RESUMEN
BACKGROUND: Patients with postural tachycardia syndrome (POTS) experience chronic symptoms of orthostatic intolerance. There are minimal data detailing the demographics, clinical features and clinical course of this condition. This online, community-based survey highlights patients' experience with POTS. It consists of the largest sample of POTS patients reported to date. OBJECTIVES: To describe the demographics, past medical history, medications, treatments and diagnostic journey for patients living with POTS. METHODS: Postural tachycardia syndrome patients completed an online, community-based, cross-sectional survey. Participants were excluded if they had not received a diagnosis of POTS from a physician. The questions focused on the patient experience and journey, rather than physiological responses. RESULTS: The final analysis included 4835 participants. POTS predominantly affects white (93%) females (94%) of childbearing age, with approximately half developing symptoms in adolescence (mode 14 years). POTS is a chronic multisystem disorder involving a broad array of symptoms, with many patients diagnosed with comorbidities in addition to POTS. POTS patients often experience lengthy delays [median (interquartile range) 24 (6-72) months] and misdiagnosis, but the diagnostic delay is improving. POTS patients can present with a myriad of symptoms most commonly including lightheadedness (99%), tachycardia (97%), presyncope (94%), headache (94%) and difficulty concentrating (94%). CONCLUSIONS: These data provide important insights into the background, clinical features and diagnostic journey of patients suffering from POTS. These data should serve as an essential step for moving forward with future studies aimed at early and accurate diagnoses of these patients leading to appropriate treatments for their symptoms.
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Síndrome de Taquicardia Postural Ortostática/psicología , Síndrome de Taquicardia Postural Ortostática/terapia , Adulto , Anciano , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Síndrome de Taquicardia Postural Ortostática/diagnóstico , Síndrome de Taquicardia Postural Ortostática/fisiopatología , Encuestas y CuestionariosRESUMEN
Overexpression of calcineurin in transgenic mouse heart results in massive cardiac hypertrophy followed by sudden death. Sudden deaths are caused by abrupt transitions from sinus rhythm to heart block (asystole) in calcineurin-overexpressing (CN) mice. Preliminary studies showed decreased maximum change in potential over time (dV/dt(max)) of phase 0 of the action potential. Accordingly, the hypothesis was tested that decreased activity of the sodium channel contributes to heart block. Profound decreases in activity of sodium currents (I(Na)) paralleled the changes in action potential characteristics. Progressive age-dependent decreases were observed such that at 42-50 days of life little sodium channel function existed. However, this was not paralleled by decreased protein expression as assessed by immunocytochemistry or by Western blot. Since calcineurin can interact with the ryanodine receptor, we assessed whether chronic in vitro treatment with BAPTA-AM, thapsigargin, and ryanodine could rescue the decrease of I(Na). All of these treatments rescued I(Na) to levels indistinguishable from wild type. The nonspecific PKC inhibitor bisindolylmaleimide I also rescued the decrease of I(Na). To assess whether decreased sodium channel activity contributes to sudden death in vivo, the response to encainide (20 mg/kg) was assessed: 6 of 10 young CN mice died because of asystole, whereas 0 of 10 wild-type mice died (P < 0.01). Moreover, encainide produced exaggerated prolongation of the QRS width in sinus beats before the heart block. Catecholamine tone appears necessary to support life in older CN mice because propranolol (1 mg/kg) triggered asystolic death in five of six CN mice. We conclude that decrease in sodium channel activity is in the common final pathway to asystole in CN mice.
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Calcineurina/metabolismo , Bloqueo Cardíaco/fisiopatología , Transducción de Señal/fisiología , Canales de Sodio/metabolismo , Potenciales de Acción/fisiología , Animales , Calcineurina/genética , Regulación hacia Abajo , Ácido Egtácico/análogos & derivados , Ácido Egtácico/farmacología , Inhibidores Enzimáticos/farmacología , Femenino , Regulación de la Expresión Génica , Bloqueo Cardíaco/metabolismo , Sistema de Conducción Cardíaco/fisiopatología , Ratones , Ratones Transgénicos , Rianodina/farmacología , Canal Liberador de Calcio Receptor de Rianodina/fisiología , Canales de Sodio/efectos de los fármacos , Canales de Sodio/genética , Tapsigargina/farmacología , Regulación hacia ArribaRESUMEN
BACKGROUND: Overexpression of calcineurin in transgenic (TG) mice results in cardiac hypertrophy and unexpected deaths. METHODS AND RESULTS: None of the TG survived beyond 24 weeks (n=38) whereas all of the wildtype (WT, n=47) survived. Prolongation of repolarization preceded the development of sustained pleomorphic ventricular tachycardia and high degree atrioventricular block, which occurred during spontaneous sudden deaths. Since depolarization-activated K(+) channels contribute dominantly to repolarization in mice, we hypothesized that the TG would decrease these K(+) currents and that the in vivo administration of cyclosporin A (CsA), a calcineurin inhibitor, would reduce this effect. CsA reversed cardiac hypertrophy: capacitance measurements of WT left ventricular myocytes (127+/-7 pF; n=45) and CsA-treated TG (129+/-14 pF; n=17) were significantly lower than in placebo-treated TG (220+/-11 pF; n=41; P<0.001 by ANOVA). Independent of whether the data fit a bi- or a tri-exponential model, the density of I(tof) was significantly reduced in TG versus WT and CsA reversed this effect. While I(tos) and I(Kslow) were also reduced in TG, CsA does not reverse this change because long-term in vivo CsA treatment of WT also reduces I(tos) and I(Kslow.) To assess whether the decreased 'repolarization reserve' contributed to arrhythmogenesis, the residual I(Kr) was blocked by dofetilide precipitating pleomorphic ventricular tachycardias. CONCLUSION: Since the downregulation of I(tof) was observed with overexpression of calcineurin and was also reversed by the calcineurin inhibitor CsA, we conclude that downregulation of I(tof) is a consequence of calcineurin overexpression.
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Calcineurina/fisiología , Muerte Súbita Cardíaca/etiología , Canales de Potasio/metabolismo , Animales , Arritmias Cardíacas/fisiopatología , Inhibidores de la Calcineurina , Ciclosporina/uso terapéutico , Electrocardiografía , Femenino , Sistema de Conducción Cardíaco , Hipertrofia Ventricular Izquierda/fisiopatología , Hipertrofia Ventricular Izquierda/prevención & control , Síndrome de QT Prolongado/fisiopatología , Ratones , Ratones Endogámicos ICR , Ratones Transgénicos , Técnicas de Placa-Clamp , Canales de Potasio/efectos de los fármacos , Tasa de SupervivenciaRESUMEN
The implantable cardioverter-defibrillator (ICD) has become a highly effective, but expensive therapy for sudden cardiac death due to ventricular tachyarrhythmias. ICD use has been increasing at 20-30% per year, and is expected to rise at a faster rate. Clinical trials have now shown that the ICD can be effective for the secondary prevention, and more recently for the primary prevention, of sudden cardiac death in selected populations. Despite the high quality trial evidence that is currently available, several issues pertaining to ICD use remain unresolved. These relate to the management of patient groups who were not included in the clinical trials, optimizing the selection of patients who will benefit from an ICD, determining the duration of survival benefit from an ICD, assessing and optimizing a patient's quality of life with an ICD, and determining the cost-effectiveness and cost-impact of the ICD. These considerations are discussed in this article.
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Desfibriladores Implantables , Taquicardia Ventricular/terapia , Ensayos Clínicos como Asunto , HumanosRESUMEN
The implantable cardioverter-defibrillator (ICD) has emerged as an effective, but expensive, therapy for arrhythmic sudden cardiac death. ICD use has been increasing by 20% to 30% per year. Clinical trials have shown that the ICD can be effective for both the primary prevention and the secondary prevention of sudden cardiac death in selected populations. Despite the available trial evidence, several issues pertaining to ICD use remain unresolved, including the treatment of patients not represented in clinical trials, the optimal selection of patients who will benefit from an ICD, the duration of benefit from an ICD, the quality of life for patients with an ICD, and both the cost-effectiveness and the cost impact of the ICD. These considerations are discussed in this article.
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Muerte Súbita Cardíaca/prevención & control , Desfibriladores Implantables , Antiarrítmicos/uso terapéutico , Arritmias Cardíacas/terapia , Ensayos Clínicos como Asunto , Análisis Costo-Beneficio , Desfibriladores Implantables/estadística & datos numéricos , Humanos , Metaanálisis como Asunto , Selección de Paciente , Guías de Práctica Clínica como Asunto , Calidad de VidaAsunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Atenolol/uso terapéutico , Síncope Vasovagal/tratamiento farmacológico , Método Doble Ciego , Humanos , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Síncope Vasovagal/etiología , Pruebas de Mesa Inclinada , Resultado del TratamientoRESUMEN
OBJECTIVE: Our purpose was to evaluate whether baseline characteristics predictive of implantable cardioverter defibrillator (ICD) efficacy in the Canadian Implantable Defibrillator Study (CIDS) are predictive in the Antiarrhythmics Versus Implantable Defibrillators (AVID) Trial. BACKGROUND: ICD therapy is superior to antiarrhythmic drug use in patients with life-threatening arrhythmias. However, identification of subgroups most likely to benefit from ICD therapy may be useful. Data from CIDS suggest that 3 characteristics (age > or =70 years, ejection fraction [EF] < or =0.35, and New York Heart Association class >II) can be combined to reliably categorize patients as likely (> or =2 characteristics) versus unlikely to benefit (<2 characteristics) from ICD therapy. METHODS: The utility of the CIDS categorization of ICD efficacy was assessed by Kaplan-Meier analysis and Cox hazards modeling. The accuracy of the CIDS score was formally tested by evaluating for interaction between categorization of benefit and treatment in a Cox model. RESULTS: ICD therapy was associated with a significantly lower risk of death in the 320 patients categorized as likely to benefit (relative risk [RR] 0.57, 95% confidence interval [CI] 0.37-0.88, P =.01) and a trend toward a lower risk of death in the 689 patients categorized as unlikely to benefit (RR 0.70, 95% CI 0.48-1.03, P =.07). Categorization of benefit was imperfect, as evidenced by a lack of statistical interaction (P =.5). Although 32 of the 42 deaths prevented by ICD therapy in AVID were in patients categorized as likely to benefit, all 42 of these patients had EF values < or =0.35. Neither advanced age nor poorer functional class predicted ICD efficacy in AVID. CONCLUSION: Of the 3 characteristics identified to predict ICD efficacy in CIDS, only depressed EF predicted ICD efficacy in AVID. Thus physicians faced with limited resources might elect to consider ICD therapy over antiarrhythmic drug use in patients with severely depressed EF values.
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Antiarrítmicos/uso terapéutico , Arritmias Cardíacas/mortalidad , Arritmias Cardíacas/terapia , Desfibriladores Implantables , Selección de Paciente , Anciano , Femenino , Predicción , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Tasa de SupervivenciaRESUMEN
Prior clinical research indicates that conduction slowing is the primary mechanism leading to the spontaneous termination of reentrant tachycardia in humans. Yet, some experimental models indicate that cycle length oscillations and enhanced conduction are important prerequisites. The role of oscillations in conduction times and enhanced conduction in the spontaneous termination of human reentrant tachycardia has not been adequately investigated. The electrophysiologic features preceding the spontaneous termination of orthodromic atrioventricular (AV) reciprocating tachycardia (RT) were evaluated in 21 patients, each of whom had a sustained (>60 seconds) and a spontaneously terminating (>/=10 beats and =60 seconds) episode of AVRT during the same electrophysiologic study. Atrio-His, His-ventricular, interventricular, ventriculoatrial and atrial conduction times were measured for each beat of spontaneously terminating AVRT and for paired beats of sustained AVRT. Beats of spontaneously terminating and sustained tachycardia were pooled and Hadi multivariate outlier analysis was used to identify whether significant beat-to-beat alterations in conduction times preceded the spontaneous termination of reentry. Cycle lengths of sustained (348+/-62 msec) and spontaneously terminating AVRT (351+/-70 msec) were similar. Significant beat-to-beat oscillations in conduction times preceded the spontaneous termination of AVRT in 10 of the 21 (48%) patients. An apparent enhancement in atrio-His or ventriculoatrial conduction times immediately preceded the spontaneous termination of AVRT in 11 patients (52%), while an apparent conduction delay occurred in only 2 patients (10%). Moreover, significant oscillations in conduction times were present in 9 of the 11 patients (82%) with enhanced conduction, but only in 1 of the 10 (10%) remaining patients (p=0.002. Conduction time oscillations, which are related to apparent enhancement in atrio-His or ventriculoatrial conduction, frequently precede the spontaneous termination of reentry in humans.
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Sistema de Conducción Cardíaco/fisiopatología , Taquicardia por Reentrada en el Nodo Atrioventricular/fisiopatología , Taquicardia Paroxística/fisiopatología , Adulto , Anciano , Electrocardiografía , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Patients surviving ventricular fibrillation (VF) or sustained ventricular tachycardia (VT) are at a high risk of death due to a recurrence of arrhythmia. The implantable cardioverter defibrillator (ICD) terminates VT or VF, but it is not known whether this device prolongs life in these patients compared with medical therapy with amiodarone. METHODS AND RESULTS: A total of 659 patients with resuscitated VF or VT or with unmonitored syncope were randomly assigned to treatment with the ICD or with amiodarone. The primary outcome measure was all-cause mortality, and the secondary outcome was arrhythmic death. A total of 328 patients were randomized to receive an ICD. A thoracotomy was done in 33, no ICD was implanted in 18, and the rest had a nonthoracotomy ICD. All 331 patients randomized to amiodarone received it initially. At 5 years, 85.4% of patients assigned to amiodarone were still receiving it at a mean dose of 255 mg/day, 28.1% of ICD patients were also receiving amiodarone, and 21.4% of amiodarone patients had received an ICD. A nonsignificant reduction in the risk of death was observed with the ICD, from 10.2% per year to 8.3% per year (19.7% relative risk reduction; 95% confidence interval, -7.7% to 40%; P=0.142). A nonsignificant reduction in the risk of arrhythmic death was observed, from 4.5% per year to 3.0% per year (32.8% relative risk reduction; 95% confidence interval, -7.2% to 57.8%; P=0.094). CONCLUSIONS: A 20% relative risk reduction occurred in all-cause mortality and a 33% reduction occurred in arrhythmic mortality with ICD therapy compared with amiodarone; this reduction did not reach statistical significance.
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Amiodarona/uso terapéutico , Antiarrítmicos/uso terapéutico , Desfibriladores Implantables , Taquicardia Ventricular/terapia , Fibrilación Ventricular/terapia , Anciano , Amiodarona/efectos adversos , Antiarrítmicos/efectos adversos , Desfibriladores Implantables/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Factores de Riesgo , Taquicardia Ventricular/tratamiento farmacológico , Taquicardia Ventricular/mortalidad , Fibrilación Ventricular/tratamiento farmacológico , Fibrilación Ventricular/mortalidadRESUMEN
Dual-chamber pacing is a promising treatment for patients with very frequent vasovagal syncope, but its cost utility is unknown. We report that the incremental cost per quality-adjusted life-year gained is $13,159 Canadian dollars (about $8,600 US dollars), and therefore this pacemaker therapy for vasovagal syncope has a favorable cost-utility ratio.
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Estimulación Cardíaca Artificial/economía , Costo de Enfermedad , Marcapaso Artificial/economía , Síncope Vasovagal/economía , Síncope Vasovagal/terapia , Adulto , Canadá , Estimulación Cardíaca Artificial/estadística & datos numéricos , Costos y Análisis de Costo , Femenino , Humanos , Masculino , Marcapaso Artificial/estadística & datos numéricos , Calidad de Vida , Prevención SecundariaRESUMEN
We propose that heart period sequences are organized similarly to sentences, with a lexicon of recurrent, similarly shaped words. These words should fulfill four criteria: universality, nonrandomness, central statistical tendencies, and specific associated physiology. Here we describe a large-magnitude, transient bradycardia (LMTB) and assess whether it constitutes a word. LMTBs were seen in 11 of 12 adult female rabbits. All shape parameters were different than those of the beat-randomized and phase-randomized surrogate sequences (P < 0.05-0.001). LMTBs were 8. 4 +/- 2.9 beats and 2.64 +/- 0.87 s long and were characterized by bradycardia of 77 +/- 49 ms over 1.09 +/- 0.49 s with a recovery to baseline over 1.56 +/- 0.61 s. The LMTBs had a slower recovery than onset in 9 of 11 rabbits and were highly peaked in 10 of 11 rabbits (P < 0.05). Scalar, magnitude, and shape parameters had values with central statistical tendencies. About 76% of LMTBs were accompanied by hypotension (mean -6.1 +/- 3.9 mmHg) that lagged 2 beats behind the onset of the bradycardia and that correlated with the bradycardia (-10.5 +/- 4.1 ms/mmHg). Thus transient bradycardic events are a distinct "word" in the lexicon of heart rate variability.
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Bradicardia/fisiopatología , Frecuencia Cardíaca , Animales , Femenino , Modelos Biológicos , Conejos , Factores de TiempoRESUMEN
Currently the analysis of clinical trials for treatment of paroxysmal atrial fibrillation (PAF) relies on the assumption that the events are distributed according to a Poisson distribution. We contend that the occurrence of PAF events are clearly not Poisson and tend to occur in clusters. A candidate parametric model of the inter-event interval, the Weibull distribution, is presented. When the events are distributed according to a Poisson distribution, the time to the first event (TFE) has the same distribution as the inter-event intervals (IEI) due to the 'memoryless' property of the Poisson distribution, hence the TFE can be used instead of the IEI. When the events do not form a Poisson distribution, the TFE does not have the same distribution as the IEI. We show that for the Weibull distribution, when the TFE is used to model the IEI, both the mean and the survivor distribution are biased. The bias in the survivor function is a function both of time and the parameters of the distribution. Therefore when two groups have different parameters for their distributions (as in the case of different treatment effects), the discrepancy between the survivor distribution of the IEI and the survivor distribution of the TFE is affected differentially. We demonstrate the low coverage probabilities of the mean and the survivor function which result when the underlying distribution is Weibull with shape parameter kappa < 1.0. It is likely that this problem will arise for other clustered event processes. This suggests that careful empirical investigation of the distribution of IEI for recurrent events is necessary before choosing to analyse the data using the TFE.
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Fibrilación Atrial/fisiopatología , Sesgo , Ensayos Clínicos como Asunto , Modelos Biológicos , Fibrilación Atrial/terapia , Simulación por Computador , Humanos , Análisis Numérico Asistido por Computador , Marcapaso Artificial , Distribución de Poisson , Procesos Estocásticos , Factores de TiempoRESUMEN
OBJECTIVE: To determine electroencephalographic (EEG) changes occurring during syncope induced by headup tilt table testing. DESIGN: Prospective observational study. SETTING: Calgary General Hospital Syncope Clinic, Calgary, Alberta. PATIENTS: Eighteen patients with a history of recurrent syncope who developed syncope while undergoing diagnostic isoproterenol tilt table testing. INTERVENTIONS: Continuous EEGs were recorded in 18 sequentially consenting patients while they underwent diagnostic headup tilt table testing. MAIN RESULTS: Patients developed presyncope after 2.6 +/- 2.4 mins and syncope after 3.7 +/- 2.5 minutes. Systolic blood pressure dropped from 117 +/- 17 mmHg to 65 +/- 9 mmHg, and heart rate dropped from 124 +/- 26 beats/min to 65 +/- 27 beats/min. Fourteen patients developed presyncope, while five developed syncope without appreciable presyncope. Abnormal EEGs were recorded in 13 of 14 patients during presyncope and in 18 of 18 patients during syncope. No patients developed EEG abnormalities before the onset of presyncope, and the proportion of patients with EEG abnormalities gradually increased throughout presyncope. During presyncope, theta and delta wave slowing, and background suppression were noted in eight of 14, nine of 14 and one of 14 patients, respectively. During syncope, theta and delta wave slowing, and background suppression were noted in nine of 18, 11 of 18 and six of 18 patients, respectively (not significant versus presyncope). There were strikingly abrupt changes in the EEG rhythm within 15 s of the transition to syncope in 14 of 18 patients. Six patients developed new theta wave slowing, 11 developed new delta wave slowing, and seven developed background suppression. No epileptiform activity was recorded. CONCLUSIONS: Both presyncope and syncope induced by tilt testing are associated with EEG abnormalities, and no single EEG pattern is pathognomonic of either. The transition from presyncope to syncope is marked by abrupt EEG changes.
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Electroencefalografía , Síncope/etiología , Pruebas de Mesa Inclinada/efectos adversos , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Síncope/diagnósticoRESUMEN
Many chaos detection methods have proven inherently ambiguous in that they yield similar results for chaotic signals and correlated noise. The purpose of this work was to determine whether human resting heart period sequences have global properties characteristic of chaotic systems. We investigated the inherent global organization of heart period sequences by quantifying how the information content of the embedded sequences varied as a function of scale. We compared the information scaling characteristics of 60-min heart period sequences obtained from 10 healthy resting volunteers with those obtained from numerous periodic and chaotic control sequences. The information scaling properties of the heart period sequences were significantly different from those obtained for the controls, particularly at the coarsest scales (P = 0.0003 vs. low-dimensional periodic controls; P = 0.0005 vs. low-dimensional chaotic controls; P = 0.0003 vs. low-dimensional periodic and chaotic controls). We also showed that nondeterministic components, such as large tachycardic (or bradycardic) events or aperiodic fluctuations, can lead to scaling characteristics similar to those observed for the resting heart period sequences. This, in addition to previous evidence from spectral, nonlinear predictability and lexical studies, favors an events-based approach to understanding heart rate variability.
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Frecuencia Cardíaca/fisiología , Dinámicas no Lineales , Adulto , Femenino , Humanos , MasculinoRESUMEN
The follow-up prevalence of electrogram-confirmed spontaneous ventricular tachycardia with a cycle length of >280 ms (53%) exceeds the prevalence of ventricular fibrillation (23%) in patients whose only spontaneous arrhythmia before implantable cardioverter defibrillator implantation was ventricular fibrillation. Antitachycardia pacing therapy safely terminates most (89%) of these slower ventricular tachycardia episodes, recommending the use of tiered-therapy devices and anticipatory activation of ventricular tachycardia detection and treatment algorithms for ventricular fibrillation patients who receive an implantable cardioverter defibrillator.
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Electrocardiografía/métodos , Marcapaso Artificial , Telemetría , Fibrilación Ventricular/terapia , Femenino , Estudios de Seguimiento , Frecuencia Cardíaca , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Fibrilación Ventricular/fisiopatologíaRESUMEN
OBJECTIVES: We sought to compare efficacies of therapy for ventricular tachyarrhythmias selected by programmed stimulation using two different patient response efficacy criteria: <5 versus <16 repetitive ventricular responses. BACKGROUND: Therapy selection for ventricular tachyarrhythmias by programmed stimulation requires definition of a patient response that predicts long-term efficacy. Such definitions have not been previously compared prospectively. METHODS: Patients with sustained ventricular tachyarrhythmias were randomized to therapy selection using either the <5 or <16 repetitive response criterion of predicted effective therapy. The primary end point was sudden death or recurrence of ventricular tachyarrhythmia requiring intervention. RESULTS: Predicted effective drug therapy was found for 23 (34%) of 68 patients randomized to the <5 criterion and 29 (36%) of 81 patients randomized to the <16 criterion (p = NS). Definition of therapy required 3.0 +/- 1.6 drug trials (mean +/- SD) in patients randomized to the <5 criterion and 2.9 +/- 1.8 trials in patients randomized to the <16 criterion (p = NS). Patients randomized to the <5 criterion had a lower 2-year probability of the primary end point (0.20 +/- 0.05) than did patients randomized to the <16 criterion (0.33 +/- 0.05, one-tailed p = 0.004). The advantage of the <5 criterion was also seen in subgroup analyses involving patients with and without an initial drug efficacy prediction. CONCLUSIONS: The programmed stimulation approach to the selection of antiarrhythmic therapy for ventricular tachyarrhythmias using a patient response criterion of <5 repetitive ventricular responses results in a lower probability of recurrence of ventricular tachyarrhythmia than does use of a <16 repetitive response criterion.
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Antiarrítmicos/uso terapéutico , Taquicardia Ventricular/tratamiento farmacológico , Análisis Actuarial , Anciano , Muerte Súbita Cardíaca , Estimulación Eléctrica , Electrofisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Recurrencia , Análisis de Supervivencia , Taquicardia Ventricular/fisiopatologíaAsunto(s)
Síncope Vasovagal/etiología , Pruebas de Mesa Inclinada/efectos adversos , Estudios de Seguimiento , Predicción , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Recurrencia , Estudios Retrospectivos , Estrés Psicológico , Síncope Vasovagal/fisiopatología , Síncope Vasovagal/prevención & control , Pruebas de Mesa Inclinada/psicologíaRESUMEN
Developmental shortening of cardiac action potential duration in mouse appears to result, at least in part, from replacement of the rapid component of the delayed rectifying potassium current (IKr) with the transient outward current (ItO1). This developmental decrease in the IKr current density was paralleled by a loss of the high affinity [3H]-dofetilide binding site and loss of prolongation of action potential duration by dofetilide. Since glucocorticoid treatment prevented the developmental shortening of action potential duration in rats in the perinatal period, we hypothesized that chronic dexamethasone treatment would alter the developmental loss of IKr channel expression in mice. Accordingly, 10-day-old mice were randomly allocated to chronic in vivo dexamethasone treatment (1 mg/kg) or placebo treatment for 3-5 days. At 15 days of life, transmembrane action potentials were recorded in right ventricular endocardium and [3H]-dofetilide equilibrium binding studies were performed. The baseline action potential duration in the dexamethasone-treated animals was significantly greater than that in the control group (66+/-3 v 54+/-10 ms, respectively; P<0.01). Moreover, dofetilide significantly prolonged action potential duration in the dexamethasone-treated animals, but had no effect on the placebo-treated group (P<0.01). In addition, a high affinity [3H]-dofetilide binding site (Kd 96+/-21 nM and Bmax 69+/-13 fmoles/mg protein) was observed in the dexamethasone-treated group (n=5), whereas no specific [3H]-dofetilide binding was observed in the placebo-treated group. In conclusion, dexamethasone modulates developmental regulation of IKr channel expression in mouse ventricle.