Efectos del control de la frecuencia cardiaca mediante ivabradina sobre los parámetros hemodinámicos en un modelo porcino de insuficiencia cardiaca aguda

INTRODUCCIÓN Y OBJETIVOS: La reducción de la frecuencia cardiaca (FC) en los pacientes en insuficiencia cardiaca aguda (ICA) podría ser beneficiosa al disminuir el consumo miocárdico de oxígeno y aumentar el tiempo de llenado diastólico. La ivabradina se postula como una opción atractiva en este contexto. El objetivo de este estudio fue, de forma previa a su aplicación en humanos, describir el efecto de la ivabradina sobre la FC, los parámetros hemodinámicos y las proteínas de degradación de la matriz extracelular en un modelo porcino de ICA. MÉTODOS: Se incluyeron 18 cerdas a las que se ocluyó la arteria descendente anterior mediante el inflado de un balón durante 45 minutos. Se administró noradrenalina, dobutamina y suero salino hasta alcanzar una FC > 90lpm y una presión de enclavamiento pulmonar > 18mmHg. Los parámetros hemodinámicos se registraron a través de catéteres insertados en aorta y yugular. Tras el desinflado del balón, se estabilizó al animal durante 15 minutos para su posterior aleatorización abierta a grupo control (n=9) o ivabradina (n=9). La ivabradina se administró por vía intravenosa a una dosis de 0,3mg/kg. Se registraron los parámetros hemodinámicos de forma basal y cada 15 minutos hasta transcurrida 1 hora desde la administración del fármaco. Además, se cuantificó el daño tisular miocárdico a los 6 días del infarto a través de técnicas histológicas e inmunohistoquímicas. RESULTADOS: La ivabradina se asoció, a los 15 minutos de su administración, a una reducción significativa de la FC (88.4±12.0lpm vs. 122.7±17.3lpm; p<0.01) y a un aumento del volumen latido (68.8±13.7ml vs. 52.4±11.5ml; p=0.01). No se modificó la presión arterial sistémica, pulmonar o la presión de enclavamiento pulmonar. Sin embargo, sí que se objetivó una ligera reducción del gasto cardiaco (-5.2% vs. +15.0% a los 15 minutos de la administración del fármaco; p=0.03) en los animales del grupo ivabradina. A nivel histológico y molecular, la ivabradina se asoció a una menor área de tejido infartado y a una menor expresión de las proteínas degradadoras de la matriz extracelular EMMPRIN y MMP-9. Por contra, la cantidad de microvesículas en sangre y en orina conteniendo EMMPRIN resultó significativamente mayor en el grupo ivabradina. CONCLUSIONES: La ivabradina permite una reducción de la FC en un modelo porcino de ICA sin modificar la presión arterial sistémica ni las presiones de llenado izquierdas. Sin embargo, una reducción excesiva de la FC podría asociarse a una leve disminución del gasto cardiaco. Por otro lado, nuestros hallazgos histológicos e inumohistoquímicos permiten postular la hipótesis de que la ivabradina podría contribuir a la preservación de la matriz extracelular mediante la encapsulación de enzimas degradadoras en forma de microvesículas liberadas a sangre y a orina

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

Dimensiones de la aurícula izquierda en pacientes con ictus isquémico criptogénico como método para predecir el desarrollo de fibrilación auricular.

Objective: To determine whether the left atrial size can predict the development of atrial fibrillation (AF) in patients with embolic stroke of undetermined source (ESUS).Methods: Patients with ischemic stroke were included prospectively (January 2015-July 2015) when ESUS was suspected. Clinical and cardiac imaging data were recorded. Patients with cardiac failure were excluded.Results: a total of 55 patients were included. Medium age was 71 years. The proportion of patients who developed AF during the follow-up (1 year) was 23, 63%. 10 % of patients did not have any vascular risk factor. Basal ECG was normal in 98% of cases. The left atrial size volume was 36, 08 ml in patients who developed AF and 27, 14 ml in patients who did not.Conclusions: In patients with ESUS, left atrial size dimensions do not predict the occurrence of AF.Objetivos. Determinar si el grado de dilatación de aurícula izquierda (AI) nos permitirían predecir la existencia de fibrilación auricular (FA) subyacente en pacientes con ictus embólico de origen indeterminado.Material y métodos. Se incluyeron de manera prospectiva pacientes que acudieron como Código Ictus a nuestro centro (Enero 2015-Julio 2015), con sospecha etiológica de embolia sin arritmia documentada. Se documentaron datos clínicos y de imagen cardíaca.Resultados. Un total de 55 pacientes fueron incluidos en el estudio. La edad media fue de 71 años. El porcentaje de pacientes que desarrollaron FA durante el seguimiento (1 año) fue del 23,63%. Un 10% de los pacientes no presentaban ningún factor de riesgovascular clásico. El ECG basal fue normal en el 98%. El volumen medio de AI en ETT ajustado por superficie corporal fue de 36,08 ml en pacientes que desarrollaron FA y de 27,14 ml en aquellos que no la desarrollaron.Conclusiones. En pacientes con ictus isquémico con sospecha mecanismo embólico las dimensiones de la aurícula izquierda no predicen el desarrollo de FA a medio plaz

Left atrial size in patients with cryptogenic stroke as a predictor of occurrence of atrial fibrillation

Objective: To determine whether the left atrial size can predict the development of atrial fibrillation (AF) in patients with embolic stroke of undetermined source (ESUS). Methods: Patients with ischemic stroke were included prospectively (January 2015-July 2015) when ESUS was suspected. Clinical and cardiac imaging data were recorded. Patients with cardiac failure were excluded. Results: a total of 55 patients were included. Medium age was 71 years. The proportion of patients who developed AF during the follow-up (1 year) was 23, 63%. 10 % of patients did not have any vascular risk factor. Basal ECG was normal in 98% of cases. The left atrial size volume was 36, 08 ml in patients who developed AF and 27, 14 ml in patients who did not. Conclusions: In patients with ESUS, left atrial size dimensions do not predict the occurrence of AF

Frailty is an independent prognostic marker in elderly patients with myocardial infarction.

Acute coronary syndrome (ACS) patients are increasingly older. Conventional prognostic scales include chronological age but do not consider vulnerability. In elderly patients, a frail phenotype represents a better reflection of biological age. This study aims to determine the prevalence of frailty and its influence on patients age ≥75 years with ACS. Patients age ≥75 years admitted due to type 1 myocardial infarction were included in 2 tertiary hospitals, and clinical data were collected prospectively. Frailty was defined at admission using the previously validated Survey of Health Ageing and Retirement in Europe Frailty Index (SHARE-FI) tool. The primary endpoint was the combination of death or nonfatal myocardial reinfarction during a follow-up of 6 months. Major bleeding (hemoglobin decrease ≥3 g/dL or transfusion needed) and readmission rates were also explored. A total of 234 consecutive patients were included. Frail patients (40.2%) had a higher-risk profile, based on higher age and comorbidities. On multivariate analysis, frailty was an independent predictor of the combination of death or nonfatal myocardial reinfarction (adjusted hazard ratio [aHR]: 2.54, 95% confidence interval [CI]: 1.12-5.79), an independent predictor of the combination of death, nonfatal myocardial reinfarction, or major bleeding (aHR: 2.14, 95% CI: 1.13-4.04), and an independent predictor of readmission (aHR: 1.80, 95% CI: 1.00-3.22). Frailty phenotype at admission is common among elderly patients with ACS and is an independent predictor for severe adverse events. It should be considered in future risk-stratification models