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Background: There is a lack of knowledge about the real incidence of acute coronary syndrome (ACS) in patients with COVID-19, their clinical characteristics, and their prognoses., Objective: We investigated the incidence, clinical characteristics, risk factors, and outcomes of ACS in patients with COVID-19 in the emergency department., Methods: We retrospectively reviewed all COVID-19 patients diagnosed with ACS in 62 Spanish emergency departments between March and April 2020 (the first wave of COVID-19). We formed 2 control groups: COVID-19 patients without ACS (control A) and non-COVID-19 patients with ACS (control B). Unadjusted comparisons between cases and control subjects were performed regarding 58 characteristics and outcomes., Results: We identified 110 patients with ACS in 74,814 patients with COVID-19 attending the ED (1.48% [95% confidence interval {CI} 1.21-1.78%]). This incidence was lower than that observed in non-COVID-19 patients (3.64% [95% CI 3.54-3.74%]; odds ratio [OR] 0.40 [95% CI 0.33-0.49]). The clinical characteristics of patients with COVID-19 associated with a higher risk of presenting ACS were: previous coronary artery disease, age ≥60 years, hypertension, chest pain, raised troponin, and hypoxemia. The need for hospitalization and admission to intensive care and in-hospital mortality were higher in cases than in control group A (adjusted OR [aOR] 6.36 [95% CI 1.84-22.1], aOR 4.63 [95% CI 1.88-11.4], and aOR 2.46 [95% CI 1.15-5.25]). When comparing cases with control group B, the aOR of admission to intensive care was 0.41 (95% CI 0.21-0.80), while the aOR for in-hospital mortality was 5.94 (95% CI 2.84-12.4)., Conclusions: The incidence of ACS in patients with COVID-19 attending the emergency department was low, around 1.48%, but could be increased in some circumstances. Patients with COVID-19 with ACS had a worse prognosis than control subjects with higher in-hospital mortality., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The accuracy of current prediction tools for ischaemic and bleeding events after an acute coronary syndrome (ACS) remains insufficient for individualised patient management strategies. We developed a machine learning-based risk stratification model to predict all-cause death, recurrent acute myocardial infarction, and major bleeding after ACS., Methods: Different machine learning models for the prediction of 1-year post-discharge all-cause death, myocardial infarction, and major bleeding (defined as Bleeding Academic Research Consortium type 3 or 5) were trained on a cohort of 19 826 adult patients with ACS (split into a training cohort [80%] and internal validation cohort [20%]) from the BleeMACS and RENAMI registries, which included patients across several continents. 25 clinical features routinely assessed at discharge were used to inform the models. The best-performing model for each study outcome (the PRAISE score) was tested in an external validation cohort of 3444 patients with ACS pooled from a randomised controlled trial and three prospective registries. Model performance was assessed according to a range of learning metrics including area under the receiver operating characteristic curve (AUC)., Findings: The PRAISE score showed an AUC of 0·82 (95% CI 0·78-0·85) in the internal validation cohort and 0·92 (0·90-0·93) in the external validation cohort for 1-year all-cause death; an AUC of 0·74 (0·70-0·78) in the internal validation cohort and 0·81 (0·76-0·85) in the external validation cohort for 1-year myocardial infarction; and an AUC of 0·70 (0·66-0·75) in the internal validation cohort and 0·86 (0·82-0·89) in the external validation cohort for 1-year major bleeding., Interpretation: A machine learning-based approach for the identification of predictors of events after an ACS is feasible and effective. The PRAISE score showed accurate discriminative capabilities for the prediction of all-cause death, myocardial infarction, and major bleeding, and might be useful to guide clinical decision making., Funding: None., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Epidemiological studies found that increases in the concentrations of airborne particulate matter (PM) smaller than 10 microns diameter (PM 10 ) in the ambient air due to desert dust outbreaks contribute to global burden of diseases, primarily as a result of increased risk of cardiovascular morbidity and mortality. No studies have investigated the possible association between desert dust inhalation and airway inflammation in patients with ischemic heart disease (IHD). Induced sputum was collected in 38 patients and analyzed to determine markers of airway inflammation (Transforming Growth Factor-β1 [TGF-β1] and hydroxyproline) concentrations. For the purpose of the investigation, PM 10 and reactive gases concentrations measured in the European Air Quality Network implemented in the Canary Islands were also used. We identified Saharan desert dust using meteorology and dust models. Patients affected by smoking, chronic obstructive pulmonary disease (COPD), asthma, pulmonary abnormalities, acute bronchial or pulmonary disease were excluded. The median of age of patients was 64.71 years (56.35-71.54) and 14 (38.84%) of them were women. TGF-β1 and hydroxyproline in sputum were highly associated to PM 10 inhalation from the Saharan desert. According to a regression model, an increase of 1 µg/m 3 of PM 10 concentrations due to desert dust, results in an increase of 3.84 pg/gwt of TGF-β1 (R2 adjusted = 89.69%) and of 0.80 μg/gwt of hydroxyproline (R 2 adjusted = 85.28%) in the sputum of patients. The results of this study indicate that the exposure to high PM 10 concentrations due to Saharan dust events are associated with intense inflammatory reaction in the airway mucosae of IHD-patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The PRECISE-DAPT and PARIS risk scores (RSs) were recently developed to help clinicians at individualizing the optimal dual antiplatelet therapy duration (DAPT) after percutaneous coronary intervention (PCI). Nevertheless, external validation of these RSs it has not yet been performed in ACS (acute coronary syndrome) patients treated with prasugrel or ticagrelor in a real- world scenario., Methods: 4424 ACS patients who underwent PCI and survived to hospital discharge, from January 2012 to December 2016 at 12 European centers, were included. PRECISE-DAPT and PARIS bleeding RS, as well as PARIS ischemic RS, were computed, and their performance at predicting major bleeding (MB; BARC type 3 or 5) and ischemic events (MI and stent thrombosis) during follow up was compared., Results: After a median follow-up of 14 (interquartile range 12-20.9) months, 83 (1.88%) patients developed MB and 133 (3.0%) suffered an ischemic episode. PRECISE-DAPT performed better than PARIS bleeding RS (c-statistic = 0.653 vs. 0.593; p = .01 for comparison) in predicting MB. The RSs performance for MB prediction remained consistent in STEMI patients (c-statistic = 0.632 vs 0.575) or in those treated with prasugrel (c-statistic = 0.623 vs 0.586). PARIS ischemic RS exhibited superior discrimination in predicting ischemic complications compared to PRECISE-DAPT (c-statistic = 0.604 vs 0.568 p = .05 for comparison)., Conclusion: Our data provide support to the use of PRECISE-DAPT in MB risk stratification for patients receiving DAPT in form of aspirin and prasugrel or ticagrelor whereas the PARIS ischemic RS has potential to complement the risk prediction with respect to ischemic events., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background and Aims: Adherence to the Mediterranean diet (MedDiet) has been associated with prolonged survival in older individuals. However, it is unknown whether adherence to MedDiet is associated with the prognosis in older patients scheduled to undergo cardiac resynchronization therapy (CRT). The aim of this study was to evaluate the association between adherence to the MedDiet and clinical outcomes at 12 months follow-up after CRT implantation in older patients., Methods and Results: Patients adherents to the MedDiet, defined as ≥ 9 of 14 points using the PREDIMED (Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Study) questionnaire, was assessed before device implantation in patient's ≥ 70 years candidates for CRT. The primary outcome was a combined endpoint at 12 months follow-up after CRT implantation, defined as cardiovascular death, cardiac transplantation or decompensated heart failure. The cohort study consisted of 284 patients with a mean age of 73 ± 3 years. One hundred and fifty-nine (55.9%) patients were classified as adherent to the MedDiet. Seventy (24.6%) patients showed the combined endpoint at one year follow-up. Subjects who did not developed the combined endpoint had higher proportion of adherent patients to the MedDiet compared to patients who developed the combined endpoint (85% vs 67.1%, p = 0.002). After adjustment by possible confounders, the adherence to the MedDiet was a protective and significant predictor of the combined endpoint (HR = 0.42, 95% CI 0.22-0.81; p = 0.01)., Conclusion: Adherence to the MedDiet is inversely associated with outcome in older patients following CRT., (Copyright © 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Objectives: To evaluate "real life" incidence and independent predictors of major bleeding defined in ACS patients treated with PCI and current standard antithrombotic therapy with prasugrel or ticagrelor., Methods and Results: The RENAMI project is a multicenter retrospective observational registry enrolling 4424 patients with ACS treated with PCI and prasugrel or ticagrelor plus aspirin. Primary endpoint was MACE (major adverse cardiovascular events). Secondary endpoints included each component of MACE, cardiovascular death (CV death), recurrence of ACS (reACS) and stroke. Eighty three (1.8%) patients developed out of hospital major bleedings after 14.1 ± 6.2 months. These patients had higher rates of MACE (14.5% vs 4.4%; p = 0.001) and of all-cause death (11% vs 2.1%; p < 0.001). Independent predictors of major bleeding were age >75 years (OR 2.00; 95% CI 1.18-3.41; p = 0.010) and female sex (OR 1.66; 95% CI 1.02-2.70; p = 0.041). BARC 3-5 bleeding was independently associated with all-cause mortality (OR 3.46; 95% CI 1.64-7.31; p 0.001)., Conclusion: In ACS patients treated with PCI and ticagrelor or prasugrel, BARC 3-5 bleedings despite being uncommon negatively impacted on prognosis. Old and female patients are at increased risk, offering clinical indications for tailoring dual antiplatelet therapy., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Cardiac resynchronization therapy (CRT) is an effective treatment for left ventricular reverse remodeling (LVRR) in patients with congestive heart failure (HF) and ventricular dyssynchrony. Melatonin is a secretory product of the pineal gland with highly beneficial effects from any tissues including the heart. Herein, we investigated whether the response to CRT is associated with levels of melatonin before CRT implantation in patients with HF and ventricular dyssynchrony., Methods: Diurnal melatonin levels were performed in serum from 93 patients with HF and ventricular dyssynchrony before CRT implantation. Moreover, we calculated the MADIT-CRT score. Evaluation of patients at 1-year follow-up included an echocardiographic study since the patients were categorized as responders if they presented both a reduction in left ventricular end-systolic volume index >10% and an increase in left ventricular ejection fraction >10%., Results: At 1-year, 34 patients (36.5%) were considered responders to CRT according to the predefined criteria. The diurnal melatonin levels were significantly lower in the non-responder group (9.9±2.84 vs 14.7±2.32pg/mL). After adjustment by multivariate analysis, diurnal serum melatonin levels (P<0.001) and diabetes mellitus (P=0.03) were predictors of LVRR. On Cox regression analysis, diurnal serum melatonin levels (P<0.001) and left atrial volume<40mL/m(2) (P=0.04) remained independent predictors of the adverse clinical events. The area under of curve for the prediction LVRR of melatonin (0.91, 95%CI 0.85-0.97; P<0.001) was significantly higher compared to MADIT-CRT score (0.69, 95%CI 0.58-0.80; P=0.002)., Conclusion: Diurnal levels of melatonin before CRT implantation are associated with LVRR at 12month follow-up., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: The presence of effort induced angina, positive exercise stress test responses and angiographically normal coronary arteries defines cardiac syndrome X (CSX). Its pathogenesis, although mostly attributed to endothelial dysfunction and coronary microcirculation abnormalities, is incompletely understood. The soluble CD40 ligand (sCD40L) has multiple autocrine, paracrine and endocrine actions that may lead to endothelial dysfunction and atherothrombosis. We sought to investigate the relationship among sCD40L levels and ischemic burden in patients with CSX and whether sCD40L levels are increased in patients with CSX compared to control subjects., Methods: We assessed 30 prospectively enrolled patients with CSX and 28 apparently healthy subjects matched for coronary risk factors. All CSX patients and control subjects underwent myocardial perfusion scintigraphy. The summed difference score is taken to be an index of ischemic burden. This was classified as mildly, moderately and severely abnormal. White blood cells, sCD40L and C-reactive protein (CRP) concentrations were measured at peak exercise., Results: At peak exercise, sCD40L levels were significantly greater in CSX patients than in the control group (P=0.008). Similarly, white blood cell count and CRP levels were higher in patients with CSX than in normal controls (P=0.02). After multivariable adjustment, sCD40L (P=0.03) was the only independent predictor of severe ischemic burden in CSX patients., Conclusions: The present study showed for the first time that sCD40L is associated with ischemic burden in patients with CSX. The potential role of this inflammatory molecule in the pathogenesis of CSX deserves investigation in future studies., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: Left ventricle remodeling (LVR) is a relatively common and unfavourable event occurring after acute myocardial infarction. A link exists between inflammation and LVR. Neopterin, a marker of inflammation and macrophage activation, is a predictor of left ventricular dysfunction in patients with coronary artery disease. We therefore sought to assess whether both neopterin and brain natriuretic peptide (BNP), a marker of LV dysfunction and patient outcome, correlate with LVR in patients with ST-segment elevation myocardial infarction (STEMI)., Methods: We prospectively assessed 108 STEMI patients (age 64 + or - 11 years; 85% male) undergoing primary percutaneous coronary intervention (PCI) who were assessed echocardiographycally assessment was performed at 96 + or - 10h after the onset of symptoms and 12 month after STEMI. LVR was defined as >20% increase in LV end-diastolic volume at 12 months of follow-up compared to baseline. Neopterin and BNP serum concentrations were measured immediately before primary PCI., Results: At 1 year, 21 patients (19%) showed LVR and 87 (81%) had no LVR. Patients with LVR had higher levels of neopterin at study entry (7.45 + or - 1.04 vs 5.19 + or - 1.39 nmol/L; p<0.001). After adjustment for relevant confounders, neopterin levels were found to be an independent predictor of LVR (OR ranging from [3.10, CI 95% 1.928-4.990, p<0.001] to [3.32, CI 95% 1.999-5.532, p<0.001]). ROC analysis showed an area under the curve of 0.901 for neopterin (CI 95% 0.84-0.96, p<0.0001) compared to 0.579 for BNP (CI 95% 0.409-0.748) regarding LVR., Conclusions: In STEMI patients undergoing primary PCI, high neopterin levels - but not BNP - predict LVR at 1-year follow-up., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Introduction: CD40 ligand has been suggested to play a pathogenic role in atherogenesis and coronary artery disease progression. Clinical studies suggest that intravenous (IV) abciximab administration attenuates the acute inflammatory response associated with percutaneous coronary intervention (PCI). The anti-inflammatory effects of intracoronary (IC) versus IV administration of abciximab have not been systematically investigated. We assessed changes in soluble CD40 ligand (sCD40L) concentrations in response to IC versus IV abciximab in patients with ST-elevation myocardial infarction (STEMI) undergoing thrombus-aspirating device during primary PCI., Methods: Patients were randomized to receive IC (n=25) or IV (n=25) bolus abciximab followed in every case by a 12-h IV abciximab infusion. sCD40L was measured immediately before the administration of abciximab (baseline) and 60min post bolus administration., Results: Clinical baseline and angiographic characteristics were similar in both patient groups. Similarly, there were no significant differences in baseline serum sCD40L levels in the IC group compared to IV group (116.6+/-42.13pg/mL vs 124.9+/-43.04pg/mL, P=0.49). At 60min post PCI, however, sCD40L levels decreased by 23% (P<0.001) in the IC group and by 11% (P<0.001) in the IV group. sCD40L levels 60min post PCI were significantly reduced, particularly in the IC group compared to the IV group (73.04+/-12.21pg/mL vs 99.92+/-25.89pg/mL, P<0.001)., Conclusion: In STEMI patients undergoing primary PCI, IC bolus administration of abciximab was associated with a larger reduction in sCD40L levels compared to standard IV bolus. Whether this more powerful anti-inflammatory effect of IC abciximab translates into improved clinical outcomes deserves investigation.

Objective: To investigate the possible association between admission ischemia modified albumin (IMA) levels and ST-segment resolution (STR) in ST-segment elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PCI)., Materials and Methods: We studied 117 patients with a first STEMI within 6h of the onset of pain. Admission serum IMA concentration was measured using a validated assay. The worst single electrocardiogram lead before and 90min after primary PCI was analyzed, and patients were divided into two groups according to the degree of STR: complete (> or =70%) or incomplete (<70%)., Results: Of the 117 patients, 70 (60%) had complete STR, and 47 (40%) incomplete STR. Serum IMA concentrations were significantly higher in patients that had incomplete STR (0.383+/-0.060A.U. vs. 0.297+/-0.056A.U., p<0.001). IMA levels >0.325A.U. demonstrated a sensitivity of 91.4% and a specificity of 45.7% for the diagnosis of incomplete STR; the area under the receiver operator characteristic curve was 0.849 (95% CI 0.77-0.92, p=0.0001). Moreover, IMA values were an independent predictor of incomplete STR even after adjustment for potential confounders (OR 2.34; 95% CI 1.20-4.64, p=0.01)., Conclusions: IMA may be a useful biomarker for the identification of incomplete STR in STEMI patients presenting to hospital within 6h of the onset of pain.

Background: Levosimendan is a new calcium sensitizer with positive inotropic properties. In previous studies, it has recently been shown that levosimendan improves the Doppler echocardiographic parameters of the left ventricular (LV) diastolic function in patients with anterior acute myocardial infarction. We sought to evaluate the effects of levosimendan compared to dobutamine on LV diastolic function, using conventional transmitral Doppler, in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) who subsequently developed cardiogenic shock., Methods: We randomized 22 consecutive STEMI patients with cardiogenic shock after primary PCI to levosimendan or dobutamine infusion and we also analyzed the diastolic function using conventional transmitral Doppler flow., Results: Twenty-four hours after the initiation of the drug infusion, patients treated with levosimendan (n=11) showed a significant reduction of the isovolumetric relaxation time (116+/-15.2-70.4+/-10.8 ms; P<.001), and a significant increase of the E/A ratio (0.6+/-0.3-1.4+/-0.5; P<.001). In the dobutamine group (n=11), no statistically significant differences were noted in the echocardiographic Doppler indexes., Conclusion: Levosimendan seems to be effective in improving the Doppler echocardiographic parameters of LV diastolic function in patients with STEMI revascularised by primary PCI who developed cardiogenic shock.

Introduction: It has been proposed that reactive oxygen species (ROS) generated during myocardial ischemia-reperfusion modify the N-terminus of serum albumin resulting in ischemia-modified albumin (IMA) formation. Likewise, several recent publications provide evidence that melatonin, a circadian endogenously produced indolamine, is a direct scavenger of ROS. We sought to investigate the relationship between IMA and melatonin in ST- elevation myocardial infarction (STEMI)., Methods: We compared IMA and melatonin levels in 27 patients with STEMI undergoing primary angioplasty and 20 age- and gender-matched healthy normal subjects. Blood samples were drawn at 02:00h (night period) and 09:00h (day period) while patients were resting, to assess IMA and melatonin., Results: In both groups, melatonin concentrations maintained a diurnal variation, but the difference between nocturnal and diurnal levels was less in the STEMI-patients than in the control group (p<0.001). In contrast to findings about melatonin, IMA levels showed no diurnal variations in control subjects. However, the STEMI group showed a diurnal fluctuation with significantly higher levels at 02:00h (p<0.01). The association between IMA and melatonin remained statistically significant after adjustment for cardiovascular risk factors. An inverse correlation between IMA and melatonin at 02:00h and at 09:00h was observed, with respective r-values of -0.42 (p<0.03) and -0.57 (p<0.002)., Conclusions: Circulating IMA is negatively correlated to melatonin in STEMI-patients. Our results suggest that melatonin might exert a beneficial effect as a radical scavenger in a human model of myocardial ischemia-reperfusion.