LQT5 masquerading as LQT2: a dominant negative effect of KCNE1-D85N rare polymorphism on KCNH2 current.

AIMS: KCNE1 encodes an auxiliary subunit of cardiac potassium channels. Loss-of-function variations in this gene have been associated with the LQT5 form of the long QT syndrome (LQTS), secondary to reduction of I(Ks) current. We present a case in which a D85N rare polymorphism in KCNE1 is associated with an LQT2 phenotype. METHODS AND RESULTS: An 11-year old competitive athlete presented with mild bradycardia and a QTc interval of 470 ms. An LQT2 phenotype, consisting of low-voltage bifid T waves, was evident in the right precordial electrocardiogram leads. During the tachycardia phase following adenosine, QTc increased to 620 ms. Genetic analysis revealed a rare heterozygous polymorphism in KCNE1 predicting the substitution of asparagine for aspartic acid at position 85 of minK (D85N). Patch clamp experiments showed that KCNE1-D85N, when co-expressed with KCNH2 in TSA201 cells, significantly reduced I(Kr). Homozygous co-expression of the mutant with KCNH2 reduced I(Kr) tail current by 85%, whereas heterozygous co-expression reduced the current by 52%, demonstrating for the first time a dominant-negative effect of D85N to reduce I(Kr). Co-expression of the mutant with KCNQ1, either homozygously or heterozygously, produced no change in I(Ks). CONCLUSIONS: Our results suggest that a rare polymorphism KCNE1-D85N underlies the development of an LQT2 phenotype in this young athlete by interacting with KCNH2 to cause a dominant-negative effect to reduce I(Kr). Our data provide further evidence in support of the promiscuity of potassium channel ß subunits in modulating the function of multiple potassium channels leading to a diversity of clinical phenotypes.

Qual a contribuição do tilt training (treinamento postural) na prevenção da síncope vasovagal ? / Tilt training: does it have a role in preventing vasovagal syncope? / ¿Cuál es el aporte del tilt training (entrenamiento postural) a la prevención del síncope vasovagal?

Histórico: A síncope vasovagal é um dos quadros clínicos mais comuns em adultos jovens. Estudos anteriores demonstram a eficácia do tilt training (treinamento postural) no tratamento desse transtorno clínico. Realizou-se um estudo prospectivo e randomizado com o objetivo de avaliar a contribuição do tilt training no tratamento de adultos jovens acometidos pela síncope vasovagal. Métodos: Quarenta e seis soldados , 25 dos quais do sexo masculino, média de idade de 19,4 mais ou menos 0,8 anos e diagnóstico clínico de síncope vasovagal pelo tilt teste, foram divididos aleatoriamente em dois grupos: um grupo controle e outro acometido de tilt training diariamente, por três meses. Nos dois grupos, os participantes foram instruídos a aumentar a ingestão de líquidos e sal e evitar situações indutoras de síncope, tais como permanecer em pé por períodos longos. Resultados: A adesão ao programa de treinamento, caracterizada pela realização de 50 por cento ou mais das sessões diárias de tilt training, foi de 91 por cento durante o primeiro mês, caindo para 58 por cento nos três meses. Os que realizaram o treinamento apresentaram uma média (distância interquartilica) e 5,0 episódios de síncope (0,5 a 16,0) durante um ano de acompanhamento, enquanto o grupo controle apresentou média de 2,0 episódios (0 a 6,0, P igual 0,737). Após a randomização não houve diferença significativa no tempo de ocorrência do primeiro episódio entre os dois grupos: média de 1,0 por mês (0,5 a 2,0) no grupo em tratamento...

Background: Vasovagal syncope is one of the most common medical conditions in young adults. Previous trials have shown effectiveness of tilt training in treating this condition. We conducted a prospective, randomized study in order to evaluate the role of tilt-training in young adults with vasovagal syncope. Methods: Forty-six soldiers (mean age 19.4 ± 0.8 years, 25 males), with a clinical diagnosis of vasovagal syncope supported by positive tilt test, were randomized to either three months of daily tilt training (treatment group), or no training (control group). Patients in both groups were instructed to increase fluid and salt intake, and to refrain from syncope-inducing situations, such as prolonged standing. Results: Compliance, defined as performing 50% or more of the tilt training daily sessions, was 91% during the first month, and declined to 58% during three months. Treatment group patients had a median (interquartile range) of 5.0 (0.5–16.0) syncope episodes during one-year follow up, compared to a median of 2.0 (0–6.0) episodes in the control group (P = 0.737). Also, there was no difference in time to first syncope after randomization between groups: a median of 1.0 (0.5–2.0) month in the treatment group, compared to 0.8 (0.5–2.0) month in the control group (P = 0.336). Conclusions: Adding daily three-month tilt training to modifications in lifestyle does not improve treatment results in youngadults with vasovagal syncope. Good compliance is difficult to achieve in a tilt training program.

Historial: El síncope vasovagal es uno de los cuadros clínicos más comunes en adultos jóvenes. Estudios anteriores han demostrado la eficiencia del tilt training (entrenamiento postural) en el tratamiento de ese trastorno clínico. Se llevó a cabo un estudio prospectivo y randomizado con el objetivo de evaluar el aporte del tilt training al tratamiento de adultos jóvenes acometidos por el síncope vasovagal. Métodos: Cuarenta y seis soldados, 25 de ellos del sexo masculino, promedio de edad de 19,4 ± 0,8 años y diagnóstico clínico de síncope vasovagal por el tilt test, fueron divididos aleatoriamente en dos grupos: un grupo control y otro sometido a tilt training diariamente, por tres meses. En ambos grupos, los participantes fueron instruidos a aumentar la ingesta de líquidos y sal y evitar situaciones inductoras del síncope, tales como permanecer en pie por largos períodos. Resultados: La adhesión al programa de entrenamiento, caracterizada por la realización del 50% o más de las sesiones diarias de tilt training, fue del 91% durante el primer mes, bajando al 58% a los tres meses. Quienes llevaron a cabo el entrenamiento presentaron un promedio (distancia intercuartílica) de 5,0 episodios de síncope (0,5 a 16,0) durante un año de acompañamiento, mientras el grupo control presentó un promedio de 2,0 episodios (0 a 6,0; P = 0,737). Tras la randomización, no hubo diferencia significativa en el tiempo de ocurrencia del primer episodio de síncope entre ambos grupos: promedio de 1,0 por mes (0,5 a 2,0) en el grupo en tratamiento y 0,8 (0,5 a 2,0) en el grupo control (P = 0,336). Conclusiones: La realización diaria del tilt training, aliada a los cambios de estilo de vida, no produjo mejora en el resultado del tratamiento de adultos jóvenes con síncope vasovagal. Se verificó asimismo la dificultad de obtener buena adhesión al programa de entrenamiento postural.

Tilt training: does it have a role in preventing vasovagal syncope?

BACKGROUND: Vasovagal syncope is one of the most common medical conditions in young adults. Previous trials have shown effectiveness of tilt training in treating this condition. We conducted a prospective, randomized study in order to evaluate the role of tilt-training in young adults with vasovagal syncope. METHODS: Forty-six soldiers (mean age 19.4 +/- 0.8 years, 25 males), with a clinical diagnosis of vasovagal syncope supported by positive tilt test, were randomized to either three months of daily tilt training (treatment group), or no training (control group). Patients in both groups were instructed to increase fluid and salt intake, and to refrain from syncope-inducing situations, such as prolonged standing. RESULTS: Compliance, defined as performing 50% or more of the tilt training daily sessions, was 91% during the first month, and declined to 58% during three months. Treatment group patients had a median (interquartile range) of 5.0 (0.5-16.0) syncope episodes during one-year follow up, compared to a median of 2.0 (0-6.0) episodes in the control group (P = 0.737). Also, there was no difference in time to first syncope after randomization between groups: a median of 1.0 (0.5-2.0) month in the treatment group, compared to 0.8 (0.5-2.0) month in the control group (P = 0.336). CONCLUSIONS: Adding daily three-month tilt training to modifications in lifestyle does not improve treatment results in young adults with vasovagal syncope. Good compliance is difficult to achieve in a tilt training program.

A novel form of familial bidirectional ventricular tachycardia.

We evaluated a family with 30 members, 3 of whom had incessant polymorphous and bidirectional ventricular tachycardia (VT) that was electrocardiographically similar to that described in other familial polymorphic VT series; the VT was unrelated to exercise and asymptomatic. More subtle, but morphologically similar, ventricular arrhythmias were detected in 3 other family members. Genes related to intracellular calcium transport were specifically excluded.