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BackgroundLong‐term outcomes of percutaneous coronary intervention (PCI) based on patients’ decision‐making ability have not been studied. Our objective was to assess long‐term outcomes after PCI in patients who provided individual versus surrogate consent.Methods and ResultsData were collected retrospectively for patients who underwent PCI at Cleveland Clinic between January 1, 2015 and December 31, 2016. Inclusion criteria consisted of hospitalized patients aged ≥20 years who had PCI. Patients with outpatient PCI, or major surgery 30 days before or 90 days after PCI, were excluded. Patients who underwent PCI with surrogate consent versus individual consent were matched using the propensity analysis. Kaplan–Meier, log rank,t‐statistic, and χ2tests were used for statistical analysis. The study was approved by the Institutional Review Board at Cleveland Clinic, Ohio. Of 3136 patients who underwent PCI during the study period, 183 had surrogate consent. Propensity matching yielded 149 patients from each group. Two‐year all‐cause mortality was significantly higher in the surrogate consent group (38 [25.5%] versus 16 [10.7%] deaths, log‐rankχ2=10.16,Pχ2=8.36,P=0.003).ConclusionsPatients with surrogate consent had significantly higher all‐cause mortality and higher major adverse cardiac events when compared with patients with individual consent. This study emphasizes the fact that patients with an inability to give consent are at high risk and may need special attention in postprocedural and postdischarge care.

Background We sought to determine (1) long‐term outcomes in patients presenting with documented Takotsubo syndrome (TS), (2) whether left ventricular global longitudinal strain (LV‐GLS) provides incremental prognostic value, and (3) prognostic cutoffs of LV ejection fraction (LVEF) and LV‐GLS during an acute TS episode. Methods and Results We studied 650 patients with TS (aged 66±14 years, 88% women) who were diagnosed clinically and angiographically between 2006 and 2018. Baseline LVEF and LV‐GLS (using velocity vector imaging) were recorded. The primary end point was all‐cause mortality. TS triggers were unknown (34%), emotional (16%), physical (41%), and neurologic (10%). Mean LVEF and LV‐GLS were 36±10% and −11.6±0.4%; in addition, 94% patients had LVEF P P P Conclusions Patients with TS with a neurologic or physical trigger had significantly worse survival than those without such a trigger, with baseline LVEF and LV‐GLS providing incremental prognostic value.

Coronary artery disease (CAD) is the leading cause of death, and genetic factors contribute significantly to risk of CAD. This study aims to identify new CAD genetic loci through a large-scale linkage analysis of 24 large and multigenerational families with 433 family members (GeneQuest II). All family members were genotyped with markers spaced by every 10 cM and a model-free nonparametric linkage (NPL-all) analysis was carried out. Two highly significant CAD loci were identified on chromosome 17q21.2 (NPL score of 6.20) and 7p22.2 (NPL score of 5.19). We also identified four loci with significant NPL scores between 4.09 and 4.99 on 2q33.3, 3q29, 5q13.2 and 9q22.33. Similar analyses in individual families confirmed the six significant CAD loci and identified seven new highly significant linkages on 9p24.2, 9q34.2, 12q13.13, 15q26.1, 17q22, 20p12.3, and 22q12.1, and two significant loci on 2q11.2 and 11q14.1. Two loci on 3q29 and 9q22.33 were also successfully replicated in our previous linkage analysis of 428 nuclear families. Moreover, two published risk variants, SNP rs46522 in UBE2Z and SNP rs6725887 in WDR12 by GWAS, were found within the 17q21.2 and 2q33.3 loci. These studies lay a foundation for future identification of causative variants and genes for CAD.

Purpose: Patients with recurrent high-grade gliomas (HGG) are usually managed with alkylating chemotherapy ± bevacizumab. However, prognosis remains very poor. Preclinically, we showed that HGGs are a target for arginine depletion with pegargiminase (ADI-PEG20) due to epimutations of argininosuccinate synthetase (ASS1) and/or argininosuccinate lyase (ASL). Moreover, ADI-PEG20 disrupts pyrimidine pools in ASS1-deficient HGGs, thereby impacting sensitivity to the antifolate, pemetrexed. Patients and Methods: We expanded a phase I trial of ADI-PEG20 with pemetrexed and cisplatin (ADIPEMCIS) to patients with ASS1-deficient recurrent HGGs (NCT02029690). Patients were enrolled (01/16–06/17) to receive weekly ADI-PEG20 36 mg/m2 intramuscularly plus pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 intravenously once every 3 weeks for up to 6 cycles. Patients with disease control were allowed ADI-PEG20 maintenance. The primary endpoints were safety, tolerability, and preliminary estimates of efficacy. Results: Ten ASS1-deficient heavily pretreated patients were treated with ADIPEMCIS therapy. Treatment was well tolerated with the majority of adverse events being Common Terminology Criteria for Adverse Events v4.03 grade 1-2. The best overall response was stable disease in 8 patients (80%). Plasma arginine was suppressed significantly below baseline with a reciprocal increase in citrulline during the sampling period. The anti–ADI-PEG20 antibody titer rose during the first 4 weeks of treatment before reaching a plateau. Median progression-free survival (PFS) was 5.2 months (95% confidence interval (CI), 2.5–20.8) and overall survival was 6.3 months (95% CI, 1.8–9.7). Conclusions: In this recurrent HGG study, ADIPEMCIS was well tolerated and compares favorably to historical controls. Additional trials of ADI-PEG20 in HGG are planned.

Aims: Of patients with atrial fibrillation (AF), approximately 10% undergo percutaneous coronary intervention (PCI). We studied the safety and efficacy of dual vs. triple antithrombotic therapy (DAT vs. TAT) in this population., Methods and results: A systematic review and meta-analysis was conducted using PubMed, Embase, EBSCO, Cochrane database of systematic reviews, Web of Science, and relevant meeting abstracts for Phase 3, randomized trials that compared DAT vs. TAT in patients with AF following PCI. Four trials including 5317 patients were included, of whom 3039 (57%) received DAT. Compared with the TAT arm, Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding showed a reduction by 47% in the DAT arm [4.3% vs. 9.0%; hazard ratio (HR) 0.53, 95% credible interval (CrI) 0.36–0.85, I2 = 42.9%]. In addition, there was no difference in the trial-defined major adverse cardiac events (MACE) (10.4% vs. 10.0%, HR 0.85, 95% CrI 0.48–1.29, I2 = 58.4%), or in individual outcomes of all-cause mortality, cardiac death, myocardial infarction, stent thrombosis, or stroke between the two arms., Conclusion: Compared with TAT, DAT shows a reduction in TIMI major or minor bleeding by 47% with comparable outcomes of MACE. Our findings support the concept that DAT may be a better option than TAT in many patients with AF following PCI.

Item does not contain fulltext OBJECTIVES: The authors sought to identify and verify independent correlates of device thrombosis from an analysis of multicenter trials and registries. BACKGROUND: Recent analyses suggest an increased risk of device thrombosis with Absorb bioresorbable vascular scaffold (Abbott Vascular, Santa Clara, California) implantation compared with metallic drug-eluting stents, and data from moderate size studies suggest a risk relationship to vessel size and technique. METHODS: From 8,771 consecutively treated patients, 105 patients (1.2%) were identified with scaffold thrombosis within 1 year of implantation. They were matched 2:1 with controls selected randomly from nonthrombosis patients. Data-restricted multiple logistic analysis was used to identify significant independent covariates of the outcome. RESULTS: Early (within 1 month) scaffold thrombosis occurred in 69 patients and late (1 to 12 months) thrombosis occurred in 36 patients. Modelling found significant correlations of thrombosis to be final minimal lumen diameter 1.1:1 balloon/scaffold ratio (OR: 2.3; p = 0.022), and reference vessel diameter

Background— The aim of this analysis was to determine the long-term prognostic value of lower serum chloride in patients with stable chronic heart failure. Electrolyte abnormalities are prevalent in patients with chronic heart failure. Little is known regarding the prognostic implications of lower serum chloride. Methods and Results— Serum chloride was measured in 1673 consecutively consented stable patients with a history of heart failure undergoing elective diagnostic coronary angiography. All patients were followed for 5-year all-cause mortality, and survival models were adjusted for variables that confounded the chloride–risk relationship. The average chloride level was 102±4 mEq/L. Over 6772 person-years of follow-up, there were 547 deaths. Lower chloride (per standard deviation decrease) was associated with a higher adjusted risk of mortality (hazard ratio 1.29, 95% confidence interval 1.12–1.49; P P =0.03) when added to a multivariable model (with a resultant C-statistic of 0.70), in which sodium levels were not prognostic ( P =0.30). In comparison to those with above first quartile chloride (≥101 mEq/L) and sodium (≥138 meq/L), subjects with first quartile chloride had a higher adjusted mortality risk, whether they had first quartile sodium (hazard ratio 1.35, 95% confidence interval 1.08–1.69; P =0.008) or higher (hazard ratio 1.43, 95% confidence interval 1.12–1.85; P =0.005). However, subjects with first quartile sodium but above first quartile chloride had no association with mortality ( P =0.67). Conclusions— Lower serum chloride levels are independently and incrementally associated with increased mortality risk in patients with chronic heart failure. A better understanding of the biological role of serum chloride is warranted.

Antithrombotic management of patients with atrial fibrillation (AF) undergoing coronary stenting is complicated by the need for anticoagulant therapy for stroke prevention and dual antiplatelet therapy for prevention of stent thrombosis and coronary events. Triple antithrombotic therapy, typically comprising warfarin, aspirin, and clopidogrel, is associated with a high risk of bleeding. A modest-sized trial of oral anticoagulation with warfarin and clopidogrel without aspirin showed improvements in both bleeding and thrombotic events compared with triple therapy, but large trials are lacking. The RE-DUAL PCI trial (NCT 02164864) is a phase 3b, a strategy of prospective, randomized, open-label, blinded-endpoint trial. The main objective is to evaluate dual antithrombotic therapy with dabigatran etexilate (110 or 150 mg twice daily) and a P2Y12 inhibtor (either clopidogrel or ticagrelor) compared with triple antithrombotic therapy with warfarin, a P2Y12 inhibtor (either clopidogrel or ticagrelor, and low-dose aspirin (for 1 or 3 months, depending on stent type) in nonvalvular AF patients who have undergone percutaneous coronary intervention with stenting. The primary endpoint is time to first International Society of Thrombosis and Hemostasis major bleeding event or clinically relevant nonmajor bleeding event. Secondary endpoints are the composite of all cause death or thrombotic events (myocardial infarction, or stroke/systemic embolism) and unplanned revascularization; death or thrombotic events; individual outcome events; death, myocardial infarction, or stroke; and unplanned revascularization. A hierarchical procedure for multiple testing will be used. The plan is to randomize similar to 2500 patients at approximately 550 centers worldwide to try to identify new treatment strategies for this patient population.

The majority of first-time angiography patients are without obstructive coronary artery disease (CAD). A blood gene expression score (GES) for obstructive CAD likelihood was validated in the PREDICT study, but its relation to major adverse cardiovascular events (MACE) and revascularization was not assessed. Patients (N = 1,160) were followed up for MACE and revascularization 1 year post-index angiography and GES, with 1,116 completing follow-up. The 30-day event rate was 23% and a further 2.2% at 12 months. The GES was associated with MACE/revascularizations (p 15 trended towards increased >30 days MACE/revascularization likelihood (odds ratio = 2.59, 95% confidence interval = 0.89–9.14, p = 0.082). MACE incidence overall was 1.5% (17 of 1,116) and 3 of 17 patients had GES ≤15. For the total low GES group (N = 396), negative predictive value was 90% for MACE/revascularization and >99% for MACE alone, identifying a group of patients without obstructive CAD and highly unlikely to suffer MACE within 12 months. Electronic supplementary material The online version of this article (doi:10.1007/s12265-012-9353-z) contains supplementary material, which is available to authorized users.

Background— Recent genome-wide association studies (GWAS) have identified several novel loci that reproducibly associate with coronary artery disease (CAD) and/or myocardial infarction risk. However, known common CAD risk variants explain only 10% of the predicted genetic heritability of the disease, suggesting that important genetic signals remain to be discovered. Methods and Results— We performed a discovery meta-analysis of 5 GWAS involving 13 949 subjects (7123 cases, 6826 control subjects) imputed at approximately 5 million single nucleotide polymorphisms, using pilot 1000 Genomes–based haplotypes. Promising loci were followed up in an additional 5 studies with 11 032 subjects (5211 cases, 5821 control subjects). A novel CAD locus on chromosome 6p21.3 in the major histocompatibility complex (MHC) between HCG27 and HLA-C was identified and achieved genome-wide significance in the combined analysis (rs3869109; p discovery =3.3×10 −7 , p replication =5.3×10 −4 p combined =1.12×10 −9 ). A subanalysis combining discovery GWAS showed an attenuation of significance when stringent corrections for European population structure were used ( P =4.1×10 −10 versus 3.2×10 −7 ), suggesting that the observed signal is partly confounded due to population stratification. This gene dense region plays an important role in inflammation, immunity, and self–cell recognition. To determine whether the underlying association was driven by MHC class I alleles, we statistically imputed common HLA alleles into the discovery subjects; however, no single common HLA type contributed significantly or fully explained the observed association. Conclusions— We have identified a novel locus in the MHC associated with CAD. MHC genes regulate inflammation and T-cell responses that contribute importantly to the initiation and propagation of atherosclerosis. Further laboratory studies will be required to understand the biological basis of this association and identify the causative allele(s).

AIMS: Lipoprotein-associated phospholipase A2 (Lp-PLA2) generates proinflammatory and proatherogenic compounds in the arterial vascular wall and is a potential therapeutic target in coronary heart disease (CHD). We searched for genetic loci related to Lp-PLA2 mass or activity by a genome-wide association study as part of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. METHODS AND RESULTS: In meta-analyses of findings from five population-based studies, comprising 13 664 subjects, variants at two loci (PLA2G7, CETP) were associated with Lp-PLA2 mass. The strongest signal was at rs1805017 in PLA2G7 [P = 2.4 × 10(-23), log Lp-PLA2 difference per allele (beta): 0.043]. Variants at six loci were associated with Lp-PLA2 activity (PLA2G7, APOC1, CELSR2, LDL, ZNF259, SCARB1), among which the strongest signals were at rs4420638, near the APOE-APOC1-APOC4-APOC2 cluster [P = 4.9 × 10(-30); log Lp-PLA2 difference per allele (beta): -0.054]. There were no significant gene-environment interactions between these eight polymorphisms associated with Lp-PLA2 mass or activity and age, sex, body mass index, or smoking status. Four of the polymorphisms (in APOC1, CELSR2, SCARB1, ZNF259), but not PLA2G7, were significantly associated with CHD in a second study. CONCLUSION: Levels of Lp-PLA2 mass and activity were associated with PLA2G7, the gene coding for this protein. Lipoprotein-associated phospholipase A2 activity was also strongly associated with genetic variants related to low-density lipoprotein cholesterol levels.

Contains fulltext : 97601.pdf (Publisher’s version ) (Closed access) Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value < 1 x 10(-5)) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p < 1 x 10(-5)). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 x 10(-10), odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression. 9 p.

BACKGROUND Hypertension is a risk factor for coronary heart disease (CHD), but the causes of hypertension remain largely unknown. Genetic variation is thought to contribute to the etiology of hypertension. We tested a single-nucleotide polymorphism (SNP) (Lys67Arg, rs197922) in the Golgi SNAP Receptor Complex Member 2 (GOSR2) gene for association with hypertension and blood pressure (BP). We chose this SNP because it was nominally associated with CHD in earlier studies. Further, GOSR2 is located in a linkage region for hypertension and BP in human and animal studies. METHODS We used logistic and linear regression to test associations of the GOSR2 SNP with hypertension and BP among 3,528 blacks and 9,861 whites from the Atherosclerosis Risk in Communities (ARIC) study. Race-specific regression models of hypertension were adjusted for age and gender. Regression models of BP were further adjusted for antihypertensive medication use. RESULTS The GOSR2 Lys67 allele was associated with hypertension in whites (odds ratio (OR) = 1.09, P = 0.01) but not blacks (OR = 0.96, P = 0.47). The Lys67 allele was associated with increased systolic BP (SBP) in both races (0.87 mm Hg, P < 0.001 among whites and 1.05 mm Hg, P = 0.05 among blacks). A similar association in whites was observed for the GOSR2 SNP and SBP in the Women's Genome Health Study (WGHS) (OR = 1.03, P = 0.04). The OR remained unchanged after adjustment for antihypertensive medication use (OR = 1.03, P = 0.11), though it was no longer statistically significant. CONCLUSIONS We found evidence that a SNP in GOSR2 is modestly associated with hypertension in whites from the ARIC study and the WGHS.

ObjectivesThis study sought to improve methodology for predicting post–percutaneous coronary intervention (PCI) mortality.BackgroundRecently, an increased proportion of post-PCI deaths caused by noncardiac causes has been suggested, often in rapidly triaged patients resuscitated from sudden cardiac death or presenting with cardiogenic shock. Older risk adjustment algorithms may not adequately reflect these issues.MethodsConsecutive patients undergoing PCI from 2000 to 2009 were randomly divided into training (n = 8,966) and validation (n = 8,891) cohorts. The 2010 ACC-NCDR (American College of Cardiology–National Cardiovascular Data Registry) mortality algorithm was applied to the training cohort and its highest risk decile, separately. Variables describing general and neurological status at admission were then tested for their additional predictive capability and new algorithms developed. These were tested in the validation cohort, using receiver-operator characteristic curve, Hosmer-Lemeshow, and reclassification measures as principal outcome measures.ResultsIn-hospital mortality was 1.0%, of which 52.2% had noncardiac causes or major contributions. Baseline model C-statistics for the total and upper decile training cohorts were 0.904 and 0.830. The Aldrete score (addressing consciousness, respiration, skin color, muscle function, and circulation) and neurology scores added incremental information, resulting in improved validation cohort C-statistics (entire group: 0.883 to 0.914, p < 0.001; high-risk decile: 0.829 to 0.874, p < 0.001). Reclassification of the ACC-NCDR

Conventional therapy for cardiogenic shock complicating acute myocardial infarction continues to be associated with a high in-hospital mortality rate. Hemodynamic support with new mechanical devices and emergency coronary revascularization may alter the long-term prognosis for patients with this complication. Between July 1985 and March 1990, 68 patients presented to the University of Michigan with acute myocardial infarction and cardiogenic shock. Interventions performed included thrombolytic therapy (46%), intraaortic balloon pump counterpulsation (70%), cardiac catheterization (86%), coronary angioplasty (73%), emergency coronary artery bypass grafting/ventricular septal defect repair (15%), Hemopump insertion (11%), percutaneous cardiopulmonary support (4%) and ventricular assist device (3%).The 30-day survival rate was significantly better in patients who had successful angioplasty of the infarct-related artery than in patients with failed angioplasty (61% vs. 7%, p = 0.002) or no attempt at angioplasty (61% vs. 14%, p = 0.003). This difference was maintained over the 1-year follow-up period. The only clinical variable that predicted survival was age

This study sought to determine whether clinical variables can be used to identify patients at high risk of recurrent spontaneous myocardial ischemia or hemodynamic compromise during the 1st 4 days after intravenous thrombolysis for acute myocardial infarction. Of 288 patients randomly assigned to a conservative postthrombolysis strategy, 54 (19%) required urgent cardiac catheterization within 24 h; 75 (26%) underwent urgent cardiac catheterization within 4 days of admission. Of the clinical variables examined by multiple logistic regression analysis, only patient age and anterior wall myocardial infarction correlated with the need for urgent cardiac catheterization (p = 0.0016 and p = 0.017, respectively). Compared with recombinant tissue-type plasminogen activator or urokinase monotherapy, combination therapy with these agents was associated with a lower need for acute intervention during the 1st 24 h after admission, but the difference did not reach statistical significance (14% for combination therapy vs. 21 % for each agent alone, p = 0.30). Of the 75 patients undergoing urgent coronary angiography, only 39% had an occluded infarct-related artery. Emergency coronary angioplasty was performed in 49% of the patients and coronary artery bypass graft surgery was performed urgently in 3%. Despite these interventions, the need for urgent cardiac catheterization was associated with an in-hospital mortality rate of 7% (vs. 3% in the group not requiring urgent angiography, p = 0.36); mean left ventricular ejection fraction was 50.5 ± 11% (vs. 54.3 ± 10.8%, p = 0.12) and regional infarct zone wall motion was −2.68 ± 1.07 SD/chord (vs. −2.46 ± 1.19 SD/chord; p = 0.44). These data suggest that a relatively large proportion of patients treated conservatively after thrombolytic therapy require early triage to urgent coronary angiography; 2) baseline clinical characteristics are poorly predictive of the need for urgent intervention; and 3) despite ready access to facilities for aggressive intervention, the in-hospital clinical outcome of this group of patients appears to be poorer than that of patients without recurrent ischemia or hemodynamic instability.

Objectives We sought to determine whether gender influences the results of paclitaxel-eluting stent implantation. Background The TAXUS-IV trial demonstrated the safety and effectiveness of the slow-release, polymer-based, paclitaxel-eluting TAXUS stent compared to bare-metal stents in patients undergoing elective coronary intervention. Whether these results are generalizable to women is not known. Methods A total of 1,314 patients with coronary lesions 10- to 28-mm long in 2.5- to 3.75-mm vessels were randomized to TAXUS stent versus bare-metal EXPRESS stents (Boston Scientific Corp., Natick, Massachusetts). Outcomes examined were stratified by gender. Results A total of 662 patients (including 187 women) were assigned to the TAXUS stent, and 652 (180 women) received the control stent. Women were older than men, and had more hypertension, diabetes, renal insufficiency, unstable angina, and heart failure, but less smoking. Among patients receiving the TAXUS stent, women compared with men had higher unadjusted one-year rates of target lesion revascularization (TLR) (7.6% vs. 3.2%, p = 0.03), though female gender was not an independent predictor of TLR (odds ratio [OR] = 1.72 [95% confidence interval (CI) 0.68 to 4.37], p = 0.25). Moreover, restenosis rates were similar in men and women treated with the TAXUS stent (8.6% vs. 7.6%, respectively, p = 0.80), as was late loss (0.22 vs. 0.23 mm, p = 0.90). Compared to control stents, treatment with the TAXUS stent in women resulted in a significant reduction in nine-month restenosis (8.6% vs. 29.2%, p = 0.0001) and one-year TLR (7.6% vs. 14.9%, p = 0.02). The only independent predictor of freedom from restenosis in women was randomization to the TAXUS stent (OR = 0.28 [95% CI 0.11 to 0.74], p = 0.01). Conclusions The benefits of the paclitaxel-eluting stent in reducing clinical and angiographic restenosis are generalizable to women.

Objectives. We investigated the hypothesis that abciximab might lead to a differential effect among patients with different lesion morphologies; hence, its cost/benefit ratio would be optimized if it were used selectively on the basis of baseline angiographic findings. Background. Major complications of coronary angioplasty occur in 4% to 9% of patients. In the Evaluation of 7E3 for the Prevention of Ischemic Complications (EPIC) and Evaluation of PTCA To Improve Long-term Outcome with abciximab GPIIb/IIIa Receptor Blockade (EPILOG) trials, abciximab decreased the ischemic complications after intervention by 35% to 56%. However, the cost of this agent is appreciable, and there remain concerns about the safety of its readministration. Methods. There were 1,362 patients in EPIC and 2,792 patients in EPILOG randomized to either bolus plus an infusion of abciximab or placebo, administered with aspirin and heparin at the time of the coronary intervention. Data from these studies were combined, and a differential effect of abciximab in relation to baseline lesion morphology on 30-day risk of death, myocardial infarction or urgent intervention was investigated using the Breslow Day test for statistical interaction. Results. Abciximab consistently reduced the relative risk of complications across all lesion morphologies studied, with the possible exception of patients treated with degenerated saphenous vein grafts (risk with placebo 16.3% vs. risk with abciximab 18.6%, Breslow Day test for interaction, p = 0.08). However, the absolute reduction of risk was somewhat greater in patients with more complex B2 or C lesions (7.6% and 5.8%, respectively) than in patients with morphologically simpler A or B1 lesions (3.7% and 3.2%, respectively). Conclusions. The reduction of early adverse ischemic events associated with angioplasty by abciximab occurs largely independent of pretreatment morphology.

To evaluate the predictors and likelihood of success for coronary angioplasty performed in the setting of acute myocardial infarction, 300 consecutive patients with 321 coronary stenoses were studied retrospectively. Success was defined as final diameter stenosis 30% (p = 0.001); 2) no arterial bend ≥45° at the site of angioplasty (p = 0.008); and 3) no triple vessel disease (p = 0.014). In 144 subtotal occlusions (TIMI flow grade ≥2), procedural success was achieved in 84.7% and was predicted by 1) absence of thrombus >5 mm (p = 0.023), and 2) absence of other stenoses 250% in the same artery (p = 0.043), whereas patency without further emergency intervention was achieved in 71.7% and was predicted only by patient age ⪯60 years and absence of cardiogenic shock. Time to angioplasty, the specific artery dilated and other angiographic features of the stenosis to be dilated were not important predictors of outcome.Knowledge of the likelihood of success may allow more judicious use of coronary angioplasty in this setting: in particular, 1) consideration of immediate bypass surgery in the presence of TIMI flow grade ⪯1 and two or more risk factors for angioplasty failure (ejection fraction ⪯30%, occlusion at a bend or triple vessel disease) or in-hospital surgical standby if surgery is not immediately available; and 2) avoidance of immediate angioplasty in the presence of a) well maintained coronary flow and no reason for high risk of reocclusion, b) a large thrombus, c) multiple stenoses in the artery to be dilated, or d) patient age >60 years.

Objectives The goal of this study was to evaluate the mortality benefit of beta-blockers after successful percutaneous coronary intervention (PCI). Background Beta-blockers reduce mortality after myocardial infarction (MI), though limited data are available regarding their role after successful PCI. Methods Each year from 1993 through 1999, the first 1,000 consecutive patients undergoing PCI were systematically followed up. Patients presenting with acute or recent MI, shock, or unsuccessful revascularization procedures were excluded from the analysis. Clinical, procedural, and follow-up data of beta-blocker-treated and non-beta-blocker-treated patients were compared. A multivariate survival analysis model using propensity analysis was used to adjust for heterogeneity between the two groups. Results Of the 4,553 patients, 2,056 (45%) were treated with beta-blockers at the time of the procedure. Beta-blocker therapy was associated with a mortality reduction from 1.3% to 0.8% at 30 days (p = 0.13) and a reduction from 6.0% to 3.9% at one year (p = 0.0014). This survival benefit of beta-blockers was independent of left ventricular function, diabetic status, history of hypertension, or history of MI. Using propensity analysis, beta-blocker therapy remained an independent predictor for one-year survival after PCI (hazard ratio, 0.63; 95% confidence interval, 0.46 to 0.87; p = 0.0054). Conclusions Within this large prospective registry, beta-blocker use was associated with a marked long-term survival benefit among patients undergoing successful elective percutaneous coronary revascularization.

OBJECTIVES The purpose of this study was to determine how risks associated with increasing age differed in patients treated with percutaneous transluminal coronary angioplasty versus thrombolysis. BACKGROUND Advancing age is a risk factor for adverse outcome in patients with acute myocardial infarction. Primary angioplasty has been thought to be particularly beneficial in higher risk patients including the elderly. There is, however, limited data on any differential incremental benefit of angioplasty compared with thrombolysis in candidates for either treatment. METHODS In the GUSTO-IIb angioplasty substudy, 1,138 patients were randomized to receive primary angioplasty or accelerated tissue-type plasminogen activator (t-PA). The effect of age on outcome was assessed as a discrete and continuous variable for each treatment group. Models using age as a linear factor as well as cubic spline transformations were used for the major end points of 30-day death or disabling stroke; death or reinfarction; and death, reinfarction or disabling stroke. RESULTS For each 10-year patient group, outcome was improved with angioplasty (n = 565) compared with t-PA (n = 573). Irrespective of treatment, however, risk increased with age. After adjusting for baseline characteristics, each increment of 10 years of age increased the risk of death or myocardial infarction by 1.32 (95% confidence interval 1.04 to 1.76, p = 0.022). For all adverse outcomes, this incremental effect of increasing age was constant. CONCLUSIONS Advancing age is associated with worse outcomes, and the risks increase in proportion to age. Although primary angioplasty improves outcomes over thrombolysis, it does not appear to be more beneficial in older than in younger patient groups. The incremental adverse effect of age does not vary by treatment strategy.

To assess the 3 year risk of anterior myocardial infarction in patients with left anterior descending coronary artery territory disease (30 to 100% stenosis), National Heart, Lung, and Blood Institute (NHLBI) Coronary Artery Surgery Study (CASS) registry patients were identified who were 1) medically treated, and 2) had evidence of viable anterior myocardium at the time of baseline angiography. Prospectively, 118 patients having an anterior infarction within 3 years of baseline angiography were identified from annual follow-up of 4,535 medically treated patients who had left anterior descending coronary artery disease and viable anterior myocardium. From the large residual pool of patients without infarction, 141 were randomly selected from a stratified matrix to represent the entire group. The maximal percent stenosis was estimated by the CASS multiple angiographers, by a current single observer rereading and by contemporary computer measurement techniques. Absolute lumen dimension was assessed by computer measurement. The 3 year risk of anterior infarction was 2% for patients with their most severe left anterior descending stenosis less than 50%, 6% for patients with one such stenosis greater than or equal to 50% and 11% for patients with two or more such stenoses greater than or equal to 50% (p less than 0.02). Stenoses of 90 to 98% had the highest (15%) 3 year risk of anterior myocardial infarction. The three methods used to measure maximal percent stenosis differed little with regard to their predictiveness. Absolute lumen dimension was less predictive of risk. These results may provide a more rational basis on which to base coronary revascularization decisions.

To define the clinical, angiographic and procedural correlates of quantitative coronary dimensions after directional coronary atherectomy, 400 lesions in 378 patients were analyzed with use of qualitative morphologic and quantitative angiographic methods. Successful atherectomy, defined by a less than 75% residual area stenosis, tissue retrieval and the absence of in-hospital ischemic complications, was performed in 351 lesions (87.7%). After atherectomy, minimal cross-sectional area increased from 1.2 +/- 1.1 to 6.6 +/- 4.4 mm2 (p less than 0.001) and percent area stenosis was reduced from 87 +/- 10% to 31 +/- 42% (p less than 0.001). By univariate analysis, device size (p less than 0.001) and left circumflex artery lesion location (p = 0.004) were associated with a larger final minimal cross-sectional area. Conversely, restenotic lesion (p = 0.002), lesion length greater than or equal to 10 mm (p = 0.018) and lesion calcification (p = 0.035) were quantitatively associated with a smaller final minimum cross-sectional area. With use of stepwise multivariate analysis to control for the reference area, atherectomy device size (p = 0.003) and left circumflex lesion location (p = 0.007) were independently associated with a larger final minimal cross-sectional area, whereas restenotic lesion (p = 0.010), diffuse proximal disease (p = 0.033), lesion length greater than or equal to 10 mm (p = 0.026) and lesion calcification (p = 0.081) were significantly correlated with a smaller final minimal cross-sectional area. The number of specimens excised, the number of atherectomy passes and atherectomy balloon inflation pressure did not correlate with the final minimal cross-sectional area. Thus, directional atherectomy results in marked improvement of coronary lumen dimensions, at least in part correlated with the presence of certain clinical, angiographic and procedural factors at the time of atherectomy.

Alice K. Jacobs, MD, FACC, FAHA, Chair Jeffrey L. Anderson, MD, FACC, FAHA, Chair-Elect Nancy Albert, PhD, CCNS, CCRN, FAHA Mark A. Creager, MD, FACC, FAHA Steven M. Ettinger, MD, FACC Robert A. Guyton, MD, FACC Jonathan L. Halperin, MD, FACC, FAHA Judith S. Hochman, MD, FACC, FAHA

Objectives. A case-control analysis was performed to compare clinical outcome after intracoronary stenting with that after conventional therapy for abrupt vessel closure.Background. Previous studies have demonstrated that stenting after abrupt vessel closure results in marked angiographic improvement and preservation of coronary flow, leading to the anticipation of similar improvement in clinical outcome.Methods. Sixty-one of 92 consecutive patients treated at two clinical sites by intracoronary stenting for abrupt vessel closure were matched, according to angiographic features of closure and estimated left ventricular mass threatened by ischemia, with patients treated conventionally during the 18 months before stent availability. In 33 pairs of matched patients, vessel closure was established; in 28 pairs, it was threatened (coronary dissection or worsening stenosis with preservation of normal anterograde flow). Baseline clinical and angiographic characteristics were comparable in the two matched groups. Patients with indeterminate mechanisms of total occlusion (31%) or dissections 15 mm long (18%) were infrequently represented. Stents were successfully deployed in 60 of 61 patients at a median of 52 min (range 3 to 269) after the onset of closure.Results. When compared with conventional treatment, stenting resulted in less residual stenosis (26% vs. 49% diameter stenosis, p < 0.001), a greater likelihood of restoration of Thrombolysis in Myocardial Infarction (TIMI) grade 3 blood flow (97% vs. 72%, p < 0.001) and a reduction in the need for emergency bypass surgery (4.9% vs. 18%, p = 0.02). However, the incidence of Q wave myocardial infarction was nearly the same in the two groups (32% vs. 20%, respectively, p = NS). In the group with stenting, peak creatine kinase level and the frequency of Q wave infarction after established vessel closure increased with the time to stent placement (p = 0.001 and 0.054, respectively); the incidence of procedure-related Q wave infarction in patients who underwent stenting within 45 min of closure was very low (3.9%). In-hospital death occurred in 3.3% of patients in each treatment group. At a mean of 6.3 months of follow-up after hospital discharge, survival free from late cardiac death, myocardial infarction; bypass surgery or coronary angioplasty was 74.9% and 81.3% in the stent and the control treatment group, respectively (p = NS).Conclusions. Although early treatment of established vessel closure by intracoronary stenting was associated with a low incidence of both myocardial infarction and emergency bypass surgery, the likelihood or severity of infarction was not reduced among those in whom stents were implanted later. Patients with threatened vessel closure could not be shown to benefit from stent treatment. These data provide preliminary indications for stent placement in the acute period to be validated in larger randomized studies.

Over a 5 year period at three centers, 53 patients underwent percutaneous transluminal angioplasty of a right coronary artery ostial stenosis. The procedure was successful in 42 patients (79%) and unsuccessful in 11, of whom 5 (9.4%) required emergency coronary artery bypass grafting because of abrupt closure. The right coronary ostial lesion had distinctive technical requirements to achieve success, including high pressure balloon inflation (10 ± 4 atm) and the need for unconventional right coronary guide catheters. Technical factors that account for increased difficulty in these patients include: 1) problems with guide catheter impaction and ostial trauma; 2) inability to inflate the balloon with adequate guide catheter support; and 3) need for increased intracoronary manipulation. The stenoses were quite discrete (4 ± 5 mm) and calcified in the majority (40) of the 53 patients. Long-term follow-up (mean 12.5 months, range 4 to 60) of these patients demonstrated clinical recurrence of angina in 20 patients (48%) and angiographically proved restenosis in 16 (38%). Repeat coronary angioplasty was successful in three of six patients for relief of symptoms for over 6 months. In conclusion, angioplasty of the right coronary ostial lesion compared with nonostial dilation leads to 1) a subopto\nal early success rate; 2) an apparent high risk of emergency bypass surgery; and 3) a high restenosis rate. Careful assessment of the patient with this lesion and improved technology appear to be warranted.

ObjectivesThe aim of this study was to assess risk of inpatient surgery at any time after percutaneous coronary intervention (PCI) with drug-eluting stents (DES).BackgroundRisk of adverse events, including stent thrombosis (ST), in patients undergoing surgical procedures with prior DES remains poorly defined.MethodsOutcomes of consecutive patients having inpatient surgical procedures after PCI with DES, placed from April 28, 2003 until December 31, 2006 at a tertiary-care medical center, were studied. Primary and secondary end points were 30-day post-operative risk of the Academic Research Consortium (ARC) definite and modified probable definitions of ST and combined 30-day post-operative risk of death, nonfatal myocardial infarction (MI), or ST, respectively. Multivariable logistic regression analyses were used to determine independent risk factors.ResultsSix hundred six inpatient surgeries on 481 patients with a mean time from PCI to surgery of 1.07 ± 0.89 years were evaluated. The primary and secondary end points occurred after 11 (2.0%) and 56 (9%) surgeries, respectively. Risk of the combined end point and ST decreased significantly in the first 1 to 6 months after PCI (p < 0.0001 and p < 0.014, respectively); however, risk persisted when time between PCI and surgery was >12 months. Independent correlates of the combined end point include emergency surgery, antecedent MI, the pre-operative use of intravenous heparin, and atherosclerotic lesion length treated with DES. Oral antiplatelet status at time of surgery was not a correlate of events.ConclusionsRisk of 30-day post-operative adverse events, including ST, remains significantly higher when surgery is performed soon after PCI, while intermediate-term risk extending at least 2 to 3 years remains important.

Objectives. The purpose of this study was to determine the effect of incomplete revascularization by percutaneous transluminal coronary angioplasty in patients with multivessel disease on adverse long-term cardiac events (death, coronary artery bypass surgery or myocardial infarction) and to develop an optimal definition of adequate revascularization based on clinical outcome. Background. The effect of incomplete coronary revascularization by coronary angioplasty on long-term adverse clinical events remains controversial. Methods. Three hundred seventy well characterized patients were followed-up for 27 ± 16 months after angioplasty. Mean patient age was 58 ± 11 years; 72% were male; 70% had two-vessel disease (≥50% diameter stenosis by caliper measurement); and the mean left ventricular ejection fraction was 58 ± 11% (range 20% to 85%). Angioplasty was successfully accomplished in 339 patients (91.6%), but complete revascularization by the standard definition (no residual >-50% stenosis in a coronary artery ≥1.5 mm in diameter) was achieved in only 91 patients (25%). Results. Three-year event-free survival (i.e., freedom from death, myocardial infarction, coronary artery bypass surgery) in the entire cohort was 76.5%. By the standard definition, complete revascularization was strongly and negatively associated (p = 0.003) with long-term cardiac events, even after correction for the effects of other independent correlates of events, using Cox proportional hazard regression analysis. Seventeen other definitions, evaluating the severity and extent of residual stenoses and whether they were associated with contractile myocardium, were tested to find that which best stratified late event-free survival and had an outcome with complete revascularization no worse than that associated with the standard definition. The best definition for the entire cohort, having more predictive value than the standard definition, allowed

Complications that occurred in 247 patients who underwent successful elective stenting to native coronary arteries with the Palmaz-Schatz balloon expandable stent included subacute thrombosis in 7 patients (2.8%), myocardial infarction in 3 (1.2%), death 3 (1.2%), urgent bypass surgery in 4 (1.6%) and major bleeding events in 24 (9.7%). Angiographic restenosis occurred in 21 (20%) of 103 patients who received a single stent.Subgroup analysis, however, revealed that restenosis of a single stent occurred in 3 (7%) of 45 patients without prior angioplasty compared with 25 (27%) of 91 patients with prior angioplasty. Patients with “suboptimal” angioplasty results (dissection) who received a single stent seemed to have a higher thrombosis rate perioperatively (4 [4%] of 98), but no higher incidence of restenosis (7 [15%] of 46) than that of the total group of patients who received 3 single stent.Coronary stenting may be a valuable adjunct to coronary angioplasty in carefully selected patients. Complication rates are similar to show of routine angioplasty; however, angiographic restenosis may be reduced in certain subsets of patients.

Objectives. The aim of this study was to evaluate the predictors and clinical sequelae of stent thrombosis.Background. Although coronary artery stenting is being increasingly applied, the major unique complication of stent thrombosis is not well characterized.Methods. We studied 145 patients who underwent coronary artery stenting with the Gianturco-Roubin flexible coil design for abrupt vessel closure or to prevent restenosis. There were 17 stented vessel closures (11.7%), 7 as a result of acute (10%), occurring predominantly in eccentric lesions and in patients with unstable angina pectoris. This complication is associated with significant adverse clinical outcomes and may be reduced by more intensive anticoagulation yet, in a delicate balance, can be precipitated by inadequate heparin therapy.

The study of potentially effective drug therapies and mechanical devices for the prevention of restenosis after percutaneous coronary revascularization was relied heavily on the use of experimental animal models. To date, >50 experimental studies have been reported and have suggested that at least nine different classes of pharmacologic agents inhibit the intimal proliferative response to arterial injury. However, no pharmacologic intervention has yet been shown to reproducibly reduce the incidence of restenosis after coronary balloon angioplasty in humans. To identify the reasons for the apparent nonspecificity of the animal models and to determine which model should most reliably predict the efficacy of individual therapies in humans, the distinguishing characteristics of the experimental models were compared. Particular attention was paid to the size and morphologic structure of the treated artery, the susceptibility of the species to spontaneous and diet-induced arterial disease, the nature of the stimulus to intimal proliferation and several practical and logistic considerations. Finally, the reported efficacies of specific drug therapies in the respective animal models and in humans were compared. This review suggests that significant interspecies and occasionally intraspecies differences do exist among the respective animal models, particularly in the extent and composition of the neointimal thickening. These differences appear to reflect not only differences in the nature and extent of the arterial injury, but also intrinsic differences among the species in drug and lipid metabolism and in the activity of the coagulation and fibrinolytic systems. These differences may account for the variability in sensitivity of these models to pharmacologic interventions and should be considered carefully in the interpretation of experimental studies of new devices and of apparently effective pharmacologic therapies.