[Role of the sympathetic nervous system in vasovagal syncope and rationale for beta-blockers and norepinephrine transporter inhibitors]. / Papel del sistema nervioso simpático en el síncope vasovagal y justificación del uso de betabloqueadores e inhibidores del transportador de noradrenalina.

Vasovagal or neurocardiogenic syncope is a common clinical situation and, as with other entities associated with orthostatic intolerance, the underlying condition is a dysfunction of the autonomic nervous system. This article reviews various aspects of vasovagal syncope, including its relationship with orthostatic intolerance and the role of the autonomic nervous system in it. A brief history of the problem is given, as well as a description of how the names and associated concepts have evolved. The response of the sympathetic system to orthostatic stress, the physiology of the baroreflex system and the neurohumoral changes that occur with standing are analyzed. Evidence is presented of the involvement of the autonomic nervous system, including studies of heart rate variability, microneurography, cardiac innervation, and molecular genetic studies. Finally, we describe different studies on the use of beta-blockers and norepinephrine transporter inhibitors (sibutramine, reboxetine) and the rationality of their use to prevent this type of syncope.

El síncope vasovagal o neurocardiogénico es una situación clínica común, y así como en otras entidades asociadas con la intolerancia ortostática, la condición de base es una disfunción del sistema nervioso autónomo. En este artículo se revisan diversos aspectos sobre el síncope vasovagal, incluyendo su relación con la intolerancia ortostática y el papel que juega el sistema nervioso autónomo. Se da una breve reseña histórica del problema, así como una descripción de la forma en que han evolucionado los términos y conceptos asociados al mismo. Se hace un análisis sobre la respuesta del sistema nervioso simpático al estrés ortostático, la fisiología del sistema barorreflejo y los cambios neurohumorales que ocurren. Se muestra evidencia sobre el papel del sistema nervioso autónomo, incluyendo estudios sobre variabilidad de la frecuencia cardiaca, microneurografía, inervación cardiaca y estudios genéticos moleculares. Finalmente, se describen diferentes estudios sobre el uso de betabloqueadores e inhibidores del transportador de noradrenalina (sibutramina, reboxetina) y la justificación de su uso en la prevención de este tipo de síncope.

[Comparison of metoprolol vs clonazepam as a first treatment choice among patients with neurocardiogenic syncope]. / Comparación de metoprolol versus clonazepam como tratamiento de primera intención en pacientes con síncope neurocardiogénico.

OBJECTIVE: We compared the effects of a metoprolol and clonazepam in patients with neurocardiogenic syncope. METHODS: We compared the effects of a metoprolol and clonazepam in a prospective, randomised trial in 54 patients. Patients were randomly assigned to metoprolol (starting dose 50 mg bid) or clonazepam (starting dose 0.5 mg qd). We assessed a primary combined endpoint of syncope and pre-syncope on a follow-up of 12 months. RESULTS: The primary combined endpoint of syncope and presyncope occurred in the metoprolol group in 3, 4, and 10% of patients at 3, 6, and 12 months respectively. In the clonazepam group it was no recurrence in the first 6 months, and 5% recurrence at 12 months follow-up (nonsignificant differences between groups). Clinical symptoms commonly associated with neurally mediated syncope were decreased similarly in both treatment groups, in the metoprolol group from 5.2+/-2.5 to 1.9+/-2.1 (p < 0.001) and in the clonazepam group from 5.5+/-2.5 to 1.5+/-2.2 (p<0.001). CONCLUSIONS: Pharmacological treatment of neurocardiogenic syncope with metoprolol or clonazepam resulted in similar prevention of syncope and presyncope. Both treatments decreased clinical symptoms but complete symptomatic resolution was rarely observed.

Comparación de metoprolol versus clonazepam como tratamiento de primera intención en pacientes con síncope neurocardiogénico / Comparison of metoprolol vs clonazepam as a first treatment choice among patients with neurocardiogenic syncope

Objetivo: Comparar la eficacia de metoprolol versus clonazepam como tratamiento de primera intención en pacientes con síncope neurocardiogénico. Material y métodos: Se llevó a cabo estudio prospectivo, longitudinal y aleatorizado en el que se evaluó el efecto del metoprolol (50 mg dos veces al día) versus clonazepam (0.5 mg una vez al día) sobre la sintomatología asociada a los tres meses y la recurrencia de síncope a 12 meses. La distribución de los datos fue normal, el análisis estadístico se realizó por métodos paramétricos considerándose significancia estadística una p≤0.05. Resultados: De 54 pacientes, 32 fueron tratados con metoprolol y 22 con clonazepam. No hubo diferencias en las características basales entre ambos grupos. El número de síntomas por paciente se redujo en el grupo de metoprolol de 5.2±2.5 a 1.9±2.1 (p<0.001), y en el grupo de clonazepam de 5.5±2.5 a 1.5±2.2 (p<0.001). La recurrencia de síncope a los 12 meses fue de 10% en el primer grupo y de 5% en el grupo de clonazepam, sin diferencia estadísticamente significativa. Conclusiones: El tratamiento con metoprolol o clonazepam disminuye en forma significativa los síntomas de distonía neurovegetativa asociados y la recurrencia de síncope es similar con ambos tratamientos.

OBJECTIVE: We compared the effects of a metoprolol and clonazepam in patients with neurocardiogenic syncope. METHODS: We compared the effects of a metoprolol and clonazepam in a prospective, randomised trial in 54 patients. Patients were randomly assigned to metoprolol (starting dose 50 mg bid) or clonazepam (starting dose 0.5 mg qd). We assessed a primary combined endpoint of syncope and pre-syncope on a follow-up of 12 months. RESULTS: The primary combined endpoint of syncope and presyncope occurred in the metoprolol group in 3, 4, and 10% of patients at 3, 6, and 12 months respectively. In the clonazepam group it was no recurrence in the first 6 months, and 5% recurrence at 12 months follow-up (nonsignificant differences between groups). Clinical symptoms commonly associated with neurally mediated syncope were decreased similarly in both treatment groups, in the metoprolol group from 5.2+/-2.5 to 1.9+/-2.1 (p < 0.001) and in the clonazepam group from 5.5+/-2.5 to 1.5+/-2.2 (p<0.001). CONCLUSIONS: Pharmacological treatment of neurocardiogenic syncope with metoprolol or clonazepam resulted in similar prevention of syncope and presyncope. Both treatments decreased clinical symptoms but complete symptomatic resolution was rarely observed.

Tilt teste no diagnóstico diferencial da epilepsia resistente ao tratamento / Tilt table test in the differential diagnosis of refractory epilepsy

A epilepsia é uma das causas mais freqüentes de distúrbios neurológicos em adultos jovens. Relatamos um caso em que uma paciente conviveu durante doze anos com o diagnóstico de epilepsia resistente ao tratamento, quando, na verdade, a causa de seus sintomas pôde ser encontrada com a realização do teste de inclinação (tilt teste). O cardiologista deve estar alerta para o possível diagnóstico de síncope neurocardiogênica em pacientes previamente diagnosticados como portadores de epilepsia, especialmente naqueles com difícil controle terapêutico.

Epilepsy is one of the most frequent causes of neurological disorders in young adults. We report the case of a patient who lived with the diagnosis of refractory epilepsy for twelve years, when actually the cause of the symptoms could be found with the performance of a tilt table test. Cardiologists should be aware of the possible diagnosis of neurocardiogenic syncope in patients previously diagnosed with epilepsy, especially in those with difficult therapeutic control.

[Clinical outcome of patients with neurocardiogenic syncope (NCS) after therapy interruption]. / Evolução clínica de pacientes com síncope neurocardiogênica (SNC) após suspensão da terapia específica.

OBJECTIVE: To evaluate the outcome of patients with NCS after interruption of pharmacological therapy and to investigate the possible clinical variables predicting recurrence. METHODS: Thirty-seven patients (age 31+/-16 years) with refractory recurrent NCS being 19 females where prospectively studied. All patients became asymptomatic and had a negative tilt table test (TT) after pharmacological therapy. The treatment was interrupted and one month later, a new TT with no medication was carried out. The probability free of symptoms recurrence was analyzed according to sex, age, number of syncope episodes previously to the treatment, clinical history time, treatment time, drug free from treatment time and TT result. RESULTS: Twenty-two patients (59%) presented recurrence during a mean follow-up of 21+/-19.7 months. The variables related to greater recurrence were number of previous syncope (p=0.0248), positive TT after interruption of the therapy (p=0.0002) and female gender (p=0.0131). CONCLUSIONS: Most of the very symptomatic patients with NCS present recurrence after the suppression of a specific therapy. A TT carried out after treatment discontinuation can identify patients with higher risk of recurrence, specially in the first year of follow-up.

Evolução clínica de pacientes com síncope neurocardiogênica (SNC) após suspensão da terapia específica / Clinical outcome of patients with neurocardiogenic syncope (NCS) after therapy interruption

OBJETIVO: Avaliar a evolução clínica de pacientes com SNC após a suspensão do tratamento farmacológico e investigar as possíveis variáveis clínicas preditivas de recidiva. MÉTODOS: Trinta e sete pacientes (média de idade de 31 ± 16 anos) com SNC recidivante refratária, dos quais 19 eram mulheres, foram estudados prospectivamente. Todos os pacientes estavam assintomáticos e apresentaram teste de inclinação ortostática (TI) negativo após a introdução da terapia farmacológica. Um novo TI foi realizado um mês após a suspensão do tratamento. A probabilidade livre de sintomas foi analisada de acordo com sexo, idade, número de síncopes prévias ao tratamento, tempo de história clínica, tempo de tratamento, resultado do TI após interrupção do tratamento e período sem medicação. RESULTADOS: Vinte e dois pacientes (59 por cento) apresentaram recidiva durante um acompanhamento médio de 21 ± 19,7 meses. As variáveis relacionadas com maior recidiva foram número de síncopes anteriores (p = 0,0248), TI positivo após a suspensão da terapia (p = 0,0002) e sexo feminino (p = 0,0131). CONCLUSÕES: A maior parte dos pacientes altamente sintomáticos com SNC apresenta recidiva após a supressão do tratamento. A realização do TI após a suspensão do tratamento pode identificar os pacientes com maior risco de recidiva, sobretudo durante o primeiro ano de acompanhamento.

Tilt table test in the differential diagnosis of refractory "epilepsy".

Epilepsy is one of the most frequent causes of neurological disorders in young adults. We report the case of a patient who lived with the diagnosis of refractory epilepsy for twelve years, when actually the cause of the symptoms could be found with the performance of a tilt table test. Cardiologists should be aware of the possible diagnosis of neurocardiogenic syncope in patients previously diagnosed with epilepsy, especially in those with difficult therapeutic control.

Aproximación terapéutica al síncope neurocardiogénico / Therapeutic approach to the neuro-cardiogenic syncope

Desde la implementación en 1986 de la prueba de la mesa basculante para el diagnóstico de pacientes con síncope recurrente de origen no aclarado, el síncope neurocardiogénico se constituyó como la forma prevalente del síncope. A pesar de su importancia en términos de salud pública, la fisiopatología del síncope neurocardiogénico no se ha aclarado completamente, lo que dificulta la adopción de un enfoque terapéutico apropiado. El manejo inial del síncope neurocardiogénico consiste en medidas generales que incluyen la educación de los pacientes y estrategias para incrementar el volumen plasmático y obtener una mayor tolerancia al ortostatismo. El manejo farmacológico, se basa en múltiples alternativas derivadas de las alteraciones fisiopatológicas establecidas. Este artículo expone alguna evidencia existente sobre el tratamiento del síncope neurocardiogénico e identifica las opciones terapéuticas más acertadas para mejorar el pronóstico de estos pacientes

Does a role exist for tilting-guided therapy in the management of neurocardiogenic syncope?

PURPOSE: Upright tilt-table testing (UTT) is an useful method for identifying patients with neurocardiogenic syncope, but its role in the evaluation of therapeutic efficacy is controversial. The aim of this study was to determine the correlation between negative UTT after therapy introduction (acute efficacy) and symptom recurrence during follow-up (chronic efficacy). METHODS: We studied 56 severely symptomatic patients (age 27 +/- 19 years) with recurrent (7 +/-12 episodes) neurocardiogenic syncope (positive UTT). Once empirical pharmacological therapy was initiated, all patients underwent another UTT (therapeutic evaluation test - TET). Therapy was not modified after TET results. The probability of symptom recurrence was analyzed with the Kaplan-Meier method and compared by log-rank test in patients with negative and positive TET. RESULTS: Negative UTT after therapy was related to a significantly lower probability of recurrence during follow-up (4.9 versus 52.4% in 12 months, P<0.0001). CONCLUSION: A good correlation exists between acute and long-term efficacy of pharmacological therapy for neurocardiogenic syncope, so that serial UTT may be considered a good method for identifying an effective therapeutic strategy.

Síncope neurocardiogénico / Neurocardiogenic syncope

El síncope cardiogénico es uno de los llamados síncopes reflejos. Es un trastorno muy frecuente y su diagnóstico es relativamente fácil si se tiene en mente. Hasta hace algunos años, muchos de estos síncopes se catalogaban como de causa desconocida. El uso de la prueba de inclinación ha permitido un estudio más completo de estos enfermos y por lo tanto un tratamiento más adecuado. En este artículo se hace una revisión de algunos conceptos generales de esta entidad, así como su fisiopatología, características clínicas de los pacientes, respuesta a la prueba de inclinación y tratamiento tanto farmacológico como no farmacológico.

Síncopes y tilt test / Syncope and tilt test

El síncope se define como una pérdida brusca y fugaz del conocimiento y del tono postural debida a una isquemia y anoxia cerebrales transitorias que regresan sin dejar secuelas neurológicas. Se presenta una clasificación fisiopatológica de los síncopes que los agrupa en cardiogénicos, vasogénicos, neurogénicos y psicogénicos. Se señala que los más frecuentes con los síncopes vaso-vagales; que los más serios son los cardiogénicos y que los menos frecuentes son los neurogénicos y psicogénicos. Se describe el Tilt Test y se señala su utilidad en el diagnóstico de los síncopes vaso-vagales

[Neurocardiogenic syncope in children]. / Síncope neurocardiogénico en población pediátrica.

Between december of 1994 and june 1997, 90 children and adolescents were referred to the Shaio Clinic Foundation for evaluation of recurrent unexplained syncope. Head-up tilt testing was positive in 45 (50%), 23 male, with a mean age of 12.7 years (range 5-17 years). The response during Head-up tilt testing was predominantly vasodepressor (57%), followed by mixed in 24% and cardioinhibitory in the remaining 17%. The majority of patients had a positive response during pharmacological phase with isoproterenol infusion at a mean time of 17 +/- 8 minutes. Head-up tilt is a safe diagnostic test and defines the cause of unexplained syncope in up to 50% of children and young adults with recurrent syncope. The management was based on education, control of risk factors and psychological and/or physical rehabilitation. In the 15.2 months follow up we observed complete remission or a significant reduction of symptoms in 95% of the cases. Only 5% of the patients persisted or had worsening of their symptoms.

Síncope neurocardiogénico cardio-inhibitorio en niños y adolescentes: características clínicas, tratamiento y evolución / Neurocardiogenic syncope in children and adolescents: clinical course and treatment

Los síndromes de hipotensión arterial ortostáticos constituyen las principales causas que explican muchos de los síncopes de etiología no precisada. En la mayoría de los pacientes pediátricos se documenta síncope neurocardiogénico mixto y vasodepresor t, en menor proporción, síncope cardioinhibitorio. El pronóstico de este último subgrupo no está del todo dilucidado. El objetivo del presente trabajo fue evaluar las características clínicas, tratamiento y evolución de los síncopes cardio-inhibitorios, definidos como IIA y IIB según clasificación del grupo VASIS, en un grupo de niños y adolescentes. Se estudió prospectivamente a 100 niños y adolescentes de 8 a 16 años de edad, con síncope o pre-síncope de etiología no precisada, desde 1/1/98 hasta 1/7/99. Se practicó test de Tilt a todos según recomendaciones del ACC Expert Consensus Document. 52 por ciento no presentó alteraciones. 10 por ciento presentó síncope neurocardiogénico cardioinhibitorio, 34 por ciento síncope neurocardiogénico mixto y vasodepresor, 4 por ciento pooling venoso patológico, 3 por ciento síndrome de taquicardia postural ortostática, 1 por ciento prolongación del QT. En el grupo de pacientes con síncope cardio-inhibitorio, la edad promedio fue de 12 ñ 2 años (4 mujeres y 6 hombres). Ninguno requirió isoprotenol para reproducir el síncope cardio-inhibitorio. 5/10 presentaron mioclonías y no hubo traumatismos secundarios. Casi todos presentaron más de 5 episodios sincopales (8/10) e historia de más de 1 año de evolución (9/10). 9/10 fueron síncopes cardio-inhibitorios tipo IIA y 1/10 de tipo IIB. El tipo de tratamiento fue individual y dependió del médico tratante. Un paciente requirió marcapaso (tipo IIB). El seguimiento promedio fue de 6 meses (3 a 13 meses), con excelente respuesta clínica. Conclusiones: En población pediátrica, 10 por ciento de los síncopes de etiología no precisada correspondió a síncope cardioinhibitorio. La mayoría recibió tratamiento farmacológico por períodos relativamente breves (2-3 meses) o no recibió tratamiento, con excelente respuesta clínica a los 6 meses de seguimiento (3-13 meses)

Síncope Neurocardiogénico en población pediátrica / Neurocardiogenic syncope in children

Entre diciembre de 1994 y junio de 1997, 90 niños y adolescentes fueron enviados a la Fundación Clínica Shaio para evaluación de síncope recurrente e inexplicable. La prueba de mesa basculante fue positiva en 45 (50 por ciento) de los casos. 23 hombres y 22 mujeres con una edad media de 12,7 años (rango 5-17 años). La respuesta durante la prueba de mesa basculante fue predominantemente vasodepresora (57 por ciento) seguida por la respuesta tipo mixta en 24 por ciento de los casos y cardioinhibitoria en el 17 por ciento. La mayoría de los pacientes presentaron la respuesta positiva durante la fase farmacológica con infusión de isoproterenol. La duración de la prueba fue en promedio de 17 ñ 8 minutos. La prueba de mesa basculante es un método diagnóstico seguro y determina la causa del síncope inexplicable en el 50 por ciento de los niños y adolescentes con síncope recurrente. El manejo incluyó educación, control de los factores de riesgo y rehabilitación física y/o psicológica. En los 15,2 meses de seguimiento se observó una remisión completa o reducción significativa de los síntomas en el 95 por ciento de los casos. Solamente en el 5 por ciento de los casos persistieron o empeoraron los síntomas

The evaluation and management of syncope in children

Syncope or reversible loss of consciousness is common in children, experienced by about 20 percent of the paediatric population at least once, and accounts for about 6 percent of hospital admissions. The evaluation of these patients may be expensive and unrewarding. Their symptom complex arouse extremes anxiety, for the most part unwarranted, in family, friends, teachers and physicians, resulting in restriction in activity. The most common cause of syncope in this population is neurally medicated, a benign condition which can often be easily treated by reassurance, situational avoidance and simple medication to augment cardiac output and/or to blunt the responsible neural reflex. Occasionally, syncope may be a manifestation of a serious or life threatening cardiac disorder, which requires more in depth evaluation and treatment to reduce the symptoms and the risk of sudden death. A stepwise approach to evaluation can categorize these patients to avoid unnecessary expense and anxiety while at the same time recognising the more serious cardiac disorders. A careful history of the episodes, family history and physical examination, together with a 12 lead electrocardiogram, may be all that is necessary to evaluate a simple faint. With more complex symptoms, especially with recurrence, a head up tilt examination is useful. More detailed evaluation can be reserved for those for whom there is a high index of suspicion based on their previous results. This common sense approach to the evaluation of syncope could allay anxiety and reduce physical activity restrictions and costs in an already economically exhausted care system.(AU)

Neurocardiology. Neurogenic syncope.

Neurogenic syncope is one of the most frequent causes of recurrent syncope in patients with structurally normal heart. The mechanisms leading to neurogenic syncope remain poorly understood. Evidence recently obtained from several laboratories suggests that impaired arterial baroreflex adaptation to orthostatic stress, in addition to cessation of vasoconstrictive sympathetic traffic, contributes to the development of hypotension and bradycardia that determine the vasovagal response. Neurogenic syncope encompasses a wide range of reflexogenic syncope that includes the vasovagal type, micturition syncope, carotid sinus hypersensitivity and post-prandial syncope. Head-up tilt testing has become the diagnostic tool of choice for the evaluation of patients with recurrent neurogenic syncope, providing an acceptable sensitivity and high specificity that is largely dependent on the type of tilt protocol used to induce neurogenic syncope. This chapter will review the pathophysiology, diagnosis and therapeutic approach to the patient with neurogenic syncope.

[Vasovagal syncope. Management with propanthelin bromide]. / Síncope vagotónico. Manejo con bromuro de propantelina.

OBJECTIVE: To study propanthelin bromide efficacy in preventing vasovagal syncope relapse. SETTING: HGZ No. 3 IMSS, Mazatlán, Sinaloa, México, from 1992 to 1995. PATIENTS: 10 patients with vasovagal syncope were selected from 41 syncope patients. DESIGN: Prospective longitudinal. MEASURES: clinical charts, neurologic and cardiologic evaluation, electrocardiogram, electroencephalogram, C.A.T., Holter, stress test and chest X rays were made. In 10 patients, 15 to 30 mg of propanthelin bromide thrice a day were administered, 12 month survey on was made measured. RESULTS: Of the 10 patients, 7 were women mean age 18 years. In 9 of them no recurrence was evident abandoned 1 treatment, 4 had side effects. CONCLUSIONS: Propanthelin bromide decreases vasovagal syncope episodes with few side effects.