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Aims Previous analyses on sex differences in case fatality rates at population-level data had limited adjustment for key patient clinical characteristics thought to be associated with coronavirus disease 2019 (COVID-19) outcomes. We aimed to estimate the risk of specific organ dysfunctions and mortality in women and men. Methods and results This retrospective cross-sectional study included 17 hospitals within 5 European countries participating in the International Survey of Acute Coronavirus Syndromes COVID-19 (NCT05188612). Participants were individuals hospitalized with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from March 2020 to February 2022. Risk-adjusted ratios (RRs) of in-hospital mortality, acute respiratory failure (ARF), acute heart failure (AHF), and acute kidney injury (AKI) were calculated for women vs. men. Estimates were evaluated by inverse probability weighting and logistic regression models. The overall care cohort included 4499 patients with COVID-19-associated hospitalizations. Of these, 1524 (33.9%) were admitted to intensive care unit (ICU), and 1117 (24.8%) died during hospitalization. Compared with men, women were less likely to be admitted to ICU [RR: 0.80; 95% confidence interval (CI): 0.71–0.91]. In general wards (GWs) and ICU cohorts, the adjusted women-to-men RRs for in-hospital mortality were of 1.13 (95% CI: 0.90–1.42) and 0.86 (95% CI: 0.70–1.05; pinteraction = 0.04). Development of AHF, AKI, and ARF was associated with increased mortality risk (odds ratios: 2.27, 95% CI: 1.73–2.98; 3.85, 95% CI: 3.21–4.63; and 3.95, 95% CI: 3.04–5.14, respectively). The adjusted RRs for AKI and ARF were comparable among women and men regardless of intensity of care. In contrast, female sex was associated with higher odds for AHF in GW, but not in ICU (RRs: 1.25; 95% CI: 0.94–1.67 vs. 0.83; 95% CI: 0.59–1.16, pinteraction = 0.04). Conclusions Women in GW were at increased risk of AHF and in-hospital mortality for COVID-19 compared with men. For patients receiving ICU care, fatal complications including AHF and mortality appeared to be independent of sex. Equitable access to COVID-19 ICU care is needed to minimize the unfavourable outcome of women presenting with COVID-19-related complications.

Abstract: Heart failure (HF) is a common cause of morbimortality with different etiopathogenesis and prognosis between men and women. This review provides a brief overview of gender-based differences in response to pharmacological therapies of heart failure with or without reduced ejection fraction (EF). It focuses on the differences in therapy outcomes with angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARBs), angiotensin neprilysin inhibitors (ARNI), beta-adrenergic blockers, mineralocorticoid/ aldosterone receptor antagonists, diuretics, ivabradine and digoxin. The baseline data originate from randomised controlled trials (RCTs) and large registries. We conclude that current guidelines recommending similar therapeutic approaches for both men and women are appropriate, while additional consideration should be given to different approaches regarding the use of ARBs, ACEi, and digoxin. Based on the available data, the ARBs might be considered a first-line therapy of HR for women instead of ACEi. Moreover, female patients should have stricter digoxin monitoring due to higher sensitivity and increased risk of complications. Finally, women are underrepresented in current clinical trials, and therefore future trials should aim to balance the gender recruitment disparity allowing sub-group analysis and comparisons between genders to guide individualised therapeutic strategies and appropriately targeted preventative steps.

There is uncertainty regarding the impact of statins on the risk of atherosclerotic cardiovascular disease (ASCVD) and its major complication, acute heart failure (AHF).The aim of this study was to investigate whether previous statin therapy translates into lower AHF events and improved survival from AHF among patients presenting with an acute coronary syndrome (ACS) as a first manifestation of ASCVD.Data were drawn from the International Survey of Acute Coronary Syndromes Archives. The study participants consisted of 14,542 Caucasian patients presenting with ACS without previous ASCVD events. Statin users before the index event were compared with nonusers by using inverse probability weighting models. Estimates were compared by test of interaction on the log scale. Main outcome measures were the incidence of AHF according to Killip class and the rate of 30-day all-cause mortality in patients presenting with AHF.Previous statin therapy was associated with a significantly decreased rate of AHF on admission (4.3% absolute risk reduction; risk ratio [RR]: 0.72; 95% CI: 0.62-0.83) regardless of younger (40-75 years) or older age (interaction P = 0.27) and sex (interaction P = 0.22). Moreover, previous statin therapy predicted a lower risk of 30-day mortality in the subset of patients presenting with AHF on admission (5.2 % absolute risk reduction; RR: 0.71; 95% CI: 0.50-0.99).Among adults presenting with ACS as a first manifestation of ASCVD, previous statin therapy is associated with a reduced risk of AHF and improved survival from AHF. (International Survey of Acute Coronary Syndromes [ISACS] Archives; NCT04008173).

A partir da análise de uma instigante passagem, relativa à imagem das mãos da personagem principal da obra São Bernardo, de Graciliano Ramos, escrita no ano de 1934, objetivamos, com este trabalho, explicitar como a vida e a arte se entrelaçam quando em pauta práticas, representações e apropriações. Esse enlace servirá como ponto de reflexão para um fazer diferenciado, em se tratando da literatura no campo da educação. Para tanto, o referencial teórico será o estudo do crítico francês Roger Chartier (1988), acerca da A história cultural: entre práticas e representações.

Abstract: Coronary artery disease (CAD) is the leading cause of mortality globally. Although sub-stantial advances have been made in the diagnosis, management, and risk stratification of CAD, there is still a need for novel diagnostic biomarkers and new therapeutic targets to prevent the epi-demic of the disease. Recently, growing evidence has linked dysregulated microRNAs (miRNAs) to cardiovascular diseases, including CAD. miRNAs are endogenous, stable, single-stranded, short, non-coding RNAs, and may have utility as diagnostic and prognostic biomarkers for CAD. Dysreg-ulated miRNAs are involved in regulating lipid and glucose homeostasis pathways, renin-angiotensin-aldosterone pathways, inflammation, endothelial and vascular smooth cell phenotypes promoting atherosclerotic plaque development, progression, and instability. Additionally, miRNAs are stable and easily accessible in the extracellular space, may reside in microvesicles, and are de-tectable in serum or plasma, making them attractive biomarkers for the diagnosis and prognosis of cardiovascular disease. Accumulating studies suggest that miRNAs could be useful biomarkers for early discrimination of patients presenting with myocarditis or Takotsubo syndrome from those with a diagnosis of acute myocardial infarction, early prognostication of patients presenting with acute coronary syndromes, and accurate detection of left ventricular remodeling after a chronic or acute ischemic event. Moreover, miRNAs represent potential novel therapeutic targets for CAD or other cardiovascular diseases. This review provides an overview of the effects of the entire spec-trum of CAD, its major risk factors, and complications on levels of circulating miRNAs, as well as the limitations and challenges of their potential clinical applications.

Background The debate about statins in primary prevention of cardiovascular (CV) disease is still alive, especially in old and very old adults. Purpose We undertook a propensity match-weighted cohort study to investigate whether statin treatment recommendations translate into improved cardiovascular (CV) outcomes in the current routine clinical care of the elderly. Methods We included in our analysis 5,619 people aged 65 years or older from the ISACS (International Survey of Acute Coronary Syndrome) Archives (NCT04008173) who presented to hospital with a first manifestation of CV disease. Participants were stratified as statin users versus nonusers and as old (65 to 75 years) versus very old (76 years or over) adults. We estimated the effects of statins on the most severe clinical manifestation of CV disease, namely ST segment elevation myocardial infarction (STEMI), using inverse probability of treatment weighting models. Estimates were compared by test of interaction on the log scale. Results The risk of STEMI was much lower in statin users than in nonusers in both patients aged 65 to 75 years (14.7% absolute risk reduction; relative risk [RR] ratio: 0.55, 95% CI 0.45 to 0.66) and those aged 76 years and older (13.3% absolute risk reduction; RR ratio: 0.58, 95% CI 0.46 to 0.72). Estimates were similar in patients with and without history of hypercholesterolemia (interaction test; p value= 0.2408). Proportional reductions in STEMI diminished with female sex in the old (p for interaction=0.002), but not in the very old age (p for interaction=0.26). We also observed a remarkable reduction in the risk of 30- day mortality from STEMI with statin therapy in both age groups (10.2% absolute risk reduction; RR ratio: 0.39; 95% CI 0.23 – 0.68 for patients aged 76 or over and 3.8% absolute risk reduction; RR ratio 0.37; 95% CI 0.17 – 0.82 for patients aged 65 to 75 years old; interaction test, p value=0.4570). Conclusion Preventive statin therapy in the elderly reduces the risk of STEMI with benefits in mortality from STEMI, irrespective of the presence of a history of hypercholesterolemia. This effect persists after the age of 76 years. Benefits are less pronounced in women. Funding Acknowledgement Type of funding sources: None.

Background: Patients with malignancies may have a high pro-thrombotic status as well as a high risk of hemorrhagic events either due to the tumor or its treatment.For this reason, these patients have always been excluded from randomized clinical trial on percutaneous coronary intervention (PCI). Aim: To investigate the safety of PCI in patients with malignancies admitted for an AMI. Methods and Results: Retrospective analysis on an international European ACS registry. Primary endpoint: 30-day mortality. Secondary endpoint: periprocedural-complications. There were 273 patients (35% women) with AMI and malignancies. Colon (19%), prostate (14%), breast (13%), lung (8%) and blood (8%) malignancies were the most frequents type of cancer. Women and men had similar age (68 ±11.5 vs 69.1 ±11.5, p=ns). STEMI was in 56% of patients (with no significant gender difference: 51% men vs 65% women, p=0.09). PCI was performed in 64% of patients (with primary PCI in 75% of STEMI). The rate of complications during cardiac catheterization and intervention was 6.5% (2.1% distal embolization, 2.1% no-reflow, 0.7% acute closure, 0.7% dissection, 0.7% perforation, none major bleeding). Nobody among patients that had cardiac catheterization and intervention complications died during hospital stay. In-hospital mortality was 5.9%. The group of patients treated with PCI had a significantly lower rate of death then that of those treated non invasively (1.7% vs 13.1%, p Conclusion: These preliminary data from real word support the safety use of PCI in patients with malignancies and ACS, which have always been excluded from randomized clinical trial.

Le malattie cardiovascolari continuano a rappresentare la principale causa di morte e disabilità. Questo libro, dedicato a tale tema cruciale della medicina, è stato pensato per offrire uno strumento innovativo e agile a studenti di medicina, medici e specialisti, cardiologi e non, interessati ad approfondire tutti i temi principali pertinenti. La novità dell’opera rientra precisamente nella geometria dei capitoli, tutti scritti da esperti riconosciuti della materia. In particolare, il lettore vi troverà sempre all’inizio di ogni contributo un caso clinico pertinente all’argomento, quindi una sintesi del tema fisiopatologico o clinico specifico, e infine uno studio scientifico commentato, tale da metterne in luce, oltre ai risultati, uno o più aspetti metodologici di rilievo. La sezione centrale si avvicina per forma e contenuti ad altri testi di cardiologia, ma l’abbinamento caso clinico - sintesi del tema - studio scientifico costituisce una novità sostanziale.

Introduction: The use of digitalis has been plagued by controversy since its initial use. Previous observations have shown that digoxin can be safely used in patients with chronic heart failure (HF), but concern remains about the effects of digoxin on mortality in patients with incident HF in the acute setting, especially in those with myocardial infarction. Hypothesis: We aimed to determine the relationship between digoxin use and outcomes in hospitalized patients with acute coronary syndromes (ACS) complicated by HF accounting for sex difference and prior heart diseases. Methods: We analyzed information on 88,774 patients presenting with acute HF (Killip class ≥2) in the International Survey of Acute Coronary Syndromes (ISACS)-Archives (NCT04008173) registry, 4,722 (18.7%) who received digoxin on hospital admission. Patients with pre-existing nonischemic congestive cardiomyopathy and without HF were excluded, leaving a final study population of 25,187 patients. The main outcome measure was all-cause 30-day mortality. Estimates were evaluated by inverse probability of treatment weighting models. Results: Women who received digoxin had a higher rate of death than women who did not receive it (33.8% vs. 29.2 %; relative risk [RR] ratio:1.24;95 % confidence interval [CI]: 1.12-1.37). Similar odds for mortality with digoxin were observed in men (28.5 % vs. 24.9 %; RR ratio 1.20; 95% CI:1.10-1.32). Comparable results were obtained in patients with no prior coronary heart disease (RR ratios:1.26; 95 % CI: 1.10 to 1.45 in women and RR:1.21; 95 % CI: 1.06 to 1.39 in men) and those in sinus rhythm at admission (RR ratios:1.34; 95% CI 1.15 to 1.54 in women and 1.26; 95% CI 1.10 to 1.45 in men). Conclusions: Digoxin therapy is associated with an increased risk of early death among women and men with ACS complicated by HF. This finding highlights the need for re-examination of digoxin use in the clinical setting of ACS

Introduction: We investigate whether treatment recommendations for statins in primary prevention of cardiovascular disease (CVD) based on sex, age and risk factors translate to better CV outcomes in current routine clinical care. Methods: We studied a propensity match-weighted cohort of 14,542 Caucasian patients presenting with a first manifestation of CVD from the International Survey of Acute Coronary Syndromes (ISACS) Archives databank (NCT04008173) . Main outcome measures were the incidence of ST segment elevation myocardial infarction (STEMI) and acute heart failure (HF) on hospital admission. Results: Prior statin use was associated with a significantly decreased rate of STEMI (absolute difference 10.2%; RR ratio, 0.64; 95%CI 0.58 to 0.71) and acute HF (absolute difference 4.3%; RR ratio 0.72, 95% CI 0.62 to 0.83). Benefits were not attenuated when controlling for age 75 years and older (RR ratios 0.59, 95% CI 0.46 to 0.75 for STEMI and 0.66, 95% CI 0.50 to 0.87 for HF). Statin therapy had no effect in patients with 10-year ASCVD risk threshold less than 10% (RR ratios:0.85,95%CI:0.66- 1.08 for STEMI and 0.85,95%CI:0.60-1.20 for HF). Reductions in major CV events with statins diminished with female sex (interaction p=0.0200 for STEMI, and 0.2180 for HF). Moreover, statin use determined a lower risk of 30-day mortality in patients presenting with HF on admission (5.2 % absolute risk reduction and a 29% relative risk reduction). Conclusions: Prevention statin therapy reduces the risk of STEMI and acute HF with benefit in mortality from HF. The most gain is attained in male sex and in subjects with 10-year ASCVD risk ≥10%

Background There are a range of traditional risk factors for COVID-19, but it is not well established if there are also psychiatric related risk factors. These factors could increase angiotensin-converting enzyme 2 expression and potentiate COVID-19 cell entry. Purpose We aimed to assess if psychiatric disorders and antipsychotic treatments represent risk factors for COVID-19 worst outcomes. Methods We describe the demographics, symptoms, therapeutic management, and survival outcomes of COVID-19 in the population who were admitted in a single academic hospital in Northern Italy between March 1 and June 30, 2020. Patients were determined to have COVID-19 if they had a positive SARS-CoV-19 swab. We used logistic regression analyses to control for confounding by concomitant risk factors for COVID-19 and for therapeutic management of comorbidities including psychiatric disorders and antipsychotic related drugs. Results Among 609 patients, in-hospital death occurred in 120 (19.7%). A psychiatric disorder in the previous years was overrepresented (p Conclusions Antipsychotic drugs might be an independent risk factor for COVID-19 adverse outcomes. Although preliminary, our findings have implications for clinical services as they provide crucial information for understanding who is at greatest risk for COVID-19. Funding Acknowledgement Type of funding sources: None.

Subjects affected by ischemic heart disease with non-obstructive coronary arteries constitute a population that has received increasing attention over the past two decades. Since the first studies with coronary angiography, female patients have been reported to have non-obstructive coronary artery disease more frequently than their male counterparts, both in stable and acute clinical settings. Although traditionally considered a relatively infrequent and low-risk form of myocardial ischemia, its impact on clinical practice is undeniable, especially when it comes to infarction, where the prognosis is not as benign as previously assumed. Unfortunately, despite increasing awareness, there are still several questions left unanswered regarding diagnosis, risk stratification and treatment. The purpose of this review is to provide state of the art update on the current evidence available on gender differences in clinical characteristics, management and prognosis of ischemic heart disease with non-obstructive coronary arteries, both in the acute and stable clinical settings.

Background and aims: An increasing proportion of women believe that smoking few cigarettes daily substantially reduces their risk of developing cardiovascular (CV) related disorders. The effect of low intensity smoking is still largely understudied. We investigated the relation among sex, age, cigarette smoking and ST segment elevation myocardial infarction (STEMI) as initial manifestation of CV disease. Methods: We analyzed data of 50,713 acute coronary syndrome patients with no prior manifestation of CV disease from the ISACS-Archives (NCT04008173) registry. We compared the rates of STEMI in current smokers (n = 11,530) versus nonsmokers (n = 39,183). Results: In the young middle age group (

Background Studies from countries with high public health expenditure (PHE) have reported a decline of the rates of mortality from cardiovascular disease (CVD).Given that most mortality from CVD occurs in countries with low and middle PHE, there is a need for broader information on the relationship between variability in disease burden and outcomes in such countries. Purpose The aim of this study was to evaluate the relation among risk factors, revascularization therapies and short-term mortality from acute coronary syndromes (ACS) in patient admitted to hospitals in middle versus low PHE countries. Methods Data were derived from 18,704 patients admitted to 41 hospitals referring data to the ISACS-TC registry (NCT0128776). Patients were divided in two groups:low and middle PHE. Bosnia and Herzegovina,Croatia,Hungary,Italy,and Serbia have high PHE values, whereas Macedonia, Romania, Lithuania, Russian Federation, Kosovo,Moldova, and Montenegro, have low values. Main outcome measure was 30-day mortality. We used logistic-regression models to assess the effect of variables on the associations of interest. Results There were 18,704 patients admitted to hospital for an ACS. Of these patients, 45% were in the low PHE group and 55% in the middle PHE group. Patients in middle PHE group were older (64% vs 61%), had higher prevalence of traditional risk factors, namely hypertension (75% vs 66%), hypercholesterolemia (55% vs 31%), diabetes (28.58% vs 23.10%), and positive family history of coronary artery disease (45.66% vs 17.56) as compared with patients in the low PHE group.Furthermore, patients in the middle PHE group had more frequently history of prior ischemic heart disease and higher rate of ST segment elevation myocardial infarction (STEMI) as clinical presentation (63.91 vs 61.98). The crude 30-day mortality rate was 6.97% in the middle PHE and 5,82% in the low PHE group. After multivariable adjustment for comorbidities and treatment covariates, patients in the middle PHE group had a better outcome compared with those in the low PHE group (OR 0.64; 95% CI 0.45–0.93).As most patients presented to hospital with STEMI we performed separate analyses for such patients and stratified outcomes in function of time to hospital presentation from initial symptom onset. The odds of mortality were still lower in patients in the middle PHE group (OR 0.41; 95% CI 0.22–0.76) if they presented within 6 hours from symptom onset.In contrast there were no difference in outcomes between middle and low PHE groups (OR 0.69; 95% CI 0.34–1.44) in patients with delayed presentation.This held true even in patients undergoing primary percutaneous intervention (OR 1.02; 95% CI 0.43–2.39). Conclusions There are significant costs and infrastructure limitations that prohibit most countries with low PHE from having timely admission to hospital of patients with suspected ACS. Currently, many of the Eastern European countries are facing an enormous burden of mortality from CVD. Funding Acknowledgement Type of funding source: None

This article offers an updated and comprehensive overview of major findings on the effects of statin treatment in patients with chronic angina but without any epicardial coronary artery with obstructive lesion.

Cardiovascular diseases and cancer are the leading cause of morbidity and mortality globally. Cardiotoxicity from chemotherapeutic agents results in substantial morbidity and mortality in cancer survivors and patients with active cancer. Cardiotoxicity induced by 5-fluorouracil (5-FU) has been well established, yet its incidence, mechanisms, and manifestation remain poorly defined. Ischemia secondary to coronary artery vasospasm is thought to be the most frequent cardiotoxic effect of 5-FU. The available evidence of 5-FU-induced epicardial coronary artery spasm and coronary microvascular dysfunction suggests that endothelial dysfunction or primary vascular smooth muscle dysfunction (an endothelial-independent mechanism) are the possible contributing factors to this form of cardiotoxicity. In patients with 5-FU-related coronary artery vasospasm, termination of chemotherapy and administration of nitrates or calcium channel blockers may improve ischemic symptoms. However, there are variable results after administration of nitrates or calcium channel blockers in patients treated with 5-FU presumed to have myocardial ischemia, suggesting mechanisms other than impaired vasodilatory response. Clinicians should investigate whether chest pain and ECG changes can reasonably be attributed to 5-FU-induced cardiotoxicity. More prospective data and clinical randomized trials are required to understand and mitigate potentially adverse outcomes from 5-FU-induced cardiotoxicity.

Background Patients with diabetes and non-ST elevation acute coronary syndrome (NSTE-ACS) have an increased risk of mortality and adverse outcomes following percutaneous coronary intervention (PCI). Purpose We aimed to investigate the impact of early, within 24 hours PCI compared with only routine medical treatment on clinical outcomes in a large international cohort of patients with NSTE-ACS and diabetes. Methods We identified 1,250 patients with diabetes and NSTE-ACS from a registry-based population between October 2010 and April 2016. The primary endpoint was 30-day all-cause mortality. The secondary endpoint was the composite outcome of 30-day all-cause mortality and left ventricular dysfunction (ejection fraction Results Of 1,250 NSTE-ACS first-day survivors with diabetes (median age 67 years; 59%, men), 470 (37.6%) received early PCI and 780 routine medical treatment. The overall 30-day all-cause mortality rates were higher in the routine medical treatment than the early PCI group (6.3% vs. 2.5%). The prediction results of the MC algorithms accounted for only one interaction term that was statistically significant: age ≥65 years. After propensity-matched analysis as well as IPTW, early PCI was associated with reduced 30-day all-cause mortality in the older age (OR: 0.35; 95% CI: 0.14 to 0.92 and 0.43; 95% CI: 0.21 to 0.86, respectively), whereas younger age had no association with the primary endpoint. Similar results were also obtained for the secondary endpoint. Conclusions Among patients with diabetes hospitalized for NSTE-ACS, an early, within 24 hours, PCI strategy is associated with reduced odds of 30-day mortality only for patients aged 65 years or over. MC algorithms provide accurate identification of treatment effect modifiers.

Background Although guidelines from the European Society of Cardiology and American Heart Association/American College of Cardiology recommend early percutaneous coronary intervention (PCI) in all patients with non-ST-elevation myocardial infarction/ unstable angina (NSTE-ACS), in day-to-day practice persists uncertainty as to whether to follow guidelines in patients aged 75 years or older. Indeed, recommendations are based on large randomized trials where patients aged 75 years or older are under-represented. Purpose We aimed to investigate whether patients aged 75 years or older would benefit from an early invasive strategy versus a conservative strategy. We also analyzed the factors associated with the choice of an early PCI in this population. Methods The research was conducted on the population of the International Survey of Acute Coronary Syndromes (ISACS-TC) registry. The study population consisted of 6826 eligible patients with NSTE-ACS. Of these patients, 1496 were 75 years old or older and were included in the analysis. The primary outcome measure was 30-day mortality. Key secondary outcomes were bleeding complications during the index hospitalization. Multivariate logistic regression analyses were conducted to establish outcomes and factors associated with outcomes. We evaluated specific ranges of ages: 75–79 years, 80–84 years, and 85 years or over. Further, data were sorted by sex and diabetes mellitus status. Results The mean age of our study population was 80.0 (interquartile range: 77–82) years old. Elderly patients treated with early PCI and medical therapy were significantly younger than those treated with only medical therapy were (78.9 vs 80.5, p Conclusions In the real-life clinical setting, early PCI is a safe and efficacious treatment option in very elderly patients presenting with NSTE-ACS. Revascularization is better than medical therapy whatever the age is.

Background: It remains uncertain whether female sex is itself a strong risk factor for worse outcomes in ACS. We hypothesized that sex differences in vulnerability to heart failure after ACS may modify the association between sex and outcomes Methods: Data were drawn from the ISACS-Archives network of registries (NCT04008173). The study population consisted of 87,812 patients with known time from symptom onset to hospital presentation. Participants were stratified by ACS subtypes: STEMI and NSTEACS Data on presenting heart failure symptoms were collected from medical record abstraction. Heart failure was categorized as Killip class >2. Time from symptom onset to hospital presentation was categorized as early (≤120 minutes) or late (>120 minutes). The primary outcome measure was 30-day mortality. Estimates were performed using a parametric balancing strategy by weighting and compared by test of interaction on the log scale Results: Among the study sample, 30922 (35.2%) patients were women. Patient outcomes varied according to subtype of ACS. The mortality rates at 30-days were significantly higher among women vs men in STEMI (RR:1.65; 95%CI: 1.56-1.73) compared with NSTEACS (RR:1.18; 95%CI: 1.09-1.28; P interaction

Background: Controversies persist about the role of statins in primary prevention of atherosclerotic cardiovascular disease (ASCVD). We sought to determine whether initiation of statin therapy for primary prevention of cardiovascular disease may lead to a reduction in cardiovascular outcomes across age, sex, and risk factors. Methods: We investigated 14,542 patients aged ≥40 years presenting to hospitals with ACS as first manifestation of cardiovascular disease from 2010 to 2019 in the ISACS Archives network of registries (NCT04008173). Individual risk of STEMI, acute heart failure (HF) on hospital admission and all-cause 30-day mortality were assessed using inverse probability of treatment weighting models matching for concomitant medications. Acute HF was defined as Killip class≥ 2. Estimates were compared by test of interaction on the log scale. Results: Among the study population 12.5% of patients were on statin therapy. Mean (SD) estimated 10-year risk for ASCVD was 25.8 (17.9) in statin users vs 22.5 (17.1) in non-users. The risk of STEMI was much lower in the statin-users than in the non-users (relative risk [RR] ratio 0.64; 95%CI 0.58-0.71). This effect persisted in both sexes, but was substantially stronger in men (absolute reduction: 11.5%; RR ratio: 0.61, 95%CI: 0.54-0.69) than in women (absolute reduction: 6.3%; RR ratio: 0.76, 95% CI: 0.64-0.90, p interaction=0.02). These benefits translated into reductions in acute HF on hospital admission with statin therapy for both women (RR ratio 0.66, 95%CI: 0.53-0.83) and men (RR ratio 0.74, 95%CI 0.62-0.89; p interaction=0.22). No effect on the rates of STEMI or acute HF was noted in patients with 10-year ASCVD risk lower than 10% for either sex. Acute HF was predictive of mortality at 30 days both in women and in men. Conclusion: Preventive statin therapy reduces the risk of STEMI as initial manifestation of cardiovascular disease and acute HF with potential benefits in mortality. The most gain is attained in male subjects with 10-year CV risk equal or more than 10%.

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.

Background: To investigate the impact of early, within 24 hours, percutaneous coronary intervention (PCI) compared with only routine medical treatment on clinical outcomes in a large international cohort of patients with non-ST elevation acute coronary syndrome (NSTE-ACS) and diabetes. Methods: Cohort study using a population- based registry (International Survey of Acute Coronary Syndromes in Transitional Countries [ISACS-TC]) enrolled in 41 hospitals participating in the ISACS-TC in 12 European countries between October 2010 and April 2016. We identified 1,250 patients with diabetes and NSTE-ACS. The primary endpoint was 30-day all-cause mortality. The secondary endpoint was the composite outcome of 30-day all-cause mortality and left ventricular dysfunction (ejection fraction < 40%). We undertook analyses to explore the heterogeneity of treatment effects using meta-classification (MC) algorithms followed by propensity score matching and inverse probability-of-treatment weighting (IPTW) from a landmark of 24 hours from hospitalization. Findings: Of 1,250 NSTE-ACS first-day survivors with diabetes (median age 67 year; 59%, men), 470 (38%) received early PCI and 780 routine medical treatment. The overall 30-day all-cause mortality rates were higher in the routine medical treatment than the early PCI group (6·3% vs. 2·5%). The prediction results of the MC algorithms accounted for only one interaction term that was statistically significant: age ≥ 65 years. After propensity-matched analysis as well as IPTW, early PCI was associated with reduced 30-day all-cause mortality in the older age (OR: 0·35; 95%CI: 0·14 to 0·92 and 0·43; 95%CI: 0·21 to 0·86, respectively), whereas younger age had no association with the primary endpoint. Similar results were also obtained for the secondary endpoint. Interpretation: Among patients with diabetes hospitalized for NSTE-ACS, an early, within 24 hours, PCI strategy is associated with reduced odds of 30-day mortality only for patients aged 65 years or over. MC algorithms provide accurate identification of treatment effect modifiers. Funding Statement: None Declaration of Interests: No competing interest exist. Ethics Approval Statement: The study was approved by the local research ethics committee from each hospital.

Takotsubo syndrome (TTS) is a recently identified acute heart syndrome, characterized by regional wall motion abnormalities not justified by the presence of significant coronary artery obstruction. Clinically, TTS closely resembles acute coronary syndromes (ACS) and therefore differential diagnosis may be an important obstacle for its correct clinical management. The prevalence of TTS is estimated to be around 2% of acute myocardial infarctions, and the number of diagnoses has increased in recent years, possibly reflecting our growing understanding of this condition. Given the similarities between TTS and ACS, clinical presentation in these patients is equivocal. However, numerous peculiar traits have been observed, such as the greater prevalence in postmenopausal women and the presence of stressful triggers. Many pathogenetic hypotheses for TTS, such as catecholamine overload and microvascular dysfunction, have been proposed. None of these have been capable of independently explaining the underlying mechanisms. The diagnostic criteria proposed by the Heart Failure Association of the European Society of Cardiology represent a novel attempt to introduce semiquantitative parameters, yet further scientific validation is needed. Contrary to previous opinions, TTS is not always benign, considering the relatively high prevalence of acute complications, an estimated in-hospital mortality similar to that of acute myocardial infarction (1–8%), and a significant rate of recurrences and persistence of symptoms. Clinical management of TTS has been largely based on empirical experience related to ACS, and therefore pharmacological strategies are partially overlapping. An issue of the utmost importance is the lack of randomized prospective data validating diagnostic criteria, risk stratification, and specific therapeutic approaches.

Background: Patients with malignancies may have high pro-thrombotic status as well as a high risk of hemorrhagic events either due to the tumor or its treatment.For this reason, these patients have always been excluded from randomized clinical trials on percutaneous coronary intervention (PCI). Aim: To investigate the safety of PCI in patients with malignancies admitted for an AMI. Methods and Results: Retrospective analysis on an international European ACS registry. Primary endpoint: 30-day mortality. Secondary endpoint: periprocedural complications. There were 273 patients (35% women) with AMI and malignancies. Colon (19%), prostate (14%), breast (13%), lung (8%) and blood (8%) malignancies were the most frequent type of cancer. Women and men had similar age (68 ±11.5 vs 69.1 ±11.5, p=ns). STEMI was in 56% of patients (with no significant gender difference: 51% men vs 65% women, p=0.09). PCI was performed in 64% of patients (with primary PCI in 75% of STEMI). The rate of complications during cardiac catheterization and intervention was 6.5% (2.1% distal embolization, 2.1% no-reflow, 0.7% acute closure, 0.7% dissection, 0.7% perforation, none major bleeding). Nobody among patients that had cardiac catheterization and intervention complications died during hospital stay. In-hospital mortality was 5.9%. The group of patients treated with PCI had a significantly lower rate of death then that of those treated non invasively (1.7% vs 13.1%, p