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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 = 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 routinemedical 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. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

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

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 ( NCT 01218776) 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.

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 hypercho-lesterolemia (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 600 mg 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 300 mg clopidogrel loading dose, did not significantly impact the occurrence of the no-reflow. Conclusions: We found that pre-procedural administration of 600 mg loading dose of clopidogrel and/or unfractioned heparin is associated with reduced incidence of no-reflow. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

The aim of this study was to determine if earlier administration of oral beta-blocker therapy in patients with acute coronary syndromes (ACSs) is associated with increased short-term survival and improved left ventricular (LV) function. We studied 11,581 patients enrolled in the International Survey of Acute Coronary Syndromes in Transitional Countries (ISACS-TC) registry from January 2010 to June 2014. Of these patients, 6,117 were excluded as they received intravenous beta-blockers or remained free of any beta-blocker treatment during hospital stay, 23 with unknown timing of oral beta-blocker administration was unknown and 182 because they had death before oral beta-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 24 hours) during hospital stay in the remaining 3,882 patients. Early beta-blocker therapy was significantly associated with reduced in-hospital mortality (odds ratio [OR] 0.41, 95% confidence interval [CI] 0.21 to 0.80) and reduced incidence of severe LV dysfunction (OR 0.57, 95% CI 0.42 to 0.78). Significant mortality benefits with early beta-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 beta-blocker therapy should be a priority with a higher probability of improving LV function and in-hospital survival. Patients presenting with acute pulmonary edema or cardiogenic shock should be excluded from this early treatment regimen.

Histological specimen and textbook schematics evoke static pictures of vascular networks. However, the concept of a static system is grossly misleading as vessels and their arrangement into networks exhibit a high degree of adaptation in vessel tone and vessel wall structure.1–3 These adaptive responses include the fast adjustment of vessel diameter by changes in smooth muscle tone, the slower changes of structural vessel diameter, the addition or removal of vessels by angiogenesis (sprouting/splitting), or vascular pruning ( Figure 1 ). It is relevant to distinguish physiological adaptation, maintaining an adequate state of perfusion as well as perfusion reserve, from mal-adaptation, which may occur in the context of pathological conditions, such as a persistent increase in blood pressure. There are also differences between regulatory mechanisms in larger vessels (e.g. remodelling at the site of epicardial stenosis) and those in the microcirculation. Even within the microcirculation vascular control mechanisms are highly dependent on vessel size and type and the extent of changes in vasomotor tone and structure seem to increase with decreasing vessel size.4,5 Adaptive processes in the microcirculation are increasingly emerging as being crucial for maintenance of physiological function and for the development of relevant pathological conditions. This part of the coronary circulation, exhibiting that functional and structural plasticity requires more attention in both basic and clinical science as the basis to develop improved diagnostic and therapeutic approaches. Consequently, the present review will focus on adaptive events occurring in the coronary microcirculation which is beyond the domain of catheter investigation and intravascular imaging. Figure 1 Dynamics of vascular adaptation at various time scale (angioadaptation).57 While tone provides a rapid mechanism to adjust perfusion …

Background: Although coronary heart disease (CHD) mainly occurs in patients over the age of 50, younger patients can be affected as well. Most studies have used an age cut-off of 45 years to define “young” patients with CHD or acute coronary syndrome (ACS). We used this definition to investigate clinical characteristics and outcomes of ACS young patients in a large international cohort. Methods: Between 2010 and April 2016, 14931 ACS patients were enrolled in the ISACS-TC registry (ClinicalTrials.gov NCT01218776). Of these patients, 1182 (8%) were aged ≤ 45 years old (mean age 40.3 yrs, 15.8% female). The primary end-point was STEMI as index event and 30 day all cause mortality. Percent diameter stenosis of 50% or less were defined as insignificant coronary disease. Results: ST segment elevation myocardial infarction (STEMI) is the most common clinical manifestation of ACS in the younger cases (68 vs 59.6%). Younger patients had a higher incidence of insignificant coronary disease (7.6 vs 5.4%) and single vessel disease (67 vs 52.5%). Conversely, three-vessel disease was less common (7.7 vs 16.3%) in the younger patients. Smoking was the most important risk factor in this population (61.9 vs 34.9%). Predictors of ACS in the young population included male sex (OR 1.84), smoking habit (OR 2.29), family history of CHD (OR 1.72) and higher BMI (OR 1.05). Thirty day unadjusted day survival rates were 98.6 vs 93.1% for young and older patients. After adjusting for baseline characteristics, medications at admission and invasive procedures, age ≤ 45 years old was a predictor of survival in men (OR 0.19, 95% CI 0.07-0.48), but not in women (OR 0.85, 95% CI 0.36-2.04). Younger women had worse outcomes than men of a similar age (OR 5.85, 95% CI 1.92-17.77). Conclusions: ACS at a young age is characterized by less severe coronary disease and worse clinical presentation. Women have higher mortality than men. Factors underlying ACS in young patients and higher mortality rates in female sex warrant further investigation.

Background: Conflicting information exists on sex based differences in outcomes after pPCI. Worse outcomes after pPCI in women may be due to delay in presentation Methods: We, investigated the relationship among sex, prehospital delays and risks of adverse short clinical outcomes after pPCI using the ISACS-TC (NCT01218776) registry from 2010 - 2015. The study populations consisted of 6679 pts with STEMI who had pPCI within 24h of symptom onset. Multivariate logistic regression models were adjusted to covariates significantly different between groups in univariate analysis.The primary endpoint was 30 day mortality Results: Compared with a hospital admission greater than 2h, a time of 2h or less was associated with a lower incidence of death (6.5% vs 8.9%). Admission delays >2h were significantly more frequent in women than in men (67.7% vs 32.3%). There were no significant sex differences in door to balloon times (median: 45 vs 45 min). Unadjusted 30 days mortality was significantly higher in women than men (12.2% vs 6.6%). After multivariable adjustment, women remained significantly associated with a higher risk of death, OR: 1.33 CI 1.07- 1.66. Sex differences were no longer observed in the cohort, when the analysis was restricted to patients with hospital admission ≤2h, OR 0.89 CI 0.52-1.53 Conclusions: Among patients undergoing pPCI, women have a significantly higher risk of short-term mortality than men.