Edina Cenko

Exploring in-hospital death from myocardial infarction in Eastern Europe: From the international registry of acute coronary syndromes in transitional countries (ISACS-TC); on the behalf of the working group on coronary pathophysiology & microcirculation of the European Society of Cardiology

INTRODUCTIONnThe 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.nnnCONCLUSIONnIn-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.

Unfractionated heparin-clopidogrel combination in ST-elevation myocardial infarction not receiving reperfusion therapy.

OBJECTIVEnWe 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.nnnMETHODSnThis 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.nnnRESULTSnAfter 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, pxa0=xa00.06). The risk of major hemorrhage was nearly similar with combined UFH-clopidogrel therapy (1.4%) as compared with UFH alone (1.9%), pxa0=xa00.67.nnnCONCLUSIONnUFH - 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.

Reperfusion therapy for ST-elevation acute myocardial infarction in Eastern Europe: the ISACS-TC registry

AimsnWidespread 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.nnnMethods and resultsnData 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).nnnConclusionsnA 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.

Vasotonic Angina as a Cause of Myocardial Ischemia in Women.

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).

The no-reflow phenomenon in the young and in the elderly

BACKGROUNDnThe 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.nnnMETHODSnData 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.nnnRESULTSnNo-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.nnnCONCLUSIONSnWe found that pre-procedural administration of 600mg loading dose of clopidogrel and/or unfractioned heparin is associated with reduced incidence of no-reflow.

Primary percutaneous coronary intervention in octogenarians

BACKGROUNDnLimited 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.nnnMETHODSn2225 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.nnnRESULTSnThirty-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.nnnCONCLUSIONSnAge 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.

Persisting chest pain in nonobstructive coronary artery disease

This editorial refers to ‘Natural history of patients with insignificant coronary artery disease’, by R. Tavella et al ., on page 117. nnChest pain is the most common symptom of coronary artery disease (CAD) prompting subjects to seek attention from physicians. Angina is an important predictor of outcomes and to a large extent determines health-related quality of life (HRQoL) even in the overall apparently health population.1 Furthermore, physical disability caused by angina has an impact on prognosis as well as on HRQoL.2 Early reports have demonstrated the value of supplementing the clinical presentation of angina with angiographic information.3 Angiography does not miss significant life-threatening disease. The severity and the extent of obstructive coronary lesions demonstrated by angiography are powerful predictors of death. Clinical presentation is also a strong predictor of mortality, as type and severity of chest pain act indirectly as predictors because of their association with the severity of the coronary stenosis. For this reason, studies designed to evaluate the influence of medical or interventional therapy on survival and/or HRQoL should utilize angiographic findings in the selection of groups of patients. The results of the study by Tavella et al .4 are at variance with these ‘rules of thumb’. These authors looked at patients with stable CAD and reported 1% of recurrence of myocardial infarction in a group of 253 patients with chest pain and non-obstructive CAD who were followed for 12 months. Similar outcomes were found in those patients labelled as obstructive CAD who, indeed, had clinically negligible differences in prognosis: 1% death and 1% myocardial infarction during the same time span. Similarity was even more when evaluating HRQoL status in the two groups of patients. These findings raise several important issues.nnThe population reported by Tavella et al .4 was highly selected in … nn[↵][1]*Corresponding author. Tel: +39 051 347290, Fax: +39 051 347290, Email: raffaele.bugiardini{at}unibo.itnn [1]: #xref-corresp-1-1

Invasive versus conservative strategy in acute coronary syndromes: The paradox in women's outcomes

BACKGROUNDnWe 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.nnnMETHODSnFrom 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.nnnRESULTSnWomen 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).nnnCONCLUSIONSnWe 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.

SEX-RELATED DIFFERENCES IN ACUTE CORONARY CARE AMONG PATIENTS WITH MYOCARDIAL INFARCTION: THE ROLE OF PRE-HOSPITAL DELAY

We sought to investigate sex-related differences in access to care among patients with myocardial infarction (STEMI) in order to identify gender-related factors associated with outcomes.nnWe studied 7457 patients enrolled in the ISACS-TC registry 2010-2014 ([ClinicalTrials.gov][1] [NCT01218776][2

SEX-BASED DIFFERENCES IN SHORT TERM SURVIVAL AFTER PRIMARY PERCUTANEOUS CORONARY INTERVENTION: THE ROLE OF SYSTEM DELAY

Conflicting information exists on sex based differences in outcomes after pPCI. Worse outcomes after pPCI in women may be due to delay in presentationnnWe, investigated the relationship among sex, prehospital delays and risks of adverse short clinical outcomes after pPCI using the ISACS-TC ([