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.

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.

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.

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.

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.

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.

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.

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

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.

[Gastroprotective effect of honey in Holtzman rats with piroxicam-induced gastric ulcer]. / Efecto gastroprotector de la miel de abeja en ratas Holtzman con úlceras gástricas inducidas por piroxicam.

OBJECTIVE: To determine the effect of treatment with honey in piroxicam-induced gastric ulcer in Holtzman rats. MATERIALS AND METHODS: 48 eight-week old female Holtzman rats, weights between 100 and 200 grams, were divided into 6 treatment groups as follow: Group A: water; Group B: piroxicam (30 mg/kg); Group C: omeprazole (5 mg/kg) and piroxicam (30 mg/kg); Group D: honey (2.5 g/kg) and piroxicam (30 mg/kg); Group E: honey (5 g/kg) and piroxicam (30 mg/kg); Group F: honey (7.5 g/kg) and piroxicam (30 mg/kg). Macroscopic studies, using Scion Image, and microscopic histological section of gastric mucosa were performed after the interventions. RESULTS: The results of the macroscopic studies showed statistically significant differences for both doses of honey at 6 g/kg and 7.5 g/kg when compared to piroxicam (p=0.016 and p=0.001 respectively) and the gastroprotective effect was similar when compared to omeprazole (p>0.05). Microscopic studies showed statistically significant differences only for dose at 7.5 g/kg when compared to piroxicam (p=0.0018) and the gastroprotective effect was similar to omeprazole (p=1). CONCLUSION: Dose of honey at 7.5 g/kg showed gastroprotective effect at microscopic and macroscopic studies when compared to omeprazole.

Efecto gastroprotector de la miel de abeja en ratas Holtzman con úlceras gástricas inducidas por piroxicam

Objetivo: Determinar el efecto de la miel de abeja sobre úlceras gástricas inducidas por piroxicam en ratas Holtzman. Material y método: Se trabajó con 48 ratas hembra Holtzman de ocho semanas de edad con pesos entre 100 y 200 g, divididas en 6 grupos, con las siguientes intervenciones: Grupo A: agua; Grupo B: piroxicam (30 mg/kg); Grupo C: omeprazol (5 mg/kg) y piroxicam (30 mg/kg); Grupo D: miel (2,5 g/kg) y piroxicam (30 mg/kg); Grupo E: miel (5 g/kg) y piroxicam (30 mg/kg); Grupo F: miel (7,5 g/kg) y piroxicam (30 mg/kg). Luego de las intervenciones se realizaron estudios macroscópicos de las lesiones de la mucosa gástrica mediante el paquete Scion Image® y microscópicos, por estudio histológico. Resultados: El estudio macroscópico determinó que la miel a dosis de 5 g/kg y 7,5 g/kg se asoció a úlceras gástricas significativamente menores que el piroxicam (p=0,016 y p=0,001 respectivamente); por otro lado, el efecto gastroprotector de ambas dosis fue similar al omeprazol (p>0,05). En el estudio microscópico, se halló que solo la miel a dosis de 7,5 g/kg tuvo lesiones significativamente menores al piroxicam (p=0,0018), además que el efecto gastroprotector fue similar al omeprazol (p=1). Conclusiones: La miel a dosis 7,5 g/kg mostró un efecto gastroprotector similar al del omeprazol tanto a nivel macroscópico y microscópico. La miel a dosis de 5 g/kg tuvo un efecto gastroprotector similar al omeprazol, solo a nivel macroscópico.

Objective: To determine the effect of treatment with honey in piroxicam-induced gastric ulcer in Holtzman rats. Materials and methods: 48 eight-week old female Holtzman rats, weights between 100 and 200 grams, were divided into 6 treatment groups as follow: Group A: water; Group B: piroxicam (30 mg/kg); Group C: omeprazole (5 mg/kg) and piroxicam (30 mg/kg); Group D: honey (2.5 g/kg) and piroxicam (30 mg/kg); Group E: honey (5 g/kg) and piroxicam (30 mg/kg); Group F: honey (7.5 g/kg) and piroxicam (30 mg/kg). Macroscopic studies, using Scion Image, and microscopic histological section of gastric mucosa were performed after the interventions. Results: The results of the macroscopic studies showed statistically significant differences for both doses of honey at 6 g/kg and 7.5 g/kg when compared to piroxicam (p=0.016 and p=0.001 respectively) and the gastroprotective effect was similar when compared to omeprazole (p>0.05). Microscopic studies showed statistically significant differences only for dose at 7.5 g/kg when compared to piroxicam (p=0.0018) and the gastroprotective effect was similar to omeprazole (p=1). Conclusion: Dose of honey at 7.5 g/kg showed gastroprotective effect at microscopic and macroscopic studies when compared to omeprazole.

Safety threshold of R-wave amplitudes in patients with implantable cardioverter defibrillator.

OBJECTIVE: A safety threshold for baseline rhythm R-wave amplitudes during follow-up of implantable cardioverter defibrillators (ICD) has not been established. We aimed to analyse the amplitude distribution and undersensing rate during spontaneous episodes of ventricular fibrillation (VF), and define a safety amplitude threshold for baseline R-waves. METHODS: Data were obtained from an observational multicentre registry conducted at 48 centres in Spain. Baseline R-wave amplitudes and VF events were prospectively registered by remote monitoring. Signal processing algorithms were used to compare amplitudes of baseline R-waves with VF R-waves. All undersensed R-waves after the blanking period (120 ms) were manually marked. RESULTS: We studied 2507 patients from August 2011 to September 2014, which yielded 229 VF episodes (cycle length 189.6±29.1 ms) from 83 patients that were suitable for R-wave comparisons (follow-up 2.7±2.6 years). The majority (77.6%) of VF R-waves (n=13953) showed lower amplitudes than the reference baseline R-wave. The decrease in VF amplitude was progressively attenuated among subgroups of baseline R-wave amplitude (≥17; ≥12 to <17; ≥7 to <12; ≥2.2 to <7 mV) from the highest to the lowest: median deviations -51.2% to +22.4%, respectively (p=0.027). There were no significant differences in undersensing rates of VF R-waves among subgroups. Both the normalised histogram distribution and the undersensing risk function obtained from the ≥2.2 to <7 mV subgroup enabled the prediction that baseline R-wave amplitudes ≤2.5 mV (interquartile range: 2.3-2.8 mV) may lead to ≥25% of undersensed VF R-waves. CONCLUSIONS: Baseline R-wave amplitudes ≤2.5 mV during follow-up of patients with ICDs may lead to high risk of delayed detection of VF. TRIAL REGISTRATION NUMBER: NCT01561144; results.

Atrial Rate-Responsive Pacing and Incidence of Sustained Atrial Arrhythmias in Patients with Implantable Cardioverter Defibrillators.

BACKGROUND: Atrial rate-responsive pacing (RRP) has proved to be safe in pacemaker recipients with chronotropic incompetence. Although RRP is available in all current implantable cardioverter defibrillators (ICDs), the outcomes of this pacing mode in ICD patients are unknown. The aim is to evaluate the relationship between atrial RRP and atrial arrhythmias in ICD recipients. METHODS: Dual-chamber and triple-chamber ICD patients were included in this multicenter cohort study. Patients with permanent atrial fibrillation (AF) or VVI pacing mode were excluded. The number and duration of atrial tachycardia (AT)/AF episodes were assessed. RESULTS: Data from 415 patients and 80,707 AT/AF episodes (median duration: 0.4 hours) were collected after a 21.3 ± 14.1-month follow-up. Atrial RRP was programmed in 90 (21.7%) patients and was associated with a higher atrial pacing percentage in the overall study population (51.2 ± 33.8% vs 18.4 ± 25.7%, P < 0.001) and to a higher ventricular pacing percentage among dual-chamber devices (22.3 ± 37.6% vs 9.3 ± 25%, P < 0.001). Independent factors associated with sustained AT/AF episodes (>23 hours) were previous AF (odds ratio [OR]: 7.98; 95% confidence interval [CI]: 4.11-15.47; P < 0.001) and atrial RRP (OR: 3.58; 95% CI: 1.82-7.03; P < 0.001). RRP was related to a lower sustained AT/AF episodes-free survival both in patients with a history of AF (43% vs 70%, P = 0.035) and without a history of AF (82% vs 97%, P = 0.004) at 2 years. CONCLUSIONS: Atrial RRP in ICD patients was related to a higher incidence of sustained atrial arrhythmias. This pacing mode may have an atrial proarrhythmic effect on ICD patients, especially among those with a history of AF.

An Automatic Algorithm Based on Morphological Stability During Fast Ventricular Arrhythmias Predicts Successful Antitachycardia Pacing in ICD Patients: A Multicenter Study.

BACKGROUND: Different types of ventricular arrhythmias (monomorphic ventricular tachycardia [VT], polymorphic VT, or ventricular fibrillation) can be detected by implantable cardiac defibrillators (ICDs) in fast VT zone. The efficacy of antitachycardia pacing (ATP) depends on the type of the treated arrhythmia. We hypothesized that an automatic algorithm based on morphological affinity of ICD far-field electrograms during tachycardia can predict ATP success and the need of shock. METHODS: The algorithm was evaluated on ventricular arrhythmias recorded in CareLink ICD remote monitoring system (Medtronic Inc., Minneapolis, MN, USA). Patients were selected if first ATP programmed was a burst of eight pulses at 88% coupling interval and if a far-field electrogram was available. The algorithm calculated a stability coefficient (SC) for all their stored ATP-treated fast ventricular arrhythmia (VA) episodes (LC 200-300 ms), analyzing the morphology homogeneity of the last eight recorded far-field electrograms before ventricular arrhythmias detection. RESULTS: Inclusion criteria were fulfilled by 717 patients from 29 centers. Three hundred and twenty fast VA were recorded in 103 patients. A higher SC was observed in episodes terminated with the first-ATP (0.78 [0.72-0.84] vs 0.74 [0.60-0.84]; P = 0.006). These differences were especially marked among the 62 episodes of very fast VA (CL ≤250 ms) (0.77 [0.74-0.85] vs 0.64 [0.51-0.8]; P = 0.006). In the multivariate analysis, a SC > 70% was independently associated with a higher likelihood of first-ATP success (odds ratio [OR] = 2.5; [95% confidence interval (CI) = 1.4-4.5], P = 0.001) and a lower need of shock (OR = 0.37; [95% CI = 0.2-0.7], P = 0.002). CONCLUSION: This automatic algorithm (stability coefficient) shows that ATP therapy response can be predicted in fast ventricular arrhythmias through morphology evaluation.

Etiology and Programming Effects on Shock Efficacy in ICD Recipients.

BACKGROUND: We sought to assess the efficacy of high-energy shocks to restore rhythm and predictors of success in patients with sustained ventricular arrhythmias and implantable cardioverter defibrillator (ICD). METHODS AND RESULTS: Data from 162 patients included in the UMBRELLA study that experienced one or more episodes of ventricular tachycardia (VT) for which ICD shocks of at least 30 Joules were delivered (appropriate high-energy shocks) were analyzed. In total, 456 ventricular arrhythmia episodes were registered. Forty four episodes (9.6%) from 39 patients (24%) had at least one ineffective high-energy shock delivered. Hypertrophic cardiomyopathy was more frequent among patients with unsuccessful shocks (10.3% vs 2.4%). Patients with ineffective shocks had higher proportion of sustained monomorphic ventricular arrhythmias (86.4%; the other 13.6% were sustained polymorphic and ventricular fibrillation [VF]) compared with patients with all their shocks effective (62.9%, P = 0.02). No statistical differences were found between groups in time from detection to the high-energy shock delivery, in tachycardia cycle length, or in antitachycardia pacing, but patients with ineffective high-energy shocks had higher proportion of previously ineffective low-energy shock (9.1% vs 0.5%, P = 0.01). CONCLUSION: We found a substantial rate of ineffective high-energy shocks for the treatment of VT or VF in patients with ICD. High-energy shock efficacy seems to be reduced by hypertrophic cardiomyopathy and by the administration of previous low-energy shocks.

Shock Reduction With Multiple Bursts of Antitachycardia Pacing Therapies to Treat Fast Ventricular Tachyarrhythmias in Patients With Implantable Cardioverter Defibrillators: A Multicenter Study.

INTRODUCTION: An empirical sequence of burst antitachycardia pacing (ATP) is effective in terminating fast ventricular tachycardias (FVT) in patients with implantable cardioverter-defibrillators (ICDs). We aimed to determine whether multiple ATP bursts for termination of FVT results in shock reduction compared to a single ATP burst. METHODS AND RESULTS: We analyzed data from the Umbrella trial, a multicenter prospective observational study of ICD patients followed by the CareLink Monitoring System. We compared the safety and effectiveness of a single ATP burst (Group 1) with a strategy of successive ATP sequences (Group 2) for termination of FVT episodes (cycle lengths 250-320 milliseconds) before shock therapy. Over a mean follow-up of 35 months, a total of 650 FVT episodes were detected in 154 patients (mean cycle length: 299 ± 18 milliseconds). Effectiveness of the first burst ATP in Group 1 was 73% and shocks were required in 27% of episodes. Effectiveness of the first burst ATP in Group 2 was 77%, and this increased to 91% with the third or successive ATP bursts. Shocks were required in 9% of episodes in group 2, representing a 67% reduction in the need of high-energy shocks. Median duration of FVT episodes and mortality in both groups were similar. Multivariate analysis indicated that programming multiple ATP bursts (OR 3.4, 95%CI 1.7-6.8, P = 0.001) was an independent predictor of ATP effectiveness. CONCLUSION: This study provides first evidence that a strategy of multiple burst ATP sequences for termination of FVT episodes leads to a clinically meaningful reduction in the need for shocks.

Perfil clínico e incidencia de arritmias ventriculares de los pacientes sometidos a recambio de generador de desfibrilador en España / Clinical profile and incidence of ventricular arrhythmia in patients undergoing defibrillator generator replacement in Spain

Introducción y objetivos. Se ha demostrado que los desfibriladores automáticos implantables reducen la mortalidad de ciertos pacientes con cardiopatía. El recambio de su batería es una situación frecuente en la práctica clínica, hasta un 30% de los implantes. El beneficio/riesgo del desfibrilador no es constante en el tiempo, y debe revaluarse en el momento del recambio. El objetivo del estudio es conocer las características clínicas y la incidencia de terapias del desfibrilador en los pacientes sometidos a un recambio de generador. Métodos. Se realizó un estudio retrospectivo multicéntrico basado en los pacientes del registro nacional UMBRELLA, sometidos a recambio por agotamiento de la batería del desfibrilador. Se analizó la incidencia de arritmias ventriculares mediante monitorización a distancia. Se analizaron los factores de riesgo de arritmia ventricular sostenida tras el recambio. Resultados. Se incluyó a 354 pacientes (media de edad, 61,8 ± 14,5 años; varones, 80%; prevención secundaria, 42%; arritmias ventriculares en el generador explantado, 62%). Tras un seguimiento de 25 meses, 70 pacientes (20%) presentaron terapias apropiadas y 8 (2,3%) tuvieron descargas inapropiadas. El sexo masculino, la presencia de cardiopatía estructural, la insuficiencia cardiaca y la ausencia de resincronización fueron predictores independientes de la aparición de arritmias ventriculares. Conclusiones. Una quinta parte de los pacientes tiene terapias apropiadas de desfibrilador en los primeros 2 años desde el recambio de generador. El conocimiento de los factores asociados a la aparición de arritmias tras el recambio puede ser útil para optimizar el rendimiento de la terapia (AU)

Introduction and objectives. Implantable cardioverter-defibrillators reduce mortality in some patients with heart disease. Battery replacement is a frequent occurrence in clinical practice and is required in up to 30% of implants. The benefit/risk ratio of defibrillators varies over time and should be reevaluated at the time of replacement. The aim of this study was to determine the clinical characteristics and incidence of defibrillator therapies in patients who underwent generator replacement. Results. A total of 354 patients were included (mean age [standard deviation], 61.8 [14.5] years; men, 80%; secondary prevention, 42%; ventricular arrhythmias in the explanted generator, 62%). After a 25-month follow-up, 70 patients (20%) received appropriate therapies and 8 (2.3%) received inappropriate discharges. Male sex, structural heart disease, heart failure, and the absence of resynchronization were independent predictors of ventricular arrhythmia occurrence. Conclusions. One-fifth of patients had appropriate defibrillator therapies in the first 2 years after generator replacement. Determination of the factors associated with arrhythmia occurrence after replacement may be useful to optimize implantable cardioverter-defibrillator treatment (AU)

Clinical profile and incidence of ventricular arrhythmia in patients undergoing defibrillator generator replacement in Spain.

INTRODUCTION AND OBJECTIVES: Implantable cardioverter-defibrillators reduce mortality in some patients with heart disease. Battery replacement is a frequent occurrence in clinical practice and is required in up to 30% of implants. The benefit/risk ratio of defibrillators varies over time and should be reevaluated at the time of replacement. The aim of this study was to determine the clinical characteristics and incidence of defibrillator therapies in patients who underwent generator replacement. METHODS: This multicenter retrospective study involved patients from the UMBRELLA national registry who underwent replacement due to defibrillator battery depletion. The incidence of ventricular arrhythmias was determined via remote monitoring. Risk factors for sustained ventricular arrhythmia after replacement were analyzed. RESULTS: A total of 354 patients were included (mean age [standard deviation], 61.8 [14.5] years; men, 80%; secondary prevention, 42%; ventricular arrhythmias in the explanted generator, 62%). After a 25-month follow-up, 70 patients (20%) received appropriate therapies and 8 (2.3%) received inappropriate discharges. Male sex, structural heart disease, heart failure, and the absence of resynchronization were independent predictors of ventricular arrhythmia occurrence. CONCLUSIONS: One-fifth of patients had appropriate defibrillator therapies in the first 2 years after generator replacement. Determination of the factors associated with arrhythmia occurrence after replacement may be useful to optimize implantable cardioverter-defibrillator treatment.

Prolonged inflation of coronary angioplasty balloon as treatment for subocclusive dissection of the coronary sinus during implantation of a coronary sinus pacing lead.

Cardiac resynchronization therapy with biventricular stimulation is an accepted treatment procedure for patients with severe heart failure (NYHA class III/IV), low left ventricle ejection fraction, and left bundle branch block, in spite of optimal medical treatment (Smith, S. C. Jr, Feldman, T. E., Hirshfeld, J. W. Jr, Jacobs, A. K., Kern, M. J., King, S. B. et al. Circulation, 113(7), e166-e286, (2006)). In the ventricular resynchronization procedure, an electrode must be implanted, via the coronary sinus (CS), in a coronary vein of the left ventricle (LV). Insertion of guide catheters and guide wires through the CS towards the target vein may produce more or less extensive dissections and staining which makes visualizing the target vein opening difficult and gives rise to deferment of the procedure. We describe a case of CS dissection, produced by the catheter guide, resulting in a venous wall flap which impeded further advancement of the lead. This was treated with prolonged inflation of a coronary angioplasty balloon, which allowed completion of the procedure in the same surgical intervention. To our knowledge, this is the first report of the successful use of a coronary angioplasty balloon to resolve this complication of electrode implantation.