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Showing papers in "European Heart Journal in 2007"


Journal ArticleDOI
TL;DR: The ESC Guidelines and Expert Consensus Documents as mentioned in this paper summarize and evaluate all currently available evidence on a particular issue with the aim to assist physicians in selecting the best management strategies for a typical patient, suffering from a given condition, taking into account the impact on outcome, as well as the risk-benefit ratio of particular diagnostic or therapeutic means.
Abstract: Guidelines and Expert Consensus Documents summarize and evaluate all currently available evidence on a particular issue with the aim to assist physicians in selecting the best management strategies for a typical patient, suffering from a given condition, taking into account the impact on outcome, as well as the risk–benefit ratio of particular diagnostic or therapeutic means. Guidelines are not substitutes for textbooks. The legal implications of medical guidelines have been discussed previously. A great number of Guidelines and Expert Consensus Documents have been issued in recent years by the European Society of Cardiology (ESC) as well as by other societies and organizations. Because of the impact on clinical practice, quality criteria for development of guidelines have been established in order to make all decisions transparent to the user. The recommendations for formulating and issuing ESC Guidelines and Expert Consensus Documents can be found on the ESC web site (http://www.escardio.org/knowledge/guidelines/rules). In brief, experts in the field are selected and undertake a comprehensive review of the published evidence for management and/or prevention of a given condition. A critical evaluation of diagnostic and therapeutic procedures is performed, including assessment of the risk–benefit ratio. Estimates of expected health outcomes for larger societies are included, where data exist. The level of evidence and the strength of recommendation of particular treatment options are weighed and graded according to predefined scales, as outlined in the tables below. The experts of the writing panels have provided disclosure statements of all relationships they may have which might be perceived as real or potential sources of conflicts of interest. These disclosure forms are kept on file at the European Heart House, headquarters of the ESC. Any changes in conflict of interest that arise during the writing period must be notified to the ESC. The Task Force report was entirely …

3,317 citations


Journal ArticleDOI
TL;DR: Information on myocardial infarction attack rates can provide useful data regarding the burden of coronary artery disease within and across populations, especially if standardized data are collected in a manner that demonstrates the distinction between incident and recurrent events.
Abstract: ![Graphic][1] Myocardial infarction is a major cause of death and disability worldwide. Coronary atherosclerosis is a chronic disease with stable and unstable periods. During unstable periods with activated inflammation in the vascular wall, patients may develop a myocardial infarction. Myocardial infarction may be a minor event in a lifelong chronic disease, it may even go undetected, but it may also be a major catastrophic event leading to sudden death or severe haemodynamic deterioration. A myocardial infarction may be the first manifestation of coronary artery disease, or it may occur, repeatedly, in patients with established disease. Information on myocardial infarction attack rates can provide useful data regarding the burden of coronary artery disease within and across populations, especially if standardized data are collected in a manner that demonstrates the distinction between incident and recurrent events. From the epidemiological point of view, the incidence of myocardial infarction in a population can be used as a proxy for the prevalence of coronary artery disease in that population. Furthermore, the term myocardial infarction has major psychological and legal implications for the individual and society. It is an indicator of one of the leading health problems in the world, and it is an outcome measure in clinical trials and observational studies. With these perspectives, myocardial infarction may be defined from a number of different clinical, electrocardiographic, biochemical, imaging, and pathological characteristics. In the past, a general consensus existed for the clinical syndrome designated as myocardial infarction. In studies of disease prevalence, the World Health Organization (WHO) defined myocardial infarction from symptoms, ECG abnormalities, and enzymes. However, the development of more sensitive and specific serological biomarkers and precise imaging techniques allows detection of ever smaller amounts of myocardial necrosis. Accordingly, current clinical practice, health care delivery systems, as well as epidemiology and clinical trials all require a … [1]: /embed/inline-graphic-1.gif

3,193 citations


Journal ArticleDOI
TL;DR: The updated strategies for the diagnosis and exclusion of HFNEF are useful not only for individual patient management but also for patient recruitment in future clinical trials exploring therapies forHFNEF.
Abstract: Diastolic heart failure (DHF) currently accounts for more than 50% of all heart failure patients. DHF is also referred to as heart failure with normal left ventricular (LV) ejection fraction (HFNEF) to indicate that HFNEF could be a precursor of heart failure with reduced LVEF. Because of improved cardiac imaging and because of widespread clinical use of plasma levels of natriuretic peptides, diagnostic criteria for HFNEF needed to be updated. The diagnosis of HFNEF requires the following conditions to be satisfied: (i) signs or symptoms of heart failure; (ii) normal or mildly abnormal systolic LV function; (iii) evidence of diastolic LV dysfunction. Normal or mildly abnormal systolic LV function implies both an LVEF > 50% and an LV end-diastolic volume index (LVEDVI) 16 mmHg or mean pulmonary capillary wedge pressure >12 mmHg) or non-invasively by tissue Doppler (TD) (E/E' > 15). If TD yields an E/E' ratio suggestive of diastolic LV dysfunction (15 > E/E' > 8), additional non-invasive investigations are required for diagnostic evidence of diastolic LV dysfunction. These can consist of blood flow Doppler of mitral valve or pulmonary veins, echo measures of LV mass index or left atrial volume index, electrocardiographic evidence of atrial fibrillation, or plasma levels of natriuretic peptides. If plasma levels of natriuretic peptides are elevated, diagnostic evidence of diastolic LV dysfunction also requires additional non-invasive investigations such as TD, blood flow Doppler of mitral valve or pulmonary veins, echo measures of LV mass index or left atrial volume index, or electrocardiographic evidence of atrial fibrillation. A similar strategy with focus on a high negative predictive value of successive investigations is proposed for the exclusion of HFNEF in patients with breathlessness and no signs of congestion. The updated strategies for the diagnosis and exclusion of HFNEF are useful not only for individual patient management but also for patient recruitment in future clinical trials exploring therapies for HFNEF.

2,578 citations


Journal ArticleDOI
TL;DR: This document, The European Society of Cardiology Working Group on Myocardial and Pericardial Diseases presents an update of the existing classification scheme, to help clinicians look beyond generic diagnostic labels in order to reach more specific diagnoses.
Abstract: In biology, classification systems are used to promote understanding and systematic discussion through the use of logical groups and hierarchies In clinical medicine, similar principles are used to standardise the nomenclature of disease For more than three decades, heart muscle diseases have been classified into primary or idiopathic myocardial diseases (cardiomyopathies) and secondary disorders that have similar morphological appearances, but which are caused by an identifiable pathology such as coronary artery disease or myocardial infiltration (specific heart muscle diseases) In this document, The European Society of Cardiology Working Group on Myocardial and Pericardial Diseases presents an update of the existing classification scheme The aim is to help clinicians look beyond generic diagnostic labels in order to reach more specific diagnoses

2,370 citations


Journal ArticleDOI
TL;DR: Guidelines and Expert Consensus Documents summarize and evaluate all currently available evidence on a particular issue with the aim to assist physicians in selecting the best management strategies for a typical patient, suffering from a given condition, taking into account the impact on outcome, as well as the risk–benefit ratio of particular diagnostic or therapeutic means.
Abstract: Guidelines and Expert Consensus Documents summarize and evaluate all currently available evidence on a particular issue with the aim to assist physicians in selecting the best management strategies for a typical patient, suffering from a given condition, taking into account the impact on outcome, as well as the risk–benefit ratio of particular diagnostic or therapeutic means. Guidelines are no substitutes for textbooks. The legal implications of medical guidelines have been discussed previously. A great number of Guidelines and Expert Consensus Documents have been issued in recent years by the European Society of Cardiology (ESC) as well as by other societies and organizations. Because of the impact on clinical practice, quality criteria for development of guidelines have been established in order to make all decisions transparent to the user. The recommendations for formulating and issuing ESC Guidelines and Expert Consensus Documents can be found on the ESC website (http://www.escardio.org/knowledge/guidelines/rules). In brief, experts in the field are selected and undertake a comprehensive review of the published evidence for management and/or prevention of a given condition. A critical evaluation of diagnostic and therapeutic procedures is performed including assessment of the risk–benefit ratio. Estimates of expected health outcomes for larger societies are included, where data exist. The level of evidence and the strength of recommendation of particular treatment options are weighed and graded according to pre-defined scales, as outlined in Tables 1 and 2 . View this table: Table 1 Classes of recommendations View this table: Table 2 Levels of evidence The experts of the writing panels have provided disclosure statements of all relationships they may have which might be perceived as real or potential sources of conflicts of interest. These disclosure forms are kept on file at the European Heart House, headquarters of the ESC. Any changes in conflict of interest that arise during the writing period must be notified to the …

1,960 citations


Journal ArticleDOI
TL;DR: The European Society of Hypertension (ESH) and the European Society Of Cardiology (ESC) as mentioned in this paper decided not to produce their own guidelines on the diagnosis and treatment of hypertension but to endorse the guidelines on hypertension issued by the World Health Organization (WHO) and International Society of hypertension (ISH)1,2 with some adaptation to reflect the situation in Europe.
Abstract: For several years the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC) decided not to produce their own guidelines on the diagnosis and treatment of hypertension but to endorse the guidelines on hypertension issued by the World Health Organization (WHO) and International Society of Hypertension (ISH)1,2 with some adaptation to reflect the situation in Europe. However, in 2003 the decision was taken to publish ESH/ESC specific guidelines3 based on the fact that, because the WHO/ISH Guidelines address countries widely varying in the extent of their health care and availability of economic resource, they contain diagnostic and therapeutic recommendations that may be not totally appropriate for European countries. In Europe care provisions may often allow a more in-depth diagnostic assessment of cardiovascular risk and organ damage of hypertensive individuals as well as a wider choice of antihypertensive treatment. The 2003 ESH/ESC Guidelines3 were well received by the clinical world and have been the most widely quoted paper in the medical literature in the last two years.4 However, since 2003 considerable additional evidence on important issues related to diagnostic and treatment approaches to hypertension has become available and therefore updating of the previous guidelines has been found advisable. In preparing the new guidelines the Committee established by the ESH and ESC has agreed to adhere to the principles informing the 2003 Guidelines, namely 1) to try to offer the best available and most balanced recommendation to all health care providers involved in the management of hypertension, 2) to address this aim again by an extensive and critical review of the data accompanied by a series of boxes where specific recommendations are given, as well as by a concise set of practice recommendations to be published soon thereafter as already done in 2003; …

1,760 citations


Journal ArticleDOI
TL;DR: The ultimate intent of this document is to provide an understanding of the range of acceptable approaches for the use of EMB while recognizing that individual patient care decisions depend on factors not well reflected in the published literature, such as local availability of specialized facilities, cardiovascular pathology expertise, and operator experience.
Abstract: The role of endomyocardial biopsy (EMB) in the diagnosis and treatment of adult and pediatric cardiovascular disease remains controversial, and the practice varies widely even among cardiovascular centers of excellence. A need for EMB exists because specific myocardial disorders that have unique prognoses and treatment are seldom diagnosed by noninvasive testing.1 Informed clinical decision making that weighs the risks of EMB against the incremental diagnostic, prognostic, and therapeutic value of the procedure is especially challenging for nonspecialists because the relevant published literature is usually cited according to specific cardiac diseases, which are only diagnosed after EMB. To define the current role of EMB in the management of cardiovascular disease, a multidisciplinary group of experts in cardiomyopathies and cardiovascular pathology was convened by the American Heart Association (AHA), the American College of Cardiology (ACC), and the European Society of Cardiology (ESC). The present Writing Group was charged with reviewing the published literature on the role of EMB in cardiovascular diseases, summarizing this information, and making useful recommendations for clinical practice with classifications of recommendations and levels of evidence. The Writing Group identified 14 clinical scenarios in which the incremental diagnostic, prognostic, and therapeutic value of EMB could be estimated and compared with the procedural risks. The recommendations contained in the present joint Scientific Statement are derived from a comprehensive review of the published literature on specific cardiomyopathies, arrhythmias, and cardiac tumors and are categorized according to presenting clinical syndrome rather than pathologically confirmed disease. The ultimate intent of this document is to provide an understanding of the range of acceptable approaches for the use of EMB while recognizing that individual patient care decisions depend on factors not well reflected in the published literature, such as local availability of specialized facilities, cardiovascular pathology expertise, and operator experience. The use of EMB …

1,050 citations


Journal ArticleDOI
TL;DR: WHR and WC are significantly associated with the risk of incident CVD events and these simple measures of abdominal obesity should be incorporated into CVD risk assessments.
Abstract: Aims The objectives of this study were to determine the association of waist circumference (WC) and waist-to-hip ratio (WHR) with the risk of incident cardiovascular disease (CVD) events and to determine whether the strength of association of WC and WHR with CVD risk is different. Methods and results This meta-regression analysis used a search strategy of keywords and MeSH terms to identify prospective cohort studies and randomized clinical trials of CVD risk and abdominal obesity from the Medline, Embase, and Cochrane databases. Fifteen articles ( n = 258 114 participants, 4355 CVD events) reporting CVD risk by categorical and continuous measures of WC and WHR were included. For a 1 cm increase in WC, the relative risk (RR) of a CVD event increased by 2% (95% CI: 1–3%) overall after adjusting for age, cohort year, or treatment. For a 0.01 U increase in WHR, the RR increased by 5% (95% CI: 4–7%). These results were consistent in men and women. Overall risk estimates comparing the extreme quantiles of each measure suggested that WHR was more strongly associated with CVD than that for WC (WHR: RR = 1.95, 95% CI: 1.55–2.44; WC: RR = 1.63, 95% CI: 1.31–2.04), although this difference was not significant. The strength of association for each measure was similar in men and women. Conclusion WHR and WC are significantly associated with the risk of incident CVD events. These simple measures of abdominal obesity should be incorporated into CVD risk assessments.

968 citations


Journal ArticleDOI
TL;DR: The ESC Guidelines and Expert Consensus Documents summarize and evaluate all currently available evidence on a particular issue with the aim to assist physicians in selecting the best management strategies for a typical patient, suffering from a given condition, taking into account the impact on outcome, as well as the risk-benefit ratio of particular diagnostic or therapeutic means as mentioned in this paper.
Abstract: Guidelines and Expert Consensus Documents summarize and evaluate all currently available evidence on a particular issue with the aim to assist physicians in selecting the best management strategies for a typical patient, suffering from a given condition, taking into account the impact on outcome, as well as the risk–benefit ratio of particular diagnostic or therapeutic means. Guidelines are no substitutes for textbooks. The legal implications of medical guidelines have been discussed previously. A great number of Guidelines and Expert Consensus Documents have been issued in recent years by the European Society of Cardiology (ESC) as well as by other societies and organizations. Because of the impact on clinical practice, quality criteria for development of guidelines have been established in order to make all decisions transparent to the user. The recommendations for formulating and issuing ESC Guidelines and Expert Consensus Documents can be found on the ESC website (http://www.escardio.org/knowledge/guidelines/rules). In brief, experts in the field are selected and undertake a comprehensive review of the published evidence for management and/or prevention of a given condition. A critical evaluation of diagnostic and therapeutic procedures is performed including the assessment of the risk/benefit ratio. Estimates of expected health outcomes for larger societies are included, where data exist. The level of evidence and the strength of recommendation of particular treatment options are weighed and graded according to pre-defined scales, as outlined in Tables 1 and 2 . View this table: Table 1 Classes of recommendations View this table: Table 2 Levels of evidence The experts of the writing panels have provided disclosure statements of all relationships they may have which might be perceived as real or potential sources of conflicts of interest. These disclosure forms are kept on file at the European Heart House, headquarters of the ESC. Any changes in conflict of interest that arise during the writing period must be notified …

888 citations


Journal ArticleDOI
TL;DR: Impaired LVEF, older age, and comorbidity were the most striking characteristics of patients who were denied surgery in patients with severe symptomatic mitral regurgitation who are denied surgery.
Abstract: Aim To identify the proportion and characteristics of patients with severe symptomatic mitral regurgita tion (MR) who are denied surgery. Methods and results In the Euro Heart Survey on valvular heart disease, 396 patients had severe symptomatic MR as assessed by Doppler-echocardiography (grade >= 3/4) and New York Heart Association class 11 or greater. Patient characteristics were analysed according to the decision to operate or not. A decision not to operate was taken in 193 patients (49%). In multivariable analysis, decreased left ventricular ejection fraction (LVEF) [OR= 1.39 per 10% decrease, 95% CI (1.17-1.66), P = 0.0002], non-ischaemic aetiology [OR = 4.44, 95% CI (1.96-10.76), P = 0.0006], older age [OR = 1.40 per 10-year increase, 95% CI(1.15-1.72), P=0.001], increased Charlson comorbidity index [OR= 1.38 per 1 point increase, 95% CI (1.12-1.72), P = 0.004], and grade 3 MR [OR = 2.23, 95% CI (1.28-3.29), P = 0.005] were associated with the decision not to operate. One-year survival was 96.0 +/- 1.4% in patients with a positive decision for intervention vs. 89.5 +/- 2.3% in those with a negative decision (P = 0.02). Conclusion Surgery was denied in 49% of patients with severe symptomatic MR. Impaired LVEF, older age, and comorbidity were the most striking characteristics of patients who were denied surgery. The weight of age and LVEF in the decision do not seem justified according to current knowledge.

775 citations


Journal ArticleDOI
TL;DR: The RV contains prognostic information in IPAH and a large RV volume, low SV, and a reduced LV volume are strong independent predictors of mortality and treatment failure.
Abstract: Aims This study investigated the relationship between right ventricular (RV) structure and function and survival in idiopathic pulmonary arterial hypertension (IPAH). Methods and results In 64 patients, cardiac magnetic resonance, right heart catheterization, and the six-minute walk test (6MWT) were performed at baseline and after 1-year follow-up. RV structure and function were analysed as predictors of mortality. During a mean follow-up of 32 months, 19 patients died. A low stroke volume (SV), RV dilatation, and impaired left ventricular (LV) filling independently predicted mortality. In addition, a further decrease in SV, progressive RV dilatation, and further decrease in LV end-diastolic volume (LVEDV) at 1-year follow-up were the strongest predictors of mortality. According to Kaplan–Meier survival curves, survival was lower in patients with an inframedian SV index ≤ 25 mL/m2, a supramedian RV end-diastolic volume index ≥ 84 mL/m2, and an inframedian LVEDV≤40 mL/m2. Conclusions The RV contains prognostic information in IPAH. A large RV volume, low SV, and a reduced LV volume are strong independent predictors of mortality and treatment failure.

Journal ArticleDOI
TL;DR: ‘Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes’ recently published in European Heart Journal 1 rightly dedicates space to the pitfalls that can be encountered when reading presentation ECGs, but there is an important omission.
Abstract: ‘Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes: The Task Force for the Diagnosis and Treatment of Non-ST-Segment Elevation Acute Coronary Syndromes of the European Society of Cardiology’ recently published in European Heart Journal 1 rightly dedicates space to the pitfalls that can be encountered when reading presentation ECGs. However, we wish to draw attention to what we think is an important omission. No reference is made in this context to acute aortic syndrome (AAS)—a condition in …

Journal ArticleDOI
TL;DR: Improved 1 year clinical outcomes in patients with acute myocardial infarction receiving intracoronary administration of bone marrow-derived progenitors cells (BMCs) after successful reperfusion therapy are shown.
Abstract: Aims To investigate the clinical outcome after intracoronary administration of autologous progenitor cells in patients with acute myocardial infarction (AMI). Methods and results Using a double-blind, placebo-controlled multicentre trial design, we randomized 204 patients with successfully reperfused AMI to receive intracoronary infusion of bone-marrow-derived progenitor cells (BMCs) or placebo medium into the infarct artery 3-7 days after successful infarct reperfusion therapy. At 12 months, the pre-specified cumulative endpoint of death, myocardial infarction, or necessity for revascularization was significantly reduced in the BMC group compared with placebo (P=0.009). Likewise, the combined endpoint death, recurrence of myocardial infarction, and rehospitalization for heart failure was significantly (P=0.006) reduced in patients receiving intracoronary BMC administration. Intracoronary administration of BMC remained a significant predictor of a favourable clinical outcome by Cox regression analysis, adjusting for classical predictors of poor outcome after AMI. Conclusion Intracoronary administration of BMCs is associated with a significant reduction of the occurrence of major adverse cardiovascular events after AMI. Large-scale studies are warranted to confirm the effects of BMC administration on mortality and morbidity in patients with AMIs.

Journal ArticleDOI
TL;DR: This first experience documents the feasibility of prospective ECG-gating for CTCA with diagnostic image quality at a low radiation dose, favouring HR <63 b.p.m. (P < 0.001).
Abstract: Aims To determine the feasibility of prospective electrocardiogram (ECG)-gating to achieve low-dose computed tomography coronary angiography (CTCA). Methods and results Forty-one consecutive patients with suspected ( n = 35) or known coronary artery disease ( n = 6) underwent 64-slice CTCA using prospective ECG-gating. Individual radiation dose exposure was estimated from the dose-length product. Two independent readers semi-quantitatively assessed the overall image quality on a five-point scale and measured vessel attenuation in each coronary segment. One patient was excluded for atrial fibrillation. Mean effective radiation dose was 2.1 ± 0.6 mSv (range, 1.1–3.0 mSv). Image quality was inversely related to heart rate (HR) (57.3 ± 6.2, range 39–66 b.p.m.; r = 0.58, P 63 b.p.m. ( P < 0.001). Conclusion This first experience documents the feasibility of prospective ECG-gating for CTCA with diagnostic image quality at a low radiation dose (1.1–3.0 mSv), favouring HR <63 b.p.m.

Journal ArticleDOI
TL;DR: Hyponatraemia in hospitalized patients with heart failure is relatively common and is associated with longer hospital stays and higher in-hospital and early post-discharge mortality.
Abstract: Aims Hyponatraemia has been shown to be an independent predictor of mortality in selected patients with heart failure enrolled in clinical trials. The predictive value of hyponatraemia has not been evaluated in unselected patients hospitalized with heart failure. Methods and results OPTIMIZE-HF is a registry and performance-improvement programme for patients hospitalized with heart failure and includes a subgroup with 60–90 day follow-up data. The relationship between admission serum sodium concentration and clinical outcomes was analysed in 48 612 patients from 259 hospitals. Admission serum sodium levels were analysed both as a continuous variable and by grouping patients with admission Na <135 and Na ≥ 135 mmol/L. Patients with hyponatraemia (Na <135 mmol/L) at the time of hospital admission had modest differences in baseline clinical characteristics and management during hospitalization compared with patients who had serum sodium ≥135 mmol/L. Patients with hyponatraemia were more likely to be Caucasian, have lower admission systolic blood pressure, and receive intravenous inotropes during hospitalization. Patients with hyponatraemia had significantly higher rates of in-hospital and follow-up mortality and longer hospital stays, although no difference in re-admission rates was observed. After adjusting for differences with multivariable analysis, the risk of in-hospital death increased by 19.5%, the risk of follow-up mortality by 10%, and the risk of death or rehospitalization by 8% for each 3 mmol/L decrease in admission serum sodium below 140 mmol/L. Conclusion Hyponatraemia in hospitalized patients with heart failure is relatively common and is associated with longer hospital stays and higher in-hospital and early post-discharge mortality. Re-admission rates were equally high in patients with or without hyponatraemia.

Journal ArticleDOI
TL;DR: Six major platelet function tests are not equally effective in measuring aspirin's antiplatelet effect and correlate poorly amongst themselves, and the clinical usefulness of the different assays to classify correctly patients as aspirin resistant remains undetermined.
Abstract: Aims We sought to compare the results obtained from six major platelet function tests in the assessment of the prevalence of aspirin resistance in patients with stable coronary artery disease. Methods and results 201 patients with stable coronary artery disease receiving daily aspirin therapy (≥80 mg) were recruited. Platelet aggregation was measured by: (i) light transmission aggregometry (LTA) after stimulation with 1.6 mM of arachidonic acid (AA), (ii) LTA after adenosine diphosphate (ADP) (5, 10, and 20 µM) stimulation, (iii) whole blood aggregometry, (iv) PFA-100®, (v) VerifyNow Aspirin®; urinary 11-dehydro-thromboxane B2 concentrations were also measured. Eight patients (4%, 95% CI 0.01–0.07) were deemed resistant to aspirin by LTA and AA. The prevalence of aspirin resistance varied according to the assay used: 10.3–51.7% for LTA using ADP as the agonist, 18.0% for whole blood aggregometry, 59.5% for PFA-100®, 6.7% for VerifyNow Aspirin®, and finally, 22.9% by measuring urinary 11-dehydro-thromboxane B2 concentrations. Results from these tests showed poor correlation and agreement between themselves. Conclusion Platelet function tests are not equally effective in measuring aspirin's antiplatelet effect and correlate poorly amongst themselves. The clinical usefulness of the different assays to classify correctly patients as aspirin resistant remains undetermined.

Journal ArticleDOI
TL;DR: In aspirin-treated subjects with coronary artery disease, prasugrel 60/10 mg provides faster onset and greater inhibition of P2Y(12) receptor-mediated platelet aggregation than clopidogrel 600/75 mg, because of greater and more efficient generation of the active metabolite.
Abstract: Aims P2Y12 receptor antagonism and platelet inhibition by prasugrel vs. clopidogrel were investigated in patients with stable coronary artery disease. Methods and results One hundred and ten aspirin treated subjects were randomized to double-blind treatment with clopidogrel ( n = 55) 600 mg loading dose (LD) and 75 mg maintenance dose (MD) or prasugrel ( n = 55) 60 mg LD and 10 mg MD for 28 days. Concentrations of prasugrel and clopidogrel active metabolites were determined. Platelet aggregation to 20 µM adenosine diphosphate, measured by light transmission aggregometry, was reported as maximal platelet aggregation (MPA). P2Y12 function was assessed by the vasodilator-stimulated phosphoprotein assay and reported as platelet reactivity index (PRI). The same pharmacodynamic measurements were performed after ex vivo addition of clopidogrel’s active metabolite. At 2 h post-LD, mean MPA was 31 vs. 55%, and mean PRI 8.3 vs. 55.9% for prasugrel and clopidogrel, respectively ( P < 0.001). During MD on day 14 and 28, mean MPA was 42 vs. 54% and mean PRI was 25 vs. 51%, respectively ( P < 0.001). Peak level of the active metabolite and P2Y12 inhibition occurred earlier and was greater with prasugrel ( P < 0.001). Mean area under the time-concentration curve (AUC; μM·h) of the respective active metabolite was higher with prasugrel vs. clopidogrel post-LD (1.11 vs. 0.24) and post-MD (0.16 vs. 0.062). Ex vivo addition of clopidogrel’s active metabolite further reduced PRI in all patients whose platelets were not already maximally inhibited. Conclusion In aspirin-treated subjects with coronary artery disease, prasugrel 60/10 mg provides faster onset and greater inhibition of P2Y12 receptor-mediated platelet aggregation than clopidogrel 600/75 mg, because of greater and more efficient generation of the active metabolite.

Journal ArticleDOI
TL;DR: Patients with extensive CAD in vessels remote from the infarct-related artery have reduced reperfusion success and an adverse prognosis following primary PCI in AMI and future studies regarding the optimal treatment of patients with multivessel disease and AMI are warranted.
Abstract: Aims We sought to investigate the impact of multivessel coronary artery disease (CAD) on reperfusion success and prognosis following primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). The influence of multivessel disease on myocardial reperfusion and subsequent survival after primary PCI has not been studied. Methods and results In the CADILLAC trial, primary PCI was performed in 2082 patients of any age with AMI within 12 h of symptom onset. Myocardial perfusion post-PCI assessed by ST-segment recovery and myocardial blush and clinical outcomes were stratified by the extent of CAD. Single-, double-, and triple-vessel disease were present in 1066 (51.2%), 692 (33.2%), and 324 (15.6%) patients, respectively. Patients with multivessel disease compared with those with single-vessel disease undergoing primary PCI were significantly more likely to have absent ST-segment recovery (13.3 vs. 7.4%, P = 0.01), though the rates of post-procedural TIMI-3 flow (89.7 vs. 88.9%, P = 0.66) and grade 2 or 3 myocardial blush (51.2 vs. 51.5%, P = 0.91) in the infarct vessel were comparable. By 1 year, the cumulative incidence of death for patients with single-, double-, and triple-vessel disease was 3.2, 4.4, and 7.8%, respectively ( P = 0.003), and the composite rate of major adverse cardiac events (MACE) was 14.8, 19.5, and 23.6%, respectively ( P = 0.0006). By multivariable analysis, the presence of triple-vessel disease was the strongest predictor of 1-year death [hazard ratio (HR) = 2.60, P = 0.009], death and re-infarction (HR = 1.88, P = 0.03), and MACE (HR = 1.80, P = 0.0009). Conclusion Patients with extensive CAD in vessels remote from the infarct-related artery have reduced reperfusion success and an adverse prognosis following primary PCI in AMI. Future studies regarding the optimal treatment of patients with multivessel disease and AMI are warranted.

Journal ArticleDOI
TL;DR: Cell isolation protocols have a major impact on the functional activity of bone marrow-derived progenitor cells and additional functional testing appears to be mandatory to assure proper cell function before embarking on clinical cell therapy trials.
Abstract: Aim The recently published REPAIR-AMI and ASTAMI trial showed differences in contractile recovery of left ventricular function after infusion of bone marrow-derived cells in acute myocardial infarction. Since the trials used different protocols for cell isolation and storage (REPAIR-AMI: Ficoll, storage in X-vivo 10 medium plus serum; ASTAMI: Lymphoprep, storage in NaCl plus plasma), we compared the functional activity of BMC isolated by the two different protocols. Methods and results The recovery of total cell number, colony-forming units (CFU), and the number of mesenchymal stem cells were significantly reduced to 77 ± 4%, 83 ± 16%, and 65 ± 15%, respectively, when using the ASTAMI protocol compared with the REPAIR protocol. The capacity of the isolated BMC to migrate in response to stromal cell-derived factor 1 (SDF-1) was profoundly reduced when using the ASTAMI cell isolation procedure (42 ± 8% and 78 ± 3% reduction in healthy and CAD-patient cells, respectively). Finally, infusion of BMC into a hindlimb ischaemia model demonstrated a significantly blunted blood-flow-recovery by BMC isolated with the ASTAMI protocol (54 ± 6% of the effect obtained by REPAIR cells). Comparison of the individual steps identified the use of NaCl and plasma for cell storage as major factors for functional impairment of the BMC. Conclusion Cell isolation protocols have a major impact on the functional activity of bone marrow-derived progenitor cells. The assessment of cell number and viability may not entirely reflect the functional capacity of cells in vivo . Additional functional testing appears to be mandatory to assure proper cell function before embarking on clinical cell therapy trials.

Journal ArticleDOI
TL;DR: An unexpectedly high percentage of patients with heart failure fulfilling current echocardiographic criteria for LVNC is demonstrated, which might be explained by a hitherto underestimated cause of heart failure, but the comparison with controls suggests that current diagnostic criteria are too sensitive, particularly in black individuals.
Abstract: Aims Left-ventricular non-compaction (LVNC) is characterized by excessive and prominent left-ventricular (LV) trabeculations and may be associated with systolic dysfunction in advanced disease. We sought to determine the proportion of patients fulfilling LVNC criteria in an adult population referred to a heart failure clinic using current diagnostic criteria. Methods and results One hundred and ninety-nine patients [age 63.5 ± 15.9 years, 124 (62.3%) males] with LV systolic impairment were studied. All underwent clinical examination, electrocardiography, and 2-D echocardiography. The number of patients fulfilling diagnostic criteria for LVNC was retrospectively determined using three published definitions. Results were compared with 60 prospectively evaluated normal controls (age 35.7 ± 13.5 years; 31 males, 30 blacks). Forty-seven patients (23.6%) fulfilled one or more echocardiographic definitions for LVNC. Patients fulfilling LVNC criteria were younger ( P = 0.002), had larger LV end-diastolic dimension ( P < 0.001), and smaller left atrial size ( P = 0.01). LVNC was more common in black individuals (35.5 vs. 16.2%, P = 0.003). Five controls (four blacks) fulfilled one or more LVNC criteria. Conclusions This study demonstrates an unexpectedly high percentage of patients with heart failure fulfilling current echocardiographic criteria for LVNC. This might be explained by a hitherto underestimated cause of heart failure, but the comparison with controls suggests that current diagnostic criteria are too sensitive, particularly in black individuals.

Journal ArticleDOI
TL;DR: TTC is accompanied by severe morphological alterations potentially resulting from catecholamine excess followed by microcirculatory dysfunction and direct cardiotoxicity, however, the affected myocardium represents a high potential of structural reconstitution which correlates with the rapid functional recovery.
Abstract: Aims To gain more insight into the phenomenon of Tako-Tsubo cardiomyopathy (TTC), the purpose of the present study was to investigate the myocardial structure in the acute phase of TTC and after functional recovery. Methods and results We studied eight patients presenting with TTC diagnosed by coronary angiography, ventriculography, magnetic resonance imaging, and echocardiography. Serial myocardial biopsies were taken during the phase of severely impaired left ventricular function and after functional recovery. Specimens were examined by light and electron microscope as well as immunohistochemistry. Additionally, specific methods detecting different types of cell death and measurements of virus titer were performed. All patients showed the typical contractile pattern of TTC and complete functional recovery within 12 ± 3 days. In ‘acute’ biopsies, many vacuoles of different size were found contributing to cellular hypertrophy. PAS staining revealed intracellular accumulation of glycogen. Additionally, structural deteriorations characterized by disorganization of contractile and cytoskeletal proteins could be detected. The extracellular matrix proteins were increased. Signs of oncotic and apoptotic cell death were absent. After functional recovery, all described alterations showed a nearly complete reversibility. Conclusion TTC is accompanied by severe morphological alterations potentially resulting from catecholamine excess followed by microcirculatory dysfunction and direct cardiotoxicity. However, the affected myocardium represents a high potential of structural reconstitution which correlates with the rapid functional recovery.

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TL;DR: Multivariable regression analysis suggests that preserved LV twist and circumferential strain may contribute to normal EF in patients with diastolic heart failure, and LV longitudinal and radial strains are reduced, but circumFerential deformation and twist are normal in DHF patients.
Abstract: Aims To examine myocardial deformation and rotation in patients with heart failure, and elucidate the underlying mechanisms that account for normal ejection fraction (EF) in patients with diastolic heart failure (DHF). Methods and results Fifty consecutive patients presenting with congestive heart failure (age: 58 ± 16 years) underwent simultaneous right heart catheterization and transthoracic echocardiography. Left ventricular (LV) volumes, mass, EF, meridional, and circumferential wall stress were measured in addition to haemodynamic measurements. 2-D speckle tracking was applied to measure longitudinal, radial, and circumferential strain and twist. Twist was reduced only in patients with systolic heart failure (SHF: 5 ± 2°, DHF: 13 ± 6°, control: 14 ± 5°, P 0.05), though it was significantly lower in patients with SHF (−7 ± 3%, P < 0.05). Importantly, longitudinal (DHF:−12%, SHF: −4%, control: −19%, P < 0.001) and radial (DHF: 28 ± 9%, SHF: 14 ± 8%, control: 47 ± 7%, P < 0.001) strains were significantly lower in both heart failure groups than in controls, and were depressed to a larger extent in SHF patients than in those with DHF (both P < 0.05). Conclusion LV longitudinal and radial strains are reduced, but circumferential deformation and twist are normal in DHF patients. On the other hand, in patients with SHF, longitudinal, radial, and circumferential deformation, and twist are all reduced. Multivariable regression analysis suggests that preserved LV twist and circumferential strain may contribute to normal EF in patients with DHF.

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TL;DR: This is the first study to show that not only bone marrow-derived cells but also ADSCs engrafted in the infarct region 4 weeks after intracoronary cell transplantation and improved cardiac function and perfusion via angiogenesis.
Abstract: Aims This study was designed to assess whether intracoronary application of adipose tissue-derived stem cells (ADSCs) compared with bone marrow-derived stem cells (BMSCs) and control could improve cardiac function after 30 days in a porcine acute myocardial infarction/reperfusion model. Methods and results An acute transmural porcine myocardial infarction was induced by inflating an angioplasty balloon for 180 min in the mid-left anterior descending artery. Two million cultured autologous stem cells were intracoronary injected through the central lumen of the inflated balloon catheter. Analysis of scintigraphic data obtained after 28 ± 3 days showed that both absolute and relative perfusion defect decreased significantly after intracoronary administration of ADSCs or BMSCs (relative 30 or 31%, respectively), compared with carrier administration alone (12%, P = 0.048). Left ventricular ejection fraction after 4 weeks increased significantly more after ADSC and BMSC administration than after carrier administration: 11.39 ± 4.62 and 9.59 ± 7.95%, respectively vs. 1.95 ± 4.7%, P = 0.02). The relative thickness of the ventricular wall in the infarction area after cell administration was significantly greater than that after carrier administration. The vascular density of the border zone also improved. The grafted cells co-localized with von Willebrand factor and alpha-smooth muscle actin and incorporated into newly formed vessels. Conclusion This is the first study to show that not only bone marrow-derived cells but also ADSCs engrafted in the infarct region 4 weeks after intracoronary cell transplantation and improved cardiac function and perfusion via angiogenesis.

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TL;DR: An expert consensus of required outcome parameters in seven relevant outcome domains, namely death, stroke, symptoms and quality of life, rhythm, left ventricular function, cost, and emerging outcome parameters, are described.
Abstract: Atrial fibrillation (AF), the most common atrial arrhythmia, has a complex aetiology and causes relevant morbidity and mortality due to different mechanisms, including but not limited to stroke, heart failure, and tachy- or bradyarrhythmia. Current therapeutic options (rate control, rhythm control, antithrombotic therapy, ‘upstream therapy’) only prevent a part of this burden of disease. Several new treatment modalities are therefore under evaluation in controlled trials. Given the multifold clinical consequences of AF, trials in AF patients should assess the effect of therapy in each of the main outcome domains. This paper describes an expert consensus of required outcome parameters in seven relevant outcome domains, namely death, stroke, symptoms and quality of life, rhythm, left ventricular function, cost, and emerging outcome parameters. In addition to these ‘requirements’ for outcome assessment in AF trials, further, more detailed outcome parameters are described. In addition to a careful selection of a relevant primary outcome parameter, coverage of outcomes in all major domains of AF-related morbidity and mortality is desirable for any clinical trial in AF.

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TL;DR: In myocarditis, biventricular dysfunction at diagnosis was the main predictor of death/transplantation and AHA identified immune-mediatedMyocarditis in the majority of cases, and viral genome was a univariate predictor of adverse prognosis.
Abstract: Aims Myocarditis may be idiopathic, viral, and/or immune; frequency of these forms and prognosis are ill-defined. We aimed at identifying aetiopathogenetic and prognostic markers in myocarditis, including viral genome on endomyocardial biopsy (EMB) by polymerase chain reaction (PCR) and serum anti-heart autoantibodies (AHA). Methods and results We studied 174 patients, 110 males, aged 36 ± 18 years, median follow-up 23.5 months, range 10–54; 85 patients had active myocarditis and 89 borderline myocarditis (no diffuse or severe inflammation) (Dallas criteria). Serum AHA were detected by indirect immunofluorescence. PCR was used to detect virus. Six-year actuarial survival was 73%. AHA were found in 56% of patients and positive PCR in 26%. Univariate predictors of death/transplantation were young age, longer symptom duration, giant cell myocarditis, NYHA II–IV, positive PCR, presentation with LV dysfunction, clinical signs/symptoms of heart failure, and echocardiographic and haemodynamic indexes of cardiac dysfunction. By Cox univariate analysis, highest risk was conferred by clinical signs/symptoms of left (HR = 4.3, CI 1.7–10.8, P = 0.002) and right heart failure (HR 3.4, CI 1.5–7.3, P = 0.002). Conclusion In myocarditis, biventricular dysfunction at diagnosis was the main predictor of death/transplantation. AHA identified immune-mediated myocarditis in the majority of cases. Viral genome was a univariate predictor of adverse prognosis. Our approach of using AHA and positive PCR as aetiopathogenetic markers should help patient selection and recruitment in future studies on aetiological therapy.

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TL;DR: CMR is a valuable adjunct to conventional investigations in a diagnostically challenging and important group of patients with troponin-positive chest pain and unobstructed coronary arteries.
Abstract: Aims Troponin measurement is used in the assessment and risk stratification of patients presenting acutely with chest pain when the main cause of elevation is coronary artery disease. However, some patients have no coronary obstruction on angiography, leading to diagnostic uncertainty. We evaluated the incremental diagnostic value of cardiovascular magnetic resonance (CMR) in these patients. Methods and results Sixty consecutive patients (mean age 44 years, 72% male) with a troponin-positive episode of chest pain and unobstructed coronary arteries were recruited within 3 months of initial presentation. All patients underwent CMR with cine imaging, T2-weighted imaging for detection of inflammation, and late gadolinium enhancement imaging for detection of infarction/fibrosis. An identifiable basis for troponin elevation was established in 65% of patients. The commonest underlying cause was myocarditis (50%), followed by myocardial infarction (11.6%) and cardiomyopathy (3.4%). In the 35% of patients where no clear diagnosis was identified by CMR, significant myocardial infarction/fibrosis was excluded. Conclusion CMR is a valuable adjunct to conventional investigations in a diagnostically challenging and important group of patients with troponin-positive chest pain and unobstructed coronary arteries.

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TL;DR: Hypertension and LAD are independent pre-procedural predictors of AF recurrence after CPVA to treat AF and may help in patient selection for AF ablation.
Abstract: Aims The success rate of circumferential pulmonary vein ablation (CPVA) to treat atrial fibrillation (AF) ranges from 60 to 90%, depending on the series. The objective of the study was to identify predictors of AF recurrence after a standardized CPVA procedure. Methods and results A series of 148 consecutive patients undergoing CPVA for symptomatic paroxysmal (60.8%), persistent (23.6%), or permanent (15.5%) AF refractory to antiarrhythmic drugs were included in the study. CPVA with the creation of supplementary block lines along the posterior wall and mitral isthmus was performed and a minimum of 6 months follow-up completed in all patients. Structural heart disease was present in 19.6% and hypertension in 33.8% of patients. After 13.1 ± 8.4 months follow-up, 73.6% of patients were free of AF recurrences after a mean of 1.18 ± 0.45 procedures/patient (one procedure in 85.2%, two procedures in 14.8%, and three procedures in 2.7%). Univariable analysis showed that the risk of AF recurrence increases with age (HR 1.03; 95% CI 1.00–1.06, P = 0.031), with the presence of previous hypertension (HR 2.7; 95% CI 1.43–5.07, P = 0.002), and if AF is permanent (HR 2.23; 95% CI 1.08–4.59, P = 0.042). In addition, larger anteroposterior left atrial diameter (LAD) (HR 1.11; 95% CI 1.05–1.18, P = 0.001) and larger left ventricular end-systolic diameter (HR 1.07; 95% CI 1.00–1.15, P = 0.029) prior to the procedure were associated with AF recurrence after CPVA. Cox regression analysis showed that hypertension (OR = 2.8; 95% CI 1.5–5.4; P = 0.002) and LAD (OR = 1.1; 95% CI 1.05–1.19, P < 0.001) were independent predictors of AF recurrence. The mean predicted proportion of patients with AF recurrence after CPVA of the multivariable model showed a linear relationship with the increase in LAD prior to the procedure. The presence of hypertension further increased the mean predicted proportion of patients with AF recurrence at each LAD. Conclusion Hypertension and LAD are independent pre-procedural predictors of AF recurrence after CPVA to treat AF. These data may help in patient selection for AF ablation.

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TL;DR: A four- to five-fold increase in the risk of death, MI, and stroke at 30 days has been observed in patients with bleeding events, as compared to those without, both in the short- and long-term.
Abstract: Over the last two decades, major improvements in clinical outcome have been achieved in the management of acute coronary syndromes (ACS), with or without ST-segment elevation. In both these clinical settings, the pharmacological approach comprising anti-platelet agents, (or a combination thereof), anticoagulants, thrombolytic treatment in case of ST-elevation MI (STEMI) combined with mechanical or surgical revascularization or reperfusion, has led to a dramatic reduction in the rate of ischaemic events, namely death, death/myocardial infarction (MI), or death/MI/stroke. However, this has been achieved at the cost of a higher risk of bleeding complications, which were considered, until recently, to be inherent to ACS management, and to be a side effect devoid of serious clinical implications, except for intra-cranial bleeding. Bleeding complications were thought to be the price to pay for the improvement in the risk of ischaemic events, and were considered to be easily controlled, particularly thanks to a liberal transfusion policy. In this context, the risk factors for bleeding have been identified, and include baseline characteristics, such as age, female gender, renal failure, diabetes, and heart failure. In addition, the number and dosage of anti-thrombotic drugs, the use of fibrinolytic treatments, and the use of invasive strategies, required to achieve mechanical reperfusion or revascularization, also play an important role.1,2 However, over the last 5 years, it has become clear that bleeding complications occurring during the initial phase of ACS have a considerable impact on prognosis, especially in terms of death, MI, and stroke, both in the short- and long-term. A four- to five-fold increase in the risk of death, MI, and stroke at 30 days has been observed in patients with bleeding events, as compared to those without.2–4 The potential mechanisms by which … Corresponding author. Tel: +33 381 668 539; fax: +33 381 668 582. E-mail address : jpbassan{at}univ-fcomte.fr

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TL;DR: The high diagnostic accuracy of 64-SCTA validates this non-invasive technique as a potential alternative to CCA in carefully selected populations suspected for coronary stenosis.
Abstract: Aims To evaluate the diagnostic accuracy of 64-slice multi-detector computed tomography coronary angiography (64-SCTA) compared with the standard reference conventional coronary angiography (CCA). Methods and results Based on a systematic search, 27 studies including 1740 patients were eligible for meta-analyses. Nineteen studies examined native coronary arteries ( n = 1,251), four studies examined coronary artery by-pass grafts (CABG) ( n = 271), and five studies examined coronary stents ( n = 270). Overall 18 920 segments were assessable and 810 (4%) were unassessable. The prevalence of native coronary artery stenosis in per-segment (19 studies) and per-patients (13 studies) populations were 19 and 57.5% respectively. Accuracy tests with 95% confidence intervals comparing 64-SCTA vs. CCA showed that sensitivity, specificity, positive predictive and negative predictive values for native coronary arteries were 86(85–87), 96(95.5–96.5), 83, and 96.5% by per-segment analysis; 97.5(96–99), 91(87.5–94), 93, and 96.5% by per-patient analysis; 98.5(96–99.5), 96(93.5–97.5), 92 and 99% for CABGs; 80(70–88.5), 95(92–97), 80, and 95% for stent restenosis; and 87(86.5–88), 96(95.5–96.5), 83.5, and 97% by overall per-segment analysis. Conclusion The high diagnostic accuracy of 64-SCTA validates this non-invasive technique as a potential alternative to CCA in carefully selected populations suspected for coronary stenosis.

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TL;DR: The use of drug-eluting stents in patients with acute ST-segment elevation myocardial infarction is safe and improves clinical outcomes by reducing the risk of reintervention compared with bare-metal stents.
Abstract: Aims To compare the efficacy and safety of drug-eluting stents vs. bare-metal stents in patients with acute ST-segment elevation myocardial infarction. Methods and results We performed a meta-analysis of eight randomized trials comparing drug-eluting stents (sirolimus-eluting or paclitaxel-eluting stents) with bare-metal stents in 2786 patients with acute ST-segment elevation myocardial infarction. All patients were followed up for a mean of 12.0–24.2 months. Individual data were available for seven trials with 2476 patients. The primary efficacy endpoint was the need for reintervention (target lesion revascularization). The primary safety endpoint was stent thrombosis. Other outcomes of interest were death and recurrent myocardial infarction. Drug-eluting stents significantly reduced the risk of reintervention, hazard ratio of 0.38 (95% CI, 0.29–0.50), P < 0.001. The overall risk of stent thrombosis: hazard ratio of 0.80 (95% CI, 0.46–1.39), P = 0.43; death: hazard ratio of 0.76 (95% CI, 0.53–1.10), P = 0.14; and recurrent myocardial infarction: hazard ratio of 0.72 (95% CI, 0.48–1.08, P = 0.11) was not significantly different for patients receiving drug-eluting stents vs. bare-metal stents. Conclusion The use of drug-eluting stents in patients with acute ST-segment elevation myocardial infarction is safe and improves clinical outcomes by reducing the risk of reintervention compared with bare-metal stents.