Improvement in quality of life with sacubitril/ /valsartan in cardiac resynchronization non-responders: The RESINA (RESynchronization plus an Inhibitor of Neprilysin/Angiotensin) registry.

BACKGROUND: Clinical management of cardiac resynchronization therapy (CRT) non-responders is difficult, and their prognosis is poor. The aim of the present study was to evaluate whether treatment with sacubitril/valsartan can improve quality of life (QoL) parameters in these patients. METHODS: Thirty five non-responders to CRT were included (75 ± 7 years, 28% females, mean left ventricular ejection fraction 28 ± 8%, 54% non-ischemic cardiomyopathy) with maximally optimized drug therapy and New York Heart Association class II-III. They were all on angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers and were switched to sacubitril/valsartan. One week before and 6 months after initiation of the therapy they completed both the Minnesota Living with Heart Failure (MLWHF) and the 12-item Kansas City Cardiomyopathy Questionnaires (KCCQ-12). The primary outcome was the effect of sacubitril/valsartan on the physical, clinical, social and emotional QoL parameters and number of hospitalizations. RESULTS: The mean total scores of both questionnaires improved from baseline to the follow-up visit at 6-months (KCCQ-12 40 ± 10 to 47 ± 10; p < 0.001; MLWHF 40 ± 15 to 29 ± 15; p < 0.001). The best results were seen in the KCCQ-12 total symptom domains (77% improvement), the MLWHF physical domain (81% improvement), and the MLWHF emotional domain (71% improvement). Two patients died during follow-up. The mean number of hospitalizations reduced significantly (1 ± 0.6 vs. 0.5 ± 0.8; p = 0.003) CONCLUSIONS: In CRT non-responders, sacubitril/valsartan significantly improved overall QoL, physical limitations and emotional domains and reduced the number of hospitalizations.

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.

A novel simple, fast, and safe approach for effective superior vena cava isolation using the third-generation cryoballoon.

BACKGROUND: Superior vena cava (SVC) isolation with radiofrequency energy remains a challenge due to potential side effects, especially phrenic nerve (PN) or sinus node injury. The purpose of this study was to evaluate the feasibility of a novel SVC isolation technique using the third-generation cryoballoon (CB3). METHODS: Patients undergoing atrial fibrillation (AF) ablation were prospectively included. The procedure was performed with the CB3, beginning with the pulmonary veins and ending with SVC isolation. During applications in the SVC, continuous PN capture and sinus rate were monitored. Once reached SVC isolation during the application, 60 s more was applied, with no bonus application. If after 90 s the SVC was not isolated, application was stopped. A maximum number of four applications were permitted. RESULTS: Thirty patients (62 ± 9 years; 74% male, 78% paroxysmal AF) were included. No SVC activity was observed in two patients. Success rate for SVC isolation was 89%. Mean number of applications per patient was 2.3 ± 1. Mean time to SVC isolation was 37 ± 20  s. Mean duration of application was 92 ± 15 s. Mean total time of procedure for SVC isolation was 218 ± 43 s. We recorded only two complications: one transient PN palsy and one short and transient sinus arrest. After a mean follow-up of 5 ± 2 months, 89% are free from arrhythmia recurrence. CONCLUSIONS: We present a promising simple SVC-isolation technique using CB3, featuring a high success rate and very low incidence of complications.

Detecting Atrial Fibrillation in Patients With an Embolic Stroke of Undetermined Source (from the DAF-ESUS registry).

Atrial fibrillation (AF) causes a substantial proportion of embolic strokes of undeterminded source (ESUS). Effective detection of subclinical AF (SCAF) has important therapeutic implications. We conducted a prospective study to determine the prevalence of SCAF in patients with ESUS through of a 21-day Holter monitoring. In an early-monitoring group, Holter was initiated immediately after hospital discharge. The results were compared with a previous cohort of patients in whom the Holter was initiated at least 1 week after hospital discharge (late-monitoring group). We included 100 patients (50 each group; 69 ± 13 years, 56% male). Mean time from ESUS to Holter was 1.2 ± 1 day in the early-monitoring group and 30 ± 15 days in the late-monitoring group. SCAF was detected in 22% of patients in the early-monitoring and 6% in the late-monitoring group (p <0.05). Patients with SCAF were older (77 ± 9 vs 67 ± 11 years, p <0.05), with a higher rate of left atrial enlargement (50% vs 20%, p<0.05), renal impairment (28% vs 5%; p<0.01), and a slower mean heart rate (55 ± 6 vs 70 ± 6 beats/min; p<0.001). On multivariate analysis, the presence of persistent bradycardia (≤60 beats/min) in the 21-day Holter was a powerful and significant risk factor for SCAF. In conclusion, the sooner 21-day Holter electrocardiogram monitoring is initiated after ESUS, the more likely SCAF can be detected. Sinus bradycardia is a powerful predictor of SCAF in patients with ESUS.

P-wave and interatrial block: New predictor for atrial high rate episodes in patients with cardiac implantable electronic devices.

BACKGROUND: The presence of interatrial block (IAB) is associated with the development of atrial fibrillation (AF). The aim of this study was to determine whether P-wave duration and presence of IAB before the implantation of a cardiac implantable electronic device (CIED) are associated with the presence of atrial high rate episodes (AHRE), during long-term follow-up. METHODS: 380 patients (57% men; 75 ± 10 years) were included. IAB was defined according to the International Consensus Criteria. AHRE was defined as an episode of atrial rate ≥225 beats/min with a minimum duration of 5 minutes. RESULTS: Documented paroxysmal AF before the implantation was present in 24% of the patients; 80% had hypertension and 32% structural heart disease. Mean P-wave duration was 123 ± 23 ms, and 39% of the patients had IAB (32% partial, 7% advanced). After a mean follow-up of 18 ± 12 months, 33% of the patients presented AHRE. Patients with AHRE had a P-wave duration significantly longer (130 ± 24 ms vs 119 ± 21 ms; P < 0.001) and a greater prevalence of IAB (53% vs 32%; P < 0.001). In a multivariate analysis, predictors of AHRE were: IAB (odds ratio [OR] 2.1; 95% confidence interval [CI] [1.3-3.4], P < 0.001) and previous paroxysmal AF (OR 2.6; 95% CI [1.5-4.3], P < 0.001). In patients without previous AF, the presence of IAB was also a significant predictor of AHRE (OR 3.1; 95% CI [1.8-5.5], P < 0.001). CONCLUSIONS: IAB is a strong predictor of AHRE in patients with CIED. This finding is independent of the presence of prior paroxysmal AF.

Seguridad del implante ambulatorio de desfibrilador automático implantable / Safety of outpatient implantation of the implantable cardioverter-defibrillator

Introducción y objetivos. Es importante desarrollar estrategias que reduzcan los costes sanitarios y mejoren la atención de los pacientes. El objetivo de nuestro estudio es analizar la seguridad del implante ambulatorio de desfibriladores automáticos implantables. Métodos. Se estudió retrospectivamente a 401 pacientes consecutivos a los que se implantó un desfibrilador automático implantable entre 2007 y 2012. Se comparó la tasa de complicaciones relacionadas con la intervención de los 232 (58%) pacientes cuyo implante se programó como ambulatorio frente a los 169 (42%) intervenidos durante ingreso hospitalario. Resultados. La media de edad era 62 ± 14 años; 336 (84%) pacientes eran varones. Los pacientes ambulatorios tuvieron, en comparación con los hospitalizados, menor fracción de eyección del ventrículo izquierdo y mayor porcentaje de indicación por prevención primaria de muerte súbita. Sólo 21 pacientes (9%) del grupo ambulatorio requirieron ingreso hospitalario. La tasa de complicaciones hasta el tercer mes tras el implante fue similar en los dos grupos (el 6,0% en ambulatorios frente al 5,3% en ingresados; p = 0,763). En el análisis multivariable, solo el tratamiento anticoagulante previo se relacionó con la presencia de complicaciones (odds ratio = 3,2; intervalo de confianza del 95%, 1,4-7,4; p < 0,01), principalmente por un incremento en la tasa de hematomas de la bolsa del dispositivo. Cada implante ambulatorio supuso un ahorro de 735 euros. Conclusiones. El implante ambulatorio de desfibrilador automático implantable es seguro y reduce los costes. En pacientes con tratamiento anticoagulante crónico, se incrementa el riesgo de complicaciones, por lo que debería recomendarse un control específico (AU)

Introduction and objectives. Strategies are needed to reduce health care costs and improve patient care. The objective of our study was to analyze the safety of outpatient implantation of cardioverter-defibrillators. Methods. A retrospective study was conducted in 401 consecutive patients who received an implantable cardioverter-defibrillator between 2007 and 2012. The rate of intervention-related complications was compared between 232 patients (58%) whose implantation was performed in the outpatient setting and 169 patients (42%) whose intervention was performed in the inpatient setting. Results. The mean age (standard deviation) of the patients was 62 (14) years; 336 (84%) were male. Outpatients had lower left ventricular ejection fraction and a higher percentage had an indication for primary prevention of sudden death, compared to inpatients. Only 21 outpatients (9%) required subsequent hospitalization. The rate of complications until the third month postimplantation was similar for outpatients (6.0%) and inpatients (5.3%); P = .763. In multivariate analysis, only previous anticoagulant therapy was related to the presence of complications (odds ratio = 3.2; 95% confidence interval, 1.4-7.4; P < .01), mainly due to an increased rate of pocket hematomas. Each outpatient implantation saved approximately €735. Conclusions. Outpatient implantation of implantable cardioverter-defibrillators is safe and reduces costs. Close observation is recommended for patients receiving chronic anticoagulation therapy due to an increased risk of complications (AU)

Safety of Outpatient Implantation of the Implantable Cardioverter-defibrillator.

INTRODUCTION AND OBJECTIVES: Strategies are needed to reduce health care costs and improve patient care. The objective of our study was to analyze the safety of outpatient implantation of cardioverter-defibrillators. METHODS: A retrospective study was conducted in 401 consecutive patients who received an implantable cardioverter-defibrillator between 2007 and 2012. The rate of intervention-related complications was compared between 232 patients (58%) whose implantation was performed in the outpatient setting and 169 patients (42%) whose intervention was performed in the inpatient setting. RESULTS: The mean age (standard deviation) of the patients was 62 (14) years; 336 (84%) were male. Outpatients had lower left ventricular ejection fraction and a higher percentage had an indication for primary prevention of sudden death, compared to inpatients. Only 21 outpatients (9%) required subsequent hospitalization. The rate of complications until the third month postimplantation was similar for outpatients (6.0%) and inpatients (5.3%); P = .763. In multivariate analysis, only previous anticoagulant therapy was related to the presence of complications (odds ratio = 3.2; 95% confidence interval, 1.4-7.4; P < .01), mainly due to an increased rate of pocket hematomas. Each outpatient implantation saved approximately €735. CONCLUSIONS: Outpatient implantation of implantable cardioverter-defibrillators is safe and reduces costs. Close observation is recommended for patients receiving chronic anticoagulation therapy due to an increased risk of complications.