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Objectives: The study sought to investigate the relationship between post-procedural asymmetry, expansion, and eccentricity indices of metallic everolimus-eluting stent (EES) and bioresorbable vascular scaffold (BVS) and their respective impact on clinical events at 1-year follow-up., Background: Mechanical properties of a fully BVS are inherently different from those of permanent metallic stent., Methods: The ABSORB II (A bioresorbable everolimus-eluting scaffold versus a metallic everolimus-eluting stent for ischaemic heart disease caused by de-novo native coronary artery lesions) trial compared the BVS and metallic EES in the treatment of a de novo coronary artery stenosis. Protocol-mandated intravascular ultrasound imaging was performed pre- and post-procedure in 470 patients (162 metallic EES and 308 BVS). Asymmetry index (AI) was calculated per lesion as: (1 - minimum scaffold/stent diameter/maximum scaffold/stent diameter). Expansion index and optimal scaffold/stent expansion followed the definition of the MUSIC (Multicenter Ultrasound Stenting in Coronaries) study. Eccentricity index (EI) was calculated as the ratio of minimum and maximum scaffold/stent diameter per cross section. The incidence of device-oriented composite endpoint (DoCE) was collected., Results: Post-procedure, the metallic EES group was more symmetric and concentric than the BVS group. Only 8.0% of the BVS arm and 20.0% of the metallic EES arm achieved optimal scaffold/stent expansion (p < 0.001). At 1 year, there was no difference in the DoCE between both devices (BVS 5.2% vs. EES 3.1%; p = 0.29). Post-procedural devices asymmetry and eccentricity were related to higher event rates while there was no relevance to the expansion status. Subsequent multivariate analysis identified that post-procedural AI >0.30 is an independent predictor of DoCE (hazard ratio: 3.43; 95% confidence interval: 1.08 to 10.92; p = 0.037)., Conclusions: BVS implantation is more frequently associated with post-procedural asymmetric and eccentric morphology compared to metallic EES. Post-procedural devices asymmetry were independently associated with DoCE following percutaneous coronary intervention. However, this approach should be viewed as hypothesis generating due to low event rates. (ABSORB II Randomized Controlled Trial [ABSORB II]; NCT01425281)., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The purpose of this study was to compare the effect of dual antiplatelet therapy [clopidogrel + aspirin (ASA)] with respect to ASA on the protein expression of platelets from controlled type-2 diabetic patients with stable coronary ischemia. Patients had been taking ASA (100 mg day) and they were randomized to receive (n = 29) or not (n = 28) 75 mg day clopidogrel for 12 ± 2 weeks in a blind form. Protein expression was analyzed by two-dimensional electrophoresis and mass spectrometry. The protein expression of a limited number of proteins such as actin-binding protein isotypes 2 and 5, lactate dehydrogenase, serotransferrin isotype 4, protein disulfide isomerase-A3 isotype 1, fibrinogen beta chain isotype 5, Ras-related protein Rab-7b isotypes 1 and 6, and immunoglobulin heavy chain was changed after dual antiplatelet therapy. Plasma level of platelet factor 4 (PF4), an in vivo marker of platelet activity, was not different between both groups. These changes suggest lower platelet reactivity after dual antiplatelet therapy in the studied patients. However, the variation in platelet proteome was lower than it would be initially expected, taking into account the apparent clinical beneficial effects of dual antiplatelet therapy. PF4 plasma level was not further decreased in the platelets treated for a longer time than 9-12 months with ASA + clopidogrel, as compared with ASA alone., (Copyright © 2012 Wiley Periodicals, Inc.)

Aspirin resistance or aspirin non-responsiveness is a recently described phenomenon which has been consistently associated with an increased risk of cardiovascular events. This study was designed to determine the effects of an additional dose of 100 mg of aspirin on platelet function and proportion of aspirin non-responders using the platelet function analyzer-100 (PFA-100), in a well characterized population of stable coronary heart disease patients already on long-term aspirin treatment. Platelet function was assessed using PFA-100 in 141 patients (64.8 ± 10.1 years, 87.9% men) on long-term aspirin treatment (100 mg/day) before and 1 h after "in site" oral aspirin administration (100 mg). Prevalence of aspirin non-responders using PFA-100 was 50.7% (95% confidence interval 42.4-59). One hour after 100 mg of oral aspirin, reassessment of aspirin effects showed a prevalence of non-responders using PFA of 35.0% (95% CI 27.3-43.2) (P < 0.001 vs. pre-dose proportion). Using the PFA-100 system, reassessment of platelet function following oral administration of daily aspirin dosage significantly reduces the number of stable coronary disease patients considered to be non-responders to such treatment.

Background: New-generation coronary stents that release zotarolimus or everolimus have been shown to reduce the risk of restenosis. However, it is unclear whether there are differences in efficacy and safety between the two types of stents on the basis of prospectively adjudicated end points endorsed by the Food and Drug Administration., Methods: In this multicenter, noninferiority trial with minimal exclusion criteria, we randomly assigned 2292 patients to undergo treatment with coronary stents releasing either zotarolimus or everolimus. Twenty percent of patients were randomly selected for repeat angiography at 13 months. The primary end point was target-lesion failure, defined as a composite of death from cardiac causes, any myocardial infarction (not clearly attributable to a nontarget vessel), or clinically indicated target-lesion revascularization within 12 months. The secondary angiographic end point was the extent of in-stent stenosis at 13 months., Results: At least one off-label criterion for stent placement was present in 66% of patients. The zotarolimus-eluting stent was noninferior to the everolimus-eluting stent with respect to the primary end point, which occurred in 8.2% and 8.3% of patients, respectively (P<0.001 for noninferiority). There were no significant between-group differences in the rate of death from cardiac causes, any myocardial infarction, or revascularization. The rate of stent thrombosis was 2.3% in the zotarolimus-stent group and 1.5% in the everolimus-stent group (P=0.17). The zotarolimus-eluting stent was also noninferior regarding the degree (+/-SD) of in-stent stenosis (21.65+/-14.42% for zotarolimus vs. 19.76+/-14.64% for everolimus, P=0.04 for noninferiority). In-stent late lumen loss was 0.27+/-0.43 mm in the zotarolimus-stent group versus 0.19+/-0.40 mm in the everolimus-stent group (P=0.08). There were no significant between-group differences in the rate of adverse events., Conclusions: At 13 months, the new-generation zotarolimus-eluting stent was found to be noninferior to the everolimus-eluting stent in a population of patients who had minimal exclusion criteria. (ClinicalTrials.gov number, NCT00617084.), (2010 Massachusetts Medical Society)

Objectives: We evaluated the pharmacokinetics of the eluted everolimus by assessing systemic drug release and distribution of everolimus-eluting stents., Background: Drugs eluted by a coronary stent might cause adverse events such as tumors, infections, or noncardiac death. The systemic exposure of the drugs is unknown because there are only limited data about pharmacokinetics of drug-eluting stents in humans., Methods: Venous blood samples in a subset of 39 patients were drawn just before implantation of the first stent (baseline, 0-minute time point) and at 10 and 30 minutes and 1, 2, 4, 6, 12, 24, 36, 48, 72, 168, and 720 hours (30 days) after completion of implantation of the last stent. Whole blood concentrations of everolimus were determined using a sensitive validated high-performance liquid chromatography mass spectrometry/mass spectrometry method., Results: The total dose of everolimus received by the patients ranged from 53 to 588 microg. The last time point up to which whole blood concentrations could be quantified ranged per patient from 4 to 720 hours after implantation of the last stent. Across all dose levels, individual T(max) values ranged from 0.13 and 2.17 hours; individual C(max) ranged from 0.14 to 2.79 ng/mL., Conclusion: This study confirms the limited exposure to the systemic circulation of the eluted drug with the use of the XIENCE V Everolimus-Eluting Coronary Stent System (Abbott Vascular, Santa Clara, CA). Therefore, a systemic cause of adverse events is unlikely.

Objectives: The aim of this study was to examine the impact of overlapping bare-metal stent (BMS) and three different formulations of drug-eluting stent (DES) on intimal hyperplasia (IH) response of patients with diabetes mellitus (DM)., Methods: Forty-nine DM patients treated with overlapping BMS (19 lesions), sirolimus-eluting stent (SES 12 lesions), paclitaxel-eluting stent (PES 8 lesions) or tacrolimus-eluting stent (TES 10 lesions) were studied. Baseline and 9-month follow-up volumetric intravascular vascular ultrasound (IVUS) and quantitative coronary angiography (QCA) analysis were performed in the entire stented segment and in the overlapped (OL) and non-overlapped (non-OL) subsegments. Clinical outcomes were evaluated at 1-year follow-up., Results: Post-procedure (PO-) QCA measurements were similar in all stent groups, and between OL and non-OL subsegments in each individual type of stents. Percent IH was lower in SES and PES vs. BMS (p < 0.05). Percent IH was significantly greater in OL subsegment compared with non-OL subsegment in BMS (p < 0.05), but not in all type of DES groups. SES showed significantly less %IH compared with PES and TES in OL and non-OL subsegments. Vessel area at the OL remained unchanged from PO to FU in all type of DES and BMS groups. There were no aneurysm formation and no stent thrombosis up to 1-year follow-up., Conclusions: Overlapping BMS is associated with enhanced IH response in diabetic patients, whereas overlapping DES, particularly SES and PES, appear effective to inhibit IH without detectable late vascular adverse effects.

Introduction and Objectives: The aim of this study was to describe the changes observed in clinical practice in our interventional cardiology unit over the last 20 years., Methods: Between January 1, 1986 and December 31, 2005, >or=17,204 percutaneous transluminal coronary angioplasties (PTCAs) were performed at our center. They were analyzed in four periods of 5 years each. After each procedure, prospective data on patient, procedural, and outcome variables were recorded. The data were analyzed with regard to when the procedure was performed, and the patients' sex and age (i.e., < or >or=75 years). Data from 2006 were used as a reference, but were not included in the analysis., Results: The number of PTCAs increased significantly. Over the time period, mean patient age increased (from 57[10] years to 62[12] years for males and from 66[10] years to 70[11] years for females), and there were significant increases in the proportions of women (from 16% to 22%) and patients aged >75 years (from 7% to 22%). Among men, the incidence of smoking decreased while that of hypertension, diabetes and hyperlipemia increased. Among women, however, there was no change in risk factors. The numbers of urgent and emergent procedures (17% of PTCAs were for acute myocardial infarction in 2006) increased in both sexes and age groups, more ad hoc procedures were carried out, and more lesions were treated, usually with a stent. Over time, the success rate increased and the complication rate decreased in both sexes and age groups. In-hospital mortality for all procedures, except those for acute myocardial infarction, was 0.7% in males and 1.4% in females (P=.012)., Conclusions: Significant changes were observed over the last 20 years in the baseline characteristics of, the techniques used in, and the outcomes obtained in patients undergoing percutaneous coronary intervention.

Our aim was to analyze the plasma proteome in aspirin (acetylsalicylic acid [ASA])-sensitive and ASA-resistant coronary ischemic patients. Plasma from 19 ASA-sensitive and 19 ASA-resistant patients was analyzed. For the proteomic study, two-dimensional electrophoresis was performed. The expression of one isotype of the fibrinogen gamma chain and three isotypes of haptoglobin was increased in ASA-resistant patients. Three vitamin D binding protein isotypes were increased in ASA-resistant patients. In vitro incubation of vitamin D binding protein (DBP) with blood from healthy volunteers reduced the inhibitory effect of ASA on thromboxane A2 production. DBP may be a new regulator of the inhibitory effect of ASA on platelets.

Objectives: A predefined intravascular ultrasound (IVUS) substudy was performed to evaluate the vascular effects of sirolimus-eluting stent (SES) versus bare-metal stent (BMS)., Background: The Diabetes and Sirolimus-Eluting Stent (DIABETES) trial is a prospective, multicenter, randomized, controlled trial aimed at demonstrating the efficacy of the SES compared with BMS in diabetic patients., Methods: Serial intravascular ultrasound analyses were performed in 140 lesions (SES = 75; BMS = 65) immediately after stent implantation and at nine-month follow-up. Vessel, luminal, and stent mean areas and volumes were evaluated at both edges and within the stented segment. Qualitative assessment of residual dissections and stent apposition were also performed., Results: Baseline clinical and angiographic characteristics were similar between groups. At 9 months, in-stent neointimal hyperplasia (NIH) mean area and volume were significantly reduced in the SES group (median NIH area 0.01 mm2 [0.0 to 0.1] vs. 2.0 mm2 [1.0 to 2.9] and median NIH volume 0.11 mm3 [0 to 2.1] vs. 35.3 mm3 [16.6 to 62.6]; both p < 0.0001). In the SES group, stent edges evidenced significant increase in lumen dimensions mainly due to significant increase in vessel volume, whereas those of the BMS group presented vessel shrinkage leading to significant lumen reduction. Late acquired incomplete stent apposition was observed in 11 lesions (14.7%) in the SES group and 0 in the BMS group (p = 0.001). At one year, no stent thromboses occurred in malapposed stents., Conclusions: The SES implantation effectively inhibits NIH in diabetic patients. The antirestenotic effect of SES is also appreciated at the stent edges. Late acquired stent malapposition is a frequent phenomenon in diabetic patients treated with SES.

An intraluminal echolucent tissue, dubbed "black hole," has been identified by intravascular ultrasonography after intracoronary brachytherapy. This study reports the characteristics and incidence of the black hole in patients treated with drug-eluting stent implantation using a sirolimus-eluting stent (SES). We included intravascular ultrasound data from the Compassionate Use of Sirolimus-Eluting Stent (SECURE, n = 61 lesions) registry, a study involving patients in whom previous brachytherapy had failed, and the DIABETES trial (n = 165 lesions), a multicenter, randomized study comparing SES versus bare metal stents in diabetic patients. Intravascular ultrasound follow-up was scheduled at 8 months (SECURE trial, post-brachytherapy population) and 9 months (DIABETES trial). In the SECURE population, a black hole was observed in 10 patients (19.6%). Seven black hole segments had significant intimal hyperplasia (> 10%). A black hole accounted for 27% of total intraluminal tissue. In the DIABETES trial, 2 patients (2.5%) in the SES group and none in the bare metal stent group showed echolucent intimal hyperplasia. In conclusion, a black hole occurred frequently after implantation of a SES in patients in whom intracoronary brachytherapy had previously failed. Black holes were also identified in a nonirradiated population, although the incidence was lower than in the post-brachytherapy patients. Bare metal stents were not associated with this phenomenon.

Background: Among patients with acute myocardial infarction (AMI) referred for primary percutaneous coronary intervention (PCI), those with multivessel disease have worse clinical outcomes. This study sought to elucidate the impact of a chronic occlusion in a noninfarct vessel among patients with multivessel disease undergoing PCI for AMI., Methods and Results: We studied 630 patients with AMI treated with PCI within 12 hours of symptom onset. Three groups of patients were defined: Group 1 (single-vessel disease; n = 345); Group 2 (multivessel disease with no chronic coronary occlusion in another vessel; n = 201); and Group 3 (chronic coronary occlusion in another vessel; n = 84). The probability of being free from events was lower in patients with multivessel disease than in Group 1 (84 +/- 2% vs. 92 +/- 1% at 30 days; 71 +/- 3% vs. 81 +/- 3% at 2 years; Log-Rank: p = 0.001; Breslow: p < 0.001 ), and in Group 3 than in Group 2 (76 +/- 5% vs. 87 +/- 2% at 30 days; 63 +/- 6% vs.75 +/- 4% at 2 years; Log-Rank: p = 0.014; Breslow: p = 0.008 ). Freedom from cardiac death was lower in patients with multivessel disease than in Group 1 (88 +/- 2% vs. 94 +/- 1% at 30 days; 84 +/- 2% vs. 91 +/- 2% at 2 years; Log-Rank: p = 0.003; Breslow: p = 0.002), and in Group 3 than in Group 2 (82 +/- 4% vs. 90 +/- 2% at 30 days; 77 +/- 5% vs. 88 +/- 3% at 2 years; Log-Rank and Breslow: p = 0.020). Among patients with multivessel disease, the presence of cardiogenic shock, left main disease and anterior location, but not the presence of a chronic occlusion in another vessel, were independent predictors of mortality., Conclusion: Among patients with AMI and multivessel disease, those with a chronic occlusion in a noninfarct-related vessel constitute a subgroup with very poor clinical outcomes.

A broad variability in patient response to dual antiplatelet treatment has been described during the first month of treatment. Data on platelet function profiles in patients on dual antiplatelet therapy for a more sustained period are limited. Whether gene sequence variations of the glycoprotein Ia/IIa receptor influence platelet aggregation in these patients is also unknown. The aim of this study was to characterize platelet aggregation profiles in patients on dual antiplatelet treatment (aspirin plus clopidogrel) for >1 month and to assess whether these may be influenced by the C807T polymorphism of the glycoprotein Ia gene. We included 82 patients, who were divided into 2 groups: carriers (CT + TT genotypes; n = 51) and noncarriers (CC genotype; n = 31) of the mutant T allele. Platelet aggregation was assessed using light transmittance aggregometry after stimuli with adenosine diphosphate (20 micromol/L), collagen (6 microg/ml), and epinephrine (20 micromol/L). A significant variability in the distribution of platelet aggregation was observed in the overall study population, as well as in carriers and noncarriers of the T allele. T allele carriers had increased platelet aggregation compared with noncarriers after stimuli with adenosine diphosphate, collagen, and epinephrine (p <0.05 for all platelet aggregation assays). Thus, platelet aggregation varied significantly in patients on long-term dual antiplatelet treatment and was increased in T allele carriers of the 807C/T polymorphism of the glycoprotein Ia gene. These findings may contribute to the increased ischemic risk observed in these patients.

To assess platelet function profiles in diabetic and nondiabetic patients on aspirin and clopidogrel therapy, two patient populations were included to investigate the 1) acute effects of a 300-mg clopidogrel loading dose (group 1, n = 52) and 2) long-term effects of clopidogrel (group 2, n = 120) on platelet function in diabetic compared with nondiabetic patients already on aspirin treatment. Patients were stratified according to the presence of type 2 diabetes. Platelet aggregation was assessed using light transmittance aggregometry (groups 1 and 2). Platelet activation (P-selectin expression and PAC-1 binding) was determined using whole-blood flow cytometry (group 2). Clopidogrel response was also assessed. In group 1, platelet aggregation was significantly increased in diabetic (n = 16) compared with nondiabetic (n = 36) patients at baseline and up to 24 h following a 300-mg loading dose (P = 0.005). In group 2, platelet aggregation and activation were increased in diabetic (n = 60) compared with nondiabetic (n = 60) subjects (P < 0.05 for all platelet function assays). Diabetic subjects had a higher number of clopidogrel nonresponders (P = 0.04). Diabetic patients have increased platelet reactivity compared with nondiabetic subjects on combined aspirin and clopidogrel treatment. Reduced sensitivity to antiplatelet drugs may contribute to the increased atherothombotic risk in diabetic patients.

Aim: The aim of the study was to evaluate the compromise of side branches when jailed by a coronary stent implanted without balloon predilation., Patients and Methods: 56 patients in which at least a coronary stent was implanted without balloon predilation and covering a side brach (58 stents, 1.04 +/- 0.19 per patient) were studied. The effect of direct coronary stent implantation over side branch flow, as well as the characteristics associated were studied., Results: The main vessel was left anterior descending in 63%, left circumflex in 21%, right coronary in 14%, and left main in one case. An angiographic successful result in the main vessel was obtained in all cases. Coronary flow was TIMI 3, 2, 1, and 0 in 95%, 3%, 0%, and 2% before the procedure, in comparison with 86%, 2%, 3%, and 9% after stent implantation (p = 0.204). The incidence of side branch occlusion was 12% (7/58). In one case, the side branch was dilated across the stent struts, and thus the rate of side branch loss at the end of the procedure was 10% (6/58). In cases of side branch occlusion, there was a more severe stenosis at its origin before stent implantation (30.2 +/-31.3% vs 16.8 +/- 11.1%, p = 0.028). Fifty percent of side branches occluded after direct coronary stent implantation and angiographically re-evaluated at follow-up became patent, and 88% of side branches not affected after stent implantation remained patent at 6.2+/-1.9 months., Conclusion: The rate of side branch occlusion after direct stent implantation in our series was 12%, that is not different from that reported for conventional stent implantation. Thus, the decision of using direct or conventional coronary stenting should not be conditioned by the presence of side branches arising from the target lesion.

Data on percutaneous coronary intervention (PCI) in nonagenarians are very scarce. The investigators present a series of 26 nonagenarians who underwent PCI (29 lesions, 1.1 +/- 0.3 per patient). Most (96%) had acute coronary syndrome at presentation, 27% underwent primary PCI for acute myocardial infarctions, and 54% had multivessel disease. Angiographically successful results were obtained in 24 patients (92%), and coronary stents were used in 81%. Five patients (19%) died during hospitalization. In-hospital mortality was significantly greater in patients with Killip class III or IV at presentation (100% vs 9%, p = 0.001), in those in whom the procedure was a primary PCI for acute myocardial infarction (57% vs 5%, p = 0.010), and in the presence of angiographic failure (100% vs 13%, p = 0.031). In-hospital mortality was 0% after excluding patients in cardiogenic shock and those with primary PCI. Thus, most nonagenarians who undergo PCI have a high-risk profile. However, PCI achieves a successful angiographic result in most patients. Mortality is high but concentrated in patients in cardiogenic shock and with primary angioplasty as PCI.

Background: The combination of aspirin and clopidogrel remains the most frequent dual antiplatelet therapy in patients with acute coronary syndrome or undergoing percutaneous coronary intervention. Clopidogrel, a P2Y12 adenosine diphosphate (ADP) platelet receptor inhibitor requires transformation by cytochrome P450 (CYP) in the liver to produce an active metabolite. On the other hand, ivabradine is an effective antianginal drug that is also metabolized by the CYP enzyme, acting as a weak inhibitor. Our aim is to evaluate the impact of ivabradine on platelet reactivity in patients receiving clopidogrel and to evaluate the possible pharmacodynamic interactions between them. Methods: This is a prospective, observational, post-authorization pharmacodynamic study including patients treated with aspirin and clopidogrel and initiating ivabradine. Patients with platelet abnormalities and those treated with anticoagulants or other CYP inhibitors were excluded. A platelet aggregation test was performed at baseline before the first dose of ivabradine and repeated after 4 weeks of treatment. The primary endpoint was inhibition of platelet aggregation (IPA) after 20 mM ADP stimulation. Results: A total of 34 patients were initially recruited; eight patients were excluded, leaving 25 patients for final analysis. All patients had chronic ischemic heart disease. The maximum ivabradine dosage of 7.5 mg twice daily was achieved in seven patients (28%). After 4 weeks of treatment with ivabradine, no significant differences were found in maximal platelet aggregation from baseline, as assessed with 20 μM ADP stimulation. In addition, no significant difference in IPA from baseline was detected after stimulation with ADP 5 μM, arachidonic acid, thrombin receptor-activated peptide 25 μM, and platelet reactivity index. Conclusion: Ivabradine did not alter antiplatelet response to clopidogrel in patients treated concomitantly with both drugs. [ABSTRACT FROM AUTHOR]

Intravenous adenosine infusion produces coronary and systemic vasodilatation, generally leading to systemic hypotension. However, adenosine-induced hypotension during stable hyperemia is heterogeneous, and its relevance to coronary stenoses assessment with fractional flow reserve (FFR) remains largely unknown.FFR, coronary flow reserve, and index of microcirculatory resistance were measured in 93 stenosed arteries (79 patients). Clinical and intracoronary measurements were analyzed among tertiles of the percentage degree of adenosine-induced hypotension, defined as follows: %ΔPa=-[100-(hyperemic aortic pressure×100/baseline aortic pressure)]. Overall, %ΔPa was -13.6±12.0%. Body mass index was associated with %ΔPa (r=0.258; P=0.025) and obesity, an independent predictor of profound adenosine-induced hypotension (tertile 3 of %ΔPa; odds ratio, 3.95 [95% confidence interval, 1.48-10.54]; P=0.006). %ΔPa was associated with index of microcirculatory resistance (ρ=0.311; P=0.002), coronary flow reserve (r=-0.246; P=0.017), and marginally with FFR (r=0.203; P=0.051). However, index of microcirculatory resistance (β=0.003; P<0.001) and not %ΔPa (β=-0.001; P=0.564) was a predictor of FFR. Compared with tertiles 1 and 2 of %ΔPa (n=62 [66.6%]), stenoses assessed during profound adenosine-induced hypotension (n=31 [33.3%]) had lower index of microcirculatory resistance (12.4 [8.6-22.7] versus 20 [15.8-35.5]; P=0.001) and FFR values (0.77±0.13 versus 0.83±0.12; P=0.021), as well as a nonsignificant increase in coronary flow reserve (2.5±1.1 versus 2.2±0.87; P=0.170).The modification of systemic blood pressure during intravenous adenosine infusion is related to hyperemic microcirculatory resistance in the heart. Profound adenosine-induced hypotension is associated with obesity, lower coronary microcirculatory resistance, and lower FFR values. [ABSTRACT FROM AUTHOR]

Objective This prospective study sought to assess the diagnostic value of optical coherence tomography (OCT) compared with intravascular ultrasound (IVUS) in patients presenting with stent thrombosis (ST). Design and setting Although the role of IVUS in this setting has been described, the potential diagnostic value of OCT in patients suffering ST remains poorly defined. Catheterization Laboratory, University Hospital. Patients and interventions Fifteen consecutive patients with ST undergoing rescue coronary interventions under combined IVUS/OCT imaging guidance were analysed. Mean outcome measures Analysis and comparison of OCT and IVUS findings before and after interventions. Results Before intervention, OCT visualised the responsible thrombus in all patients (thrombus area 4.762.5 mm2, stent obstruction 82614%). Minimal stent area was 4.762.1 mm2 leading to severe stent underexpansion (expansion 60621%). Although red or mixed thrombus (14 patients) induced partial strut shadowing (total length 12.366 mm), malapposition (six patients), inflow-outflow disease (five patients), uncovered struts (nine patients) and associated in-stent restenosis (five patients, four showing neoatherogenesis) was clearly recognised. IVUS disclosed similar findings but achieved poorer visualisation of thrombuselumen interface and strut malapposition, and failed to recognise uncovered struts and associated neoatherosclerosis. After interventions, OCT demonstrated a reduced thrombus burden (2.461.6 mm2) and stent obstruction (24614%) with improvements in stent area (6.862.9 mm2) and expansion (75621%) (all p<0.05). IVUS and OCT findings proved to be complementary. Conclusions OCT provides unique insights on the underlying substrate of ST and may be used to optimise results in these challenging interventions. In this setting, OCT and IVUS have complementary diagnostic values. [ABSTRACT FROM AUTHOR]

Objectives: This study assessed the ability of the SYNTAX score (SXscore) to stratify risk in patients treated with percutaneous coronary intervention (PCI) using zotarolimus-eluting or everolimus-eluting stents. Background: The SXscore can identify patients treated with PCI who are at highest risk of adverse events. Methods: The SXscore was calculated prospectively in 2,033 of the 2,292 patients enrolled in the RESOLUTE All Comers study (RESOLUTE III All Comers Trial: A Randomized Comparison of a Zotarolimus-Eluting Stent With an Everolimus-Eluting Stent for Percutaneous Coronary Intervention). Clinical outcomes in terms of a patient-oriented composite endpoint (POCE) of all-cause death, myocardial infarction (MI), and repeat revascularization; the individual components of POCE; target lesion failure (TLF) (a composite of cardiac death, target-vessel MI, and clinically driven target lesion revascularization); and stent thrombosis were subsequently stratified according to SXscore tertiles: SXscoreLOW ≤9 (n = 698), 9 MID ≤17 (n = 676); SXscoreHIGH >17 (n = 659). Results: At 12-month follow-up, rates of POCE, MI, repeat revascularization, TLF, and the composite of death/MI were all significantly higher in patients in the highest SXscore tercile. Rates of stent thrombosis were all highest in the SXscoreHIGH tertile (p > 0.05). After multivariate adjustment, the SXscore was identified as an independent predictor of POCE, MI, repeat revascularization, and TLF (p < 0.05 for all). At 12-month follow-up, the SXscore, ACEF score, and Clinical SXscore had C-statistics of 0.57, 0.78, and 0.67, respectively, for mortality and of 0.62, 0.56, 0.63, respectively, for POCE. No significant between-stent differences were observed for TLF or POCE in any of the SXscore tertiles. Conclusions: The SYNTAX score is able to stratify risk amongst an all-comers population treated with PCI with second-generation drug-eluting stents (DES); however, improvements can be made with the inclusion of clinical variables. (RESOLUTE III All Comers Trial: A Randomized Comparison of a Zotarolimus-Eluting Stent With an Everolimus-Eluting Stent for Percutaneous Coronary Intervention; NCT00617084) [Copyright &y& Elsevier]

Copyright of Revista Española de Cardiología (18855857) is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revista Española de Cardiología (18855857) is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives: Our purpose was to evaluate long-term mortality and identify factors associated with 1-year mortality in patients who underwent elective percutaneous coronary intervention (PCI). Background: While long-term outcomes in PCI patients have been reported previously, limited data are currently available regarding the comparative long-term outcomes in PCI patients who receive enoxaparin versus intravenous unfractionated heparin (UFH). Methods: We conducted a follow-up analysis of clinical outcomes at 1 year in patients enrolled in the STEEPLE (SafeTy and Efficacy of Enoxaparin in Percutaneous coronary intervention patients, an internationaL randomized Evaluation) trial of 3,528 patients undergoing elective PCI. Patients were randomized to receive either intravenous 0.50-mg/kg or 0.75-mg/kg enoxaparin or intravenous UFH during elective PCI procedures. All-cause mortality at 1 year after index PCI was the main outcome measure. Results: Mortality rates were 1.4%, 2.0%, and 1.5% from 1 month to 1 year, and 2.3%, 2.2%, and 1.9% from randomization to 1 year, after index PCI in patients receiving 0.50 mg/kg enoxaparin, 0.75 mg/kg enoxaparin, and UFH, respectively. Multivariate analysis identified nonfatal myocardial infarction and/or urgent target vessel revascularization up to 30 days after index PCI (hazard ratio: 3.5, 95% confidence interval: 1.7 to 7.3; p < 0.001), and major bleeding within 48 h (hazard ratio: 3.0, 95% confidence interval: 1.1 to 8.5; p = 0.04) as the strongest independent risk factors for 1-year mortality. Conclusions: The 1-year mortality rates were low and comparable between patients receiving enoxaparin and UFH during elective PCI. Periprocedural ischemic or bleeding events were the strongest independent predictors of 1-year mortality. (The STEEPLE Trial; NCT00077844) [Copyright &y& Elsevier]

Copyright of Revista Española de Cardiología (18855857) is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: Aims: The identification of valuable markers of sudden cardiac death (SCD) in patients with established HF remains a challenge. We sought to assess the value of clinical, echocardiographic and biochemical variables to predict SCD in a consecutive cohort of patients with heart failure (HF) due to systolic dysfunction. Methods: A cohort of 494 patients with established HF had baseline echocardiographic and NT-proBNP measurements and were followed for 942±323 days. Results: Fifty patients suffered SCD. Independent predictors of SCD were indexed LA size >26 mm/m2 (HR 2.8; 95% CI 1.5–5.0; p =0.0007), NT-proBNP >908 ng/L (HR 3.1; 95% CI 1.5–6.7; p =0.003), history of myocardial infarction (HR 2.3; 95% CI 1.3–4.1; p =0.007), peripheral oedema (HR 2.1; 95% CI 1.1–3.9; p =0.02), and diabetes mellitus (HR 1.9; 95% CI 1.1–3.3; p =0.03). NYHA functional class, left ventricular ejection fraction and glomerular filtration rate were not independent predictors of SCD in this cohort. Notably, the combination of both LA size >26 mm/m2 and NT-proBNP >908 ng/L increased the risk of SCD (HR 4.3; 95% CI 2.5–7.6; p <0.0001). At 36 months, risk of SCD in patients with indexed LA size ≤26 mm/m2 and NT-proBNP ≤908 ng/L was 3%, while in patients with indexed LA size >26 mm/m2 and NT-proBNP >908 ng/L reached 25% (p <0.0001). Conclusions: Among HF patients, indexed LA size and NT-proBNP levels are more useful to stratify risk of SCD than other clinical, echocardiographic or biochemical variables. The combination of these two parameters should be considered for predicting SCD in patients with HF. [Copyright &y& Elsevier]

Copyright of Revista Española de Cardiología (18855857) is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Platelet membrane receptors play a pivotal role in thrombus formation. Expression of platelet membrane receptors are under genetic control and gene sequence variations of receptors pivotal to thrombotic formation have been hypothesized to contribute to different degrees of individual response to aspirin. The aim of the present study was to investigate the impact of functional genetic polymorphisms of platelet membrane receptors on aspirin sensitivity assessed by means of the PFA-100 system in patients with coronary artery disease. Gene sequence variations of three platelet membrane receptors (GPIa/IIa, P2Y12, GPIIb/IIIa) pivotal to thrombus formation were assessed in 76 patients with coronary artery disease on chronic aspirin treatment. Patients with reduced sensitivity to aspirin were defined when closure-times of collagen/epinephrine cartridges ≤193 seconds and coined as PFA-100 non-responders. PFA-100 non-responders were observed in 33% of patients. Patients with diabetes mellitus were more frequently PFA-100 non-responders. Closure times of collagen/ADP coated cartridges were reduced in PFA-100 non-responders. The genotype distribution was similar in PFA-100 responder and non-responder patients for all three genotypes and did not vary in contemporaneous carriers of allelic variants. In conclusion, in vitro determined sensitivity to aspirin assessed using PFA-100 is not associated with gene sequence variations of platelet membrane receptors key to thrombus formation. [ABSTRACT FROM AUTHOR]

Inflammation and platelet activation are critical phenomena in the setting of acute coronary syndromes. Platelets may contribute to increase ischemic injury by enhancing the inflammatory response of leukocytes and endothelial myocardial cells. Pharmacological inhibition of platelet activation prevents ischemic complications in patients with coronary diseases. Agents directed against the integrin glycoprotein IIb/IIIa (GP IIb/IIIa) receptor not only inhibit platelet aggregation but also have been demonstrated to limit the inflammatory response in acute coronary syndromes. The question then raised is if the inhibition of platelet activation by other mechanisms than the blockade of GP IIb/IIIa may also exert anti-inflammatory effects. The aim of the present study was to analyze if clopidogrel may exert anti-inflammatory effects during the acute phase of myocardial infarction.A ligature was placed around the left anterior descending coronary artery of New Zealand White rabbits. After 15 min of ischemia, the myocardium was reperfused and the ischemic coronary artery was isolated 24 h after the ischemia. A group of ischemic rabbits was given a single oral dose of clopidogrel (20 mg kg−1) just after the arterial occlusion and the animal was recovered. Sham-operated animals served as control.P-selectin expression was significantly increased in infarcted rabbits with respect to control rabbits. Clopidogrel administration reduced P-selectin expression with respect to untreated infarcted rabbits. CD40 ligand and tissue factor expression was increased in the ischemic coronary artery and reduced after clopidogrel administration. Clopidogrel also protected endothelial nitric oxide synthase protein expression in the ischemic coronary artery, a protein that has been found downregulated under inflammatory conditions.In conclusion, inhibition of platelet activation by clopidogrel exerted anti-inflammatory effects on the ischemic coronary artery.British Journal of Pharmacology (2005) 146, 419–424. doi:10.1038/sj.bjp.0706340; published online 25 July 2005 [ABSTRACT FROM AUTHOR]

The primary objective of the present study was to assess the feasibility and the safety of the Seaquence™ stent (CathNet-Science) deployment for the treatment of coronary artery disease and the event-free survival of patients treated with this coronary stent. The study was conducted as a multicenter, prospective, observational registry. Patients with stable or unstable angina pectoris who were candidates for percutaneous coronary intervention with elective stenting of one single de novo lesion in a native coronary artery ≥3 mm in diameter were included in the study. Clinical follow-up was performed at 1 month and 9 months. Major adverse coronary events (MACE), that is, cardiac death, myocardial infarction, and target vessel revascularization (re-PTCA or CABG), were recorded over a period of 9 months. Using this stent, a 99% in-hospital success rate was achieved. A total of 17 patients presented MACE (8.7%) during the whole follow-up period and target lesion revascularization was needed for 14 (7.1%) patients. Using multivariate analysis only some clinical parameters (patients treated for unstable angina, with a history of CABG or of female gender) were found as independent predictors of MACE after coronary stenting. Procedural related factors, angiographic characteristics, or reference diameter were not found to influence clinical outcome. Because the study was performed in patients with a high proportion of complex lesions (relative high-risk nonselected population with nearly one third calcified lesions, many long and type B2 and C lesions) we can conclude that the coronary Seaquence™ stent can be considered as a stent of reference in routine practice. (J Interven Cardiol 2004;17:9–15) [ABSTRACT FROM AUTHOR]

AIMS: This study examined the six-month angiographic results of direct coronary stenting, and compared the nine-month safety, efficacy and cost of this strategy versus stenting after balloon predilatation. METHODS: In phase I of VELVET, 122 patients (mean age = 62.3 ± 10.1 years, 77% male, 11% with diabetes) with angina pectoris or myocardial ischemia resulting from a single de novo 51% to 95% coronary stenosis underwent direct stenting. The endpoints of phase I included angiographic findings and rates of major adverse cardiac events up to six months of follow-up. In phase II, 401 patients (mean age = 61.3 ± 10.8 years, 79% male, 16% with diabetes) with angina pectoris or documented myocar-dial ischemia resulting from single or multiple, de novo or restenotic, coronary lesions were randomized between direct stenting and stenting after predilatation. The immediate angiographic results, and clinical outcomes and costs associated with the two treatment strategies up to nine months of follow-up were compared. RESULTS: In phase I the mean diameter stenosis immediately before and after the procedure, and at six months was 61.7±9.4%, 13.5±6.3%, and 33.6±16.2%, respectively. The six-month binary restenosis rate was 11%. The overall rate of major adverse cardiac events, including two non-cardiac deaths, was 9.8%. In phase II, the success rates of the intended delivery strategies were 87.9% and 97.9% for direct stenting and predi-latation, respectively (p < 0.001), while the procedural success rates were similar (93.9% vs 96.5%). Over a follow-up period of nine months, major adverse cardiac events rates were 12.0% and 10.9% in patients randomized to direct stenting and predilatation, respectively (non-significant). Analyses of the costs incurred up to nine months in each treatment group revealed a mean saving of &uro;362 per patient in favor of the direct stenting strategy (non-significant). CONCLUSIONS: Compared with a strategy of... [ABSTRACT FROM AUTHOR]

BACKGROUND: Although safety and efficacy of the NIR™ stent have been reported, the long-term angiographic and clinical outcomes have yet to be investigated. The FINESS-II study (First International NIR Endovascular Stent Study) was designed to assess the procedural safety of single 9 and 16 mm NIR stent implantation, the six-month restenosis rate and finally the six- and 12-month clinical outcome of patients treated with this novel coronary stent. METHODS: Patients with angina and a single de novo lesion in a native coronary artery of >3 and <5 mm diameter were included in this multicentre, prospective, observational trial. Clinical follow-up was obtained at one, six and 12 months. Angiography was performed before and after the stent implantation and at six months. The primary endpoint included major adverse cardiac events (death, myocardial infarction and target lesion revascularization) within 30 days after the procedure. Major bleeding complications and subacute stent thrombosis within the first 30 days were also reported as specific endpoints. Secondary endpoints were major cardiac-event-free survival at six- and 12-month follow-up and angiographic restenosis at six months. RESULTS: A total of 156 patients (81% male, mean age 60 ± 10 years), with stable (54%), unstable (40%) angina pectoris or silent ischemia (6%) were enrolled. The target vessel diameter was 2.94 ± 0.54 mm. The minimal lumen diameter pre, post and at follow-up was 1.04 ± 0.32 mm, 2.64 ± 0.42 mm and 1.88 ± 0.63 mm, respectively. Restenosis rate according to the >50% diameter stenosis criterion at six month follow-up was 19% (26/136). At 12 months, the event-free survival rate was 83% (two deaths, one Q-wave and three non-Q-wave myocardial infarctions, four bypass surgery and 17 target lesion revascularizations), while 87% of the patients were free of angina pectoris. CONCLUSION: the outcome of the FINESS-II trial is comparable to those observed in previous stent trials (Benestent II), indicating that the coronary NIR stent is safe and effective as a primary device for the treatment of native coronary artery lesions in patients with (un)stable angina pectoris. [ABSTRACT FROM AUTHOR]

The article presents a case study of an 85 year old man who presented to the emergency room of a hospital with nonradiating, midsternal chest pressure with associated dyspnea. A discussion of diagnostic testing which was conducted on the man, and led to him receiving a diagnosis of a bilateral pulmonary embolism with an unusual pattern of right ventricular wall motion, is presented.

A response by Borja Ibanez et al. to a letter to the editor about their article "Effect of Early Metoprolol on Infarct Size in ST-Segment-Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention: The Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction (METOCARD-CNIC) Trial," in the 2013 issue is presented.

In the ABSORB trial, the feasibility of using a fully bioabsorbable everolimus-eluting stent (BVS; Abbott Vascular, Santa Clara, CA) in patients with ischemia and a single de novo coronary lesion was investigated. Some important concerns about the efficacy of this device were raised by this study. The in-stent late loss with the BVS (0.44 mm) was comparable to that seen with some drug-eluting stents currently on the market, and the late lumen loss was primarily due to reduction in stent area. Technical improvements aimed at definitively preventing late vessel recoil and negative remodeling, as well as clarification of the behavior of these devices with longer follow-up, are needed before fully bioabsorbable drug-eluting stents can be considered a therapeutic option for patients with coronary artery disease. [ABSTRACT FROM AUTHOR]

Background: Patients with small coronary arteries are at high risk for complications after percutaneous coronary intervention (PCI). The objective of our study was to investigate the correlation between angiography, intravascular ultrasound (IVUS), and fractional flow reserve (FFR) in patients with moderate stenoses in small (<2.8 mm) coronary arteries. Methods and Results: Sixty consecutive patients, of 800 scheduled for PCI during the study period, were prospectively enrolled in the study. The FFR was measured after a 2-minute infusion of adenosine. For the preprocedural assessments, 60 patients underwent an FFR measurement, 56 underwent an IVUS, and 60 underwent an angiography; for the postprocedural assessments, 22 patients underwent an FFR measurement, 18 underwent an IVUS, and 22 underwent an angiography. The jeopardy score for the target vessel was calculated. Data were analyzed by an independent core laboratory. Patients with an FFR >0.75 were deferred from PCI. Patients were stratified in 2 groups according to their FFR values (≤0.75 vs >0.75) and were followed for 1 year. Significant (FFR ≤0.75) coronary stenosis was observed in only 35% of the patients. The mean preprocedural FFR values were 0.79 ± 0.13 for the overall population, 0.64 ± 0.08 for the patients with an FFR ≤0.75, and 0.87 ± 0.06 for the patients with an FFR >0.75. There was no correlation between angiography, IVUS, and FFR. The jeopardy score was inversely correlated with FFR (R = −0.32). Only a third of the patients with optimal stenting defined by IVUS achieved an FFR >0.90. After 1 year, 24% of the patients with an FFR ≤0.75 required a repeat PCI. There was no occurrence of myocardial infarction or death, and only 2.6% of the patients deferred from PCI required revascularization. Conclusion: Anatomical parameters are limited in determining the hemodynamic significance of small coronary disease. Most moderate stenoses in small coronaries could be safely deferred from PCI based on FFR. [Copyright &y& Elsevier]

Objectives: We sought to evaluate the impact of unstable coronary artery disease (CAD) on short- and mid-term outcomes in patients with multivessel disease treated by multiple sirolimus-eluting stents (SES) as part of ARTS II (Arterial Revascularization Therapies Study Part II). Background: The differential safety/efficacy profile of SES when implanted in patients with unstable angina (UA) in comparison with stable angina (SA) undergoing multivessel intervention is largely unknown. Methods: Between February 2003 and November 2003, 607 patients at 45 participating centers were treated; 221 of them (36%) presented with UA. Results: At 30 days, the cumulative rate of death, myocardial infarction—defined as any creatine kinase (CK)/CK-myocardial band elevation beyond the upper limit of normal—cerebrovascular accident, and repeat revascularization (i.e., major adverse cardiac and cerebrovascular events [MACCEs]) was 19.9% in both groups. Angiographic subacute stent occlusion was documented in 1 (0.5%) and 4 (1%) patients in the UA and SA groups, respectively. At 1 year, the cumulative incidence of MACCEs was 27.1% in the UA and 24.9% in the SA group (p = 0.56). Two late occlusions occurred, both in the SA group. After adjustment for baseline and procedural characteristics, the presence of UA was not identified as an independent predictor of MACCE (hazard ratio 0.94; 95% confidence interval 0.41 to 2.12; p = 0.88). These findings remained consistent after increasing the CK/CK-myocardial band threshold to define periprocedural myocardial infarction up to at least 3 or 5 times the upper limit of normal. Conclusions: In ARTS II, an unstable clinical presentation did not exert a negative impact on short- and mid-term outcome after SES implantation for multivessel disease. (ARTS II Trial; http://clinicaltrials.gov/ct/show/NCT00235170?order=1; NCT00235170). [Copyright &y& Elsevier]

A polymorphic marker of the gene encoding the interleukin-1 (IL-1) receptor antagonist has been recently reported to be associated with risk of coronary artery disease. However, no prospective studies of the IL-1 gene cluster in relation to the occurrence of restenosis, a major complication of percutaneous transluminal coronary angioplasty (PTCA), have so far been conducted. We had the opportunity to investigate this question in a large, prospective cohort characterized by quantitative coronary angiography in all subjects. The IL1A A114S, IL1B −511C>T, IL1B 3953T>C, IL1RI exon1B T>C, and IL1RN VNTR (intron 2) polymorphisms were characterized in a cohort of 779 patients of whom 342 (“cases”) had developed restenosis (as defined by >50% loss of lumen compared to immediate post-procedure results) at repeat angiography at 6 months post-PTCA. All observed genotype frequencies were in Hardy–Weinberg equilibrium. Frequencies for the rare alleles were: IL1A S, 0.29 (cases), 0.28 (controls); IL1B T, 0.31 (cases), and 0.33 (controls); IL1B C, 0.23 (cases), 0.24 (controls); IL1RI C, 0.34 (cases), 0.35 (controls); and IL1RN 2, 0.29 (cases), 0.29 (controls), respectively. There was no evidence for an association between genotype and restenosis or degree of lumen loss (adjusted for covariables). Our data indicate that the common variants in the IL-1 cluster genes are not associated with incidence of restenosis after PTCA. [Copyright &y& Elsevier]

Background: Although previous observational studies have documented late luminal enlargement and expansive remodeling following implantation of a bioresorbable vascular scaffold (BVS), no comparison with metallic stents has been conducted in a randomized fashion.Objectives: This study sought to compare vessel remodeling patterns after either Absorb BVS or Xience metallic drug-eluting stent (DES) implantation (Abbott Vascular, Santa Clara, California) and determine the independent predictors of remodeling.Methods: In the ABSORB II randomized trial, 383 lesions (n = 359) were investigated by intravenous ultrasound both post-procedure and at 3-year follow-up. According to vessel and lumen area changes over 3 years, we categorized 9 patterns of vessel remodeling that were beyond the reproducibility of lumen and vessel area measurements.Results: The relative change in mean vessel area was significantly greater with the BVS compared to the DES (6.7 ± 12.6% vs. 2.9 ± 11.5%; p = 0.003); the relative change in mean lumen area was significantly different between the 2 arms (1.4 ± 19.1% vs. -1.9 ± 10.5%, respectively; p = 0.031). Multivariate analysis indicated that use of the BVS, female sex, balloon-artery ratio >1.25, expansion index ≥0.8, previous percutaneous coronary intervention, and higher level of low-density lipoprotein cholesterol were independent predictors of expansive remodeling. Furthermore, in the BVS arm, necrotic core pre-procedure was an independent determinant of expansive remodeling.Conclusions: Expansive vessel wall remodeling was more frequent and intense with the BVS than the metallic DES and could be determined by patient baseline characteristics and periprocedural factors. The clinical effect of the observed lumen and vessel remodeling must be investigated in further large clinical studies to optimize the clinical outcome of patients and lesions treated by bioresorbable scaffolds. (ABSORB II Randomized Controlled Trial; NCT01425281). [ABSTRACT FROM AUTHOR]

Background It is widely accepted that edema occurs early in the ischemic zone and persists in stable form for at least 1 week after myocardial ischemia/reperfusion. However, there are no longitudinal studies covering from very early (minutes) to late (1 week) reperfusion stages confirming this phenomenon. Objectives This study sought to perform a comprehensive longitudinal imaging and histological characterization of the edematous reaction after experimental myocardial ischemia/reperfusion. Methods The study population consisted of 25 instrumented Large-White pigs (30 kg to 40 kg). Closed-chest 40-min ischemia/reperfusion was performed in 20 pigs, which were sacrificed at 120 min (n = 5), 24 h (n = 5), 4 days (n = 5), and 7 days (n = 5) after reperfusion and processed for histological quantification of myocardial water content. Cardiac magnetic resonance (CMR) scans with T2-weighted short-tau inversion recovery and T2-mapping sequences were performed at every follow-up stage until sacrifice. Five additional pigs sacrificed after baseline CMR served as controls. Results In all pigs, reperfusion was associated with a significant increase in T2 relaxation times in the ischemic region. On 24-h CMR, ischemic myocardium T2 times returned to normal values (similar to those seen pre-infarction). Thereafter, ischemic myocardium-T2 times in CMR performed on days 4 and 7 after reperfusion progressively and systematically increased. On day 7 CMR, T2 relaxation times were as high as those observed at reperfusion. Myocardial water content analysis in the ischemic region showed a parallel bimodal pattern: 2 high water content peaks at reperfusion and at day 7, and a significant decrease at 24 h. Conclusions Contrary to the accepted view, myocardial edema during the first week after ischemia/reperfusion follows a bimodal pattern. The initial wave appears abruptly upon reperfusion and dissipates at 24 h. Conversely, the deferred wave of edema appears progressively days after ischemia/reperfusion and is maximal around day 7 after reperfusion. [ABSTRACT FROM AUTHOR]

Background The prospective, randomized FREEDOM (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes) trial found coronary artery bypass graft surgery (CABG) was associated with better clinical outcomes than percutaneous coronary intervention (PCI) in patients with diabetes and multivessel disease, managed with or without insulin. Objectives In this subgroup analysis of the FREEDOM trial, we examined the association of long-term clinical outcomes after revascularization in patients with insulin-treated diabetes mellitus (ITDM) compared with patients not treated with insulin. Methods A total of 1,850 FREEDOM subjects had an index revascularization procedure performed: 956 underwent PCI with drug-eluting stents (DES), and 894 underwent CABG. A total of 602 patients (32.5%) had ITDM (PCI/DES n = 325, 34%; CABG n = 277, 31%). Subjects were classified according to ITDM versus non-ITDM, with comparison of PCI/DES versus CABG for each group. Interaction analyses were performed for treatment by diabetes mellitus (DM) status alone and for treatment by DM status by coronary lesion complexity. Analyses were performed for the primary outcome composite of death/stroke/myocardial infarction (MI) using all available follow-up data. Results The overall 5-year event rate of death/stroke/MI was significantly higher in ITDM versus non-ITDM patients (28.7% vs. 19.5%, p < 0.001), which persisted even after adjustment for multiple baseline factors, angiographic complexity, and revascularization treatment group (death/stroke/MI hazard ratio [HR]: 1.35, 95% confidence interval [CI]: 1.06 to 1.73, p = 0.014). With respect to the primary composite endpoint, CABG was superior to PCI/DES in both DM types and the magnitude of treatment effect was similar (interaction p = 0.40) for ITDM (PCI vs. CABG HR: 1.21; 95% CI: 0.87 to 1.69) and non-ITDM patients (PCI vs. CABG HR: 1.46; 95% CI 1.10 to 1.94), even after adjusting for the angiographic SYNTAX score level. Based on 5-year event rates, the number needed to treat with CABG versus PCI to prevent 1 event is 12.7 in ITDM and 13.2 in non-ITDM. Conclusions In patients with diabetes and multivessel coronary artery disease, the rate of major adverse cardiovascular events (death, MI, or stroke) is higher in patients treated with insulin than in those not treated with insulin. Furthermore, we did not detect a significant difference in the magnitude of PCI versus CABG treatment effect for patients treated with insulin and those not treated with insulin. (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes [FREEDOM]; NCT00086450 ). [ABSTRACT FROM AUTHOR]

Background: In chronic ischemic heart disease, focal stenosis, diffuse atherosclerotic narrowings, and microcirculatory dysfunction (MCD) contribute to limit myocardial flow. The prevalence of these ischemic heart disease levels in fractional flow reserve (FFR) interrogated vessels remains largely unknown.Methods and Results: Using intracoronary measurements, 91 coronaries (78 patients) with intermediate stenoses were classified in 4 FFR and coronary flow reserve (CFR) agreement groups, using FFR>0.80 and CFR<2 as cutoffs. Index of microcirculatory resistance (IMR) and atherosclerotic burden (Gensini score) were also assessed. MCD was assumed when IMR≥29.1 (75(th) percentile). Fifty-four (59.3%) vessels had normal FFR, from which only 20 (37%) presented both normal CFR and IMR. Among vessels with FFR>0.80, most (63%) presented disturbed hemodynamics: abnormal CFR in 28 (52%) and MCD in 18 (33%). Vessels with FFR>0.80 presented higher IMR [adjusted mean 27.6 (95% confidence interval, 23.4-31.8)] than those with FFR≤0.80 [17.3 (95% confidence interval, 13.0-21.7), p=0.001]. Atherosclerotic burden was inversely correlated with CFR (r=-0.207, P=0.055), and in vessels with FFR>0.80 and CFR<2 (n=28, 39%), IMR had a wide dispersion (7-72.7 U), suggesting a combination of diffuse atherosclerotic narrowings and MCD. Vessels with FFR≤0.80 and normal CFR presented the lowest IMR, suggesting a preserved microcirculation.Conclusions: A substantial number of coronary arteries with stenoses showing an FFR>0.80 present disturbed hemodynamics. Integration of FFR, CFR, and IMR supports the existence of differentiated patterns of ischemic heart disease that combine focal and diffuse coronary narrowings with variable degrees of MCD. [ABSTRACT FROM AUTHOR]

Objectives: This study sought to assess the diagnostic value of optical coherence tomography (OCT) in patients with suspected spontaneous coronary artery dissection (SCAD). Background: SCAD is a rare but challenging clinical entity. Methods: Following a prospective protocol, OCT was performed in 17 consecutive patients with a clinical and angiographic suspicion of SCD from a total of 5,002 patients undergoing coronary angiography. A conservative management strategy was followed. Results: OCT ruled out the diagnosis of SCAD in 6 patients with coronary artery disease (atherosclerotic plaques and/or intracoronary thrombus). In 11 patients (age 48 ± 9 years, 9 female), OCT confirmed the presence of SCAD. A double-lumen or intramural hematoma image was visualized in all cases. However, only 3 patients presented an intimal “flap” on angiography. OCT readily identified the intimal rupture site (n = 7), the thickness (348 ± 84 μm) and length (31 ± 9 mm) of the intimomedial membrane, the area of the true (1.1 ± 0.5 mm2) and false lumen (5.9 ± 2.1 mm2), the associated intramural hematoma (n = 9), and thrombi in the true or false lumens (n = 11). Most of these findings were angiographically silent. After stenting (n = 4), OCT disclosed adequate stent coverage, expansion, and apposition, but also residual intramural hematoma at the stented site (abluminal) and at the distal vessel. Conclusions: OCT provides unique insights in patients with SCAD that allow an early diagnosis and adequate management. Most of these findings are undetectable by angiography. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to assess the association between genetic variants of the insulin receptor substrate (IRS)-1 gene, platelet function, and long-term outcomes in patients with type 2 diabetes mellitus (DM) and stable coronary artery disease while on aspirin and clopidogrel therapy. Background: The effects of pharmacogenetic determinants on platelet function and cardiovascular outcomes in type DM patients are unknown. Methods: The association between IRS-1 genetic variants, platelet function, and the risk of major adverse cardiac events (MACE) at 2 years was assessed in 187 patients with type 2 DM and stable coronary artery disease on maintenance aspirin and clopidogrel therapy. Results: Seven tag single nucleotide polymorphisms were selected. Individuals with high platelet reactivity were more frequent among carriers of the C allele (GC and CC genotypes; approximately 20% of population) of the rs956115 marker (44.4% vs. 20.5%; odds ratio: 3.1, 95% confidence interval [CI]: 1.44 to 6.67; p = 0.006). These patients were at higher risk of MACE (28.0% vs. 10.9%; hazard ratio: 2.90, 95% CI: 1.38 to 6.11; p = 0.005). The C allele carriers of the rs956115 marker were more commonly associated with a hyperreactive platelet phenotype. This was confirmed in an external validation cohort of patients with type 2 DM but not in an external validation cohort of patients without DM. Carriers of the C allele of the rs956115 marker also had a significantly higher risk of MACE compared with noncarriers (30.6% vs. 11.4%; hazard ratio: 2.88, 95% CI: 1.35 to 6.14; p = 0.006). Conclusions: Type 2 DM patients who are carriers of the C allele of the rs956115 marker of the IRS-1 gene have a hyperreactive platelet phenotype and increased risk of MACE. [ABSTRACT FROM AUTHOR]

Objectives: We sought to assess the impact of renal function on platelet reactivity in patients with diabetes mellitus (DM) and coronary artery disease on aspirin and clopidogrel therapy. Background: Diabetes mellitus is a key risk factor for chronic kidney disease (CKD). In aspirin-treated DM patients the presence of moderate/severe CKD is associated with reduced clinical efficacy of adjunctive clopidogrel therapy. Whether these findings may be attributed to differences in clopidogrel-induced effects is unknown. Methods: This was a cross-sectional observational study in which DM patients taking maintenance aspirin and clopidogrel therapy were studied. Patients were categorized into 2 groups according to the presence or absence of moderate/severe CKD. Platelet aggregation after adenosine diphosphate (ADP) and collagen stimuli were assessed with light transmittance aggregometry and defined patients with high post-treatment platelet reactivity (HPPR). Markers of platelet activation, including glycoprotein IIb/IIIa activation and P-selectin expression, were also determined using flow cytometry. Results: A total of 306 DM patients were analyzed. Patients with moderate/severe CKD (n = 84) had significantly higher ADP-induced (60 ± 13% vs. 52 ± 15%, p = 0.001) and collagen-induced (49 ± 20% vs. 41 ± 20%, p = 0.004) platelet aggregation compared with those without (n = 222). After adjustment for potential confounders, patients with moderate/severe CKD were more likely to have HPPR after ADP (adjusted odds ratio: 3.8, 95% confidence interval: 1.7 to 8.5, p = 0.001) and collagen (adjusted odds ratio: 2.4; 95% confidence interval: 1.1 to 5.4; p = 0.029) stimuli. Markers of platelet activation were significantly increased in patients with HPPR. Conclusions: In DM patients with coronary artery disease taking maintenance aspirin and clopidogrel therapy, impaired renal function is associated with reduced clopidogrel-induced antiplatelet effects and a greater prevalence of HPPR. [Copyright &y& Elsevier]

Abstract: Background: Although invasive management of ST segment elevation myocardial infarction has improved the clinical outcome, cardiogenic shock (CS) remains an important issue. Our purpose was to asses the utility of the initial electrocardiogram in detecting patients who are at increased risk of CS after percutaneous coronary intervention for acute myocardial infarction. Methods: We evaluated 508 consecutive patients admitted in our Coronary Unit and treated by primary angioplasty within 12 h of an ST segment elevation myocardial infarction. Patients with cardiogenic shock at admission were excluded. Two groups were defined according to the presence of distortion of the terminal portion of the QRS in two or more adjacent leads (group 1) or the absence of this pattern (group 2). Results: There were 99 patients (20%) in group 1 and 409 (80%) in group 2. CS developed in 38 patients, 18 in group 1 (18%) and 20 in group 2 (5%), p <0.001. Seventeen patients died in hospital, 6 in group 1 (6%) and 11 in group 2 (3%), p 0.094. Multivariate analysis including clinical, electrocardiographic and angiographic variables showed distortion of the QRS as an independent predictor of cardiogenic shock (odds ratio 3.17, 95% confidence interval 1.44 to 6.96, p 0.004), together with Killip class at admission and TIMI 3 flow after revascularization. Conclusions: Distortion of the terminal portion of the QRS complex is a strong predictor of cardiogenic shock in STEMI patients. Close hemodynamic monitoring should be warranted in patients showing this electrocardiographic pattern. [Copyright &y& Elsevier]

Abstract: Background: Among patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI), those with multivessel disease have worse prognosis, mainly due to a higher frequency of cardiogenic shock (CS) at admission. The aim of this study was to identify clinical and angiographic characteristics of patients with STEMI, multivessel disease and CS at admission referred to primary PCI. Methods: We studied 630 patients with STEMI treated with primary PCI within 12 h after symptoms onset. Multivessel disease was defined as the presence of ≥50% stenosis in ≥2 major epicardial arteries. Multivessel disease was documented in 276 patients (44%), these patients comprising the study population. Clinical, angiographic and procedural variables were compared between those with and without CS. A logistic regression analysis was performed to identify the independent predictors of CS among patients with multivessel disease. Results: Among patients with multivessel disease, 45 (16%) had CS at admission. The independent predictors of CS in patients with multivessel disease were: STEMI anterior [OR 2.05; 95% CI 1.0 to 4.1; p =0.044], female gender [odds ratio (OR) 2.49; 95% confidence intervals (CI) 1.1 to 5.3; p =0.021], proximal culprit lesion [OR 3.8; 95% CI 1.7 to 8.5; p <0.001], and chronic occlusion of other coronary arteries [OR 4.48; 95% CI 2.1 to 9.1; p <0.001]. Conclusions: Among patients with STEMI and multivessel disease, CS is especially frequent in STEMI anterior, female gender, proximal culprit lesion, and chronic occlusion of other vessels. [Copyright &y& Elsevier]

Antiplatelet therapy is the cornerstone of treatment for patients with acute coronary syndromes and/or undergoing percutaneous coronary interventions. Clopidogrel, in combination with aspirin, is currently the antiplatelet treatment of choice for prevention of stent thrombosis, and clinical trials have shown that, in high-risk patients, prolonged dual antiplatelet treatment is more effective than aspirin alone in preventing major cardiovascular events. However, despite the use of clopidogrel, a considerable number of patients continue to have cardiovascular events. Numerous in vitro studies have shown that individual responsiveness to clopidogrel is not uniform in all patients and is subject to inter- and intraindividual variability. Notably, there is a growing degree of evidence that recurrence of ischemic complications may be attributed to poor response to clopidogrel. The mechanisms leading to poor clopidogrel effects are not fully elucidated and are likely multifactorial. Although the gold standard definition to assess antiplatelet drug response has not been fully established, there is sufficient evidence to support that persistence of enhanced platelet reactivity despite the use of clopidogrel is a clinically relevant entity. This paper reviews the impact of individual response variability to clopidogrel on clinical outcomes and current and future directions for its management. [Copyright &y& Elsevier]