Search

Experience with bioresorbable vascular scaffolds (BVSs) outside clinical trials is scarce, and data from "real-world" use are needed. In particular, there are few data on scaffold thrombosis (ST). We report our experience with ST in our all-comer BVS population (n = 339) and review the literature on the topic. Four cases (1.2%) of early definite ST were identified. Multiple risk factors were present in all 4 cases. Optical coherence tomography ruled out mechanical causes of ST in 2 cases, whereas scaffold underexpansion was observed in 1 case. Twelve BVS series have been published to date. Total sample size includes 1393 patients, with 13 cases of definite ST (0.9%), which is similar to long-term second-generation drug-eluting stent thrombosis rate (1.0%). Eleven of these cases were early ST (8 during the first week). Six of these 11 cases occurred in patients who received a BVS in the setting of an acute coronary syndrome (ACS). It can be speculated that the prothrombotic milieu of ACS, coupled with the unfavorable peristrut rheology of BVSs, might promote ST early after implantation, particularly if other concomitant risk factors are present.

Aim: High-density lipoproteins (HDLs) have several potentially protective vascular effects. Most clinical studies of therapies targeting HDL have failed to show benefits vs. placebo., Objective: To investigate the effects of an HDL-mimetic agent on atherosclerosis by intravascular ultrasonography (IVUS) and quantitative coronary angiography (QCA)., Design and Setting: A prospective, double-blinded, randomized trial was conducted at 51 centres in the USA, the Netherlands, Canada, and France. Intravascular ultrasonography and QCA were performed to assess coronary atherosclerosis at baseline and 3 (2-5) weeks after the last study infusion., Patients: Five hundred and seven patients were randomized; 417 and 461 had paired IVUS and QCA measurements, respectively., Intervention: Patients were randomized to receive 6 weekly infusions of placebo, 3 mg/kg, 6 mg/kg, or 12 mg/kg CER-001., Main Outcome Measures: The primary efficacy parameter was the nominal change in the total atheroma volume. Nominal changes in per cent atheroma volume on IVUS and coronary scores on QCA were also pre-specified endpoints., Results: The nominal change in the total atheroma volume (adjusted means) was -2.71, -3.13, -1.50, and -3.05 mm(3) with placebo, CER-001 3 mg/kg, 6 mg/kg, and 12 mg/kg, respectively (primary analysis of 12 mg/kg vs. placebo: P = 0.81). There was also no difference among groups for the nominal change in per cent atheroma volume (0.02, -0.02, 0.01, and 0.19%; nominal P = 0.53 for 12 mg/kg vs. placebo). Change in the coronary artery score was -0.022, -0.036, -0.022, and -0.015 mm (nominal P = 0.25, 0.99, 0.55), and change in the cumulative coronary stenosis score was -0.51, 2.65, 0.71, and -0.77% (compared with placebo, nominal P = 0.85 for 12 mg/kg and nominal P = 0.01 for 3 mg/kg). The number of patients with major cardiovascular events was 10 (8.3%), 16 (13.3%), 17 (13.7%), and 12 (9.8%) in the four groups., Conclusion: CER-001 infusions did not reduce coronary atherosclerosis on IVUS and QCA when compared with placebo. Whether CER-001 administered in other regimens or to other populations could favourably affect atherosclerosis must await further study. Name of the trial registry: Clinicaltrials.gov; Registry's URL: http://clinicaltrials.gov/ct2/show/NCT01201837?term=cer-001&rank=2;, Trial Registration Number: NCT01201837., (© The Author 2014. Published by Oxford University Press on behalf of the European Society of Cardiology.)

We aimed to describe the impact of the vascular access used when patients are treated with primary percutaneous coronary intervention (PPCI) and to assess whether this translates into differences in angiographic outcomes. Patients with ST-elevation myocardial infarction who underwent PPCI were divided into 3 groups: successful radial access (RA), successful femoral access (FA), and Crossover (failed RA with need for bailout FA) groups. Vascular access-related time (VART) was defined as the delay in PPCI that can be attributed to vascular access-related issues. Study end point was the final corrected Thrombolysis In Myocardial Infarction frame count. Multivariable analysis was used to identify predictors of RA failure (RAF: FA + Crossover). We included 241 patients (RA, n = 172; FA, n = 49; Crossover, n = 20). Mean VART was longer in Crossover (10.3 [8.8 to 12.4] minutes), relative to RA (4.1 [3.2 to 5.5] minutes) and FA (4.6 [3.4 to 8.4] minutes, p <0.001). A similar situation was found for time-to-first device (Crossover 22.5 [20.3 to 32.0], RA 15.0 [12.0 to 19.8]; FA 17.9 [13.5 to 22.3] minutes, p <0.001) and total procedure time (Crossover 60.3 [51.6 to 71.5], RA 46.8 [38.1 to 59.7], FA 52.3 [41.9 to 74.7] minutes, p <0.001). No differences in corrected Thrombolysis In Myocardial Infarction frame count were observed (Crossover 26 [18 to 32] frames, RA 24 [18 to 32] frames, FA 25 [16 to 34] frames, p = 0.625). Killip class IV (odds ratio [OR] 3.628, 95% confidence interval [CI] 1.098 to 11.981, p = 0.035), cardiopulmonary resuscitation before arrival (OR 3.572, 95% CI 1.028 to 12.407, p = 0.045), and glomerular filtration rate (OR 0.861, 95% CI 0.758 to 0.978, p = 0.021) were independent predictors of RA failure. In conclusion, in the setting of PPCI, radial-to-FA crossover can lead to VART delays that do not affect angiographic outcomes, in comparison with successful RA., (Copyright © 2014 Elsevier Inc. All rights reserved.)

In this case report, we provide the first detailed description of an intermittent mechanical kink of a right internal thoracic artery (ITA) graft to the left anterior descending coronary artery secondary to respiratory movements, and its assessment by pressure wire derived fractional flow reserve (FFR). The patient presented with recurrent unstable angina and documented anterior/anterolateral ischemia. Persistent symptoms were attributed to the ITA kink and stenting was planned on clinical grounds. However, the lesion proved not physiologically significant when FFR was assessed after intermittency related to respiratory movements was documented. Complex stenting was therefore avoided and medical therapy was prescribed for distal diagonal disease. We therefore propose that intermittency should be actively investigated when a kink is documented in a coronary bypass graft by conventional angiography (using dedicated angiographic evaluation in maximal inspiration and expiration). Furthermore, when this type of lesion is encountered, we suggest that it should be assessed physiologically using pressure wire derived FFR before potentially complex interventions are considered., (Copyright © 2013 Wiley Periodicals, Inc.)

Plaque rupture in atherosclerosis is the primary cause of potentially deadly coronary events, yet about 40% of ruptures occur away from the plaque cap shoulders and cannot be fully explained with the current biomechanical theories. Here, cap buckling is considered as a potential destabilizing factor which increases the propensity of the atherosclerotic plaque to rupture and which may also explain plaque failure away from the cap shoulders. To investigate this phenomenon, quasistatic 2D finite element simulations are performed, considering the salient geometrical and nonlinear material properties of diverse atherosclerotic plaques over the range of physiological loads. The numerical results indicate that buckling may displace the location of the peak von Mises stresses in the deflected caps. Plaque buckling, together with its deleterious effects is further observed experimentally in plaque caps using a physical model of deformable mock coronary arteries with fibroatheroma. Moreover, an analytical approach combining quasistatic equilibrium equations with the Navier-Bresse formulas is used to demonstrate the buckling potential of a simplified arched slender cap under intraluminal pressure and supported by foundations. This analysis shows that plaque caps - calcified, fibrotic or cellular - may buckle in specific undulated shapes once submitted to critical loads. Finally, a preliminary analysis of intravascular ultrasonography recordings of patients with atherosclerotic coronary arteries corroborates the numerical, experimental and theoretical findings and shows that various plaque caps buckle in vivo. By displacing the sites of high stresses in the plaque cap, buckling may explain the atherosclerotic plaque cap rupture at various locations, including cap shoulders., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objectives: The study aimed to evaluate inclacumab for the reduction of myocardial damage during a percutaneous coronary intervention (PCI) in patients with non-ST-segment elevation myocardial infarction., Background: P-selectin is an adhesion molecule involved in interactions between endothelial cells, platelets, and leukocytes. Inclacumab is a recombinant monoclonal antibody against P-selectin, with potential anti-inflammatory, antithrombotic, and antiatherogenic properties., Methods: Patients (N = 544) with non-ST-segment elevation myocardial infarction scheduled for coronary angiography and possible ad hoc PCI were randomized to receive 1 pre-procedural infusion of inclacumab 5 or 20 mg/kg or placebo. The primary endpoint, evaluated in patients who underwent PCI, received study medication, and had available efficacy data (n = 322), was the change in troponin I from baseline at 16 and 24 h after PCI., Results: There was no effect of inclacumab 5 mg/kg. Placebo-adjusted geometric mean percent changes in troponin I with inclacumab 20 mg/kg were -24.4% at 24 h (p = 0.05) and -22.4% at 16 h (p = 0.07). Peak troponin I was reduced by 23.8% (p = 0.05) and area under the curve over 24 h by 33.9% (p = 0.08). Creatine kinase-myocardial band yielded similar results, with changes of -17.4% at 24 h (p = 0.06) and -16.3% at 16 h (p = 0.09). The incidence of creatine kinase-myocardial band increases >3 times the upper limit of normal within 24 h was 18.3% and 8.9% in the placebo and inclacumab 20-mg/kg groups, respectively (p = 0.05). Placebo-adjusted changes in soluble P-selectin level were -9.5% (p = 0.25) and -22.0% (p < 0.01) with inclacumab 5 and 20 mg/kg. There was no significant difference in adverse events between groups., Conclusions: Inclacumab appears to reduce myocardial damage after PCI in patients with non-ST-segment elevation myocardial infarction. (A Study of RO4905417 in Patients With Non ST-Elevation Myocardial Infarction [Non-STEMI] Undergoing Percutaneous Coronary Intervention; NCT01327183)., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: To conduct a meta-analysis of studies comparing immediate versus delayed stenting in populations where primary percutaneous coronary intervention (PCI) or early invasive revascularisation was the initial mode of reperfusion., Methods and Results: We identified five non-randomised studies and one randomised trial for a total of 590 patients in studies comparing immediate to delayed stenting in populations where primary PCI or early invasive revascularisation was the initial mode of reperfusion. In non-randomised studies, delayed stenting was associated with a reduction of procedure-related angiographic events (OR=0.13, 95% credible interval [CrI]: 0.03- 0.36). No differences were observed in the rates of major bleeding (OR=0.81, 95% CrI: 0.01-13.42) and major adverse cardiac events (OR=0.40, 95% CrI: 0.09-1.91), between delayed and immediate stenting. In one randomised trial, delayed stenting was associated with a reduction in myocardial infarction during hospitalisation (39% vs. 60%; relative risk [RR]=0.55, 95% confidence interval [CI]: 0.39-0.80). None of the patients assigned to delayed stenting experienced a major adverse cardiac event in the interval between the initial angiogram and the stenting., Conclusions: Delayed stent implantation is associated with better angiographic outcomes. Randomised trials are required to assess whether delayed stenting translates into better long-term cardiac outcomes.

In the present report, we review the phenotypes of coronary artery disease (CAD) patients unsuitable for revascularization procedures. We then analyze these phenotypes and propose a simple angiographic-based classification for patients with CAD unsuitable for revascularization. Under this classification, the following four distinct angiographic phenotypes are proposed: (1) suspected cardiac syndrome X; (2) limited territory at risk; (3) diffuse thread-like coronary atherosclerosis; and (4) end-stage CAD. It is hoped that such a classification system, as well as the general principles described in this report, will help to standardize the collection of epidemiological data on patients with refractory angina (RFA) and advanced CAD. It is also hoped that this system will be useful to extend the principles of clinical equipoise to the development of clinical trials of innovative therapies or devices for the treatment of RFA. Finally, we anticipate that the elaboration of this system, the first of its type in the literature, will stimulate discussion of what we feel to be a subject that has received insufficient attention in the literature, and ultimately to improved management of a challenging patient population., (Copyright © 2012 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Refractory angina (RFA) is a debilitating disease characterized by cardiac pain resistant to conventional treatments for coronary artery disease including nitrates, calcium-channel and β-adrenoceptor blockade, vasculoprotective agents, percutaneous coronary interventions, and coronary artery bypass grafting. The mortality rate of patients living with RFA is not known but is thought to be in the range of approximately 3%. These individuals suffer severely impaired health-related quality of life with recurrent and sustained pain, poor general health status, psychological distress, impaired role functioning, and activity restriction. Effective care for RFA sufferers in Canada is critically underdeveloped. These guidelines are predicated upon a 2009 Canadian Cardiovascular Society (CCS) Position Statement which identified that underlying the problem of RFA management is the lack of a formalized, coordinated, interprofessional strategy between the cardiovascular and pain science/clinical communities. The guidelines are therefore a joint initiative of the CCS and the Canadian Pain Society (CPS) and make practice recommendations about treatment options for RFA that are based on the best available evidence. Concluding summary recommendations are also made, giving direction to future clinical practice and research on RFA management in Canada., (Copyright © 2012 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Due to anatomical variability in the distribution and size of septal perforator arteries, not all patients are ideal candidates for alcohol septal ablation. Myocardial contrast echocardiography is essential in selecting the appropriate septal branch. We report a case where the target septal artery did not originate from the left anterior descending artery, but from the first diagonal branch., (Copyright © 2012 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Pulmonary hypertension is highly prevalent in advanced heart failure (HF) despite optimal medical and device therapies. The objective of this investigation was to report on a single centre's experience of open-label chronic sildenafil therapy in patients with advanced HF., Methods: We conducted a retrospective systematic medical record review of all patients evaluated at our institution for heart transplantation who had also been treated with chronic sildenafil therapy. Baseline demographics, comorbidities, and concomitant medications, as well as the results of laboratory investigations and physiological testing, were abstracted from patient medical records. Change in systolic and mean pulmonary artery pressure (PAP), transpulmonary gradient, cardiac output and cardiac index, and selected laboratory parameters was analyzed by means of the Wilcoxon rank sum test. Outcomes of interest included New York Heart Association (NYHA) functional class after 6 months of therapy and adverse effects attributable to sildenafil., Results: The 16 patients undergoing evaluation for cardiac transplantation combined for 4166 patient-days on sildenafil, with a mean dose of 102.5 ± 54.0 mg/d. None discontinued because of side effects. At 6 months, there was an improvement in the cardiac index (P = 0.014) and systolic PAP (P = 0.049) without any significant change in other hemodynamic parameters. Ten patients (62.5%) experienced an improvement in their NYHA functional class, 8 (50%) received a heart transplantation, and 2 (12.5%) improved sufficiently to be removed from the transplant list., Conclusion: Chronic sildenafil therapy was well tolerated and associated with improved functional capacity and decreased systolic PAP. Properly controlled randomized studies of the long-term usefulness of sildenafil therapy in advanced HF populations are warranted., (Copyright © 2012 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Vascular inflammation can lead to plaque instability and acute coronary syndromes (ACS). Viruses produce potent immunomodulating proteins that regulate key inflammatory pathways. A myxoma virus-derived serpin Serp-1 reduces inflammatory cell invasion and plaque growth in vascular injury models. Our objective was to evaluate the safety and efficacy of Serp-1 in patients with ACS undergoing percutaneous coronary intervention., Methods and Results: This double-blind pilot trial included 48 ACS patients undergoing percutaneous coronary intervention randomly assigned to Serp-1 at doses of 5 μg/kg (n=19) or 15 μg/kg (n=17) or to placebo (n=12). Serp-1 was given by intravenous bolus immediately before intervention and 24 and 48 hours later. Patients were assessed for safety (primary objective) and efficacy outcomes, including biomarker analysis. In-stent neointimal hyperplasia was evaluated by intravascular ultrasound at 6 months. Key safety outcomes including coagulation parameters and adverse events did not differ between Serp-1 and placebo groups. A dose-dependent reduction in troponin I levels was observed with Serp-1 at 8, 16, 24, and 54 hours (P<0.05) and in creatine kinase-MB levels at 8, 16, and 24 hours after dose (P<0.05). The composite of death, myocardial infarction, or coronary revascularization occurred in 2 of 12 patients with placebo, 5 of 19 in the low-dose group, and none of 17 patients with the high-dose (P=0.058). Intravascular ultrasound did not detect changes in neointimal hyperplasia among groups., Conclusions: This is the first study of a viral serpin demonstrating its safety in ACS patients. The significant reduction in myocardial damage biomarkers supports further assessment of Serp-1 in ACS patients undergoing stent deployment., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00243308.

Background: Left main coronary artery (LMCA) disease influences survival; however, the predictors of LMCA changes over time are incompletely understood., Methods: Paired intravascular ultrasound (IVUS) and core laboratory analyses were performed in a standardized fashion in 207 subjects (mean +/- SD age 58 +/- 10 years, 80% men). The average follow-up duration was 18 months (range 12-24 months). The IVUS measurements were first obtained at the smallest lumen area and the largest plaque area at follow-up and the corresponding positions in the LMCA were then measured at baseline., Results: The LMCA percentage of atheroma area at baseline was 38.2% +/- 11.8%, and 133 patients (64%) experienced an increase in percentage of atheroma area. Change in lumen area correlated positively with change in total vessel area (R = 0.85, P < .0001) and negatively with change in percentage of atheroma area (R = -0.58, P < .0001). Change in plaque area correlated well with change in total vessel area (R = 0.64, P < .0001) but only weakly with change in lumen area (r = 0.14, P = .039). Although LMCA length correlated negatively with baseline lumen area and total vessel area, it did not correlate with their changes over time. On multivariable analyses, current smoking predicted an increase in percentage of atheroma area (P = .0013) and plaque area (P = .0041). Height negatively predicted change in percentage of atheroma area (P = .001)., Conclusions: The LMCA lumen dimensions are more tightly linked with remodeling than with atheroma progression/regression., (Copyright (c) 2010 Mosby, Inc. All rights reserved.)

Background: Production of leukotrienes by 5-lipoxygenase (5-LO) has been linked to unstable atherosclerotic plaques and cardiovascular events. VIA-2291 is a potent 5-LO inhibitor., Methods and Results: In a double-blinded study, 191 patients were randomly assigned 3 weeks after an acute coronary syndrome to receive 25, 50, or 100 mg VIA-2291 or placebo daily for 12 weeks. The primary study end point, whole blood stimulated leukotriene LTB4 at trough drug level, was reduced in all VIA-2291 groups (P<0.0001) in a dose-dependent fashion, with approximately 80% inhibition in >90% of patients in the 100-mg group. A significant reduction of urine leukotriene LTE4 was obtained in all dose groups. No serious adverse events were considered related to study drug. A subset of 93 patients who had undergone a 64-slice coronary CT examination at baseline continued on study medication for a total of 24 weeks and underwent a repeat scan. Five of these patients withdrew or were noncompliant and 28 had nonevaluable scans. Among the 60 remaining patients, new coronary plaques were observed in 5 of 18 (27.8%) placebo-treated patients and in 2 of 42 (4.8%) VIA-2291-treated patients (P=0.01). A reduction in noncalcified plaque volume at 24 weeks versus placebo was observed in VIA-2291-treated groups in the 34 of these 60 patients in whom this end point was analyzable (P<0.01)., Conclusions: VIA-2291 reduces leukotriene production at 12 weeks after an acute coronary syndrome. Preliminary data from the CT substudy suggest that such a reduction in leukotriene production may influence atherosclerosis; however, this requires confirmation in a larger study. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00358826.

Aims/hypothesis: We sought to understand the relationships between glycaemic status and both severity and progression of coronary artery disease (CAD), the leading cause of death in diabetes., Methods: Baseline fasting blood glucose (FBG) and HbA1c (%)were measured in 426 patients with known or suspected stable CAD, who underwent coronary artery intravascular ultrasound(IVUS) at baseline and after a mean follow-up period of 664 days (range 257 to 961). The patients were categorised as normoglycaemic (n=226, 53%), or as having impaired fasting glucose (n=118, 28%) or diabetes (n=82, 19%)., Results: The maximum percentage coronary atheroma area at baseline was greater in diabetic patients (73.33+/-8.86%) than in those with normoglycaemia (69.08+/-10.43%; p=0.001) and impaired fasting glucose (69.32+/-9.59%; p=0.0031). In averaged IVUS measurements of the 30-mm target segment(n=332 participants), change in percentage atheroma area during follow-up was also greater in the diabetes (1.86+/-3.90%) than in other groups (0.28+/-3.32% and 0.56+/-2.96%,p=0.0047 global). FBG correlated with maximum percentage atheroma area at baseline (r=0.17; p=0.0003). HbA1c also correlated with maximum percentage atheroma area at baseline (r=0.26; p=0.0001) and with change in maximum plaque area (r=0.16; p=0.016). A similar pattern of results occurred with plaque volume. The relationships between diabetes or HbA1c and both IVUS measurements of plaque burden and remodelling persisted after adjustment., Conclusions/interpretation: Fasting blood glucose, HbA1c and the presence of diabetes are associated with the severity and progression of coronary atherosclerosis. These observations support the hypothesis that better glycaemic control may favourably influence CAD in patients with abnormal glucose tolerance or diabetes.

Background: Recent improvements in multidetector computed tomography (MDCT) with 64-slice scanners have allowed acquisition of a coronary study in 5 s to 6 s, with good temporal and spatial resolution. Previous studies have reported an underestimation of plaque burden by MDCT. Whether shorter scan times can allow correct assessment of plaque volume requires comparison with intravascular ultrasound (IVUS)., Methods: Patients (n=30) scheduled for coronary angiography also underwent MDCT and IVUS examinations within 96 h. MDCT examination was performed with a 64-slice scanner. Nitroglycerin was administered before all imaging procedures. MDCT, quantitative coronary angiography (QCA) and IVUS analyses were performed by observers blinded to other results. Plaque volumes were determined by MDCT and IVUS in one vessel, and maximum percentage diameter stenosis was identified in each coronary segment by MDCT and QCA., Results: The mean (+ or - SD) plaque volume was determined to be 179.1 + or - 78.9 mm(3) by MDCT and 176.1 + or - 87.9 mm(3) by IVUS. There was a strong positive correlation for plaque volume between MDCT and IVUS (r=0.84, P<0.0001). Percentage diameter stenosis assessed by MDCT and QCA also correlated well (r=0.88 per patient and r=0.87 per vessel, P<0.0001 for both). The maximum percentage diameter stenosis per vessel was 38.1 + or - 30.2% with MDCT and 34.1 + or - 27.6% with QCA. The sensitivity and specificity of MDCT in detecting stenoses above 50% per vessel were 100% and 91.0%, respectively., Conclusions: Plaque volumes measured by 64-slice MDCT and IVUS correlate well, without systematic underestimation. The sensitivity and specificity of MDCT to detect stenoses greater than 50% by QCA are excellent with the administration of nitroglycerin before imaging.

No data exist on the acute effects of statin therapy on human coronary atherosclerotic plaques. The objective of our study was to evaluate the early (<2 months) effects of newly initiated statin therapy on coronary atherosclerosis as evaluated by intravascular ultrasonography. The study population consisted of 74 patients (mean age 58 +/- 8 years) who had been included in the ERASE trial (evaluating the effects of reconstituted high-density lipoprotein infusions). All patients underwent serial intravascular ultrasonographic (IVUS) evaluation at baseline (3 +/- 2 days after an acute coronary syndrome [ACS]) and after 6 +/- 1 weeks of follow-up. Statin therapy was initiated after ACS in 36 patients who received < or =1 dose of statins before baseline IVUS examination (newly initiated statin therapy group), and 38 patients were already on a stable statin dose before the ACS (long-term statin therapy group). Atorvastatin at a dose of 40 mg/day was the most common regimen in the 2 groups. Percent changes in atheroma volume (prespecified primary efficacy parameter) were -4.71 +/- 0.96% in the newly initiated statin therapy group (p <0.0001) and -0.54 +/- 0.89% in the long-term statin therapy group (p = 0.546; p = 0.002 for comparison between groups). Median nominal changes in atheroma volume were -9.10 mm(3) (interquartile range -12.56 to -3.73, p <0.0001 vs baseline) and 1.21 mm(3) (interquartile range -6.41 to 3.76, p = 0.429 vs baseline) in the newly initiated and long-term statin therapy groups, respectively (p = 0.003 for comparison between groups). Greater decreases in total cholesterol (r = 0.25, p = 0.035), ratio of total to high-density lipoprotein cholesterol (r = 0.28, p = 0.018), and high-sensitivity C-reactive protein (r = 0.31, p = 0.046, for patients with high-sensitivity C-reactive protein measurements within 7 days after IVUS examination) were associated with larger percent changes in atheroma volume. In conclusion, newly initiated statin therapy is associated with rapid regression of coronary atherosclerosis within 2 months. This effect was in part associated with decreases in atherogenic lipid and inflammatory parameters. These results provide insight into the rapid clinical benefits of statin therapy after an ACS.

Objectives: The objective of this study was to compare the level of platelet inhibition achieved by 3 different clopidogrel loading regimens in patients undergoing elective angiography and percutaneous coronary intervention when appropriate., Background: Optimal platelet inhibition is a key therapeutic goal for patients undergoing percutaneous coronary intervention. Although 600 mg has been described as the maximum absorbed dose when given as a single bolus, the effects of 2 boluses given 24 h apart have not been described., Methods: Patients (n = 148) were randomly assigned to one of 3 regimens: Group A, clopidogrel 300 mg the day before (>or=15 h) + 75 mg the morning of the procedure; Group B, clopidogrel 600 mg the morning of the procedure (>or=2 h); and Group C, clopidogrel 600 mg the day before (>or=15 h) and 600 mg the morning of the procedure (>or=2 h). Blood samples were obtained at baseline and immediately before angiography. Peak and late platelet aggregation were measured in platelet rich plasma, with researchers blinded to treatment allocation., Results: There was a consistent difference favoring Group C in all aggregation parameters. Percent inhibition in Groups A, B, and C was 31.4%, 29.0%, and 49.5%, respectively, for peak aggregation (5 micromol/l adenosine diphosphate; p < 0.0001) and 54.1%, 57.7%, and 81.1%, respectively, for late aggregation (p < 0.0001). Similar striking reductions were observed when 20 micromol/l adenosine diphosphate was used. All comparisons between Group C and the other 2 groups were statistically significant, and those between Groups A and B were not., Conclusions: Clopidogrel 600-mg double bolus achieves greater platelet inhibition than conventional single loading doses.

Background: The antioxidant AGI-1067 was shown to reduce experimental atherosclerosis. The present study originally intended to study restenosis as a primary endpoint but was subsequently modified to primarily investigate the effects of AGI-1067 on coronary atherosclerosis., Methods and Results: This placebo-controlled randomized trial assessed the effects of AGI-1067 280 mg qd started before percutaneous coronary intervention (PCI) and administered for 12 months after PCI on atherosclerosis progression as assessed by coronary intravascular ultrasound (IVUS). Among patients with IVUS examinations considered technically adequate both at baseline and follow-up upon central laboratory assessments (n=232), plaque volume was not significantly modified with placebo (least squares mean change: -0.4mm(3), P=0.85 versus baseline), but was significantly reduced by -4.0mm(3) at end of treatment in the AGI-1067 group (P=0.001 versus baseline, P=0.12 versus placebo). LDL-cholesterol varied by -9% and +4% in the placebo and AGI-1067 groups, respectively (P<0.05 between groups), and HDL-cholesterol was reduced by 1% with placebo and 14% with AGI-1067 (P<0.05 between groups). Plasma myeloperoxidase was reduced by 6% with AGI-1067 (P<0.05) but hs-CRP was not significantly different between groups., Conclusions: Atherosclerosis regression (-4.0mm(3)) was observed in patients treated with AGI-1067, although this was not significantly different from placebo. The anti-inflammatory effect of AGI-1067 is supported by reduced levels of myeloperoxidase.

Aims: Collateral arteries are a common but inconsistent finding in coronary heart disease (CHD). We endeavoured to review the methods for coronary artery collateral assessment, the predictors and clinical importance of collateral blood flow, and the potential for therapeutic augmentation of collateral anastomoses., Methods and Results: While many methods have been used to assess collateral blood flow only a few have been formally validated. Collateral flow index, as determined by measurement of intra-coronary pressure or flow velocity, is the most robust measure of collateral flow. These techniques have led to important advances in our understanding of collateral artery function. Coronary collateral arteries may prevent myocardial ischaemia in healthy subjects and in patients with CHD. A functional collateral circulation may lead to reduced ischaemia, preservation of ventricular function, and an improved prognosis. Recent trials have demonstrated that vascular progenitor cell therapies may improve ventricular function following acute myocardial infarction, raising the possibility of effective biological treatments to improve myocardial blood flow and prognosis in CHD., Conclusions: Coronary collateral anastomoses represent a prognostically important adaptive response in patients with CHD. Therapeutic augmentation of collaterals with emerging biological therapies represents a desirable goal for treating CHD patients.

We assessed vascular changes during atherosclerosis regression. Compensatory enlargement of coronary arteries accommodates plaque burden during atherosclerosis development. Lipid-lowering therapy has altered the natural history of coronary atherosclerosis, but the arterial changes that occur during disease regression need to be clarified. Intravascular ultrasound was performed at baseline and after approximately 18 months in 432 patients with coronary disease. Mean plaque, lumen, and total vessel area were computed in a 30-mm coronary segment of interest. Mean low-density lipoprotein cholesterol level was 2.4 mmol/L, and 88% of patients received statins. Overall, changes in plaque and total vessel areas were highly correlated (r = 0.82, p <0.0001). Among the 227 patients with plaque regression, the plaque area decrease was -0.58 +/- 0.54 mm(2), and changes in total vessel and lumen areas were -1.02 +/- 1.10 and -0.44 +/- 0.86 mm(2), respectively. The decrease in plaque area correlated better with the change in total vessel area (r = 0.64, p <0.0001) than with the change in lumen area (r = 0.20, p = 0.003). The relation between plaque regression and decrease in total vessel area was significantly better (p = 0.019) for patients with a >40% atheroma area (r = 0.72; p <0.0001) than for those with

Background: Epidemiological information on patients with acute coronary syndromes managed in specialized cardiac centres is limited., Objective: To report the evolution of demographics, treatment and outcome of patients admitted to a tertiary coronary care unit (CCU) over a 17-year period., Methods: A prospective database of 18,719 patients admitted from April 1986 to March 2003 in a 21-bed CCU was analyzed., Results: From 1986 to 2003, the number of admissions increased from 937 to 1577 per year, while the length of stay declined from 7.5 to 3.5 days. The mean age increased from 58.4 to 63.4 years, and the proportion of men remained stable at approximately 70%. The use of coronary angiograms increased from 49.8% to 81.1% in all patients, while fibrinolysis dropped to 0.4%. In-hospital mortality decreased from 9% to 1.5%. The percentage of overall instrumentation (arterial line, central venous catheter, temporary pacemaker, Swan-Ganz catheter and intra-aortic balloon pump) decreased from 38% to 8.1%. From 1995 to 2003, the proportion of stenting during percutaneous transluminal coronary angioplasty increased dramatically from 0% to 86%. In the past five years, surgical revascularization has remained stable at approximately 20% of all admissions. The proportion of patients discharged with a noncoronary chest pain diagnosis has remained constant at approximately 4%., Interpretation: There has been a tremendous increase in efficiency, with an approximate doubling of the admissions turnover rate in a tertiary CCU. Patients with acute coronary syndromes are stratified faster and treated more invasively. Therapeutic advances are reflected by an almost linear 0.5% per year decrease in in-hospital mortality.

Diabetes is associated with a two- to fourfold increase in cardiovascular morbidity and mortality, and clinical manifestations of atherosclerosis are the leading causes of death in diabetic populations. Because there are reports of benefits associated with active treatment of ischemia, including revascularization, findings from pathological and angiographic studies confirming more diffuse and distal atherosclerosis in diabetic patients highlight the value of angiography to define the optimal therapeutic strategy in these patients. While coronary angiography cannot be recommended as a screening test for asymptomatic or mildly symptomatic patients with diabetes, it should be emphasized that it is necessary to determine the severity of the underlying atherosclerotic disease, especially the presence of left main, three-vessel or proximal left anterior descending artery disease in patients deemed to be at moderate or high risk on the basis of the clinical evaluation and noninvasive testing. Angiography remains the only helpful modality in determining the suitability of the coronary vessels for either percutaneous interventions or surgical bypass when indicated.

Clinicians involved in the care of patients with cardiovascular conditions have recently been confronted with an important body of literature linking inflammation and cardiovascular disease. Indeed, the level of systemic inflammation as measured by circulating levels of C-reactive protein (CRP) has been linked to prognosis in patients with atherosclerotic disease, congestive heart failure, atrial fibrillation, myocarditis, aortic valve disease and heart transplantation. In addition, a number of basic science reports suggest an active role for CRP in the pathophysiology of cardiovascular diseases. This article explores the potential role of CRP in disease initiation, progression, and clinical manifestations and reviews its role in the prediction of future events in clinical practice. Therapeutic interventions to decrease circulating levels of CRP are also reviewed.

Background: Percutaneous coronary intervention induces an early inflammatory reaction. The intensity of such a reaction as measured by high-sensitivity C-reactive protein has been correlated with recurrent ischemic events, but its association with restenosis remains uncertain., Objectives: To characterize the type and duration of the postangioplasty inflammatory reaction and to identify new inflammatory markers correlating with restenosis., Methods: Fifty-three consecutive patients who underwent successful balloon angioplasty were studied. Levels of specific inflammatory markers were measured before intervention, and at one-month and six-month follow-up. Six-month clinical and angiographic follow-up was conducted in all patients, and quantitative coronary analysis was systematically performed., Results: Levels of soluble CD40 ligand (sCD40L) and matrix metalloproteinase-2 showed a rise and fall pattern over six months, with peak levels measured at one month (P < 0.0001), while levels of soluble vascular cell adhesion molecule-1 increased after angioplasty and remained elevated at six months (P = 0.07). Plasma levels of sCD40L at one month correlated with angiographic late loss (r = 0.48, P = 0.001) and were predictive of six-month restenosis (area under receiver operating characteristic curve 0.75 [95% CI 0.61 to 0.88])., Conclusions: The results imply that inflammation persists for at least one month following angioplasty and that future therapeutic interventions targeting inflammation to prevent restenosis should be active during this period. Furthermore, the ability of sCD40L levels to predict restenosis at six months may indicate the relevance of this pathway as a therapeutic target for restenosis prevention.

Objectives: The goal of this study was to demonstrate that intravascular ultrasound (IVUS) examination of native coronary arteries does not result in an acceleration of the atherosclerotic process., Background: Intravascular ultrasound is increasingly used to assess the effects of pharmacologic agents on atherosclerosis., Methods: Intravascular ultrasound examinations of one coronary artery and coronary angiography were performed in 525 patients at baseline. Patients then underwent a follow-up angiogram 18 to 24 months later. All end points were evaluated in IVUS-related and non-IVUS arteries using quantitative coronary analysis. The study end points were the coronary change score (per-patient mean of minimum lumen diameter changes for all lesions measured), occurrence of new coronary lesions, and progression of preexistent lesions at follow-up. Acute angiographic and clinical complications were also analyzed., Results: Coronary change score was -0.06 +/- 0.23 mm and -0.05 +/- 0.21 mm for IVUS-related and non-IVUS arteries, respectively (p = 0.35). The increase in percent diameter stenosis from baseline to follow-up was 0.8 +/- 6.7% and 1.2 +/- 7.0% in the IVUS-related and non-IVUS arteries (p = 0.29). New lesions occurred in 3.6% and 3.9% of IVUS-related and non-IVUS arteries, respectively (p = 0.84). When all coronary lesions were considered, the incidence of lesion progression was not significantly different between IVUS-related (11.6%) and non-IVUS (9.8%) arteries. Coronary spasm occurred in 1.9% of IVUS procedures, and there was one case of acute occlusion with no long-term sequelae., Conclusions: Intravascular ultrasound does not significantly accelerate atherosclerosis in native coronary arteries and can be used safely to assess progression/regression in clinical trials.

Objective: The objective of this study was to determine the effects of angiotensin-converting enzyme inhibition (ACEI) versus long-acting calcium-channel blockade (CCB) on atrial fibrillation (AF) in patients with hypertension., Background: Atrial fibrillation is the most common significant cardiac arrhythmia, and angiotensin II has been implicated in its pathophysiology., Methods: This was a retrospective, longitudinal cohort study from a database of 8 million people in the U.S. Patients age > or =18 years with hypertension were eligible if they filled a prescription for either an ACEI or a CCB between January 1995 and June 1999. The use of all other antihypertensive medications was permitted. Patient chronic disease burden was assessed using a modified Charlson index. Patients were matched on a propensity score generated from a logistic regression model. A survival analysis approach was used to compare the incidence of AF between groups. The final cohorts were evaluated until June 2002, and the average follow-up was 4.5 years., Results: After cohort matching, 10,926 patients were included in the analysis and divided equally into the ACEI and CCB groups. Mean patient age was 65 years. The adjusted hazards ratio (95% confidence interval [CI]) in the ACEI versus CCB groups for the entire follow-up period was 0.85 (95% CI: 0.74 to 0.97) for new-onset AF, and the adjusted incidence ratio for AF-related hospitalizations was 0.74 (95% CI: 0.62 to 0.89)., Conclusions: Angiotensin-converting enzyme inhibition was associated with a reduced incidence of AF for patients with hypertension in a usual care setting. These results need to be confirmed in a large-scale randomized clinical trial.

Atherosclerosis is a systemic disease in which vascular inflammation plays a key role. Indeed, inflammation is closely linked to atherosclerotic disease at all stages, from silent progression to clinical manifestations. There is now strong epidemiologic evidence that mediators of inflammation, like C-reactive protein, predict cardiovascular risk independently of "classical" risk factors. Consequently, new disease-modifying drugs targeting inflammation are under investigation and may change the approach to treatment of atherosclerosis in the near future.

Purpose of Review: In this article, the authors intend to provide an update on clinical trials of pharmacologic prevention of restenosis after percutaneous coronary interventions, placed in the perspective of the use of orally administered therapy for the prevention of atherosclerosis progression and clinical events., Recent Findings: AGI-1067, the mono-succinic acid ester of probucol, is a phenolic antioxidant member of a novel class of agents termed v-protectants. It has strong antioxidant properties equipotent to those of probucol and antiinflammatory properties. It inhibits gene expression of VCAM-1 and MCP-1 and has been effective at preventing atherosclerosis in all tested animal models including the non-human primate. In the Canadian Antioxidant Restenosis Trial (CART) 1, AGI-1067 and probucol improved lumen dimensions at the site of percutaneous coronary intervention. AGI-1067 also improved luminal dimensions of non-intervened coronary reference segments in the Canadian Antioxidant Restenosis Trial, which suggests a direct antiatherosclerosis effect. Probucol reduced post-percutaneous coronary intervention restenosis and progression of carotid atherosclerosis in other clinical trials. Although statins reduce atherosclerotic events, they do not appear to have a significant effect on restenosis. The failure of folate therapy to protect against restenosis in the Folate After Coronary Intervention Trial (FACIT) occurred despite significant reductions in homocysteine levels., Summary: Prevention of both post-percutaneous coronary intervention restenosis and atherosclerosis progression with a pharmacologic agent such as AGI-1067 may be an attractive treatment paradigm. Two important trials that test the antioxidant/antiinflammatory hypothesis are ongoing with AGI-1067: the Canadian Atherosclerosis and Restenosis Trial 2, which assesses its value for the reduction of both atherosclerosis progression and post-percutaneous coronary interventions restenosis, and the Aggressive Reduction of Inflammation Stops Events (ARISE) trial which is evaluating its effects on cardiovascular events.

AGI-1067, the monosuccinic acid ester of probucol, is a phenolic antioxidant member of a novel class of agents termed vascular protectants. It has strong antioxidant properties, equipotent to those of probucol, and anti-inflammatory properties. It inhibits gene expression of vascular cell adhesion molecule-1 and monocyte chemotactic protein-1 and has been effective at preventing atherosclerosis in all tested animal models. It also improved luminal dimensions of reference segments in the percutaneous coronary intervention (PCI) vessels in the CART-1 clinical trial, which suggests a direct anti-atherosclerosis effect. Two important trials that test the antioxidant/anti-inflammatory hypothesis are ongoing with AGI-1067: the Canadian Atherosclerosis and Restenosis Trial, which assesses its value for the reduction of both atherosclerosis progression in non-PCI vessels and post-PCI restenosis, and the Aggressive Reduction of Inflammation Stops Events trial, which is evaluating the effects of AGI-1067 on hard cardiovascular outcomes.

Background: Recent reports of fatal ticlopidine-induced blood dyscrasias have led many interventional cardiologists to administer clopidogrel instead of ticlopidine for coronary stenting. Most studies have demonstrated similar outcomes and a more favourable safety profile supporting this change in practice patterns., Objectives: To assess the clinical outcomes in patients who received clopidogrel rather than ticlopidine after coronary stenting., Methods: Between June 1996 and December 1998, 652 patients received a clopidogrel-based periprocedural regimen (300 mg loading dose followed by 75 mg daily in addition to acetylsalicylic acid 325 mg daily) and 1717 patients received a ticlopidine-based regimen (500 mg loading dose followed by 250 mg bid in addition to acetylsalicylic acid 325 mg daily). In-hospital and 30-day outcomes were assessed in the two groups., Results: At 30 days, unadjusted mortality was 0.3% in the clopidogrel group versus 1.5% in the ticlopidine group, and myocardial infarction (MI) was also reduced in the clopidogrel group (4.0% versus 6.5%). No difference was found in the rate of repeat revascularization (1.4% versus 1.2%). The combination of death/MI/repeat revascularization at 30 days was reduced by 32%, an absolute difference of 2.9% (6.2% versus 9.1%). On multivariate analysis, clopidogrel was found to be an independent predictor of freedom from nonfatal MI (odds ratio [OR] 0.64, 95% CI 0.41 to 0.99, P=0.04), the composite of death or MI (OR 0.62, 95% CI 0.40 to 0.95, P=0.03) and the composite of death/MI/revascularization (OR 0.69, 95% CI 0.48 to 1.00, P=0.05)., Conclusion: After coronary stenting, in a large, nonrandomized, consecutive patient experience, clopidogrel appears to be associated with more favourable clinical outcomes than ticlopidine, without increasing the risk of bleeding or peripheral vascular complications.

Background: AGI-1067, a metabolically stable modification of probucol, is an equipotent antioxidant to probucol but is pharmacologically distinct. In a multicenter trial, we studied whether AGI-1067 reduces restenosis assessed by intravascular ultrasound (IVUS) after percutaneous coronary intervention (PCI) compared with placebo and probucol used as a positive control., Methods and Results: Two weeks before PCI, 305 patients were randomly assigned to 1 of 5 treatment groups: placebo, probucol 500 mg BID, or AGI-1067 70, 140, or 280 mg once daily. Patients were treated for 2 weeks before and 4 weeks after PCI. Baseline and 6-month follow-up IVUS were interpreted by a blinded core laboratory. Stents were used in 85% of patients. Luminal area at the PCI site at follow-up was 2.66+/-1.58 mm2 for placebo, 3.69+/-2.69 mm2 for probucol, 2.75+/-1.76 mm2 for AGI-1067 70 mg, 3.17+/-2.26 mm2 for AGI-1067 140 mg, and 3.36+/-2.12 mm2 for AGI-1067 280 mg (P=0.02 for the dose-response relationship; P< or =0.05 for AGI-1067 280 mg and probucol versus placebo). There was a mean narrowing of 5.3 mm3 of reference segment lumen in the placebo group and an enlargement in the AGI-1067 140- and 280-mg groups at follow-up (P=0.05 for 140 mg). An increase in QTc interval >60 ms occurred in 4.8% of placebo patients, 17.4% of probucol patients, and 4.8%, 2.4%, and 2.5% of patients in the AGI-1067 groups (P=0.02)., Conclusions: AGI-1067 and probucol reduce restenosis after PCI. In contrast to probucol, AGI-1067 did not cause prolongation of the QTc interval and improved lumen dimensions of reference segments, suggestive of a direct effect on atherosclerosis.

Background: Although statins have been shown to be beneficial in the management of hyperlipidemia and the reduction of cardiovascular morbidity and mortality, rates of major cardiovascular events remain high despite their use. Inhibition of the acyl coenzyme A: cholesterol acyltransferase (ACAT) enzyme in the arterial wall may prevent excess accumulation of cholesteryl esters in macrophages. In addition to ACAT inhibitor monotherapy, combination of a statin with an ACAT inhibitor may be a promising approach to further prevent the progression of atherosclerosis., Methods: This report describes the design and methodologic features of a double-blind, randomized, placebo-controlled trial to assess the effect of the ACAT inhibitor avasimibe at 50-, 250-, and 750-mg daily dosages on the progression of coronary atherosclerosis as assessed by intravascular ultrasound (IVUS). All patients receive background lipid-lowering therapy when necessary. The study population consists of patients with at least one 20% to 50% diameter stenosis in a coronary artery with a reference diameter of > or =2.5 mm. IVUS and coronary angiography are performed at baseline and repeated at 24 months. The primary study end point is the change from baseline in plaque volume in a 30-mm segment of the coronary artery assessed by 3-dimensional IVUS. Several other IVUS and angiographic end points are measured., Conclusions: The Avasimibe and Progression of coronary Lesions assessed by intravascular UltraSound (A-PLUS) trial is among the first large imaging trials to use IVUS as a primary end point and assesses the effects of the ACAT inhibitor avasimibe on atherosclerosis progression.

Background: The antioxidant probucol reduced coronary restenosis in the MultiVitamins and Probucol (MVP) trial by improving vascular remodelling. Whether calcification limits the extent of adaptive vessel enlargement is not known., Objective: To determine whether plaque composition at the dilated site affects probucol-induced vascular remodelling after angioplasty., Patients and Methods: Beginning 30 days before percutaneous transluminal coronary angioplasty (PTCA), 317 patients received either probucol, vitamins, probucol and vitamins, or placebo. Patients were then treated for six months after PTCA. Intravascular ultrasound (IVUS) was performed post-PTCA and at follow-up in 94 patients (111 segments). The cross-section for serial analysis was the one at the angioplasty site with the smallest lumen area at follow-up. Quantitative analysis consisted of measurements of lumen area and external elastic membrane (EEM) area. The selected cross-section was also divided into five regions according to the type of plaque present (calcific, fibrotic, hypoechoic, fibrohypoechoic or normal). Plaque characterization scores (PCS) (PCS for arc, area, inner perimeter and outer perimeter) were calculated using weighting factors., Results: There were no interactions between potential PCS covariates and probucol main effect on changes in lumenal, EEM and wall area. There were no significant PCS covariates in the model for change in EEM as they were all removed using a backward stepwise procedure. The last potential covariate (area PCS) had a significance level of P=0.48. In contrast, probucol significantly influenced the change in EEM over time (P=0.003)., Conclusion: Plaque composition at the dilated site does not appear to influence probucol-induced vascular remodelling after angioplasty.

Objectives: We sought to determine whether clopidogrel is at least as efficacious as ticlopidine., Background: Several trials have supported the enhanced safety and tolerability of clopidogrel compared with ticlopidine after coronary stent deployment. However, none of these individual trials were powered to detect possible differences in the efficacy for reducing ischemic end points., Methods: Published data from trials and registries that compared clopidogrel with ticlopidine in patients receiving coronary stents were pooled, and a formal meta-analysis was performed. The rate of 30-day major adverse cardiac events (MACE), as defined in each trial, was used as the primary end point., Results: There were a total of 13,955 patients. The pooled rate of major adverse cardiac events was 2.10% in the clopidogrel group and 4.04% in the ticlopidine group. After adjustment for heterogeneity in the trials, the odds ratio (OR) of having an ischemic event with clopidogrel, as compared with ticlopidine, was 0.72 (95% confidence interval [CI] 0.59 to 0.89, p = 0.002). Mortality was also lower in the clopidogrel group compared with the ticlopidine group-0.48% versus 1.09% (OR 0.55, 95% CI 0.37 to 0.82; p = 0.003)., Conclusions: Based on all available evidence from randomized clinical trials or registries, clopidogrel, in addition to better tolerability and fewer side effects, is at least as efficacious as ticlopidine in reducing MACE. This finding may be due to the more rapid onset of an antiplatelet effect seen with the loading dose of clopidogrel, which was used in most of these studies, or to better patient compliance with clopidogrel therapy. Therefore, clopidogrel plus aspirin should replace ticlopidine plus aspirin as the standard antiplatelet regimen after stent deployment.

The aim of this review is to give an overview of the field of restenosis prevention with antioxidants, put in the perspective of their potential use for the prevention of atherosclerosis progression. Compelling evidence points to oxidative stress as an important trigger in the complex chain of events leading to atherosclerosis. There is also evidence that oxidative stress occurs early after angioplasty. Reactive oxygen species (ROS) can induce endothelial dysfunction and macrophage activation, resulting in the release of cytokines and growth factors that stimulate matrix remodeling and smooth muscle cell proliferation. The accumulation of new extracellular matrix and smooth muscle cells will result in the neointimal formation responsible for lumen narrowing after stent deployment and which contributes to that after balloon angioplasty. In addition, oxidation processes are involved in the cross-linking of collagen fibers, and this coupled with smooth muscle cell contraction and endothelial dysfunction may result in long-term vascular constriction or lack of adaptive vascular remodeling after balloon angioplasty. The powerful antioxidant probucol has been shown to prevent coronary restenosis after balloon angioplasty in the Multivitamins and Probucol (MVP) trial and other clinical studies. However, prolongation of the QT interval with probucol remains a long-term safety concern. AGI-1067, a metabolically stable analog of probucol, is a vascular protectant with strong antioxidant properties as potent to those of probucol. There has been no evidence of prolongation of the QT interval with AGI-1067 in initial clinical studies. The anti-restenosis properties of AGI-1067 are being assessed in the Canadian Antioxidant Restenosis Trial (CART)-1. Considering that oxidative stress and inflammation may persist for a prolonged period after stent placement, treatment with AGI-1067 for the entire period of risk after percutaneous coronary intervention (PCI) [instead of only 4 weeks in CART-1] may result in enhanced protection against luminal renarrowing. This hypothesis will be tested in the randomized, multicenter CART-2 trial. AGI-1067 has been effective at preventing atherosclerosis in all tested animal models, including the low density lipoprotein receptor-deficient and apo-E knockout mice. This has potentially important implications, as PCI and local approaches to prevent restenosis such as coated stents are not expected to prevent atherosclerosis progression, myocardial infarction and cardiovascular death. As the ultimate goal of therapy for patients with coronary artery disease must remain prevention of disease progression and atherosclerosis-related events, CART-2 will test the value of AGI-1067 for the reduction of both post-PCI restenosis and atherosclerosis progression.

We hypothesized that certain clinical and angiographic characteristics on presentation predict suboptimal infarct artery flow after percutaneous intervention during acute myocardial infarction (AMI). The goal of angioplasty (percutaneous transluminal coronary angioplasty [PTCA]) during AMI is the prompt restoration of normal flow to achieve myocardial reperfusion. However, inadequate epicardial coronary flow is observed in 10% to 20% of patients. From 2 large randomized trials-Global Use of Strategies To open Occluded arteries in Acute Coronary Syndromes-IIb, and Randomized Placebo-Controlled Trial of Platelet glycoprotein IIb/IIIa Blockade With Primary Angioplasty for Acute Myocardial Infarction-patients undergoing primary PTCA during AMI were included in the analysis. A multivariate logistic model was used to identify factors associated with final Thrombolysis In Myocardial Infarction (TIMI) flow grade < or =2. The 891 patients were aged (mean +/- SD) 61 +/- 12 years, 75% were men, and 39% had an anterior wall AMI. Patients underwent PTCA within 4.8 +/- 3.2 hours from the onset of chest pain. The incidence of final TIMI 3 flow was 81%. TIMI flow grade < or =2 was independently associated with increasing age (odds ratio [OR] 1.39 for every 10 years, 95% confidence interval [CI] 1.19 to 1.62), increasing heart rate (OR 1.16 for every 10 beats, 95% CI 1.05 to 1.28), and presence of visible thrombus on baseline angiogram (OR 1.89, 95% CI 1.18 to 3.05). Conversely, baseline TIMI 2 or 3 flow grade (OR 0.46, 95% CI 0.28 to 0.75) and left circumflex intervention (OR 0.42, 95% CI 0.23 to 0.79) correlated with normal postprocedural coronary flow. Mortality was significantly higher in patients with TIMI < or =2 than TIMI 3 flow grade (10.2% vs 1.5%, p <0.001, respectively). Thus, angiographic evidence of thrombus and 2 pivotal clinical characteristics, advanced age and elevated heart rate, predict lack of adequate coronary reperfusion. Conversely, the presence of normal or near-normal coronary flow before intervention correlates with a good angiographic result. Mortality risk is increased in patients with postprocedural suboptimal angiographic coronary flow.

Fibrinolytic drugs given within 6-12 h of onset of symptoms have reduced mortality by approximately 30%. However, even the most efficacious regimens are associated with only a 55% reperfusion rate at 90 min. In contrast, primary angioplasty (without fibrinolysis) yields to reperfusion in 75-95% of cases. This therapy, when compared with fibrinolysis, is associated with lower early mortality and reinfarction rates. Therefore, there is a need to find a therapy that would have the speed and ease of administration of intravenous lysis and the efficacy of primary angioplasty in re-establishing normal myocardial tissue perfusion. This article will review the rationale for the use of partial-dose lytic agents combined with platelet glycoprotein IIb/IIIa inhibitors for the treatment of acute myocardial infarction. The available and upcoming data on this subject will also be reviewed.

We compared in-hospital femoral complications of Angio-Seal, Perclose, and manual compression in consecutive patients who underwent percutaneous coronary interventions in the era of glycoprotein IIb/IIIa platelet inhibition. Femoral closure devices have a similar overall risk profile as manual compression, even in patients treated with glycoprotein IIb/IIIa platelet inhibition, although certain rare complications such as retroperitoneal hemorrhage and severe access-site infection may be more common with the use of these devices.

Background: Previous trials testing stents compared with balloon angioplasty excluded patients with complex lesions and did not assess the effect of adjunctive platelet IIb/IIIa inhibition. This analysis sought to assess the effect of stenting and abciximab specifically for patients with complex lesions., Methods and Results: Patients with complex lesions (long, tandem, severely calcified, restenotic, thrombotic, or ostial; total occlusions; bifurcations; saphenous vein grafts; and multivessel interventions) from the Evaluation of PTCA to Improve Long-Term Outcome by c7E3 GP IIb/IIIa Receptor Blockade (EPILOG) and the Evaluation of Platelet IIb/IIIa Inhibitor for Stenting (EPISTENT) trials were included in the analysis. The 1-year combined death or myocardial infarction rates in the 4 treatment groups were as follows: balloon angioplasty/placebo, 14.2%; stent/placebo, 15.8%; balloon angioplasty/abciximab, 7.6%; and stent/abciximab, 8.0% (P<0.001). Death rates were 3.2%, 3.1%, 2.1%, and 0.5%, respectively (P=0.03). The incidence of target vessel revascularization at 1 year was 30.5%, 18.0%, 24.4%, and 19.7% in the 4 groups, respectively (P<0.001). After adjustment for baseline differences, multivariate analysis demonstrated that the rate of death or myocardial infarction was independently reduced by balloon angioplasty/abciximab (hazard ratio, 0.51; P<0.001) and stent/abciximab (hazard ratio, 0.60; P=0.02) but was not affected by the use of stents alone. Conversely, target vessel revascularization was reduced by stent/placebo (hazard ratio, 0.53; P<0.001), stent/abciximab (hazard ratio, 0.58; P<0.001), and balloon angioplasty/abciximab (hazard ratio, 0.74; P=0.006) compared with balloon angioplasty/placebo, respectively., Conclusions: The combination of stenting and abciximab during percutaneous coronary interventions for patients with angiographically complex lesions confers additive long-term benefit with respect to death, myocardial infarction, and target vessel revascularization.

PTCA and stenting now form an integral part of therapy for acute coronary syndromes and are important in achieving the optimal clinical outcome.

Background: Intravascular ultrasound is a sensitive tool to study transplant vasculopathy. However, there is no consensus regarding the methodology for imaging protocol. The impact of single versus multiple epicardial vessel imaging in determining the prevalence of transplant vasculopathy has not been determined. This study examines the benefit of three-vessel imaging versus one-vessel imaging in detecting transplant vasculopathy., Methods and Results: One hundred eleven transplant recipients with intravascular ultrasound imaging at baseline (within 2 months of transplantation) were studied: 107 at 1-year, 53 at 2-year and 41 at 3-year follow-up. A total of 222 arteries, 519 segments and 772 sites were analyzed (94 LAD, 65 LCX and 65 RCA). The prevalence of transplant vasculopathy lesions was 27%, 41% and 58% at 1 year, 39%, 55% and 71% at 2 years and 39%, 55% and 74% at 3 years for patients with one-, two- and three-vessel imaging, respectively. Single- or two-vessel disease was present in 23% (7) and 32% (10) patients with three-vessel imaging, leading to the potential mislabeling of these 17 (55%) patients as "disease free" if they underwent only single-vessel imaging., Conclusions: Multivessel imaging is more sensitive in detecting the transplant vasculopathy lesions compared to single-vessel imaging. This important variable should be considered when designing and interpreting trials utilizing intravascular imaging derived end-point.