Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042510 (ventricular fibrillation)
 10,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The congenital long QT syndrome is characterised by the presence of syncopes due to torsades de pointe which may degenerate to ventricular fibrillation and cause sudden death. These syncopes occur in young subjects with electrocardiographic abnormalities and prolongation of the QT interval. Patients with the autosomally dominant transmitted Romano-Ward syndrome with normal audition are classically opposed to those with the Jervell and Lange-Nielsen autosomally recessive syndrome who have bilateral total deafness. Our understanding of the congenital long QT syndrome has improved in recent years with respect to the physiopathology, diagnosis and treatment, due to research in the fields of genetics, electrocardiography and electrophysiology. The diagnosis is based on analysis of the phenotype and genotypes. A family enquiry is always necessary to detect unrecognised forms. Five culprit genes have been identified for the Romano-Ward syndrome. All code for subunits of sodium or potassium channels: two a subunits of the potassium channels (QVLQT1 for LQT1, HERG for LQT2), the a subunit of the sodium channel INa (SCN5A for LQT3), and two regulatory subunits of potassium channels (KCNE1 for LQT5 regulating the KvLQT1 channel and MiRP1 regulating HERG). The concept of genetic heterogeneity of the congenital long QT syndrome may thus be understood: different genes may be responsible for the same phenotype. Except for specific cases, the usual treatment is life-long betablocker therapy and the avoidance of a large number of drugs, the list of which is continually updated. A multicentre trial is underway to validate betablocker therapy for the prevention of cardiac events in a LQT1 genotype population. Prospective studies will be necessary to assess gene-specific treatments.
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PMID:[Present concepts of congenital long QT syndrome]. 1081 97

The congenital long QT syndrome (LQTS) is a variable clinical and genetic entity characterised by prolongation of the QT interval on the ECG associated with the risk of serious ventricular arrhythmias (torsades de pointe, ventricular fibrillation) which may cause syncope and sudden death in patients with otherwise normal hearts. To date, 6 loci have been identified with the genes responsible for the forms LQT1, LQT2, LQT5 and LQT6, coding for the potassium channels (KCNQ1, HERG, KCNE1 and KCNE2, respectively) which, in the heterozygote state, are responsible for the main forms of LQTS without deafness and, in the homozygote state (KCNQ1 and KCNE1) for the recessive forms of LQTS with or without deafness. The gene for the LQT3 form codes for the cardiac sodium channel (SCN5A). The genetic variability observed in the LQTS corresponds to the diversity of cardiac ionic channels implicated in the genesis of the action potential, so making the LQTS a disease of the ionic channels or a "channelopathy". The potential severity of the prognosis justifies testing of subjects with long QT intervals on the ECG and Holter recording. In order to identify subjects with the genetic abnormality who are asymptomatic, these investigations associated with genetic testing should be made in all close members of the family of an affected person. The major problem remains the evaluation of the risk of sudden death in asymptomatic subjects with a genetic abnormality. At present, in the absence of clearly proven prognostic factors and in the knowledge that effective treatment without major secondary effects is available, all patients should be given prophylactic betablocker therapy.
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PMID:[Value of genetic testing in the management of the congenital long QT syndrome]. 1283 49

Delayed rectifier K+ current (IK) is the major outward current responsible for ventricular repolarization. Two components of IK (IKr and IKs) have been identified in many mammalian species including humans. IKr plays a pivotal role in normal ventricular repolarization. A prolongation of action potential duration (APD) under a variety of conditions would favor the activation of IKs so that to prevent excessive repolarization delay causing early afterdepolarization. The pore-forming a subunits of IKr and IKs are composed of HERG (KCNH2) and KvLQT1 (KCNQ1), respectively. KvLQT1 is associated with a function-altering beta subunit, minK to form IKs. HERG may be associated with mink (KCNE1) and/or minK-related protein (MiRP1) to form IKr, but the issue remains to be established. IKs is enhanced, whereas IKr is usually attenuated by beta-adrenergic stimulation via cyclic adenosine 3',5'-monophosphate (cAMP)/protein kinase A-dependent pathways. There exist regional differences in the density of IKr and IKs transmurally (endo-epicardial) and along the apico-basal axis, contributing to the spatial heterogeneity of ventricular repolarization. A decrease of IKr or IKs by mutations in either HERG, KvLQT1, or KCNE family results in inherited long QT syndrome (LQTS) with high risk for Torsades de pointes (TdP)-type polymorphic ventricular tachycardia and ventricular fibrillation. As to the pharmacological treatment and prevention of ventricular tachyarrhythmias, selectively block of IKs is expected to be more beneficial than selectively block of IKr in terms of homogeneous prolongation of refractoriness at high heart rates especially in diseased hearts including myocardial ischemia.
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PMID:Two components of delayed rectifier K+ current in heart: molecular basis, functional diversity, and contribution to repolarization. 1476 99

Mutations in cardiac potassium and sodium channel genes are responsible for several hereditary cardiac arrhythmia syndromes. We established a denaturing high-performance liquid chromatography (DHPLC) protocol for rapid mutation screening of these genes, and reported mutations and variations identified by this method. We included 28 patients with Brugada syndrome, 4 with congenital long QT syndrome (LQTS), 11 with drug-induced LQTS, 4 with idiopathic ventricular fibrillation, and 50 normal volunteers. Polymerase chain reactions were performed to amplify the entire coding region of these genes. DHPLC was used to screen for heteroduplexes then DNA sequencing was performed. With this method, we identified the mutation(s) in all four patients with congenital LQTS (KCNQ1 A341V, KCNH2 N633D, KCNH2 2768Cdel and KCNE1 K70 N Y81C double mutations). We also identified the SCN5A A551T mutation in 1 of the 28 patients with Brugada syndrome. All the above-mentioned mutations were novel except KCNQ1 A341V. No mutations were identified in patients with drug-induced LQTS or idiopathic ventricular fibrillation. In total, 25 single nucleotide polymorphisms were identified, 10 of which were novel. In conclusion, DHPLC is a sensitive and rapid method for detection of cardiac sodium and potassium channel gene mutations.
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PMID:Denaturing high-performance liquid chromatography screening of the long QT syndrome-related cardiac sodium and potassium channel genes and identification of novel mutations and single nucleotide polymorphisms. 3203 10

LQTS (long QT syndrome) is an important cause of cardiac sudden death. LQTS is characterized by a prolongation of the QT interval on an electrocardiogram. This prolongation predisposes the individual to torsade-de-pointes and subsequent sudden death by ventricular fibrillation. Mutations in a number of genes that encode ion channels have been implicated in LQTS. Hereditary mutations in the alpha- and beta-subunits, KCNQ1 and KCNE1 respectively, of the K(+) channel pore I(Ks) are the commonest cause of LQTS and account for LQTS types 1 and 5 respectively (LQT1 and LQT5). Recently, it has been shown that disease pathogenesis in LQT1 can be influenced by the abnormal trafficking of KCNQ1. In comparison, whether defective trafficking of KCNE1 plays a role in LQT5 is less well established.
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PMID:The role of abnormal trafficking of KCNE1 in long QT syndrome 5. 1795 82

Out-of-hospital cardiac arrest in pediatric population is rare and predominantly has respiratory aetiology. Authors present the relatively unique case of out-of hospital cardiac arrest in 5-years old pediatric patient due to ventricular fibrillation (VF) as the initial rhythm during the advanced life support. The patient was resuscitated by his parents and the initial rhythm was VF. After defibrillation the patient was admitted to the pediatric intensive care were another two episodes of VF was detected and treated. After standard postresuscitation care, patient was weaned from sedation and extubated with good neurologic outcome. Genetic screening of the 7 genes associated with cardiac channelopathies (KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, RYR2, CASQ2) found mutation in gene KCHN2 and gene SCN5A, that were according to actual data considered benign. This case highlights the need for automated external defibrillator implementation in basic life support also in pediatric population and possible role of genetic predisposition in emergence of fibrillation.
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PMID:Out-of-Hospital Cardiac Arrest Due to Ventricular Fibrillation in a 5-Year-Old Pediatric Patient. 2948 4

A 14-year-old boy collapsed suddenly after a basketball game and was transported to our hospital after recovering from ventricular fibrillation by an automated external defibrillator. He had experienced loss of consciousness twice and has been examined for suspected long-QT syndrome at another hospital. The 12-lead electrocardiogram on admission revealed a prolonged QTc interval of 480 milliseconds. After the patient recovered without any sequelae, computed tomography revealed an anomalous left coronary artery arising from the opposite sinus of Valsalva and coursing between the aorta and the pulmonary artery. Furthermore, genetic testing identified a KCNE1-D85N abnormality. An anomalous coronary artery is one of the major causes of sudden death in young people; therefore, surgical revascularization is recommended for left coronary arteries arising from the contralateral sinus and coursing between the aorta and the pulmonary artery, regardless of myocardial ischemia. Transient myocardial ischemia may have exaggerated the instability from the arrhythmic substrate, even though KCNE1-D85N abnormalities alone are not thought to cause fatal arrhythmias. Besides routine electrocardiography, further examinations, including imaging and genetic testing, can characterize the pathophysiology of fatal cardiac disease.
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PMID:Cardiac Arrest Associated with Both an Anomalous Left Coronary Artery and KCNE1 Polymorphism. 3130 27

The cardiac ventricular action potential depends on several voltage-gated ion channels, including NaV, CaV, and KV channels. Mutations in these channels can cause Long QT Syndrome (LQTS) which increases the risk for ventricular fibrillation and sudden cardiac death. Polyunsaturated fatty acids (PUFAs) have emerged as potential therapeutics for LQTS because they are modulators of voltage-gated ion channels. Here we demonstrate that PUFA analogues vary in their selectivity for human voltage-gated ion channels involved in the ventricular action potential. The effects of specific PUFA analogues range from selective for a specific ion channel to broadly modulating cardiac ion channels from all three families (NaV, CaV, and KV). In addition, a PUFA analogue selective for the cardiac IKs channel (Kv7.1/KCNE1) is effective in shortening the cardiac action potential in human-induced pluripotent stem cell-derived cardiomyocytes. Our data suggest that PUFA analogues could potentially be developed as therapeutics for LQTS and cardiac arrhythmia.
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PMID:Polyunsaturated fatty acid analogues differentially affect cardiac NaV, CaV, and KV channels through unique mechanisms. 3255 5