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Background: New onset of atrial fibrillation (AF) after cardiovascular surgery is associated with increased risk of complications and length of hospital stay. Identification of patients at high risk of post-operative AF (POAF) may help to act with preventive strategies having clinical and economic relevance., Objective: The focus of this review is to summarize findings on biomarkers of myocardial fibrosis (PICP and PIIINP), profibrotic mediators (TGF-beta1), extracellular matrix remodeling (MMP-9), myocardial stretch (BNP and NTpro-BNP), inflammation (interleukins, C-reactive protein and sCD40L), and myocardial necrosis (high-sensitivity troponin T), biomarkers, that can be used in clinical practice to stratify patients at risk for POAF., Method: We searched English-language studies on MEDLINE and PubMed. Evidence synthesis was based on cohort studies, clinical trials and meta-analysis data. International clinical practice guidelines were reviewed, as well., Results: Factors such as cardiac remodelling, atrial pressure, surgery trauma, inflammation, oxidative stress, and sympathetic/parasympathetic activation have been implicated in the development of POAF. On the basis of multifactorial mechanism underlying the onset of POAF, several studies have investigated the predictive value of some serum biomarkers. To date, there are promising preliminary data on the clinical utility of PICP, PIINP, TGF-β1 and sCD40L, whereas data on NT-proBNP, BNP, CRP, IL- 6, and hs-cTnT are controversial., Conclusion: Although some studies have shown promising results, there is a need for future larger studies with longer follow-up, before applying biomarkers as tools for POAF risk-stratification into clinical practice., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Although acute coronary syndrome (ACS) mainly occurs in individuals >60 years, younger adults can be affected as well. Women continue to be at higher risk of 30-day mortality after ST-segment elevation myocardial infarction (STEMI) even in the current era of percutaneous coronary intervention (PCI). Importantly, the excess mortality among women is only significant at younger ages. Previous work has suggested that the reason for the differences in outcome is likely multifactorial and may partially be explained by some of the following factors: atypical presentation, delayed presentation, under-recognition of STEMI at initial medical contact, and underuse of medications because of concern regarding increased risk of bleeding. While these hypotheses may be true in some occasions, recent studies pointed out that the proportion of women presenting within 2 h after symptom onset was greater in the younger than in older cohorts. In addition, sex differences in administration of adjunctive medical therapies were greater in the older than in the younger cohort. Thus, there is not any one of the abovementioned factors able to explain the increase in mortality in the young women. Disparities alone could not account for the gap in mortality across sexes. Unless the effects of sex are studied, we will continue to have gaps in the knowledge of potential different mechanisms leading young women and men to die after ACS, which may result in missed opportunities for implementing a better health in our community. Randomizing or balancing the sexes as well as powering studies to detect sex differences is warranted in future research., (Copyright © 2018. Published by Elsevier Inc.)

Importance: Previous works have shown that women hospitalized with ST-segment elevation myocardial infarction (STEMI) have higher short-term mortality rates than men. However, it is unclear if these differences persist among patients undergoing contemporary primary percutaneous coronary intervention (PCI)., Objective: To investigate whether the risk of 30-day mortality after STEMI is higher in women than men and, if so, to assess the role of age, medications, and primary PCI in this excess of risk., Design, Setting, and Participants: From January 2010 to January 2016, a total of 8834 patients were hospitalized and received medical treatment for STEMI in 41 hospitals referring data to the International Survey of Acute Coronary Syndromes in Transitional Countries (ISACS-TC) registry (NCT01218776)., Exposures: Demographics, baseline characteristics, clinical profile, and pharmacological treatment within 24 hours and primary PCI., Main Outcomes and Measures: Adjusted 30-day mortality rates estimated using inverse probability of treatment weighted (IPTW) logistic regression models., Results: There were 2657 women with a mean (SD) age of 66.1 (11.6) years and 6177 men with a mean (SD) age of 59.9 (11.7) years included in the study. Thirty-day mortality was significantly higher for women than for men (11.6% vs 6.0%, P < .001). The gap in sex-specific mortality narrowed if restricting the analysis to men and women undergoing primary PCI (7.1% vs 3.3%, P < .001). After multivariable adjustment for comorbidities and treatment covariates, women under 60 had higher early mortality risk than men of the same age category (OR, 1.88; 95% CI, 1.04-3.26; P = .02). The risk in the subgroups aged 60 to 74 years and over 75 years was not significantly different between sexes (OR, 1.28; 95% CI, 0.88-1.88; P = .19 and OR, 1.17; 95% CI, 0.80-1.73; P = .40; respectively). After IPTW adjustment for baseline clinical covariates, the relationship among sex, age category, and 30-day mortality was similar (OR, 1.56 [95% CI, 1.05-2.3]; OR, 1.49 [95% CI, 1.15-1.92]; and OR, 1.21 [95% CI, 0.93-1.57]; respectively)., Conclusions and Relevance: Younger age was associated with higher 30-day mortality rates in women with STEMI even after adjustment for medications, primary PCI, and other coexisting comorbidities. This difference declines after age 60 and is no longer observed in oldest women.

Prevalence of peripheral arterial disease in patients with coronary artery disease is considerably higher than in the general population. A graded increase in the risk of major cardiovascular events in a variety of clinical settings is associated with the number of arterial beds affected by peripheral arterial disease. This is not surprising, considering that both coronary artery disease and peripheral arterial disease are linked to a higher prevalence of cardiovascular risk factors and a greater incidence of atherosclerotic burden. Aggressive lipid lowering therapy is associated with less coronary and peripheral arterial disease progression and greater regression. On the contrary, blood pressure therapy should be carefully managed, considering the association of both high and low values of pressure with adverse outcomes., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Vasospastic angina is an important cause of chest pain due to coronary artery vasospasm that is related to poor quality of life and can lead to myocardial infarction, arrhythmias and death. Since its first description as "Prinzmetal or variant angina" which was believed to be a focal spam that occurred in non-obstructed epicardial coronary arteries, physician and researchers were gradually confronted with the clinical reality and came to the conclusion that the coronary artery vasospasm was considerably more polymorphic than initially described. Although mechanism leading to vasospastic angina is not completely understood, nowadays the medical community acknowledges that it exhibits a large variability in clinical practice ranging from focal to diffuse epicardial vasospasm. Main proposed mechanisms are impairment of parasympathetic activity, coronary vascular and microvascular dysfunction due to blunted response to nitric oxide endothelium-dependent coronary vasodilatation, increased release of vasoconstricts, and oxidative stress., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Although acute coronary syndrome (ACS) mainly occurs in patients >50 years, younger patients can be affected as well. We used an age cutoff of 45 years to investigate clinical characteristics and outcomes of "young" patients with ACS., Methods and Results: Between October 2010 and April 2016, 14 931 patients with ACS were enrolled in the ISACS-TC (International Survey of Acute Coronary Syndromes in Transitional Countries) registry. Of these patients, 1182 (8%) were aged ≤45 years (mean age, 40.3 years; 15.8% were women). The primary end point was 30-day all-cause mortality. Percentage diameter stenosis of ≤50% was defined as insignificant coronary disease. ST-segment-elevation myocardial infarction was the most common clinical manifestation of ACS in the young cases (68% versus 59.6%). Young patients had a higher incidence of insignificant coronary artery disease (11.4% versus 10.1%) and lesser extent of significant disease (single vessel, 62.7% versus 46.6%). The incidence of 30-day death was 1.3% versus 6.9% for the young and older patients, respectively. After correction for baseline and clinical differences, age ≤45 years was a predictor of survival in men (odds ratio, 0.24; 95% confidence interval, 0.10-0.58), but not in women (odds ratio, 1.35; 95% confidence interval, 0.50-3.62). This pattern of reversed risk among sexes held true after multivariable correction for in-hospital medications and reperfusion therapy. Moreover, younger women had worse outcomes than men of a similar age (odds ratio, 6.03; 95% confidence interval, 2.07-17.53)., Conclusion: ACS at a young age is characterized by less severe coronary disease and high prevalence of ST-segment-elevation myocardial infarction. Women have higher mortality than men. Young age is an independent predictor of lower 30-day mortality in men, but not in women., Clinical Trial Registration: URL: http://clinicaltrials.gov/. Unique identifier: NCT01218776., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background and Aims: Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are dominant inherited muscular dystrophies with multiple systemic involvement, often producing cardiac injury. This study sought to determine the clinical significance of elevated high sensitivity cardiac troponin T and I (hs-cTnT and hs-cTnI), and N-terminal pro B-type natriuretic peptide (NT-pro-BNP) in this population., Methods: Sixty DM patients (35 men and 25 women; mean age: 45.1 years, range: 12-73 years) underwent clinical cardiac investigations and measurements of serum hs-cTnT, hs-cTnI, creatine kinase (CK), and NT-proBNP. Left ventricular (LV) ejection fraction (EF) was assessed by echocardiography., Results: Genetic analysis revealed that 46 of the 60 patients were DM1, and 14 DM2. Blood measurements showed persistent elevation of hs-cTnT and CK in 55/60 DM patients (91.73%). In contrast, hs-cTnI values were persistently normal throughout the study. Only 2 patients showed an EF <50%, being the overall range of this population between 40% and 79%. We found ECG abnormalities in 19 patients. Of these patients, 13 showed first or second-degree atrio ventricular (AV) blocks (PR interval ≥ 200 ms), 4 showed a left bundle branch block (LBBB) prolonged (QRS duration ≥120 ms), and 2 had an incomplete bundle branch block (QRS duration between 110 and 119 ms). After excluding patients with EF <50%, NT-pro-BNP measurement > 125 pg/mL was an independent predictor of ECG abnormalities., Conclusions: NT-pro-BNP levels may be considered to be used clinically to identify DM patients at increased risk of developing myocardial conduction abnormalities., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Women with ST-segment-elevation myocardial infarction (STEMI) have higher mortality rates than men. We investigated whether sex-related differences in timely access to care among STEMI patients may be a factor associated with excess risk of early mortality in women., Methods and Results: We identified 6022 STEMI patients who had information on time of symptom onset to time of hospital presentation at 41 hospitals participating in the ISACS-TC (International Survey of Acute Coronary Syndromes in Transitional Countries) registry (NCT01218776) from October 2010 through April 2016. Patients were stratified into time-delay cohorts. We estimated the 30-day risk of all-cause mortality in each cohort. Despite similar delays in seeking care, the overall time from symptom onset to hospital presentation was longer for women than men (median: 270 minutes [range: 130-776] versus 240 minutes [range: 120-600]). After adjustment for baseline variables, female sex was independently associated with greater risk of 30-day mortality (odds ratio: 1.58; 95% confidence interval, 1.27-1.97). Sex differences in mortality following STEMI were no longer observed for patients having delays from symptom onset to hospital presentation of ≤1 hour (odds ratio: 0.77; 95% confidence interval, 0.29-2.02)., Conclusions: Sex difference in mortality following STEMI persists and appears to be driven by prehospital delays in hospital presentation. Women appear to be more vulnerable to prolonged untreated ischemia., Clinical Trial Registration: URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01218776., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: The objectives of this study were to evaluate the incidence of no-reflow as independent predictor of adverse events and to assess whether baseline pre-procedural treatment options may affect clinical outcomes., Methods: Data were derived from the ISACS-TC registry (NCT01218776) from October 2010 to January 2015. No-reflow was defined as post-PCI TIMI flow grades 0-1, in the absence of post-procedural significant (≥25%) residual stenosis, abrupt vessel closure, dissection, perforation, thrombus of the original target lesion, or epicardial spasm. The outcome measure was in-hospital mortality., Results: No-reflow was identified in 128 of 5997 patients who have undergone PCI (2.1%). On multivariate analysis, patients with no-reflow were more likely to be older (OR: 1.20, 95% CI: 1.01-1.44), to have a history of hypercholesterolemia (OR: 1.95, 95% CI: 1.31-2.91) and to be admitted with a diagnosis of STEMI (OR: 2.96, 95% CI: 1.85-4.72). Angiographic characteristics associated with no-reflow phenomenon were: stenosis ≥50% of the right coronary artery, presence of multivessel disease and pre-procedural TIMI blood flow grades 0-1. No-reflow was highly predictive of in-hospital mortality (17.2% vs. 4.2%; adjusted OR: 4.60, 95% CI: 2.61-8.09). Administration of pre-procedural unfractioned heparin or 600mg clopidogrel loading dose was associated with less incidence of no-reflow (OR: 0.65, 95% CI: 0.43-0.99 and 0.61, 95% CI: 0.37-1.00, respectively). Aspirin, enoxaparin, and 300mg clopidogrel loading dose, did not significantly impact the occurrence of the no-reflow., Conclusions: We found that pre-procedural administration of 600mg loading dose of clopidogrel and/or unfractioned heparin is associated with reduced incidence of no-reflow., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Limited data are available on the outcome of primary percutaneous coronary intervention (PCI) in octogenarian patients, as the elderly are under-represented in randomized trials. This study aims to provide insights on clinical characteristics, management and outcome of the elderly and very elderly presenting with STEMI., Methods: 2225 STEMI patients ≥70years old (mean age 76.8±5.1years and 53.8% men) were admitted into the network of the ISACS-TC registry. Of these patients, 72.8% were ≥70 to 79years old (elderly) and 27.2% were ≥80years old (very-elderly). The primary end-point was 30-day mortality., Results: Thirty-day mortality rates were 13.4% in the elderly and 23.9% in the very-elderly. Primary PCI decreased the unadjusted risk of death both in the elderly (OR: 0.32, 95% CI: 0.24-0.43) and very-elderly patients (OR: 0.45, 95% CI 0.30-0.68), without significant difference between groups. In the very-elderly hypertension and Killip class ≥2 were the only independent factors associated with mortality; whereas in the elderly female gender, prior stroke, chronic kidney disease and Killip class ≥2 were all factors independently associated with mortality. Factors associated with the lack of use of reperfusion were female gender and atypical chest pain in the very-elderly and in the elderly; in the elderly, however, there were some more factors, namely: history of diabetes, current smoking, prior stroke, Killip class ≥2 and history chronic kidney disease., Conclusions: Age is relevant in the prognosis of STEMI, but its importance should not be considered secondary to other major clinical factors. Primary PCI appears to have beneficial effects in the octogenarian STEMI patients., (Copyright © 2016. Published by Elsevier Ireland Ltd.)

Background: We explored benefits and risks of an early invasive compared with a conservative strategy in women versus men after non-ST elevation acute coronary syndromes (NSTE-ACS) using the ISACS-TC database., Methods: From October 2010 to May 2014, 4145 patients were diagnosed as having a NSTE-ACS. We excluded 258 patients managed with coronary bypass surgery. Of the remaining 3887 patients, 1737 underwent PCI (26% women). The primary endpoint was the composite of 30-day mortality and severe left ventricular dysfunction defined as an ejection fraction <40% at discharge., Results: Women were older and more likely to exhibit more risk factors and Killip Class ≥2 at admission as compared with men. In patients who underwent PCI, peri-procedural myocardial injury was not different among sexes (3.1% vs. 3.2%). Women undergoing PCI experienced higher rates of the composite endpoint (8.9% vs. 4.9%, p=0.002) and 30-day mortality (4.4% vs. 2.0%, p=0.008) compared with men, whereas those who managed with only routine medical therapy (RMT) did not show any sex difference in outcomes. In multivariable analysis, female sex was associated with favorable outcomes (adjusted HR for the composite endpoint: 0.72, 95% CI: 0.58-0.91) in patients managed with RMT, but not in those undergoing PCI (adjusted HR: 0.96, 95% CI: 0.61-1.52)., Conclusions: We observed a more favorable outcome in women than men when patients were managed with RMT. Women and men undergoing PCI have similar outcomes. These data suggest caution in extrapolating the results from men to women in an overall population of patients in the context of different therapeutic strategies., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Elderly patients represent an important proportion of the acute coronary syndrome (ACS) population. Furthermore, this group of ACS patients is continuously growing because of the progressive ageing of the population. The ageing process implies marked changes in patient physiology that directly impact in their risk. However, there is a differential distribution in the risk of elderly patients, revealing the existence of a discrepancy between the chronological and the "biological age". This discrepancy has highlighted the need of performing individual risk assessment in order to identify those patients at higher risk. In addition, the lack of representation of elderly patients in clinical trials leads to the underutilization of evidence-based therapies in this group of patients. All these factors influence not only the high prevalence of ACS presentation in the elderly but also their worse prognosis after suffering an ischaemic event. Herein we will explore the pathophysiological mechanisms behind the age-related changes at the vascular and the cardiac level that explain the high risk of elderly subjects of suffering ACS and their worse prognosis., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: There is conflicting information about sex differences in presentation, treatment, and outcome after acute coronary syndromes (ACS) in the era of reperfusion therapy and percutaneous coronary intervention. The aim of this study was to examine presentation, acute therapy, and outcomes of men and women with ACS with special emphasis on their relationship with younger age (≤65years)., Methods: From January 2010 to June 2015, we enrolled 5140 patients from 3 primary PCI capable hospitals. Patients were registered according to the International Survey of Acute Coronary Syndrome in Transitional Countries (ISACS-TC) registry protocol (ClinicalTrials.gov: NCT01218776). The primary outcome was the incidence of in-hospital mortality., Results: The study population was constituted by 2876 patients younger than 65years and 2294 patients older. Women were older than men in both the young (56.2±6.6 vs. 54.1±7.4) and old (74.9±6.4 vs. 73.6±6.0) age groups. There were 3421 (66.2%) patients with ST elevation ACS (STE-ACS) and 1719 (33.8%) patients without ST elevation ACS (NSTE-ACS). In STE-ACS, the percentage of patients who failed to receive reperfusion was higher in women than in men either in the young (21.7% vs. 15.8%) than in the elderly (35.2% vs. 29.6%). There was a significant higher mortality in women in the younger age group (age-adjusted OR 1.52, 95% CI: 1.01-2.29), but there was no sex difference in the older group (age-adjusted OR 1.10, 95% CI: 0.87-1.41). Significantly sex differences in mortality were not seen in NSTE-ACS patients., Conclusions: In-hospital mortality from ACS is not different between older men and women. A higher short-term mortality can be seen only in women with STEMI and age of 65 or less., (Copyright © 2016. Published by Elsevier Ireland Ltd.)

Background: Central and East European (CEE) patients with acute coronary syndromes (ACS) have worse outcomes than US and West European patients, including higher mortality rates. The aim of the International Survey of Acute Coronary Syndrome in Transitional Countries (ISACS-TC) was to define patient and treatment characteristics in order to examine whether differences in clinical and ethnic factors or healthcare organization may mediate the observed disparities in outcomes., Methods and Results: Between October 2010 and December 2015, 14,326 patients with ACS were prospectively enrolled. Of these patients 8650 (60%) had ST-segment elevation myocardial infarction (STEMI). Patients were enrolled from 41 centers in 12 countries in Europe. Standardized electronic case report forms were completed by trained study coordinators, and included fields relating to demographic factors, medical history and processes of inpatient care, supplemented with a detailed baseline interview on time delays to hospital admission. Blood sampling for genetic data were obtained at hospital discharge. Prospective individual patient follow-up was carried out with a focus on patient health (symptoms) and vital status. Thirty day follow-up was 100% complete. Difficulties were found for recruitment of patients at 6months. Publications are available at ClinicalTrials.gov: NCT01218776., Conclusions: ISACS-TC is a novel ACS registry with detailed information on CEE patients' clinical, demographic, treatment, and metabolic characteristics and health status. The concurrent enrollment of patients from some European Union founding members provides greater generalizability of the data. ISACS-TC may help to make an additional improvement in clinical outcomes of countries with economy in transition., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: A substantial proportion of elderly with ST segment elevation myocardial infarction (STEMI) do not undergo percutaneous coronary intervention (PCI). We sought to investigate factors associated with the decision not to perform coronary angiography at admission in these patients., Methods: We evaluated 1315 STEMI patients aged ≥75years old enrolled in the International Survey of Acute Coronary Syndromes in Transitional Countries (ISACS TC) registry between October 2010 and February 2015. They were compared with 6667 patients aged <75years old enrolled in the registry in the same time frame., Results: Elderly patients were less likely to undertake invasive coronary evaluation compared with younger patients (62.1% vs. 78.9; p<0.001%). In the older group there were a lower proportion of patients presenting <12h after symptom onset (66.5% vs.76.9%, p<0.001), and a higher prevalence of comorbidities. Few elderly were treated with current recommended evidence based treatments (aspirin, clopidogrel, heparins, beta-blocker, statins, and ACE-inhibitors). Logistic analysis adjusted for age and sex showed that older age was associated with underuse of coronary angiography (OR 0.46, 95% CI: 0.41-0.53, p<0.001). Clinical factors that were associated with underuse of angiography in patients over 75 were: female sex (OR: 0.77), presence of comorbidities (OR: 0.91), anemia (OR: 0.44) and late hospital admission (OR: 0.89)., Conclusions: In the ISACS-TC, more than one third of the elderly with STEMI did not undergo coronary angiography at admission. Sex, comorbidities, and late hospital admission were independent factors associated with the underuse of PCI in these patients., (Copyright © 2016. Published by Elsevier Ireland Ltd.)

Background: To evaluate the impact of comorbidities on the management and outcomes of acute coronary syndrome (ACS) patients without chest pain/discomfort (i.e. ACS without typical presentation)., Methods: Of the 11,458 ACS patients, enrolled by the International Survey of Acute Coronary Syndrome in Transitional Countries (ISACS-TC; ClinicalTrials.gov: NCT01218776), 8.7% did not have typical presentation at the initial evaluation, and 40.2% had comorbidities. The odds of atypical presentation increased proportionally with the number of comorbidities (odds ratio [OR]: 1, no-comorbid; OR: 1.64, 1 comorbidity; OR: 2.52, 2 comorbidities; OR: 4.57, ≥3 comorbidities)., Results: Stratifying the study population by the presence/absence of comorbidities and typical presentation, we found a decreasing trend for use of medications and percutaneous intervention (OR: 1, typical presentation and no-comorbidities; OR: 0.70, typical presentation and comorbidities; OR: 0.23, atypical presentation and no-comorbidities; OR: 0.18, atypical presentation and comorbidities). On the opposite, compared with patients with typical presentation and no-comorbidities (OR: 1, referent), there was an increasing trend (p<0.001) in the risk of death (OR: 2.00, OR: 2.52 and OR: 4.83) in the above subgroups. However, after adjusting for comorbidities, medications and invasive procedures, atypical presentation was not a predictor of in-hospital death. Independent predictors of poor outcome were history of stroke (OR: 2.04), chronic kidney disease (OR: 1.57), diabetes mellitus (OR: 1.49) and underuse of invasive procedures., Conclusions: In the ISACS-TC, atypical ACS presentation was often associated with comorbidities. Atypical presentation and comorbidities influenced underuse of in-hospital treatments. The latter and comorbidities are related with poor in-hospital outcome, but not atypical presentation, per se., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Randomized controlled trials (RCTs) were conflicting to support whether unstable angina versus non-ST-elevation myocardial infarction (UA/NSTEMI) patients best undergo early invasive or a conservative revascularization strategy. RCTs with cardiac biomarkers, in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials from 1975-2013 were reviewed considering all cause mortality, recurrent non-fatal myocardial infarction (MI) and their combination. Follow-up lasted from 6-24 months and the use of routine invasive strategy up to its end was associated with a significantly lower composite of all-cause mortality and recurrent non-fatal MI (Relative Risk [RR] 0.79; 95% confidence interval [CI], 0.70-0.90) in UA/NSTEMI. In NSTEMI, by the invasive strategy, there was no benefit (RR 1.19; 95% CI, 1.03-1.38). In the shorter time period, from randomization to discharge, a routine invasive strategy was associated with significantly higher odds of the combined end-point among UA/NSTEMI (RR 1.29; 95% CI, 1.05-1.58) and NSTEMI (RR 1.82; 95% CI, 1.34-2.48) patients. Therefore, in trials recruiting a large number of UA patients, by routine invasive strategy the largest benefit was seen, whereas in NSTEMI patients death and non-fatal MI were not lowered. Routine invasive treatment in UA patients is accordingly supported by the present study.

The aim of this study was to determine if earlier administration of oral β ​blocker therapy in patients with acute coronary syndromes (ACSs) is associated with an increased short-term survival rate and improved left ventricular (LV) function. We studied 11,581 patients enrolled in the International Survey of Acute Coronary Syndromes in Transitional Countries registry from January 2010 to June 2014. Of these patients, 6,117 were excluded as they received intravenous β blockers or remained free of any β ​blocker treatment during hospital stay, 23 as timing of oral β ​blocker administration was unknown, and 182 patients because they died before oral β blockers could be given. The final study population comprised 5,259 patients. The primary outcome was the incidence of in-hospital mortality. The secondary outcome was the incidence of severe LV dysfunction defined as an ejection fraction <40% at hospital discharge. Oral β blockers were administered soon (≤24 hours) after hospital admission in 1,377 patients and later (>24 hours) during hospital stay in the remaining 3,882 patients. Early β ​blocker therapy was significantly associated with reduced in-hospital mortality (odds ratio 0.41, 95% CI 0.21 to 0.80) and reduced incidence of severe LV dysfunction (odds ratio 0.57, 95% CI 0.42 to 0.78). Significant mortality benefits with early β ​blocker therapy disappeared when patients with Killip class III/IV were included as dummy variables. The results were confirmed by propensity score-matched analyses. In conclusion, in patients with ACSs, earlier administration of oral β ​blocker therapy should be a priority with a greater probability of improving LV function and in-hospital survival rate. Patients presenting with acute pulmonary edema or cardiogenic shock should be excluded from this early treatment regimen., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aims: Widespread availability of tertiary hospitals with catheterization facilities, although vigorously promoted, has yet to become a reality in many countries with economy in transition. We sought to evaluate the clinical profile and mortality of patients who were hospitalized with a diagnosis of ST-segment elevation myocardial infarction (STEMI) and either received reperfusion therapy or remained without reperfusion in Eastern Europe., Methods and Results: Data were obtained from the International Survey of Acute Coronary Syndromes in Transitional Countries (ISACS-TC; NCT01218776) on STEMI patients admitted to 57 hospitals in Eastern European countries from January 2010 to February 2015. The primary endpoint was 30-day mortality. Of 7982 patients, 65 (0.8%) had a documented contraindication to reperfusion, 5973 (75.5%) received fibrinolysis ( n = 1032) or underwent primary percutaneous coronary intervention (p-PCI; n = 4941), and 1944 patients (24.6%) did not receive any reperfusion therapy. The overall unadjusted 30-day mortality rate was 7.9%. Thirty-day mortality rates were higher in non-reperfusion patients (16.0 vs. 5.0% in the p-PCI group and 7.4% in fibrinolysis group). The strongest factors associated with not attempting reperfusion therapy among these patients were female sex (OR 1.29 CI 1.07-1.56), age (OR 1.02; CI 1.01-1.03), prior MI (OR 1.79; CI 1.38-2.32), prior cerebrovascular events (OR 1.87; CI 1.30-2.68), chronic kidney disease (OR 1.76; CI 1.22-2.53), Killip class >1 (OR 1.31; CI 1.06-1.62), and time to admission >12 h (OR 15.9; CI 13.1-19.3)., Conclusions: A substantial number of patients are still not offered any reperfusion therapy in many Eastern European countries with economy in transition, and this was associated with increased 30-day mortality. Time from symptoms onset to admission >12 h was the highest ranking among factors related to lack of reperfusion therapy. Quality improvement efforts should focus on minimizing delay to hospital admission among STEMI patients.

Background: A substantial part of literature has been centered on sex differences in the clinical aspects of ischemic heart disease (IHD). Many reports have documented differences in the presentation and risk profile between women and men. Such differences drive sex-related inequalities in the referral and treatment of IHD. Yet data are insufficient to clarify the reasons for such disparities. The objective of this review is to analyze the main gender differences regarding symptoms, diagnosis, and risk stratification of coronary heart disease in order to identify "gaps" in existing literature that need to be addressed in future research efforts., Methods: We searched English-language studies on MEDLINE and the Cochrane Database of Systematic Reviews from the database start dates to January 2016. Evidence synthesis was based on cohort studies, registry data, and clinical trial data., Results: Women do not often participate in clinical studies. In a number of articles, authors have questioned how the &quot;white male" came to be the prototype of the human research subject. Consequently although many reports continue to describe differential treatment based on patients' sex, the extent to which such inequalities are due to true sex differences in pathophysiology or whether they reflects inaccuracy in risk stratification is unclear., Conclusion: Today, even the best database is incapable in and of itself of supplying answers to the question of whether women are being treated less compared with men by the medical community.

Aims: The purpose of this review was to compare quality of care and outcomes following acute coronary syndrome (ACS) in Central and Eastern European Transitional (CEET) countries., Methods: This was a review of original ACS articles in CEET countries from PubMed, ISI Web of Science, Medline and Embase databases published in English from November 2003 to February 2014., Results: Seventeen manuscripts fulfilled the search criteria. Of 19 CEET countries studied, there were no published ACS management or outcome data for four countries. In-hospital mortality for patients with acute myocardial infarction (AMI) ranged from 6.3% in the Czech Republic to 15.3% in Latvia. In-hospital mortality for ST-elevation myocardial infarction (STEMI) ranged from 3.0% in Poland to 20.7% in Romania. For STEMI, primary percutaneous coronary intervention (PCI) ranged from 1.0% to over 92.0%, fibrinolytic therapy from 0.0% to 49.6%, and no reperfusion therapy from 7.0% to 63.0%., Conclusion: Many CEET countries do not have published ACS care and outcomes data. Of those that do, there is evidence for substantial geographical variation in early mortality. Wide variation in emergency reperfusion strategies for STEMI suggests that acute cardiac care is likely to be modifiable and if addressed could reduce mortality from ACS in CEET countries. The collection of ACS care and outcomes data across Europe must be prioritised., (© The European Society of Cardiology 2014.)

The frequency, presentation, prognosis, and treatment of myocardial ischemia differ in men and women. A large proportion of women who have "normal" coronary arteries on angiography without any significant evidence of flow-limiting disease also have biochemical or imaging evidence of myocardial ischemia. In these women it is believed to be a dysfunction of coronary microcirculation and/or macrocirculation, or vasotonic angina (VA), that leads to abnormal vasoconstriction, and potentially to myocardial infarction, ventricular arrhythmias, and sudden death. Despite having a "normal" or near normal coronary angiography, these women should therefore undergo additional testing with acetylcholine to assess endothelial function. Long-term survival is believed to be relatively good. Predictors of poorer prognosis include documentation of severe endothelial dysfunction and presence of concurrent angiographycally visible coronary atherosclerosis. Because atherosclerosis is common in patients with VA, medical and lifestyle interventions for preventing or treating atherosclerosis should be implemented when appropriate. Angiotensin converting enzyme inhibitors are the mainstays of medical therapy for VA. Other agents have been tried with variable success, including beta-blockers. There are no available data on any specific treatment of VA in women (versus men).

Objective: We sought explore the relative benefits of unfractionated heparin (UFH) compared with enoxaparin, alone or in combination with clopidogrel, in ST-segment elevation myocardial infarction (STEMI) patients not undergoing reperfusion therapy., Methods: This is a propensity score study from The International Survey on Acute Coronary Syndromes in Transition Countries (ISACS-TC/NCT01218776) on patients admitted between October 2010-June 2013. There were a total of 1175 STEMI patients who did not receive mechanical or pharmacological reperfusion. Of these, 1063 were eligible for the aim of the study, being treated with UFH (522/1175; 44.4%) or enoxaparin (541/1175; 46%). Clopidogrel in combination with UFH or enoxaparin was given to 751 (63.9%) patients. The primary endpoint was in-hospital mortality. Secondary endpoints were intracranial hemorrhages, and clinically relevant bleedings., Results: After adjustment for any confounders, UFH was associated with a lower risk of in-hospital mortality in clopidogrel users (multivariate adjusted regression analysis: odds ratio [OR]: 0.62, 95% Confidence Interval [CI] 0.41-0.94) as compared with clopidogrel non-users (OR: 0.94, 95% CI 0.55-1.60). The observed effect was not associated with combined enoxaparin and clopidogrel therapy. Major bleeding events were comparable in the enoxaparin group and UFH group (0.4% and 1.5% respectively, p = 0.06). The risk of major hemorrhage was nearly similar with combined UFH-clopidogrel therapy (1.4%) as compared with UFH alone (1.9%), p = 0.67., Conclusion: UFH - Clopidogrel combination was associated with a large mortality reduction in STEMI patients not undergoing reperfusion therapy and did not significantly increase the risk of major bleeding., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

We sought to determine the effectiveness of angiotensin-converting enzyme (ACE) inhibition and β-blocker treatment as a function of the degree of coronary artery disease (CAD) obstruction at angiography. The Evaluation of Methods and Management of Acute Coronary Events registry enrolled patients who had been hospitalized for an acute coronary syndrome. There were 1,602 patients who had cardiac catheterization that were used for this analysis. The main outcome measures were evidence-based therapies prescribed at discharge and 6-month incidence of all-cause mortality. The cohort consisted of 1,252 patients with obstructive CAD (>50% luminal diameter obstructed) and 350 patients with nonobstructive CAD. Multivariate logistic regression analysis adjusted for further medications and other clinical factors was performed. Patients with nonobstructive CAD had significantly (p <0.001) higher rates of β-blocker (77.8% vs 63.3%) and lower rates of ACE-inhibitor (57.7% vs 66.4%) prescriptions. In patients with nonobstructive CAD, ACE-inhibitor therapy was clearly associated with a lower 6-month mortality (odds ratio [OR] 0.31, 95% confidence interval [CI] 0.03 to 0.78, p = 0.004). No significant association between β-blocker use and death was found. In patients with obstructive CAD, both β blockers (OR 0.47, 95% CI 0.32 to 0.67, p <0.001) and ACE inhibitors (OR 0.47, 95% CI 0.26 to 0.87, p = 0.01) were significantly associated with a reduced risk of 6-month mortality. In conclusion, ACE-inhibitor therapy seems to be an effective first-line treatment for preventing the occurrence of mortality in patients with nonobstructive CAD., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Introduction: The aim of the current study was to investigate the outcomes of coronary reperfusion therapies and ST-segment elevation myocardial infarction (STEMI) in patients of Eastern countries with economies in transition. Federation, and Serbia. The overall population consisted of 23,486 consecutive patients admitted to hospitals from January 1(st) to December 31(st) 2009. Registry data and statistics from the Organization for Economic Cooperation and Development (OECD) countries for the same period were used for comparison (2009-2010). In-hospital mortality was between 4% and 5% in the Western countries. In comparison mortality data were significantly larger in Serbia (10.8%) and Bosnia and Herzegovina (11.2%), intermediate in Russian Federation (7.2%) and similar in Hungary (5.0%). The rates of primary percutaneous coronary intervention (primary PCI) were very low in Bosnia and Herzegovina (18.3%), low in Russian Federation (20.6%) and Serbia (22%), and high in Hungary (70%). Major risk factors for death appear to be lack of reperfusion therapy, longer time delay from symptoms onset to hospital presentation as well as the higher percentage of patients with clinical presentation in Killip class III/IV., Conclusion: In-hospital STEMI case-fatality rates ranges widely in the former Eastern Bloc countries. Beyond the quality of care provided in hospitals, differences in time delay from symptoms onset to hospital admission may strongly influence STEMI patients' outcome.

Introduction: Primary and secondary prevention of cardiovascular Disease (CVD) are major concerns and priorities. The best tools that we actually have to prevent CVD are the biomarkers. Numerous studies have shown that the presentation of cardiac disease in women is quite different from the presentation in men. Thus, one question arises "Are there any differences in biomarkers as well?" The answer to this question could open new avenues for a tailored management of cardiac diseases., Method and Results: We searched the PubMed and Medline databases for articles comparing differences between the 2 genders in terms of biomarker expression. Keywords used included "Cardiovascular biomarkers sex differences". We reviewed the role of different biomarkers in the 2 genders in relation to cardiac events., Conclusions: Differences of expressions in biomarker levels were found between the 2 genders. Further investigation should be promoted.

Patients with acute or chronic ischemic heart disease have a high incidence of depression, and a variable proportion of patients (ranging from 14% to 47%) suffer from major or subclinical depression. In addition, chronic depression has been shown to be associated with the development or progression of coronary atherosclerosis. Besides a poor quality of life, depressive symptoms in patients with ischemic heart disease result in a poor prognosis, as cardiovascular event rates are 2-2.5 times higher than in their counterparts without depressive symptoms. A variety of pathogenetic mechanisms may play a role, including pathophysiological (dysfunction of the autonomic nervous system or hypothalamic-pituitary-adrenal axis, platelet hyperaggregability, inflammation, endothelial dysfunction and genetic predisposition) and behavioral mechanisms (inadequate therapy adherence, obesity, smoking, sedentary lifestyle). However, in patients with ischemic heart disease, depression often goes undiagnosed or untreated. Several screening procedures including questionnaires for patients with heart disease, along with the help of a psychiatrist, may facilitate not only the diagnosis of depressive symptoms but also the pharmacological and/or physiotherapeutic management. The use of tricyclic antidepressant agents should be avoided in patients with heart disease, whereas selective serotonin reuptake inhibitors have been shown to be safe in this patient population. However, no evidence is available to support that use of these drugs is associated with a reduced risk of cardiovascular events at follow-up. Psychotherapy proved to be effective in reducing depressive symptoms but ineffective in improving prognosis. In this review, epidemiology and pathophysiology of depression in patients with ischemic heart disease are described, with a focus on stratification of depressive symptoms and potential therapeutic strategies.

Objectives: To compare the effectiveness of in-hospital medical therapy versus coronary revascularisation added to medical therapy in patients who stabilised after an acute coronary syndrome (ACS)., Design: Propensity score-matched cohort study from the database of the Tampere ACS registry., Setting: A single academic hospital in Finland., Participants: 1149 patients with a recent ACS, but no serious coexisting conditions: recurrent ischaemic episodes despite adequate medical therapy, haemodynamic instability, overt congestive heart failure and serious ventricular arrhythmias., Primary and Secondary Outcome Measures: The composite endpoint of major acute cardiovascular events (MACEs): unstable angina requiring rehospitalisation, stroke, myocardial infarction and all-cause mortality, at 6-month follow-up., Results: Compared with standard medical treatment, revascularisation was associated with a lower rate of MACEs at 6 months in patients of the first quintile (HR 0.81; 95% CI 0.66 to 0.99), but a higher rate of MACEs in the fifth quintile (HR 4.74, CI 1.36 to 16.49; p=0.014). There were no significant differences in the rates of MACEs in the remaining three quintiles. Patients of the first quintile were the oldest (79.7±8.3 years) and had a more significant (p<0.001) history of prior myocardial infarction (37%) and poor renal function (creatine, µmol/l: 114.9±70.7). They also showed the highest C reactive protein (7.3±9.5 mg/l) levels., Conclusions: Our findings suggest that in-hospital coronary revascularisation did not lead to any advantage with signal of possible harm in the great majority of patients who stabilised after an ACS. An early invasive management strategy may be best reserved for elderly patients having high-risk clinical features and biochemical evidence of a strong inflammatory activity.

A growing amount of data is increasingly showing the relevance of coronary microvascular dysfunction (CMVD) in several clinical contexts. This article reviews techniques and clinical investigations of the main noninvasive and invasive methods proposed to study coronary microcirculation and to identify CMVD in the presence of normal coronary arteries, also trying to provide indications for their application in clinical practice.

Heart rate variability (HRV) non-invasively assesses the activity of the autonomic nervous system. During the past 30 years, an increasing number of studies have related the imbalance of the autonomic nervous system (as assessed by HRV) to several pathophysiogical conditions, particularly in the setting of cardiovascular disease. Sudden death, coronary artery disease, heart failure, or merely cardiovascular risk factors (smoking, diabetes, hyperlipidemia, and hypertension) are the best-known clinical circumstances that can affect and/or be affected by the autonomic nervous system. Analyses of HRV variables have been proposed as a component of the clinical evaluation for patient risk stratification due to its independent prognostic information. Yet the potential for HRV to be used widely in clinical practice remains to be established., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Disclosure of potential conflicts of interest is used by biomedical journals to guarantee credibility and transparency of the scientific process. Conflict of interest disclosure, however, is not systematically nor consistently dealt with by journals. Recent joint editorial efforts paved the way towards the implementation of uniform vehicles for conflicts of interest disclosure. This paper provides a comprehensive editorial perspective on classical conflict of interest-related issues. New insights into current conflicts of interest policies and practices among European Society of Cardiology national cardiovascular journals, as derived from a cross-sectional survey using a standardized questionnaire, are discussed.

Background: The question of whether gender-related disparities still exist in the treatment and outcomes of patients presenting with acute coronary syndromes (ACS) remains controversial. Using data from 4 registries spanning a decade, we sought to determine whether sex-related differences have persisted over time and to examine the treating physician's rationale for adopting a conservative management strategy in women compared with men., Methods: From 1999 to 2008, 14,196 Canadian patients with non-ST-segment elevation ACS were recruited into the Acute Coronary Syndrome I (ACSI), ACSII, Global Registry of Acute Coronary Events (GRACE/GRACE(2)), and Canadian Registry of Acute Coronary Events (CANRACE) prospective multicenter registries., Results: Women in the study population were found to be significantly older than men and were more likely to have a history of heart failure, diabetes, or hypertension. Fewer women were treated with thienopyridines, heparin, and glycoprotein IIb/IIIa inhibitors compared with men in GRACE and CANRACE. Female gender was independently associated with a lower in-hospital use of coronary angiography (adjusted odds ratio 0.76, 95% CI 0.69-0.84, P < .001) and higher in-hospital mortality (adjusted odds ratio 1.26, 95% CI 1.02-1.56, P = .036), irrespective of age (P for interaction =.76). Underestimation of patient risk was the most common reason for not pursuing an invasive strategy in both men and women., Conclusions: Despite temporal increases in the use of invasive cardiac procedures, women with ACS are still more likely to be treated conservatively, which may be due to underestimation of patient risk. Furthermore, they have worse in-hospital outcomes. Greater awareness of this paradox may assist in bridging the gap between current guidelines and management practices., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Aims Previous studies have reported differences in the use of cardiovascular medications for acute coronary syndromes (ACSs) according to the sex of the patient. We analysed which clinical factors are associated with underutilization of evidence-based therapies in women. Methods and results From the Canadian Registry of ACS I and II, 6558 patients (4471 men and 2087 women) with a final diagnosis of ACS were selected for the current analysis. Covariates were chosen using the approach described by Blackstone. The final selected model included 23 patient clinical variables. Women were less likely than men to receive beta-blockers (75.76 vs. 79.24%; P < 0.01), lipid-modifying agents (56.37 vs. 65.44%; P < 0.0001), and angiotensin-converting enzyme (ACE)-inhibitors (55.52 vs. 59.99%; P < 0.01). Female sex and clinical decision not to investigate with cardiac catheterization were the strongest independent predictors for not receiving lipid-modifying agents and ACE-inhibitors. Age, Killip class 2, and Killip class 3/4 were significant independent predictors of underutilization of beta-blocker use. Women were older (69 ± 12 vs. 64 ± 12; P < 0.01) with a higher prevalence of Killip class ≥ 2 (19.95 vs. 15.54%; P < 0.068), and they were less likely to be referred for cardiac catheterization (41.9 vs. 49.6 %; P < 0.001). Conclusions The current findings demonstrate that underutilization of evidence-based therapies in women with ACS compared with men is associated with multiple factors related to the patient (age), the consequences of the disease (congestive heart failure), and the physician's assessment of patient risk (decision to catheterize). Female gender remains associated with underutilization of lipid-modifying agents and ACE-inhibitors despite adjustment for these confounders.

Cardiovascular disease (CVD) is the leading cause of death in women, and knowledge of the clinical consequences of atherosclerosis and CVD in women has grown tremendously over the past 20 years. Research efforts have increased and many reports on various aspects of ischaemic heart disease (IHD) in women have been published highlighting sex differences in pathophysiology, presentation, and treatment of IHD. Data, however, remain limited. A description of the state of the science, with recognition of the shortcomings of current data, is necessary to guide future research and move the field forward. In this report, we identify gaps in existing literature and make recommendations for future research. Women largely share similar cardiovascular risk factors for IHD with men; however, women with suspected or confirmed IHD have less coronary atherosclerosis than men, even though they are older and have more cardiovascular risk factors than men. Coronary endothelial dysfunction and microvascular disease have been proposed as important determinants in the aetiology and prognosis of IHD in women, but research is limited on whether sex differences in these mechanisms truly exist. Differences in the epidemiology of IHD between women and men remain largely unexplained, as we are still unable to explain why women are protected towards IHD until older age compared with men. Eventually, a better understanding of these processes and mechanisms may improve the prevention and the clinical management of IHD in women.

Key questions concerning strategies for diagnosis, prevention, and treatment of heart disease in women remain unanswered. Thrombolytic therapy has been shown to reduce mortality similarly in men and women. In addition, percutaneous coronary intervention for acute coronary syndromes is as effective in women as in men. However, after hospital discharge, medical treatment carries different benefits in men and women. Aspirin has not been definitively proven to prevent cardiovascular events in women. Men and women respond differently to statins. Men may experience a greater benefit than women from angiotensin-converting enzyme inhibitors. β-Blockers substantially improve survival in women, with possibly a greater benefit than in men. Clopidogrel appears to be equally effective in reducing cardiovascular events in both men and women. Our report will review current knowledge supporting sex differences in the diagnosis and treatment of ischemic heart disease. A clear definition of the state of the science, with recognition of the shortcomings of current data, is necessary to guide future research and move the field forward., (Copyright © 2010 Elsevier Inc. All rights reserved.)