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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.

Background: We aimed to analyze the prevalence and long-term prognostic impact of non-cardiac comorbidities in patients with reduced and preserved left-ventricular ejection fraction (EF) following ST-elevation myocardial infarction (STEMI). Method: A total of 3033 STEMI patients undergoing primary percutaneous coronary intervention (pPCI) were divided in two groups: reduced EF < 50% and preserved EF ≥ 50%. The follow-up period was 8 years. Results: Preserved EF was present in 1726 (55.4%) patients and reduced EF was present in 1389 (44.5%) patients. Non-cardiac comorbidities were more frequent in patients with reduced EF compared with patients with preserved EF (38.9% vs. 27.4%, respectively, p < 0.001). Lethal outcome was registered in 240 (17.2%) patients with reduced EF and in 40 (2.3%) patients with preserved EF, p < 0.001. Diabetes and chronic kidney disease (CKD) were independent predictors for 8-year mortality in patients with preserved EF. In patients with reduced EF, CKD was independently associated with 8-year mortality. Conclusion: In patients who had reduced EF, the prevalence of non-cardiac comorbidities was higher than in patients who had preserved EF after STEMI. Only diabetes mellitus and CKD were independently associated with 8-year mortality in analyzed patients.

Cardiomyopathies (CM) are a heterogeneous group of diseases of various etiologies that lead to morphological and functional damage to the heart. Throughout history, there have been numerous attempts to classify them, and the latest division of the European Society of Cardiology (2008) has classified all CM into four basic phenotypes: dilated CM, hypertrophic CM, restrictive CM and arrhythmogenic CM of right ventricle. Other CM are classified as unclassified. According to the form of inheritance, they are divided into familial (genetic) and non-familial forms of the disease. The importance of CM is reflected not only in their high incidence in the general population but also in the very difficult clinical presentation at the time of their diagnosis. Complaints in most patients occur gradually and quietly, and the first manifestation of the disease can be some of the fatal complications (malignant arrhythmia or systemic embolization). Distinguishing CM from hypertensive, ischemic and valvular heart disease is a difficult differential diagnostic problem that needs to be solved due to different modalities of treatment of these conditions. CM is one of the most common causes of heart failure and terminal heart failure is the leading indication for heart transplantation. Therefore, the treatment of CM aims to reduce the symptoms of heart failure (following the latest guidelines for the treatment of heart failure) and improve heart function. The frequency of malignant heart rhythm disorders and sudden cardiac death is much more common in the population of patients with CM. In addition to standard drug therapy, immunosuppressive therapy, surgical procedures, (installation of pacemakers, implantable cardioverter defibrillators, septal myectomy, installation of temporary mechanical circulatory support devices (EKMO, Impella, LVAD) are increasingly used in the treatment of these patients. Given that a large number of CM are hereditary diseases and that their treatment is often complicated, preventive examinations of the population are very important in order to timely diagnose these diseases as well as genetic screening of close relatives suffering from CM.

Mortality decline in women to a lesser extent than in men with coronary artery disease (CAD) has provoked a bigger interest in some already existing dilemmas and questions. Many studies carried out in the past three decades did not provide us with precise conclusions. Moreover, various challenges in the prevention, diagnosis, treatment and outcome of CAD in women are still remaining. The meta-analysis and the systematic review conducted in the last years have offered novel approaches to understanding CAD gender disparities in access to care and coronary disease management in women, but women are more likely to experience less favorable short- and long-term outcomes than men do. The reasons for these findings should lie in several known segments in the CAD pathophysiological mechanisms different in women and ultimately leading to a lower quality of care. Clinical presentation in women, which is often characterized by atypical chest pain and a higher prevalence of non-obstructive CAD when evaluated invasively, places women to the false-negative diagnosis of CAD and influences inadequate access to care. Clinical presentation and diagnostic methods, as well as the appropriate treatment options insufficiently examined in women, need to be better defined. The traditional CAD risk factors have a greater impact on women than on men. Unique CAD risk factors only seen in women, have recently been recognized with more attention. However, it is important to note that even in women with obstructive CAD and typical clinical presentation, invasive therapy and pharmacologic therapy are not always implemented as recommended by guidelines as in men. Women are underrepresented in CAD trials, and in current guidelines, gender differences in CAD management have not yet been justified. The underestimation of the risk of CAD in women, followed by its underdiagnosis and undertreatment, might be one of the reasons for a worse prognosis in women in comparison with men.

OBJECTIVE: In this study, we aimed to examine the prognostic impact of decreased kidney function at admission on the occurrence of new-onset atrial fibrillation (AF) in patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). METHODS: The study enrolled 3,115 consecutive patients with STEMI. Kidney function was assessed by estimation of the glomerular filtration rate (eGFR) at admission. Patients with cardiogenic shock at admission, patients on hemodialysis, and patients with a medical history of previous AF (paroxysmal, persistent, or permanent) were excluded. The follow-up period was six years. RESULTS: New-onset AF occurred in 215 (6.9%) patients, 75 (34.9%) patients presented with AF, and 140 (65.1%) patients developed AF after pPCI. The median time of AF occurrence in patients who did not present with AF was 4.5 (interquartile range 1–25) hours after pPCI. New-onset AF was associated with a higher short- and long-term mortality. In the multiple logistic regression analysis, all stages of reduced kidney function were independent predictors for the occurrence of new-onset AF, and negative prognostic impact increased with the deterioration of kidney function: eGFR

The incidence of atrial fibrillation (AF) in acute coronary syndrome (ACS) ranges from 2.3–23%. This difference in the incidence of AF is explained by the different ages of the patients in different studies and the different times of application of both reperfusion and drug therapies in acute myocardial infarction (AMI). About 6–8% of patients who underwent percutaneous intervention within AMI have an indication for oral anticoagulant therapy with vitamin K antagonists or new oral anticoagulants (NOAC).The use of oral anticoagulant therapy should be consistent with individual risk of bleeding as well as ischemic risk. Both HAS-BLED and CHA2DS2VASc scores are most commonly used for risk assessment. Except in patients with mechanical valves and antiphospholipid syndrome, NOACs have an advantage over vitamin K antagonists (VKAs). One of the advantages of NOACs is the use of fixed doses, where there is no need for successive INR controls, which increases the patient’s compliance in taking these drugs. The use of triple therapy in ACS is indicated in the case of patients with AF, mechanical valves as well as venous thromboembolism. The results of the studies showed that when choosing a P2Y12 receptor blocker, less potent P2Y12 blockers such as Clopidogrel should be chosen, due to the lower risk of bleeding. It has been proven that the presence of AF within AMI is associated with a higher degree of reinfarction, more frequent stroke, high incidence of heart failure, and there is a correlation with an increased risk of sudden cardiac death. With the appearance of AF in ACS, its rapid conversion into sinus rhythm is necessary, and in the last resort, good control of heart rate in order to avoid the occurrence of adverse clinical events.

Background: A significant proportion of patients with ST-segment elevation myocardial infarction (STEMI) have multivessel coronary artery disease (MVD), and they are at high risk for recurrent cardiac events. The aim of the present study was to analyze the impact of MVD on long-term cardiovascular mortality in STEMI patients treated with primary percutaneous coronary intervention (pPCI). Method: This study included 3,115 consecutive STEMI patients hospitalized in the Coronary Care Unit of the Clinical Centre of Serbia, between November 2005 and January 2012. Patients were divided in two groups: MVD and no MVD. MVD disease was defined as stenosis greater than 50% by visual assessment in more than one major coronary artery. Primary PCI was limited to the infarct-related artery (IRA). Cardiovascular mortality was defined as any death from cardiovascular reason (myocardial reinfarction, low-output heart failure, and sudden death). Patients presenting with cardiogenic shock were excluded. Patients were followed-up for 6 years after enrollment. Results: Among 3,115 analyzed patients, 1,352 (43.4%) patients had no MVD and 1,763 (56.6%) had MVD; among patients with MVD, 926 (52.6%) had two-vessel disease and 837 (47.4%) had three-vessel disease. Compared with patients with single-vessel disease, patients with MVD were older, had longer pain duration, and presented more often with heart failure; they were more likely to have previous coronary artery disease, diabetes, hypertension, and chronic kidney disease; post-procedural flow TIMI Conclusion: In STEMI patients treated with pPCI, the presence of MVD remained an independent predictor for higher long-term cardiovascular mortality despite early revascularization of the remaining stenosis in non-IRA.

Introduction/Objective. Patients with submassive (intermediate risk) pulmonary embolism (PE) represent a very heterogeneous group, whose therapeutic strategy still questions whether some groups of patients would have net clinical benefit from fibrinolytic therapy (FT). Methods. From the institutional pulmonary embolism registry, 116 patients with submassive PE were identified, and the relation of their outcome to FT was analyzed using the propensity score (PS) adjustment. The primary endpoint was the composite of death, in-hospital cardiopulmonary deterioration, or recurrence of PE. Safety outcomes were updated TIMI non-CABG related major and minor bleeding. Results. According to Cox regression analysis, the incidence of composite endpoint was significantly lower in patients treated with FT compared to anticoagulant therapy (AT) only (PS adjusted HR 0.22; 95% CI 0.05?0.89; p = 0.039). But, when patients were stratified into four PS quartiles, only patients in the highest PS quartile that received fibrinolysis, had significantly lower composite event rate than patients treated with AT (HR 0.20; 95% CI 0.01?0.56; p = 0.016). The overall mortality of the study group was 5.2% and there was no significant difference between the treatment groups. Total bleeding was significantly more frequent in FT patients (HR 3.07; 95% CI 1.02?13.29; p = 0.047), but not the major one. Conclusion. The use of FT was associated with a better outcome compared to AT in patients with submassive PE, but the benefit was mainly driven from those with highest values of PS, i.e. with the highest baseline risk. The rate of major bleeding was not significantly increased by FT.

Anticipation of stress induces physiological, behavioral and cognitive adjustments that are required for an appropriate response to the upcoming situation. Additional research examining the response of cardiopulmonary parameters and stress hormones during anticipation of stress in different chronic stress adaptive models is needed. As an addition to our previous research, a total of 57 subjects (16 elite male wrestlers, 21 water polo player and 20 sedentary subjects matched for age) were analyzed. Cardiopulmonary exercise testing (CPET) on a treadmill was used as the laboratory stress model; peak oxygen consumption (VO2) was obtained during CPET. Plasma levels of adrenocorticotropic hormone (ACTH), cortisol, alpha-melanocyte stimulating hormone (alpha-MSH) and N-terminal-pro-B type natriuretic peptide (NT-pro-BNP) were measured by radioimmunometric, radioimmunoassay and immunoassay sandwich technique, respectively, together with cardiopulmonary measurements, 10 minutes pre-CPET and at the initiation of CPET. The response of diastolic blood pressure and heart rate was different between groups during stress anticipation (p¼0.019, 0.049, respectively), while systolic blood pressure, peak VO2 and carbon-dioxide production responses were similar. ACTH and cortisol increased during the experimental condition, NT-pro-BNP decreased and alpha-MSH remained unchanged. All groups had similar hormonal responses during stress anticipation with the exception of the ACTH/cortisol ratio. In all three groups, DNT-pro-BNP during stress anticipation was the best independent predictor of peak VO2 (B¼36.01, r¼0.37, p¼0.001). In conclusion, the type of chronic stress exposure influences the hemodynamic response during anticipation of physical stress and the path of hormonal stress axis activation. Stress hormones released during stress anticipation may hold predictive value for overall cardiopulmonary performance during the stress condition. LAY SUMMARY The study revealed differences in hormonal and hemodynamic responses during anticipation of stress between athletes and sedentary participants. Stress hormones released during stress anticipation may hold predictive value for overall cardiopulmonary performance during the stress condition. Abbreviations: ACTH: adrenocorticitropic hormone; BSA: body surface area; BW: body weight; C: controls; CPET: cardiopulmonary exercise test; DBP: diastolic arterial blood pressure; FFM: fat-free mass; FM: fat mass; HR: heart rate; MSH: melanocyte-stimulating hormone; NT-pro-BNP: N terminal-pro-B type natriuretic peptide; SBP: systolic arterial blood pressure; VCO2: carbon dioxide production; VE: minute ventilation; VO2: oxygen consumption; W: wrestlers; WP: water polo players

Purpose: Alpha-melanocyte-stimulating hormone (alpha-MSH) has proven cardiovascular effects and plays a significant role as an endogenous countermeasure to ischemia-reperfusion injury. The aim of the current study was to examine the response of alpha-MSH during exercise in patients diagnosed with coronary artery disease (CAD) and evaluate its value in the assessment of severity and prognosis. Methods: Forty subjects with documented CAD (i.e., lesions on coronary angiography ≥ 50%) were included. Cardiopulmonary exercise testing (CPET) on a treadmill (TM) and recumbent ergometer (RE) were performed on two visits, 2–4 days apart, during 2 months of coronary angiography; subsequently, the subjects were followed up for 32 ± 10 months. At rest, at peak CPET, and after 3 min of recovery, plasma levels of alpha-MSH were measured by enzyme-linked immunosorbent assay technique. Results: Mean ejection fraction was 56.7 ± 9.6%. Alpha-MSH similarly increased from rest to peak CPET on both modalities. There were no significant differences in alpha-MSH values during testing in patients with 1,2- and 3-vesel CAD, nor in patients with a SYNTAX score 0.05). Among CPET and hormonal parameters, ∆alpha-MSH recovery/peak during RE CPET was the best predictor of cardiac event occurrence (chi-square 6.67, HR = 0.51, CI = 0.25–1.02, p = 0.010). Conclusion: ∆alpha-MSH recovery/peak during RE CPET has predictive value for CAD prognosis, demonstrating involvement of alpha-MSH in CAD and a link between stress hormones and cardiac events.

Ischemic heart disease leading to heart failure (HF) portends a high overall morbidity and mortality. A higher N-terminal-pro-B-type natriuretic peptide (NT-pro-BNP) at rest reflects HF severity and impaired cardiac output, most often secondary to reduced ejection fraction (EF). As an insufficient increase in cardiac output during exertion is common in all HF phenotypes, we examined the value of NT-pro-BNP during exercise testing as a risk stratification index for ischemic HF secondary to either reduced (HFrEF) or mid-ranged/preserved EF (HFmrEF/HFpEF). 213 patients (123 HFrEF; 90 HFmrEF/HFpEF) underwent cardiopulmonary exercise testing (CPET). NT-pro-BNP was determined at rest and peak exercise. The distribution of HFrEF and HFmrEF/HFpEF etiology in subjects with and without oxygen consumption trajectory flattening during CPET was similar (p > 0.05). Patients with HFrEF had higher plasma levels of NT-pro-BNP at rest and peak exercise than those with HFmrEF/HFpEF (984 vs. 780; 1012 vs. 845 pg/mL, p < 0.01, respectively), whereas ΔNT-pro-BNPpeak/rest was similar (60 vs. 50 pg/mL, p > 0.05). During the tracking period (22.4 ± 20.3 months) 34 patients died, and there were 2 cardiac transplantations and 3 LVAD implantations. In a multivariate regression model only the NT-pro-BNPpeak and ΔNT-pro-BNPpeak/rest were retained in the regression for the prediction of adverse events (Chi-square:8.97, p = 0.003). ROC analysis demonstrated that NT-pro-BNPpeak ≥1506 pg/mL and ΔNT-pro-BNPpeak/rest ≥108 pg/mL were optimal for identifying patients with a risk (Sn = 76.9, 74.4 %; Sp = 84.7, 80.9 %, respectively). NT-pro-BNP changes during effort and absolute peak values reached provide novel insights emerging as new and strong predictors of adverse events in HF of any EF.

Background: The Heart Failure with Preserved Ejection Fraction (HFpEF) is defined as the preserved left ventricular ejection fraction (LVEF) with the signs of heart failure, elevated natriuretic peptides, and either the evidence of the structural heart disease or diastolic dysfunction. The importance of this form of heart failure was increased after studies where the mortality rates and readmission to the hospital were founded similar as in patients with HF and reduced EF (HFrEF). Coronary microvascular ischemia, cardiomyocyte injury and stiffness could be important factors in the pathophysiology of HFpEF. Methods: The goal of this work is to analyse the relationship of HFpEF and coronary microcirculation in previous studies. Results: The useful diagnostic marker of coronary microcirculation in HFpEF may be the parameters measured by transthoracic echocardiography (TTE), the coronary flow reserve (CFR), as well as fractional flow reserve (FFR) and quantitative myocardial contrast echocardiography (MCE). Cardiac magnetic resonance (CMR) imaging represents the diagnostic gold standard in HFpEF. Coronary microvascular dysfunction in the absence of obstructive coronary artery disease (CAD) is poorly understood and may be more prevalent amongst women than men. Troponin level may be important in risk stratification of HEpEF patients. Conclusion: There are no precise answers with respect to the pathophysiological mechanism, nor are there any precise practical clinical assessment of and diagnostic method for coronary microvascular dysfunction and diastolic dysfunction. In accordance with that, there is no well-established treatment for HFpEF.

The athlete's heart is a set of morphological and functional characteristics that develop over time due to sports training. These adaptive changes result in increase in cardiac work efficiency and economy. They are manidested as cardiac muscle hypertrophy and dilation, with accompanying angiogenesis and slower heart rate, that are influenced by variable regulatory systems and genetic predisposition. The problem of sudden cardiac death in athletes, which persists despite numerous activities aimed at prevention, creates the need for a better definition of the athlete's heart, especially in terms of its differentiation from certain pathological conditions. This is of particular importance in the context of cardiac electrical activity. Right heart adaptations, hormonal regulatory mechanisms and the effects of nonphysiological adaptations during training, that may lead to pathologic alterations direction, are all relevant in the investigation of adverse cardiac events in athletes. In order to prevent sudden cardiac death in athletes, it is necessary to examine competitive athletes as well as apparently health individuals who recreationally exercise at a high volume. There are guidelines for mass screening and individual examinations, for all age groups and both genders, as well as for public service staff who require intense physical activity during their occupation. Both American and European recommendations require a detailed anamnesis and physical examination, whereas European, apart from that, require initial electrocardiography. The implementation of additional tests is necessary if the existence of any underlying pathophysiologic process is suspected. Checks should be performed before engaging in sports activities, as well as during training and competition periods. Sportsko srce predstavlja efekat morfoloških i funkcionalnih adaptacija srca koje se razvijaju tokom vremena, pod uticajem sportskog treninga. Promene na srcu kod sportista za posledicu imaju promenu efikasnosti i ekonomičnosti srčanog rada. Manifestuju se hipertrofijom i dilatacijom srca, sa pratećom angiogenezom i usporenim srčanim radom, procesima koji su pod kontrolom različitih regulatornih sistema i genetske predispozicije. Problem iznenadne srčane smrti u sportu, čija se incidenca ne smanjuje uprkos brojnim aktivnostima koje se sprovode u cilju njene prevencije, nameće potrebu boljeg definisanja sportskog srca, naročito u smislu njegovog razlikovanja od pojedinih patoloških stanja. Kod izvesnog broja sportista uočavaju se promene električne aktivnosti, te je i u tom smislu potrebno razlikovati zdravo od bolesnog srca. Poslednjih godina posebno je u fokusu definisanje adaptivnih promena desnog srca. Dodatno, postoje nova saznanja o hormonskoj regulaciji adaptivnih promena srca sportista, a istražuju se i efekti nefizioloških manipulacija u trenažnom procesu koji mogu 'skrenuti' fiziološke procese u patološkom pravcu. U cilju prevencije iznenadne srčane smrti, neophodno je redovno pregledanje kako sportista, tako i fizički aktivnog dela populacije. Aktuelne preporuke daju smernice za masovne skrininge i individualne preglede sportista, za sve starosne grupe oba pola, kao i pripadnike javnih službi koje u opisu posla imaju intenzivne fizičke napore. Dok američke preporuke zahtevaju samo detaljnu anamnezu i fizikalni pregled, evropske preporuke zahtevaju i inicijalnu elektrokardiografiju. I evropske i američke preporuke zahtevaju sprovođenje dodatnih ispitivanja kod sumnje na postojanje bilo kakvog oboljenja. Ove preglede bi trebalo obavljati pre početka trenažnog procesa, kao i tokom perioda treniranja i takmičenja.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden. The ERIC-PPCI trial was funded by a British Heart Foundation clinical study grant (grant number CS/14/3/31002) and a University College London Hospitals/University College London Biomedical Research Centre clinical research grant. The CONDI-2 trial was funded by Danish Innovation Foundation grants (grant numbers 11-108354 and 11-115818), Novo Nordisk Foundation (grant number NNF13OC0007447), and TrygFonden (grant number 109624). DJH was supported by the British Heart Foundation (grant number FS/10/039/28270), the National Institute for Health Research (NIHR) Biomedical Research Centre at University College London Hospitals, the Duke-National University Singapore Medical School, the Singapore Ministry of Health’s National Medical Research Council under its Clinician Scientist-Senior Investigator scheme (grant number NMRC/CSA-SI/0011/2017) and its Collaborative Centre Grant scheme (grant number NMRC/CGAug16C006), and the Singapore Ministry of Education Academic Research Fund Tier 2 (grant number MOE2016-T2-2-021). HEB was supported by the Novo Nordisk Foundation (grant numbers NNF14OC0013337, NNF15OC0016674). RKK is supported by the Oxford NIHR Biomedical Centre. The research was also supported by the NIHR infrastructure at Leeds. The views expressed are those of the author(s) and not necessarily those of the National Health Service, the NIHR, or the Department of Health. This article is based on the work of COST Action EU-CARDIOPROTECTION (CA16225) and supported by COST (European Cooperation in Science and Technology). We thank all study personnel for their invaluable assistance. Sí

ObjectivesThe influence of the bleeding site on long-term survival after the primary percutaneous coronary intervention (PCI) is poorly understood. This study sought to investigate the relationship between in-hospital access site versus non-access site bleeding and very late mortality in unselected patients treated with primary PCI.MethodsData of the 2715 consecutive patients with ST-segment elevation myocardial infarction treated with primary PCI, enrolled in a prospective registry of a high volume tertiary centre, were analysed. Bleeding events were assessed according to the Bleeding Academic Research Consortium (BARC) criteria. The primary outcome was 4-year mortality.ResultsThe BARC type ≥2 bleeding occurred in 171 patients (6.3%). Access site bleeding occurred in 3.8%, and non-access site bleeding in 2.5% of patients. Four-year mortality was significantly higher for patients with bleeding (BARC type ≥2) than in patients without bleeding (BARC type 0+1), (36.3% vs 16.2%, pConclusionsBoth access and non-access site BARC type ≥2 bleeding is independently associated with a high risk of 4-year mortality after primary PCI. Patients with non-access site bleeding were at higher risk of late mortality than patients with access site bleeding.

Background/Aim. The RISK-PCI is a simple score for the prediction of 30-day major adverse cardiovascular events (MACE) and mortality in patients treated with primary PCI (pPCI). The aim of the present study is to evaluate the prognostic performance of the RISK-PCI score in predicting MACE and mortality in the long-term follow-up of STEMI patients treated with pPCI. Method. The present study enrolled 2,096 STEMI patients treated with pPCI included in the RISK-PCI trial. Patients presenting with cardiogenic shock were excluded. The composite end-point MACE comprising cardiovascular mortality, nonfatal reinfarction and stroke. Patients were followed up at 6 years after enrollment. Results. One-year and 6-year MACE occurred in 229 (10.9%) and 285 (13.6%) patients, respectively; and 1-year and 6-year mortality occurred in 128 (6.2%) and 151 (7.2%) patients, respectively. The RISK-PCI score was an independent predictor for 1-year MACE (HR 1.24, 95% CI 1, 18–1.31, p<0.001), 6-year MACE (HR 1.22, 95% CI 1.16–1.28, p<0.001), 1-year mortality (HR 1.21, 95% CI 1.13–1.29, p<0.001), and 6-year mortality (HR 1.23, 95% CI 1.15–1.31, p<0.001). The discrimination of the RISK-PCI score to predict 1-year and 6-year MACE and mortality was good: for 1-year MACE c-statistic 0.78, for 6-year MACE c-statistic 0.75, for 1-year mortality c-statistic 0.87, and for 6-year mortality c-statistic 0.83. The nonsignificant Hosmer–Lemeshow goodness-of-fit estimates for 1-year MACE (p=0.619), 6-year MACE (p=0.319), 1-year mortality (p=0.258), and 6-year mortality (p=0.540) indicated a good calibration of the model. Conclusion. The RISK-PCI score demonstrates good characteristics in the assessment of the risk for the occurrence of MACE and mortality during long-term follow-up after pPCI.

Introduction: The current number of women in the reproductive phase (from 15 to 45 years) in Europe is estimated at about 105 million, with about 5 million children annually born in average. About 1% of pregnancies among women in Europe are complicated by heart disease, the risk of cardiovascular disease in pregnant women being further increased by the fact that ever older women are giving birth. Methods: Preparing this paper is based on a systematic PubMed search of existing professional databases and accessible medical journals and textbooks dealing with this subject matter. Topic: Being certainly drugs with the best anticoagulant effect in situations of high risk for thrombosis, especially in patients with mechanical prosthetic heart valves during pregnancy, vitamin K antagonists (VKA) on the other hand also entail a well-known dose-related risk of embryo toxicity, genotoxicity, and hemorrhage in the fetus and in the mother. The choice of appropriate anticoagulant depends on the stage of pregnancy. In accordance with the North-American guidelines (American College of Chest Physicians - ACCP) for women already on oral vitamin K antagonists actively trying to conceive frequent pregnancy tests, and substitution of VKA with heparin drugs when pregnant are recommended rather than VKA replacement with low molecular weight heparin (Low Molecular Weight Heparin - LMWH) when planning a pregnancy. Heparin derivatives have no embryo toxic and fetotoxic characteristic effects of VKA but they are less effective at preventing valve thrombosis, due to which they have recently been superseded by improved techniques for monitoring effects of heparin, with a mentioned made that low molecular weight heparin used in high therapeutic doses requires obligatory (on a weekly basis) monitoring of anti-factor Xa coagulation activities. Conclusion: Adequate anticoagulant therapy during pregnancy requires an analysis of risk factors for thrombosis, hemorrhage risk, consideration of comorbidities in pregnant women, especially renal function, especially taking into account the gestational age. Though it must be admitted that there is no absolutely safe anticoagulant therapy during pregnancy, a choice of the safest option regarding the stated risks for the mother and the child is of paramount importance.

Alpha-melanocyte-stimulating hormone (alpha-MSH) is a part of the hormonal stress system with proven cardiovascular effects. Heart rate recovery (HRR) following exercise is strongly correlated to overall fitness and future adverse cardiovascular events. The current study examined the predictive value of alpha-MSH for HRR following exercise testing. Cardiopulmonary exercise testing (CPET) on a treadmill was used to measure HR and oxygen consumption (V̇O2) in 16 elite male wrestlers (W), 21 water polo player (WP) and 20 sedentary subjects (C) matched for age. Plasma levels of alpha-MSH were measured by radioimmunoassay technique in four phases of CPET: 1) 10 min pre-CPET at rest; 2) at the initation of CPET; 3) at peak CPET; and 4) at the third minute of recovery. The WP group had significantly higher HRR compared to than W and C groups, who did not have significantly different values. Significant difference in alpha-MSH measurements and patterns during CPET between groups was not observed (p > 0.05). When combining all three groups, we observed a significant correlation between V̇O2 recovery and alpha-MSH recovery/peak (r = -0.3, p = 0.022). HRR and ΔHRR/peak significantly correlated with alpha-MSH at all four measurment points (r = -0.4; p < 0.01 for all). On multiple regression analysis, which included anthropometric and hormonal measures, the best independent predictor of HRR and ΔHRR/peak was alpha-MSH during recovery (B = -1.0, -0.5; SE = 0.3, 0.1; CI = -1.5 to -0.4, -0.7 to -0.2; p = 0.001 respectively). In conclusion, alpha-MSH measured during exercise recovery holds predictive value for HRR and ΔHRR/peak, suggesting a contributing role to integrative regulation of overall cardiopulmonary performance. Condensed abstract Present study examined the predictive value of alpha-melanocyte stimulating hormone (alpha-MSH) for heart rate recovery (HRR) in elite male wrestlers, water polo players and sedentary subjects matched for age. Alpha-MSH measured during exercise recovery holds predictive value for HRR and ΔHRR/peak, suggesting a contributing role to integrative regulation of overall cardiopulmonary performance., Cardiology; Physiology; Alpha-MSH, Heart rate, Recovery of exercise, Athletes.

Background: This study examined the accuracy of cardiopulmonary exercise testing (CPET) on a treadmill (TM) and recumbent ergometry (RE) in the predicting coronary artery disease (CAD) severity and prognosis. Methods: Forty Caucasian subjects, mean age 63.5 +/- 7.6, with significant coronary artery lesions (>= 50%) were included. Within two months of coronary angiography, TM and RE CPET were performed on two visits 2-4 days apart and subsequently followed up to 32 +/- 10 months. Results: Mean left ventricular ejection fraction was 56.7 +/- 9.6%. TM CPET exhibited a higher occurrence of ST segment depression >= 1 mm (71.05% vs 28.95%, p = 0.04). Subjects with 1-2 stenotic coronary arteries (SCA) demonstrated a better CPET response compared to those with 3-SCA. ROC analysis revealed a high predictive value for the ventilation/carbon dioxide production (VE/VCO2) slope obtained on TM (area 0.84, p = 0.003, Sn 88.9%, Sp 72%) in distinguishing between 1 and 2-SCA and 3-SCA. Among all CPET parameters, work efficiency (Delta VO2/Delta WR) during RE predicted cumulative cardiac events (p lt 0.01). Conclusions: CPET parameters hold predictive value for CAD severity and prognosis. CPET on a TM appears to be more reliable in the quantification of CAD compared to RE.

OBJECTIVE The aim of this study was to investigate and compare the prognostic impact of renal dysfunction (RD) at admission in patients with preserved, moderately impaired and severely impaired left ventricular systolic function following ST-elevation myocardial infarction (STEMI). METHODS We included 2436 patients with STEMI treated with primary percutaneous coronary intervention (pPCI). Patients presenting with cardiogenic shock and those on hemodyalisis were excluded. According to the left ventricular ejection fraction (EF), patients were divided in three groups: preserved left ventricular systolic function - EF >50%, moderately impaired - EF=40%-50% and severely impaired left ventricular systolic function-EF

Background/Aim. The coincidence of left ventricular systolic dysfunction (LVSD) and renal dysfunction (RD) is a strong independent predictor of adverse events in the short-term and mid-term follow-ups of patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). The aim of this study was primarily to assess the prognostic impact of the LVSD-RD combination on the 5-year all-cause mortality in patients with STEMI treated with pPCI, as well as to assess the prognostic impact of the LVSD-RD combination on the occurrence of major adverse cardiovascular events (MACEs: cardiovascular death, reinfarction, stroke and target vessel revascularization) in these patients. Methods. We analyzed 951 patients divided into 4 groups according to the presence of LVSD (ejection fraction < 40%) and/or baseline RD (creatinine clearance < 60 mL/min): group I (no LVSD, no RD); group II (LVSD, no RD); group III (RD, no LVSD); group IV (LVSD+RD). Results. The 5-year mortality rates were 2.3%, 17.6%, 11.7% and 38.3%, while the 5-year MACE rates were 8.8%, 28.4%, 18.3% and 44.4% in the groups I, II, III and IV, respectively (p < 0.001). The highest percentage of lethal outcomes and MACE was registered in the first year of follow-up in all the groups. The 1-year landmark analysis confirmed that the patients with LVSD-RD combination had the highest percentage of lethal outcomes in the period of 1 to 5 years (p = 0.028). There was a strong trend toward the significance in the occurrence of MACE among the analyzed groups in the period of 1 to 5 years (p = 0.085). In the Cox regression model the LVSD-RD combination was a strong independent predictor of 5-year mortality and the occurrence of MACE: mortality hazard ratio (HR) 4.5 (95%CI 1.9-10.8); MACE HR 2.5 (95%CI 1.4-4.5). Conclusion. The strong negative independent prognostic impact of the LVSD-RD combination persisted in the long-term follow-up of the patients with STEMI treated with pPCI.

Ventricular arrhythmias are the most common cause of mortality in patients with acute myocardial infarction. Arrhythmias in acute coronary syndrome occur because of unbalanced function of the autonomic nervous system, because of electrolyte status disturbances (hypokalemia, hypomagnesaemia, intracellular hypercalcemia) and because of slow conduction in ischemical myocardium zones. Arrhythmias contribute to acidosis and release of free oxygen radicals occurring during reperfusion of ischemic myocardium. Ventricular arrhythmias in acute myocardial infarction indicate the presence of extensive myocardial damage at a reduced left ventricular ejection fraction, and not infrequently in the formation of an aneurysm of the left ventricle. In patients with acute coronary syndrome, the most common ventricular arrhythmias are premature ventricular beats, ventricular tachycardia, ventricular flutter and fibrillation and accelerated idioventricular rhythm. Ventricular fibrillation, still the leading cause of sudden death in patients with acute coronary syndrome within the first four hours of myocardial infarction, occurs in 80 % of all ventricular fibrillations. The use of beta-blockers in the first 24 hours of acute myocardial infarction in patients with early ventricular fibrillation and tachycardia does not affect the degree of worsening heart failure and is directly associated with reduced rates of early mortality in these patients. Quick and adequate treatment of ventricular arrhythmias is a major advancement in the treatment of acute myocardial infarction.

Objectives: Despite considerable knowledge regarding the importance of stress in coronary artery disease (CAD) pathogenesis, its underestimation persists in routine clinical practice, in part attributable to lack of a standardized, objective assessment. The current study examined the ability of stress hormones to predict CAD severity and prognosis at basal conditions as well as during and following an exertional stimulus.Materials and methods: Forty Caucasian subjects with significant coronary artery lesions (50%) were included. Within 2 months of coronary angiography, cardiopulmonary exercise testing (CPET) on a recumbent ergometer was performed in conjunction with stress echocardiography (SE). At rest, peak and after 3min of recovery following CPET, plasma levels of cortisol, adrenocorticotropic hormone (ACTH) and NT-pro-brain natriuretic peptide (NT-pro-BNP) were measured by immunoassay sandwich technique, radioimmunoassay, and radioimmunometric technique, respectively. Subjects were subsequently followed a mean of 3210months.Results and discussion: Mean ejection fraction was 56.7 +/- 9.6%. Subjects with 1-2 stenotic coronary arteries (SCA) demonstrated a significantly lower plasma cortisol levels during CPET compared to those with 3-SCA (p lt .05), whereas ACTH and NT-pro-BNP were not significantly different (p>.05). Among CPET, SE, and hormonal parameters, cortisol at rest and during CPET recovery demonstrated the best predictive value in distinguishing between 1-, 2-, and 3-SCA [area under ROC curve 0.75 and 0.77 (SE=0.11, 0.10; p=.043, .04) for rest and recovery, respectively]. Cortisol peak/rest predicted cumulative cardiac events (area under ROC curve 0.75, SE=0.10, p=.049).Conclusions: Cortisol at rest and following an exercise test holds predictive value for CAD severity and prognosis, further demonstrating a link between stress and unwanted cardiac events.

Background Patients with high post-loading platelet aggregation (PPA) are at increased risk of stent thrombosis and death after primary percutaneous coronary intervention (pPCI). The objective of the present trial was to examine whether high PPA is associated with adverse clinical outcomes in pPCI patients whose therapy was modified in accordance with PPA. Methods We analyzed 961 consecutive pPCI patients who underwent pPCI between February 2008 and June 2011. High PPA was defined as PPA >50%, 24h after the loading dose. Patients with high PPA were treated with aspirin 300mg, clopidogrel 150mg or ticlopidine 500mg for 30days. The co-primary efficacy and safety end points at 30days were major adverse cardiovascular events (MACE) and major bleeding. Results We detected high PPA to clopidogrel and aspirin in 44.4% and 16.5% of patients, respectively. The rates of 30-day MACE (adjusted OR 1.76, 95% CI 1.05–2.97), definite subacute stent thrombosis (DSST, adjusted OR 2.15, 95% CI 1.09–4.22) and nonfatal infarction (adjusted OR 3.99, 95% CI 1.57–10.13) were higher in patients with high PPA to clopidogrel compared with responders. High PPA to aspirin was not associated with an adverse 30-day clinical outcome. Compared with high PPA patients who were not tailored, a significantly better outcome with respect to the primary end point was observed in the tailored group (OR 0.42, 95% CI 0.19–0.93). Conclusion High PPA to clopidogrel was an independent predictor of 30-day adverse events after pPCI. Among high PPA patients, tailoring was associated with an improved primary outcome.

The objective of the present substudy was to examine whether aspirin poor/high responsiveness (APR/AHR) is associated with increased rates of major adverse cardiovascular events (MACE) and serious bleeding after primary percutaneous coronary intervention (PPCI).We analyzed 961 consecutive ST-elevation acute myocardial infarction patients who underwent PPCI between February 2008 and June 2011. Multiplate analyser (Dynabite, Munich, Germany) was used for the assessment of platelet reactivity. APR/AHR were defined as the upper/lower quintiles of ASPI values, determined 24 h after aspirin loading. APR patients were tailored using 300 mg maintenance dose for 30 days. The co-primary end points at 30 days were: MACE (death, non-fatal infarction, ischemia-driven target vessel revascularization and ischemic stroke) and serious bleeding according to the BARC classification.One hundred and 90 patients were classified as APR, and 193 patients as AHR. At admission, compared with aspirin sensitive patients (ASP), patients with APR had more frequently diabetes, anterior infarction and heart failure, while AHR patients had reduced values of creatine kinase, leukocytes, heart rate and systolic blood pressure. Compared with ASP, the rates of 30-day primary end points did not differ neither in APR group including tailored patients (MACE, adjusted OR 1.02, 95%CI 0.47-2.17; serious bleeding, adjusted OR 1.92, 95%CI 0.79-4.63), nor in patients with AHR (MACE, adjusted OR 1.58, 95%CI 0.71-5.51; serious bleeding, adjusted OR 0.69, 95%CI 0.22-2.12).The majority of APR patients were suitable for tailoring. Neither APR including tailored patients nor AHR were associated with adverse 30-day efficacy or safety clinical outcomes.

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 ( lt = 65 years). 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 65 years 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.

Stent thrombosis (ST) is an important cause of death after primary percutaneous coronary intervention (pPCI). This substudy aimed at evaluating the usefulness of the RISK-PCI score, originally developed for the prediction of 30-day major adverse cardiovascular events, to predict the occurrence of ST after pPCI. We analyzed 1972 consecutive patients who underwent pPCI with stent implantation between February 2007 and December 2009. Early ST (EST), late ST (LST), and cumulative 1-year ST (CST) were the predefined end points. Definite, probable, and possible ST were included. Models discrimination and calibration to predict ST was tested using receiver-operating characteristics curves and the goodness-of-fit (GoF) test. Sensitivity analyses and 1000-resample bootstrapping were used to evaluate the model's performance. The rates of EST, LST, and CST were 4.6, 1.4, and 6.0 %, respectively. Compared with controls, the cumulative ST group was associated with much higher rates of adverse clinical outcomes at 30-day follow-up (adjusted odds ratio (OR) for death 6.45, adjusted OR for major bleeding 4.41) and at 12-month follow-up (adjusted OR for death 7.35, adjusted OR for major bleeding 4.56). Internal validation confirmed a reasonably good discrimination and calibration of the RISK-PCI score for the prediction of EST (area under the curve (AUC) 0.71, GoF 0.42), LST (AUC 0.69, GoF 0.36), and CST (AUC 0.70, GoF 0.22) after pPCI. ST after pPCI is associated with adverse 30-day and 1-year clinical outcomes. We conclude that the risk of ST could be accurately assessed using the RISK-PCI score, which might help in deciding upon measures aimed at preventing adverse prognosis.

Objectives Limited data exist about the prognostic significance of new-onset atrial fibrillation (AF) after contemporary primary percutaneous coronary intervention (pPCI). The objective of this study was to identify the incidence and predictors of new-onset AF and associated adverse 30-day outcomes in AF patients who underwent pPCI. Methods We analyzed 2096 patients undergoing pPCI after pretreatment with 600 mg clopidogrel. Composite 30-day major adverse cardiovascular events were the primary end point. A logistic regression model was developed to identify risk factors for the occurrence of AF and prediction of its impact on 30-day outcomes. Results AF occurred in 6.2% of patients. Older age, Killip >1 heart failure at admission, systolic blood pressure of greater than 100 mmHg at admission, creatinine clearance greater than 60 ml/min, preprocedural infarction-related artery occlusion and postprocedural thrombolysis in myocardial infarction flow less than 3 were identified as independent predictors of the occurrence of AF. Rates of 30-day major adverse cardiovascular events [adjusted odds ratio (OR) 2.39, 95% confidence interval (CI): 1.47–3.87] and 30-day death (adjusted OR 2.67, 95% CI: 1.46–4.89) were higher in AF patients compared with patients without AF. A trend toward higher rate of ischemia-driven target vessel revascularization was observed in the AF group (adjusted OR 2.61, 95% CI: 0.82–8.39, P=0.10). Conclusion New-onset AF after pPCI is associated with adverse 30-day outcomes. Accurate prediction of AF after pPCI might help deciding a more aggressive treatment approach aimed at preventing the adverse prognosis of these patients.

Background: The prognosis of patients with acute coronary syndrome (ACS) can be determined on the basis of the TIMI risk score, which is one of the scores easily applicable for quantitative risk assessment of patients. The primary objective of this paper is to assess whether the TIMI risk score significant predictor of poor outcome in our patients with STEMI, within the first month and within the first year of monitoring. A secondary aim of the study is the correlation TIMI score and ejection fraction (EF), wall motion score index (WMSI) and infarct size in the same patients during the early post-infarction period. Method: The study included 115 patients with STEMI, age 56.6 ± 10.2 years, 79 men and 36 women, who were hospitalized in the coronary care unit of CCS. TIMI risk score was calculated for all patients and based on: patient's age, previous risk factors (diabetes, hypertension and angina pectoris), and systolic blood pressure on admission rate, Killip class, weight, presence of ST elevation on the front wall or left bundle branch block and the time of onset of symptoms. Echocardiography was done within 7 days of myocardial infarction and parameters EF and WMSI were determined. Infarct size was estimated based on the maximum levels of creatine kinase (CK). Patients were followed at regular check-ups for a period of one year. Results: The cut-off value of the TIMI risk score in patients with STEMI was 4.5 with a very high specificity 85.7 % and sensitivity 81.1 %. TIMI risk score is a significant predictor of poor outcome in a one-month (RR 1.57, 95 % CI 1.28 to 1.93, p