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Background Diagnosis of acute myocardial infarction (MI) is challenging in pacemaker patients. Little is known about this patient group. Methods Patients with MI enrolled in the Swiss national AMIS Plus registry between January 2005 and December 2015 were analyzed. All patients with either paced ventricular rhythm or sinus rhythm with intrinsic ventricular conduction (IVC) were included in this study. Outcomes using crude data and propensity score matching were compared between patients with pacemaker rhythm and patients with IVC. The primary endpoint was in-hospital death. Results Data from 300 patients with paced rhythm and 27,595 with IVC were analyzed. Patients with pacemaker rhythm were older (78.2 y vs 65.4 y; p < 0.001), had more comorbidities (Charlson Index (CCI) > 1: 54.0% vs 21.1%; p < 0.001) and a higher rate of heart failure upon presentation (Killip class > 2, 11.0% vs 5.9%; p < 0.001) compared to patients with IVC. Door to balloon time in patients undergoing acute PCI is markedly delayed in contrast to patients with IVC (280 min vs 85 min; p < 0.001). Consequently, crude mortality in patients with pacemakers was high (11.3% vs 4.6%; p < 0.001). However, when analyzed with propensity matching for gender, age, CCI > 1 and Killip > 2, mortality was similar (11.2% vs 10.5%; p = 0.70). Conclusion Pacemaker patients with acute MI represent a high-risk group with doubled crude mortality compared to patients without pacemakers, due to higher age and higher Killip class. Diagnosis is difficult and results in delayed treatment. Treatment algorithms for MI with paced rhythm should possibly be adapted to those used for STEMI or new left bundle branch block. Clinical Trials Registration : NCT01305785. [ABSTRACT FROM AUTHOR]

Background: Mineralocorticoid receptor antagonists (MRA) improve outcome in the setting of post-myocardial infarction (MI) heart failure (HF).Objectives: The study sought to assess the benefit of an early MRA regimen in acute MI irrespective of the presence of HF or left ventricular (LV) dysfunction.Methods: We randomized 1,603 patients to receive an MRA regimen with a single intravenous bolus of potassium canrenoate (200 mg) followed by oral spironolactone (25 mg once daily) for 6 months in addition to standard therapy or standard therapy alone. The primary outcome of the study was the composite of death, resuscitated cardiac arrest, significant ventricular arrhythmia, indication for implantable defibrillator, or new or worsening HF at 6-month follow-up. Key secondary/safety outcomes included death and other individual components of the primary outcome and rates of hyperkalemia at 6 months.Results: The primary outcome occurred in 95 (11.8%) and 98 (12.2%) patients in the treatment and control groups, respectively (hazard ratio [HR]: 0.97; 95% confidence interval [CI]: 0.73 to 1.28). Death occurred in 11 (1.4%) and 17 (2.1%) patients in the treatment and control groups, respectively (HR: 0.65; 95% CI: 0.30 to 1.38). In a non-pre-specified exploratory analysis, the odds of death were reduced in the treatment group (3 [0.5%] vs. 15 [2.4%]; HR: 0.20; 95% CI: 0.06 to 0.70) in the subgroup of ST-segment elevation MI (n = 1,229), but not in non-ST-segment elevation MI (p for interaction = 0.01). Hyperkalemia >5.5 mmol/l(-1) occurred in 3% and 0.2% of patients in the treatment and standard therapy groups, respectively (p < 0.0001).Conclusions: The study failed to show the benefit of early MRA use in addition to standard therapy in patients admitted for MI. (Aldosterone Lethal effects Blockade in Acute myocardial infarction Treated with or without Reperfusion to improve Outcome and Survival at Six months follow-up; NCT01059136). [ABSTRACT FROM AUTHOR]

Background: Prompt reperfusion in patients with ST-segment elevation myocardial infarction (STEMI) reduces infarct size and improves survival. However, the intuitive link between infarct size and prognosis has not been convincingly demonstrated in the contemporary era.Objectives: This study sought to determine the strength of the relationship between infarct size assessed early after primary percutaneous coronary intervention (PCI) in STEMI and subsequent all-cause mortality, reinfarction, and hospitalization for heart failure.Methods: We performed a pooled patient-level analysis from 10 randomized primary PCI trials (total 2,632 patients) in which infarct size was assessed within 1 month after randomization by either cardiac magnetic resonance (CMR) imaging or technetium-99m sestamibi single-photon emission computed tomography (SPECT), with clinical follow-up for ≥ 6 months.Results: Infarct size was assessed by CMR in 1,889 patients (71.8%) and by SPECT in 743 patients (28.2%). Median (25th, 75th percentile) time to infarct size measurement was 4 days (3, 10 days) after STEMI. Median infarct size (% left ventricular myocardial mass) was 17.9% (8.0%, 29.8%), and median duration of clinical follow-up was 352 days (185, 371 days). The Kaplan-Meier estimated 1-year rates of all-cause mortality, reinfarction, and HF hospitalization were 2.2%, 2.5%, and 2.6%, respectively. A strong graded response was present between infarct size (per 5% increase) and subsequent mortality (Cox-adjusted hazard ratio: 1.19 [95% confidence interval: 1.18 to 1.20]; p < 0.0001) and hospitalization for heart failure (adjusted hazard ratio: 1.20 [95% confidence interval: 1.19 to 1.21]; p < 0.0001), independent of age, sex, diabetes, hypertension, hyperlipidemia, current smoking, left anterior descending versus non-left anterior descending infarct vessel, symptom-to-first device time, and baseline TIMI (Thrombolysis In Myocardial Infarction) flow 0/1 versus 2/3. Infarct size was not significantly related to subsequent reinfarction.Conclusions: Infarct size, measured by CMR or technetium-99m sestamibi SPECT within 1 month after primary PCI, is strongly associated with all-cause mortality and hospitalization for HF within 1 year. Infarct size may, therefore, be useful as an endpoint in clinical trials and as an important prognostic measure when caring for patients with STEMI. [ABSTRACT FROM AUTHOR]

Background Women with AMI may have worse outcomes than men. However, it is unclear if this is related to differences in treatment, treatment effect or gender specific factors. We sought to determine whether primary percutaneous intervention (PCI) has a differential impact on infarct size, myocardial perfusion and ST segment resolution in men and women with acute myocardial infarction (AMI). Methods A total of 501 AMI patients were prospectively enrolled in the EMERALD study and underwent PCI with or without distal protection. Post hoc gender subset analysis was performed. Results 501 patients (108 women, 393 men) with ST-segment elevation AMI presenting within 6 h underwent primary (or rescue) PCI with stenting and a distal protection device. Women were older, had more hypertension, less prior AMI, smaller BSA, and smaller vessel size, but had similar rates of diabetes (30% versus 20.2%, p = 0.87), LAD infarct, and time-to-reperfusion compared to men. Women more frequently had complete ST-resolution (> 70%) at 30 days (72.8% versus 59.8%, p = 0.02), and smaller infarct size compared to males (12.2 ± 19.6% versus 18.4 ± 18.5%, p = 0.006). At 6 months, TLR (6.9% versus 5.2%) and MACE (11.4% versus 10.3%) were similar for women and men. Conclusions Despite worse comorbidities, women with AMI treated with primary PCI with stenting showed similar early and midterm outcomes compared to men. [ABSTRACT FROM AUTHOR]

Background: Acute myocardial infarction (AMI) has poorer outcomes in disadvantaged populations such as those in regional and remote locations. We compared long-term outcomes associated with presentation to regional or remote hospitals among AMI patients.Methods and Results: Administrative claims data from New South Wales (27% regional and remote residents) was used to identify patients >18 years admitted to any NSW hospital with a principal diagnosis of AMI (ICD10 codes: I21·0-I21·4) between 01/07/2004 and 30/06/2008. Hospital of presentation location with a population of <250,000 was defined as regional and remote while hospitals with a population >250,000 were deemed urban. Receipt of revascularisation and mortality were analysed and adjusted for age, comorbidities and previous revascularisation. Patients were censored at death or end of the follow-up period (31 December 2009). 39,798 patients were identified with 9,393 (23.6%) regional and remote presenters. In multivariable models, regional and remote presentation was associated with reduced rates of revascularisation (OR 0.30 95%CI 0.28-0.32; p<0.001), no impact on overall mortality (HR 1.04 95%CI 0.99-1.02; p=0.11), but with increased mortality for patients presenting with STEMI (HR 1.14; 95% CI 1.06-1.23; p<0.001). The propensity analysis was consistent with these findings.Conclusions: Presentation to a regional and remote hospital was associated with lower revascularisation rates following AMI, but with a higher long-term mortality if presenting with ST segment elevation. [ABSTRACT FROM AUTHOR]

Background Low-range troponin elevations without clear coronary manifestations remain a major diagnostic challenge. We sought to determine if troponin velocity could allow for early identification of patients without an obvious cardiac diagnosis and who are at increased risk for cardiac-specific events. Methods & results All patients presenting to South Australian public hospitals between 1 September 2011 and 30 September 2012, with at least two troponin measurements during the first 6 h after ED presentation were included. Diagnoses were classified as ‘coronary’, ‘non-coronary cardiac’, and ‘non-cardiac’ using the International Classification of Diseases 10 codes. The relationship between troponin velocity and cardiac-specific mortality and combined cardiac outcome (death and myocardial infarction) was assessed using Fine and Gray competing risk models in patients with an initial troponin < 52 ng/L. Sensitivity analyses were performed using different initial and maximum troponin cut-off values. In total, 7300 patients were identified. A troponin velocity of 2.5 ng/L/h or greater in the non-cardiac (n = 2793) patient group was significantly associated with an increased risk for 12-month cardiac mortality (sub-hazard ratio [SHR] 2.90, 95% CI 1.33–6.34) and combined cardiac outcome (SHR 2.08, 95% CI 1.01–4.27). This association was consistent for coronary (n = 3835) and non-coronary cardiac (n = 672) patient groups, and remained after sensitivity analyses. Conclusions The significant association observed across all patient groups suggests that troponin velocity could be used for early risk stratification of patients with low-range troponin elevations without clear cardiac symptoms. These results may help guide future clinical trials aimed at assessing the utility of cardiac-targeted interventions in this challenging patient population. [ABSTRACT FROM AUTHOR]

Background: A lack of clarity exists about the role of complete coronary revascularization in patients presenting with non-ST-segment elevation myocardial infarction.Objectives: The aim of our study was to compare long-term outcomes in terms of major adverse cardiovascular and cerebrovascular events of 2 different complete coronary revascularization strategies in patients with non-ST-segment elevation myocardial infarction and multivessel coronary artery disease: 1-stage percutaneous coronary intervention (1S-PCI) during the index procedure versus multistage percutaneous coronary intervention (MS-PCI) complete coronary revascularization during the index hospitalization.Methods: In the SMILE (Impact of Different Treatment in Multivessel Non ST Elevation Myocardial Infarction Patients: One Stage Versus Multistaged Percutaneous Coronary Intervention) trial, 584 patients were randomly assigned in a 1:1 manner to 1S-PCI or MS-PCI. The primary study endpoint was the incidence of major adverse cardiovascular and cerebrovascular events, which were defined as cardiac death, death, reinfarction, rehospitalization for unstable angina, repeat coronary revascularization (target vessel revascularization), and stroke at 1 year.Results: The occurrence of the primary endpoint was significantly lower in the 1-stage group (1S-PCI: n = 36 [13.63%] vs. MS-PCI: n = 61 [23.19%]; hazard ratio [HR]: 0.549 [95% confidence interval (CI): 0.363 to 0.828]; p = 0.004). The 1-year rate of target vessel revascularization was significantly higher in the MS-PCI group (1S-PCI: n = 22 [8.33%] vs. MS-PCI: n = 40 [15.20%]; HR: 0.522 [95% CI: 0.310 to 0.878]; p = 0.01; p log-rank = 0.013). When the analyses were limited to cardiac death (1S-PCI: n = 9 [3.41%] vs. MS-PCI: n = 14 [5.32%]; HR: 0.624 [95% CI: 0.270 to 1.441]; p = 0.27) and myocardial infarction (1S-PCI: n = 7 [2.65%] vs. MS-PCI: n = 10 [3.80%]; HR: 0.678 [95% CI: 0.156 to 2.657]; p = 0.46), no significant differences were observed between groups.Conclusions: In multivessel non-ST-segment elevation myocardial infarction patients, complete 1-stage coronary revascularization is superior to multistage PCI in terms of major adverse cardiovascular and cerebrovascular events. (Impact of Different Treatment in Multivessel Non ST Elevation Myocardial Infarction [NSTEMI]Patients: One Stage Versus Multistaged Percutaneous Coronary Intervention [PCI] [SMILE]: NCT01478984). [ABSTRACT FROM AUTHOR]

Background: We assessed associations between intraoperative neuraxial block and postoperative epidural analgesia, and a composite primary outcome of death or non-fatal myocardial infarction, at 30 days post-randomization in POISE-2 Trial subjects.Methods: 10 010 high-risk noncardiac surgical patients were randomized aspirin or placebo and clonidine or placebo. Neuraxial block was defined as intraoperative spinal anaesthesia, or thoracic or lumbar epidural anaesthesia. Postoperative epidural analgesia was defined as postoperative epidural local anaesthetic and/or opioid administration. We used logistic regression with weighting using estimated propensity scores.Results: Neuraxial block was not associated with the primary outcome [7.5% vs 6.5%; odds ratio (OR), 0.89; 95% CI (confidence interval), 0.73-1.08; P=0.24], death (1.0% vs 1.4%; OR, 0.84; 95% CI, 0.53-1.35; P=0.48), myocardial infarction (6.9% vs 5.5%; OR, 0.91; 95% CI, 0.74-1.12; P=0.36) or stroke (0.3% vs 0.4%; OR, 1.05; 95% CI, 0.44-2.49; P=0.91). Neuraxial block was associated with less clinically important hypotension (39% vs 46%; OR, 0.90; 95% CI, 0.81-1.00; P=0.04). Postoperative epidural analgesia was not associated with the primary outcome (11.8% vs 6.2%; OR, 1.48; 95% CI, 0.89-2.48; P=0.13), death (1.3% vs 0.8%; OR, 0.84; 95% CI, 0.35-1.99; P=0.68], myocardial infarction (11.0% vs 5.7%; OR, 1.53; 95% CI, 0.90-2.61; P=0.11], stroke (0.4% vs 0.4%; OR, 0.65; 95% CI, 0.18-2.32; P=0.50] or clinically important hypotension (63% vs 36%; OR, 1.40; 95% CI, 0.95-2.09; P=0.09).Conclusions: Neuraxial block and postoperative epidural analgesia were not associated with adverse cardiovascular outcomes among POISE-2 subjects. [ABSTRACT FROM AUTHOR]

Background In cardiogenic shock (CS) renal dysfunction is an important parameter of inadequate end-organ perfusion and an independent predictor of adverse outcome. Early detection of renal dysfunction is therefore important, and novel biomarkers such as Neutrophil Gelatinase-Associated Lipocalin (NGAL), Kidney Injury Molecule 1 (KIM1) and Cystatin C (CysC) have been suggested. However, in high-risk CS patients their role for assessing renal injury has not yet been investigated in comparison to the most widely used serum creatinine. Methods This predefined substudy included 190 patients of the randomized Intraaortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II)-trial. Blood samples were collected directly during primary percutaneous coronary intervention, one day and two days after randomization. The primary endpoint for outcome assessment was 1 year mortality. Results Creatinine, NGAL and KIM-1 were significantly higher in non-survivors in comparison to survivors over time in ANOVA (p < 0.001; p = 0.002 and p = 0.04, respectively). In contrast, CysC levels were not associated with the primary endpoint (p = 0.15). Receiver operator characteristics revealed that creatinine at any time point had the best predictive value for 1 year mortality. This was also true when comparing creatinine to different equations for glomerular filtration rate. In multivariable Cox-regression analysis creatinine remained the only significant independent predictor of kidney biomarkers of time to death during the first year. Conclusions Assessment of novel biomarkers such as CysC, NGAL and KIM-1 or calculation of glomerular filtration rate provide no additional prognostic information in patients with CS complicating acute myocardial infarction in comparison to creatinine. [ABSTRACT FROM AUTHOR]

Aims This study aims to validate the joint ACCF/AHA/ESC/WHF Universal Definition of peri-procedural myocardial infarction (PMI) with high sensitivity troponin T (hsTnT). Methods A retrospective cohort study encompassing patients admitted to our institution between May 2012 and April 2013 was performed. Results 630 patients underwent percutaneous coronary interventions during the study period. Among them, 459 patients met the inclusion criteria and were eligible for analyses. 76.9% of these patients were male, while the mean age was 68.6. PMI was observed in 4.3% of the patients based on the Universal Definition. The predictors of PMI were chronic kidney disease (OR: 3.0, p=0.026), family history of cardiovascular disease (OR: 2.7, p=0.043) and use of IIb/IIIa inhibitors (OR 4.2, p=0.01). MACE was reported in 4.4% of the patients at 12 months, and was significantly and independently associated with PMI (OR 7.3, p=0.003) in a multivariate model which accounted for lesion complexity, patients’ baseline clinical information, dual-antiplatelet status at follow-up and various procedural characteristics. The post-procedural hsTnT was much higher in those who suffered MACE than those who did not (156 v.s. 43 ng/L, p<0.001). Conclusion PMI as defined by the current Universal Definition using hsTnT is an independent predictor of adverse clinical outcome at 12 months in patients undergoing PCI. Accordingly, PMI remains a clinically relevant factor in current practice and should be considered a key outcome measure in clinical trials and a potential target for therapy. [ABSTRACT FROM AUTHOR]

The article focuses on study related to analysis of bypass angioplasty revascularization investigation trials outcomes using multistate model of clinical outcomes. Topics discussed include use of cardiovascular clinical trials in detection of treatment effect and composite outcomes, diagnosis of nonfatal Q-wave myocardial infarction in patients and use of regression analysis during the study.

Background In the HORIZONS-AMI (Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial Infarction) trial, 3,602 patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) treated with bivalirudin had lower bleeding and mortality rates, but higher acute stent thrombosis rates compared with heparin + a glycoprotein IIb/IIIa inhibitor (GPI). Subsequent changes in primary PCI, including the use of potent P2Y 12 inhibitors, frequent radial intervention, and pre-hospital medication administration, were incorporated into the EUROMAX (European Ambulance Acute Coronary Syndrome Angiography) trial, which assigned 2,218 patients to bivalirudin versus heparin ± GPI before primary PCI. Objectives The goal of this study was to examine the outcomes of procedural anticoagulation with bivalirudin versus heparin ± GPI for primary PCI, given the evolution in primary PCI. Methods Databases from HORIZONS-AMI and EUROMAX were pooled for patient-level analysis. The Breslow-Day test evaluated heterogeneity between trials. Results A total of 5,800 patients were randomized to bivalirudin (n = 2,889) or heparin ± GPI (n = 2,911). The radial approach was used in 21.3% of patients, prasugrel/ticagrelor was used in 18.1% of patients, and GPI was used in 84.8% of the control group. Bivalirudin compared with heparin ± GPI resulted in reduced 30-day rates of major bleeding (4.2% vs. 7.8%; relative risk [RR]: 0.53; 95% confidence interval [CI]: 0.43 to 0.66; p < 0.0001), thrombocytopenia (1.4% vs. 2.9%, RR: 0.48; 95% CI: 0.33 to 0.71; p = 0.0002), and cardiac mortality (2.0% vs. 2.9%; RR: 0.70; 95% CI: 0.50 to 0.97; p = 0.03), with nonsignificantly different rates of reinfarction, ischemia-driven revascularization, stroke, and all-cause mortality. Bivalirudin resulted in increased acute (<24 h) stent thrombosis rates (1.2% vs. 0.2%; RR: 6.04; 95% CI: 2.55 to 14.31; p < 0.0001), with nonsignificantly different rates of subacute stent thrombosis. Composite net adverse clinical events were lower with bivalirudin (8.8% vs. 11.9%; RR: 0.74; 95% CI: 0.63 to 0.86; p < 0.0001). There was no significant heterogeneity between the 2 trials for these outcomes, and results were consistent across major subgroups. Conclusions Despite increased acute stent thrombosis, primary PCI with bivalirudin improved 30-day net clinical outcomes, with significant reductions in major bleeding, thrombocytopenia, and transfusions compared with heparin ± GPI, results that were consistent with evolution in PCI technique and pharmacotherapy. (Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial Infarction [HORIZONS-AMI]; NCT00433966 ) (European Ambulance Acute Coronary Syndrome Angiography [EUROMAX]; NCT01087723 ) [ABSTRACT FROM AUTHOR]

Ischaemia−reperfusion (IR) injury is an important cause of myocardial damage during percutaneous coronary intervention (PCI). There are few therapies in widespread clinical use which impact on IR injury and it remains an important and underutilized target for treatment in acute myocardial infarction. This review will examine the translational scientific evidence for ischaemic conditioning and pharmacological agents including conditioning mimetics such as cyclosporine, anti-inflammatory agents, and those which modify myocardial glucose metabolism. We will address the reasons why many trials have failed to demonstrate clinical benefit and emphasize the need to deliver the right therapy to the right patient, at the right time to achieve successful translation of cardioprotection from bench-to-bedside. We critique trial design and offer advice for future translational trials in the field to ensure that effective treatments can be demonstrated clinically to improve patient outcomes during PCI. [ABSTRACT FROM AUTHOR]

Abstract: Background: The incidence and treatment strategies of acute coronary syndrome (ACS) vary by region. Additionally, the clinical spectrum of ACS is changing and outcomes are improving. Aim: We assessed the incidence, treatment strategies, and outcomes of ACS for a well-defined population within a well-established network of percutaneous coronary intervention (PCI) centers and non-PCI centers. Methods: The CZECH-2 registry included 1221 consecutive patients (mean age: 68±13years; 63.4% males) admitted for suspected ACS to 32 hospitals (including 4 PCI centers) within four Czech counties (total population: 2,370,841 inhabitants) during a 2-month period. Results: The estimated incidence of confirmed ACS was 2149cases/million/year. In 374 (31%) patients, ACS was ruled out during the hospital stay. Coronary angiography (CAG) was performed in 60% of the patients overall and PCI was performed in 59% of the confirmed ACS patients. Killip classifications II–IV on admission were more common in patients with final diagnosis of non ST-elevation myocardial infarction (NSTEMI) than ST-elevation myocardial infarction (STEMI) (37.1% vs. 22.8%; p<0.001). The 30-day mortality rate was 5.7% for the whole study group, 7.3% for STEMI patients, 8.4% for NSTEMI patients, and 1.6% for patients with unstable angina pectoris (UAP), respectively. Conclusions: Almost one-third of the patients admitted for suspected ACS had a different final diagnosis. Among those with confirmed ACS, the use of CAG, PCI, CABG, and effective medications is rational. Outcome in NSTEMI patients was equivalent to those in STEMI patients, mainly due to the high-risk population in this group. [Copyright &y& Elsevier]

Objectives: Using cardiac magnetic resonance (CMR), we sought to evaluate the relative influences of mechanical, electrical, and scar properties at the left ventricular lead position (LVLP) on cardiac resynchronization therapy (CRT) response and clinical events. Background: CMR cine displacement encoding with stimulated echoes (DENSE) provides high-quality strain for overall dyssynchrony (circumferential uniformity ratio estimate [CURE] 0 to 1) and timing of onset of circumferential contraction at the LVLP. CMR DENSE, late gadolinium enhancement, and electrical timing together could improve upon other imaging modalities for evaluating the optimal LVLP. Methods: Patients had complete CMR studies and echocardiography before CRT. CRT response was defined as a 15% reduction in left ventricular end-systolic volume. Electrical activation was assessed as the time from QRS onset to LVLP electrogram (QLV). Patients were then followed for clinical events. Results: In 75 patients, multivariable logistic modeling accurately identified the 40 patients (53%) with CRT response (area under the curve: 0.95 [p < 0.0001]) based on CURE (odds ratio [OR]: 2.59/0.1 decrease), delayed circumferential contraction onset at LVLP (OR: 6.55), absent LVLP scar (OR: 14.9), and QLV (OR: 1.31/10 ms increase). The 33% of patients with CURE <0.70, absence of LVLP scar, and delayed LVLP contraction onset had a 100% response rate, whereas those with CURE ≥0.70 had a 0% CRT response rate and a 12-fold increased risk of death; the remaining patients had a mixed response profile. Conclusions: Mechanical, electrical, and scar properties at the LVLP together with CMR mechanical dyssynchrony are strongly associated with echocardiographic CRT response and clinical events after CRT. Modeling these findings holds promise for improving CRT outcomes. [Copyright &y& Elsevier]

Objectives: This study sought to report the treatment effect of ticagrelor on myocardial infarction (MI) and the strategy for and impact of event adjudication in the PLATO (Platelet Inhibition and Patient Outcomes) trial. Background: In PLATO, ticagrelor reduced cardiovascular death, MI, or stroke in patients with acute coronary syndromes (ACS). Methods: A clinical events committee (CEC) prospectively defined and adjudicated all suspected MI events, on the basis of events reported by investigators and by triggers on biomarkers. Treatment comparisons used CEC-adjudicated data, and per protocol, excluded silent MI. Results: Overall, 1,299 (610 ticagrelor, 689 clopidogrel) MIs reported by the CEC occurred during the trial. Of these, 1,097 (504 ticagrelor, 593 clopidogrel) contributed to the primary composite endpoint. Site investigators reported 1,198 (580 ticagrelor, 618 clopidogrel) MIs. Ticagrelor significantly reduced overall MI rates (12-month CEC-adjudicated Kaplan-Meier rates: 5.8% ticagrelor, 6.9% clopidogrel; hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.75 to 0.95). Nonprocedural MI (HR: 0.86; 95% CI: 0.74 to 1.01) and MI related to percutaneous coronary intervention or stent thrombosis tended to be lower with ticagrelor. MIs related to coronary artery bypass graft surgery were few, but numerical excess was observed in patients assigned ticagrelor. Analyses of overall MIs using investigator-reported data showed similar results but did not reach statistical significance (HR: 0.88; 95% CI: 0.78 to 1.00). Conclusions: In patients with ACS, ticagrelor significantly reduced the incidence of MI compared with clopidogrel, with consistent results across most MI subtypes. CEC procedures identified more MI endpoints compared with site investigators. (A Comparison of Ticagrelor [AZD6140] and Clopidogrel in Patients With Acute Coronary Syndrome [PLATO]; NCT00391872) [Copyright &y& Elsevier]

Objectives: The purpose of this study was to determine whether, in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), the reduction in cardiac mortality in those taking bivalirudin compared with unfractionated heparin plus a glycoprotein IIb/IIIa inhibitor (UFH+GPI) can be fully attributed to reduced bleeding. Background: The association between hemorrhagic complications and mortality may explain the survival benefit with bivalirudin. Methods: A total of 3,602 STEMI patients undergoing primary PCI were randomized to bivalirudin versus UFH+GPI. Three-year cardiac mortality was analyzed in patients with and without major bleeding. Results: When compared with UFH+GPI, bivalirudin resulted in lower 3-year rates of major bleeding (6.9% vs. 10.5%, hazard ratio [HR]: 0.64 [95% confidence interval (CI): 0.51 to 0.80], p < 0.0001) and cardiac mortality (2.9% vs. 5.1%, HR: 0.56 [95% CI: 0.40 to 0.80], p = 0.001). Three-year cardiac mortality was reduced in bivalirudin-treated patients with major bleeding (20 fewer deaths with bivalirudin; 5.8% vs. 14.6%, p = 0.025) and without major bleeding (18 fewer deaths with bivalirudin; 2.6% vs. 3.8%, p = 0.048). In a fully-adjusted multivariable model accounting for major bleeding and other adverse events, bivalirudin was still associated with a 43% reduction in 3-year cardiac mortality (adjusted HR: 0.57 [95% CI: 0.39 to 0.83], p = 0.003). Conclusions: Bivalirudin reduces cardiac mortality in patients with STEMI undergoing primary PCI, an effect that can only partly be attributed to prevention of bleeding. Further studies are required to identify the nonhematologic benefits of bivalirudin. (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction; NCT00433966) [Copyright &y& Elsevier]

Objectives: The aim of this study was a comparison of risk-adjusted outcomes of 3 approaches to carotid revascularization in the open heart surgery (OHS) population. Background: Without randomized clinical trials, the best approach to managing coexisting severe carotid and coronary disease remains uncertain. Staged carotid endarterectomy (CEA) followed by OHS or combined CEA and OHS are commonly used. A recent alternative is carotid artery stenting (CAS). Methods: From 1997 to 2009, 350 patients underwent carotid revascularization within 90 days before OHS at a tertiary center: 45 staged CEA-OHS, 195 combined CEA-OHS, and 110 staged CAS-OHS. The primary composite endpoint was all-cause death, stroke, and myocardial infarction (MI). Staged CAS-OHS patients had higher prevalence of previous stroke (p = 0.03) and underwent more complex OHS. Therefore, the propensity score adjusted multiphase hazard function models with modulated renewal to account for staging, and competing risks were used. Results: Using propensity analysis, staged CAS-OHS and combined CEA-OHS had similar early hazard phase composite outcomes, whereas staged CEA-OHS incurred the highest risk driven by interstage MI. Subsequently, staged CAS-OHS patients experienced significantly fewer late hazard phase events compared with both staged CEA-OHS (adjusted hazard ratio: 0.33; 95% confidence interval: 0.15 to 0.77; p = 0.01) and combined CEA-OHS (adjusted hazard ratio: 0.35; 95% confidence interval: 0.18 to 0.70; p = 0.003). Conclusions: Staged CAS-OHS and combined CEA-OHS are associated with a similar risk of death, stroke, or MI in the short term, with both being better than staged CEA-OHS. However, the outcomes significantly favor staged CAS-OHS after the first year. [Copyright &y& Elsevier]

Abstract: Background: There is ongoing debate on the optimal drug-eluting stent (DES) in diabetic patients with coronary artery disease. Biodegradable polymer drug-eluting stents (BP-DES) may potentially improve clinical outcomes in these high-risk patients. We sought to compare long-term outcomes in patients with diabetes treated with biodegradable polymer DES vs. durable polymer sirolimus-eluting stents (SES). Methods: We pooled individual patient-level data from 3 randomized clinical trials (ISAR-TEST 3, ISAR-TEST 4 and LEADERS) comparing biodegradable polymer DES with durable polymer SES. Clinical outcomes out to 4years were assessed. The primary end point was the composite of cardiac death, myocardial infarction and target-lesion revascularization. Secondary end points were target lesion revascularization and definite or probable stent thrombosis. Results: Of 1094 patients with diabetes included in the present analysis, 657 received biodegradable polymer DES and 437 durable polymer SES. At 4years, the incidence of the primary end point was similar with BP-DES versus SES (hazard ratio=0.95, 95% CI=0.74–1.21, P =0.67). Target lesion revascularization was also comparable between the groups (hazard ratio=0.89, 95% CI=0.65–1.22, P =0.47). Definite or probable stent thrombosis was significantly reduced among patients treated with BP-DES (hazard ratio=0.52, 95% CI=0.28–0.96, P =0.04), a difference driven by significantly lower stent thrombosis rates with BP-DES between 1 and 4years (hazard ratio=0.15, 95% CI=0.03–0.70, P =0.02). Conclusions: In patients with diabetes, biodegradable polymer DES, compared to durable polymer SES, were associated with comparable overall clinical outcomes during follow-up to 4years. Rates of stent thrombosis were significantly lower with BP-DES. [Copyright &y& Elsevier]

Abstract: Objective: Ascertain platelet inhibition and patient outcomes (PLATO) trial conduct. Methods: We examined information from the FDA complete response review. Results: FDA Medical Review indicated that (1) patients on ticagrelor monitored by the study sponsor had a lower odds ratio for the primary endpoint (p=0.0004) versus ticagrelor patients monitored by a third party Clinical Research Organisation (CRO) independent of the study sponsor, (2) a significant interaction existed between ticagrelor and regions monitored by the study sponsor for all cause mortality through study end in favor of ticagrelor (p=0.006), (3) ticagrelor faired worse than clopidogrel when regions were monitored independent of the study sponsor by a third party Contract Research Organisation (United States, Russia and Georgia), (OR=1.21, 95% CI: 0.91 to 1.59, p=0.2022), (4) 46% of all primary endpoint events favoring ticagrelor came from just two countries (Poland and Hungary), (5) PLATO was easy to unblind by breaking open a clopidogrel/dummy clopidogrel tablet with at least 452 patients being unblinded prior to the database lock, (6) significantly more cardiac events submitted for clopidogrel counted in the primary analysis as a myocardial infarction (MI) compared to those submitted for ticagrelor (p<0.0001), (7) significantly more ticagrelor subjects hospitalized after an index event/hospitalization were not being reported as having a primary event compared to clopidogrel (p=0.002 in favor of ticagrelor), (8) site-reported MI was not significantly reduced with ticagrelor versus clopidogrel, (9) an estimated 23 definite or possible cardiovascular events or deaths on ticagrelor were either not submitted for adjudication, inactivated, deleted or were downgraded to “softer” endpoints (this was not shown in the FDA review for clopidogrel), and (10) four FDA reviewers voted for non-approval of ticagrelor. Discussion: The FDA report highlights what appear to be multiple serious deficiencies in the reporting of the PLATO results, which clinicians will not have gleaned from the primary publication alone. Individual clinicians may therefore wish to carefully reconsider their practice of ticagrelor prescription for this indication. Guideline bodies should also evaluate the information in its totality. [Copyright &y& Elsevier]

Abstract: The renin–angiotensin aldosterone system (RAAS) is central to the pathogenesis of cardiovascular disease. RAAS inhibition can reduce blood pressure, prevent target organ damage in hypertension and diabetes, and improve outcomes in patients with heart failure and/or myocardial infarction. This review presents the history of RAAS inhibition including a summary of key heart failure, myocardial infarction, hypertension and atrial fibrillation trials. Recent developments in RAAS inhibition are discussed including implementation and optimization of current drug therapies. Finally, ongoing clinical trials, opportunities for future trials and issues related to the barriers and approvability of novel RAAS inhibitors are highlighted. [Copyright &y& Elsevier]

Previous studies have suggested that angiographically detected peristent contrast staining (PSS) at follow-up may predict subsequent very late stent thrombosis. The Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS- AMI) trial was a dual-arm, factorial, randomized trial in patients with ST-segment elevation myocardial infarctions. All follow-up angiograms (1,330 lesions in 1,115 patients, median time 13.3 months) without major cardiovascular events before follow-up angiography were analyzed at a core laboratory blinded to clinical events for the presence of PSS (defined as contrast staining outside the stent contour extending to ≥20% of the stent diameter). Corresponding follow-up intravascular ultrasound (IVUS) data (275 lesions in 248 patients) were also evaluated to assess the mechanisms of PSS. PSS was present in 23 patients (2.1%) at follow-up and was not more common with paclitaxel-eluting than with bare-metal stents. All 6 PSS patients with follow-up IVUS had stent malapposition (vs 41.2% malapposition in the follow-up IVUS cohort). Comparing poststent and follow-up IVUS, 2 patients had late acquired and 4 had persistent malapposition; all 6 showed positive vessel remodeling from baseline to follow-up (mean vessel area 22.0 ± 8.0 to 32.4 ± 11.7 mm², p = 0.07). During 3-year follow-up, stent thrombosis developed in no patient with PSS compared with 8 PSS-negative patients (0% vs 0.8%, p = 0.68). The rates of revascularization and major adverse cardiovascular events were also not increased in PSS patients. In conclusion, in the large-scale HORIZONS-AMI trial, PSS at angiographic follow-up was infrequent and was associated with late stent malapposition and positive remodeling but was independent of stent type. Identification of PSS was not associated with subsequent stent thrombosis. [ABSTRACT FROM AUTHOR]

Registry Experience at the Washington Hospital Center, DES - Taxus Liberte Versus Xience V (REWARDS TLX) is a physician-initiated, retrospective, real-world, multicenter, observational study for all patients >18 years of age subjected to percutaneous coronary intervention with everolimus-eluting stents (EESs) or paclitaxel-eluting stents (PESs). Outcomes of patients receiving a TAXUS Liberté or XIENCE V drug-eluting stent were compared. Baseline clinical, procedural, and follow-up data at 12 months were collected from 10 clinical centers by an electronic data capture system. The study''s primary end point was major adverse cardiac events: a composite of all-cause death, Q-wave myocardial infarction, target vessel revascularization, and stent thrombosis. The trial is registered with http://www.clinicaltrials.gov (NCT01134159). Data were entered for 1,195 patients (PES, n = 595; EES, n = 600). Baseline clinical characteristics were similar except for higher dyslipidemia, systemic hypertension, and family history of coronary artery disease in the EES group. In-hospital outcome was similar between groups, with an overall in-hospital stent thrombosis rate of 0.2%. The primary end point at 12 months was similar (EES 7.8% vs 10.8%, p = 0.082). Overall stent thrombosis rate was lower in the EES group (0.3% vs 1.2%, respectively, p = 0.107); however, target lesion revascularization was similar (PES, hazard ratio 1.46, 95% confidence interval 0.98 to 2.19, p = 0.064). There was no difference in overall mortality between groups. In conclusion, second-generation EESs and PESs demonstrated similar efficacy and safety profiles for broadened patient and lesion subsets compared to a selected population from the pivotal trials. However, for composite efficacy and safety end points, EESs outperformed second-generation PESs. [Copyright &y& Elsevier]

Objectives: There are limited head-to-head randomized data on patient-related versus stent-related outcomes for everolimus-eluting stents (EES) and sirolimus-eluting stents (SES). Background: In the SORT OUT IV (Scandinavian Organization for Randomized Trials With Clinical Outcome IV) trial, comparing the EES with the SES in patients with coronary artery disease, the EES was noninferior to the SES at 9 months. Methods: The primary endpoint was a composite: cardiac death, myocardial infarction (MI), definite stent thrombosis, or target vessel revascularization. Safety and efficacy outcomes at 2 years were further assessed with specific focus on patient-related composite (all death, all MI, or any revascularization) and stent-related composite outcomes (cardiac death, target vessel MI, or symptom-driven target lesion revascularization). A total of 1,390 patients were assigned to receive the EES, and 1,384 patients were assigned to receive the SES. Results: At 2 years, the composite primary endpoint occurred in 8.3% in the EES group and in 8.7% in the SES group (hazard ratio [HR]: 0.94, 95% confidence interval [CI]: 0.73 to 1.22). The patient-related outcome: 15.0% in the EES group versus 15.6% in the SES group, (HR: 0.95, 95% CI: 0.78 to 1.15), and the stent-related outcome: 5.2% in the EES group versus 5.3% in the SES group (HR: 0.97, 95% CI: 0.70 to 1.35) did not differ between groups. Rate of definite stent thrombosis was lower in the EES group (0.2% vs. 0.9%, (HR: 0.23, 95% CI: 0.07 to 0.80). Conclusions: At 2-year follow-up, the EES was found to be noninferior to the SES with regard to both patient-related and stent-related clinical outcomes. (The SORT OUT IV TRIAL [SORT OUT IV]; NCT00552877) [ABSTRACT FROM AUTHOR]

Abstract: Background: The influence of atrial fibrillation (AF) on outcome in patients with symptomatic atherosclerotic disease has not been thoroughly studied. Methods: FRENA is an ongoing registry of stable outpatients with coronary (CAD), cerebrovascular (CVD), or peripheral (PAD) artery disease. With the aim to guide therapy, we assessed the incidence of subsequent myocardial infarction (MI), ischemic stroke or major bleeding in patients with AF, according to initial presentation. Results: As of June 2011, 3848 patients were recruited: 1436 had CAD, 1104 CVD, and 1308 had PAD. Of these, 470 (12%) had AF: 151 patients with CAD, 157 with CVD, and 162 with PAD. Over a mean follow-up of 16±13months, 19 patients with AF developed acute MI, 22 ischemic stroke and 7 bled. Among AF patients with CAD, the incidence of subsequent MI (5.00 events per 100 patient-years; 95% CI: 2.54-8.91) was non-significantly higher than that of stroke (1.48; 95% CI: 0.38-4.04) or major bleeding (1.47; 95% CI: 0.37-4.01). Among those with CVD, the incidence of stroke (5.61; 95% CI: 2.95-9.75) exceeded that of MI (no events) or major bleeding (0.51; 95% CI: 1.24-6.36). Among those with PAD, the incidence of MI (4.41; 95% CI: 2.15-8.10) and stroke (3.93; 95% CI: 1.82-7.46) were similar. Conclusions: CAD patients with AF are at a higher risk of subsequent MI than of stroke. Among those with CVD, the risk of stroke far exceeds that of MI. Those with PAD have a high and similar risk for both events. [Copyright &y& Elsevier]

Abstract: Leukocyte count predicted the risk of first-time myocardial infarction and ischemic stroke. The aim of this study was to determine the role of elevated leukocyte count in non-diabetic patients admitted for acute first-ever ischemic stroke on clinical presentation and 3-year mortality. We studied 462 patients with acute first-ever ischemic stroke without diabetes mellitus or active infection at admission. Patients were classified into 2 groups according to their leukocyte count. A white blood cell (WBC) count ≥10,000/μL was defined as an elevated leukocyte count, otherwise as normal. Clinical presentation, risk factors for stroke, laboratory data, co-morbidities, and outcomes were recorded. 64 patients (13.9%) had elevated leukocytes. Multivariate logistic regression showed that an elevated platelet count was positively associated with the elevated leukocyte count, while a low serum sodium level was negatively associated with an elevated leukocyte count (P =0.008, P =0.003, respectively). An elevated leukocyte count was associated with a higher risk of a stroke in evolution (P =0.021). Multivariate Cox regression analysis revealed that an elevated leukocyte count is a significant predictor of 3-year mortality [P =0.010, HR=3.26 (1.33–7.98)]. In conclusion, higher leukocyte counts during the acute stroke stage are associated with increased risk of 3-year mortality in patients with acute, first-ever ischemic stroke. [Copyright &y& Elsevier]

Abstract: Background: Early abciximab administration in patients requiring transportation to undergo primary percutaneous coronary intervention (PPCI) has been reported to improve clinical outcome. We aimed to verify whether early administration leads to reduced infarct size (IS), assessed by delayed-enhancement magnetic resonance imaging (DE-MRI). Methods: We randomized 110 patients with acute myocardial infarction with symptom-to-diagnosis time <6h to either early (55 patients) or late (55 patients) abciximab administration. DE-MRI was performed at 4days and 6months. The primary end point was IS at 6months. Secondary end points were the rate of ST-segment elevation resolution ≥50% (STR) at 60min after PPCI, the extent of microvascular obstruction at 4days, and the change in IS and transmurality at 6months vs. 4days. Results: DE-MRI was performed in 103 patients after 4days, and in 87 at 6months. The mean IS at 6months was 13.8±9.0% in the early vs. 13.0±9.9% in the Late group (P >0.2). Similarly, microvascular obstruction and the change in IS were not significantly different. The Early group showed a significantly higher STR (94.5% vs. 80.0%, P =0.04) and a larger reduction in infarct transmurality (−9.2±7.0% vs. −5.9±6.4%; P =0.03), while a larger reduction in IS was observed only in patients with ECG-to-Cath Lab time >60min. Conclusions: Early abciximab administration did not lead to a smaller IS at 6-month DE-MRI, and was associated with a significant reduction in IS and transmurality only in patients with longer transportation time, warranting further investigation in this patient subset. [Copyright &y& Elsevier]

Cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD) is high, and the presence of CKD worsens outcomes of cardiovascular disease (CVD). CKD is associated with specific risk factors. Emerging evidence indicates that the pathology and manifestation of CVD differ in the presence of CKD. During a clinical update conference convened by the Kidney Disease: Improving Global Outcomes (KDIGO), an international group of experts defined the current state of knowledge and the implications for patient care in important topic areas, including coronary artery disease and myocardial infarction, congestive heart failure, cerebrovascular disease, atrial fibrillation, peripheral arterial disease, and sudden cardiac death. Although optimal strategies for prevention, diagnosis, and management of these complications likely should be modified in the presence of CKD, the evidence base for decision making is limited. Trials targeting CVD in patients with CKD have a large potential to improve outcomes. [ABSTRACT FROM AUTHOR]

Summary: Background: In the randomised Carotid Revascularization Endarterectomy versus Stenting Trial (CREST), the primary endpoint did not differ between carotid artery stenting and carotid endarterectomy in patients with symptomatic and asymptomatic stenosis. A prespecified secondary aim was to examine differences by sex. Methods: Patients who were asymptomatic or had had a stroke or transient ischaemic attack within 180 days before random allocation were enrolled in CREST at 117 clinical centres in the USA and Canada. The primary outcome was the composite of stroke, myocardial infarction, or death during the periprocedural period or ipsilateral stroke within 4 years. We used standard survival methods including Kaplan-Meier survival curves and sex-by-treatment interaction term to assess the relation between patient factors and risk of reaching the primary outcome. Analyses were by intention to treat. CREST is registered with ClinicalTrials.gov, NCT00004732. Findings: Between Dec 21, 2000, and July 18, 2008, 2502 patients were randomly assigned to carotid endarterectomy (n=1240) or carotid artery stenting (n=1262), 872 (34·9%) of whom were women. Rates of the primary endpoint for carotid artery stenting compared with carotid endarterectomy were 6·2% versus 6·8% in men (hazard ratio [HR] 0·99, 95% CI 0·66–1·46) and 8·9% versus 6·7% in women (1·35, 0·82–2·23). There was no significant interaction in the primary endpoint between sexes (interaction p=0·34). Periprocedural events occurred in 35 (4·3%) of 807 men assigned to carotid artery stenting compared with 40 (4·9%) of 823 assigned to carotid endarterectomy (HR 0·90, 95% CI 0·57–1·41) and 31 (6·8%) of 455 women assigned to carotid artery stenting compared with 16 (3·8%) of 417 assigned to carotid endarterectomy (1·84, 1·01–3·37; interaction p=0·064). Interpretation: Periprocedural risk of events seems to be higher in women who have carotid artery stenting than those who have carotid endarterectomy whereas there is little difference in men. Additional data are needed to confirm whether this differential risk should be taken into account in decisions for treatment of carotid disease in women. Funding: National Institute of Neurological Disorders and Stroke and Abbott Vascular Solutions (formerly Guidant). [Copyright &y& Elsevier]

American College of Cardiology/American Heart Association guidelines for management of patients with ST-segment elevation myocardial infarction (STEMI) recommend culprit artery-only revascularization (CULPRIT) based on safety concerns during noninfarct-related artery intervention. However, the data to support this safety concern are scant. Searches were performed in PubMed/EMBASE/CENTRAL for studies evaluating multivessel revascularization versus CULPRIT in patients with STEMI and multivessel disease (MVD). A multivessel revascularization strategy had to be performed at the time of CULPRIT or during the same hospitalization. Early (≤30-day) and long-term outcomes were evaluated. Among 19 studies (23 arms) that evaluated 61,764 subjects with STEMI and MVD, multivessel revascularization was performed in a minority of patients (16%). For early outcomes, there was no significant difference for outcomes of mortality, MI, stroke, and target vessel revascularization, with a 44% decrease in risk of repeat percutaneous coronary intervention and major adverse cardiovascular events (odds ratio 0.68, 95% confidence interval 0.57 to 0.81) with multivessel revascularization compared to CULPRIT. Similarly, for long-term outcomes (follow-up 2.0 ± 1.1 years), there was no difference for outcomes of MI, target vessel revascularization, and stent thrombosis, with 33%, 43%, and 53% decreases in risk of mortality, repeat percutaneous coronary intervention, coronary artery bypass grafting, respectively, and major adverse cardiovascular events (odds ratio 0.60, 95% confidence interval 0.50 to 0.72) with multivessel revascularization compared to CULPRIT. In conclusion, in patients with STEMI and MVD, multivessel revascularization appears to be safe compared to culprit artery-only revascularization. These findings support the need for a large-scale randomized trial to evaluate revascularization strategies in patients with STEMI and MVD. [Copyright &y& Elsevier]

Abstract: Background: Independent adjudication of clinical trial events is traditionally performed by physicians on a clinical event classification (CEC) committee. Objectives: The experience of the centralized CEC group of the APEX-AMI trial is described. This group adjudicated key secondary pre-specified outcome measures of congestive heart failure (CHF) and cardiogenic shock through 90days using an algorithmic approach for some events. Methods: Data were collected via an electronic data capture (EDC) tool on all subjects, and additional information was provided via EDC for patients identified by site investigators with CHF or shock. Two strategies were used to adjudicate potential events: 1) a computer algorithm (followed by physician confirmation) analyzed data to determine whether events met trial end point definitions; or 2) physician review was used if EDC data were inadequate to allow classification by algorithm. Results: Of 5745 patients, 282 suspected cardiogenic shock and 465 suspected CHF events were identified. The computer algorithm or physicians confirmed 196/282 cardiogenic shock and 277/465 CHF end points. Overall, 242/742 (32.6%) of suspected events were classified by algorithm. Of the 500 events not resolved by computer algorithm, the CEC physicians agreed with site investigator assessments in 126/277 (45%) of CHF and 151/196 (77%) of cardiogenic shock events. The CEC committee completed adjudication of all suspected 30- and 90-day CHF and cardiogenic shock events within 7days of the last patient 30-day follow-up visit and within 1day of the last patient 90-day follow-up visit. Only 27% of patients required source document collection in addition to EDC-collected information. Conclusions: A complementary approach of a computerized assessment and physician review was used in the CEC effort of the APEX-AMI trial. The algorithm categorized approximately one third of suspected CHF/cardiogenic shock events. The APEX-AMI CEC experience shows that an algorithmic approach may be a useful strategy for end point evaluation but requires validation. [Copyright &y& Elsevier]

Abstract: Background: There is a paucity of data concerning the clinical outcome of patients presenting with acute myocardial infarction (AMI) and near-normal coronary angiograms. The purpose of this study was to evaluate the clinical outcome and the prognosis of the patients with near-normal coronary angiograms who were registered in the Korean Acute Myocardial Infarction Registry (KAMIR). Methods: The subjects were divided into three groups according to findings from coronary angiograms performed between September 2005 and November 2006. Among 8510 consecutive AMI patients, 372 patients (Group I) had near-normal coronary arteries, 6136 patients (Group II) had one- or two-vessel disease, and 2002 patients (Group III) had three-vessel or left main disease. Results: Clinical characteristics, in-hospital mortality, and major cardiac adverse events (MACE) were analyzed. Group I was younger, had the lower prevalence of DM, and showed the higher percentage of previous angina history compared to the other two groups. Group III showed a higher incidence of in-hospital mortality, but there was no significant difference between Group I and Group II (2.6% in Group II and 2.2% in Group I, p =0.952). Furthermore, MACE at 1month, 6months and 12months revealed no significant difference between Groups I and II (12month MACE: 7.8% in Group I and 12.2% in Group II, p =0.359). Conclusions: Patients with near-normal coronary angiograms had similar clinical outcomes and prognosis compared with one- or two-vessel diseased patients presenting with an acute myocardial infarction. [ABSTRACT FROM AUTHOR]

Primary percutaneous coronary intervention (PCI) is the optimal method of reperfusion when performed expeditiously. Factors contributing to delays in PCI for ST-segment elevation myocardial infarction (STEMI) have not been thoroughly characterized or quantified. We sought to identify the factors associated with the delays to reperfusion in patients with STEMI undergoing primary PCI. Primary PCI was performed in 3,340 patients with STEMI in the international, multicenter Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction trial. Multivariate analysis was used to identify independent predictors of delay in achieving reperfusion from 38 baseline and procedural variables. A total of 905 patients (27.1%) presented to non-PCI hospitals and were subsequently transferred; the remainder presented to PCI hospitals. The most powerful independent predictor of the interval from symptom onset to arrival at the PCI hospital and the first door-to-balloon time was an initial presentation at a non-PCI hospital (median incremental 58- and 54-minute delay, respectively, both p <0.001). Other independent predictors of prolonged door-to-balloon times included presentation with respiratory failure (42-minute incremental delay, p = 0.003), presentation during off-work hours (11-minute incremental delay, p <0.001), and co-morbid conditions such as diabetes and heart failure. In conclusion, among patients undergoing primary PCI, presentation to a non-PCI hospital was the variable associated with the greatest delay to reperfusion. Systems of care that encourage ambulance diagnosis and direct delivery of patients with STEMI to a PCI hospital might shorten the overall door-to-balloon times and improve the clinical outcomes. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to determine whether patients taking aspirin before an acute coronary syndrome (ACS) are at higher risk of recurrent events or mortality. Background: Controversy exists whether prior aspirin use is an independent predictor of worse outcomes in patients who experience an ACS. Methods: We evaluated 66,443 ACS patients from a merged database of previous Thrombolysis in Myocardial Infarction trials. We evaluated the differences in ACS type, total mortality, and the composite end point of death, myocardial infarction (MI), recurrent ischemia, or stroke between prior aspirin and nonprior aspirin users. We used multivariate analysis to control for differences in baseline characteristics. Results: Prior aspirin users (n = 17,839) were older (63 years vs. 59 years) and had more coronary risk factors and evidence of coronary artery disease (MI, angina, prior intervention) than nonprior aspirin users (n = 48,604) (all p < 0.0001). Prior aspirin use was associated with less severe types of ACS at presentation (e.g., unstable angina > non–ST-segment elevation MI > ST-segment elevation MI) than their nonaspirin user counterparts (p < 0.0001). After multivariate analysis, there was no difference in total mortality between prior aspirin users and nonaspirin users at day 30 (odds ratio [OR]: 1.01; 95% confidence interval [CI]: 0.90 to 1.13) or by the last follow-up visit (mean 328 days) (hazard ratio: 1.03; 95% CI: 0.95 to 1.11). Prior aspirin use was modestly associated with recurrent MI (OR: 1.26; 95% CI: 1.12 to 1.43) and the composite end point (OR: 1.16; 95% CI: 1.08 to 1.24). Conclusions: Prior aspirin use was associated with more comorbidities and coronary disease and a higher risk of recurrent MI, but not mortality. As such, it should best be considered a marker of a patient population at high risk for recurrent adverse events after ACS. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to summarize the evidence of pre-procedural statin therapy to reduce periprocedure cardiovascular events. Background: Invasive procedures can result in adverse cardiovascular events, such as myocardial infarction (MI) and death. We hypothesized that statins might improve clinical outcomes when used before invasive procedures. Methods: We searched the MEDLINE, Cochrane, and clinicaltrials.gov databases from inception to February 2010 for randomized, controlled trials that examined statin therapy before invasive procedures. Invasive procedures were defined as percutaneous coronary intervention, coronary artery bypass grafting (CABG), and noncardiac surgery. We required that studies initiated statins before the procedure and reported clinical outcomes. A DerSimonian-Laird model was used to construct random-effects summary risk ratios. Results: Eight percent of the screened trials (21 of 270) met our selection criteria, which included 4,805 patients. The use of pre-procedural statins significantly reduced post-procedural MI (risk ratio [RR]: 0.57, 95% confidence interval [CI]: 0.46 to 0.70, p < 0.0001). This benefit was seen after both percutaneous coronary intervention (p < 0.0001) and noncardiac surgical procedures (p = 0.004), but not CABG (p = 0.40). All-cause mortality was nonsignificantly reduced by statin therapy (RR: 0.66, 95% CI: 0.37 to 1.17, p = 0.15). Pre-procedural statins also reduced post-CABG atrial fibrillation (RR: 0.54, 95% CI: 0.43 to 0.68, p < 0.0001). Conclusions: Statins administered before invasive procedures significantly reduce the hazard of post-procedural MI. Additionally, statins reduce the risk of atrial fibrillation after CABG. The routine use of statins before invasive procedures should be considered. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the study was to determine the prognostic significance and determinants of myocardial salvage assessed by cardiovascular magnetic resonance (CMR) in reperfused ST-segment elevation myocardial infarction. Background: In acute myocardial infarction, CMR can retrospectively detect the myocardium at risk and the irreversible injury. This allows for quantifying the extent of salvaged myocardium after reperfusion as a potential strong end point for clinical trials and outcome. Methods: We analyzed 208 consecutive ST-segment elevation myocardial infarction patients undergoing primary angioplasty <12 h after symptom onset. T2-weighted and contrast-enhanced CMR was used to calculate the myocardial salvage index (MSI). Patients were categorized into 2 groups defined by the median MSI. The primary end point of the study was occurrence of major adverse cardiovascular events defined as death, reinfarction, and occurrence of new congestive heart failure within 6 months after the index event. Results: The median MSI was 48 (interquartile range 27 to 73). Major adverse cardiovascular events were significantly lower in the MSI ≥ median group (2.9% vs. 22.1%, p < 0.001). The stepwise Cox proportional hazards model revealed that the MSI was the strongest predictor of major adverse cardiovascular events at 6-month follow-up (p < 0.001). All prognostic clinical (symptom onset to reperfusion), angiographic (Thrombolysis In Myocardial Infarction flow grade before angioplasty), and electrocardiographic (ST-segment resolution) parameters showed significant correlations with the MSI (p < 0.001 for all). Conclusions: This study for the first time demonstrates that the MSI assessed by CMR predicts the outcome in acute reperfused ST-segment elevation myocardial infarction. Therefore, MSI assessment has important implications for patient prognosis as well as for the design of future trials intended to test new reperfusion therapy efficacy. (Myocardial Salvage Assessed by Cardiovascular Magnetic Resonance—Impact on Outcome; NCT00952224). [Copyright &y& Elsevier]

Recent data on drug-eluting stents have shown improved clinical outcomes in patients with diabetes mellitus. However, the relative efficacy and safety of sirolimus-eluting stents (SES) compared with paclitaxel-eluting stents (PES) remains controversial. Therefore, a meta-analysis of randomized trials was performed to compare SES with PES exclusively in patients with diabetes. The published research was scanned by formal searches of electronic databases (PubMed, EMBASE and the Cochrane Central Register of Controlled Trials) from January 2001 to April 2009. All randomized trials involving head-to-head comparison of SES versus PES in patients with diabetes were examined for analysis. A total of 5 randomized trials were included in the present meta-analysis, involving 1,173 patients (594 in the SES group, 579 in the PES group). SES were significantly more effective in the reduction of target lesion revascularization (5.1% vs 11.4%, odds ratio [OR] 0.41, 95% confidence interval [CI] 0.26 to 0.64, p <0.001) and angiographic binary (≥50%) restenosis (5.6% vs 16.4%, OR 0.30, 95% CI 0.19 to 0.48, p <0.001) compared to PES. In contrast, the differences between SES and PES were not statistically significant with respect to cardiac death (2.2% vs 2.9%, OR 0.71, 95% CI 0.34 to 1.47, p = 0.35), myocardial infarction (1.5% vs 2.6%, OR 0.58, 95% CI 0.26 to 1.31, p = 0.19), and stent thrombosis (0.6% vs 1.2%, OR 0.57, 95% CI 0.18 to 0.84, p = 0.35). In conclusion, SES are superior to PES in reducing the incidences of restenosis and target lesion revascularization in patients with diabetes, with nonsignificant differences in terms of cardiac death, myocardial infarction, and stent thrombosis. [Copyright &y& Elsevier]

Objectives: The goal of this analysis was to determine whether intensive statin therapy, compared with moderate-dose statin therapy, leads to a reduction in major adverse cardiovascular events (MACE) among patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). Background: When compared with moderate-dose statins, intensive statin therapy reduces MACE among patients with ACS. The role of intensive statin therapy specifically among patients who undergo PCI for ACS is unknown. Methods: Outcomes were compared in 2,868 patients who underwent PCI for ACS just prior to enrollment in the PROVE IT–TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis In Myocardial Infarction 22) trial, which randomized patients to either atorvastatin 80 mg or pravastatin 40 mg daily. The incidence of the primary composite end point of all-cause mortality, myocardial infarction, unstable angina leading to hospitalization, and revascularization after 30 days and stroke was evaluated, as was the incidence of target vessel revascularization (TVR) and non-TVR during follow-up. Results: Treatment with 80 mg atorvastatin reduced the incidence of the composite end point (21.5% vs. 26.5%, hazard ratio: 0.78, 95% confidence interval: 0.67 to 0.91, p = 0.002) and lowered the incidence of both TVR (11.4% vs. 15.4%, p = 0.001) and non-TVR (8.0% vs. 10.5%, p = 0.017) compared with 40 mg pravastatin. After adjusting for on-treatment serum low-density lipoprotein cholesterol and C-reactive protein concentrations, the odds of TVR with high-dose statin therapy remained significant (odds ratio: 0.74, p = 0.015) while the odds of non-TVR did not (odds ratio: 0.92, p = 0.55). Conclusions: Among patients with ACS who undergo PCI, intensive statin therapy reduces MACE compared with moderate-dose statin therapy. The reduction in the incidence of TVR was independent of low-density lipoprotein cholesterol and C-reactive protein lowering and may therefore be due, at least in part, to a pleiotropic effect of high-dose statin therapy. (PROVE IT–TIMI 22; NCT00382460) [Copyright &y& Elsevier]

We explored the safety and quality-of-life consequences of treating patients with stable coronary disease and high-risk features initially with optimal medical therapy (OMT) alone compared to OMT plus percutaneous coronary intervention. This was a post hoc analysis of Clinical Outcomes Utilizing Revascularization and Aggressive DruG Evaluation (COURAGE) trial patients. We defined high risk as the onset of Canadian Cardiovascular Society class III angina within 2 months or stabilized acute coronary syndrome within 2 weeks of enrollment. The primary end point was death or myocardial infarction after 4.6 years. Of the 2,287 patients enrolled in the COURAGE trial, 264 (12%) were high risk and had a relative risk of 1.56 for death or myocardial infarction (p = 0.0008) compared to those with non–high-risk features. A total of 35 primary events occurred in the OMT group and 32 in the percutaneous coronary intervention plus OMT group (hazard ratio 1.11, 95% confidence interval 0.69 to 1.79; p = 0.68). No significant difference was found in the prevalence of angina between the 2 groups at 1 year. During the first year of follow-up, 30% of the OMT patients crossed over to the revascularization group. In conclusion, an initial strategy of OMT alone for high-risk patients in the COURAGE trial did not result in increased death or myocardial infarction at 4.6 years or worse angina at 1 year, but it was associated with a high rate of crossover to revascularization. [Copyright &y& Elsevier]

Abstract: Cellular cardiomyoplasty is an investigational technique that may have the potential to reduce myocardial infarct size and improve cardiac function in patients with ischemic heart disease. However, experience with this approach is still limited to a few small trials, some of which were not blinded or had other design problems. The mechanism of benefit, long-term safety, and clinical efficacy of cellular cardiomyoplasty require further study. [Copyright &y& Elsevier]

Abstract: Aim: To examine the impact of primary stent implantation versus balloon angioplasty on long-term outcome (median 8 years) in 117 patients with ST-elevation myocardial infarction (STEMI) from randomized trials. Methods: Enrolled patients were those presenting with STEMI within 12 h of symptom onset. Patients were randomized to either Palmaz–Schatz stent implantation (N =25) or balloon angioplasty (N =23) between January and November 1996; or Palmaz–Schatz (N =26), or Cordis coil stent implantation (N =24) or balloon angioplasty (N =19) between February 1998 and March 1999. Results: Patients (67±11 years) arrived to the hospital within median 2.5 h of symptom onset with Killip 1/2/3/4 grade (72/19/7/2%, respectively). The culprit lesion was located in the left anterior descending (50%), right (39%), or left circumflex coronary artery (11%) with TIMI 0/1/2/3 flow (81/5/12/2%, respectively). Clinical/angiographic features were comparable between the 2 groups. During follow-up, there was a significant reduction in cardiac mortality in the stent group (5%) compared to the angioplasty group (17%, log-rank test p =0.04). In addition, the stent group had a lower target lesion revascularization rate (28% versus 52%, p =0.008), and a significantly lower major adverse cardiac event rate (37% versus 67%, p =0.005), than the angioplasty group. Conclusion: Compared to balloon angioplasty, primary stenting resulted in a sustained beneficial effect on cardiac mortality at 8 years. [Copyright &y& Elsevier]

Abstract: Background: Acute anterior myocardial infarction (MI) caused by proximal occlusion of the left anterior descending coronary artery (LAD), is associated with unfavourable outcome and should be recognized by simple noninvasive methods like the 12-lead electrocardiogram (ECG). Methods: In a prospective post-hoc DANAMI-2 substudy we compared two pre-specified ECG patterns to determine the level of LAD occlusion. The ECG findings were correlated to coronary angiography from the acute phase. The impact on clinical outcome of ECG and angiographic signs of proximal versus distal LAD occlusion was studied. Results: In 146 patients without confounding factors on the ECG, either ST-elevation ≥0.5 mm in lead aVL or any ST-elevation in lead aVR in association with precordial ST-segment elevation in at least two contiguous leads (including V2, V3 or V4) had a sensitivity of 94%, specificity of 49%, positive predictive value of 85% and negative predictive value of 71% to predict a proximal LAD lesion. Surprisingly, ECG or angiographic signs of lesion proximality were not associated with worse outcome at 30 day or 2.7 year follow-up. Conclusions: The site of occlusion in the LAD could be reliably predicted by 12-lead ECG in patients with acute anterior MI. The prognostic significance of the level of occlusion in the LAD in the modern era of acute ST-elevation MI treatment should be reassessed. [Copyright &y& Elsevier]

We evaluated the use and outcomes of drug-eluting stents (DESs) and bare metal stents (BMSs) in a large primary percutaneous coronary intervention (PCI) acute ST-elevation myocardial infarction (MI) trial. Recently concerns have been raised with “off-label” use of DESs for short- and long-term clinical outcomes. Limited randomized data exist evaluating DESs versus BMSs in ST-elevation MI. Patients (n = 5,745) in the Assessment of Pexelizumab in Acute Myocardial Infarction (APEX-AMI) trial were categorized by stent type used. Baseline variables and clinical outcomes were collected at 90 days and 6 months. Outcomes by stent type were adjusted for using conventional multivariable predictors of 90-day mortality (age, anterior location, total ST-segment deviation, and Killip class), time to PCI, and Thrombolysis In Myocardial Infarction grade flow. Stents were deployed (at the investigator''s discretion) in 5,124 patients (89.2%) with acute MI, with DES use in 2,221 (43.3%) and BMS use in 2,903 (56.7%). Patients receiving DESs were younger (median 59 vs 63 years of age, p <0.001), had left anterior descending coronary artery PCI (57.9% vs 48.1%, p <0.001), and often were treated in the United States (58.2%). DES-treated patients had a lower adjusted mortality at 90 days (hazard ratio 0.73, 95% confidence interval [CI] 0.54 to 0.99, p = 0.046) and trended toward lower mortality (hazard ratio 0.77, 95% CI 0.58 to 1.03, p = 0.084) and recurrent MI (hazard ratio 0.81, 95% CI 0.59 to 1.11, p = 0.186) at 6 months compared with BMSs. In conclusion, in this observational analysis of stent use from a large primary percutaneous intervention for acute MI trial, DESs appear as safe as BMSs with similar 6-month clinical outcomes with regard to death and recurrent MI. [Copyright &y& Elsevier]

Summary: Aims: The Hypothermia after Cardiac Arrest (HACA) trial assessed whether mild therapeutic hypothermia improved the rate of good neurological recovery in patients after ventricular fibrillation cardiac arrest of presumed cardiac origin. We evaluated the impact of hypothermia on myocardial injury. Methods: Re-analysis of a HACA trial subset for our department (cooling, n =55; controls, n =56). Plasma levels of CK, CKMB and ST-scores were used as a measure of infarct size. Results: Area under the curve (AUC) for CK was 28,786U/l×24h (IQR 5646–44,998) in the cooling group and 20,373U/l×24h (IQR 8211–30,801) for controls (p =0.40), for CKMB AUC was 1691U/l×24h (IQR 724–3330) and 1187U/l×24h (IQR 490–2469), respectively (p =0.18). The ST score was −40% (IQR [−55]−[+16]) in the cooling group (n =23) and −22% (IQR [−84]−[+33]) for controls (n =24) (p =0.76). When the cooling group was stratified into early (≤8h) and longer (>8h) time to target temperature, the early group displayed a significantly lower CK 7340U/l×24h (IQR 3921–33,753) vs. 38,986U/l×24h (IQR 23,945–57,514, p =0.007) and a lower CKMB. Conclusion: Cooling after successful resuscitation for ventricular fibrillation cardiac arrest did not influence infarct size. Cautious interpretation of the subgroup analysis may indicate a favourable trend for early cooling. [Copyright &y& Elsevier]

Abstract: Objectives: Estimation of long-term outcome for patients suffering from acute myocardial infarction treated with primary angioplasty in an alsatian public center. Patients and methods: Two-hundred and ninety-eight patients who underwent an urgent coronarography in a non-university center, with a view to immediate angioplasty, between January 1999 and December 2001. Results: Two-hundred and sixty-four patients (88.6%) were actually treated with urgent angioplasty, which has been successful in 87.1% of cases. Hospital mortality was of 7.7%. The population was composed of 16.4% patients older than 75 and of 11.7% patients with Killip 3 or 4 at admission. Mean follow-up was 34 months, lost to follow-up rate was of 4.7%. The global survival rate was of 78.9% and eventless survival rate of 41.9%. Conclusion: Our results confirm the efficiency of angioplasty in real-life conditions as well at short-term as at long-term. [Copyright &y& Elsevier]

Although pharmacologic therapy has made impressive advances in the past decade and is the mainstay of therapy for heart failure (HF), there is still a large unmet need, because morbidity and mortality remain unacceptably high. Implanted medical devices are gaining increasing utility in this group of patients and have the potential to revolutionize the treatment of HF. The majority of devices in clinical use or under active investigation in HF can be grouped into 1 of 4 categories: devices to monitor the HF condition, devices to treat rhythm disturbances, devices to improve the mechanical efficiency of the heart, and devices to replace part or all of the heart’s function. There are several devices either approved or under development to monitor the HF condition, ranging from interactive weight scales to implantable continuous pressure monitors. The challenge is to demonstrate that this technology can improve patient outcomes. Pacemakers and implantable cardioverter defibrillators (ICDs) are used to treat heart rhythms in a broad range of patients with heart disease, but they now have a special place in HF management with the prophylactic use of ICDs in patients who have advanced systolic dysfunction. The Multicenter Automatic Defibrillator Implantation Trial (MADIT) II study demonstrated a 29% reduction in all-cause mortality with ICDs in patients with a history of a myocardial infarction and a left ventricular (LV) ejection fraction <0.30. LV and multisite pacing are means of improving the mechanical efficiency of the heart. The concept is to create a more coordinated contraction of the ventricles to overcome the inefficiency associated with conduction system delays, which are common in HF. The acute hemodynamic effect can be impressive and is immediate. Several studies of intermediate duration (3 to 6 months) have consistently demonstrated that biventricular pacing improves symptoms and exercise capacity. Mechanical methods of remodeling the heart into a more efficient shape have been under scrutiny for several years. New methods of restraining the heart with prosthetic material are under investigation in humans, with encouraging pilot results. Heart replacement has been evaluated clinically with LV assist devices for several decades. The Randomized Evaluation of Mechanical Assistance Therapy as an Alternative in Congestive Heart Failure (REMATCH) study has demonstrated a proof of concept for the use of mechanical blood pumps to improve survival, functional capacity, and symptoms. Several assist devices with such features as total implantability, improved durability, and smaller size are now under study; these may further improve the outcomes of patients. One year ago, the world witnessed the first clinical use of a totally implantable total artificial heart. Although the long-term outcomes were limited, the device demonstrated an impressive ability to improve organ function and extend survival in the population facing imminent death. Further development in this field is expected. The use of devices in HF now has a strong foothold, and the potential exists for substantially greater use of a broad range of devices in the near future. [Copyright &y& Elsevier]

Abstract: Background: Bifurcation lesions at the time of emergent PCI for STEMI are relatively common. However, there are little data regarding their significance. The objective of this study is to evaluate the impact of bifurcation lesions in the setting of emergent percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). Methods: In 391 patients who underwent primary and rescue PCI, the clinical characteristics, procedural success, and in-hospital cardiac events were compared retrospectively between the patients with and without bifurcation lesions. The PCI strategy was at the discretion of the operator. Results: The culprit artery involved a bifurcation lesion in 54/391 (14%) patients. The baseline clinical characteristics between the groups with and without bifurcation lesions were similar. The majority of bifurcation lesions (81%) were seen in the left anterior ascending (LAD) artery. All lesions were treated with the provisional stenting approach, and only 2 (3%) patients required 2 stents. There were no difference in the procedural success and the final TIMI-3 flow, but PCI of bifurcation lesion required higher amount of contrast use. There was no in-hospital MACE in the bifurcation group. The peak cardiac enzyme, left ventricular function, and length of stay were similar in these 2 groups. Conclusions: Bifurcation lesions are relatively common in emergent PCI for STEMI involving the LAD. It can be safely treated with a provisional stenting approach, and the immediate outcome is similar to non-bifurcation lesions. [Copyright &y& Elsevier]