[Use of parenteral anticoagulants in patients with coronary syndrome]. / Uso de anticoagulantes parenterales en pacientes con síndromes coronarios.

Anticoagulant treatment, together with antiplatelet therapy, plays an important role in the treatment of acute coronary syndromes. Its use is associated with a reduction in new ischemic events, stent thrombosis, and lower mortality. However, in clinical practice there is great heterogeneity in its use, leading to suboptimal results in treatment. This paper conducts a narrative review on the use of parenteral anticoagulants in patients with acute coronary syndromes, depending on the clinical scenario, as well as the revascularization strategy used and the bleeding risk. The different anticoagulant schemes available in acute coronary syndromes with and without segment ST elevation are addressed, based on the updated evidence. Finally, evidence-based strategies for risk stratification for bleeding and therapeutic management are developed.

El tratamiento anticoagulante, en conjunto con la anti agregación, cumple un rol de suma importancia en el tratamiento de los síndromes coronarios agudos. Su uso está asociado a reducción de nuevos eventos isquémicos, trombosis del stent e incluso menor mortalidad. No obstante, en la práctica clínica existe una gran heterogeneidad en su utilización, llevando a resultados subóptimos en el tratamiento. Este trabajo ofrece una revisión narrativa sobre el uso de anticoagulantes parenterales en pacientes con síndromes coronarios agudos, dependiendo del escenario clínico, así como también de la estrategia de revascularización implementada y el riesgo hemorrágico. Se abordan los diferentes esquemas anticoagulantes disponibles en síndromes coronarios agudos con y sin elevación del segmento ST, basados en la evidencia actualizada hasta la fecha. Finalmente, se desarrollan herramientas para la estratificación del riesgo de sangrado y su manejo terapéutico.

CPAP increases 6-minute walk distance after lung resection surgery.

BACKGROUND: The application of CPAP has been used to minimize postoperative pulmonary complications after lung resection surgery. The aim of this study was to quantify both the CPAP effects upon lung function and functional capacity in early postoperative lung resection, as well as to evaluate if CPAP prolongs air leak through the chest drain. METHODS: Thirty patients in the postoperative period of lung resection were allocated into 2 groups: an experimental group, consisting of 15 patients who underwent a 10 cm H(2)O CPAP, and a 15 patient control group, who performed breathing exercises. Arterial blood gas analysis, peak expiratory flow (PEF), respiratory muscle strength, spirometry, and 6-min walk test (6MWT) were assessed in the preoperative period, and repeated postoperatively on the first and on the seventh day (6MWT was repeated only on the seventh day). RESULTS: Significant increases in PEF, muscle strength, and FEV(1) between the first and seventh postoperative day were observed, both in the experimental and in the control group, whereas FVC and P(aO(2)) increased significantly between the first and seventh postoperative day only in the experimental group. The average loss in 6-min walk distance (6MWD) from preoperative to postoperative day 7 in the experimental group was significantly lower than in control group. When comparing the 2 groups, only 6MWD was statistically different (P < .001). There was no air leakage increase through the drain with the early use of CPAP. CONCLUSION: When compared to breathing exercises, CPAP increases the 6MWD in postoperative lung resection patients, without prolonging air leak through the chest drain.

[Hyperglycemia in acute coronary syndrome: multidisciplinary scientific report]. / Hiperglucemia en el síndrome coronario agudo: informe científico multidisciplinario.

Hyperglycemia with or without pre-existing diabetes mellitus, occurs frequently in the setting of acute coronary syndrome. Previous studies have demonstrated that hyperglycemia is highly prevalent and is associated with an increased risk of hospital complications and death. The underlying pathophysiology related an adverse clinical outcome to hyperglycemia is unclear, and it is uncertain whether increased serum glucose is simply a marker of adverse outcomes or their cause. Detrimental effects of hyperglycemia on the cardiovascular system are multiple. Glycemia control with insulin would prevent adverse outcomes. Numerous glucose-control protocols have been developed and tested proving to be safe and effective. In an initiative from the Emergency Council of the Argentine Society of Cardiology, local experts analyzed the management of hyperglycemia in acute coronary syndrome. The main objective of the prevent statement is to summarize the current state of knowledge on glycemic control, and to offer general recommendations regarding glucose management in the coronary care unit.

The importance of endobag use with incision-protective devices in VATS lung resection: a preliminary study.

OBJECTIVE: The advent of new techniques such as video-assisted thoracoscopic surgery (VATS) for the removal of lung segments leads to compression of the surgical specimen, with the possible dissemination of neoplastic cells. The sheer volume of surgeries performed using these techniques has caused many institutions to stop removing the surgical specimen using an endobag, even when retractors/protectors are used in the instrumentalization incision. This study aimed to collect data from patients undergoing lung resection by VATS and analyze the cytopathological results of the collected material. RESULTS: A total of 47 endobag fluid samples were collected from patients who underwent VATS. The surgical specimen was subjected to histopathological analysis, and all patients underwent pathological TNM staging. In the cytopathological analyses, only 2 (4.3%) specimens of endobag fluid aspirate were positive for neoplastic cells. In these two cases, the tumors were peripheral, both with diagnoses of moderately differentiated adenocarcinoma and with classifications of T1bN0M0 and T3N0M0. These results indicate that although there is a low incidence of tumor cells in endobag fluid, it is always better to perform surgery using all available protective measures to avoid tumor implantation in the thoracic cavity to the greatest extent possible.

[Specific pharmacological treatment guide for transthyretin amyloid cardiomyopathy, 2021]. / Guía de tratamiento farmacológico específico de la cardiomiopatía amiloidótica por transtiretina, 2021.

This clinical practice guideline for treating transthyretin amyloid (ATTR) cardiomyopathy is based on the best available evidence of clinical effectiveness. The PICO format was used to generate a list of questions focused on the effectiveness and safety of the specific treatment of patients with ATTR cardiomyopathy. The search was conducted in PubMed, Cochrane and Epistemokus, between July-August 2020, and selected articles between 2000-2020, in English and Spanish. The level of evidence and recommendations were analyzed and classified by the GRADE system. The following drugs were included in the analysis: tafamidis, diflunisal, inotersen, patisiran y doxycycline and ursodeoxycholic acid. The expert panel had an agreement that tafamidis 80mg/daily is the only available drug with moderate evidence and weak recommendation for the reduction of total mortality, cardiovascular morbidity, heart failure hospitalization and progression of the disease in patients with ATTR cardiomyopathy and NYHA class = 3. In contrast, tafamidis 20 mg/daily had low-quality evidence in this group of patients. The expert panel did not recommend inotersen, patisiran and diflunisal in patients with ATTR cardiomyopathy due to the lack of supporting evidence, local drug availability, and the potential risk of toxicity. When patients did not have access to tafamidis, the expert panel stated a weak recommendation to use doxycycline and ursodeoxycholic acid in patients with ATTR cardiomyopathy.

Con el propósito de confeccionar una guía con la mejor evidencia disponible en el tratamiento de la amiloidosis por depósito de transtiretina (ATTR), se generó un listado de preguntas en formato PICO centradas en la efectividad y seguridad y se realizó una búsqueda en PubMed, Cochrane y Epistemokus de los artículos publicados entre 2000-2020 y se incluyeron dos estudios de extensión en relación al tafamidis. Los niveles de evidencia y los grados de recomendación se basaron en el sistema GRADE, emitiéndose 11 recomendaciones para ATTRv y ATTwt. Se consideraron los siguientes fármacos: tafamidis, diflunisal, inotersen, patisiran y doxiciclina más ácido ursodesoxicolico. El grupo de expertos consensuó que el único tratamiento que demostró reducir de la mortalidad global, mortalidad cardiovascular, internaciones cardiovasculares y la progresión de la cardiopatía con un nivel moderado de evidencia fue el tafamidis 80 mg, mientras que para la formulación tafamidis 20 mg la calidad de evidencia es baja. Para inotersen y diflunisal, se formuló una recomendación en contra del tratamiento dada la falta de evidencia de calidad respecto a su efectividad, el perfil de toxicidad y la falta de disponibilidad en el ámbito local. Con respecto al patisirán, la recomendación se focalizó en la población ATTRv. El panel de expertos consensuó que el tratamiento con doxiciclina más ácido ursodeoxicólico podría ser utilizado ante la imposibilidad de iniciar tratamiento con tafamidis, recomendación débil y calidad de evidencia muy baja.

[NT-Pro-BNP levels performance before and after reversion to sinus rhythm in patients with preserved ventricular function]. / Descenso de los niveles de propéptido natriurético de tipo B-N terminal luego de la reversión de pacientes con fibrilación auricular y función ventricular conservada.

Our objective was to evaluate changes of N-terminal pro-BNP (NT-Pro-BNP) levels at baseline and after restoration to sinus rhythm in hemodynamic stable patients with lone atrial fibrillation (LAF) with preserved left ventricular function. NT-Pro-BNP levels were obtained before and after cardioversion in thirty hemodynamic stable patients with LAF and preserved left ventricular function. At baseline levels of NT-Pro BNP levels were significatively higher than a normal control group. NT-Pro-BNP levels decreased significantly following cardioversion from 529 (157-1763) to 318 (98-870) pg/ml, p < 0.0001. Decreasing of N-terminal pro-BNP concentrations was observed after any mode of cardioversion: electrical or pharmacologic, 345 (153-1151) pg/ml to 169 (86-407) pg/ml, p: 0.02 and from 1624 (541-4010) pg/ml to 856 (532-1160) pg/ml, p < 0.001, respectively. N-terminal pro-BNP decreasing was observed mainly in patients with length of LAF longer than 8 hours: 1289 (338-2103) to 410 (169-905) pg/ml, p < 0.001 but no difference was detected when such length was less than 8 hours: 274 (137-2300) to 286 (82-1440), p = NS. Our study showed that baseline levels of NT-pro-BNP decreased shortly after reversion of patients with LAF to sinus rhythm. This performance occurs predominantly in patients with LAF length of at least eight hours.

Treatment of individual predictors with neural network algorithms improves Global Registry of Acute Coronary Events score discrimination.

Objective: The aim of this study was to develop, train, and test different neural network (NN) algorithm-based models to improve the Global Registry of Acute Coronary Events (GRACE) score performance to predict in-hospital mortality after an acute coronary syndrome. Methods: We analyzed a prospective database, including 40 admission variables of 1255 patients admitted with the acute coronary syndrome in a community hospital. Individual predictors included in GRACE score were used to train and test three NN algorithm-based models (guided models), namely: one- and two-hidden layer multilayer perceptron and a radial basis function network. Three extra NNs were built using the 40 admission variables of the entire database (unguided models). Expected mortality according to GRACE score was calculated using the logistic regression equation. Results: In terms of receiver operating characteristic area and negative predictive value (NPV), almost all NN algorithms outperformed logistic regression. Only radial basis function models obtained a better accuracy level based on NPV improvement, at the expense of positive predictive value (PPV) reduction. The independent normalized importance of variables for the best unguided NN was: creatinine 100%, Killip class 61%, ejection fraction 52%, age 44%, maximum creatine-kinase level 41%, glycemia 40%, left bundle branch block 35%, and weight 33%, among the top 8 predictors. Conclusions: Treatment of individual predictors of GRACE score with NN algorithms improved accuracy and discrimination power in all models with respect to the traditional logistic regression approach; nevertheless, PPV was only marginally enhanced. Unguided variable selection would be able to achieve better results in PPV terms.

Objetivo: El objetivo fue desarrollar, entrenar y probar diferentes modelos basados en algoritmos de redes neuronales (RN) para mejorar el rendimiento del score del Registro Global de Eventos Coronarios Agudos (GRACE) para predecir la mortalidad hospitalaria después de un síndrome coronario agudo. Métodos: Analizamos una base de datos prospectiva que incluía 40 variables de ingreso de 1255 pacientes con síndrome coronario agudo en un hospital comunitario. Las variables incluidas en la puntuación GRACE se usaron para entrenar y probar tres algoritmos basados en RN (modelos guiados), a saber: perceptrones multicapa de una y dos capas ocultas y una red de función de base radial. Se construyeron tres RN adicionales utilizando las 40 variables de admisión de toda la base de datos (modelos no guiados). La mortalidad esperada según el GRACE se calculó usando la ecuación de regresión logística. Resultados: En términos del área ROC y valor predictivo negativo (VPN), casi todos los algoritmos RN superaron la regresión logística. Solo los modelos de función de base radial obtuvieron un mejor nivel de precisión basado en la mejora del VPN, pero a expensas de la reducción del valor predictivo positivo (VPP). La importancia normalizada de las variables incluidas en la mejor RN no guiada fue: creatinina 100%, clase Killip 61%, fracción de eyección 52%, edad 44%, nivel máximo de creatina quinasa 41%, glucemia 40%, bloqueo de rama izquierda 35%, y peso 33%, entre los 8 predictores principales. Conclusiones: El tratamiento de las variables del score GRACE mediante algoritmos de RN mejoró la precisión y la discriminación en todos los modelos con respecto al enfoque tradicional de regresión logística; sin embargo, el VPP solo mejoró marginalmente. La selección no guiada de variables podría mejorar los resultados en términos de PPV.

Remote ischaemic conditioning in patients with ST-elevation myocardial infarction treated with percutaneous coronary intervention: an updated meta-analysis of clinical outcomes.

BACKGROUND: All previous meta-analyses including clinical outcomes after remote ischaemic conditioning (RIC) in patients with ST-elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI) demonstrated that RIC significantly reduced all-cause mortality and major adverse cardiovascular events (MACE). Following the publication of these meta-analyses, three new randomised controlled clinical trials (RCT) including 5712 patients were reported. The objective of this study was to perform an updated meta-analysis about the effectiveness of RIC in reducing MACE in patients with STEMI undergoing PCI. METHODS: The search strategy included only RCT identified in MEDLINE, Embase, SCOPUS, and Cochrane (up to February 2020). Eligible studies included any type of RIC. The study adhered to the Preferred Reporting Items of Systematic Reviews and Meta-Analysis (PRISMA) statement. The studies quality was evaluated with Cochrane Risk of Bias tool and Jadad score. RESULTS: Twelve RCT were included in the analysis (Q = 18.8, p = 0.065, I2 = 41.5%, 95%CI 0.0-70.3). Globally, 8239 STEMI patients with 816 MACE were reported with follow-ups between 1 and 45 months. Random effects model showed no significant effect of RIC on composite clinical endpoints (OR = 0.77, 95%CI 0.59-1.01, p = 0.105). Sensitivity analysis demonstrated that only the exclusion of CONDI-2/ERIC PPCI trial modified the significance of the global effect (OR 0.66, 95%CI 0.47-0.93), favouring RIC intervention. CONCLUSIONS: The current updated meta-analysis showed that use of RIC around the time of PCI for STEMI treatment added no significant benefit for clinical outcomes assessed between 6 and 45 months after the procedure. These conclusions are in direct contrast to previously published meta-analyses.

Continuous Monitoring of Coronary Care Mortality Using the Global Registry for Acute Coronary Events (GRACE) Score.

BACKGROUND: The aim was to assess the utility of cumulative sum techniques for continuous monitoring of coronary care outcomes, applied to patients with acute coronary syndrome stratified by the Global Registry for Acute Coronary Events (GRACE) risk score. METHODS: A prospective longitudinal study to assess GRACE score for real-time monitoring of coronary care mortality in a community hospital was conducted between January 2012 and December 2017. An expected-to-observed probability of death chart for individual risk and a variable life-adjusted display were used to monitor the results. RESULTS: A total of 1,255 patients undergoing acute coronary syndrome were included in the analysis. GRACE-based variable life-adjusted plots monitoring in-hospital mortality showed that observed death rates remained in general within the expected 95% confidence limit over time, and these behaviors were similar for ST-segment elevation and non-ST-segment elevation myocardial infarction. In-hospital all-cause mortality was 2.6% for the overall population, and 56% of these cases corresponded to unexpected deaths; conversely, unexpected survival occurred in 5.2% of survivors. CONCLUSIONS: Continuous monitoring of coronary care mortality based on cumulative sum charts and the GRACE score demonstrated the occurrence of series of favorable and unfavorable outcomes on a real-time basis. Additionally, plotting the expected-to-observed probability of death for individual cases was useful to individualize unexpected deaths in low-risk patients. Although overall coronary care performance was adequate according to the GRACE score, we found that there is still some room for improvement, since over half of the deaths occurring in low-risk patients were potentially preventable.

Multicenter prospective validation of the EuroSCORE II in Argentina.

Objective: To validate prospectively in multiple centers, the accuracy and clinical utility of the European System for Cardiac Operative Risk Evaluation (EuroSCORE II) to predict the operative mortality of cardiac surgery in Argentina. Methods: Between January 2012 and February 2018, 2,000 consecutive adult patients who underwent cardiac surgery in different centers in Argentina were prospectively included. The end-point was in-hospital all-cause mortality. Discrimination, calibration, precision and clinical utility of the EuroSCORE II were evaluated in the global cohort and in the different types of surgeries, based on ROC (Receiver Operating Characteristics) curves, Hosmer-Lemeshow goodness-of-fit test, observed/expected mortality ratio, Shannon index and decision curves analysis. Results: ROC area of the EuroSCORE II was between 0.73 and 0.80 for all types of surgery, being the lowest value for coronary surgery. The observed and expected mortality was 4.3% and 3.0%, respectively (p = 0.034). The decision curve analysis showed a positive net benefit for all thresholds below 0.24, considering all type of surgeries. Conclusion: The EuroSCORE II showed an adequate performance in terms of discrimination and calibration for all types of surgery, although somewhat inferior for coronary surgery. Though in general terms this model underestimated the risk in intermediate risk groups, its overall performance was acceptable. The EuroSCORE II could be considered an optional updated generic model of operative risk stratification to predict in-hospital mortality after cardiac surgery in our context.

Objetivo: Validar, en forma prospectiva y en múltiples centros, la precisión y utilidad clínica del European System for Cardiac Operative Risk Evaluation II (EuroSCORE II) para predecir la mortalidad operatoria de la cirugía cardíaca en centros de Argentina. Método: Entre enero de 2012 y febrero de 2018 se incluyeron en forma prospectiva 2,000 pacientes consecutivos que fueron sometidos a cirugía cardíaca en diferentes centros de Argentina. El punto final fue mortalidad hospitalaria por cualquier causa. La discriminación, calibración, precisión y utilidad clínica del EuroSCORE II se evaluaron en la cohorte global y en los diferentes tipos de cirugías, basándose en las curvas Receiver Operating Characteristics (ROC), bondad de ajuste de Hosmer-Lemeshow, razón de mortalidad observada/esperada, índice de Shannon y curvas de decisión. Resultados: El área ROC del EuroSCORE II estuvo entre 0.73 y 0.80 para todo tipo de cirugía, y el valor más bajo fue para la cirugía coronaria. La mortalidad observada y esperada fue 4.3 y 3.0%, respectivamente (p = 0.034). El análisis de la curva de decisión demostró un beneficio neto positivo para los umbrales por debajo de 0.24 para todo tipo de cirugía. Conclusiones: El EuroSCORE II tuvo un desempeño adecuado en términos de discriminación y calibración para todos los tipos de cirugía, aunque algo inferior para la cirugía coronaria. Si bien en términos generales subestimó el riesgo en los grupos de riesgo intermedio, el comportamiento global fue aceptable. El EuroSCORE II podría considerarse una opción de modelo genérico y actualizado de estratificación del riesgo operatorio para predecir la mortalidad hospitalaria de la cirugía cardíaca en nuestro contexto.

Solid Indeterminate Nodules with a Radiological Stability Suggesting Benignity: A Texture Analysis of Computed Tomography Images Based on the Kurtosis and Skewness of the Nodule Volume Density Histogram.

BACKGROUND: The number of incidental findings of pulmonary nodules using imaging methods to diagnose other thoracic or extrathoracic conditions has increased, suggesting the need for in-depth radiological image analyses to identify nodule type and avoid unnecessary invasive procedures. OBJECTIVES: The present study evaluated solid indeterminate nodules with a radiological stability suggesting benignity (SINRSBs) through a texture analysis of computed tomography (CT) images. METHODS: A total of 100 chest CT scans were evaluated, including 50 cases of SINRSBs and 50 cases of malignant nodules. SINRSB CT scans were performed using the same noncontrast enhanced CT protocol and equipment; the malignant nodule data were acquired from several databases. The kurtosis (KUR) and skewness (SKW) values of these tests were determined for the whole volume of each nodule, and the histograms were classified into two basic patterns: peaks or plateaus. RESULTS: The mean (MEN) KUR values of the SINRSBs and malignant nodules were 3.37 ± 3.88 and 5.88 ± 5.11, respectively. The receiver operating characteristic (ROC) curve showed that the sensitivity and specificity for distinguishing SINRSBs from malignant nodules were 65% and 66% for KUR values >6, respectively, with an area under the curve (AUC) of 0.709 (p < 0.0001). The MEN SKW values of the SINRSBs and malignant nodules were 1.73 ± 0.94 and 2.07 ± 1.01, respectively. The ROC curve showed that the sensitivity and specificity for distinguishing malignant nodules from SINRSBs were 65% and 66% for SKW values >3.1, respectively, with an AUC of 0.709 (p < 0.0001). An analysis of the peak and plateau histograms revealed sensitivity, specificity, and accuracy values of 84%, 74%, and 79%, respectively. CONCLUSIONS: KUR, SKW, and histogram shape can help to noninvasively diagnose SINRSBs but should not be used alone or without considering clinical data.

¿De qué hablamos cuando hablamos de cuidados paliativos en insuficiencia cardíaca? / What Are We Talking About When We Talk About Palliative Care in Heart Failure?

RESUMEN La insuficiencia cardíaca (IC) es una enfermedad crónica, compleja y progresiva, con elevada morbimortalidad y creciente prevalencia. Pese al avance en las estrategias terapéuticas, destinadas a mejorar la sobrevida y reducir hospitalizaciones, la IC continúa generando un impacto negativo en la calidad de vida de los pacientes. Surge ante este reto la necesidad de desarrollar políticas de salud basadas no solo en la integridad física, sino también en la integridad psicosocial. Los cuidados paliativos (CP) hacen referencia a un cuidado especializado, interdisciplinario, enfocado en mejorar y mantener la calidad de vida de los pacientes que se enfrentan a una enfermedad con elevada morbimortalidad como lo es la IC. El propósito de la presente revisión es evaluar el impacto de la integración de los CP en el tratamiento multidisciplinario de la IC en todas las fases de la enfermedad y determinar la factibilidad de su aplicación en la práctica clínica.

ABSTRACT Heart failure is a chronic, complex and progressive disease, with high morbidity and mortality, and growing prevalence. Despite advances in therapeutic strategies to improve survival and reduce hospitalizations, heart failure still generates a negative impact on the patients' quality of life, making it necessary to develop health policies based not only on their physical but also on their psychosocial integrity. Palliative care refers to specialized, interdisciplinary care focused on improving the quality of life of patients who suffer a disease with elevated morbidity and mortality. The aim of this review is to assess the impact of the implementation of palliative care in the multidisciplinary treatment of heart failure throughout all the stages of the disease, and to determine the feasibility of its application in clinical practice.

Eficacia y seguridad en la vida real de amlodipino/irbesartán en combinación fija en el tratamiento de la hipertensión en América Latina: estudio PARCERIA / Real-life effectiveness and safety of fixed amlodipine/irbesartan in hypertension management in Latin America: the PARCERIA study

Resumen Introducción: Los estudios basados en la población latinoamericana han demostrado tasas de control de la presión arterial subóptimas. La combinación de medicamentos antihipertensivos en dosis fijas se asocia con mayor comodidad, adherencia y efectividad en comparación con la monoterapia. Objetivo: Evaluar la efectividad y seguridad en la vida real de la combinación fija de amlodipino/irbesartán en el tratamiento a largo plazo de la hipertensión en Argentina, Chile, Colombia, Guatemala y México. Materiales y método: estudio prospectivo, observacional, de cohorte única de 48 semanas, en el que se incluyeron adultos con hipertensión no controlada, tratados con una combinación fija de amlodipino/irbesartán según criterio médico y fueron seguidos en la consulta ambulatoria habitual. La presión arterial objetivo fue < 140/90 mmHg (< 130/80 mmHg para pacientes con diabetes o enfermedad renal). Resultados: Se incluyeron 509 pacientes (57.6% mujeres). La edad media (DE) y la puntuación de riesgo de Framingham a 10 años fueron 60.6 (12.5) años y 9.9 (8.78), respectivamente. Durante 48 semanas de seguimiento, 97.4% de los pacientes tomaron ≥ 80% de las dosis prescritas. Se observó mejoría en la presión arterial estadísticamente significativa y clínicamente importante (-25.7/-13.5 mmHg; p < 0.001). Se logró control en el 62.7% de los pacientes. El cumplimiento del tratamiento fue uno de los predictores significativos (p < 0.05) de la presión arterial objetivo. Ochenta y siete (17.1%) pacientes experimentaron 117 eventos adversos emergentes del tratamiento, incluidos 7 eventos graves en 5 (1.0%) pacientes. Los eventos adversos fueron generalmente leves (75.2%) y se consideró que no estaban relacionados con el tratamiento (76.1%). Los acontecimientos adversos más frecuentes fueron edema periférico (3.9% de los pacientes) y mareos (1.0%). Según las estimaciones de Kaplan-Meier, el tiempo medio (SE) hasta la interrupción del tratamiento por acontecimientos adversos fue de 32.85 (0.08) semanas. Conclusiones: El tratamiento con irbesartán/amlodipino en combinación de dosis fijas mostró efectividad clínica, con mejoría significativa de las cifras de presión, y mayor llegada a la meta en quienes cumplieron con el tratamiento. El tratamiento fue bien tolerado, con un bajo porcentaje de eventos adversos relacionados con el tratamiento, y pocos eventos graves. La combinación en dosis fija es una importante herramienta en el tratamiento de la hipertensión arterial.

Abstract Introduction: Latin American population-based studies have shown suboptimal blood pressure control rates. Fixed-dose anti-hypertensive combinations are associated with improved convenience, adherence and effectiveness compared with monotherapy. Objective: assessed the real-life effectiveness and safety of fixed amlodipine/irbesartan combination in long-term management of hypertension in Argentina, Chile, Colombia, Guatemala, and Mexico. Materials and method: this was a 48-week, prospective, observational, single-cohort study, which included adults with uncontrolled hypertension, treated with fixed amlodipine/irbesartan combination per the treating physician's judgment, were followed in routine care. Target blood pressure was < 140/90 mmHg (< 130/80 mmHg for patients with diabetes or renal disease). Results: 509 patients (57.6% females) were included. Mean (SD) age and Framingham 10-year risk-score were 60.6 (12.5) years and 9.9 (8.78), respectively. Over 48 weeks, 97.4% of patients took ≥ 80% of prescribed doses. Statistically significant and clinically important blood pressure improvements (-25.7/-13.5 mmHg; p < 0.001) were observed. Control was achieved by 62.7% of patients. Treatment compliance was one of the significant (p < 0.05) predictors of target blood pressure achievement. Eighty-seven (17.1%) patients experienced 117 treatment-emergent adverse events, including 7 serious events by 5 (1.0%) patients. Adverse events were generally mild (75.2%) and judged not to be treatment-related (76.1%). The most common adverse events were peripheral edema (3.9% of patients) and dizziness (1.0%). Based on Kaplan-Meier estimates, the mean (SE) time to adverse event-related discontinuation was 32.85 (0.08) weeks. Conclusion: Treatment with the fixed-dose combination of irbesartan/amlodipine demonstrated clinical effectiveness, with a significant improvement in blood pressure values and a higher rate of achieving the treatment goal in those who adhered to the regimen. The treatment was well-tolerated, with a low percentage of treatment-related adverse events, and few severe events. The fixed-dose combination is an important tool in the management of arterial hypertension.

Uso de anticoagulantes parenterales en pacientes con síndromes coronarios / Use of parenteral anticoagulants in patients with coro nary syndromes

Resumen El tratamiento anticoagulante, en conjunto con la anti agregación, cumple un rol de suma importancia en el tratamiento de los síndromes coronarios agudos. Su uso está asociado a reducción de nuevos eventos isquémicos, trombosis del stent e incluso menor morta lidad. No obstante, en la práctica clínica existe una gran heterogeneidad en su utilización, llevando a resultados subóptimos en el tratamiento. Este trabajo ofrece una revisión narrativa sobre el uso de anticoagulantes parenterales en pacientes con sín dromes coronarios agudos, dependiendo del escenario clínico, así como también de la estrategia de revascula rización implementada y el riesgo hemorrágico. Se abordan los diferentes esquemas anticoagulantes disponibles en síndromes coronarios agudos con y sin elevación del segmento ST, basados en la evidencia ac tualizada hasta la fecha. Finalmente, se desarrollan herramientas para la es tratificación del riesgo de sangrado y su manejo tera péutico.

Abstract Anticoagulant treatment, together with antiplatelet therapy, plays an important role in the treatment of acute coronary syndromes. Its use is associated with a reduction in new ischemic events, stent thrombosis, and lower mortality. However, in clinical practice there is great heterogene ity in its use, leading to suboptimal results in treatment. This paper conducts a narrative review on the use of parenteral anticoagulants in patients with acute coronary syndromes, depending on the clinical scenario, as well as the revascularization strategy used and the bleeding risk. The different anticoagulant schemes available in acute coronary syndromes with and without segment ST elevation are addressed, based on the updated evidence. Finally, evidence-based strategies for risk stratifi cation for bleeding and therapeutic management are developed.

Tejido adiposo epicárdico como predictor de enfermedad coronaria. ¿Un nuevo parámetro para la estratificación del riesgo cardiovascular? / Epicardial Adipose Tissue as Predictor of Coronary Artery Disease. A New Parameter to Stratify Cardiovascular Risk?

RESUMEN La asociación entre el tejido adiposo visceral y la enfermedad cardiovascular ha sido claramente establecida. Asimismo, se ha determinado que la adiposidad ectópica se asocia con un mayor riesgo cardiovascular en comparación a la adiposidad subcutánea. En este contexto, múltiples investigaciones han evaluado el rol del tejido adiposo epicárdico (TAE) en la enfermedad cardiovascular. El TAE se localiza entre la superficie miocárdica y la hoja visceral del pericardio, y puede cuantificarse mediante técnicas no invasivas como ser el ecocardiograma, la tomografía computada o la resonancia nuclear magnética. El TAE no es simplemente un órgano de depósito. Actualmente, se considera que es un tejido metabólicamente activo capaz de secretar múltiples adipoquinas que actúan mediante diferentes vías de señalización parácrina, endócrina, vasócrina y/o autócrina. La evidencia actual sugiere que el TAE puede ser un factor contribuyente en la patogénesis de la enfermedad coronaria, asociándose además con su gravedad y progresión. En ese sentido, algunos autores han postulado al TAE como un nuevo factor de riesgo cardiovascular y como un potencial blanco terapéutico. El objetivo de esta revisión es analizar la relación del TAE con la enfermedad cardiovascular, principalmente con la enfermedad coronaria.

ABSTRACT The association between visceral adipose tissue and cardiovascular disease has been clearly established. Likewise, it has been determined that ectopic adiposity is associated with a higher cardiovascular risk compared to subcutaneous adiposity. In this context, multiple investigations have evaluated the role of epicardial adipose tissue (EAT) in cardiovascular disease. EAT is located between the myocardial surface and the visceral layer of the pericardium, and can be quantified by noninvasive techniques such as echocardiography, computed tomography, or magnetic resonance imaging. The EAT is not simply a storage organ. Currently, it is considered to be a metabolically active tissue capable of secreting multiple adipokines that act through different paracrine, endocrine, vasocrine and/or autocrine signaling pathways. Current evidence suggests that EAT may be a contributing factor in the pathogenesis of coronary heart disease, as well as being associated with its severity and progression. In this sense, some authors have postulated EAT as a new cardiovascular risk factor and as a potential therapeutic target. The aim of this review is to analyze the association between EAT and cardiovascular disease, mainly coronary artery disease.

Guía de tratamiento farmacológico específico de la cardiomiopatía amiloidótica por transtiretina, 2021 / Specific pharmacological treatment guide for transthyretin amyloid cardiomyopathy, 2021

Resumen Con el propósito de confeccionar una guía con la mejor evidencia disponible en el tratamiento de la amiloidosis por depósito de transtiretina (ATTR), se generó un listado de preguntas en formato PICO centradas en la efectividad y seguridad y se realizó una búsqueda en PubMed, Cochrane y Epistemokus de los artículos publicados entre 2000-2020 y se incluyeron dos estudios de extensión en relación al tafamidis. Los niveles de evidencia y los grados de recomendación se basaron en el sistema GRADE, emitiéndose 11 recomendaciones para ATTRv y ATTwt. Se consideraron los siguientes fármacos: tafamidis, diflunisal, inotersen, patisiran y doxiciclina más ácido ursodesoxicolico. El grupo de expertos consensuó que el único tratamiento que demostró reducir de la mortalidad global, mortalidad cardiovascular, internaciones cardiovasculares y la progresión de la cardiopatía con un nivel moderado de evidencia fue el tafamidis 80 mg, mientras que para la formulación tafamidis 20 mg la calidad de evidencia es baja. Para inotersen y diflunisal, se formuló una recomendación en contra del tratamiento dada la falta de evidencia de calidad respecto a su efectividad, el perfil de toxicidad y la falta de disponibilidad en el ámbito local. Con respecto al patisirán, la recomendación se focalizó en la población ATTRv. El panel de expertos consensuó que el tratamiento con doxiciclina más ácido ursodeoxicólico podría ser utilizado ante la imposibilidad de iniciar tratamiento con tafamidis, recomendación débil y calidad de evidencia muy baja.

Abstract This clinical practice guideline for treating transthyretin amyloid (ATTR) cardiomyopathy is based on the best available evidence of clinical effectiveness. The PICO format was used to generate a list of ques tions focused on the effectiveness and safety of the specific treatment of patients with ATTR cardiomyopathy. The search was conducted in PubMed, Cochrane and Epistemokus, between July-August 2020, and selected articles between 2000-2020, in English and Spanish. The level of evidence and recommendations were analyzed and classified by the GRADE system. The following drugs were included in the analysis: tafamidis, diflunisal, inotersen, patisiran y doxycycline and ursodeoxycholic acid. The expert panel had an agreement that tafamidis 80mg/daily is the only available drug with moderate evidence and weak recommendation for the reduction of total mortality, cardiovascular morbidity, heart failure hospitalization and progression of the disease in patients with ATTR cardiomyopathy and NYHA class ≤ 3. In contrast, tafamidis 20 mg/daily had low-quality evidence in this group of patients. The expert panel did not recommend inotersen, patisiran and diflunisal in patients with ATTR cardiomyopathy due to the lack of supporting evidence, local drug availability, and the potential risk of toxicity. When patients did not have access to tafamidis, the expert panel stated a weak recommendation to use doxycycline and ursodeoxycholic acid in patients with ATTR cardiomyopathy.

Treatment of individual predictors with neural network algorithms improves Global Registry of Acute Coronary Events score discrimination / El tratamiento con redes neuronales de las variables del Global Registry of Acute Coronary mejora la discriminación del score

Abstract Objective: The aim of this study was to develop, train, and test different neural network (NN) algorithm-based models to improve the Global Registry of Acute Coronary Events (GRACE) score performance to predict in-hospital mortality after an acute coronary syndrome. Methods: We analyzed a prospective database, including 40 admission variables of 1255 patients admitted with the acute coronary syndrome in a community hospital. Individual predictors included in GRACE score were used to train and test three NN algorithm-based models (guided models), namely: one- and two-hidden layer multilayer perceptron and a radial basis function network. Three extra NNs were built using the 40 admission variables of the entire database (unguided models). Expected mortality according to GRACE score was calculated using the logistic regression equation. Results: In terms of receiver operating characteristic area and negative predictive value (NPV), almost all NN algorithms outperformed logistic regression. Only radial basis function models obtained a better accuracy level based on NPV improvement, at the expense of positive predictive value (PPV) reduction. The independent normalized importance of variables for the best unguided NN was: creatinine 100%, Killip class 61%, ejection fraction 52%, age 44%, maximum creatine-kinase level 41%, glycemia 40%, left bundle branch block 35%, and weight 33%, among the top 8 predictors. Conclusions: Treatment of individual predictors of GRACE score with NN algorithms improved accuracy and discrimination power in all models with respect to the traditional logistic regression approach; nevertheless, PPV was only marginally enhanced. Unguided variable selection would be able to achieve better results in PPV terms.

Resumen Objetivo: El objetivo fue desarrollar, entrenar y probar diferentes modelos basados en algoritmos de redes neuronales (RN) para mejorar el rendimiento del score del Registro Global de Eventos Coronarios Agudos (GRACE) para predecir la mortalidad hospitalaria después de un síndrome coronario agudo. Métodos: Analizamos una base de datos prospectiva que incluía 40 variables de ingreso de 1255 pacientes con síndrome coronario agudo en un hospital comunitario. Las variables incluidas en la puntuación GRACE se usaron para entrenar y probar tres algoritmos basados en RN (modelos guiados), a saber: perceptrones multicapa de una y dos capas ocultas y una red de función de base radial. Se construyeron tres RN adicionales utilizando las 40 variables de admisión de toda la base de datos (modelos no guiados). La mortalidad esperada según el GRACE se calculó usando la ecuación de regresión logística. Resultados: En términos del área ROC y valor predictivo negativo (VPN), casi todos los algoritmos RN superaron la regresión logística. Solo los modelos de función de base radial obtuvieron un mejor nivel de precisión basado en la mejora del VPN, pero a expensas de la reducción del valor predictivo positivo (VPP). La importancia normalizada de las variables incluidas en la mejor RN no guiada fue: creatinina 100%, clase Killip 61%, fracción de eyección 52%, edad 44%, nivel máximo de creatina quinasa 41%, glucemia 40%, bloqueo de rama izquierda 35%, y peso 33%, entre los 8 predictores principales. Conclusiones: El tratamiento de las variables del score GRACE mediante algoritmos de RN mejoró la precisión y la discriminación en todos los modelos con respecto al enfoque tradicional de regresión logística; sin embargo, el VPP solo mejoró marginalmente. La selección no guiada de variables podría mejorar los resultados en términos de PPV.

Single spot albumin to creatinine ratio: A simple marker of long-term prognosis in non-ST segment elevation acute coronary syndromes.

BACKGROUND: Microalbuminuria is a known risk factor for cardiovascular morbidity and mortality suggesting that it should be a marker of endothelial dysfunction. Albumin to creatinine ratio (ACR) is an available and rapid test for microalbuminuria determination, with a high correlation with the 24-h urine collection method. There is no prospective study that evaluates the prognostic value of ACR in patients with non ST-segment elevation acute coronary syndromes (NSTE-ACS). The purpose of our study was to detect the long-term prognostic value of ACR in patients with NSTE-ACS. METHODS: Albumin to creatinine ratio was estimated in 700 patients with NSTE-ACS at admission. Median follow-up time was 18 months. The best cutoff point of ACR for death or acute myocardial infarction was 20 mg/g. Twenty-two percent of patients had elevated ACR. RESULTS: By multivariable Cox regression analysis, ACR was an independent predictor of the clinical endpoint: odds ratio 5.8 (95% confidence interval [CI] 2-16), log-rank 2 p < 0.0001 in a model including age > 65 years, female gender, diabetes mellitus, creatinine clearance, glucose levels at admission, elevated cardiac markers (troponin T/CK-MB) and ST segment depression. The addition of ACR significantly improved GRACE score C-statistics from 0.69 (95% CI 0.59-0.83) to 0.77 (95% CI 0.65-0.88), SE 0.04, 2 p = 0.03, with a good calibration with both models. CONCLUSIONS: Albumin to creatinine ratio is an independent and accessible predictor of long-term adverse outcomes in NSTE-ACS, providing additional value for risk stratification.

Comparación pronóstica entre scores de riesgo y la aplicación de redes neuronales para la predicción de la mortalidad a corto y mediano plazo en pacientes con insuficiencia cardíaca / Prognostic Comparison between Risk Scores and Neural Networks to Predict Short- and Mid-Term Mortality in Acute Heart Failure

RESUMEN Introducción: En el contexto de la insuficiencia cardíaca (IC) existen scores de riesgo para evaluar la mortalidad por cualquier causa durante el primer año, con áreas bajo la curva ROC que oscilan entre 0,59 y 0,80. Objetivo: Desarrollar y validar un modelo basado en algoritmos de redes neuronales (RN) destinado a mejorar el rendimiento de los modelos tradicionales para predecir mortalidad a corto y mediano plazo de pacientes con IC aguda. Material y métodos: Se analizó una base de datos con 181 variables de 483 pacientes con IC aguda en un hospital de comunidad de la Ciudad de Buenos Aires (junio de 2005-junio de 2019). Se utilizaron 25 variables para calcular 5 modelos de riesgo validados para predecir la mortalidad a 30 días, 6 meses y un año: EFFECT, ADHERE, GWTG-HF, 3C-HF y ACUTE-HF. Resultados: La edad media fue 78 ± 11,1años, 58% eran varones, el 35% de las IC eran de etiología isquémico necrótica, y la fracción de eyección media fue 52% (35-60). En término de discriminación a 30 días, fueron mejores el score EFFECT (ROC: 0,68) y el 3C-HF (ROC: 0,67) que el ACUTE- HF (ROC: 0,54). A los 6 meses y al año, el score EFFECT (ROC: 0,69 y 0,69) superó al ADHERE (ROC: 0,53 y 0,56) (p=0,011 y p = 0,003, respectivamente), y los scores EFFECT GWRG-HF (ROC: 0,68 y 0,66) y 3C-HF (ROC: 0,67 y 0,67) superaron al score ACUTE-HF (ROC: 0,53 y 0,56). De los algoritmos de RN los mejores resultados se obtuvieron con un perceptrón multicapa (PMC) con dos capas ocultas. Se usó una RN de arquitectura de capas 24-9-7-2 con los siguientes resultados: ROC: 0,82, valor predictivo negativo (VPN) 93,2% y valor predictivo positivo (VPP) 66,7% para mortalidad a 30 días; ROC: 0,87, VPN: 89,1% y VPP: 78,6% para mortalidad a 6 meses; y ROC: 0,85, VPN: 85,6% y VPP: 78,9% para mortalidad al año. En términos de discriminación, los algoritmos de RN superaron a los scores tradicionales ( p <0,001). Los factores que obtuvieron ≥50% de importancia estandarizada para predecir la mortalidad a los 30 días fueron en orden descendente la creatinina sérica, la hemoglobina, la frecuencia respiratoria, la urea, el sodio, la edad y la presión arterial sistólica. Agregaron capacidad pronóstica la clase III-IV NYHA y la demencia para mortalidad a 6 meses, y la frecuencia cardíaca y la disfunción renal crónica para mortalidad al año. Conclusiones: Los modelos con algoritmos de RN fueron significativamente superiores a los scores de riesgo tradicionales en nuestros pacientes con IC. Estos hallazgos constituyen una hipótesis de trabajo a validar con una mayor muestra de casos y en forma multicéntrica.

ABSTRACT Background: Heart failure (HF) risk scores to assess all-cause mortality during the first year have areas under the ROC curve (AUC) ranging between 0.59 and 0.80 Objective: To develop and validate a neural network (NN) algorithm-based model to improve traditional scores' performance for predicting short- and mid-term mortality of patients with acute HF. Methods: A prospective clinical database was analyzed including 483 patients admitted with diagnosis of acute HF in a coronary care unit community hospital of Buenos Aires, between June 2005 and June 2019. Among 181 demographic, laboratory, treatment and follow-up variables, only 25 were selected to calculate five acute heart failure risk scores aimed to predict 30-day, 6-month and 1-year mortality: EFFECT, ADHERE, GWTG-HF, 3C-HF, and ACUTE-HF. Results: Mean age was 78 ± 11.1 years, 58% were men, 35% had ischemic necrotic HF and median left ventricular ejection fraction was 52% (35-60). At 30 days, the EFFECT score (AUC:0.68) and the 3C-HF score (AUC: 0.68) showed better performance than the ACUTE-HF score (AUC: 0.54). At 6-month and 1-year follow-up, the EFFECT score (ROC: 0.69 and 0.69) outperformed the ADHERE score (AUC: 0.53 and 0.56), and EFFECT (AUC: 0.69 and 0.69), GWRG-HF (AUC = 0.68 and 0.66), and 3C-HF (AUC:0.67 and 0.67) scores outperformed the ACUTE-HF score (AUC:0.53 and 0.56). The best results with NN algorithms were obtained with a two-hidden layer multilayer perceptron. A 24-9-7-2-layer architecture NN was used with the following results: AUC: 0.82, negative predictive value (NPV) 93.2% and positive predictive value (PPV) 66.7% for 30-day mortality; AUC: 0.87, NPV: 89.1% and PPV: 78,6% for 6-month mortality; and AUC: 0.85, NPV: 85.6% and PPV: 78.9% for 1-year mortality. In terms of discrimination, NN algorithms outperformed all the traditional scores (p <0.001). For this algorithm, the most influential factors in descending order that scored ≥50% normalized importance to predict 30-day mortality were serum creatinine, hemoglobin, respiratory rate, blood urea nitrogen, serum sodium, age and systolic blood pressure. Also, NYHA functional class III-IV and dementia added prognostic capacity to 6-month mortality, and heart rate and chronic kidney disease to 1-year mortality. Conclusions: The models with NN algorithms were significantly superior to traditional risk scores in our population of patients with HF. These findings constitute a working hypothesis to be validated with a larger and multicenter sample of cases.

Metaanálisis sobre los resultados a 30 días del implante valvular aórtico transcatéter en pacientes con riesgo intermedio en Argentina / Single-arm Meta-analysis of Argentine Studies Reporting 30-Day Mortality After Transcatheter Aortic Valve Implantation in Intermediate Risk Patients

RESUMEN Introducción: El implante valvular aórtico transcatéter (TAVI) ha mostrado ser beneficioso en los pacientes con riesgo intermedio; sin embargo,no existe ningún análisis del conjunto de los resultados del TAVI en nuestro país. Objetivos: Realizar un metaanálisis de estudios locales de grupo único sobre los resultados hospitalarios del TAVI en pacientes de riesgo intermedio en Argentina. Métodos: Se realizó una revisión sistemática utilizando estudios observacionales de TAVI identificados en MEDLINE, Embase, SCOPUS y Cochrane hasta agosto de 2019. Resultados: De los 59 estudios identificados a través de la citada búsqueda, solamente 4 estudios observacionales locales comunicaban la mortalidad a 30 días y las complicaciones posteriores al TAVI en pacientes de riesgo moderado, según el puntaje de la STS (Society of Thoracic Surgeons) -entre 4 y 7%-. En 494 pacientes, la mortalidad a 30 días fue del 4,8%. Las estimaciones ponderadas del conjunto de estudios arrojaron estos valores: accidente vascular cerebral, 2,7%; infarto de miocardio,1,0%; necesidad de marcapasos definitivo, 24,8%; fuga paravalvular moderada o grave, 16,7%; y sangrado mayor, 5,5%. Conclusiones: La eficacia demostrada del TAVI está generando una expansión de su indicación a pacientes con riesgo intermedio y bajo; sin embargo, este avance debería estar apoyado por evidencia local de su beneficio por sobre la cirugía valvular tradicional. Este metaanálisis de estudios de grupo único realizados en el país presenta la mortalidad a 30 días y las complicaciones posteriores al TAVI en pacientes de riesgo intermedio. La información actualizada de los resultados locales del TAVI servirá como un estándar en nuestro medio.

ABSTRACT Background: Transcatheter aortic valve implantation (TAVI) has been shown to be beneficial in patients with intermediate risk; however, there is no overall analysis reporting TAVI results in our country. Objectives: To conduct a single-arm meta-analysis of local studies reporting 30-day outcomes after TAVI in intermediate risk patients in Argentina. Methods: A systematic review on TAVI was performed using controlled trials and observational studies identified in MEDLINE, Embase, SCOPUS and Cochrane to August 2019. Results: Among 59 articles identified through the database search, only 4 local observational studies reported 30-day mortality and complications after TAVI in moderate-risk patients according to the STS (Society of Thoracic Surgeons) score ranging between 4 and 7%. In 494 patients, 30-day mortality was 4.8%. Weighted pooled estimates of the studies were: stroke 2.7%, myocardial infarction 1.0%, need for a definitive pacemaker 24.8%, moderate or severe periprosthetic leakage 16.7%, and major bleeding 5.5%. Conclusions: The proven efficacy of TAVI is generating an expansion of its indication to patients with intermediate and low risk, However, this shift should be supported by local evidence of its benefit over traditional valve surgery. This single-arm meta-analysis of Argentine studies presents 30-day mortality and complications after TAVI in intermediate risk patients. The updated information of the local TAVI outcomes will serve as a standard in our settings.