and angiographically documented coronary artery narrowings (group I). Eight patients with normal coronary arteries were also studied (group II).To assess leukotriene C4generation, neutrophils were incubated with calcium ionophore A 23187 (0.25 μM) and the supernatants obtained after centrifugation were analyzed for leukotriene C4by radioimmunoassay.Patients in group I had a significantly lower release of leukotriene C4from neutrophils separated from the coronary sinus blood than from those separated from aortic blood (4.33 ± 0.69 versus 5.92 ± 0.54 ng/ml, p < 0.025), whereas patients in group II had a similar rekase of kukotriene C4by the neutrophils separated from coronary sinus blood and from aortic blood (6.0 ± 0.72 versus 6.4 ± 0.66 ng/ml, p = NS). Moreover, in group I patients, a significant correlation was found (p < 0.01) between the extent of coronary artery disease (expressed by the Leaman coronary score) and the percent reduction in leukotriene C4released from neutrophils separated from coronary sinus blood as compared with leukotriene C4produced by neutrophils separated from aortic blood.These data show that neutrophils from patients with coronary artery disease have a reduced ability to produce leukotriene C4after stimulation by calcium ionophore A 23187. The release of leukotriene C4from neutrophils passing through a diseased coronary tree may contribute to the development of the inappropriate vasoconstriction associated with the endothelial dysfunction of atherosclerotic coronary vessels.

Background— Sirolimus-eluting stents have been reported to be effective in the treatment of coronary bifurcations. Still, it has not been fully clarified which strategy would provide the best results with true bifurcation lesions. Methods and Results— The CACTUS trial (Coronary bifurcations: Application of the Crushing Technique Using Sirolimus-eluting stents) is a prospective, randomized, multicenter study comparing 2 different techniques of stenting, with mandatory final kissing-balloon inflation, in true bifurcations: (1) elective “crush” stenting and (2) stenting of only the main branch, with provisional side-branch T-stenting. From August 2004 to June 2007, 350 patients were enrolled in 12 European centers. The primary angiographic end point was the in-segment restenosis rate, and the primary clinical end point was the occurrence of major adverse cardiac events (cardiac death, myocardial infarction, or target-vessel revascularization) at 6 months. At 6 months, angiographic restenosis rates were not different between the crush group (4.6% and 13.2% in the main branch and side branch, respectively) and the provisional stenting group (6.7% and 14.7% in the main branch and side branch, respectively; P =NS). Additional stenting on the side branch in the provisional stenting group was required in 31% of lesions. Rates of major adverse cardiac events were also similar in the 2 groups (15.8% in the crush group versus 15% in the provisional stenting group, P =NS). Conclusions— In most bifurcations with a significant stenosis in both branches, a provisional strategy of stenting the main branch only is effective, with the need to implant a second stent on the side branch occurring in approximately one third of cases. The implantation of 2 stents does not appear to be associated with a higher incidence of adverse events at 6 months.

The effect of propranolol administration on regional coronary haemodynamics were investigated in 14 patients with stable exertional angina and isolated left anterior descending artery disease. Thermodilution was used to measure great cardiac vein flow (GCVF) and anterior regional coronary resistance (ARCR) under control conditions, at peak atrial pacing, after i.v. propranolol administration (0.1 mg kg-1) and at the peak of repeated atrial pacing. Propranolol did not change peak pacing heart rate, systolic blood pressure or double product. Peak pacing GCVF decreased slightly but non-significantly after drug administration from 84 +/- 20 to 79 +/- 24 ml min-1, while ARCR increased, but again non-significantly, from 1.36 +/- 0.44 to 1.45 +/- 0.45. Analysis of individual patient responses revealed that propranolol prolonged peak pacing time and hence peak pacing heart rate (from 126 +/- 24 to 140 +/- 23 beats min-1, P less than 0.05) in five patients. In such patients, peak pacing systolic blood pressure was lower than the pre-propranolol atrial pacing (145 +/- 35 vs 165 +/- 33, P less than 0.001) so that double product remained unchanged. Moreover, peak pacing ARCR did not change after propranolol (pre-propranolol 1.47 +/- 0.46, after propranolol 1.40 +/- 0.56 mmHg.ml-1.min, P = ns) while it increased significantly in the nine patients who did not improve after the drug (before propranolol 1.30 +/- 0.44, after propranolol 1.48 +/- 0.41 mmHg.ml-1.min, P less than 0.02). These data suggest that the response to atrial pacing after i.v. propranolol administration is variable as some patients tolerate higher heart rates while others do not.(ABSTRACT TRUNCATED AT 250 WORDS)

To determine whether percutaneous transluminal coronary angioplasty (PTCA) would lead to neutrophil activation with subsequent discharge of proteolytic enzymes, like elastase, and oxygen free radicals, like superoxide anion, blood samples were taken from the coronary sinus and aorta in 14 patients with stable angina and one-vessel disease who underwent PTCA. Neutrophils were separated by means of the Ficoll-Hypaque system and were stimulated to detect release of elastase and generation of superoxide anion. Plasma levels of elastase were also measured by an immunoenzymatic method. PTCA was successful in all patients. Plasma elastase levels increased significantly at the end of the procedure compared with pre-PTCA values both in the coronary sinus (from 129.2 +/- 16.6 to 286.6 +/- 39.7 micrograms/l, p less than 0.005) and in the aorta (from 117.4 +/- 13.6 to 258.1 +/- 41.3 micrograms/l, p less than 0.005). On the other hand, superoxide anion released in the supernatants after neutrophil stimulation by phorbol-myristate-acetate decreased after PTCA in the coronary sinus (before PTCA, 60.1 +/- 7.1; after PTCA, 40.7 +/- 6.8 nmol 1 x 10(7) granulocytes/ml/15 min, p less than 0.05), whereas a mild but not significant decrease was observed in the aorta (from 58.3 +/- 10.9 to 55.3 +/- 8.6 nmol 1 x 10(7) granulocytes/ml/15 min, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

OBJECTIVES The aims of this study were to assess (i) the feasibility, safety and efficacy of sirolimus-eluting stents (SESs) in treating in-stent restenosis (ISR), (ii) the risk factors for recurrent ISR, and (iii) the long-term major adverse cardiac events (MACE). METHODS Between May 2002 and April 2004, 100 consecutive patients with evidence of myocardial ischaemia and 112 ISRs in native coronary arteries were treated using SESs. We evaluated the rate of procedural and clinical success, the incidence of in-hospital and long-term MACE, the recurrence rate of ISR after 6-8 months, and the risk factors for recurrent ISR and follow-up MACE. RESULTS Forty-five percent of the lesions were directly stented. After stent implantation, the minimal lumen diameter increased from 0.51 +/- 0.32 to 2.50 +/- 0.32 mm in the stents and to 2.30 +/- 0.35 mm in the lesions (acute gain 1.99 +/- 0.37 mm). The procedural success rate was 99%. The clinical success rate was 88%. MACE occurred in 2.0% of patients during hospitalisation and in 12.8% after a median follow-up of 15.1 months (interquartile range 8.4-19.7). The recurrence rate of ISR was 11.8% after a median follow-up of 7.7 months (interquartile range 7.4-8.4). The risk for recurrent ISR was significantly higher in patients with diabetes or hypertension, in those aged more than 65 years and in female patients, as well as in the lesions with a small minimal lumen diameter. Three-vessel disease and age were risk factors for MACE. CONCLUSIONS This study confirms the feasibility, safety and effectiveness of using SESs to treat ISR, and identifies a risk profile for recurrent ISR and MACE.

Aims We studied plasma erythropoietin (EPO) levels and their relation with CD34+VEGFR-2+ (mature and progenitor endothelial cells) and CD34+ CD133+VEGFR-2+, or CD34+ CD117+VEGFR-2+ (early/immature endothelial progenitors) cells in patients with acute myocardial infarction (AMI). Methods and results Fifty AMI patients undergoing percutaneous coronary intervention (PCI) within 6 h of symptom onset were enrolled. EPO, measured by ELISA, and cell subsets, by cytofluorimetric analysis, were evaluated before PCI, 24 h and 7 days afterwards. Forty-five healthy subjects (CTRLs) were studied. Plasma EPO levels were higher in AMI patients at admission, 24 h, and 7 days ( P = 0.04, P = 0.0001, P = 0.001, respectively) than in CTRLs. No correlation was evidenced between EPO and haemoglobin (Hb) or haematocrit at admission or 24 h after AMI. Differently, both Hb and haematocrit inversely correlated with EPO at day 7 ( P = 0.0016, P = 0.029, respectively). Plasma EPO levels correlated with CD34+CD133+VEGFR-2+ cells at day 7 ( P = 0.03). Conclusion AMI patients have increased plasma EPO levels until day 7. In the early phase, plasma EPO levels are Hb-independent; at day 7, an Hb-modulated increase of EPO correlates with the percentage of CD34+CD133+VEGFR-2+ cells.

Summary Background Coronary atherosclerotic-plaque thrombosis is a key event in the pathogenesis of unstable angina and myocardial infarction. Although plaque rupture or fissuring frequently occurs in atherosclerosis, only a small proportion of ruptured plaques develop thromboses. Methods Tissue-factor antigen and activity were measured in atherectomy samples from 50 consecutive patients with coronary artery disease (stable angina n=19, unstable angina n=24, and myocardial infarction n=7). Findings Median tissue-factor antigen and activity concentrations were significantly higher in plaques from patients with unstable angina and myocardial infarction than in those from patients with stable angina (antigen: 66·1 pg/mg [interquartile range 43·8–82] vs 32·4 pg/mg [9·8–43·4], p=0·0001; activity: 0·22 mU/mg [0·17–0·41] vs 0·13 mU/mg [0·05–0·16], p=0·0004). Interpretation Tissue-factor, an initiator of the coagulation cascade, may account for the different thrombotic responses to the rupture of human coronary atherosclerotic plaques.

The original aim of atherectomy was to reduce restenosis by means of aggressive plaque debulking, and the failure of large randomized trials to show any advantage of atherectomy over balloon angioplasty restricted its wider application. However, single-center registries in which aggressive debulking was performed by experienced operators have reported favorable results in terms of reduced restenosis and improved clinical outcomes when atherectomy was performed before stenting. Plaque debulking reduces the potential for plaque shift and facilitates subsequent high-pressure stent expansion, smoothes the internal vessel surface, scaffolds intimal flaps, and prevents elastic recoil. It has also been demonstrated that atherectomy can play a role in the treatment of complex lesions (ostial left anterior descending coronary artery lesions, left main lesions, and bifurcations), in which plaque shift may compromise the result of the procedure. New-generation devices have shown that atherectomy can be safely and effectively used to treat even relatively small vessels. In the current era of drug-eluting stents characterized by a considerable reduction in restenosis rates, optimal stent geometry and final luminal diameter are still important predictors of restenosis. Given the possible role of plaque shifting at the edges of a stent in causing restenosis, debulking could be added to the local drug effect in complex lesions.

Randomized clinical trials have shown that sirolimus-eluting stents (SESs) decrease restenosis rates compared with bare metal stents (BMSs), but their efficacy among patients who have diabetes mellitus remains to be established. This study investigated the effect of SES implantation in a high-risk population (i.e., patients who had diabetes and small coronary vessel disease). For this purpose, we analyzed outcomes of the subset of patients who had diabetes and were enrolled in the SES-SMART, a randomized trial that compared the results of implantation of SESs and BMSs in small coronary arteries. Twenty-nine patients who had diabetes were originally randomized to receive SESs and 45 patients received BMSs. The use of SESs was associated with approximately 60% decreases in the relative incidence of in-segment angiographic restenosis (63% vs 25%, p = 0.003) and in-segment late loss (0.76 vs 0.28 mm, p

Visceral artery pseudoaneurysms (PA) are a rare complication of abdominal surgery. Their natural history is generally unknown and unpredictable, so a repair is recommended. We report the case of a 77-year-old male with a huge PA of the hepatic artery diagnosed by computed tomography (CT) and treated successfully with percutaneous exclusion using a pericardium-covered stent. A staged CT confirmed the good result of the procedure.

The aim of this study was to compare the short- (30 days) and long-term (or = 30 days) clinical outcomes of left internal mammary artery bypass grafting (LIMA-LAD) and directional coronary atherectomy plus stent implantation (DCA + stent) in the treatment of isolated proximal left anterior descending coronary (LAD) lesions. One hundred and twenty-six patients underwent LIMA-LAD and 132 consecutive patients underwent DCA + stenting. The primary endpoint was the incidence of short- and long-term major adverse cardiac events (MACE); the secondary endpoints included any periprocedural events and long-term target vessel revascularization (TVR). We found no significant between-treatment difference in the occurrence of short-term MACE, and the long-term MACE rate per 100 person-years was 3.0 in the LIMA-LAD group and 4.6 in the DCA + stent group. After 5-year follow-up, 79% of the patients in the DCA + stent group and 89% of those in the LIMA-LAD group were still MACE-free. The risk of any periprocedural events was six times lower in the DCA + stent group, and the risk of TVR was six times higher. We conclude that both procedures lead to good short- and long-term follow-up results in isolated proximal LAD disease. As fewer periprocedural events and more TVRs occur after DCA + stenting than after LIMA-LAD, they can be considered valuable alternatives to each other.

Background— Apoptosis in human atherosclerotic coronary plaques possibly causes plaque destabilization by contributing to the weakening and breaking down of the fibrous cap. We tested the hypothesis that apoptosis is quantitatively increased in unstable atherosclerotic plaques. Methods and Results— We analyzed the expression of apoptotic genes such as BAX , CASP1 , FAS , FAS L , FOS , MDM2 , NFkB2 , P53 , PCNA , TERT , and XRCC1 in coronary plaques collected with directional coronary atherectomy from 15 patients with stable angina and 15 with acute coronary syndromes without ST elevation (ACS). Total RNA was extracted and cDNA was amplified with a specific set of primers and TaqMan probes. Apoptosis was also revealed by DNA laddering. To clarify the source of mRNAs, we performed in situ reverse transcriptase-polymerase chain reaction coupled with immunocytochemistry and found a substantial overlap between the mRNAs of the above genes and vascular smooth muscle cells. Gene expression analysis showed that the proapoptotic genes (ie, BAX , CASP1 , FAS , FAS L , FOS , NFkB2 , P53 , PCNA ) were significantly more expressed ( P MDM2 , TERT , XRCC1 ) were more transcribed ( P Conclusions— Our findings support the idea that ACS plaques are committed to apoptosis through an established meshwork of gene activation and inactivation, whereas stable angina plaques retain active cell homeostasis and repair mechanisms.

SummaryThe D allele of the insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene is associated with higher plasma and tissue ACE levels, which enhance the stimulus for neo-intimal hyperplasia. Plaque debulking before stenting reduces the plaque-related determinants of in-stent restenosis and provides an ideal clinical model for studying neointimal hyperplasia. We prospectively studied 113 consecutive patients undergoing elective DCA followed by stent implantation. The presence of I/D in ACE genome DNA was analysed by means of polymerase chain reaction. Follow-up coronary angiography was performed 6-12 months after DCA, and all of the angiograms were quantitatively analysed. The baseline clinical and angiographic characteristics of the patients with a D/D (33%), I/D (52%) and I/I (15%) genotype were well balanced. There were no significant differences in minimal lumen diameter before and after the procedure or at follow-up, and no significant differences in acute gain, late loss or the loss index. Our results indicate that ACE I/D polymorphism does not influence the risk of developing angiographic restenosis in patients undergoing DCA followed by stent implantation.

The study reports the results of directional atherectomy with an 8Fr guiding catheter-compatible atherectomy catheter in a series of 31 in-stent restenotic lesions. This preliminary experience indicates a favorable safety profile, with events limited to non-Q-wave myocardial infarction occurring in 3.6% of patients. The secondary end point regarding the incidence of angiographic restenosis at 6 months showed a high restenosis rate (65%).

The aim of this study was to evaluate the acute and long-term angiographic and clinical results of optimal plaque debulking by means of directional coronary atherectomy (DCA) followed by stent implantation for treatment of left anterior descending (LAD) ostial stenosis. Eighty consecutive patients (66 men; aged 57 +/- 10 years) with angina pectoris, documented anterior myocardial ischemia, and de novo LAD ostial stenosis prospectively underwent DCA and stent deployment. They were evaluated angiographically after 6 months and clinically for up to 30 +/- 29 months. The primary success rate was 98%. The in-hospital complications were 1 death due to in-stent subacute thrombosis 7 days after the procedure, 1 non-Q-wave myocardial infarction, and 1 retrograde left main artery dissection. The angiographic binary restenosis rate was 14.5%, and the loss index was 0.38 +/- 0.35. The target lesion revascularization (TLR) rates at 6, 12, and 24 months were 6.0%, 14.5%, and 16.3%, respectively, and the combined event rates (death, nonfatal myocardial infarction, TLR) at the same times were 8.7%, 17.5%, and 21.2%, respectively. These results indicate that the combined approach of DCA and stent implantation is feasible and safe in patients with LAD ostial lesions, has a high success rate, a low incidence of restenosis, and a good long-term outcome.

This study was undertaken to verify the hypothesis that the discrepant findings in published reports on the prevalence of thrombus in unstable angina depend on the inclusion of different clinical subsets in the various studies. We therefore correlated the clinical characteristics of patients included under the label of unstable angina with the morphologic features assessed by coronary angiography and intravascular ultrasound, and with histopathologic findings of atherectomy specimens. Fifty-eight patients with unstable angina (class B of the Braunwald classification) undergoing coronary arteriography followed by either coronary angioplasty (n = 20) or directional coronary atherectomy (n = 38) were studied. Fifteen patients were in class IB and 43 were in class II to IIIB. Among these 43 patients with angina at rest, 28 had ST-segment elevation during pain, and 15 had ST-segment depression, and 26 developed negative T waves on the baseline electrocardiogram (ECG) as a result of prolonged or repeated episodes of resting chest pain. Intravascular ultrasound examination of the culprit lesion was performed in 43 patients before the interventional procedure, and histopathologic analysis of atherectomy specimens was performed in 38 patients. Complex lesion morphology by angiography was observed in 31 patients (53%) without any significant relation to various clinical subsets. Patients in Braunwald class IB had more calcific plaques than patients in class II to IIIB (p < 0.001). Among patients with angina at rest, those with negative T waves on the baseline ECG, as well as those with transient ST elevation during pain, had a significantly higher incidence of noncalcific lesions (p = 0.001 for both). Analysis of atherectomy specimens revealed acute coronary lesions (thrombus and/or intraplaque hemorrhage) in 18 patients (47%). The incidence of acute coronary lesions was significantly higher in patients with than without negative T waves on the baseline ECG (p = 0.005), and increased further when negative T waves were combined with ST elevation during pain (p = 0.001). Multivariate analysis revealed that the presence orf negative T waves on the baseline ECG was the only explanatory variable related to the presence of acute coronary lesions by histology (p = 0.03). Patient subsets included in the broad spectrum of unstable angina have different morphologic features and incidence of acute coronary lesions by histology. These data provide an explanation for the discrepant findings in published reports on the relevance of thrombus formation in the pathogenesis of unstable angina.

This study was conducted to correlate the acute luminal enlargement achieved by three different nonsurgical revascularization procedures in 79 patients (32 treated by balloon angioplasty, 29 by directional atherectomy, and 18 by coronary stenting) with the morphologic characteristics of coronary plaques assessed by preprocedure intravascular ultrasound. The absolute luminal gain was 2.41 ± 1.54 mm 2 for balloon angioplasty, 3.17 ± 1.8 mm 2 for directional atherectomy, and 4.56 ± 1.45 mm 2 for coronary stenting ( p = 0.00005). However, when luminal gain was corrected for the external vessel area (luminal gain index), such difference was no longer present (0.22 ± 0.12 for balloon angioplasty, 0.24 ± 0.15 for directional atherectomy, and 0.30 ± 0.12 for coronary stenting, p = not significant). Concentric plaques treated by coronary stenting had a higher luminal gain index than eccentric plaques ( p = 0.01). A comparison of the three devices showed that a similar luminal gain index was achieved in soft plaques, whereas coronary stenting was superior to directional atherectomy (0.41 ± 0.10 vs 0.20 ± 0.09, p = 0.002) and balloon angioplasty (0.41 ± 0.10 vs 0.19 ± 0.08, p = 0.0005) in concentric plaques. Coronary stenting also induced a greater luminal gain index than directional atherectomy in calcific plaques (0.30 ± 0.11 vs 0.18 ± 0.09, p = 0.04). In conclusion, these data show that plaque morphology assessed by preprocedure intracoronary ultrasound influences the acute luminal enlargement achieved by different coronary interventions. The knowledge of plaque composition may be useful in guiding the choice of the device to be used to obtain a larger acute luminal gain.

The present study investigated the incidence of the histopathologic lesions and of growth factor expression in a consecutive series of directional coronary atherectomy (DCA) samples from 40 unstable angina pectoris patients without prior acute myocardial infarction and comfrom 18 patients with stable angina without previous infarction and 18 patients with restenosis. We investigated coronary thrombosis, neointimal hyperplasia, and inflammation. For unstable angina, we correlated the angiographic Ambrose plaque subtypes with the histopathologic findings. The immunophenotype of plaque cells ana the growth factor expression were assessed with specific antibodies for cell characterization and for the expression of basic fibrobiast and platelet-derived AA and AB growth factors and receptors. The incidence of coronary thrombosis was 35% in patients with unstable angina, 17% in those with stable angina, and 11% in patients with restenosis. Neointimal hyperplasia was found in 38% of unstable angina cases, in 17% of stable angina cases, and in 83% of restenosis cases. Inflammation without thrombus or accelerated progression occurred in 20% of unstable angina and 6% of stable angina samples. In 52% of unstable angina cases, inflammation coexisted with thrombosis and/or neointimal hyperplasia. In the unstable angina group, 71% of the plaques with thrombus had a corresponding angiographic pattern of complicated lesions. The growth factor expression, reported as percentage of cells immunostaining with different growth factor antibodies, was highest in restenosis, followed by unstable angina and stable angina lesions. We conclude that inflammation, thrombosis, and neointimal hyperplasia likely constitute the pathologic substrates of increasing coronary obstruction that causes unstable angina. Further studies are vital to elucidate whether accelerated progression results from organizing thrombosis, from inflammatory cell derived growth factors, or from both, and the extent to which inflammation and thrombosis exert reciprocal influences.