Cardioneuroablation: Where are we at?

Since its original description in 2005, catheter ablation techniques, commonly called cardioneuroablation, have emerged as a potential strategy for modulating autonomic function. Multiple investigators have provided observational data on the potential benefits of this technique in a variety of conditions associated with or exacerbated by increased vagal tone such as vasovagal syncope, functional atrioventricular block, and sinus node dysfunction. Patient selection, current techniques including the various mapping strategies, clinical experience, and limitations of cardioablation are reviewed. Finally, while cardioneuroablation has potential to be a treatment option for selected patients with symptoms mediated by hypervagotonia, the document outlines the important knowledge gaps that currently exist and the necessary next steps required before this technique can be widely implemented into clinical practice.

Utilidad de la midodrina para controlar el síncope vasovagal: ¿la recomienda la evidencia? / Usefulness of Midodrine for the Control of Recurrent Vasovagal Syncope: Does the Evidence Recommend it? / Utilidade da midodrina no controle da síncope vasovagal: as evidencias a recomendam?

Introducción:El síncope vasovagal es la principal causa de pérdida transitoria de la conciencia, y es un motivo de consulta cada vez más frecuente en pediatría y medicina del adulto. La midodrina es un agonista de los recepto-res alfa, de acción periférica, empleada principalmente en el manejo de la hipotensión ortostática; sin embargo, también se ha evaluado en el síncope vasovagal, con resultados prometedores.Objetivo:Analizar la evidencia más reciente sobre la utilidad de la midodrina para el control y la prevención del síncope vasovagal.Materiales y métodos: Se realizó una búsqueda bibliográfica utilizando términos de búsqueda como Vasovagal Syncope y Midodrine, así como sinónimos, que se combinaron con operadores booleanos, en cinco bases de datos, hasta octubre del 2022. Se incluyeron estudios originales, revisiones sistemáticas y metanálisis, publicados tanto en inglés como en español.Resultados:Ensayos controlados aleatorizados y revisiones sistemáticas y metanálisis difieren ligeramente entre resultados, pero estos demuestran un efecto global protector. La evidencia más reciente y completa indica que utilizar este agente reduce significativamente la positividad al realizar la prueba de la mesa inclinada y que previene la aparición de episodios sincopales.Conclusiones:Aunque la evidencia actual sobre la eficacia de la midodrina respecto a la prevención y control del síncope vasovagal es limitada, se observa un efecto protector significativo, porque disminuye el riesgo de sufrir un episodio sincopal, aproximadamente hasta en un 50 %.Palabras clave: midodrina; síncope vasovagal; síncope; adrenérgicos; medicina basada en la evidencia

Introduction: Vasovagal syncope is the main cause of transient loss of consciousness, being an in-creasingly frequent reason for consultation in pediatrics and adult medicine. Midodrine, a periphe-rally acting alpha-receptor agonist, is mainly used in the management of orthostatic hypotension. However, it has also been evaluated in vasovagal syncope, with promising results. Objective: To analyze the most recent evidence on the usefulness of midodrine for the control and prevention of vasovagal syncope. Materials and Methods: A literature search was performed using search terms such as "Vasovagal Syncope" and "Midodrine," as well as synonyms, which were combined with Boolean operators, in 5 databases until October 2022. Original studies, systematic reviews and meta-analyses, published in both English and Spanish, were included. Results: Randomized controlled trials and systematic reviews and meta-analyses differ slightly between results, but these demonstrate an overall protective effect. The most recent and complete evidence shows that using this agent significantly reduces the probability of positivity when performing the tilt table test and prevents the occurrence of syncopal episodes. Conclusions: Although current evidence on the efficacy of midodrine with respect to the prevention and control of vasovagal syncope is limited, a significant protective effect is observed, reducing the risk of suffering syncopal episode by approximately up to 50%

Introdução: a síncope vasovagal é a principal causa de perda transitória de consciência e é um motivo cada vez mais comum de consulta em pediatria e medicina de adultos. A midodrina é um agonista do receptor alfa de ação periférica usado principalmente no tratamento da hipotensão ortostática; no entanto, ela também foi avaliada na síncope vasovagal, com resultados promissores. Objetivo: Revisar as evidências mais recentes sobre a utilidade da midodrina para o controle e a pre-venção da síncope vasovagal. Materiais e métodos: Foi realizada uma pesquisa na literatura usando termos de pesquisa como Va-sovagal, Syncope e Medodrine, bem como sinônimos, que foram combinados com operadores boo-leanos, em cinco bancos de dados, até outubro de 2022. Foram incluídos estudos originais, revisões sistemáticas e metanálises, publicados em inglês e espanhol. Resultados: Os ensaios clínicos randomizados, as revisões sistemáticas e as metanálises diferem ligei-ramente entre os resultados, mas demonstram um efeito protetor geral. As evidências mais recentes e abrangentes indicam que o uso desse agente reduz significativamente a positividade no teste de inclinação da mesa e evita a ocorrência de episódios de síncope. Conclusões: Embora as evidências atuais sobre a eficácia da midodrina em relação à prevenção e ao controle da síncope vasovagal sejam limitadas, observa-se um efeito protetor significativo, pois ela diminui o risco de sofrer um episódio sincopal em aproximadamente 50%

Reflex cardioinhibitory syncope potentially related to SARS-CoV-2 infection: a case report / Síncope cardioinibitória reflexa potencialmente relacionada à infecção por SARS-CoV-2: um relato de caso

Autonomic dysfunction related to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is increasingly described in the literature. We report the case of a 30-year-old male with a background of asthma and migraine who experienced a second episode of SARS-CoV-2 infection characterized by mild respiratory symptoms. Twenty-four days after the symptom onset, he developed acute syncope. A tilt test revealed a neuromediated cardioinhibitory response with asystole (Vasovagal Syncope International Study ­ VASIS type 2B). The temporal association between SARS-CoV-2 infection and syncope seems to indicate a probable causal relationship, which requires corroboration by future studies.

Disfunção autonômica relacionada à infecção por coronavírus-2 da síndrome respiratória aguda grave (SARS-CoV-2) vem sendo cada vez mais descrita na literatura. Relatamos o caso de um homem de 30 anos de idade, com histórico de asma e enxaqueca, que apresentou um segundo episódio de infecção por SARS-CoV-2 caracterizado por sintomas respiratórios leves. Vinte e quatro dias após o início dos sintomas, desenvolveu um quadro agudo de síncope. Um teste de inclinação revelou uma resposta cardioinibitória neuromediada com assistolia (Vasovagal Syncope International Study ­ VASIS tipo 2B). A associação temporal entre infecção por SARS-CoV-2 e síncope parece indicar uma provável relação causal, a qual requer corroboração por estudos futuros.

Vasoactive Biomarkers in Patients With Vasovagal Syncope During Head-Up Tilt Test: A Case-Control Study.

Background: Vasovagal syncope (VVS) is the most common cause of syncope. Some stages of its pathophysiological mechanisms remain unclear. Vasoactive substances such as nitric oxide metabolites (NOx) and endothelin (ET) may be involved during acute orthostatic stress. Objective: To analyze plasma changes in NOx and ET and heart rate variability (HRV) in the supine positions (T1) and during the head-up tilt test (HUTT) (T2), in patients with VVS (case group) and control group. Methods: Thirty-seven patients (17 in the case group and 20 in the control group), matched for age and sex (mean aged 31.8 years) underwent HUTT with simultaneous HRV recording and venipuncture. Blood samples were collected during phases T1 and T2 and the analysis was performed without knowledge of the HUTT result. Results: In the total sample, there was an increase in NOx values (P = .014), however there was no increase in ET values from phase T1 to phase T2. Patients with VVS tended to increase plasma NOx values (P = .057) and had significantly higher plasma values compared to ET (P = .033) between phases T1 to T2. In the control group, there was no significant change in the values of these vasoactive substances. Regarding HRV, there were a decrease in the component HF (high frequency) and increased of the LF (low frequency)/HF ratio during HUTT. Conclusions: There was an increase in ET during HUTT occurred only in the case group. These patients are more likely to have an imbalance between antagonistic vasoactive biomarkers during orthostatic stress.

Crisis hipertensiva y bradicardia secundaria a intoxicación por midodrina / Hypertensive crisis and bradycardia secondary to midodrine intoxication

Resumen El síncope, definido como una pérdida transitoria de la conciencia que cursa con recuperación espontánea y completa, es secundario a un amplio grupo etiológico, incluido el de origen vasovagal desencadenado por una descarga adrenérgica u ortostatismo. El tratamiento de esta entidad incluye medidas no farmacológicas y farmacológicas, como la administración de midodrina, un agonista de los receptores a de acción periférica, usada en el control de la hipotensión ortostática y cuyo empleo ha demostrado mejoría en los síntomas de esta alteración. Se presenta el caso de una mujer de 18 años, con antecedente de síncope vasovagal en tratamiento con medidas no farmacológicas y midodrina desde seis meses antes, quien consultó al servicio de urgencias de un centro de atención de nivel IV por cuadro clínico consistente en ingestión intencionada de una sobredosis de midodrina. En el ingreso se documentaron crisis hipertensiva, bradicardia extrema y compromiso hepático y renal. Se indicó tratamiento sintomático con resolución de las alteraciones clínicas y paraclínicas e intervención del equipo de salud mental.

Abstract Syncope, defined as a transitory loss of consciousness characterised by its rapid onset, short duration, and spontaneous complete recovery, is secondary to a wide ethiological group, such as the vasovagal origin triggered by an adrenergic discharge or orthostatism. The management of this entity includes both non-pharmacological measures and pharmacological treatment such as the use of midodrine, a peripherally acting alpha receptor agonist, used in the management of orthostatic hypotension, whose use has shown improvement in the symptoms of this condition. We present a clinical case of an 18-year-old woman, with a history of vasovagal syncope under treatment with midodrine and non-pharmacological measures for 6 months, who was admitted to the emergency department of a level IV care center due to an intentional intake of midodrine overdose. Upon admission, a hypertensive crisis with extreme bradycardia, and liver and kidney involvement were documented. Symptom´s management was started with resolution of clinical and paraclinical alterations, and intervention by the mental health team.

Evaluación de la frecuencia cardiaca durante la bipedestación activa inicial en pacientes que padecen síncope vasovagal / Evaluation of the heart rate during initial active standing in patients with vasovagal syncope

Introducción: El síncope vasovagal es la causa más frecuente de pérdida breve de la conciencia, en su etiopatogenia se reporta una disfunción autonómica que puede ponerse de manifiesto en la bipedestación activa inmediata. Objetivo: Comparar la dinámica de los cambios de la frecuencia cardíaca durante la bipedestación activa inmediata, de pacientes que padecen síncope vasovagal y sujetos controles. Métodos: Se evaluaron 132 sujetos supuestamente sanos (grupo A) entre 18 y 25 años y 156 pacientes con síncopes vasovagales; fueron divididos por su respuesta ante la bipedestación prolongada, negativa 111 (grupo B) y positiva 45 (grupo C). Se registró la actividad electrocardiográfica en decúbito supino y al inicio de la bipedestación activa, se obtuvo las secuencias de intervalos RR. Se comparó la frecuencia cardíaca en los 3 grupos, con 22 indicadores (posicionales, temporales, ordinales y relacionales, promedio y de la velocidad de los cambios). Resultados: No hubo diferencias en los indicadores promedio, sin embargo, algunos que evalúan la velocidad del cambio inicial, fueron significativamente menores en el grupo A comparado con B y C (p < 0,05), mientras que los que evalúan la velocidad de recuperación, fueron significativamente menores en el grupo C comparado con A y B. Conclusión: La dinámica de los cambios de frecuencia, permitió encontrar indicadores que pueden considerarse posibles predictores de una respuesta cardiovascular inadecuada en pacientes con síncope vasovagal(AU)

Introduction: Vasovagal syncope is the most frequent cause of brief loss of consciousness, in its etiopathogenesis an autonomic dysfunction is reported that can be manifested in immediate active standing. Objective: To compare the dynamics of heart rate changes during immediate active standing of patients suffering from vasovagal syncope with control subjects. Methods: 132 supposedly healthy subjects (group A) between 18 and 25 years old and 156 patients with vasovagal syncope were evaluated, which were divided by their response to prolonged standing, negative 111 (group B) and positive 45 (group C). Electrocardiographic activity was recorded in the supine position and at the beginning of active standing, the sequences of RR intervals were obtained. The heart rate was compared in the 3 groups, using 22 indicators (positional, temporal, ordinal and relational, average and of the speed of changes). Results: Differences were not found in the average indicators in the analyzed period, however, some that evaluate the speed of the initial change were significantly lower in group A compared to B and C (p < 0.05), while others that evaluate the speed recovery rates were significantly lower in group C compared to A and B. This allows to characterize, compare and differentiate the groups studied during the complex and rapid interactions that occur in the change of position. Conclusion: The dynamic of frequency changes, allowed to find indicators, which can be considered as possible predictors of an inadequate cardiovascular response in patients with vasovagal syncope(AU)

Detección de síncope vasovagal con adaptación de la Escala de Calgary en estudiantes universitarios colombianos / Using a Calgary Scale adaptation to detect vasovagal syncope in Colombian university students

Resumen Introducción: El síncope vasovagal tiene una incidencia entre 10% y 19% en la población general, el primer episodio suele aparecer en la juventud. Objetivo: Estimar la prevalencia de síncope vasovagal en una población universitaria del sur de Colombia, utilizando una adaptación de la Escala de Calgary como cuestionario diagnóstico. Materiales y métodos: Después de la firma voluntaria del consentimiento informado, los estudiantes fueron entrevistados y se les aplicó la Escala de Calgary. Posteriormente, se realizó un cuestionario de seguimiento a los participantes positivos. Resultados: Participaron 280 estudiantes, el 17% obtuvo un puntaje positivo para síncope vasovagal. La edad media fue 21,45±5,18; con mayor positividad para el género femenino. En el seguimiento, el 10% de los positivos, consultó a urgencias por pérdida de conciencia, 4% fue ingresado a hospitalización y 10% presentó lesiones secundarias. Conclusiones: Un número representativo de participantes fue positivo en la Escala de Calgary, ninguno de ellos había recibido diagnóstico de síncope neuralmente mediado, pese a haber consultado a urgencias y/o presentar lesiones secundarias por pérdida de conciencia. Incluir la Escala de Calgary en la evaluación inicial del paciente consultante por pérdida de conciencia, podría ayudar al diagnóstico temprano de síncope vasovagal.

Abstract Introduction: Vasovagal syncope has an incidence between 10% and 19% in the general population, whose first episodes appear in youth. Objective: To estimate the prevalence of vasovagal syncope in a university student population from the southern Colombia, using a diagnostic questionnaire adapted from the Calgary Scale. Materials and methods: After voluntary signing of the informed consent form, students were surveyed through the Calgary Scale, and a subsequent follow-up questionnaire was conducted on positive participants. Results: 280 students participated in the study and 17% of them obtained a positive score for vasovagal syncope, being positive female participants the largest group. The mean age of participants was 21.45±5.18 years. At the follow-up, 10% of the positive cases had sought out treatment in emergency rooms because of consciousness loss, 4% were hospitalized, and 10% had secondary injuries. Conclusions: Even though an important number of patients was positive on the Calgary Scale, none of them had been diagnosed with neutrally mediated syncope, despite being treated in emergency rooms and/or presenting secondary lesions due to consciousness loss. The use of the Calgary Scale during the assessment of patients being treated for consciousness loss could help to early diagnose vasovagal syncope.

The Role of Beta-1 Receptor Gene Polymorphism in Beta-Blocker Therapy for Vasovagal Syncope

Background: Vasovagal syncope (VVS) is a common clinical condition involving genetic background. The role of beta-blockers in the treatment is controversial. Objective: The aim of this study was to investigate the effect of beta-1 gene polymorphism on beta-blocker therapy in patients with VVS. Methods: We included 123 patients who were diagnosed with VVS after the tilt-table test. We searched for the polymorphism Arg389Gly (rs1801253) in the beta-1 adrenoceptor gene. Results: Overall, 64 patients (52%) had Arg389Arg genotype and 59 patients (48%) had Arg389Gly genotype. The syncopal episodes of patients with Arg389Arg genotype were more frequent compared with patients having Arg389Gly genotype (total syncopal episodes [TSE], 7.9 ± 3.7 vs. 6.4 ± 3.0; p = 0.012). TSE in patients with Arg389Arg genotype decreased significantly after 18 months of beta-blocker treatment (7.9 ± 3.7 vs. 3.0 ± 1.4, p < 0.001). After 18 months of beta-blocker treatment, patients with Arg389Arg genotype had significantly fewer syncopal episodes than patients with Arg389Gly genotype (3.0 ± 1.4 vs. 6.8 ± 3.2, p < 0.001). Conclusions: Results of beta-blocker therapy in patients with Arg389Arg genotype suggest that VVS pathophysiology is a multifactorial condition, with genetic, psychological, and environmental components, and therefore, treatment selection can be based on gene polymorphism. (REV INVEST CLIN. 2020;72(5):300-7)

Cardioinhibitory syncope: from pathophysiology to treatment-should we think on cardioneuroablation?

Vasovagal syncope (VVS) is the most common type of syncope; the lone cardioinhibitory syncope represents only a small group of patients; however, the "cardioinhibitory component" is highly prevalent in reflex syncope and can be severe enough to produce asystole, lasting for a few seconds followed by a recovery to sinus beats. The environment in which syncope occurs can compromise life, and in-depth knowledge of the disease can prevent deaths and guide the appropriate management. The therapeutic cornerstone is general measures (increase water and salt) followed by pharmacologic therapy; for cardioinhibitory syncope, both treatments fail most of the time, and the next therapeutic option is pacemaker implantation. However, although the pacemaker causes a reduction in syncope, recurrence is high, and a one-time, effective, and safe intervention would be ideal. Cardioneuroablation (CNA) therapy has been proposed as a pacemaker alternative with these characteristics. CNA has shown a high reduction or even complete syncope elimination during 3 years of follow-up in some studies. Patients also reported prolonged prodromal periods, which allowed them enough time to abort the syncope. Invasive therapies like CNA require further extensive cohort studies, randomized clinical trials, and more substantial follow-up to evaluate adverse side effects. This review highlights syncope pathophysiology, dividing it into a central theory and a peripheral theory, the diagnosis explaining the head-up tilt test protocols, and treatments like CAN, representing it with figures for a simplified understanding.

POLYMORPHISMS IN ß-ADRENERGIC RECEPTORS ARE ASSOCIATED WITH INCREASED RISK TO HAVE A POSITIVE HEAD-UP TILT TABLE TEST IN PATIENTS WITH VASOVAGAL SYNCOPE.

BACKGROUND: Vasovagal syncope (VVS) is a frequent clinical condition in which a genetic background seems to be implicated. Considering that the adrenergic receptors (ARs) may play a role in VVS, the present study has as principal aim to determine if the α- and ß-AR (ADRA and ADRB) gene polymorphisms are associated with an increased risk to have a positive head-up tilt table (HUTT) test in patients with VVS. Methods: Nine polymorphisms in the ADRA1A (rs1048101, rs1383914, rs574584, and rs573542), ADRB1 (rs1801252 and rs1801253), ADRB2 (rs1042713 and rs1042714), and ADRB3 (rs4994) genes were analyzed using the 5' exonuclease TaqMan genotyping assay in a group of 134 patients with VVS. RESULTS: Under different models, the rs1801252 (OR = 8.63, 95% CI: 0.95-78.72, Precessive = 0.02), rs1042713 (OR = 1.94, 95% CI: 1.02-3.66, Padditive = 0.04), and rs4994 (OR = 2.46, 95% CI: 1.01-6.01, Pdominant = 0.042 and OR = 2.62, 95% CI: 1.04-6.63, Pover-dominant = 0.03) polymorphisms were associated with increased risk for a positive HUTT. All models were adjusted for statistically significant covariates. CONCLUSION: These results suggest that some polymorphisms of the ß-AR genes could contribute to a positive tilt test in patients with VVS.

Polymorphisms in ß-adrenergic receptors are associated with increased risk to have a positive head-up tilt table test in patients with vasovagal syncope

Abstract Background Vasovagal syncope (VVS) is a frequent clinical condition in which a genetic background seems to be implicated. Considering that the adrenergic receptors (ARs) may play a role in VVS, the present study has as principal aim to determine if the α- and β-AR (ADRA and ADRB) gene polymorphisms are associated with an increased risk to have a positive head-up tilt table (HUTT) test in patients with VVS. Methods: Nine polymorphisms in the ADRA1A (rs1048101, rs1383914, rs574584, and rs573542), ADRB1 (rs1801252 and rs1801253), ADRB2 (rs1042713 and rs1042714), and ADRB3 (rs4994) genes were analyzed using the 5’ exonuclease TaqMan genotyping assay in a group of 134 patients with VVS. Results Under different models, the rs1801252 (OR = 8.63, 95% CI: 0.95-78.72, Precessive = 0.02), rs1042713 (OR = 1.94, 95% CI: 1.02-3.66, Padditive = 0.04), and rs4994 (OR = 2.46, 95% CI: 1.01-6.01, Pdominant = 0.042 and OR = 2.62, 95% CI: 1.04-6.63, Pover-dominant = 0.03) polymorphisms were associated with increased risk for a positive HUTT. All models were adjusted for statistically significant covariates. Conclusion These results suggest that some polymorphisms of the β-AR genes could contribute to a positive tilt test in patients with VVS.

Frequency Domain Indices of Heart Rate Variability are Useful for Differentiating Vasovagal Syncope and Postural Tachycardia Syndrome in Children.

OBJECTIVE: To explore the value of frequency domain indices of heart rate variability (HRV) in the differential diagnosis between pediatric vasovagal syncope and postural tachycardia syndrome (POTS). STUDY DESIGN: Eighty-five patients aged 7-16 years with either vasovagal syncope or POTS were enrolled in the experimental group; 18 healthy children served as controls. Holter electrocardiography was used to detect HRV frequency-domain indices in patients with vasovagal syncope, patients with POTS, and control subjects. The differences in HRV indices were compared between the vasovagal syncope and POTS groups. The receiver operating characteristic (ROC) curve was calculated to analyze the predictive value of HRV for the differential diagnosis between vasovagal syncope and POTS in children. In addition, 37 children aged 7-17 years with either vasovagal syncope or POTS were recruited as an external validation group. RESULTS: The daytime ultra-low frequency (dULF), nighttime ULF (nULF), daytime very low frequency (dVLF), and nighttime VLF (nVLF) were higher in the vasovagal syncope group compared with the POTS group (P < .01 for dULF, dVLF, and nVLF; P < .05 for nULF). The dULF, nULF, dVLF, and nVLF yielded a sensitivity of 73.3%, 71.1%, 68.9%, and 62.2%, respectively, and a specificity of 72.5%, 62.5%, 60.0%, and 60.0%, respectively, to differentiate vasovagal syncope from POTS. The external validation with clinical diagnostic standard showed that a dULF cutoff value of 36.2 ms2 for differentiating POTS from vasovagal syncope yielded a sensitivity of 71.4%, a specificity of 75.0%, and an accuracy of 73.0%. CONCLUSION: dULF may be a useful measure for the differential diagnosis between vasovagal syncope and POTS in adolescents.

Acceleration Index Predicts Efficacy of Orthostatic Training on Vasovagal Syncope in Children.

OBJECTIVE: To explore the value of the acceleration index as a predictor of therapeutic response to orthostatic training in children with vasovagal syncope (VVS). STUDY DESIGN: Thirty-three children with VVS were recruited and treated with orthostatic training. The therapeutic response of each patient was evaluated after 3 months of treatment. A Pearson correlation was calculated between the acceleration index and the severity of VVS. The value of the acceleration index in predicting the therapeutic response to orthostatic training was assessed by analysis of the receiver operating characteristic curve. RESULTS: Among the 33 children with VVS, 20 were found to be responders and the remaining were nonresponders. The mean acceleration index was significantly lower in responders compared with nonresponders (21.10 ± 6.61 vs 31.36 ± 9.00; P = .001) and it was negatively correlated with positive response time in the head-up tilt test, with systolic blood pressure and with diastolic blood pressure at positive response time in the head-up tilt test (P < .05). The receiver operating characteristic curve for the predictive value of the acceleration index showed that the area under the curve was 0.827 (95% CI, 0.676-0.978; P = .002), and a cutoff value of the acceleration index of 26.77 yielded a sensitivity of 85.0% and a specificity of 69.2%. CONCLUSIONS: The acceleration index may be useful for predicting the efficacy of orthostatic training on VVS in children.

Study of impaired cardiovascular and respiratory coupling during orthostatic stress based on joint symbolic dynamics.

The present study investigates the instantaneous coupling among the cardiac, vascular, and respiratory systems, using the heart rate, respiration, and systolic and diastolic blood pressure variability in 12 healthy and 16 vasovagal syncope female subjects during a head-up tilt (HUT) testing protocol at 70° This study contributes to the coupling analysis by using a nonlinear joint symbolic dynamics (JSD) in a high-temporal resolution scheme, based on 5 min segments of the time series that are shifted every minute. For each segment, a bivariate JSD matrix was constructed to obtain global and local coupling indices in accordance to Shannon's entropy and the probability of occurrence of various bivariate words, respectively. The novel approach revealed important findings in the coupling dynamics of the systems, thus allowing the detection of group differences during the early orthostatic phase, and during the HUT test, before the occurrence of any pre-syncopal symptoms. In patients, the global indices indicated a significant decrease of cardiovascular coupling, starting at 10 min after the tilt-up, manifested by reduced baroreflex sensitivity and cardiorespiratory coupling that was initiated 8 min after the onset of the orthostatic phase (OP). A decreased autonomic control on cardiovascular-respiratory couplings was further evidenced by increased alterations of the JSD indices during the OP compared to the supine position in patients compared to controls. Furthermore, findings based on local indices demonstrated that female patients showed reductions and disengagements in cardiovascular (p < 0.001) and cardiorespiratory (p < 0.01) couplings, as early as the first 5 min and during the complete OP.

The Current Indication for Pacemaker in Patients with Cardioinhibitory Vasovagal Syncope.

The most frequent cause of syncope is vasovagal reflex. It is associated with worse quality of life, depression, fatigue and physical injury. Recurrence of vasovagal syncope is an aggravating, reaching the rate of 69%. Initial step and pharmacological treatment may not work, especially in patients with recurrent syncope without prodrome. These patients can present cardioinhibitory response with asystole. Studies were designed to analyses the effectiveness of pacemaker for prevention of syncope. In this review, nonrandomized clinical trials, open-label randomized, double-blind randomized, placebo-controlled, and studies based on tilt test or Implantable Loop Recorder findings will be discussed.

Uso de marcapasos con sensor de asa cerrada en pacientes con síncope vasovagal refractario al tratamiento médico / Use of closed loop sensor pacing system in patients with vasovagal syncope refractory to medical treatment

Introducción: Estudios previos no han encontrado un beneficio claro relacionado con el uso de marcapasos en síncope cardioinhibitorio; sin embargo, la mayoría de estos fueron realizados con marcapasos con algoritmos de estimulación basados en la caída abrupta de la frecuencia cardíaca. Objetivo: Evaluar el impacto de la estimulación cardiaca utilizando marcapasos con sensor de asa cerrada en el número de síncopes e impacto en la calidad de vida de los pacientes con síncope vasovagal refractario al manejo médico. Métodos: Se registraron de manera prospectiva todos los pacientes con diagnóstico de síncope vasovagal refractario a manejo médico a quienes se les implantó un marcapasos bicameral con sensor de asa cerrada durante el periodo comprendido entre agosto de 2008 y agosto de 2013. Se evaluó la frecuencia de eventos sincopales y la calidad de vida (por medio del cuestionario SFSQ) antes y después del implante del dispositivo. Resultados: Se incluyeron 51 pacientes (27 mujeres, 53%), con promedio de edad de 52,98 ± 16,88 años y un seguimiento de 20,19 ± 14,64 meses. Se registraron 30 casos (58,8%) de síncope cardioinhibitorio, 20 (39,21%) de mixto y 1 (1,9%) de vasodepresor. El número de síncopes posterior al implante del dispositivo con sensor de asa cerrada, disminuyó en forma estadísticamente significativa. Se registraron un total de 198 síncopes antes del implante del marcapasos, valor que descendió a 10 luego del implante (reducción del 94,9%). Los pacientes experimentaron 3,88 ± 3,52 síncopes previo al implante, los cuales disminuyeron hasta 0,19 ± 0,63 episodios postimplante (p <0,001). La calidad de vida mejoró después del implante: el puntaje promedio SFSQ por paciente preimplante, fue de 70,19 ± 24,5 vs. 15,88 ± 13,73 postimplante (p = 0,000). Conclusión: El implante de un marcapasos con sensor de asa cerrada en pacientes con síncope vasovagal refractario a manejo médico, mostró una disminución significativa en el número de síncopes y mejoría en la calidad de vida.

Introduction: Previous studies have not found a clear benefit related to the use of pacemakers in cardioinhibitory syncopes; however, most of them were conducted with pacing systems using stimulation algorithms based in the abrupt drop of the heart rate. Objetive: To assess the impact of cardiac stimulation using a closed loop sensor pacemaker in the number of syncopes and its impact in the quality of life of patients with a vasovagal syncope refractory to medical treatment. Methods: Prospective registration of patients diagnosed with vasovagal syncope refractory to medical treatment, who were implanted a bicameral closed loop sensor pacemaker between August 2008 and August 2013. Frequency of syncopal events and quality of life (using the SFSQ) were assessed before and after implanting the device. Results: 51 patients were included (27 women, 53%), with an average age of 52.98 ± 16.88 and a follow-up of 20.19 ± 14.64 months. 30 cases (58.8%) of cardioinhibitory syncope were registered, 20 (39.21%) were mixed and 1 (1.9%) was vasodepressor. The number of syncopes after the implantation of the closed loop sensor device was significantly reduced. Before the pacemaker was implanted, the total of registered syncopes was 198, a value that was reduced to 10 after the implantation (a 94.9% drop). Patients experienced 3.88 ± 3.52 before the implantation, and they decreased to 0.19 ± 0.63 episodes postimplant (p <0.001). Quality of life improved after the implantation: patient average SFSQ score before the implantation was of 70.19 ± 24.5 vs. 15.88 ± 13.73 postimplant (p = 0.000). Conclusion: Implanting a closed loop sensor pacemaker in patients with vasovagal syncope refractory to medical treatment revealed a significant decrease in the number of syncopes and an improvement in the quality of life.

[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.