Outcomes and predictive value of the 2MACE score in patients with atrial fibrillation treated with rivaroxaban in a prospective, multicenter observational study: The EMIR study

atrial fibrillation (AF) treated with rivaroxaban and to improve the accuracy of 2MACE. Methods: This was a post-authorization and observational study of AF adults treated with rivaroxaban for ≥ 6 months. The primary endpoint was any of the major adverse cardiac events (MACE), namely, cardiovas cular death, non-fatal myocardial infarction, and myocardial revascularization. The area under the curve (AUC) was calculated to evaluate the performance of 2MACE, and a new score, 2MACER to predict MACE. Results: A total of 1433 patients were included (74.2 ± 9.7 years, CHA2DS2-VASc 3.5 ± 1.5, 26.9% 2MACE ≥ 3). The annual event rates (follow-up 2.5 years) were 1.07% for MACE, 0.66% for throm boembolic events and 1.04% for major bleeding. Patients with 2MACE ≥ 3 (vs. < 3) had higher risk of stroke/systemic embolism/transient ischemic attack (odds ratio [OR] 5.270; 95% confidence interval [CI] 2.216–12.532), major bleeding (OR 4.624; 95% CI 2.163–9.882), MACE (OR 3.202; 95% CI 1.548–6.626) and cardiovascular death (OR 3.395; 95% CI 1.396–8.259). 2MACE was recalcu lated giving 1 more point to patients with baseline a glomerular filtration rate < 50 mL/min/1.73 m2 (2MACER); (2MACER vs. 2MACE: IDI 0.1%, p = 0.126; NRI 23.9%, p = 0.125; AUC: 0.651 [95% CI 0.547–0.755] vs. 0.638 [95% CI 0.534–0.742], respectively; p = 0.361). Conclusions: In clinical practice, AF patients anticoagulated with rivaroxaban exhibit a low risk of events. 2MACE score acts as a modest predictor of a higher risk of adverse outcomes in this population. 2MACER did not significantly increase the ability of 2MACE to predict MACE. (Cardiol J 2022; 29, 4: 601–609

Impact of heart failure on the clinical profile and outcomes in patients with atrial fibrillation treated with rivaroxaban. Data from the EMIR study

Background: The aim of this study was to analyze the impact of the presence of heart failure (HF) on the clinical profile and outcomes in patients with atrial fibrillation (AF) anticoagulated with rivaroxaban. Methods: Observational and non-interventional study that included AF adults recruited from 79 Spanish centers, anticoagulated with rivaroxaban ≥ 6 months before inclusion. Data were analyzed according to baseline HF status. Results: Out of 1,433 patients, 326 (22.7%) had HF at baseline. Compared to patients without HF, HF patients were older (75.3 ± 9.9 vs. 73.8 ± 9.6 years; p = 0.01), had more diabetes (36.5% vs. 24.3%; p < 0.01), coronary artery disease (28.2% vs. 12.9%; p < 0.01), renal insufficiency (31.7% vs. 22.6%; p = 0.01), higher CHA2DS2-VASc (4.5 ± 1.6 vs. 3.2 ± 1.4; p < 0.01) and HAS-BLED (1.8 ± 1.1 vs. 1.5 ± 1.0; p < 0.01). After a median follow-up of 2.5 years, among HF patients, annual rates of stroke/ /systemic embolism/transient ischemic attack, major adverse cardiovascular events (MACE) (non-fatal myocardial infarction, revascularization and cardiovascular death), cardiovascular death, and major bleeding were 1.2%, 3.0%, 2.0%, and 1.4%, respectively. Compared to those patients without HF, HF patients had greater annual rates of MACE (3.0% vs. 0.5%; p < 0.01) and cardiovascular death (2.0% vs. 0.2%; p < 0.01), without significant differences regarding other outcomes, including thromboembolic or bleeding events. Previous HF was an independent predictor of MACE (odds ratio 3.4; 95% confidence interval 1.6–7.3; p = 0.002) but not for thromboembolic events or major bleeding. Conclusions: Among AF patients anticoagulated with rivaroxaban, HF patients had a worse clinical profile and a higher MACE risk and cardiovascular mortality. HF was independently associated with the development of MACE, but not with thromboembolic events or major bleeding. (Cardiol J 2022; 29, 6: 936–947)

Toxoplasma gondii en mujeres embarazadas en la provincia de El Oro, 2014 / Toxoplasma gondii in pregnant women in the province of El Oro, 2014

El objetivo de la presente investigación fue determinar los anticuerpos IgG- IgM de anti toxoplasma gondii en mujeres embarazadas, atendidas en una casa de salud privada, siendo el principal reservorio de esta infección el gato doméstico (Feliscatus), puede ocurrir en cualquier etapa  del embarazo, es muy  importante detectar en el primer trimestre  para evitar  trastornos del sistema nervioso central y retinocoroiditis.  El método clínico que se utilizó para el diagnóstico de los anticuerpos IgG-IgM fue electroquimiolumisencia de alta sensibilidad, los resultados obtenidos de anticuerpos IgG contra T. gondii en embarazadas, fue 16% IgG-IgM seropositivo para anti T. gondii, en relación con las mujeres embarazadas con serología positiva para T. gondii decreció linealmente con la edad de la paciente, siendo el grupo de 20-25años el más afectado 40(12%) para IgG positivo y IgM 25(10%), lo que referencia acerca de la prevalencia del Toxoplasma gondii. ABSTRACTThe aim of this study was the determination of IgM antibodies IgG anti toxoplasma gondii in pregnant women, attended in a private health place, being the main reservoir of this infection the domestic cat (Felis catus), can occur at any stage of pregnancy, it is important to detect the first trimester of pregnancy to prevent disorders of the central nervous system and retinochoroiditis. The clinical method used was electroquimiolumisencia high sensitivity for the diagnosis of IgG - IgM antibodies, the results of IgG antibodies against T. gondii in pregnant women was 16% IgG anti-IgM seropositive for T. gondii, in relation of pregnant women with positive serology for T. gondii decreased linearly with the age of the patient, being the group most affected 20-25años 40 (12%) for IgG and IgM positive 25 (10%) giving reference on prevalence of Toxoplasma gondii

In-hospital outcomes of mechanical complications in acute myocardial infarction: Analysis from a nationwide Spanish database

Background: Mechanical complications represent an important cause of mortality in myocardial infarction (MI) patients. This is a nationwide study performed to evaluate possible changes in epidemiology or prognosis of these complications with current available strategies.Methods: Information was obtained from the minimum basis data set of the Spanish National Health System, including all hospitalizations for acute myocardial infarction (AMI) from 2010 to 2015. Risk-standardized in-hospital mortality ratio was calculated using multilevel risk adjustment models.Results: A total of 241,760 AMI episodes were analyzed, MI mechanical complications were observed in 842 patients: cardiac tamponade in 587, ventricular septal rupture in 126, and mitral regurgitation due to papillary muscle or chordae tendineae rupture in 155 (there was more than one complication in 21 patients). In-hospital mortality was 59.5%. On multivariate adjustment, variables with significant impact on in-hospital mortality were: age (OR 1.06; 95% CI 1.04-1.07; p < 0.001), ST-segment elevation AMI (OR 2.91; 95% CI 1.88-4.5; p < 0.001), cardiogenic shock (OR 2.35; 95% CI 1.66-3.32; p < 0.001), cardio-respiratory failure (OR 3.48; 95% CI 2.37-5.09; p < 0.001), and chronic obstructive pulmonary disease (OR 1.85; 95% CI 1.07-3.20; p < 0.001). No significant trends in risk-adjusted in-hospital mortality were detected (IRR 0.997; p = 0.109). Cardiac intensive care unit availability and more experience with mechanical complications management were associated with lower adjusted mortality rates (56.7 ± 5.8 vs. 60.1 ± 4.5; and 57 ± 6.1 vs. 59.9 ± 5.6, respectively; p < 0.001).Conclusions: Mechanical complications occur in 3.5 per thousand AMI, with no significant trends to better survival over the past few years. Advanced age, cardiogenic shock and cardio-respiratory failure are the most important risk factors for in-hospital mortality. Higher experience and specialized cardiac intensive care units are associated with better outcomes

Ivabradine in acute heart failure: Effects on heart rate and hemodynamic parameters in a randomized and controlled swine trial

Background: Acute heart failure patients could benefit from heart rate reduction, as myocardial consumption and oxidative stress are related to tachycardia. Ivabradine could have a clinical role attenuating catecholamine-induced tachycardia. The aim of this study was to evaluate hemodynamic effects of ivabradine in a swine model of acute heart failure. Methods: Myocardial infarction was induced by 45 min left anterior descending artery balloon occlusion in 18 anesthetized pigs. An infusion of dobutamine and noradrenaline was maintained aiming to preserve adequate hemodynamic support, accompanied by fluid administration to obtain a pulmonary wedged pressure ≥ 18 mmHg. After reperfusion, rhythm and hemodynamic stabilization, the animals were randomized to 0.3 mg/kg ivabradine intravenously (n = 9) or placebo (n = 9). Hemodynamic parameters were observed over a 60 min period. Results: Ivabradine was associated with a significant reduction in heart rate (88.4 ± 12.0 bpm vs. 122.7 ± 17.3 bpm after 15 min of ivabradine/placebo infusion, p &lt; 0.01) and an increase in stroke volume (68.8 ± 13.7 mL vs. 52.4 ± 11.5 mL after 15 min, p = 0.01). There were no significant differences in systemic or pulmonary arterial pressure, or significant changes in pulmonary capillary pressure. However, after 15 min, cardiac output was significantly reduced with ivabradine (–5.2% vs. +15.0% variation in ivabradine/placebo group, p = 0.03), and central venous pressure increased (+4.2% vs. –19.7% variation, p &lt; 0.01). Conclusions: Ivabradine reduces heart rate and increases stroke volume without modifying systemic or left filling pressures in a swine model of acute heart failure. However, an excessive heart rate reduction could lead to a decrease in cardiac output and an increase in right filling pressures. Future studies with specific heart rate targets are needed

Ivabradine in acute heart failure: Effects on heart rate and hemodynamic parameters in a randomized and controlled swine trial.

Background: Acute heart failure patients could benefit from heart rate reduction, as myocardial consumption and oxidative stress are related to tachycardia. Ivabradine could have a clinical role attenuating catecholamine-induced tachycardia. The aim of this study was to evaluate hemodynamic effects of ivabradine in a swine model of acute heart failure. Methods: Myocardial infarction was induced by 45 min left anterior descending artery balloon occlusion in 18 anesthetized pigs. An infusion of dobutamine and noradrenaline was maintained aiming to preserve adequate hemodynamic support, accompanied by fluid administration to obtain a pulmonary wedged pressure ≥ 18 mmHg. After reperfusion, rhythm and hemodynamic stabilization, the animals were randomized to 0.3 mg/kg ivabradine intravenously (n = 9) or placebo (n = 9). Hemodynamic parameters were observed over a 60 min period. Results: Ivabradine was associated with a significant reduction in heart rate (88.4 ± 12.0 bpm vs. 122.7 ± 17.3 bpm after 15 min of ivabradine/placebo infusion, p < 0.01) and an increase in stroke volume (68.8 ± 13.7 mL vs. 52.4 ± 11.5 mL after 15 min, p = 0.01). There were no significant differences in systemic or pulmonary arterial pressure, or significant changes in pulmonary capillary pressure. However, after 15 min, cardiac output was significantly reduced with ivabradine (–5.2% vs. +15.0% variation in ivabradine/placebo group, p = 0.03), and central venous pressure increased (+4.2% vs. – 19.7% variation, p < 0.01). Conclusions: Ivabradine reduces heart rate and increases stroke volume without modifying systemic or left filling pressures in a swine model of acute heart failure. However, an excessive heart rate reduction could lead to a decrease in cardiac output and an increase in right filling pressures. Future studies with specific heart rate targets are needed.pre-print2533 K

Optimal surgical timing after post-infarction ventricular septal rupture

Background: Ventricular septal rupture (VSR) following acute myocardial infarction (AMI) is a dan-gerous condition. Surgical VSR closure is the definitive therapy, but there is controversy regarding the surgical timing and the bridging therapy between diagnosis and intervention. The objective of this study is to analyze the ideal time of surgical repair and to establish the contribution of mechanical circulatory support (MCS) devices on the prognosis. Methods: We designed an observational, retrospective, multicenter study, selecting all consecutive patients with post-AMI VSR between January 1, 2008 and December 31, 2018, with non-exclusion criteria. The main objective of this study was to analyze the optimal timing for surgical repair of post-AMI VSR. Second- ary endpoints were to determine which factors could influence mortality in the patients of the surgical group. Results: A total of 141 patients were included. We identified lower mortality rates with an odds ratio of 0.3 (0.1 & ndash;0.9) in patients operated on from day 4 compared with the surgical mortality in the first 24 hours after VSR diagnosis. The use of MCS was more frequent in patients treated with surgery, par- ticularly for intra-aortic balloon pump (IABP; 79.6% vs. 37.8%, p < 0.001), but also for veno-arterial extracorporeal membrane oxygenation (VA-ECMO; 18.2% vs. 6.4%, p = 0.134). Total mortality was 91.5% for conservative management and 52.3% with surgical repair (p < 0.001). Conclusions: In our study, we observed that the lowest mortality rates in patients with surgical repair of post-AMI VSR were observed in patients operated on from day 4 after diagnosis of VSR, compared to earlier interventions. (Cardiol J 2022; 29, 5: 773 & ndash;781

In-hospital outcomes of mechanical complications in acute myocardial infarction: Analysis from a nationwide Spanish database

Background: Mechanical complications represent an important cause of mortality in myocardial infarction (MI) patients. This is a nationwide study performed to evaluate possible changes in epidemiology or prognosis of these complications with current available strategies.Methods: Information was obtained from the minimum basis data set of the Spanish National Health System, including all hospitalizations for acute myocardial infarction (AMI) from 2010 to 2015. Risk-standardized in-hospital mortality ratio was calculated using multilevel risk adjustment models.Results: A total of 241,760 AMI episodes were analyzed, MI mechanical complications were observed in 842 patients: cardiac tamponade in 587, ventricular septal rupture in 126, and mitral regurgitation due to papillary muscle or chordae tendineae rupture in 155 (there was more than one complication in 21 patients). In-hospital mortality was 59.5%. On multivariate adjustment, variables with significant impact on in-hospital mortality were: age (OR 1.06; 95% CI 1.04–1.07; p &lt; 0.001), ST-segment elevation AMI (OR 2.91; 95% CI 1.88–4.5; p &lt; 0.001), cardiogenic shock (OR 2.35; 95% CI 1.66–3.32; p &lt; 0.001), cardio-respiratory failure (OR 3.48; 95% CI 2.37–5.09; p &lt; 0.001), and chronic obstructive pulmonary disease (OR 1.85; 95% CI 1.07–3.20; p &lt; 0.001). No significant trends in risk-adjusted in-hospital mortality were detected (IRR 0.997; p = 0.109). Cardiac intensive care unit availability and more experience with mechanical complications management were associated with lower adjusted mortality rates (56.7 ± 5.8 vs. 60.1 ± 4.5; and 57 ± 6.1 vs. 59.9 ± 5.6, respectively; p &lt; 0.001).Conclusions: Mechanical complications occur in 3.5 per thousand AMI, with no significant trends to better survival over the past few years. Advanced age, cardiogenic shock and cardio-respiratory failure are the most important risk factors for in-hospital mortality. Higher experience and specialized cardiac intensive care units are associated with better outcomes

Structure-Guided Approach for the Development of MUC1-Glycopeptide-Based Cancer Vaccines with Predictable Responses

Mucin-1 (MUC1) glycopeptides are exceptional candidates for potential cancer vaccines. However, their autoantigenic nature often results in a weak immune response. To overcome this drawback, we carefully engineered synthetic antigens with precise chemical modifications. To be effective and stimulate an anti-MUC1 response, artificial antigens must mimic the conformational dynamics of natural antigens in solution and have an equivalent or higher binding affinity to anti-MUC1 antibodies than their natural counterparts. As a proof of concept, we have developed a glycopeptide that contains noncanonical amino acid (2S,3R)-3-hydroxynorvaline. The unnatural antigen fulfills these two properties and effectively mimics the threonine-derived antigen. On the one hand, conformational analysis in water shows that this surrogate explores a landscape similar to that of the natural variant. On the other hand, the presence of an additional methylene group in the side chain of this analog compared to the threonine residue enhances a CH/π interaction in the antigen/antibody complex. Despite an enthalpy–entropy balance, this synthetic glycopeptide has a binding affinity slightly higher than that of its natural counterpart. When conjugated with gold nanoparticles, the vaccine candidate stimulates the formation of specific anti-MUC1 IgG antibodies in mice and shows efficacy comparable to that of the natural derivative. The antibodies also exhibit cross-reactivity to selectively target, for example, human breast cancer cells. This investigation relied on numerous analytical (e.g., NMR spectroscopy and X-ray crystallography) and biophysical techniques and molecular dynamics simulations to characterize the antigen–antibody interactions. This workflow streamlines the synthetic process, saves time, and reduces the need for extensive, animal-intensive immunization procedures. These advances underscore the promise of structure-based rational design in the advance of cancer vaccine development