ABSTRACT
Renal impairment confers worse prognosis in patients with atrial fibrillation (AF) but there is scarce evidence about the influence of direct-acting oral anticoagulants in routine clinical practice. Herein, we compared clinical outcomes between patients with AF with and without renal impairment on rivaroxaban and investigated predictors for clinical outcomes in patients with AF with renal impairment. This was a multicenter study including patients with AF on rivaroxaban for at least 6 months. During 2.5 years follow-up, ischemic strokes (IS)/transient ischemic attacks (TIA)/systemic embolisms (SE)/myocardial infarctions (MI), major bleeding, and major adverse cardiovascular events (MACE) were recorded. Creatinine clearance (CrCl) was estimated using the Cockroft-Gault equation, renal impairment was defined as a CrCl <60 ml/min, and 1,433 patients (34.8% with CrCl <60 ml/min) were included. Patients with CrCl <60 ml/min showed higher event rates for major bleeding (1.87%/year vs 0.62%/year; p = 0.003) and MACE (1.97%/year vs 0.62%/year; p = 0.002) but similar event rates for IS/TIA/SE/MI (0.66%/year vs 0.67%/year; p = 0.955). In patients with renal impairment, CHA2DS2-VASc was associated with higher risk of IS/TIA/SE/MI; HAS-BLED and any dependency level were associated with higher risk of major bleeding; and male gender and heart failure were associated with higher risk of MACE. Antiplatelets were independently associated with increased risk of IS/TIA/SE/MI and MACE. In conclusion, in patients with AF on rivaroxaban, the incidence of IS/TIA/SE/MI did not increase in those with renal impairment, suggesting that rivaroxaban may be an effective option in this subgroup. In patients with AF, male gender, heart failure, dependency, antiplatelets, CHA2DS2-VASc, and HAS-BLED were associated with increased risk of adverse outcomes.
Subject(s)
Atrial Fibrillation , Heart Failure , Ischemic Attack, Transient , Myocardial Infarction , Renal Insufficiency , Stroke , Humans , Male , Rivaroxaban , Atrial Fibrillation/complications , Atrial Fibrillation/drug therapy , Atrial Fibrillation/epidemiology , Stroke/epidemiology , Stroke/etiology , Stroke/prevention & control , Ischemic Attack, Transient/epidemiology , Hemorrhage/chemically induced , Hemorrhage/epidemiology , Hemorrhage/complications , Renal Insufficiency/complications , Renal Insufficiency/epidemiology , Myocardial Infarction/epidemiology , Heart Failure/complications , Anticoagulants/therapeutic use , Risk FactorsABSTRACT
BACKGROUND: Pharmacological options for rate control in atrial fibrillation are scarce. Ivabradine was postulated to reduce the ventricular rate in this setting. OBJECTIVES: The objectives of this study were to evaluate the mechanism of inhibition of atrioventricular conduction produced by ivabradine and to determine its efficacy and safety in atrial fibrillation. METHODS: The effects of ivabradine on atrioventricular node and ventricular cells were studied by in vitro whole-cell patch-clamp experiments and mathematical simulation of human action potentials. In parallel, a multicenter, randomized, open-label, phase III clinical trial compared ivabradine with digoxin for uncontrolled permanent atrial fibrillation despite ß-blocker or calcium channel blocker treatment. RESULTS: Ivabradine 1 µM inhibited "funny" current and rapidly activating delayed rectifier potassium channel current by 28.9% and 22.8%, respectively (P < .05). The sodium channel current and L-type calcium channel current were reduced only at 10 µM. Ivabradine slowed the firing frequency of a modeled human atrioventricular node action potential by 10.6% and induced a minimal prolongation of ventricular action potential. Thirty-five (51.5%) patients were randomized to ivabradine and 33 (49.5%) to digoxin. The mean daytime heart rate decreased by 11.6 beats/min (-11.5%) in the ivabradine arm (P = .02) vs 19.6 (-20.6%) in the digoxin arm (P < .001), although the noninferiority margin of efficacy was not met (Z = -1.95; P = .97). The primary safety end point occurred in 3 patients (8.6%) on ivabradine and in 8 (24.2%) on digoxin (P = .10). CONCLUSION: Ivabradine produced a moderate rate reduction in patients with permanent atrial fibrillation. The inhibition of funny current in the atrioventricular node seems to be the main mechanism responsible for this reduction. Compared with digoxin, ivabradine was less effective, was better tolerated, and had a similar rate of serious adverse events.
Subject(s)
Atrial Fibrillation , Humans , Ivabradine/therapeutic use , Atrial Fibrillation/drug therapy , Heart Rate/physiology , Digoxin/therapeutic use , Adrenergic beta-Antagonists/therapeutic useABSTRACT
INTRODUCCIÓN Y OBJETIVOS: La ivabradina es un inhibidor de la corriente If, principal determinante de la función marcapasos del nódulo sinusal, aprobado como antianginoso y para tratar la insuficiencia cardiaca. Existen indicios sobre su capacidad para inhibir la conducción a través del nódulo auriculoventricular (NAV). Sobre esta base, el proyecto BRAKE-AF plantea el uso de ivabradina como agente cronotrópico negativo en fibrilación auricular (FA). MÉTODOS: Se realizará un ensayo clínico multicéntrico de fase III, aleatorizado, abierto, en paralelo, con diseño de no inferioridad, para comparar la ivabradina frente a la digoxina en 232 pacientes con FA permanente no controlada con bloqueadores beta o antagonistas del calcio; el objetivo primario es la reducción de la frecuencia cardiaca media diurna en un Holter de 24 h a los 3 meses. El ensayo se apoyará en un estudio electrofisiológico que analizará el efecto de la ivabradina en el potencial de acción del NAV humano, utilizando un modelo experimental en células de ovario de hámster chino transfectadas con el ADN que codifica la expresión de los distintos canales que componen dicho potencial de acción, registrando las corrientes iónicas mediante la técnica del parche de membrana. RESULTADOS: Se obtendrá información tanto del efecto de la ivabradina en las corrientes iónicas y el potencial de acción del NAV como de su eficacia y su seguridad en pacientes con FA permanente. CONCLUSIONES: Los resultados del proyecto BRAKE-AF podrían permitir que la ivabradina se incluyera en el limitado arsenal de fármacos disponibles actualmente para el control de frecuencia en la FA
INTRODUCTION AND OBJECTIVES: Ivabradine is an inhibitor of the If channel, the main determinant of the pacemaker function of the sinus node. The drug has been approved for the treatment of angina and heart failure. There is some evidence of its role as an inhibitor of atrial-ventricular node (AVN) conduction. The aim of the BRAKE-AF project is to assess ivabradine use for rate control in atrial fibrillation (AF). METHODS: A multicenter, randomized, parallel, open-label, noninferiority phase III clinical trial will be conducted to compare ivabradine vs digoxin in 232 patients with uncontrolled permanent AF despite beta-blockers or calcium channel blockers. The primary efficacy endpoint is the reduction in daytime heart rate measured by 24-hour Holter monitoring at 3 months. This clinical trial will be supported by an electrophysiological study of the effect of ivabradine on the action potential of the human AVN. To do this, an experimental model will be used with Chinese hamster ovarium cells transfected with the DNA encoding the expression of the t channels involved in this action potential and recording of the ionic currents with patch clamp techniques. RESULTS: New data will be obtained on the effect of ivabradine on the human AVN and its safety and efficacy in patients with permanent AF. CONCLUSIONS: The results of the BRAKE-AF project might allow inclusion of ivabradine within the limited arsenal of drugs currently available for rate control in AF
Subject(s)
Humans , Animals , Female , Young Adult , Aged , Aged, 80 and over , Ivabradine/pharmacology , Atrial Fibrillation/drug therapy , Cardiovascular Agents/pharmacology , Digoxin/pharmacology , Anti-Arrhythmia Agents/pharmacology , Patch-Clamp Techniques , Action Potentials , Atrial Fibrillation/physiopathology , Heart Rate/drug effectsABSTRACT
INTRODUCTION AND OBJECTIVES: Ivabradine is an inhibitor of the If channel, the main determinant of the pacemaker function of the sinus node. The drug has been approved for the treatment of angina and heart failure. There is some evidence of its role as an inhibitor of atrial-ventricular node (AVN) conduction. The aim of the BRAKE-AF project is to assess ivabradine use for rate control in atrial fibrillation (AF). METHODS: A multicenter, randomized, parallel, open-label, noninferiority phase III clinical trial will be conducted to compare ivabradine vs digoxin in 232 patients with uncontrolled permanent AF despite beta-blockers or calcium channel blockers. The primary efficacy endpoint is the reduction in daytime heart rate measured by 24-hour Holter monitoring at 3 months. This clinical trial will be supported by an electrophysiological study of the effect of ivabradine on the action potential of the human AVN. To do this, an experimental model will be used with Chinese hamster ovarium cells transfected with the DNA encoding the expression of the t channels involved in this action potential and recording of the ionic currents with patch clamp techniques. RESULTS: New data will be obtained on the effect of ivabradine on the human AVN and its safety and efficacy in patients with permanent AF. CONCLUSIONS: The results of the BRAKE-AF project might allow inclusion of ivabradine within the limited arsenal of drugs currently available for rate control in AF. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Identifier: NCT03718273.
Subject(s)
Anti-Arrhythmia Agents/therapeutic use , Atrial Fibrillation/drug therapy , Cardiovascular Agents/therapeutic use , Digoxin/therapeutic use , Heart Rate/drug effects , Ivabradine/therapeutic use , Equivalence Trials as Topic , Heart Rate/physiology , Humans , Treatment OutcomeABSTRACT
We report the entrapment of Pulmonary Vein Ablation Catheter (Medtronic, Minneapolis, MN, USA) and its guidewire within the right pulmonary veins in two patients. The catheters could be retrieved without complications but they were disabled in both cases. This nondescribed incident should be recognized by PVAC users since it may be a source of potential severe complications during pulmonary vein isolation procedures.
Subject(s)
Atrial Fibrillation/surgery , Catheter Ablation/adverse effects , Catheter Ablation/instrumentation , Pulmonary Veins/surgery , Aged , Device Removal , Equipment Design , Female , Fluoroscopy , HumansABSTRACT
Se revisan las aportaciones psicológicas, neurocientíficas y biológicas en las que se fundamenta el Protocolo de Exploración Neuropsicológica del Aprendizaje Relacional-InfantoJuvenil (PENpAR-IJ) diseñado por la primera autora y con el que se trabaja en la Sección de Psiquiatría Infanto-Juvenil del Hospital Clínico Universitario Lozano Blesa de Zaragoza. Se hará hincapié en la necesidad de integrar conocimientos científicos vigentes sobre la mente. Se revisarán así mismo, contribuciones sobre la Teoría de la Mente y las habilidades mentalistas en distintos trastornos mentales para concluir con una presentación del PENpAR-IJ. En el presente artículo se recogen las Bases Psicológicas y en otros dos posteriores, las temáticas restantes (AU)
We review the psychological, neuroscience and biological contributions performed on the Relational Learning. They are considered the bases of the Protocol for the Neuropsychological Exploration of the Relational Learning-Child/Adolescent (PENpAR-IJ), designed by the first authoress and we work with in the Sec-tion of Child and Adolescent Psychiatry of the University Clinic Hospital Lozano Blesa of Zaragoza. It emphasizes the need to move towards integration of scientific knowledge about the mind. We review the contributions of the theory of mind in different mental disorders. And we conclude with the presentation of PENpAR-IJ. In this article we collect the Psychological Bases and in the others one the remaining topics (AU)
Subject(s)
Humans , Child , Adolescent , Learning , Emotions , Psychological Theory , Neuropsychology/methods , Child Psychiatry , Adolescent Psychiatry , Facial Expression , 35170ABSTRACT
En un artículo anterior se inicia la revisión de las aportaciones psicológicas, neurocientíficas y biológicas en las que se fundamenta el Protocolo de Exploración Neuropsicológica del Aprendizaje Relacional-InfantoJuvenil (PENpAR-IJ) diseñado por la primera autora y con el que se trabaja en la Sección de Psiquiatría Infanto-Juvenil del Hospital Clínico Universitario Lozano Blesa de Zaragoza. Se hará hincapié en la necesidad de integrar conocimientos científicos vigentes sobre la mente. Se revisarán así mismo, contribuciones sobre la Teoría de la Mente y las habilidades mentalistas en distintos trastornos mentales para concluir con una presentación del PENpAR-IJ. En el presente artículo se continúa la exposición de las bases psicológicas y neurocientíficas (AU)
In a previous paper starts reviewing the psychological contributions performed on the Relational Learning. They are considered the bases of the Protocol for the Neuropsychological Exploration of the Relational Learning-Child/Adolescent (PENpAR-IJ), designed by the first authoress and we work with in the Section of Child and Adolescent Psychiatry of the University Clinic Hospital Lozano Blesa of Zaragoza. It emphasizes the need to move towards integration of scientific knowledge about the mind. We review the contributions of the theory of mind in different mental disorders. And we conclude with the presentation of PENpAR-IJ. In this article we collect the Psychological Bases and in the others one the remaining topics. In this article we continue exposition of the psychological and neurosciencience bases (AU)
Subject(s)
Child , Adolescent , Humans , Learning , Emotions , Psychological Theory , Neuropsychology/methods , Child Psychiatry , Adolescent Psychiatry , 35170ABSTRACT
En artículos anteriores se inicia la revisión de las aportaciones psicológicas, neurocientíficas y biológicas en las que se fundamenta el Protocolo de Exploración Neuropsicológica del Aprendizaje Relacional-InfantoJuvenil (PENpAR-IJ) diseñado por la primera autora y con el que se trabaja en la Sección de Psiquiatría Infanto-Juvenil del Hospital Clínico Universitario Lozano Blesa de Zaragoza. Se hace hincapié en la necesidad de in-tegrar conocimientos científicos vigentes sobre la mente. Se revisan así mismo, contribuciones sobre la teoría de la mente y las habilidades mentalistas en distintos trastornos mentales para concluir con una presentación del PENpAR-IJ (AU)
In previous papers starts reviewing the contributions psychological, neuroscience and biological contributions perfor-med on the Relational Learning. They are considered the bases of the Protocol for the Neuropsychological Exploration of the Relational Learning-Child/Adolescent (PENpAR-IJ), designed by the first authoress and we work with in the Section of Child and Adolescent Psychiatry of the University Clinic Hospital Lozano Blesa of Zaragoza. It emphasizes the need to move towards integration of scientific knowledge about the mind. We review the contributions of the theory of mind in different mental disorders. And we conclude with the presentation of PENpAR-IJ (AU)
Subject(s)
Humans , Child , Adolescent , Learning , Emotions , Psychological Theory , Neuropsychology/methods , Child Psychiatry , Adolescent Psychiatry , 35170ABSTRACT
Se realiza una revisión de las aportaciones que fundamentan el concepto de apego y vinculación temprana como fenómenos que marcan el cauce para el desarrollo psicológico, la constitución del self y el establecimiento de relaciones objetales intra e interpersonales, así como la capacidad adaptativa de los individuos y sus sistemas familiares. A su vez, se relacionan con hallazgos neuropsicológicos y biológicos recientes. Se presenta una demanda clínica para ejemplificar la importancia de una sistemática de exploración e intervención en la primera infancia (AU)
A review of the contributions that underlie the concept of attachment and linking early as phenomena that mark the channel for the psychological development, the formation of self and the establishment of intra and interpersonal objectals relationships, as well as the adaptive capacity of individuals and their relatives. In turn, is related to recent findings neuropsychological and biological. It presents a clinical demand to exemplify the importance of a systematic exploration and intervention in early childhood (AU)
