Response rate in cardiac resynchronization therapy patients implanted with a left ventricular quadripolar lead and the MultiPoint™ pacing feature early activated. QUARTO III.

BACKGROUND: Although cardiac resynchronization therapy (CRT) is beneficial in most heart failure patients, up to 40% do not respond to CRT. It has been suggested that multipoint left ventricle pacing (MPP) would increase the response rate. AIM: To assess the CRT response rate at 6 months in patients implanted with a CRT device with the MPP feature activated early after the implant. METHODS: This was a multicentre, prospective, open-label and non-randomized study. The primary endpoint was response to biventricular pacing defined as >15% relative reduction in left ventricular end-systolic volume (LVESV) comparing echocardiography measurements performed at baseline and 6 months by a core laboratory. Among secondary endpoints the combined endpoint of mortality or all-cause hospitalizations was evaluated. Primary study endpoint and clinical outcomes were compared to a Quarto II control cohort. RESULTS: Totally, 105 patients were included. The response rate was 64.6% (97.5% lower confidence bound 53%). Mean relative reduction in LVESV was 25.3%, and mean absolute increase in LVEF was 9.4%. The subjects with device programmed using anatomical approach showed a trend towards higher responder rate than those using the electrical approach (72% vs. 61.1%, p = 0.32). Finally, the combined incidence of mortality and or all-cause hospitalizations at 6 month was 12.4%. CONCLUSIONS: Early activation of MPP was not associated to an advantage increasing echocardiography responders to CRT at 6 months of follow-up. Nevertheless, patients programmed using widest pacing cathodes had a numerically higher responder rate. Finally, early activation of MPP was associated to a low incidence of clinical endpoints at 6 months of follow-up.

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.

Factores predictores de aparición de fibrilación auricular en pacientes con miocardiopatía dilatada / Predicting factors of atrial fibrillation in patients with dilated cardiomyopathy

Resumen Introducción El uso de terapia anticoagulante en pacientes con miocardiopatía dilatada es controvertido. El riesgo hemorrágico hace que habitualmente no se use en pacientes en ritmo sinusal. Objetivo Analizar los factores predictores de fibrilación auricular (FA) en pacientes con miocardiopatía dilatada y fracción de eyección del ventrículo izquierdo (FEVI) < 40. Método: Se estudiaron los pacientes incluidos en el registro multicéntrico UMBRELLA a quienes se había implantado un desfibrilador (DAI) bicameral o tricameral y que presentaban miocardiopatía dilatada isquémica o no isquémica y FEVI < 40%. Se definió FA como cualquier episodio > 30 segundos de duración y una frecuencia auricular > 175 latidos por minuto. Resultados Se incluyeron 684 enfermos. La mediana de edad fue de 70 años (rango intercuartílico [RIQ]: 62-77). El 79.1% eran varones. La FEVI fue < 30% en el 76.3%. El 87.3% presentaban insuficiencia cardiaca (ICC) clínica. Se implantó un DAI resincronizador en el 59.5%. El 51.2% tenían bloqueo de rama izquierda del haz de His y el 7.1% de rama derecha (BRDHH). Se documentó FA en el 49% de los enfermos con una mediana de seguimiento de 29.93 meses (RIQ: 14.78-45.63). Las variables que se relacionaron con la aparición de FA fueron la presencia de ICC (hazard ratio [HR]: 2; intervalo de confianza del 95% [IC 95%]: 1.31-3.04; p = 0.001), el BRDHH (HR: 1.48; IC 95%: 1-2-18; p = 0.045), el ictus previo (HR: 2.11; IC 95%: 1.4-3.19; p < 0.001) y la edad > 75 años (HR: 1.21; IC 95%: 1.05-1.40; p = 0.008). Conclusiones La edad > 75 años, el BRDHH, la ICC y el ictus previo predicen la aparición de FA en la población con miocardiopatía dilatada y FEVI < 40%.

Abstract Introduction Anticoagulant treatment in patients with dilated cardiomyopathy and sinus rhythm is controversial due to haemorrhage risk. Objective To analyze the factors predicting atrial fibrillation (AF) in patients with dilated cardiomyopathy and ejection fraction (LVEF) < 40%. Method All patients included in UMBRELLA multicentre registry without AF, who had a dual or three-chamber implantable cardiac defibrillator (ICD), dilated cardiomyopathy and LVEF < 40% were included. AF was defined as any episode > 30 seconds of duration and atrial frequency > 175 bpm. Results 684 patients were included. Median age was 70 years (IQR 62-77); 79.1% were male. LVEF was < 30% in 76.3% of cases; 87.3% presented clinical heart failure (CHF). A CRT-D was implanted in 59.5%; 51.2% of patients presented Left Bundle Branch Block (LBBB) and 7.1% presented Right Bundle Branch Block (RBBB). AF was documented in 49% of patients, with a median follow-up of 29.93 months (IQR: 14.78-45.63). The presence of CHF (HR: 2; 95% CI: 1.31-3.04; p = 0.001), RBBB (HR: 1.48; 95% CI: 1-2-18; p = 0.045), previous stroke (HR: 2.11; 95% CI: 1.4-3.19; p < 0.001) and age > 75 years (HR: 1.21; 95% CI: 1.05-1.40; p = 0.008) were associated with diagnosis of AF. Conclusions Age > 75 years, RBBB, CHF and previous stroke are predictors of AF development in the population with dilated cardiomyopathy and LVEF < 40%.

Predictores e impacto de la adopción de programación basada en la evidencia en la incidencia de terapias del desfibrilador automático implantable / Predictors of adoption and impact of evidence-based programming on the incidence of implantable cardioverter-defibrillator therapies

Introducción y objetivos El estudio ADVANCE III mostró una reducción de terapias del desfibrilador automático implantable (DAI) con el empleo de tiempos de detección de arritmia prolongados. Se describe la adopción y el impacto de dicha estrategia en la incidencia de terapias del DAI. Métodos Estudio observacional retrospectivo de pacientes con implante de DAI Medtronic (2005-2016) en un registro multicéntrico (UMBRELLA-NCT01561144). Se describe la evolución de la adopción de programación ADVANCE en relación con: publicación del estudio, implementación de una campaña de formación y publicación de un consenso de expertos. Se identificaron con regresión logística los predictores de la adopción. Se comparó la incidencia de terapias en pacientes con y sin programación ADVANCE estimando la razón de tasas de incidencia ajustada (RTIa) mediante regresión binomial negativa. Resultados Se incluyó a 3.528 pacientes. Se utilizó la estrategia ADVANCE en el 20% del total y el 44% al final del estudio. La adopción se incrementó tras publicarse el estudio ADVANCE, y en menor grado tras la campaña de formación y consenso de expertos. Predictores de la adopción: DAI con detección nominal 30/40 (ORa=4,4; IC95%, 3,5-5,4), implantador electrofisiólogo (ORa=1,7; IC95%, 1,4-2,2) y prevención secundaria (ORa=3,2; IC95%, 2,6-3,9). El implante de DAI bicameral (ORa=0,6; IC95%, 0,5-0,8) o tricameral (ORa=0,5; IC95%, 0,4-0,7) se asoció con menor adopción. La programación ADVANCE se asoció con reducción de terapias totales (RTIa=0,77; IC95%, 0,69-0,86) y choques inapropiados (RTIa=0,66; IC95%, 0,52-0,85). Conclusiones La adopción de la programación ADVANCE es poco amplia y puede mejorarse mediante una adecuada selección de los parámetros nominales. Emplearla se asocia con una reducción de las terapias del DAI. (AU)

Introduction and objectives The ADVANCE III trial showed that a delayed-detection strategy reduces implantable cardioverter-defibrillator (ICD) therapies. Here, we describe the adherence to and predictors of ADVANCE adoption and compare ICD therapy rates between patients with and without ADVANCE programming. Methods This observational retrospective study analyzed patients implanted with Medtronic ICDs included from 2005 to 2016 in a Spanish national multicenter registry (UMBRELLA database; ClinicalTrials.gov, NCT01561144). Changes in ADVANCE programming adoption were described in relation to a) publication of the ADVANCE trial, b) implementation of an “ADVANCE awareness” campaign, and c) publication of an expert consensus statement. Multivariate logistic regression identified predictors of adoption. Therapy incidence rates were compared between groups by estimating the adjusted incidence rate ratio (aIRR) using negative binomial regression. Results A total of 3528 patients were included. An ADVANCE strategy was used in 20% overall and in 44% at the end of the study. ADVANCE III adoption increased after trial publication, with less growth after an “ADVANCE awareness” campaign and after expert consensus statement publication. Predictors of ADVANCE adoption were as follows: ICD device with a nominal number of intervals to detect 30/40 (aOR, 4.4; 95%CI, 3.5-5.4), implantation by an electrophysiologist (aOR, 1.7; 95%CI, 1.4-2.2), and secondary prevention (aOR, 3.2; 95%CI, 2.6-3.9). Dual-chamber ICDs (aOR, 0.6; 95%CI, 0.5-0.8) and cardiac resynchronization-defibrillators (aOR, 0.5; 95%CI, 0.4-0.7) were associated with lower adoption. ADVANCE programming was associated with reduced total therapy burden (aIRR, 0.77; 95%CI, 0.69-0.86) and fewer inappropriate shocks (aIRR, 0.66; 95%CI, 0.52-0.85). Conclusions ADVANCE adoption remains modest and can be improved through evidence-driven selection of nominal ICD settings. ... (AU)

The clinical impact of untreated slow ventricular tachycardia in patients carrying implantable cardiac defibrillators.

INTRODUCTION: The clinical impact of slow ventricular tachycardia (VT), occurring in patients carrying implantable cardiac defibrillators (ICD), is still under debate. METHODS AND RESULTS: From the UMBRELLA registry (multicenter, observational, and prospective study on patients with ICD), 659 episodes of slow VT were observed in 97 patients. Untreated slow VT (n = 93) had longer duration (23.7 min, CI95%: 10-39), compared with episodes treated effectively by anti-tachycardia pacing (ATP; n = 527; 0.32 min, IC95%: 0.22-0, 48) or shock (n = 39; 1 min, CI95%: 0.8-1.2). Despite of longer duration, the time to the first contact with the medical services was similar to those episodes treated by ATP (50 days [CI95%: 45-55] vs. 41 days [CI95%: 39-44]). However, both were significantly longer than the time observed in episodes treated with shock (10 days, CI95%: 6-15). This tendency was maintained with successive interrogations of the device (2nd and 3rd). There were no significant differences in mortality during follow-up (48 ± 16 months), neither other adverse outcomes, between patients who presented untreated slow TV and those who did not (log-rank p = 0.28). In a Cox regression analysis, the variable "presenting untreated episodes of slow VT" was not able to predict mortality. However, being in sinus rhythm (vs. atrial fibrillation, OR: 0.31, p = 0.009), narrower QRS (OR: 1.036, p = 0.037) and diabetes (OR 4.673, p = 0.049) appropriately predict survival. CONCLUSIONS: Untreated slow VT does not significantly worsen patient prognosis. Our results support the limitation of therapies to ATP only, thus avoiding therapies that have been associated with increased risk of morbidity and mortality.

Long-Term Outcomes Among a Nationwide Cohort of Patients Using an Implantable Cardioverter-Defibrillator: UMBRELLA Study Final Results.

Background Large-scale studies describing modern populations using an implantable cardioverter-defibrillator (ICD) are lacking. We aimed to analyze the incidence of arrhythmia, device interventions, and mortality in a broad spectrum of real-world ICD patients with different heart disorders. Methods and Results The UMBRELLA study is a prospective, multicenter, nationwide study of contemporary patients using an ICD followed up by remote monitoring, with a blinded review of arrhythmic episodes. From November 2005 to November 2017, 4296 patients were followed up. After 46.6±27.3 months, 16 067 episodes of sustained ventricular arrhythmia occurred in 1344 patients (31.3%). Appropriate ICD therapy occurred in 27.3% of study population. Patients with ischemic cardiomyopathy (hazard ratio [HR], 1.51; 95% CI, 1.29-1.78), dilated cardiomyopathy (HR, 1.28; 95% CI, 1.07-1.53), and valvular heart disease (HR, 1.94; 95% CI, 1.43-2.62) exhibited a higher risk of appropriate ICD therapies, whereas patients with hypertrophic cardiomyopathy (HR, 0.72; 95% CI, 0.54-0.96) and Brugada syndrome (HR, 0.25; 95% CI, 0.14-0.45) showed a lower risk. All-cause death was 13.4% at follow-up. Ischemic cardiomyopathy (HR, 3.09; 95% CI, 2.58-5.90), dilated cardiomyopathy (HR, 3.33; 95% CI, 2.18-5.10), and valvular heart disease (HR, 3.97; 95% CI, 2.25-6.99) had the worst prognoses. Delayed high-rate detection was enabled in 39.7% of patients, and single-zone programming occurred in 52.6% of primary prevention patients. Both parameters correlated with lower risk of first appropriate ICD therapy, with no excess risk of mortality. The rate of inappropriate shocks at follow-up was low (6%) and did not differ among type of ICD but was lower in SmartShock-capable devices. Conclusions Irrespective of the cause, contemporary ICD patients with heart failure-related disorders had a similar risk of ICD life-saving interventions and death. Current ICD programming recommendations still need to be implemented. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NTC01561144.

Predictors of adoption and impact of evidence-based programming on the incidence of implantable cardioverter-defibrillator therapies.

INTRODUCTION AND OBJECTIVES: The ADVANCE III trial showed that a delayed-detection strategy reduces implantable cardioverter-defibrillator (ICD) therapies. Here, we describe the adherence to and predictors of ADVANCE adoption and compare ICD therapy rates between patients with and without ADVANCE programming. METHODS: This observational retrospective study analyzed patients implanted with Medtronic ICDs included from 2005 to 2016 in a Spanish national multicenter registry (UMBRELLA database; ClinicalTrials.gov, NCT01561144). Changes in ADVANCE programming adoption were described in relation to a) publication of the ADVANCE trial, b) implementation of an "ADVANCE awareness" campaign, and c) publication of an expert consensus statement. Multivariate logistic regression identified predictors of adoption. Therapy incidence rates were compared between groups by estimating the adjusted incidence rate ratio (aIRR) using negative binomial regression. RESULTS: A total of 3528 patients were included. An ADVANCE strategy was used in 20% overall and in 44% at the end of the study. ADVANCE III adoption increased after trial publication, with less growth after an "ADVANCE awareness" campaign and after expert consensus statement publication. Predictors of ADVANCE adoption were as follows: ICD device with a nominal number of intervals to detect 30/40 (aOR, 4.4; 95%CI, 3.5-5.4), implantation by an electrophysiologist (aOR, 1.7; 95%CI, 1.4-2.2), and secondary prevention (aOR, 3.2; 95%CI, 2.6-3.9). Dual-chamber ICDs (aOR, 0.6; 95%CI, 0.5-0.8) and cardiac resynchronization-defibrillators (aOR, 0.5; 95%CI, 0.4-0.7) were associated with lower adoption. ADVANCE programming was associated with reduced total therapy burden (aIRR, 0.77; 95%CI, 0.69-0.86) and fewer inappropriate shocks (aIRR, 0.66; 95%CI, 0.52-0.85). CONCLUSIONS: ADVANCE adoption remains modest and can be improved through evidence-driven selection of nominal ICD settings. ADVANCE programming is associated with reduced therapy rates in real-world ICD recipients.

Bloqueo auriculoventricular en pacientes en tratamiento con fármacos bradicardizantes. Variables predictoras de la necesidad de implante de marcapasos / Atrioventricular block in patients undergoing treatment with bradycardic drugs. Predictors of pacemaker requirement

INTRODUCCIÓN Y OBJETIVOS: El bloqueo auriculoventricular (BAV) en presencia de fármacos bradicardizantes (FBZ) puede ser reversible, y está en controversia el implante de marcapasos. El objetivo es analizar la necesidad de tratamiento con marcapasos a medio plazo, tras la suspensión de los FBZ, e identificar factores predictores. MÉTODOS: Se estudió a una cohorte de pacientes que acudieron a urgencias con BAV de alto grado mientras tomaban FBZ. Se estudió la persistencia de BAV tras la interrupción del fármaco, la recurrencia en los pacientes con resolución del BAV y las variables predictoras asociadas con la necesidad de marcapasos a los 3 años de seguimiento. RESULTADOS: De 127 pacientes (edad, 79 [71-83] años), en 60 (47,2%) se resolvió el BAV; de estos, en 40 (66,6%) el BAV recurrió en los 24 meses de seguimiento medio; 107 pacientes (84,3%) tuvieron indicación de implante de marcapasos pese a suspenderse los FBZ. Las variables asociadas con la necesidad de marcapasos a los 3 años en el multivariable fueron: frecuencia cardiaca<35 lpm (OR=8,12; IC95%, 1,82-36,17); síntomas diferentes del síncope (OR=4,09; IC95%, 1,18-14,13) y QRS ancho (OR=5,65; IC95%, 1,77-18,04). El tratamiento con antiarrítmicos no se asoció con necesidad de marcapasos (OR=0,12; IC95%, 0,02-0,66). CONCLUSIONES: Más del 80% de los pacientes con BAV secundario a FBZ precisan implante de marcapasos a pesar de suspenderlos; los predictores son el QRS ancho, la frecuencia cardiaca <35 lpm y la presentación clínica distinta del síncope

INTRODUCTION AND OBJECTIVES: Atrioventricular block (AVB) in the presence of bradycardic drugs (BD) can be reversible, and pacemaker implantation is controversial. Our objective was to analyze the pacemaker implantation rate in the mid-term, after BD suspension, and to identify predictive factors. METHODS: We performed a cohort study that included patients attending the emergency department with high-grade AVB in the context of BD. We studied the persistence of AVB after BD discontinuation, recurrence in patients with AVB resolution, and the predictive variables associated with pacemaker requirement at 3 years. RESULTS: Of 127 patients included (age, 79 [71-83] years), BAV resolved in 60 (47.2%); among these patients, recurrence occurred during the 24-month median follow-up in 40 (66.6%). Pacemaker implantation was required in 107 patients (84.3%), despite BD discontinuation. On multivariable analysis, the variables associated with pacemaker need at 3 years were heart rate <35 bpm (OR, 8.12; 95%CI, 1.82-36.17), symptoms other than syncope (OR, 4.09; 95%CI, 1.18-14.13), and wide QRS (OR, 5.65; 95%CI, 1.77-18.04). Concomitant antiarrhythmic treatment was associated with AVB resolution (OR, 0.12; 95%CI, 0.02-0.66). CONCLUSIONS: More than 80% of patients with AVB secondary to BD require pacemaker implantation despite drug discontinuation. Predictive variables were wide QRS, heart rate <35 bpm, and clinical presentation other than syncope

Antitachycardia pacing for shock prevention in patients with hypertrophic cardiomyopathy and ventricular tachycardia.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) carries an increased risk of sudden death due to ventricular arrhythmias (VAs). The implantable cardioverter-defibrillator (ICD) is a well-established therapy for treatment of VA. Monomorphic ventricular tachycardias (MVTs) are frequent in HCM patients and suitable for antitachycardia pacing (ATP) termination. OBJECTIVE: The purpose of this study was to describe ventricular tachycardia (VT) characteristics in a population of HCM patients with ICD and to study the effectiveness and safety of ATP for MVT. METHODS: Data were obtained from the multicenter prospective observational UMBRELLA trial, which included all patients with HCM and ICD followed by the CareLink Monitoring System. All episodes of VA were collected and analyzed. ATP effectiveness and safety were described, and factors related to ATP effectiveness were studied with generalized estimating equation (GEE) models. RESULTS: Among 251 patients followed for 47 months, 67 (26.7%) were implanted as secondary prevention. Fifty-six patients presented 326 episodes of VA (286 [87%] MVT). Mean cycle length was 312 ± 64 ms. Among 264 MVTs that received ICD therapy, 202 (76.5%) were ATP terminated. The first ATP burst was effective in 169 episodes (68.4%), and overall effectiveness of the first or second ATP burst was 73.8%. Multivariate GEE-adjusted analysis showed 2 variables related to ATP effectiveness: programming fast VT zone On vs Off (odds ratio [OR] 2.4; 95% confidence interval [CI] 1.5-5.2; P = .03) and programming ≥2 ATP bursts vs 1 burst only (OR 1.6; 95% CI 1.2-3.4; P = .04; and OR 2.9; 95% CI 1.8-6.3; P = .02; respectively). CONCLUSION: MVT is the predominant VA in HCM patients with ICD. ATP is highly effective in terminating the majority of MVTs, and its proved effectiveness should guide device selection and programming in order to avoid unnecessary high-energy shocks.

Premature ventricular contractions in patients with an implantable cardioverter defibrillator cardiac resynchronization therapy device: Results from the UMBRELLA registry.

BACKGROUND: Premature ventricular contractions (PVC) are known to reduce the percentage of biventricular (BiV) pacing in patients with cardiac resynchronization (CRT), decreasing the clinical response. The aim of this study was to evaluate the prevalence of a high PVC burden, as well as therapeutic action (pharmacotherapy, catheter ablation or device programming), in a large CRT implantable-defibrillator (CRT-D) population. METHODS: Patients with a CRT-D device from the UMBRELLA multicenter prospective remote monitoring registry were included. The PVC count was collected from each remote monitoring transmission. Patients were divided into two high (≥1 transmission ≥200/≥400 PVC/h, respectively) and one low (all transmissions <200 PVC/h) PVC count groups. The PVC burden following a high PVC count transmission was calculated. RESULTS: Of 1268 patients, 135 (11%) and 43 (3.4%) presented high PVC count (≥200/≥400 PVC/h, respectively). The majority of patients in the high PVC groups were not treated (61 [79%] and 32 [74%], respectively. Considering the untreated patients in the high PVC groups, median PVC/h was 199 (interquartile range [IQR]: 196) and 271 (IQR: 330), respectively. The PVC burden (proportion of time with PVC/h ≥ 200/≥400) was 40% (IQR 70) and 29% (IQR 59), respectively. CONCLUSION: A significant proportion of CRT-D patients presented a high PVC count, however, few received treatment. In the untreated patients with a high PVC count, the PVC burden during follow-up varied substantially. Several consecutive recordings of a high PVC count should be warranted before considering therapeutic action such as catheter ablation.

Atrioventricular block in patients undergoing treatment with bradycardic drugs. Predictors of pacemaker requirement.

INTRODUCTION AND OBJECTIVES: Atrioventricular block (AVB) in the presence of bradycardic drugs (BD) can be reversible, and pacemaker implantation is controversial. Our objective was to analyze the pacemaker implantation rate in the mid-term, after BD suspension, and to identify predictive factors. METHODS: We performed a cohort study that included patients attending the emergency department with high-grade AVB in the context of BD. We studied the persistence of AVB after BD discontinuation, recurrence in patients with AVB resolution, and the predictive variables associated with pacemaker requirement at 3 years. RESULTS: Of 127 patients included (age, 79 [71-83] years), BAV resolved in 60 (47.2%); among these patients, recurrence occurred during the 24-month median follow-up in 40 (66.6%). Pacemaker implantation was required in 107 patients (84.3%), despite BD discontinuation. On multivariable analysis, the variables associated with pacemaker need at 3 years were heart rate <35 bpm (OR, 8.12; 95%CI, 1.82-36.17), symptoms other than syncope (OR, 4.09; 95%CI, 1.18-14.13), and wide QRS (OR, 5.65; 95%CI, 1.77-18.04). Concomitant antiarrhythmic treatment was associated with AVB resolution (OR, 0.12; 95%CI, 0.02-0.66). CONCLUSIONS: More than 80% of patients with AVB secondary to BD require pacemaker implantation despite drug discontinuation. Predictive variables were wide QRS, heart rate <35 bpm, and clinical presentation other than syncope.

Personalized monitoring of electrical remodelling during atrial fibrillation progression via remote transmissions from implantable devices.

AIMS: Atrial electrical remodelling (AER) is a transitional period associated with the progression and long-term maintenance of atrial fibrillation (AF). We aimed to study the progression of AER in individual patients with implantable devices and AF episodes. METHODS AND RESULTS: Observational multicentre study (51 centres) including 4618 patients with implantable cardioverter-defibrillator +/-resynchronization therapy (ICD/CRT-D) and 352 patients (2 centres) with pacemakers (median follow-up: 3.4 years). Atrial activation rate (AAR) was quantified as the frequency of the dominant peak in the signal spectrum of AF episodes with atrial bipolar electrograms. Patients with complete progression of AER, from paroxysmal AF episodes to electrically remodelled persistent AF, were used to depict patient-specific AER slopes. A total of 34 712 AF tracings from 830 patients (87 with pacemakers) were suitable for the study. Complete progression of AER was documented in 216 patients (16 with pacemakers). Patients with persistent AF after completion of AER showed ∼30% faster AAR than patients with paroxysmal AF. The slope of AAR changes during AF progression revealed patient-specific patterns that correlated with the time-to-completion of AER (R2 = 0.85). Pacemaker patients were older than patients with ICD/CRT-Ds (78.3 vs. 67.2 year olds, respectively, P < 0.001) and had a shorter median time-to-completion of AER (24.9 vs. 93.5 days, respectively, P = 0.016). Remote transmissions in patients with ICD/CRT-D devices enabled the estimation of the time-to-completion of AER using the predicted slope of AAR changes from initiation to completion of electrical remodelling (R2 = 0.45). CONCLUSION: The AF progression shows patient-specific patterns of AER, which can be estimated using available remote-monitoring technology.

Prognostic role of NYHA class in heart failure patients undergoing primary prevention ICD therapy.

AIMS: Concerns about the prognostic value of NYHA functional class (FC) in heart failure (HF) patients carrying a prophylactic implantable cardioverter defibrillator (ICD) are still present. We aimed to compare whether mortality and arrhythmic risk were different, in a cohort of HF patients undergoing ICD-only implant, according to their FC. METHODS AND RESULTS: HF patients with left ventricle ejection fraction (LVEF) ≤35%, undergoing first prophylactic ICD-only implant were collected from a multicentre nationwide registry (2006-2015). Six hundred and twenty-one patients were identified (101 patients in NYHA I; 411 in NYHA II; 109 in NYHA III). After a mean follow-up of 4.4 years (±2.1), 126 patients died (20.3%). All-cause mortality risk was higher in symptomatic patients: 13.9% in NYHA I patients, 18.3% in NYHA II patients (HR: 1.8, 95% CI 1.1-3.2), and 32.9% in NYHA III patients (HR: 3.9, 95% CI 2.1-7.3). Seventy-eight out of all deaths were due to cardiovascular causes (12.6%). Cardiovascular mortality risk was also higher in symptomatic patients: 6.9% in NYHA I patients, 11% in NYHA II patients (HR: 2.2, 95% CI 1.1-4.9), and 23.9% in NYHA III (HR: 5.5, 95% CI 2.4-12.7). One hundred and seventeen patients received a first appropriate ICD therapy (19.4%). Arrhythmia free survival did not differ among study groups [20.8% in NYHA I patients, 18.7% in NYHA II (HR: 1.1, 95% CI 0.6-1.7) and 20.8% in NYHA III patients (HR: 1.3, 95% CI 0.7-2.5)]. NYHA class independently predicted cardiovascular mortality (NYHA III vs. NYHA I: HR, 4.7; 95% CI, 1.7-12.8, P = 0.002; NYHA II vs. NYHA I: HR, 2.1, 95% CI, 1.0-5.6, P = 0.05) but not all-cause death (NYHA III vs. NYHA I: HR: 1.8, 95% CI 0.8-3.9, P = 0.11; NYHA II vs. NYHA I: HR, 1.1, 95% CI 0.6-2.2, P = 0.71;). Atrial fibrillation, chronic kidney disease, and diabetes emerged as predictors of both all-cause death [(HR: 1.8, 95% CI 1.2-2.8, P = 0.005), (HR: 2.2, 95% CI 1.4-3.4, P < 0.001), (HR: 2.0, 95% CI 1.3-3.1, P = 0.001), respectively] and cardiovascular mortality [(HR: 1.8, 95% CI 1.1-3.1, P = 0.02), (HR: 3.1, 95% CI 1.8-5.4, P < 0.001), (HR: 1.7, 95% CI 1.1-3, P = 0.032), respectively]. CONCLUSIONS: Mortality in HF patients undergoing prophylactic ICD implantation was higher in symptomatic patients. NYHA functional class along with other comorbidities might be helpful to identify a subgroup of ICD carriers with poorer prognosis and higher risk of cardiovascular death.

Single-brand dual-chamber discriminators to prevent inappropriate shocks in patients implanted with prophylactic implantable cardioverter defibrillators: a propensity-weighted comparison of single- and dual-chamber devices.

PURPOSE: Comparisons of the efficacy of dual- vs. single-chamber implantable cardioverter defibrillators (ICDs) in preventing inappropriate shocks have had contradictory results. We investigated whether dual-chamber devices have a lower risk of inappropriate shocks and the specific role of supraventricular tachycardia (SVT) discriminators. METHODS: All heart failure (HF) patients without an indication for pacing and implanted with a prophylactic ICD were recruited from the nationwide multicenter UMBRELLA registry. Arrhythmic events were collected by remote monitoring and reviewed by a committee of experts. RESULTS: Among 782 patients, single-chamber ICDs were implanted in 537 (68.7%) and dual-chamber devices in 245 (31.3%). During a mean follow-up of 52.2 ± 24.5 months, 109 inappropriate shocks were delivered in 49 patients (6.2%). In the propensity-score-matched analysis, dual-chamber ICDs were related to lower rates of inappropriate shocks as compared to single-chamber devices (0.9% vs. 11.8%, p = < 0.001, log-rank test). In multivariable Cox proportional analysis, independent predictors of inappropriate shock were history of atrial fibrillation (hazard ratio (HR) = 2.78, CI 1.37-5.64, p = 0.004), chronic kidney disease (HR = 6.15, CI 2.82-13.53, p < 0.001), and non-ischemic cardiomyopathy (HR = 2.84, CI 1.54-5.23, p = 0.001). Among ICD settings, PR logic was the only discriminator independently related to a reduced risk of inappropriate shocks (HR = 0.18, CI 0.06-0.48, p = 0.001), along with an SVT limit enabled over 200 bpm (HR = 0.24, CI 0.11-0.51, p < 0.001). CONCLUSIONS: In this nationwide cohort of primary prevention ICD-only patients, dual-chamber devices were related to lower risk of inappropriate shocks compared to single-chamber ICDs. Besides, PR logic and SVT limit > 200 bpm emerged as protective factors.

Survival and arrhythmic risk among ischemic and non-ischemic heart failure patients with prophylactic implantable cardioverter defibrillator only therapy: A propensity score-matched analysis.

BACKGROUND: Concerns about the efficacy of prophylactic ICD in non-ischemic cardiomyopathy (NICM) heart failure (HF) patients are still present. We aimed to assess whether survival and arrhythmic risk were different among ischemic cardiomyopathy (ICM) and NICM ICD-only patients, along with specific predictors for mortality. METHODS: HF patients undergoing ICD-only implant were extracted from the nationwide multicenter UMBRELLA registry. Arrhythmic events were collected by remote monitoring and reviewed by a committee of experts. RESULTS: 782 patients (556 ICM; 226 NICM) were recruited: mean ejection fraction of 26.6%; 83.4% in NYHA class II-III; mean QRS duration of 108.9 ms (only 14.9% with QRS > 130 ms). After 4.35 years of mean follow-up, all-cause mortality rate was 4.2%/year. In propensity-score (PS) analysis no survival differences between ICM and NICM subgroups appeared (mortality rates: 19.4% vs. 20%, p = 0.375). Age (hazard ratio [HR] = 1.02, p = 0.009), diabetes (HR = 2.61, p ≤ 0.001), chronic obstructive pulmonary disease (HR = 2.13, p = 0.002), and previous HF (HR = 2.28, p = 0.027) correlated with increased mortality for the entire population, however atrial fibrillation (AF) (HR = 2.68, p = 0.002) and chronic kidney disease (HR = 3.74, p ≤ 0.001) emerged as specific predictors in NICM patients. At follow-up, 134 patients (17.1%) were delivered a first appropriate ICD therapy (5.1%/year) without significant differences between ICM and NICM patients in the PS analysis (17.6% vs. 15.8%, p = 0.968). ICD shocks were associated with a higher mortality (HR = 2.88, p < 0.001) but longer detection windows (HR = 0.57, p = 0.042) correlated with fewer appropriate therapies. CONCLUSIONS: Mortality and arrhythmia free survival is similar among ICM and NICM HF patients undergoing ICD-only implant for primary prevention strategy.

Rentabilidad del estudio genético mediante técnicas de next-generation sequencing masiva de pacientes con miocardiopatía arritmogénica de alto riesgo / Usefulness of genetic study by next-generation sequencing in high-risk arrhythmogenic cardiomyopathy

Introducción y objetivos: La miocardiopatía arritmogénica del ventrículo derecho (MCAVD) es una cardiopatía hereditaria definida por la sustitución progresiva de miocardio ventricular derecho por tejido fibroadiposo. Es causa frecuente de la muerte súbita de jóvenes atletas. El objetivo del presente estudio es conocer la incidencia de variantes desmosómicas patogénicas o probablemente patogénicas en pacientes con MCAVD definitiva de alto riesgo. Métodos: El estudio de cohortes retrospectivo observacional incluyó a 36 pacientes diagnosticados de MCAVD definitiva de alto riesgo en nuestro hospital entre enero de 1998 y enero de 2015. El análisis genético se realizó con next-generation sequencing. Resultados: La mayoría eran varones (28 pacientes, 78%) con una media de edad al diagnóstico de 45 ± 18 años. Se detectó al menos 1 variante desmosómica patogénica o probablemente patogénica en 26 de los 35 casos índice (74%): 5 nonsense, 14 frameshift, 1 splice y 6 missense. En 15 pacientes (71%) se encontraron mutaciones nuevas. La presencia o la ausencia de mutaciones desmosómicas o la naturaleza de estas no se asociaron con características electrocardiográficas, clínicas, arrítmicas, anatómicas o pronósticas específicas. Conclusiones: La incidencia de variantes desmosómicas patogénicas o probablemente patogénicas en MCAVD definitiva de alto riesgo fue muy alta, con mayoría de mutaciones que causan truncamiento. La presencia de mutaciones desmosómicas no se asoció con el pronóstico

Introduction and objectives: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by progressive fibrofatty replacement of predominantly right ventricular myocardium. This cardiomyopathy is a frequent cause of sudden cardiac death in young people and athletes. The aim of our study was to determine the incidence of pathological or likely pathological desmosomal mutations in patients with high-risk definite ARVC. Methods: This was an observational, retrospective cohort study, which included 36 patients diagnosed with high-risk ARVC in our hospital between January 1998 and January 2015. Genetic analysis was performed using next-generation sequencing. Results: Most patients were male (28 patients, 78%) with a mean age at diagnosis of 45 ± 18 years. A pathogenic or probably pathogenic desmosomal mutation was detected in 26 of the 35 index cases (74%): 5 nonsense, 14 frameshift, 1 splice, and 6 missense. Novel mutations were found in 15 patients (71%). The presence or absence of desmosomal mutations causing the disease and the type of mutation were not associated with specific electrocardiographic, clinical, arrhythmic, anatomic, or prognostic characteristics. Conclusions: The incidence of pathological or likely pathological desmosomal mutations in ARVC is very high, with most mutations causing truncation. The presence of desmosomal mutations was not associated with prognosis

Taquicardias ventriculares rápidas en pacientes con desfibrilador implantable: reducción de choques mediante terapia antitaquicárdica antes y durante la carga / Shock reduction with antitachycardia pacing before and during charging for fast ventricular tachycardias in patients with implantable defibrillators

Introducción y objetivos: Las taquicardias ventriculares rápidas en zona de fibrilación ventricular en pacientes con desfibriladores implantables son susceptibles de terminación mediante estimulación antitaquicárdica (EA). Algunos fabricantes permiten la programación de 2 ráfagas de EA: antes de la carga (AC) y durante la carga (DC). Nuestro objetivo es describir la efectividad y la seguridad de la EA AC y DC en las taquicardias ventriculares rápidas en zona de fibrilación ventricular en pacientes con desfibriladores implantables en la práctica clínica diaria. Métodos: Los datos proceden del ensayo multicéntrico UMBRELLA, y se incluyó a los pacientes portadores de desfibriladores implantables seguidos por el sistema de monitorización a distancia CareLink. Se incluyeron las taquicardias ventriculares rápidas en la zona de fibrilación ventricular hasta una longitud de ciclo de 200 ms y tratadas con EA AC y/o DC. Resultados: Se revisaron 542 episodios en 240 pacientes. Dos ráfagas de EA (AC/DC) se programaron en 291 episodios (el 53,7%, 87 pacientes) mientras que 251 (el 46,3%, 153 pacientes) tuvieron 1 sola EA DC. Los episodios terminados por 1 EA DC fueron 139: el 55,4% de eficacia (ajustado por las ecuaciones de estimación generalizada, el 60,4%). Los episodios terminados por 1 o 2 EA (AC/DC) fueron 256, el 88% de efectividad (ajustado por las ecuaciones de estimación generalizada, el 79,3%). La OR para la eficacia de la EA AC/DC frente a DC fue 2,5 (IC95%, 1,5-4,1; p < 0,001). Los episodios con descarga de alta energía fueron 112 (45%) con EA DC frente a 35 (12%) con EA AC/DC (reducción absoluta del 73%). La media de duración de los episodios con descarga fue de 16 s con EA DC frente a 19 s con EA AC/DC (p = 0,07). Conclusiones: La EA DC en la zona de fibrilación ventricular en taquicardias ventriculares rápidas es moderadamente eficaz. La adición de una ráfaga de EA AC aumenta la efectividad general, reduce la necesidad de descargas y no prolonga el episodio

Introduction and objectives: Fast ventricular tachycardias in the ventricular fibrillation zone in patients with an implantable cardioverter-defibrillator are susceptible to antitachycardia pacing (ATP) termination. Some manufacturers allow programming 2 ATP bursts: before charging (BC) and during (DC) charging. The aim of this study was to describe the safety and effectiveness of ATP BC and DC for fast ventricular tachycardias in the ventricular fibrillation zone in patients with an implantable cardioverter-defibrillator in daily clinical practice. Methods: Data proceeded from the multicenter UMBRELLA trial, including implantable cardioverter-defibrillator patients followed up by the CareLink monitoring system. Fast ventricular tachycardias in the ventricular fibrillation zone until a cycle length of 200 ms with ATP BC and/or ATP DC were included. Results: We reviewed 542 episodes in 240 patients. Two ATP bursts (BC/DC) were programmed in 291 episodes (53.7%, 87 patients), while 251 episodes (46.3%, 153 patients) had 1 ATP burst only DC. The number of episodes terminated by 1 ATP DC was 139, representing 55.4% effectiveness (generalized estimating equation-adjusted 60.4%). There were 256 episodes terminated by 1 or 2 ATP (BC/DC), representing 88% effectiveness (generalized estimating equation-adjusted 79.3%); the OR for ATP effectiveness BC/DC vs DC was 2.5, 95%CI, 1.5-4.1; P < .001. Shocked episodes were 112 (45%) for ATP DC vs 35 (12%) for ATP BC/DC, representing an absolute reduction of 73%. The mean shocked episode duration was 16 seconds for ATP DC vs 19 seconds for ATP BC/DC (P = .07). Conclusions: The ATP DC in the ventricular fibrillation zone for fast ventricular tachycardia is moderately effective. Adding an ATP burst BC increases the overall effectiveness, reduces the need for shocks, and does not prolong episode duration

Impact of dynamic physical exercise on high-risk definite arrhythmogenic right ventricular cardiomyopathy.

INTRODUCTION: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is an inherited cardiomyopathy characterized by ventricular arrhythmias and heart failure. The variable phenotype suggesting that determined environmental factors may have an influence. The aim of our study was to discover the impact of the dynamic physical activity on patients with high-risk definite ARVC/D. METHODS AND RESULTS: Collection of data on physical activity at the time of diagnosis was conducted at an in-person clinical interview. The intensity of the activity was classified in accordance with the mean frequency of weekly physical exercise sessions in the 10 years before diagnosis and into the following three groups of dynamic activity: high/competitive (>3 h/wk), moderate (1 to 3 h) and minimal/inactive (<1 h). Seventeen patients practiced high dynamic physical activities. The intensity of dynamic activity was classified into three groups: 8 of high intensity, 9 moderate, and 19 inactive. The first major arrhythmic event and occurrence of severe right ventricular dysfunction were earlier in the high-intensity exercise group, followed by the moderate intensity group and at a later age in the low-intensity/inactive group. CONCLUSIONS: Dynamic exercise could be directly associated with the severity of the phenotype in relation to the precocity of major ventricular arrhythmic events and right ventricular systolic dysfunction in patients with high-risk definite ARVC/D.

Usefulness of Genetic Study by Next-generation Sequencing in High-risk Arrhythmogenic Cardiomyopathy.

INTRODUCTION AND OBJECTIVES: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by progressive fibrofatty replacement of predominantly right ventricular myocardium. This cardiomyopathy is a frequent cause of sudden cardiac death in young people and athletes. The aim of our study was to determine the incidence of pathological or likely pathological desmosomal mutations in patients with high-risk definite ARVC. METHODS: This was an observational, retrospective cohort study, which included 36 patients diagnosed with high-risk ARVC in our hospital between January 1998 and January 2015. Genetic analysis was performed using next-generation sequencing. RESULTS: Most patients were male (28 patients, 78%) with a mean age at diagnosis of 45 ± 18 years. A pathogenic or probably pathogenic desmosomal mutation was detected in 26 of the 35 index cases (74%): 5 nonsense, 14 frameshift, 1 splice, and 6 missense. Novel mutations were found in 15 patients (71%). The presence or absence of desmosomal mutations causing the disease and the type of mutation were not associated with specific electrocardiographic, clinical, arrhythmic, anatomic, or prognostic characteristics. CONCLUSIONS: The incidence of pathological or likely pathological desmosomal mutations in ARVC is very high, with most mutations causing truncation. The presence of desmosomal mutations was not associated with prognosis.

Shock Reduction With Antitachycardia Pacing Before and During Charging for Fast Ventricular Tachycardias in Patients With Implantable Defibrillators.

INTRODUCTION AND OBJECTIVES: Fast ventricular tachycardias in the ventricular fibrillation zone in patients with an implantable cardioverter-defibrillator are susceptible to antitachycardia pacing (ATP) termination. Some manufacturers allow programming 2 ATP bursts: before charging (BC) and during (DC) charging. The aim of this study was to describe the safety and effectiveness of ATP BC and DC for fast ventricular tachycardias in the ventricular fibrillation zone in patients with an implantable cardioverter-defibrillator in daily clinical practice. METHODS: Data proceeded from the multicenter UMBRELLA trial, including implantable cardioverter-defibrillator patients followed up by the CareLink monitoring system. Fast ventricular tachycardias in the ventricular fibrillation zone until a cycle length of 200ms with ATP BC and/or ATP DC were included. RESULTS: We reviewed 542 episodes in 240 patients. Two ATP bursts (BC/DC) were programmed in 291 episodes (53.7%, 87 patients), while 251 episodes (46.3%, 153 patients) had 1 ATP burst only DC. The number of episodes terminated by 1 ATP DC was 139, representing 55.4% effectiveness (generalized estimating equation-adjusted 60.4%). There were 256 episodes terminated by 1 or 2 ATP (BC/DC), representing 88% effectiveness (generalized estimating equation-adjusted 79.3%); the OR for ATP effectiveness BC/DC vs DC was 2.5, 95%CI, 1.5-4.1; P <.001. Shocked episodes were 112 (45%) for ATP DC vs 35 (12%) for ATP BC/DC, representing an absolute reduction of 73%. The mean shocked episode duration was 16seconds for ATP DC vs 19seconds for ATP BC/DC (P=.07). CONCLUSIONS: The ATP DC in the ventricular fibrillation zone for fast ventricular tachycardia is moderately effective. Adding an ATP burst BC increases the overall effectiveness, reduces the need for shocks, and does not prolong episode duration.