Exploring the interplay between extracellular pH and Dronedarone's pharmacological effects on cardiac function.

Dronedarone (DRN) is a clinically used drug to mitigate arrhythmias with multichannel block properties, including the sodium channel Nav1.5. Extracellular acidification is known to change the pharmacological properties of several antiarrhythmic drugs. Here, we explore how modification in extracellular pH (pHe) shapes the pharmacological profile of DRN upon Nav1.5 sodium current (INa) and in the ex vivo heart preparation. Embryonic human kidney cells (HEK293T/17) were used to transiently express the human isoform of Nav1.5 α-subunit. Patch-Clamp technique was employed to study INa. Neurotoxin-II (ATX-II) was used to induce the late sodium current (INaLate). Additionally, ex vivo Wistar male rat preparations in the Langendorff system were utilized to study electrocardiogram (ECG) waves. DRN preferentially binds to the closed state inactivation mode of Nav1.5 at pHe 7.0. The recovery from INa inactivation was delayed in the presence of DRN in both pHe 7.0 and 7.4, and the use-dependent properties were distinct at pHe 7.0 and 7.4. However, the potency of DRN upon the peak INa, the voltage dependence for activation, and the steady-state inactivation curves were not altered in both pHe tested. Also, the pHe did not change the ability of DRN to block INaLate. Lastly, DRN in a concentration and pH dependent manner modulated the QRS complex, QT and RR interval in clinically relevant concentration. Thus, the pharmacological properties of DRN upon Nav1.5 and ex vivo heart preparation partially depend on the pHe. The pHe changed the biological effect of DRN in the heart electrical function in relevant clinical concentration.

Interaction of the antiarrhythmic drug Amiodarone with the sodium channel Nav1.5 depends on the extracellular pH.

INTRODUCTION: Amiodarone (AMD) is a clinically used drug to treat arrhythmias with significant effect upon the cardiac sodium channel Nav1.5. AMD has a pKa of 6.56, and changes in extracellular pH (pHe) may alter its pharmacological properties. Here we explored how changes in pHe impacts the pharmacological properties of AMD upon human-Nav1.5-sodium-current (INa) and in ex vivo rat hearts. METHODS: Embryonic-human-kidney-cells (HEK293) were used to transiently express the human alpha-subunit of NaV1.5 channels and the isolated heart of Wistar rats were used. Patch-Clamp technique was deployed to study INa and for electrocardiogram (ECG) evaluation the ex vivo heart preparation in the Langendorff system was applied. RESULTS: The potency of AMD upon peak INa was ∼25x higher in pHe 7.0 when compared to pHe 7.4. Voltage dependence for activation did not differ among all groups. AMD shifted the steady-state inactivation curve to more hyperpolarized potentials, with similar magnitudes for both pHes. The recovery from INa inactivation was delayed in the presence of AMD with similar profile in both pHes. Interestingly, the use-dependent properties of AMD was distinct at pHe 7.0 and 7.4. Finally, AMD was able to change the ex vivo ECG profile, however at pHe 7.0+AMD a larger increase in the RR and QRS duration and in the QT interval when compared to pHe 7.4 was found. CONCLUSIONS: The pharmacological properties of AMD upon NaV1.5 and isolated heart preparation depends on the pHe and its use in vivo during extracellular acidosis may cause a distinct biological response in the heart tissue.

Efecto electromecánico de los antiarrítmicos clase Ic durante el tratamiento de arritmias auriculares en cardiopatías congénitas / Electromechanical effect of Ic class antiarrhythmic drugs during the treatment of atrial arrhythmias in congenital heart diseases

Introducción: los fármacos antiarrítmicos son la primera línea de tratamiento para el control de las taquiarritmias en el paciente pediátrico. La terapéutica con drogas clase Ic en los pacientes con cardiopatías congénitas ha sido limitada, por los reportes que demostraron incremento de la mortalidad en los sujetos con cardiopatías estructurales. Objetivo: valorar el efecto de los antiarrítmicos clase Ic sobre los fenómenos electro-mecánicos cardiacos en los niños con cardiopatías congénitas con arritmias auriculares. Métodos: se realizó un estudio analítico, observacional, longitudinal y prospectivo en los pacientes con cardiopatías congénitas que desarrollaron arritmias auriculares, tratados con antiarrítmicos clase Ic en el Cardiocentro Pediátrico William Soler Se analizaron variables electrocardiográficas, así como estimación de la función sistodiastólica mediante el ecocardiograma. Resultados: fueron evaluados 46 pacientes, 25 tratados con flecainida (grupo I) y 21 con propafenona (grupo II) durante 4,57±0,86 años. La taquicardia por reentrada intraatrial fue la arritmia de mayor incidencia (58,69 por ciento), mientras que, la tetralogía de Fallot, el defecto cardiaco más común (36,9 por ciento). Las variables electrocardiográficas no sufrieron variaciones nítidas durante el seguimiento. El análisis comparativo intragrupal demostró la preservación de la función sistólica en la totalidad de los sujetos (I, p= 0,275; II, p= 0,262). Comportamiento análogo exhibió la función diastólica, expresada en el índice de Tei (I, p= 0,244; II, p= 0,286). Conclusiones: la utilización de antiarrítmicos clase Ic en los pacientes pediátricos con cardiopatías congénitas no se asocia a largo plazo con alteraciones electrocardiográficas significativas ni compromiso de la función sistodiastólica, por lo que se recomienda su uso en esta población(AU)

Introduction: antiarrhythmic drugs are the first line of treatment for the control of tachyarrhythmias in pediatric patients. Therapy with Ic class drugs in patients with congenital heart disease has been limited, mainly due to reports that showed an increase in mortality in patients with structural heart disease. Objective: to assess the effect of Ic class antiarrhythmic drugs on cardiac electro-mechanical phenomena in children with congenital heart disease with atrial arrhythmias. Methods: an analytical, observational, longitudinal and prospective study was performed in patients with congenital heart diseases who developed atrial arrhythmias treated with Ic class antiarrhythmic drugs in William Soler Pediatric Cardiocenter. Electrocardiographic variables were analyzed, as well as the estimation of systo-diastolic function by echocardiography. Results: 46 patients were evaluated, 25 treated with flecainide (group I) and 21 with propafenone (group II) during 4.57 ± 0.86 years. The intra-atrial reentrant tachycardia was the arrhythmia with the highest incidence (58.69 percent); while tetralogy of Fallot was the most common cardiac defect (36.9 percent). The electrocardiographic variables did not undergo sharp variations during the follow-up. The intergroup comparative analysis showed the preservation of systolic function in all subjects (I, p= 0.275; II, p= 0.262). Analogous behavior showed diastolic function, that was expressed in the Tei index (I, p= 0.244; II, p= 0.286). Conclusions: the use of Ic class antiarrhythmic drugs in pediatric patients with congenital heart disease is not associated in the long term with significant electrocardiographic alterations or compromise of systo-diastolic function, so its use is recommended in this population(AU)

Implantable cardioverter-defibrillator in Chagas heart disease: A systematic review and meta-analysis of observational studies.

BACKGROUND: In patients with Chagas cardiomyopathy (ChCM), sudden cardiac death (SCD) is the leading cause of mortality. Implantable cardioverter-defibrillator (ICD) is a well-established therapy for secondary prevention in patients with structural heart disease, but there are conflicting opinions regarding its efficacy and safety in patients with ChCM. The aim of this meta-analysis was to assess the efficacy of the ICD for secondary prevention in patients with ChCM, comparing mortality as the primary outcome of patients treated with ICD with those treated with amiodarone. METHODS: We systematically searched five databases for studies assessing mortality outcomes in patients with ChCM and sustained ventricular tachycardia (VT) treated with ICD implantation or with amiodarone. The results of studies were pooled using random-effects modeling. RESULTS: There was no randomized clinical trial comparing efficacy of ICD versus medical treatment in patients with ChCM. Six observational studies were included, totalizing 115 patients in amiodarone group and 483 patients in ICD group. The mortality outcome in the ICD population was 9.7 per 100 patient-years of follow-up (95%CI 5.7-13.7) and 9.6 per 100 patient-years in the amiodarone group (95%CI 6.7-12.4) (p = 0.95). Meta-regression did not show any association with LV ejection fraction (p = 0.32), age (p = 0.44), beta-blocker (p = 0.33) or angiotensin-converting enzyme inhibitors (p = 0.096) usage. CONCLUSION: The best available evidence derived from small observational studies suggests that ICD therapy in secondary prevention of sudden death (VT or resuscitated SCD) is not associated with lower rate of all-cause mortality in patients with ChCM. Randomized controlled trials are needed to answer this question.

Efecto electromecánico de los antiarrítmicos clase Ic durante el tratamiento de arritmias auriculares en cardiopatías congénitas / Electromechanical effect of Ic class antiarrhythmic drugs during the treatment of atrial arrhythmias in congenital heart diseases

Introducción: los fármacos antiarrítmicos son la primera línea de tratamiento para el control de las taquiarritmias en el paciente pediátrico. La terapéutica con drogas clase Ic en los pacientes con cardiopatías congénitas ha sido limitada, por los reportes que demostraron incremento de la mortalidad en los sujetos con cardiopatías estructurales. Objetivo: valorar el efecto de los antiarrítmicos clase Ic sobre los fenómenos electro-mecánicos cardiacos en los niños con cardiopatías congénitas con arritmias auriculares. Métodos: se realizó un estudio analítico, observacional, longitudinal y prospectivo en los pacientes con cardiopatías congénitas que desarrollaron arritmias auriculares, tratados con antiarrítmicos clase Ic en el Cardiocentro Pediátrico William Soler . Se analizaron variables electrocardiográficas, así como estimación de la función sistodiastólica mediante el ecocardiograma. Resultados: fueron evaluados 46 pacientes, 25 tratados con flecainida (grupo I) y 21 con propafenona (grupo II) durante 4,57±0,86 años. La taquicardia por reentrada intraatrial fue la arritmia de mayor incidencia (58,69 por ciento), mientras que, la tetralogía de Fallot, el defecto cardiaco más común (36,9 por ciento). Las variables electrocardiográficas no sufrieron variaciones nítidas durante el seguimiento. El análisis comparativo intragrupal demostró la preservación de la función sistólica en la totalidad de los sujetos (I, p= 0,275; II, p= 0,262). Comportamiento análogo exhibió la función diastólica, expresada en el índice de Tei (I, p= 0,244; II, p= 0,286). Conclusiones: la utilización de antiarrítmicos clase Ic en los pacientes pediátricos con cardiopatías congénitas no se asocia a largo plazo con alteraciones electrocardiográficas significativas ni compromiso de la función sistodiastólica, por lo que se recomienda su uso en esta población(AU)

Introduction: antiarrhythmic drugs are the first line of treatment for the control of tachyarrhythmias in pediatric patients. Therapy with Ic class drugs in patients with congenital heart disease has been limited, mainly due to reports that showed an increase in mortality in patients with structural heart disease. Objective: to assess the effect of Ic class antiarrhythmic drugs on cardiac electro-mechanical phenomena in children with congenital heart disease with atrial arrhythmias. Methods: an analytical, observational, longitudinal and prospective study was performed in patients with congenital heart diseases who developed atrial arrhythmias treated with Ic class antiarrhythmic drugs in William Soler Pediatric Cardiocenter. Electrocardiographic variables were analyzed, as well as the estimation of systo-diastolic function by echocardiography. Results: 46 patients were evaluated, 25 treated with flecainide (group I) and 21 with propafenone (group II) during 4.57 ± 0.86 years. The intra-atrial reentrant tachycardia was the arrhythmia with the highest incidence (58.69 percent); while tetralogy of Fallot was the most common cardiac defect (36.9 percent). The electrocardiographic variables did not undergo sharp variations during the follow-up. The intergroup comparative analysis showed the preservation of systolic function in all subjects (I, p= 0.275; II, p= 0.262). Analogous behavior showed diastolic function, that was expressed in the Tei index (I, p= 0.244; II, p= 0.286). Conclusions: the use of Ic class antiarrhythmic drugs in pediatric patients with congenital heart disease is not associated in the long term with significant electrocardiographic alterations or compromise of systo-diastolic function, so its use is recommended in this population(AU)

Electrical Storm in Patients with Implantable Cardioverter-defibrillators: A Practical Overview.

Electrical storm (ES) is an increasingly common medical emergency characterized by clustered episodes of sustained ventricular arrhythmias (VAs) that lead to repeated appropriate implantable cardioverter-defibrillator (ICD) therapies. A diagnosis of ES can be made with the occurrence of three or more sustained episodes of VAs, or of three or more appropriate ICD therapies within 24 hours in patients with implanted devices. ES is associated with poor outcomes in patients with structural heart disease, particularly those with severe left ventricular dysfunction. In large clinical trials involving patients with ICDs for primary and secondary prevention, ES appears to be a predictor of cardiac death, with notably higher rates of mortality soon after the event. ES management is challenging and requires special medical attention with accurate patient risk stratification and a multidisciplinary approach that includes the use of pharmacologic therapies such as antiarrhythmic drugs (AADs) and interventional approaches like catheter ablation, surgical ablation, or sympathetic neuromodulation. Initial management involves determining and addressing the underlying ischemia, any electrolyte imbalances, and/or other causative factors. Hemodynamic support needs to be considered in high-risk patients with unstable VAs or those with severe comorbidities such as low left ventricular ejection fraction, advanced New York Heart Association class, and/or chronic pulmonary disease. Following the acute phase of ES, treatment should shift towards maximizing therapeutic efforts to address heart failure, performing revascularization, and preventing subsequent VAs. In the present manuscript, we offer an overview of the most relevant clinical aspects of ES with regard to novel therapeutic strategies.

Estado actual de la ablación de la fibrilación auricular / Current status on atrial fibrillation ablation

La fibrilación auricular es la arritmia más común en la práctica clínica. La ablación se considera el tratamiento de elección (indicación clase I) en los pacientes sintomáticos con recurrencias a pesar del tratamiento con fármacos antiarrítmicos. El presente artículo revisa tanto los mecanismos propuestos de esta arritmia como las diferentes metodologías de ablación con catéter y sus indicaciones.

Summary Atrial fibrillation is the most common arrhythmia in clinical practice. Catheter ablation is the treatment of choice (Class I indication) for symptomatic patients with recurrences despite antiarrhythmic drugs. The present article reviews the proposed mechanisms of this arrhythmia and the different ablation methods and indications.

Atrial fibrillation: an observational study with outpatients.

BACKGROUND: Atrial fibrillation (AF) is the most common sustained arrhythmia with serious clinical consequences in the absence of treatment. However, there are limited data on the treatment of these patients in Argentina. The objective was to describe the therapeutic management of patients with nonacute AF by Argentinean cardiologists and to determine the incidence of clinical events after 12 months follow-up. METHODS: The Atrial Fibrillation study in Argentina (FARAON) was an observational, descriptive, prospective, national, and multicentric study that included outpatients with AF, followed for 12 months. The study included 38 sites in Argentina. Each researcher included the first 10 patients who met the inclusion criteria of being over 21 and also being an AF carrier documented by electrocardiogram or Holter within 12 months prior to or at the time of enrollment. RESULTS: A total of 373 patients were included, mean age 70 ± 11.5 years, 40% women; 65% had AF rhythm at the time of inclusion, 57% had permanent AF, and 56% were asymptomatic. At the time of enrollment, 40% of physicians opted for rhythm control strategy. ß-blockers and amiodarone were the most used drugs. Patients with rhythm control drugs had higher success rate than those with frequency control drug therapy (80% vs 57%). CONCLUSION: Cardiologists in Argentina receive patients with AF that are mostly permanent AF. More than half of the patients are asymptomatic. They opt primarily by controlling the pace. When choosing antiarrhythmic drugs, nearly half of them indicated amiodarone.

EFECTO DEL FÁRMACO CLOROQUINA EN LA TERMINACIÓN DE UN ROTOR DURANTE FIBRILACIÓN AURICULAR PAROXÍSTICA. ESTUDIO DE SIMULACIÓN / CHLOROQUINE DRUG EFFECT ON A ROTOR TERMINATION DURING PAROXYSMAL ATRIAL FIBRILLATION. A SIMULATION STUDY / O EFEITO DO MEDICAMENTO CLOROQUINA NO FECHAMENTO DE UM ROTOR DURANTE FIBRILAÇÃO ATRIAL PAROXÍSTICA. SIMULAÇÃO ESTUDO

La fibrilación auricular (FA) es la arritmia más común. Algunos episodios de FA son mantenidos por rotores. La FA paroxística (FAp) se refiere a episodios recurrentes que se autolimitan. Si la FAp no se trata puede convertirse en crónica. Se ha demostrado que la inhibición de las corrientes I KACh e I K1 contribuye a la terminación de la FA. El fármaco antimalárico cloroquina, al inhibir estas corrientes podría ser un fármaco antiarrítmico eficaz en humanos. El objetivo del trabajo es simular los efectos de la cloroquina y estudiar su eficacia en la terminación de un rotor en condiciones de FAp. Para esto, se desarrolló un modelo 2D de tejido auricular en condiciones de FAp. Se implementó un modelo del efecto de la cloroquina sobre las corrientes I K1 e I KACh para estudiar su eficacia en la terminación de un rotor simulado. La cloroquina alargó el potencial de acción a medida que se incrementó su concentración. A concentraciones de 0.3 µM y superiores, finalizó la actividad del rotor. Este es el primer trabajo que ha desarrollado modelos matemáticos del fármaco cloroquina para estudiar su efecto en la terminación de un rotor. Los resultados sugieren que la cloroquina podría ser un potente agente antiarrítmico en el tratamiento de la FAp.

Atrial fibrillation (AF) is the most common arrhythmia. Some AF episodes are maintained by rotors. Paroxysmal AF (pAF) refers to self-limiting recurrent episodes. If the pAF is not treated it could become chronic. It has been demonstrated that inhibition of the I K1 and I KACh currents contributes to AF termination. Antimalarial drug chloroquine by inhibiting these currents could be an effective antiarrhythmic drug in humans. The aim of this work is to simulate the effects of chloroquine and study their effectiveness in the rotor termination in pAF conditions. For this, we developed a 2D model of atrial tissue under pAF conditions. We implemented a model of the effect of chloroquine on I K1 and I KACh currents to study its effectiveness in the termination of a simulated rotor. Chloroquine lengthened the action potential as the concentration increased. At concentrations of 0.3 µM and higher, the activity of the rotor finished. This is the first work that developed a chloroquine mathematical models to study its effect on the rotor termination. The results suggest that chloroquine could be a potent antiarrhythmic drug for the pAF treatment.

A fibrilhação auricular (FA) é a arritmia mais comum. Alguns episódios de FA são mantidos por rotores. A FA paroxística (FAp) refere-se a episódios recorrentes que são autolimitantes. Se a FAP não tem nenhum tratamento, pode se tornar crônica. Tem sido demonstrado que a inibição das correntes I KACh e I K1 contribui para o término da AF. O medeicamento antimalárico cloroquina, para inibir essas correntes poderia ser um medicamento anti-arrítmico eficaz em seres humanos. O objetivo deste trabalho é simular os efeitos da cloroquina e estudar a sua eficácia na terminação de um rotor capaz em condições FAp. Para isso, um modelo 2D foi desenvolvido de tecido auricular em condições de FAp. foi implementado um modelo do efeito da Cloroquina sobre as corrente I K1 e I KACh para estudar a sua eficácia na terminação de um rotor simulado. A Cloroquina alongou o potencial de ação na medida em que foi aumentada a sua concentração. Em concentrações de 0,3 µM e superiores, terminou a atividade do rotor. Este é o primeiro trabalho que desenvolveu modelos matemáticos do medicamento cloroquina para estudar seu efeito sobre a terminação de um rotor. Os resultados sugerem que a cloroquina poderia ser um potente agente anti-arrítmico para o tratamento de FAp.

Principios básicos de las nuevas estrategias farmacológicas antiarrítmicas en fibrilación auricular / Basic mechanisms of the new antiarrhythmic drugs in atrial fibrillation

La fibrilación auricular (FA) es la arritmia crónica sostenida más frecuente en la población general. A pesar de los últimos avances tecnológicos y en el entendimiento de sus mecanismos, derivados de modelos experimentales, así como de los procedimientos de ablación en pacientes con FA, los fármacos antiarrítmicos siguen siendo la principal estrategia para la cardioversión y mantenimiento del ritmo sinusal. Nuevas generaciones de fármacos antiarrítmicos han llegado a la práctica clínica, y otros se encuentran en fase de experimentación. Los nuevos fármacos actúan de forma más específica sobre corrientes iónicas auriculares, y al mismo tiempo involucradas en el mantenimiento de la arritmia. Paralelamente, cada vez se da más importancia a la necesidad de actuar sobre el sustrato arritmogénico auricular y los factores que lo promueven, implicados en el mantenimiento a largo plazo de la arritmia (terapias upstream). La presente revisión tiene como objetivo exponer las actuales líneas de desarrollo en fármacos antiarrítmicos y terapias para prevención o retraso del remodelado auricular, con base a los conocimientos mecanísticos que hoy en día se involucran en el mantenimiento de la FA.

Atrial fibrillation (AF) is the most common sustained arrhythmia seen in clinical practice. Despite of new technological breakthroughs and the understanding of the mechanisms underlying AF, based on animal models and ablation procedures in patients, the antiarrhythmic drugs remain the main therapeutic strategy to restore and maintain the sinus rhythm. New antiarrhythmic drugs are already available in the clinical practice and many others are under development. The new antiarrhythmic drugs have the capability to block atrial-specific ionic currents, which are involved in the maintenance of the arrhythmia. Parallel, increasing evidence supports the use of compounds to regulate the arrhythmogenic atrial substrate involved in the long-term maintenance of the arrhythmia (upstream therapies). This article reviews the new antiarrhythmic drugs and upstream therapies, based on the current knowledge of the mechanisms involved in the maintenance of AF.

Taquicardia ectópica congénita de la unión: Tratamiento farmacológico en el primer año de vida / Congenital junctional ectopic tachycardia: Pharmacologic management during infancy

La forma congénita de la taquicardia ectópica de la unión (TEU) es una arritmia poco frecuente que suele presentar dificultades en su manejo farmacológico, con altas tasas de morbilidad y mortalidad. El objetivo de este trabajo fue informar la experiencia en el seguimiento y el tratamiento de esta forma de taquicardia supraventricular en pacientes menores de un año. Se identificaron siete pacientes con TEU congénita en 28 meses de seguimiento entre 2008 y 2010. El diagnóstico fue realizado en el primer día de vida en cuatro pacientes y dentro de los 150 días de vida en los 3 restantes. Sólo dos presentaron miocardiopatía dilatada. Ninguno presentó cardiopatía estructural. Se utilizó amiodarona en todos los pacientes, en un caso como única droga, asociándose a propanolol en cuatro. En un paciente se asoció flecainida a estos dos fármacos y en otro se la combinó con amiodarona. En un tiempo de seguimiento con un rango de 1-28 meses (media 12.2 meses, mediana 9.75 meses) en tres de los pacientes se consiguió obtener ritmo sinusal alternante con taquicardia nodal lenta; ninguno presentó efectos adversos secundarios a la medicación, ni deterioro de la función ventricular. Hubo sólo una muerte en el grupo estudiado. En conclusión, la combinación de fármacos antiarrítmicos (amiodarona más propranolol y eventualmente flecainida) constituye una alternativa válida para un adecuado control de la TEU congénita en pacientes menores de un año de edad.

Congenital junctional ectopic tachycardia (JET) is a rare arrhythmia that can be refractory to medical therapy with high morbidity and mortality rates. The aim of this study was to report our experience with pharmacologic management of congenital JET in infants. Seven patients with congenital JET were identified between 2008 and 2010. Only two of them presented dilated cardiomyopathy. There were no congenital structural defects. Amiodarone was given to all the patients, as single therapy in one, and in combination with propranolol in four. In one patient flecainide was administered together with amiodarone and propranolol, and in another patient was used combined with amiodarone. During follow- up with an average time of 12.2 months (median 9.75 months, range 1-28 months), sinus rhythm alternating with slow junctional tachycardia was successfully achieved in 3 patients; no side effects were detected. There was only one death in our study group. The combination of different antiarrhythmics (amiodarone plus propranolol, and eventually flecainide) is a valid option for rhythm control and management of JET in infants.

Diseño de un registro multicéntrico para evaluar control de ritmo contra control de la frecuencia en fibrilación auricular: Registro Mexicano de Fibrilación Auricular (ReMeFA) / Design of a multicenter registry to evaluate rhythm versus rate control in atrial fibrillation: Atrial Fibrillation Mexican Registry (ReMeFA)

La fibrilación auricular es una arritmia muy frecuente y afecta predominantemente a individuos mayores de 70 años. Se dispone de poca información sobre su manejo en México por lo que se diseñó el Registro Mexicano de Fibrilación Auricular (ReMeFA). Método: Se trata de un estudio multicéntrico, observacional, prospectivo sobre el tratamiento de la fibrilación auricular. Se incluyeron sujetos de ambos géneros, mayores de 18 años de edad, con fibrilación auricular documentada. Se excluyeron aquellos con fibrilación auricular secundaria a una causa reversible, sometidos a ablación de venas pulmonares (quirúrgica o por catéter), portadores de marcapasos o desfibriladores, aquellos con expectativa de vida menor a un año o incapacitados física o mentalmente para cumplir con los requisitos del protocolo. Se recolectaron datos clínicos y demográficos en forma basal y en visitas programadas a los seis y doce meses. Especialmente, se recabó información acerca del tratamiento farmacológico para control del ritmo o de la frecuencia. Resultados preliminares: Entre el ocho de diciembre y el 29 de julio de 2009 se incluyeron 1201 pacientes provenientes de 79 centros, con diagnóstico de fibrilación auricular. Conclusión: El registro proporcionará información valiosa sobre las estrategias actualmente empleadas en la República Mexicana para el tratamiento de la fibrilación auricular, sea mediante control del ritmo o control de la frecuencia.

Atrial fibrillation is the most common arrhythmia, predominantly affecting individuals older than 70 years of age. There is little information about its management in Mexico, for this purpose the Mexican Registry of Atrial Fibrillation (ReMeFa) was designed. Methods: ReMeFA is a prospective multicentric, observational registry concerning the treatment of atrial fibrillation in Mexico. It includes patients 18 years and older, from both genders, with documented atrial fibrillation. Patients with secondary atrial fibrillation from a reversible cause, previous treatment with pulmonary vein ablation (percutaneous or surgical), pacemakers or defibrillators, and with a life expectancy of less than one year, physically or mentally impaired for completing the protocol were excluded. Clinical and demographic data were collected at enrollment and in two scheduled visits at 6 and 12 months. Information about pharmacologic treatment for rhythm or rate control was particularly obtained. Preliminary results: Between December 2008 to July 2009, 1201 patients from 79 centers were enrolled. Conclusion: This registry will provide valuable information about the strategy chosen by physicians in Mexico for the treatment of atrial fibrillation.

Pulmonary Vein Sleeves as a Pharmacologic Model for the Study of Atrial Fibrillation.

OBJECTIVES: To review the electrophysiologic effects of antiarrhythmic agents in pulmonary veins (PV) sleeve preparations. BACKGROUND: Ectopic activity arising from the PV plays a prominent role in the development of atrial fibrillation. METHODS: Transmembrane action potentials were recorded from canine superfused left superior or inferior PV sleeves using standard microelectrode techniques. Acetylcholine (ACh, 1 µM), isoproterenol (1 µM), high calcium ([Ca2+]o=5.4mM) or a combination was used to induce early or delayed afterdepolarizations (EADs or DADs) and triggered activity. RESULTS: In canine PV sleeves, ranolazine (10 µM) induced a marked use-dependent decrease in Vmax, a rate-dependent abbreviation of action potential duration (APD), but a rate-dependent increase in effective refractory period due to the development of post-repolarization refractoriness and eliminates rate-dependent delayed and late phase 3 early afterdepolarizations (DADs and EADs)-induced triggered activity induced by high calcium, isoproterenol, acetylcholine of their combination together with rapid pacing. Chronic amiodarone induced a prolongation of APD, a marked decrease in Vmax, and prevented the development of DADs and late phase 3 EADs-induced triggered activity. Combination of ranolazine and chronic amiodarone act synergistically to cause potent use-dependent depression of sodium channel-dependent parameters in PV sleeves but not ventricular tissues. CONCLUSIONS: The PV sleeve preparation is a useful model for the study of pharmacologic agents for the treatment of atrial fibrillation. The effectiveness of these agents in arrhythmias induced in PV sleeves may indicate an antiarrhythmic action in eliminating the triggers responsible for AF.

Fibrilação atrial aguda na unidade de emergência: qual a droga ideal para rápida reversäo ao ritmo sinusal? / Acute Atrial Fibrillation. Which is the Best Drug for Sinus Rhythm Conversion in the Emergency Room ?

Objetivo - Comparar o tempo e o índice de sucesso para reversäo da fibrilaçäo atrial (FA) aguda, com o uso de amiodarona, procainamida ou quinidina. Métodos - Aleatoriamente, 60 pacientes com FA aguda foram divididos em três grupos, recebendo o grupo quinidina (GQ), constituído de 21 pacientes, digital EV + quinidina até 600mg VO; o grupo procainamida (GP) com 23 pacientes, digital EV + 10mg/kg de procainamida EV e o grupo amiodarona (GA), com 16 pacientes 5mg/kg de amiodarona EV. O período de observaçäo foi de no máximo 4h, através de Holter. Na análise estatíca foi utilizado o teste de x2 com o método de Kruskall-Wallis, considerando-se significativo p<0,05. Resultados - Os três grupos foram similares quanto a idade, sexo e tempo de instalaçäo da FA. A reversäo ocorreu em 71,4 por cento dos casos no GQ, em 47,8 por cento no GP e em 50 por cento no GA, (p>0,05). O tempo para reversäo em minutos foi de 112 + ou - 43 no G!, de 44,1 + ou - 28 no GP, de 20 + ou - 13 no GA, sendo menor e estatisticamente significante no GP e, principalmente, no GA (p= 0,001) em relaçäo ao GQ. Os efeitos colaterais foram mais freqüentes no GP, embora sem significância estatística. Conclusäo - A amiodarona, especialmente na ausência de cardiopatia de base, é uma boa opçäo para maior rapidez na reversäo da FA, enquanto a quinidina propicia maior taxa de reversäo, com menos efeitos colaterais