Ivabradine for controlling heart rate in permanent atrial fibrillation: A translational clinical trial.

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.

Seasonal influence on sleep apnoea recorded daily by pacemakers.

PURPOSE: Obstructive sleep apnoea (OSA) and cardiac conduction disorders are pathologies with a rising prevalence due to increased life expectancy. Upper airway patency is affected by environmental factors that may be associated with seasonal periods. The ability to record the degree of nocturnal apnoea on a daily basis may provide a more accurate picture of seasonal variability. METHODS: This study used an observational, cross-sectional design recruiting consecutive patients with Sorin/Livanova/Microport® pacemakers. The study assessed the seasonal influence on the daily degree of nocturnal apnoea over a minimum period of 180 days. The respiratory events were recorded using a pacemaker-integrated detection algorithm based on transthoracic impedance variation. A generalised linear repeated measure mixed model was used to study the seasonal effect. RESULTS: A sample of 101 subjects with a mean of 227 valid nights was compiled. Summer was associated with higher RDI (respiratory disturbance index) values and winter with lower values. The mean daily RDI ratio in summer was 1.099 times higher than in winter. CONCLUSIONS: Slight seasonal influences on the degree of nocturnal apnoea were detected through the daily observation of an unselected sample of pacemaker wearers. The degree of apnoea is higher in warmer months and lower in colder months.

Distinct spectral dynamics of implanted cardiac defibrillator signals in spontaneous termination of polymorphic ventricular tachycardia and fibrillation in patients with electrical and structural diseases.

AIMS: To determine the spectral dynamics of early spontaneous polymorphic ventricular tachycardia and ventricular fibrillation (PVT/VF) in humans. METHODS AND RESULTS: Fifty-eight self-terminated and 173 shock-terminated episodes of spontaneously initiated PVT/VF recorded by Medtronic implanted cardiac defibrillators (ICDs) in 87 patients with various cardiac pathologies were analyzed by short fast Fourier transform of shifting segments to determine the dynamics of dominant frequency (DF) and regularity index (RI). The progression in the intensity of DF and RI accumulations further quantified the time course of spectral characteristics of the episodes. Episodes of self-terminated PVT/VF lasted 8.6 s [95% confidence interval (CI): 8.1-9.1] and shock-terminated lasted 13.9 s (13.6-14.3) (P < 0.001). Recordings from patients with primarily electrical pathologies displayed higher DF and RI values than those from patients with primarily structural pathologies (P < 0.05) independently of ventricular function or antiarrhythmic drug therapy. Regardless of the underlying pathology, the average DF and RI intensities were lower in self-terminated than shock-terminated episodes [DF: 3.67 (4.04-4.58) vs. 4.32 (3.46-3.93) Hz, P < 0.001; RI: 0.53 (0.48-0.56) vs. 0.63 (0.60-0.65), P < 0.001]. In a multivariate analysis controlled by the type of pathology and clinical variables, regularity remained an independent predictor of self-termination [hazard ratio: 0.954 (0.928-0.980)]. Receiver operating characteristic (ROC) curve analysis of DF and RI intensities demonstrated increased predictability for self-termination in time with 95% CI above the 0.5 cut-off limit at about t = 8.6 s and t = 6.95 s, respectively. CONCLUSION: Consistent with the notion that fast organized sources maintain PVT/VF in humans, reduction of frequency and regularity correlates with early self-termination. Our findings might help generate ICD methods aiming to reduce inappropriate shock deliveries.

Impact of Coronavirus Disease 2019 on Cardiac Arrhythmia Care: Experience of a Spanish Tertiary Hospital During the Health Crisis Triggered by the First Wave of the Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has resulted in a deep restructuring of cardiovascular care, especially in the setting of cardiac arrhythmia units, which are characterized by a wide variety of clinical and interventional activities. We describe the experience of a large university hospital deeply hit during the COVID-19 health crisis (first outbreak of the pandemic), focusing on the exceptional measures implemented and their impact in terms of outcomes. We performed a retrospective study comparing the human and structural resources and the activity of a cardiac arrhythmia unit in a Spanish tertiary hospital for two consecutive periods: from January 12, 2020, to March 8, 2020 ("pre-COVID stage"), and from March 9, 2020, to May 2, 2020 ("COVID stage"). Data were contextualized within the number of confirmed COVID-19 cases in the region of Madrid. The measures implemented were promotion of non-face-to-face consultations, selection of urgent procedures, design of a "COVID-free" circuit for outpatient interventions, and protocolization for patients with COVID-19. A total of 3,526 consultations and 362 procedures were performed. During the COVID stage, the number of consultations remained stable, and the electrophysiology rooms' activity decreased by 55.2% with a relative increase in the number of urgent-hospitalized cases attended (11.8% COVID-19-positive patients). The electrophysiology rooms' activity returned to "normal" in the last week of the COVID stage, with no contagion being detected among patients or professionals. In conclusion, the measures implemented allowed us to respond safely and efficiently to the health care needs of patients with arrhythmias during the COVID-19 crisis and may be useful for other institutions facing similar situations.

Complete interatrial block in a left-atrial dependent atrioventricular node.

INTRODUCTION: A middle-age woman underwent an electrophysiologic study due to recurrent atypical atrial flutter. METHODS AND RESULT: Radiofrequency ablation of cavotricuspid isthmus and anterior mitral line was performed. During energy delivery on the anterior left atrial wall, interatrial dissociation and complete block of the sinus impulse to the atrioventricular (AV) node was observed. AV node activation became dependent on a subsidiary left atrial rhythm. CONCLUSION: Anatomical location of intra and inter-atrial connections must be taken into account when performing extensive ablation procedures, specially in cases with prior cardiac surgeries.

¿Hay un nuevo fármaco disponible para el control de la frecuencia cardiaca de pacientes con fibrilación auricular permanente? Respuesta / Do we have a new drug for heart rate control in patients with permanent atrial fibrillation? Response

No disponible

Primera experiencia en España de la modulación de la contractilidad cardiaca. Una nueva alternativa para los pacientes con insuficiencia cardiaca / First experience in Spain of cardiac contractility modulation. A new alternative for patients with heart failure

No disponible

Wolff Parkinson white pattern in Danon disease: When preexcitation is not what it seems.

Danondisease is a rare genetic disorder with an X-linked dominant inheritance affecting both skeletal and cardiac muscle. Its characteristic cardiac phenotype consists on a severe, non-obstructive and concentric hypertrophic cardiomyopathy (HCM) usually associated with a Wolff-Parkinson-White (WPW) type preexcitation pattern. Whether this corresponds to the presence of an AV or another type of accessory pathways, such as fasciculoventricular pathways (FVP) remains controversial in the literature. However, we describe the case of a teenager with Danon disease and preexcitation who develops a first degree AV block without any change in his QRS morphology, fact that favors the hypothesis of the presence of a FVP. This finding has important clinical implications in the management and prognosis of these complex patients. The absence of an AV accessory pathway decreases their risk of potential SCD in the context of a fast atrial arrhythmia and their chances of having a reentrant AV tachycardia.

Ivabradina para el control crónico de la frecuencia cardiaca en fibrilación auricular permanente. Diseño del proyecto BRAKE-AF / Ivabradine for chronic heart rate control in persistent atrial fibrillation. Design of the BRAKE-AF project

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

Ivabradine for chronic heart rate control in persistent atrial fibrillation. Design of the BRAKE-AF project.

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.

Resultados en España de la encuesta de la Sociedad Europea de Cardiología sobre terapia de resincronización cardiaca (CRT-Survey II) / Spanish results of the Second European Cardiac resynchronization therapy survey (CRT-Survey II)

Introducción y objetivos: Se describen los resultados en España de la segunda encuesta de la Sociedad Europea de Cardiología sobre terapia de resincronización cardiaca (CRT-Survey II) y se comparan con los de los demás países participantes. Métodos: Pacientes a los que se implantó un dispositivo de terapia de resincronización cardiaca entre octubre de 2015 y diciembre de 2016 en 36 centros participantes. Se recogieron datos sobre las características basales de los pacientes y del implante, y un seguimiento a corto plazo hasta el alta hospitalaria. Resultados: La tasa de éxito del implante fue del 95,9%. La mediana [intervalo intercuartílico] de implantes anuales/centro en España fue significativamente menor que en los demás países participantes: 30 [21-50] frente a 55 [33-100] implantes/año (p=0,00003). En los centros españoles hubo una menor proporción de pacientes de edad ≥ 75 años (el 27,9 frente al 32,4%; p=0,0071), una mayor proporción de pacientes en clase funcional II de la New York Heart Association (el 46,9 frente al 36,9%; p <0,00001) y un mayor porcentaje de pacientes con criterios electrocardiográficos de bloqueo de rama izquierda (el 82,9 frente al 74,6%; p <0,00001). La media de la estancia hospitalaria fue menor en los centros españoles (5,8+/-8,5 frente a 6,4+/-11,6; p <0,00001) y una mayor proporción de pacientes recibieron un cable de ventrículo izquierdo cuadripolar (el 74 frente al 56%; p <0,00001) y fueron seguidos a distancia (el 55,8 frente al 27,7%; p <0,00001). Conclusiones: La encuesta CRT-Survey II muestra que en España hay una menor proporción de pacientes de 75 o más años que reciben un dispositivo de terapia de resincronización cardiaca, una mayor proporción de pacientes en clase funcional II de la New York Heart Association, con bloqueo completo de la rama izquierda del haz de His y con seguimiento a distancia, con estancias hospitalarias significativamente menores

Introduction and objectives: We describe the results for Spain of the Second European Cardiac Resynchronization Therapy Survey (CRT-Survey II) and compare them with those of the other participating countries. Methods: We included patients undergoing CRT device implantation between October 2015 and December 2016 in 36 participating Spanish centers. We registered the patients' baseline characteristics, implant procedure data, and short-term follow-up information until hospital discharge. Results: Implant success was achieved in 95.9%. The median [interquartile range] annual implantation rate by center was significantly lower in Spain than in the other participating countries: 30 implants/y [21-50] vs 55 implants/y [33-100]; P=.00003. In Spanish centers, there was a lower proportion of patients ≥ 75 years (27.9% vs 32.4%; P=.0071), a higher proportion in NYHA class II (46.9% vs 36.9%, P <.00001), and a higher percentage with electrocardiographic criteria of left bundle branch block (82.9% vs 74.6%; P <.00001). The mean length of hospital stay was significantly lower in Spanish centers (5.8+/-8.5 days vs 6.4+/-11.6; P <.00001). Spanish patients were more likely to receive a quadripolar LV lead (74% vs 56%, P <.00001) and to be followed up by remote monitoring (55.8% vs 27.7%; P <.00001). Conclusions: The CRT-Survey II shows that, compared with other participating countries, fewer patients in Spain aged ≥ 75 years received a CRT device, while more patients were in New York Heart Association functional class II and had left bundle branch block. In addition, the length of hospital stay was shorter, and there was greater use of quadripolar LV leads and remote CRT monitoring

Subcutaneous implantable cardioverter defibrillators in patients with left ventricular assist devices: case report and comprehensive review.

BACKGROUND: Left ventricular assist devices (LVAD) are increasingly used in patients with advanced heart failure, many of whom have been or will be implanted with an implantable cardioverter defibrillator (ICD). Interaction between both devices is a matter of concern. Subcutaneous ICD (S-ICD) obtains its signals through subcutaneous vectors, which poses special challenges with regards to adequate performance following LVAD implantation. CASE SUMMARY: We describe the case of a 24-year-old man implanted with an S-ICD because of idiopathic dilated cardiomyopathy, severe biventricular dysfunction, and self-limiting sustained ventricular tachycardias. After the implantation of a HeartMate 3™ (Left Ventricular Assist System, Abbott) several months later, the S-ICD became useless because of inappropriate sensing due to electromagnetic interference and attenuation of QRS voltage. DISCUSSION: We reviewed the reported cases in PubMed about the concomitant use of S-ICD and LVAD. Seven case reports about the performance of S-ICD in patients with an LVAD were identified, with discordant results. From these articles, we analyse the potential causes for these differing results. Pump location and operating rates in LVAD, as well as changes in the subcutaneous-electrocardiogram detected by the S-ICD after LVAD implantation are related to sensing disturbances when used in the same patient.