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BACKGROUND: Digoxin is a widely prescribed drug for congestive heart failure and atrial fibrillation. Digoxin has a narrow therapeutic index and toxicity can develop quite easily. Digoxin immune fab (DIF) is an effective treatment for toxicity, however there are limited studies characterizing its impact on clinical outcomes in real-world clinical practice. OBJECTIVES: The aim of this study was to identify factors and healthcare outcomes associated with digoxin immune fab (DIF) treatment in patients with confirmed/suspected digoxin toxicity. METHODS: An IRB-approved retrospective chart review of digoxin toxic patients (2011-2020) presenting at an academic healthcare system was conducted. Demographic and clinical data were collected. Patients were stratified by DIF treatment versus non-DIF treatment. DIF utilization patterns (appropriate, use when not indicated, or underutilized) were determined using pre-defined criteria. Severe digoxin toxicity was defined as having one or more of the following: mental status disturbances, antiarrhythmic therapy, acute renal impairment or dehydration, serum digoxin concentration (SDC) > 4 ng/mL, or serum K+ > 5 mEq/mL. Logistic multivariable regression analysis evaluated factors associated with DIF use. All statistical analyses were performed in R version 4.1. RESULTS: Data from 96 patients (non-DIF treated group = 49; DIF treated group = 47) were analyzed. DIF was used appropriately in 70 patients (73%), underutilized in 19 (20%), and administered to 7 (7%) patients when it was not indicated. Several clinical parameters differentiated the DIF from the non-DIF group (p < 0.05) including higher mean SDC (3.41 ± 1.63 vs 2.87 ± 1.17), higher mean potassium (5.33 ± 1.48 vs 4.55 ± 0.87), more toxicity severity (85% vs 49%), and more likely to require cardiac pacing (26% vs 4%). Digoxin toxicity resolved sooner in the DIF group (coefficient - 0.702, 95% CI - 1.137 to - 0.267) (p < 0.01) and they had shorter intensive care unit lengths of stay (12.4 ± 20.3 vs 24.4 ± 28.7 days; p = 0.018). The all-cause mortality rate in patients appropriately managed with DIF therapy versus those patients where DIF was underutilized was 11% and 21%, respectively. CONCLUSIONS: Based on our study population, DIF therapy appears to be beneficial in limiting duration of toxicity and intensive care unit lengths of stay in digoxin toxic patients. Although DIF was appropriately utilized in most cases, there was a relatively high proportion of cases in which DIF treatment was either underutilized or not indicated.
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BACKGROUND: Spinal cord stimulation (SCS) reduces the incidence of ventricular tachyarrhythmias in experimental models. This study investigated the effects of long-term SCS on ventricular function in a postinfarction canine heart failure model. METHODS AND RESULTS: In stage 1, dogs underwent implantable cardioverter-defibrillator implantation and embolization of the left anterior descending artery followed by right ventricular pacing (240 ppm) for 3 weeks to produce heart failure. In stage 2, 28 surviving animals were assigned to the SCS (delivered at the T4/T5 spinal region for 2 hours 3 times a day), medicine (MED; carvedilol therapy at 12.5 mg PO BID), or control (CTRL; no therapy) group for the initial phase 1 study. In a subsequent phase 2 study, 32 stage 1 survivors were equally randomized to the SCS, MEDS (carvedilol plus ramipril 2.5 mg PO QD), SCS plus MEDS (concurrent therapy), or CTRL group. Animals were monitored for 5 weeks (phase 1) or 10 weeks (phase 2). In stage 3, all phase 1 animals underwent circumflex artery balloon occlusion for 1 hour. In the SCS group, left ventricular ejection fraction was 65+/-5% at baseline, 17+/-3% at the end of stage 1, and 47+/-7% at the end of stage 2. In the MED group, left ventricular ejection fraction was 61+/-4% at baseline, 18+/-3% at the end of stage 1, and 34+/-4% at the end of stage 2. In the CTRL group, left ventricular ejection fraction was 64+/-5% at baseline, 19+/-5% at the end of stage 1, and 28+/-3% at the end of stage 2. Left ventricular ejection fraction was significantly improved in the SCS compared with the MED and CTRL groups (P<0.001 for both). The mean number of spontaneous nonsustained ventricular tachyarrhythmias during stage 2 and the occurrence of ischemic ventricular tachyarrhythmias during stage 3 also were significantly decreased in the SCS (27+/-17 and 27%, respectively; P<0.03) and MED (58+/-42 and 33%; P<0.05) versus CTRL (88+/-52 and 76%) group. After 10 weeks in the phase 2 studies, the greatest recovery in ejection fraction was noted in the SCS (52+/-5%) and SCS+MEDS (46+/-4%) groups compared with the MEDS (38+/-2%) and CTRL (31+/-4%) groups. CONCLUSIONS: SCS significantly improved cardiac contractile function and decreased ventricular arrhythmias in canine heart failure.
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Estimulación Cardíaca Artificial/métodos , Modelos Animales de Enfermedad , Insuficiencia Cardíaca/terapia , Infarto del Miocardio/terapia , Taquicardia Ventricular/terapia , Función Ventricular/fisiología , Animales , Desfibriladores Implantables , Perros , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/fisiopatología , Masculino , Infarto del Miocardio/complicaciones , Infarto del Miocardio/fisiopatología , Médula Espinal/fisiología , Taquicardia Ventricular/etiología , Taquicardia Ventricular/fisiopatologíaRESUMEN
PURPOSE: We prospectively determined whether preimplant myocardial perfusion imaging (MPI) predicts outcome with biventricular pacing (BiVP). METHODS: Single-photon emission computed tomography (SPECT) MPI, left ventricular (LV) volumes, ejection fraction (EF), 6-min hall walk (6MW) were assessed at baseline and at 4 months in 19 patients with ischemic cardiomyopathy undergoing BiVP. Clinical and hemodynamic responses were correlated with MPI. RESULTS: Lower global myocardial scar burden predicted hemodynamic response to BiVP, while higher burden was associated with poor response. Clinical improvement with BiVP occurred in 12 (63%) of the patients. Clinical BiVP responders had lower rest/stress MPI score difference. There was a close negative correlation between MPI reversibility and increased 6MW distance. CONCLUSIONS: Baseline MPI is associated with clinical and hemodynamic response to BiVP: greater myocardial scar burden is predictive of poor hemodynamic response, while higher ischemic burden is predictive of poor clinical response. There is a differential response to BiVP by clinical and hemodynamic criteria.
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Estimulación Cardíaca Artificial , Isquemia Miocárdica/diagnóstico por imagen , Isquemia Miocárdica/terapia , Tomografía Computarizada de Emisión de Fotón Único , Anciano , Prueba de Esfuerzo , Femenino , Humanos , Masculino , Isquemia Miocárdica/fisiopatología , Estudios Prospectivos , Calidad de Vida , Radiofármacos , Estadísticas no Paramétricas , Tecnecio Tc 99m SestamibiRESUMEN
Basic and clinical evidence suggests that omega-3 (n-3) polyunsaturated fatty acids (PUFAs) decrease fatal arrhythmias and infarct sizes. This study investigated if pericardial delivery of n-3 PUFAs would protect the myocardium from ischemic damages and arrhythmias. Acute myocardial infarctions were induced in 23 pigs with either 45 min balloon inflations or clamp occlusions of the left anterior descending coronary arteries and 180 min reperfusion. Docosahexaenoic acid (C22:6n-3, DHA, 45 mg), one of the main n-3 PUFAs in fish oil, was infused within the pericardial space only during the 40-min stabilizing phase, 45 min ischemia and initial 5 min reperfusion. Hemodynamics and cardiac functions were very similar between the DHA-treated and control groups. However, DHA therapy significantly reduced infarct sizes from 56.8 +/- 4.9% for controls (n = 12) to 28.8 +/- 7.9% (P < 0.01) for DHA-treated animals (n = 11). Compared with controls, DHA-treated animals significantly decreased heart rates and reduced ventricular arrhythmia scores during ischemia. Furthermore, three (25%) control animals experienced eight episodes of ventricular fibrillation (VF), and two died subsequent to unsuccessful defibrillation. In contrast, only 1 (9%) of 11 DHA-treated pigs elicited one episode of VF that was successfully converted via defibrillation to normal rhythm; thus, mortality was reduced from 17% in the controls to 0% in the DHA-treated animals. These data demonstrate that pericardial infusion of n-3 PUFA DHA can significantly reduce both malignant arrhythmias and infarct sizes in a porcine infarct model. Pericardial administration of n-3 PUFAs could represent a novel approach to treating or preventing myocardial infarctions.
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Arritmias Cardíacas/prevención & control , Cardiotónicos/administración & dosificación , Ácidos Docosahexaenoicos/administración & dosificación , Hemodinámica/efectos de los fármacos , Infarto del Miocardio/prevención & control , Daño por Reperfusión Miocárdica/prevención & control , Miocardio/patología , Pericardio/efectos de los fármacos , Animales , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/patología , Arritmias Cardíacas/fisiopatología , Presión Sanguínea/efectos de los fármacos , Gasto Cardíaco/efectos de los fármacos , Cardiotónicos/metabolismo , Modelos Animales de Enfermedad , Ácidos Docosahexaenoicos/metabolismo , Frecuencia Cardíaca/efectos de los fármacos , Infusiones Parenterales , Masculino , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Infarto del Miocardio/fisiopatología , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/patología , Daño por Reperfusión Miocárdica/fisiopatología , Orquiectomía , Pericardio/metabolismo , Pericardio/patología , Pericardio/fisiopatología , Porcinos , Fibrilación Ventricular/patología , Fibrilación Ventricular/fisiopatología , Fibrilación Ventricular/prevención & control , Función Ventricular Izquierda/efectos de los fármacos , Presión Ventricular/efectos de los fármacosRESUMEN
BACKGROUND: Optimizing atrioventricular (AV) delay during biventricular (BiV) pacemaker implantation can require substantial resources. Hence, a simpler method is desirable. We hypothesized that interatrial conduction time (IACT), measured at the time of BiV device implant, could be a surrogate value for the optimal AV delay. OBJECTIVE: This study determined the relationship between paced IACT and the optimal paced AV delay (PAV), as determined by echocardiography. METHODS: Consecutive subjects (N = 25; age = 66 +/- 10 years; M/F: 17/8) undergoing BiV pacemaker implantation and in sinus rhythm were included. Cannulation of the coronary sinus (CS) was at the operator's discretion. A quadripolar electrophysiology catheter was inserted via the guiding sheath into the inferiolateral CS to measure left atrial depolarization. The IACT was calculated as the interval between right atrial stimulation artifact and earliest deflection on the coronary sinus catheter electrogram. Subsequently, during atrial pacing the PAV was determined using transmitral pulsed wave Doppler echocardiography (iterative method). The relationship between paced IACT and PAV was then determined. RESULTS: The mean +/- SD paced IACT and PAV were 126 +/- 25 msec and 157 +/- 23 msec, respectively. There was a strong positive correlation between the paced IACT and PAV (r = 0.73, P < 0.001). The equation describing the relationship was PAV = 0.68 * (IACT + 104) msec. CONCLUSIONS: The paced IACT has a strong correlation with the echo derived optimal PAV. This method may be used to program PAV intervals without need for echocardiography in patients undergoing BiV pacemaker implantation.
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Estimulación Cardíaca Artificial/métodos , Sistema de Conducción Cardíaco/diagnóstico por imagen , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/terapia , Marcapaso Artificial , Anciano , Femenino , Humanos , Masculino , Valor Predictivo de las Pruebas , Implantación de Prótesis/métodos , Resultado del Tratamiento , UltrasonografíaRESUMEN
BACKGROUND: Pharmacological ventricular rate control is an acceptable atrial fibrillation (AF) therapy limited by systemic toxicity. We postulate that focal catheter-based drug delivery into the atrioventricular nodal (AVN) region may effectively control ventricular rate during AF without systemic toxicity. This study evaluated the effects of focally administered acetylcholine on AVN conduction and refractoriness during sinus rhythm and AF. METHODS AND RESULTS: Canines (n=7) were anesthetized and instrumented to assess cardiac electrophysiology and blood pressure. A custom drug delivery catheter was implanted in the AVN region. Incremental doses of acetylcholine starting at 10 microg/min were infused until complete AV block was achieved. Acetylcholine induced dose-dependent AV block. AF induction and electrophysiology measurements were performed during baseline and acetylcholine-induced first-degree and third-degree AV block. During AF, infusion of acetylcholine decreased ventricular rates from 182+/-32 to 77+/-28 and 28+/-8 bpm (first-degree and third-degree AV block, respectively; P<0.05). At the first-degree AV block dose, AVN effective refractory period increased from 186+/-37 to 282+/-33 ms, and Wenckebach cycle length increased from 271+/-29 to 378+/-58 ms (P<0.05). The first-degree AV block dose prolonged AV and AH intervals by 26% and 23% (P<0.05), whereas AA intervals and blood pressure remained unchanged, demonstrating a local effect. All effects were reversed 20 minutes after infusion was stopped. CONCLUSIONS: Focal acetylcholine delivery into the AVN increased AVN refractoriness and significantly decreased ventricular rate response during induced AF in a dose-related, reversible manner without systemic side effects. This may represent a novel therapy for AF whereby ventricular rate is controlled with the use of an implantable drug delivery system.
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Fibrilación Atrial/tratamiento farmacológico , Nodo Atrioventricular/fisiopatología , Catéteres de Permanencia , Frecuencia Cardíaca/fisiología , Conducción Nerviosa/fisiología , Acetilcolina/administración & dosificación , Acetilcolina/uso terapéutico , Animales , Modelos Animales de Enfermedad , Perros , Sistemas de Liberación de Medicamentos , Femenino , Masculino , Vasodilatadores/administración & dosificación , Vasodilatadores/uso terapéuticoRESUMEN
INTRODUCTION: Implantable atrial defibrillators (IADs) have proved to be safe and effective in the management of atrial fibrillation. A potential limitation of self-activated IAD therapy is patient-reported pain and anxiety. The main objective of the present study was to determine whether triazolam improved patient perception of the shock experience or altered patient memory of shock discomfort relative to placebo. METHODS AND RESULTS: A total of 15 men and women (mean age: 59 +/- 6 years) were enrolled in this double-blind, placebo-controlled, crossover study of triazolam. Randomized study medication was administered orally 75 minutes prior to scheduled atrial shock delivery. Patient perception of the shock experience was assessed along with sedation, memory, anxiety, and mood. Triazolam reduced mean pre-shock anxiety (t= 2.98, df = 14, P = 0.01) and shock-related pain (t= 2.74, df = 13, P = 0.01) and intensity (t= 2.64, df = 13, P = 0.018) relative to placebo. Similarly, participants recalled less discomfort the morning after shock with triazolam than with placebo (t= 2.82, df = 11, P = 0.017). CONCLUSIONS: This study was the first to investigate the use of an oral benzodiazepine administered prior to patient-activated shock delivery with an IAD. Our data indicate that oral triazolam is beneficial in decreasing pain and anxiety associated with self-activated atrial defibrillation. If triazolam provides a similar benefit in the community to that which has been reported here, this medication could be offered to patients as an adjunct to intermittent IAD therapy.
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Adyuvantes Anestésicos/administración & dosificación , Ansiedad/tratamiento farmacológico , Fibrilación Atrial/terapia , Sedación Consciente/métodos , Cardioversión Eléctrica/efectos adversos , Dolor/tratamiento farmacológico , Triazolam/administración & dosificación , Administración Oral , Adulto , Anciano , Ansiedad/etiología , Fibrilación Atrial/complicaciones , Estudios Cruzados , Desfibriladores Implantables , Método Doble Ciego , Cardioversión Eléctrica/instrumentación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Dolor/etiología , Resultado del TratamientoRESUMEN
AIMS: Previous studies have demonstrated that ambulatory atrial defibrillation shocks delivered by an implantable cardioverter-defibrillator (ICD) are safe and effective, but poorly tolerated. Separate studies have demonstrated the utility of single oral bolus propafenone for conversion of recent-onset atrial fibrillation (AF); however, most patients were hospitalized, had no structural heart disease, were taking no other antiarrhythmic drugs, and were not exposed to concomitant shock. We hypothesized that a single oral bolus dose of propafenone given early after onset would be a safe and effective adjunct to ICD-based AF therapy and improve overall therapy tolerance. METHODS AND RESULTS: A randomized three-way crossover study design was used to compare three strategies, deployed in the ambulatory setting early after AF episode onset in 35 ICD patients with advanced, drug refractory episodic/persistent syndromes, many of whom had structural heart disease and were taking other antiarrhythmic drugs: (i) single oral bolus propafenone (600 mg), followed by ICD shock if necessary; (ii) single oral bolus placebo, followed by ICD shock if necessary; and (iii) no oral bolus therapy and ICD shock if necessary (no bolus). Antiarrhythmic efficacy, defined by the restoration of sinus rhythm within 24 h, was similar during propafenone (81%) and no-bolus strategies (84%); both were significantly higher than during placebo strategy (62%). Propafenone was well tolerated and not associated with proarrhythmia. Shock use was significantly lower during propafenone strategy (19%) than during no-bolus strategy (55%); this was correlated with improved patient tolerance. CONCLUSION: Adjunctive use of single oral bolus propafenone is safe and effective in patients with an ICD and improves patient tolerance of device-based AF therapy.
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Antiarrítmicos/administración & dosificación , Fibrilación Atrial/terapia , Desfibriladores Implantables , Propafenona/administración & dosificación , Administración Oral , Terapia Combinada , Estudios Cruzados , Femenino , Humanos , MasculinoRESUMEN
BACKGROUND: Intrathecal clonidine (ITC) is used clinically to manage neuropathic pain but frequently causes hypotension and bradycardia due to centrally mediated sympatholytic effects. OBJECTIVES: The purpose of this study was to evaluate the cardiac electrophysiologic effects of thoracic ITC and its effects on ischemia-provoked ventricular arrhythmias. METHODS: Twelve mongrel dogs with healed myocardial infarctions and heart failure were evaluated. ITC was delivered locally via catheter to the T2-T4 spinal segments and was dosed to reduce heart rate (HR) by >20% to 25%. Electrophysiologic testing was performed before and after ITC. Transient (4-minute) myocardial ischemia was induced via left circumflex coronary artery occlusion on two separate occasions to provoke ventricular arrhythmias (ventricular tachycardia [VT]/ventricular fibrillation [VF]). Ischemic episodes were separated by 1 to 2 days, and dogs were randomly assigned to receive ITC or intrathecal saline flush (control) prior to the first or the second ischemic episode. RESULTS: ITC produced significant decrease in HR (31%) and increases in PR interval (22%), Wenckebach cycle length (122%), and atrial and ventricular effective refractory periods (19% and 9%, respectively) but had no significant effect on systemic blood pressure. The occurrence of VT/VF was reduced from 9 of 12 to 3 of 12 dogs when ITC was administered prior to transient myocardial ischemia (P = .04). ITC also blunted ischemia-induced HR increase by 74%. CONCLUSION: ITC reduced ischemia-induced VT/VF in a canine model of healed myocardial infarction with superimposed heart failure and acute ischemia. Results from electrophysiologic testing were consistent with a clonidine-induced reduction in cardiac sympathetic activity from the spinal cord. These data suggest that ITC administration may be a novel approach to treating ventricular arrhythmias.
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Agonistas alfa-Adrenérgicos/administración & dosificación , Clonidina/administración & dosificación , Insuficiencia Cardíaca/terapia , Infarto del Miocardio/terapia , Taquicardia Ventricular/prevención & control , Fibrilación Ventricular/prevención & control , Animales , Presión Sanguínea/efectos de los fármacos , Modelos Animales de Enfermedad , Perros , Técnicas Electrofisiológicas Cardíacas , Insuficiencia Cardíaca/fisiopatología , Frecuencia Cardíaca/efectos de los fármacos , Inyecciones Espinales , Precondicionamiento Isquémico Miocárdico , Infarto del Miocardio/fisiopatología , Marcapaso Artificial , Taquicardia Ventricular/fisiopatología , Disfunción Ventricular Izquierda/fisiopatología , Disfunción Ventricular Izquierda/terapia , Fibrilación Ventricular/fisiopatologíaRESUMEN
BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with a variety of symptoms such as dizziness, palpitations, shortness of breath, and other signs of heart failure, which in turn impact quality of life (QOL). Implantable cardioverter defibrillators with atrial therapies (ICDs-ATs) have been shown to reduce AF symptoms and improve QOL in select AF samples. METHOD: This study examined the strength of relationships between objective (device-detected AF events) versus subjective (emotional symptoms) data and AF symptoms (number) reported as part of the Patient Atrial Shock Survey of Acceptance and Tolerance Study (N = 96, 72% men, M age = 65, SD = 12). Depression and anxiety were assessed via the Center for Epidemiological Studies--Depression Scale and the-State Trait Anxiety Inventory. AF disease burden was measured via a number of device-detected AF episodes and the Atrial Tachyarrhythmia Symptom Severity Scale. RESULTS: Hierarchical multiple regression analysis indicated that negative emotions accounted for a significant 13.2% of unique variance in AF symptom score (F change (1, 54) = 9.625, P = 0.003). On the other hand, the number of device-detected AF episodes accounted for non-significant 8.2% of unique variance in the AF symptom score (P = 0.167). The full model explained 25.7% of the variance in AF symptom score (F(6, 54) = 3.110, P = 0.011). Specifically, greater number of treated AF episodes (beta= 0.251, P = 0.043) and higher levels of negative emotions (beta= 0.369, P = 0.003) predicted greater number of reported AF symptoms. CONCLUSION: Therefore, psychological distress may be a significant confounding factor affecting patient's report of AF symptoms rather than the actual experience of recurrent AF episodes.
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Fibrilación Atrial/fisiopatología , Fibrilación Atrial/psicología , Anciano , Ansiedad/epidemiología , Ansiedad/etiología , Fibrilación Atrial/terapia , Desfibriladores Implantables , Depresión/epidemiología , Depresión/etiología , Análisis Factorial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Calidad de Vida , Encuestas y CuestionariosRESUMEN
BACKGROUND: Thoracic spinal cord stimulation (SCS) is a promising therapy in treating refractory angina. This study was designed to investigate SCS with regard to the risk of arrhythmias during myocardial ischemia and its cardiac electrophysiological effects. METHODS AND RESULTS: We studied 22 dogs with healed anterior myocardial infarction (MI) and superimposed heart failure (HF) induced by rapid ventricular pacing. SCS was applied at the dorsal T1-T2 segments of the spinal cord (at 50 Hz, 0.2 ms) for 15 minutes. Transient (2-minute) myocardial ischemia was induced on 2 separate occasions (no SCS and SCS) to provoke ventricular arrhythmias (ventricular tachycardia/ventricular fibrillation; VT/VF). Ischemic episodes were separated by 90 minutes, and dogs were randomly assigned to receive SCS or no SCS before the first or second ischemic episode. SCS reduced the occurrence of VT/VF from 59% to 23% when SCS was applied during transient myocardial ischemia (odds ratio, 0.36; 95% confidence interval, 0.1626 to 0.5646; P=0.0009). SCS also decreased sinus rate by 7.5+/-14 bpm (P=0.048), increased the PR interval by 11.1+/-14.7 ms (P=0.009), and reduced systolic blood pressure by 9.8+/-13.6 mm Hg (P=0.02). CONCLUSIONS: Thoracic SCS appears to protect against ischemic VT/VF in a canine model of healed MI and HF. SCS reduced sinus rate and systolic blood pressure, changes consistent with the previously known antisympathetic effect of SCS, which may have contributed to the antiarrhythmic benefits.
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Arritmias Cardíacas/prevención & control , Estimulación Eléctrica/métodos , Isquemia Miocárdica/complicaciones , Médula Espinal , Fibrilación Ventricular/prevención & control , Animales , Arritmias Cardíacas/etiología , Presión Sanguínea , Modelos Animales de Enfermedad , Perros , Insuficiencia Cardíaca/complicaciones , Frecuencia Cardíaca , Ventrículos Cardíacos , Infarto del Miocardio/complicaciones , Infarto del Miocardio/mortalidad , Riesgo , Tórax , Resultado del Tratamiento , Fibrilación Ventricular/etiologíaRESUMEN
PURPOSE: The hypothesis that intrapericardial (ip.) ibutilide administration would terminate pacing-induced sustained atrial fibrillation (AF) and ibutilide distribution were tested. METHODS AND RESULTS: Sustained (> or =24 hours) AF was induced by 59 +/- 20 day rapid atrial pacing in 19 dogs. After sustained AF was present, the atrial pacemaker was turned off and 9 open chest dogs received 0.015 mg/kg ibutilide (37 degrees C) in 30 ml saline into the pericardial sac. Ten control dogs received 30 ml saline (37 degrees C) ip. QT intervals, right ventricular monophasic action potential duration at 90% of repolarization (RV-MAPD(90)), AF mean cycle length (AFCL(m)), systolic- and diastolic intraarterial blood pressures, intrapericardial-, right atrial- and ventricular pressures, cardiac output and ibutilide concentrations were measured. If AF persisted after the 1st drug infusion, dual site rapid atrial pacing (DRAP) simultaneously from the high right atrium and coronary sinus was performed to terminate AF. If it was ineffective, a 2nd ip. drug infusion in the same fashion as the 1st one, was attempted. There was no significant difference in AF termination [5/9 (56%) in ibutilide treated and 3/10 (30%) in control dogs] between the two groups. DRAP never terminated AF. The AF duration did not differ between the two groups. Compared with control, ibutilide treatment prolonged significantly AFCL(m) (p < 0.001) and non-significantly QT, RV-MAPD(90). No significant difference was found in systolic and diastolic blood pressure and cardiac output between the two groups. The two orders of magnitude greater ibutilide concentration in the pericardial fluid than that in the femoral vein decreased rapidly over time, drug concentration was greatest in the atria, smaller in the ventricular myocardium, with a trend decreasing from the epi- to endocardium. CONCLUSIONS: Despite a significant atrial electrophysiological effect, ip. delivery of ibutilide did not result in higher AF termination rate compared with control.
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Antiarrítmicos/farmacología , Fibrilación Atrial/tratamiento farmacológico , Sulfonamidas/farmacología , Animales , Antiarrítmicos/administración & dosificación , Modelos Animales de Enfermedad , Perros , Relación Dosis-Respuesta a Droga , Electrocardiografía , Técnicas Electrofisiológicas Cardíacas , Femenino , Atrios Cardíacos/efectos de los fármacos , Instilación de Medicamentos , Masculino , Pericardio , Sulfonamidas/administración & dosificación , Factores de Tiempo , Insuficiencia del TratamientoRESUMEN
Acceptability of the atrial defibrillator is partly limited by concerns about shock related anxiety and discomfort. Sedation and/or automatic cardioversion therapy during sleep may ease shock discomfort and improve patient acceptability. Three atrial cardioversion techniques were compared: patient-activated cardioversion with sedation, automatic night cardioversion with sedation, and automatic night cardioversion without sedation. Sedation was oral midazolam (15 mg). Fifteen patients aged 60 +/- 13 years were assigned each strategy randomly for three consecutive episodes of persistent atrial fibrillation requiring cardioversion. Patients completed questionnaires for multiple parameters immediately and again at 24 hours postcardioversion. Atrial cardioversion strategies with oral sedation (patient-activated and automatic) significantly reduced shock recall by 77% (P < 0.005), therapy dissatisfaction by 57%-71% (P < 0.03), shock discomfort by 61%-73% (P < 0.01), shock pain by 79%-83% (P < 0.001), and shock intensity by 73%-77% (P < 0.03), compared to automatic night cardioversion without sedation (P < 0.02). Atrial shock pain was short-lived and caused little disruption to the patients' daily routines. Automatic night cardioversion without sedation, resulted in sleep disturbances not seen with the other strategies (42% vs 0%, P < 0.001) as well as concerns about future pain or discomfort. Twelve patients (80%) chose patient-activated cardioversion with sedation as their preferred treatment, and three (20%) remainder chose automatic night cardioversion with sedation. Ninety percent of patients chose automatic night cardioversion without sedation as the least acceptable therapy. Sedation significantly increases atrial shock acceptability regardless of cardioversion method. Shocks without sedation are significantly less acceptable to patients using the atrial defibrillators.
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Fibrilación Atrial/terapia , Desfibriladores Implantables , Hipnóticos y Sedantes/administración & dosificación , Midazolam/administración & dosificación , Aceptación de la Atención de Salud , Ansiedad/etiología , Estudios Cruzados , Desfibriladores Implantables/efectos adversos , Desfibriladores Implantables/psicología , Cardioversión Eléctrica/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dolor/etiología , Dolor/psicología , Satisfacción del Paciente , Percepción , Trastornos del Sueño-Vigilia/etiologíaRESUMEN
An implantable cardioverter defibrillator with atrial therapies (ICD-ATs) is an effective therapy to manage atrial tacharrhythmias. Acceptance of this therapy is limited by atrial shock related anxiety and discomfort. Inhaled nitrous oxide (N2O) is a potent sedative-analgesic-anxiolytic agent that may mitigate shock discomfort and anxiety and improve patient ICD-AT acceptance. ICD-AT patients with more than one ambulatory atrial shock within 12 months were enrolled and grouped by ICD-AT shock method; awake (n = 9) or asleep (n = 4) when ambulatory ICD-AT shock is delivered. A baseline questionnaire assessed the most recent ambulatory ICD-AT shock (3 +/- 3 months). A 65% N2O/35% O2 mixture was inhaled for 4 minutes followed by an ICD-AT test shock (18 +/- 8 J). The test shock mimicked the awake shock method. The test shock experience during N2O was evaluated via questionnaire immediately following and 24 hours after the shock. Shock related anxiety, intensity, pain, and discomfort were assessed using a ten-point rank scale. Baseline test shock scores were similar between the shock method groups. In the awake shock method group, N2O greatly reduced preshock anxiety by 48% (6.4 +/- 2.4 to 3.3 +/- 2.0, or), and shock related intensity (5.9 +/- 3.1 to 3.3 +/- 2.5), pain (5.0 +/- 2.6 to 2.0 +/- 2.1), and discomfort (5.6 +/- 2.4 to 1.3 +/- 1.4) from baseline values by 45%, 60%, and 78% (P < 0.05), respectively. The asleep shock method group reported no changes in shock related anxiety, intensity, pain, or discomfort. Atrial shock concern, assessed via a five-point rank scale (5 = extreme concern) was improved by N2O but only in the awake group (3.1 +/- 1.0 baseline to 1.6 +/- 0.5 N2O, P = 0.008). There were no adverse events with N2O and patients fully recovered within 5 minutes after N2O. In conclusion, 65% N2O greatly reduced shock related pain and discomfort, and significantly reduced atrial shock concern but only in the awake shock method group. The benefits of N2O therapy may expand the use and acceptability of ICD-AT therapy into a larger atrial fibrillation cohort.
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Analgésicos no Narcóticos , Ansiolíticos , Fibrilación Atrial/terapia , Cardioversión Eléctrica/efectos adversos , Hipnóticos y Sedantes , Óxido Nitroso , Administración por Inhalación , Anciano , Analgésicos no Narcóticos/administración & dosificación , Ansiolíticos/administración & dosificación , Desfibriladores Implantables , Femenino , Humanos , Hipnóticos y Sedantes/administración & dosificación , Masculino , Óxido Nitroso/administración & dosificación , Dolor/tratamiento farmacológico , Encuestas y CuestionariosRESUMEN
INTRODUCTION: The Medtronic Jewel AF 7250 is an implantable cardioverter defibrillator with atrial and ventricular therapies (ICD-AT). The ICD-AT is effective in managing atrial tachyarrhythmias (atrial fibrillation [AF]), but patient acceptance remains an issue. This aim of this study was to measure ICD-AT acceptance. METHODS AND RESULTS: ICD-AT acceptance was evaluated in 96 patients enrolled in the "Jewel AF-AF-Only Study" for > or =3 months of follow-up (mean 19 months). Patients were mostly men (72%; age 65 +/- 12 years). Clinical data and a written survey (75% response rate) were used to quantify demographics, AF frequency and symptoms, atrial defibrillation therapy, quality of life (QOL), psychosocial distress, and ICD-AT therapy acceptance. From implant to survey, AF symptom and severity scores decreased by 18% (P < or = 0.05), and QOL (SF-36) scores increased by 15% to 50% (P < or = 0.05). ICD-AT therapy acceptance was high, with 71.3% of patients scoring in the 75th percentile on the Florida Patient Acceptance Survey. ICD-AT acceptance was correlated with the Physical Component Scale and Mental Health Component Scale scores of the SF-36 (r = 0.28 and 0.35, respectively). ICD-AT acceptance was negatively correlated with depressive symptomatology (r =-0.59), trait anxiety (r =-0.48), illness intrusiveness (r =-0.55), and AF symptom and severity scores (r =-0.26). ICD-AT acceptance did not correlate with preimplant cardioversions, number of atrial shocks, AF episodes detected by the device, or device implant duration. CONCLUSION: Most patients accepted ICD-AT therapy. Patients were more likely to accept ICD-AT if they had less psychosocial distress, greater QOL, and lower AF symptom burden.
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Fibrilación Atrial/terapia , Recolección de Datos , Desfibriladores Implantables , Aceptación de la Atención de Salud , Adulto , Anciano , Anciano de 80 o más Años , Fibrilación Atrial/psicología , Actitud Frente a la Muerte , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Psicometría , Calidad de Vida/psicología , Autoimagen , Perfil de Impacto de Enfermedad , Estadística como Asunto , Resultado del TratamientoRESUMEN
BACKGROUND: Patient perspectives about their illness experiences, symptoms, and treatment are essential aspects of quality of life and provide direction for patient and provider decision making regarding innovative therapies such as implantable devices for arrhythmia. PURPOSE: The purpose of this qualitative study was to describe: 1) the experience of patients living with symptomatic, drug-refractory atrial fibrillation (AF) and 2) patient experiences and acceptance of treatment with the implantable cardioverter defibrillator (ICD) with atrial therapies (ICD-AT) including ventricular and atrial defibrillation therapy. PARTICIPANTS: Subjects were 3 women and 8 men, 35 to 80 years of age, who received the Medtronic Jewel AF 7250 ICD-AT as therapy for recurrent, drug-refractory AF, had a history of AF for 3 to 20 years and had experienced multiple treatment modalities including frequent external cardioversion in an effort to control their AF. METHODS: A semi-structured interview addressed experiences of symptoms and prior treatment for AF and experiences, concerns, and perceived benefits of the ICD-AT. Interviews were recorded and transcribed verbatim. Narratives were coded and categorized using Atlas Ti(R) software. Qualitative interpretive analysis methods were used to identify key themes. RESULTS: Before ICD-AT, patient themes focused on AF that was: 1) misdiagnosed, minimized, and poorly treated; 2) distressful because of frequent and intense AF symptoms (fatigue, dizziness, shortness of breath, and anxiety) before ICD-AT; 3) limiting of activities of daily living; 4) associated with distress from enduring previous treatment; and 5) associated with the continuous pursuit of successful treatment and maintenance of normalcy. Decision making regarding ICD-AT therapy included weighing symptom or treatment distress versus anticipated risks or benefits, hope for better outcomes, and lack of options. After ICD-AT, themes included positive perceptions of the device because of AF symptom relief, ability to resume normalcy, and medication tolerance; incorporation of shock experiences into life routines; and patient suggestions regarding preparation and social support. IMPLICATIONS: Symptoms of AF have a major negative impact on overall quality of life. Treatment with the ICD-AT confers a sense of security and reduced symptom distress. Greater provider attention to patient preparation and facilitating social support are important for future ICD-AT patient care.
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Fibrilación Atrial/psicología , Fibrilación Atrial/terapia , Desfibriladores Implantables , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Entrevistas como Asunto , Masculino , Persona de Mediana Edad , Satisfacción del PacienteRESUMEN
INTRODUCTION: The Medtronic ICD-AT has atrial/ventricular therapies, which can be programmed to deliver atrial defibrillation during sleep, intended to potentially decrease shock anxiety/pain and lifestyle disruption. However, these shocks may diminish sleep quality. This study examined atrial shock characteristics (i.e., mode, frequency), AF symptoms, and psychological factors as determinants of sleep quality. METHODS AND RESULTS: The 96 ICD-AT patients were mostly men (72%; M age 65 +/- 12 years) and implanted for 1.6 years (SD = 0.8 years). Patients were divided into shock groups based on the proportion of mode (> or =90%) of total atrial shocks received. Patients were grouped into either automatic-nocturnal shock group (8 P.M.-8 A.M.; n = 35) or manual-awake shock group (n = 42). Psychological measures included Pittsburgh Sleep Quality Index (PSQI), Center for Epidemiology Studies-Depression Scale, State-Trait Anxiety Inventory, and Illness Intrusiveness Rating Scale. Atrial fibrillation disease burden was assessed via atrial symptom score and atrial shock use. PSQI global scores were similar between manual (7.67 +/- 2.53) and automatic shock (8.20 +/- 2.93) groups. A multiple hierarchical regression analysis indicated that no atrial shock variables were predictive of sleep quality; yet, both AF symptom (B = 0.226, P = 0.040) and depression (B = 0.392, P = 0.034) scores predicted diminished sleep quality, accounting for 42% of the variance in global sleep quality (P < 0.001). CONCLUSION: These results suggest that atrial defibrillation therapy does not have a deleterious impact on sleep. However, the significance of AF symptoms and depression indicate that comprehensive care of both physical and psychological symptomatology may improve sleep quality in ICD-AT patients.
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Fibrilación Atrial/fisiopatología , Fibrilación Atrial/terapia , Desfibriladores Implantables , Cardioversión Eléctrica , Sueño , Anciano , Ritmo Circadiano , Depresión/etiología , Cardioversión Eléctrica/efectos adversos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las PruebasRESUMEN
An experimental model of conduction velocity (CV) and refractory period dispersion was established to determine which variable is a determinant of myocardial vulnerability. Anesthetized swine were instrumented with a left anterior descending coronary artery catheter for regional infusion of lidocaine (n = 6), low-dose d-sotalol (n = 4), high-dose d-sotalol (n = 6), or saline (n = 6), to create dispersion in CV (lidocaine), refractoriness (d-sotalol), or neither (saline). Ventricular fibrillation thresholds (VFTs) and refractory periods were determined at five sites (one drug perfused, four non-drug perfused). CV was determined in one drug-perfused area (left ventricular epicardial apex) and one non-drug perfused area (right ventricular epicardial base). Lidocaine and low- and high-dose d-sotalol increased VFT when stimuli were delivered in the drug-perfused area. However, lidocaine decreased VFT when stimuli were delivered at non-drug perfused areas by an average of 52%. Neither d-sotalol dose affected VFT when stimuli were delivered in non-drug perfused areas. Lidocaine increased CV dispersion by 18-26 cm/s but did not alter refractoriness. Both d-sotalol doses increased dispersion in refractoriness by 15-27 ms but did not alter CV. Saline did not affect either variable. Regional lidocaine had profibrillatory effects when stimuli were delivered in non-drug perfused areas, whereas regional d-sotalol did not. Hence, CV dispersion is a more likely determinant of myocardial vulnerability than refractoriness.