Favorable Safety Experience of Local Dental Anesthesia in ICD Recipients with Cardiac Channelopathies

Abstract Background Dental anesthetic management in implantable cardioverter defibrillator (ICD) recipients with cardiac channelopathies (CCh) can be challenging due to the potential risk of life-threatening arrhythmias and appropriate ICD therapies during procedural time. Objectives The present study assessed the hypothesis that the use of local dental anesthesia with 2% lidocaine with 1:100,000 epinephrine or without a vasoconstrictor can be safe in selected ICD and CCh patients, not resulting in life-threatening events (LTE). Methods Restorative dental treatment under local dental anesthesia was made in two sessions, with a wash-out period of 7 days (cross-over trial), conducting with a 28h - Holter monitoring, and 12-lead electrocardiography, digital sphygmomanometry, and anxiety scale assessments in 3 time periods. Statistical analysis carried out the paired Student's t test and the Wilcoxon signed-rank test. In all cases, a significance level of 5% was adopted. All patients were in stable condition with no recent events before dental care. Results Twenty-four consecutive procedures were performed in 12 patients (9 women, 3 men) with CCh and ICD: 7 (58.3%) had long QT syndrome (LQTS), 4 (33.3%) Brugada syndrome (BrS), and 1 (8.3%) Catecholaminergic polymorphic ventricular tachycardia (CPVT). Holter analysis showed no increased heart rate (HR) or sustained arrhythmias. Blood pressure (BP), electrocardiographic changes and anxiety measurement showed no statistically significant differences. No LTE occurred during dental treatment, regardless of the type of anesthesia. Conclusion Lidocaine administration, with or without epinephrine, can be safely used in selected CCh-ICD patients without LTE. These preliminary findings need to be confirmed in a larger population with ICD and CCh.

Research Progress and Forensic Application of Postmortem Genetic Testing in Hereditary Cardiac Diseases / 法医学杂志

Hereditary cardiac disease accounts for a large proportion of sudden cardiac death (SCD) in young adults. Hereditary cardiac disease can be divided into hereditary structural heart disease and channelopathies. Hereditary structural heart disease mainly includes hereditary cardiomyopathy, which results in arhythmia, heart failure and SCD. The autopsy and histopathological examinations of SCD caused by channelopathies lack characteristic morphological manifestations. Therefore, how to determine the cause of death in the process of examination has become one of the urgent problems to be solved in forensic identification. Based on the review of recent domestic and foreign research results on channelopathies and hereditary cardiomyopathy, this paper systematically reviews the pathogenesis and molecular genetics of channelopathies and hereditary cardiomyopathy, and discusses the application of postmortem genetic testing in forensic identification, to provide reference for forensic pathology research and identification of SCD.

Thyrotoxic periodic paralysis: A retrospective, observational study from India

Background & objectives: Thyrotoxic periodic paralysis (TPP) is an endocrine emergency presenting with acute-onset flaccid paralysis in a patient having thyrotoxicosis accompanied by hypokalaemia. This study was conducted to evaluate the clinical profile of patients with TPP presenting to three centres in India. Methods: This retrospective, observational study was conducted at three tertiary care Armed Forces medical centres, located at Lucknow, Kolkata and Delhi. The history, clinical features, treatment details and outcomes were evaluated. Results: Of the 244 patients with thyrotoxicosis, 15 were diagnosed with TPP and included in the study. These 15 patients (14 male and 1 female) had 32 episodes of TPP which were analyzed. The mean age was 30.2�2 yr (range: 21-39), and overt thyrotoxicosis was seen in all patients except one who had subclinical hyperthyroidism. Graves' disease was the most common cause of thyrotoxicosis (13/15) and the remaining two patients had subacute thyroiditis and gestational thyrotoxicosis. Hypokalaemia (serum potassium <3.5 mmol/l) was seen in 12 patients, and the mean serum potassium was 3.2�9 mmol/l (range: 2.1-4.9). All patients had flaccid weakness, predominantly involving the lower limb with no bulbar, respiratory or cranial nerve involvement. The average duration of paralysis was 10.6�7 h (range: 3-28 h). Interpretation & conclusions: Our study demonstrated an early age of presentation and presence of clinical and biochemical thyrotoxicosis in majority of patients with TPP. Hypokalaemia may not always be evident in patients with TPP.

Pain insensitivity in a child with a de novo interstitial deletion of the long arm of the chromosome 4: Case report / Insensibilidad al dolor en un niño con una deleción intersticial de novo del brazo largo del cromosoma 4

Terminal and interstitial deletions of the distal segment of the long arm of chromosome 4 (Cr4q del) are not common genetic disorders. The severity of the phenotype is correlated with the size of the deletion because small deletions have little clinical impact, whereas large deletions are usually associated with multiple congenital anomalies, postnatal growth failure, and moderate to severe intellectual disability. Alteration in pain tolerance has not been included among these features, also in case of large deletions. The purpose of this report is to document a case of a child affected by interstitial Cr4q del, expressing pain insensitivity as clinical feature not previously described. We also offer a discussion on genetic disorders featuring pain insensitivity/indifference. Case report. A Caucasian girl aged 12 came to our observation for a developmental delay with multiple congenital abnormalities and moderate intellectual disability (IQ 47). A de novo interstitial Cr4 del between band q31.3 and q32.2 (Cr4 del q31.3 to q32.2) was found. The child also expresses no evidence of pain perception to injures which normally evoke pain. Consequently, she is affected by severe disability caused by painless injuries and self-injurious behaviours, such as excessive self-rubbing and scratching. The neurological examination manifested high pain threshold with preserved tactile sensitivity. Conclusions. This is the first report of pain insensitivity in a patient with a specific genetic deletion involving the interstitial region of the distal long arm of Cr4. Moreover, this report could serve as a useful model to better understand mechanisms of pain perception and its modulation.

Canalopatías en muerte súbita: Relevancia clínica de autopsia molecular / Channelopathies in sudden death: Clinical relevance of molecular autopsy

ResumenLas canalopatías abarcan una serie síndromes arrítmicos caracterizados por una presentación inicial de muerte súbita o síncope, en personas en su mayoría jóvenes y conocidas sanas, que poseen una autopsia normal. Éstas se deben a mutaciones en los genes que codifican para canales iónicos de los miocitos cardíacos, así como las proteínas asociadas a si funcionamiento o traducción. Dada su asociación hereditaria, los familiares podrían tener un riesgo aumentado de presentar el trastorno pese a estar asintomáticas. Allí radica la importancia del mapeo genético en aquellas autopsias en las que no se ha identificado la causa de muerte. La autopsia molecular permite buscar e identificar estas mutaciones y correlacionar la muerte súbita con una canalopatía. Lo cual resulta esencial para la evaluación del riesgo y la prevención de otro episodio de muerte súbita cardíaca en familiares portadores.En este artículo se exponen las canalopatías más importantes asociadas a muerte súbita, y el impacto del mapeo genético en la prevención y manejo en familiares portadores.

AbstractChannelopathies include a series of syndromes characteristic of an initial presentation of sudden death or syncope, in persons mostly young and known healthy, who have a normal autopsy. These are due to mutations in the genes encoding ionic channels of cardiac myocytes, as well as the proteins associated with whether functioning or translation. Because of their hereditary association, relatives may be at increased risk of developing the disorder despite being asymptomatic. There lies the importance of genetic mapping in those autopsies in which the cause of death has not been identified. Molecular autopsy allows searching and identifying these mutations and correlating sudden death with a channelopathy. This is essential for the evaluation of risk and prevention of another episode of sudden cardiac death in family members. This article discusses the most important channelopathies associated with sudden death, and the impact of genetic mapping on prevention and management in family members.

Síndrome del QT largo y muerte súbita cardiovascular / Long QT syndrome and sudden cardiovascular death

Fundamento: el síndrome de QT largo es una canalopatía arritmogénica, caracterizada por una grave alteración en la repolarización ventricular, traducida electrocardiográficamente por una prolongación del intervalo QT, que predispone a la muerte súbita por arritmias ventriculares malignas, del tipo torsada de punta. Objetivo: presentar un caso de síndrome QT poco frecuente en nuestro medio. Caso Clínico: paciente de 31 años de edad con antecedente de salud, que ingresó en dos ocasiones durante su embarazo por cifras elevadas de tensión arterial en el año 2013. Presentó varios cuadros de sincope del cual se recuperaba espontáneamente. Ingresó en enero de 2014 por trastornos dispépticos y epigastralgia, al estar hospitalizada hizo un cuadro de sincope y taquicardia ventricular documentadas por electrocardiograma, donde llegó hacer torsada de punta y parada cardiorrespiratoria, por lo que fue necesario la reanimación cardiorrespiratoria y entubación endotraqueal, así se mantuvo 48 horas y salió de este cuadro. Se trasladó al instituto de cardiología en ciudad de la habana, donde fue estudiada por el equipo de arritmias y se decidió la implantación de un dispositivo de desfibrilación automático implantable.

Background: long QT syndrome is an arrhythmogenic canalopathy characterized by a serious alteration in the ventricular repolarization, translated electrocardiographically by a prolongation of the QT interval that predispose to sudden death caused by malignant ventricular arrhythmias tracing in torsades de pointes. Objective: to present the clinical case of a patient with this syndrome that is infrequent in our environment. Clinical case: a thirty-one-year-old patient with antecedents of being a healthy person, who was admitted in the hospital twice during her pregnancy because of high arterial pressure in 2013. The patient presented syncope manifestations from which she recovered spontaneously. In January 2014, the patient is admitted in the hospital with dyspeptic disorders and epigastralgia. After being admitted, the patient presented syncope manifestations and ventricular tachycardia exhibited on the electrocardiogram tracing in torsades de pointes and cardiac arrest. It was necessary to perform a cardiopulmonary resuscitation and endotracheal intubation. The patient presented this combination of manifestations for 48 hours. She is sent to the Cardiology Institute of Havana where she is studied by the arrhythmia medical team and the implantation of an implantable cardioverter-defibrillator is decided.

Muerte súbita cardiaca en el corazón estructuralmente normal: una actualización / Sudden cardiac death in individuals with normal hearts: an update

La muerte súbita (MS) es un evento trágico que representa un grave problema de salud. Se estima que causa cerca de 4-5 millones de decesos por año en todo el mundo. La MS se define como la muerte ocurrida en el lapso de 1 h en una persona sin signos previos de fatalidad; puede denominarse «recuperada¼, cuando el paciente afectado sobrevive al episodio potencialmente fatal ya sea por reanimación cardiopulmonar o desfibrilación efectiva. Las canalopatías arritmogénicas son alteraciones funcionales de los canales iónicos del corazón, generalmente condicionados por mutaciones en los genes que los codifican y dan lugar a diversos tipos de arritmias que pueden culminar en MS, el deceso ocurre normalmente antes de los 40 años y el corazón en estudio de autopsia suele ser estructuralmente normal. En la presente revisión presentamos las principales causas de MS en el contexto del corazón estructuralmente normal y discutimos el abordaje que se debe dar a los pacientes y familiares de víctimas que han experimentado éste trágico evento.

Sudden death (SD) is a tragic event and a world-wide health problem. Every year, near 4-5 million people experience SD. SD is defined as the death occurred in 1 h after the onset of symptoms in a person without previous signs of fatality. It can be named «recovered SD¼ when the case received medical attention, cardiac reanimation effective defibrillation or both, surviving the fatal arrhythmia. Cardiac channelopathies are a group of diseases characterized by abnormal ion channel function due to genetic mutations in ion channel genes, providing increased susceptibility to develop cardiac arrhythmias and SD. Usually the death occurs before 40 years of age and in the autopsy the heart is normal. In this review we discuss the main cardiac channelopathies involved in sudden cardiac death along with current management of cases and family members that have experienced such tragic event.

Channelopathies / 소아과

Channelopathies are a heterogeneous group of disorders resulting from the dysfunction of ion channels located in the membranes of all cells and many cellular organelles. These include diseases of the nervous system (e.g., generalized epilepsy with febrile seizures plus, familial hemiplegic migraine, episodic ataxia, and hyperkalemic and hypokalemic periodic paralysis), the cardiovascular system (e.g., long QT syndrome, short QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia), the respiratory system (e.g., cystic fibrosis), the endocrine system (e.g., neonatal diabetes mellitus, familial hyperinsulinemic hypoglycemia, thyrotoxic hypokalemic periodic paralysis, and familial hyperaldosteronism), the urinary system (e.g., Bartter syndrome, nephrogenic diabetes insipidus, autosomal-dominant polycystic kidney disease, and hypomagnesemia with secondary hypocalcemia), and the immune system (e.g., myasthenia gravis, neuromyelitis optica, Isaac syndrome, and anti-NMDA [N-methyl-D-aspartate] receptor encephalitis). The field of channelopathies is expanding rapidly, as is the utility of molecular-genetic and electrophysiological studies. This review provides a brief overview and update of channelopathies, with a focus on recent advances in the pathophysiological mechanisms that may help clinicians better understand, diagnose, and develop treatments for these diseases.

The large-conductance calcium-activated potassium channel holds the key to the conundrum of familial hypokalemic periodic paralysis / 소아과

PURPOSE: Familial hypokalemic periodic paralysis (HOKPP) is an autosomal dominant channelopathy characterized by episodic attacks of muscle weakness and hypokalemia. Mutations in the calcium channel gene, CACNA1S, or the sodium channel gene, SCN4A, have been found to be responsible for HOKPP; however, the mechanism that causes hypokalemia remains to be determined. The aim of this study was to improve the understanding of this mechanism by investigating the expression of calcium-activated potassium (KCa) channel genes in HOKPP patients. METHODS: We measured the intracellular calcium concentration with fura-2-acetoxymethyl ester in skeletal muscle cells of HOKPP patients and healthy individuals. We examined the mRNA and protein expression of KCa channel genes (KCNMA1, KCNN1, KCNN2, KCNN3, and KCNN4) in both cell types. RESULTS: Patient cells exhibited higher cytosolic calcium levels than normal cells. Quantitative reverse transcription polymerase chain reaction analysis showed that the mRNA levels of the KCa channel genes did not significantly differ between patient and normal cells. However, western blot analysis showed that protein levels of the KCNMA1 gene, which encodes KCa1.1 channels (also called big potassium channels), were significantly lower in the membrane fraction and higher in the cytosolic fraction of patient cells than normal cells. When patient cells were exposed to 50 mM potassium buffer, which was used to induce depolarization, the altered subcellular distribution of BK channels remained unchanged. CONCLUSION: These findings suggest a novel mechanism for the development of hypokalemia and paralysis in HOKPP and demonstrate a connection between disease-associated mutations in calcium/sodium channels and pathogenic changes in nonmutant potassium channels.

Transmissão hereditária da morte súbita cardíaca nas canalopatias / Hereditary transmission of sudden cardiac death in channelopathies

O caso clínico sugere uma forma rara de canalopatia mista, cujo sintoma clínico e eletrocardiográfico indicava taquicardia ventricular polimórfica catecolaminérgica (TVPC). Porém, ao realizar o teste ergométrico, no pós-esforço, quando há predomínio do sistema nervoso parassimpático, nota-se a indução de eletrocardiograma (ECG) compatível com Brugada do tipo I. Outro aspecto importante foi a transmissão hereditária observada neste caso, em que os avós do paciente eram primos de primeiro grau e houve seis casos de morte súbita cardíaca (MSC) nas gerações subsequentes, com irmão que teve MSC aos 5 anos durante uma crise de choro, mostrando um importante fator genético e familiar relacionado às canalopatias.

The clinical case suggests a rare form of mixed channelopathy, whose clinical and electrocardiographic symptom suggested catecholaminergic polymorphic ventricular tachycardia (CPVT). However, when the exercise test was performed, during post-exercise, where there is a predominance of the parasympathetic nervous system, there was an electrocardiogram (ECG) induction compatible with Brugada type I. Another important aspect was the hereditary transmission observed in this patient, whose grandfathers were first cousins, and 6 cases of sudden cardiac death (SCD) were observed in subsequent generations and one brother had SCD at 5 years of age during a crying episode, showing an important genetic and familial factor related to channelopathies.

Síndrome de QT corto / Short QT syndrome

El síndrome de QT corto es una canalopatía hereditaria caracterizada por un anormal acortamiento del intervalo QT (IQT), por un riesgo incrementado para el desarrollo de fibrilación auricular y/o arritmias ventriculares malignas y por la ausencia de cardiopatía estructural. Es una enfermedad heterogénea y se han identificado mutaciones en los genes codificadores de los canales de potasio y de calcio. Un incremento en las corrientes neta de salida de potasio o una disminución en al entrada de calcio favorecen el acortamiento heterogéneo de la repolarización ventricular. La marcada abreviación de la longitud de onda del circuito es un factor arritmogénico adicional. El curso clínico oscila desde formas asintomáticas hasta fibrilación auricular paroxística o permanente, síncope, arritmias ventriculares y muerte súbita. El electrocardiograma muestra IQT 220-360 ms, ondas T altas y puntiagudas, prolongación del intervalo pico-final de la onda T e IQT rígido. Es poco frecuente, pero importante por el riesgo elevado de muerte súbita, que en ocasiones puede ser el debut. Puede presentarse solapado al síndrome de Brugada y a la repolarización precoz. El diagnóstico precisa excluir las causas secundarias que acortan el IQT y la no identificación de una mutación no lo excluye. La estimulación eléctrica programada tiene pobre valor diagnóstico y pronóstico. En los sujetos con muerte súbita abortada o con arritmias ventriculares con compromiso hemodinámica, el desfibrilador es la terapéutica de elección. La quinidina es una opción terapéutica alternativa

The short QT syndrome is an inherited channelopathy characterized by an abnormal shortening of the QT interval (QTI), an increased risk of developing atrial fibrillation and/or malignant ventricular arrhythmias, and the absence of structural heart disease. It is a heterogeneous disease and mutations have been identified in the genes encoding potassium and calcium channels. An increase in potassium net efflux or a decrease in calcium influx facilitate the heterogeneous shortening of ventricular repolarization. A marked shortening of the wavelength of the circuit is an additional arrhythmogenic factor. The clinical course ranges from asymptomatic forms to paroxysmal or permanent atrial fibrillation, syncope, ventricular arrhythmias and sudden death. The ECG shows QTI 220-360 ms, high and sharp T waves, prolongation of the final peak interval of the T wave, and QTI drive. It is a rare disease whose importance lies in the high risk of sudden death, which may sometimes be its debut. It may overlap Brugada syndrome and early repolarization. Diagnosis requires excluding secondary causes of QTI shortening. Failure to identify a mutation does not exclude it. Programmed electrical stimulation has a low diagnostic and prognostic value. Defibrillation is the therapy of choice for patients with aborted sudden death or ventricular arrhythmias with hemodynamic compromise. Quinidine is an alternative therapeutic option

Taquicardia ventricular polimórfica catecolaminérgica / Catecholaminergic polymorphic ventricular tachycardia

La taquicardia ventricular polimórfica catecolaminérgica es una canalopatía caracterizada por la inducción de arritmias ventriculares polimórficas en presencia de catecolaminas. Deberá sospecharse en todo paciente joven, en especial niño o adolescente, que presente síncopes relacionados con el ejercicio físico o el estrés emocional, que no tenga cardiopatía estructural y que su electrocardiograma muestre un intervalo QT normal. Es poco frecuente, pero importante por el riesgo elevado de muerte súbita, que en ocasiones puede ser el debut. Las arritmias ventriculares son polimórficas o bidireccionales, fácilmente inducibles con el ejercicio físico y con infusión de isuprel, tienen un umbral predecible y una complejidad progresiva. Los antecedentes patológicos familiares de muerte súbita se observan entre el 30 y 40 pociento de los pacientes. Se han identificado 2 mutaciones genéticas causantes de la entidad (receptores de rianodina 2, con herencia autosómica dominante y calsecuestrina 2, con herencia autosómica reseciva); pero solo entre 50-55 porciento de los enfermos se ha testado una mutación causal. Las mutaciones condicionan la fuga de Ca2+ del retículo sarcoplásmico que favorece el origen de posdespolarizaciones tardías, las que inducirán la actividad ectópica ventricular. Los Ô-bloqueadores son el tratamiento de elección. El desfibrilador automático implantable está indicado en los pacientes recuperados de un evento de muerte súbita y en los sintomáticos a pesar del tratamiento farmacológico. La denervación simpática cardíaca izquierda, el verapamilo, la flecainida y la propafenona, son opciones alternativas en los sintomáticos a pesar del uso de β-bloqueadores

Catecholaminergic polymorphic ventricular tachycardia is a channelopathy characterized by the induction of polymorphic ventricular arrhythmias in the presence of catecholamines. It should be suspected in any young patient, especially a child or adolescent, presenting with syncope associated with physical exercise or emotional stress, with no structural heart disease and an ECG showing a normal QT interval. It is a rare disease, its importance lying in the high risk of sudden death, which may sometimes be its debut. Ventricular arrhythmias may be polymorphic or bidirectional. They are highly inducible by physical exercise and Isuprel infusion, their threshold is predictable and their complexity progressive. A family history of sudden death is reported in 30 to 40 percent of patients. Two genetic mutations have been identified as causes of the condition (ryanodine receptor 2 with autosomal dominant inheritance and calsequestrin 2, with autosomal recessive inheritance). However, a causal mutation has been found in only 50-55 percent of patients. Mutations influence sarcoplasmic reticulum Ca 2+ leak, facilitating the appearance of late post-depolarisations, which will in turn induce ventricular ectopic activity. Beta-blockers are the treatment of choice. The automatic implantable defibrillator is indicated in patients recovered from a sudden death event and in those who remain symptomatic despite medical therapy. Left cardiac sympathetic denervation, verapamil, flecainide and propafenone are alternative options for patients who remain symptomatic despite the use of beta-blockers

Canalopatías iónicas: generalidades y panorámica actual / Ion channelopathies: Overview and current status

Se presenta un panorama actual sobre las enfermedades de los canales iónicos cardíacos, con sus características comunes y algunas particularidades. Son síndromes arritmogénicos hereditarios por disfunciones en el tráfico de los canales iónicos al nivel de la membrana (mutaciones en los genes que codifican proteínas, con ganancia o pérdida de función), arritmias peligrosas para la vida, síncopes y muerte súbita, sin anormalidades estructurales gruesas detectables por los métodos convencionales. Estas enfermedades han experimentado un vertiginoso desarrollo en su entendimiento, diagnóstico y terapéutica en las últimas 2 décadas y se vislumbra un futuro promisorio con la genética molecular. Son diagnósticos de exclusión, se eliminan las cardiopatías estructurales, los trastornos electrolíticos y metabólicos, otras causas eléctricas y el empleo de fármacos antiarrítmicos. Se presentan en jóvenes aparentemente sanos, cuyo debut puede ser una arritmia ventricular maligna o un evento de muerte súbita, del cual solo es reanimado el 5 porciento. Comprenden un espectro clínico muy amplio, desde los asintomáticos (signos eléctricos, no síndromes), hasta los que fallecen. Su frecuencia real no se conoce debido a: muerte, diagnóstico erróneo, signos mínimos, intermitentes u ocultos. Se incorporan nuevas entidades, algunas se superponen y es muy difícil estratificar riesgo antes del debut. Se han creado registros internacionales. Se presentan los datos de nuestro Registro Nacional cubano de canalopatías en pacientes reanimados de eventos de muerte súbita seguidos durante 10 años

An overview is presented of the current status of cardiac ion channel diseases, their common characteristics and some distinguishing features. Ion channelopathies are inherited arrhythmogenic syndromes caused by ion channel traffic dysfunctions at membrane level (mutations in protein-encoding genes with gain or loss of function), life-threatening arrhythmias, syncope and sudden death, without any gross structural abnormality detectable by conventional methods. The past two decades have witnessed speedy progress in the understanding, diagnosis and treatment of these diseases, a situation which will continue to be as promising in the future with the application of molecular genetics. They are exclusion diagnoses. Structural heart diseases, electrolyte and metabolic disorders, other electrical causes and the use of antiarrhythmic drugs are all discarded. They appear in seemingly healthy young persons, whose debut may be a malignant ventricular arrhythmia or a sudden death event, from which only 5 percent are reanimated. They have a very broad clinical spectrum, ranging from asymptomatic cases (electrical signs, no syndromes) to fatal cases. Their actual frequency is unknown, due to: death, erroneous diagnosis, and minimal, intermittent or hidden signs. New diseases are incorporated, some overlap and it is very difficult to stratify risk before the debut. International registries have been developed. The paper presents the data contained in the Cuban National Channelopathy Register for patients reanimated from sudden death events and followed up for 10 years

Intervalo QT corto intermitente en un paciente con muerte súbita cardiaca / Intermittent short QT interval in a patient with sudden cardiac death

Se presenta el caso de un hombre de 21 años de edad, sin cardiopatía estructural demostrable por los métodos convencionales, reanimado de un episodio de muerte súbita cardiaca. Su historia familiar incluye dos hermanos muertos súbitamente en el primer año de vida. El paciente tuvo diez episodios de taquicardia ventricular (varios de ellos registrados), uno de ellos lo llevó al evento de muerte del cual fue reanimado. Las anormalidades electrocardiográficas fueron un intervalo QT corto intermitente (280 ms), un QT corregido de 320 ms y un segmento ST corto. Con posterioridad el intervalo QT retornó a cifras normales (360 ms o más); ocasionalmente midió 335 ms (no tan corto como el inicial). El estudio electrofisiológico fue normal (intervalos AH y HV, períodos refractarios, no inducibilidad de la arritmia). El paciente rechazó la opción de cardioversor desfibrilador automático implantable y recibe amiodarona hasta la actualidad (200 mg/día), no ha repetido la arritmia en cuatro años. Los electrocardiogramas seriados son muy importantes para identificar pacientes con intervalo QT corto intermitente. El acortamiento del intervalo onda J-T pico es relevante. La arritmia puede ser fibrilación o taquicardia ventriculares.

This paper presents a 21 years-old-male without structural heart disease who was reanimated from a sudden cardiac death event. His familial history included two siblings suddenly dead in their first year of life. The patient had 10 episodes of ventricular tachycardia (some of them were registered). Electrocardiographically abnormalities were an intermittent short QT interval (280 ms), short QTc (320 ms) and a short ST segment. QT interval subsequently returned to a normal range (360 ms or more), while occasionally a length of 335 ms was recorded. The electrophysiological study findings (AH and HV intervals, refractory periods) were normal. The patient refused the implantable cardioverter defibrillator and he is receiving oral amiodarone (200 mg/day). The evolution has been satisfactory along four years. Sequential electrocardiograms are very important to identify patients with an intermittent short QT interval. Shortening of the interval J wave-Tpeak is also relevant. Related arrhythmias could be ventricular tachycardia or fibrillation.

A genética das epilepsias: [revisão] / The genetics of epilepsies: [review]

OBJETIVO: Discutir alguns dos aspectos genéticos clínicos e moleculares de novas descobertas no campo da genética das epilepsias e relacioná-las com indicações importantes para a melhor compreensão dos mecanismos subjacentes a algumas síndromes epilépticas monogênicas. FONTES DOS DADOS: Muitos desenhos de estudo foram usados através dos anos, incluindo estudos familiares e pesquisas genético-epidemiológicas. Mais recentemente, estudos de genética molecular e estratégias de descoberta de genes foram usados para revelar os mecanismos moleculares e celulares envolvidas em diversas síndromes epilépticas mendelianas. SÍNTESE DOS DADOS: A importância dos fatores genéticos em epilepsias é reconhecida desde os tempos de Hipócrates. CONCLUSÕES: Nos tempos modernos, muitos estudos demonstraram a existência de um componente hereditário nas epilepsias generalizadas e focais. Nas últimas duas décadas, diversas famílias segregando diferentes tipos de epilepsia monogência foram descritas, o que levou ao progresso na caracterização dos defeitos moleculares nestas famílias.

OBJECTIVES: To discuss some of the clinical and molecular genetic aspects of new discoveries in the field of the genetics of the epilepsies and relate these with relevant clues for a better understanding of the mechanisms underlying some of the monogenic epilepsy syndromes. SOURCES: Many study designs have been performed over the years and these include family-based studies, genetic-epidemiology surveys. More recently, molecular genetics studies and gene discovery strategies have been used to unravel the molecular and cell mechanisms involved in several Mendelian epilepsy syndromes. SUMMARY OF THE FINDINGS: The importance of genetic factors in the epilepsies has been recognized since the time of Hippocrates. CONCLUSIONS: In the modern era, many studies have demonstrated the existence of an inherited component in the generalized and focal epilepsies and in the last 2 decades a number of families segregating different types of monogenic epilepsy have been described, leading to progresses in the characterization of the molecular defects in these families.

Nuevas perspectivas en el síndrome de QT largo / New perspectives in long QT syndrome

Long QT Syndrome (LQTS) is a cardiac channelopathy characterized by prolonged ventricular repolarization and increased risk to sudden death secondary to ventricular dysrrhythmias. Was the first cardiac channelopathy described and is probably the best understood. After a decade of the sentinel identification of ion channel mutation in LQTS, genotype-phenotype correlations have been developed along with important improvement in risk stratification and genetic guided-treatment. Genetic screening has shown that LQTS is more frequent than expected and interestingly, ethnic specific polymorphism conferring increased susceptibility to drug induced QT prolongation and torsades de pointes have been identified. A better understanding of ventricular arrhythmias as an adverse effect of ion channel binding drugs, allow the development of more safety formulas and better control of this public health problem. Progress in understanding the molecular basis of LQTS has been remarkable; eight different genes have been identified, however still 25% of patients remain genotype-negative. This article is an overview of the main LQTS knowledge developed during the last years.

El síndrome de QT largo (SQTL) es una canalopatía que genera grave alteración en la repolarización ventricular predispone a arritmias malignas y muerte súbita. Fue la primera canalopatía arritmogénica descrita y quizá la mejor entendida hasta ahora. Transcurrida ya más de una década de la identificación de la primera mutación asociada al SQTL, se ha hecho evidente que este trastorno es mucho más frecuente de lo que inicialmente se pensaba; los avances en el conocimiento de la fisiopatología molecular de esta enfermedad han permitido hacer una correlación genotipo-fenotipo, optimizando el tratamiento y permitiendo estratificar el riesgo en forma precisa. Se ha logrado entender con mayor detalle los efectos adversos de distintas drogas que interactúan con los canales iónicos, permitiendo así generar fármacos más seguros y, en su defecto, monitorizar de cerca aquellos que a pesar de tener este efecto adverso, es necesaria su administración. Los avances son importantes pero no todo está dicho, 25% de los casos no tienen mutaciones en los genes descritos hasta la fecha, por lo que el SQTL continúa siendo motivo de investigación. El presente artículo constituye un resumen de los principales conceptos desarrollados en los últimos diez años que han sido cruciales en el manejo de esta enfermedad.

Revisión de tema: Canalopatías epilépticas / Epileptic channelopathies

Se hace una revisión actualizada sobre las epilepsias debidas a alteraciones de los diferentes canales iónicos, con énfasis en su presentación clínica y genotipificación. Se plantean someramente las bases del enfoque farmacológico del tratamiento

Thies an up to date review of the genotypic and phenotypic characteristics of epileptic channelopathies is presented and the bases for a pharmacologic approach to treatment are briefly described.