			Home About us Contact

Congenital Long QT Syndrome (congenital + long_qt_syndrome)

Distribution by Scientific Domains

Medical Sciences	83%
Life Sciences	16%

Selected Abstracts

The Effect of Antihistamine Cetirizine on Ventricular Repolarization in Congenital Long QT Syndrome

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 7 2007
ANNA-MARI HEKKALA M.D.
Introduction: Many drugs are known to block cardiac potassium channels, thus prolonging QT interval and predisposing to malignant arrhythmias. Patients with congenital long QT syndrome are particularly vulnerable, but usually electrophysiological effects of drugs have not been assessed in these patients at risk. Methods: Fifteen asymptomatic patients with type 1 (LQT1), 15 patients with type 2 (LQT2) long QT syndrome, and 15 healthy volunteers took a placebo and cetirizine 10 mg. In addition, healthy volunteers took cetirizine 50 mg. The study was single-blinded and randomized. Exercise tests were performed during stable plasma concentrations. The electrocardiogram was recorded with a body surface potential mapping system (BSPM). Data were analyzed with an automated analyze program. QT intervals to the T wave apex and T wave end and their difference (Tp-e) were determined at rest and at specified heart rates during and after exercise. Results: Cetirizine did not lengthen the QT intervals at rest or during exercise and recovery in any group. It shortened Tp-e at rest in LQT1 and LQT2 patients and during exercise test in LQT1 patients, thus slightly decreasing electrocardiographic transmural dispersion of repolarization. Conclusions: Cetirizine does not adversely modify ventricular repolarization in types 1 and 2 long QT syndrome, suggesting that it might be used safely in these long QT syndrome patients. [source]

Video-Assisted Thoracoscopic Sympathectomy for Congenital Long QT Syndromes

PACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 4p1 2003
JIANFENG LI
LI, J., et al.: Video-Assisted Thoracoscopic Sympathectomy for Congenital Long QT Syndromes. The feasibility, safety, and effectiveness of video-assisted thoracoscopic sympathectomy (VATS) for congenital long QT syndrome were assessed in four patients who had frequent syncopal events before the surgeries. Under general anaesthesia, the pleural cavity was entered via two small incisions in the left third and fifth intercostal spaces at the mid-axillary line. The left thoracic sympathetic chain was identified and resected from T2-T5. The lower one third of the left stellate ganglion was also resected. VATS resulted in a significant shortening in corrected QT intervals (QTc) in three patients, the average QTc of the four patients immediately before and after VATS was538 ± 76and512 ± 57 ms, respectively(P = 0.047). The heart rate remained unchanged after the VATS (67 ± 4vs69 ± 4 beats/min, P > 0.05). There were no major perioperative complications apart from mild ptosis of the left upper eyelid in one patient who recovered in the following days. There was no recurrence in syncopal events after a 3-month follow-up. VATS is a safe and effective technique for left cardiac sympathectomy in patients with congenital long QT syndromes. (PACE 2003; 26[Pt. I]:870,873) [source]

Zebrafish as a model for long QT syndrome: the evidence and the means of manipulating zebrafish gene expression

ACTA PHYSIOLOGICA, Issue 3 2010
I. U. S. Leong
Abstract Congenital long QT syndrome (LQT) is a group of cardiac disorders associated with the dysfunction of cardiac ion channels. It is characterized by prolongation of the QT-interval, episodes of syncope and even sudden death. Individuals may remain asymptomatic for most of their lives while others present with severe symptoms. This heterogeneity in phenotype makes diagnosis difficult with a greater emphasis on more targeted therapy. As a means of understanding the molecular mechanisms underlying LQT syndrome, evaluating the effect of modifier genes on disease severity as well as to test new therapies, the development of model systems remains an important research tool. Mice have predominantly been the animal model of choice for cardiac arrhythmia research, but there have been varying degrees of success in recapitulating the human symptoms; the mouse cardiac action potential (AP) and surface electrocardiograms exhibit major differences from those of the human heart. Against this background, the zebrafish is an emerging vertebrate disease modelling species that offers advantages in analysing LQT syndrome, not least because its cardiac AP much more closely resembles that of the human. This article highlights the use and potential of this species in LQT syndrome modelling, and as a platform for the in vivo assessment of putative disease-causing mutations in LQT genes, and of therapeutic interventions. [source]

A new approach to long QT syndrome mutation detection by Sequenom MassARRAY® system

ELECTROPHORESIS, Issue 10 2010
Catarina Allegue
Abstract Congenital long QT syndrome is an inherited cardiac disorder characterized by a prolonged QT interval and polymorphic ventricular arrhythmias that could result in recurrent syncope, seizures or sudden death as the most dramatic event. Until now QT interval mutations have been described in 12 genes, where the majority of mutations reside in three genes KCNQ1, KCNH2, and SCN5A. Diagnosis and prognosis are directly related with the gene and mutation involved. We have developed a diagnostic approach for long QT syndrome and Brugada syndrome based on published mutations and Sequenom MassArray® system. Three diagnostic tests have been developed, oriented to each of the three most prevalent genes in the long QT syndrome. A total of 433 mutations are analyzed in 38 multiplex reactions, allowing their detection in about 48,h. Tests were validated on 502 samples from individuals with different clinical conditions and family history. The average call rates obtained for each of the tests were 93, 83, and 73% in KCNQ1, KCNH2, and SCNA, respectively. Sequenom MassARRAY mutation detection is a reliable, highly flexible, and cost-efficient alternative to conventional methods for genetic testing in long QT syndrome and Brugada syndrome, facilitating flexible upgrades of the version of the test presented here with the inclusion of new mutations. [source]

Evidence for a Single Nucleotide Polymorphism in the KCNQ1 Potassium Channel that Underlies Susceptibility to Life-Threatening Arrhythmias

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 11 2001
TOMOYUKI KUBOTA M.D.
Ion Channel Polymorphism and Cardiac Arrhythmia. Introduction: Congenital long QT syndrome (LQTS) is a genetically heterogeneous arrhythmogenic disorder caused by mutations in at least five different genes encoding cardiac ion channels. It was suggested recently that common polymorphisms of LQTS-associated genes might modify arrhythmia susceptibility in potential gene carriers. Methods and Results: We examined the known LQTS genes in 95 patients with definitive or suspected LQTS. Exon-specific polymerase chain reaction single-strand conformation polymorphism and direct sequence analyses identified six patients who carried only a single nucleotide polymorphism in KCNQ1 that is found in , 11% of the Japanese population. This 1727G> A substitution that changes the sense of its coding sequence from glycine to serine at position 643 (G643S) was mostly associated with a milder phenotype, often precipitated by hypokalemia and bradyarrhythmias. When heterologously examined by voltage-clamp experiments, the in vitro cellular phenotype caused by the single nucleotide polymorphism revealed that G643S- KCNQ1 forms functional homomultimeric channels, producing a significantly smaller current than that of the wild-type (WT) channels. Coexpression of WT- KCNQ1 and G643S- KCNQ1 with KCNE1 resulted in , 30% reduction in the slow delayed rectifier K+ current IKs without much alteration in the kinetic properties except its deactivation process, suggesting that the G643S substitution had a weaker dominant-negative effect on the heteromultimeric channel complexes. Conclusion: We demonstrate that a common polymorphism in the KCNQ1 potassium channel could be a molecular basis for mild IKs dysfunction that, in the presence of appropriate precipitating factors, might predispose potential gene carriers to life-threatening arrhythmias in a specific population. [source]

The Effect of Antihistamine Cetirizine on Ventricular Repolarization in Congenital Long QT Syndrome

Prolonged Atrial Action Potential Durations and Polymorphic Atrial Tachyarrhythmias in Patients with Long QT Syndrome

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 10 2003
PAULUS KIRCHHOF M.D.
Introduction: Prolongation of the QT interval and torsades de pointes tachycardias due to altered expression or function of repolarizing ion channels are the hallmark of congenital long QT syndrome (LQTS). The same ion channels also contribute to atrial repolarization, and familial atrial fibrillation may be associated with a mutated KVLQT1 gene. We therefore assessed atrial action potential characteristics and atrial arrhythmias in LQTS patients. Methods and Results: Monophasic action potentials (MAPs) were simultaneously recorded from the right atrial appendage and the inferolateral right atrium in 10 patients with LQTS (8 with identifiable genotype) and compared to 7 control patients. Atrial arrhythmias also were compared to MAPs recorded in patients with persistent (n = 10) and induced (n = 4) atrial fibrillation. Atrial action potential durations (APD) and effective refractory periods (ERP) were prolonged in LQTS patients at cycle lengths of 300 to 500 msec (APD prolongation 30,41 msec; ERP prolongation 26,52 msec; all P < 0.05). Short episodes of polymorphic atrial tachyarrhythmias (polyAT, duration 4,175 sec) occurred spontaneously or during pauses after pacing in 5 of 10 LQTS patients, but not in controls (P < 0.05). P waves showed undulating axis during polyAT. Cycle lengths of polyAT were longer than during persistent and induced atrial fibrillation. Afterdepolarizations preceded polyAT in 2 patients. The electrical restitution curve was shifted to longer APD in LQTS patients and to even longer APD in LQTS patients with polyAT. Conclusion: This group of LQTS patients has altered atrial electrophysiology: action potentials are prolonged, and polyAT occurs. PolyAT appears to be a specific arrhythmia of LQTS reminiscent of an atrial form of "torsades de pointes."(J Cardiovasc Electrophysiol, Vol. 14, pp ***-***, October 2003) [source]

A cardiac sodium channel mutation identified in Brugada syndrome associated with atrial standstill

JOURNAL OF INTERNAL MEDICINE, Issue 1 2004
N. Takehara
Abstract., Takehara N, Makita N, Kawabe J, Sato N, Kawamura Y, Kitabatake A, Kikuchi K (Asahikawa Medical College, Asahikawa; Hokkaido University Graduate School of Medicine, Sapporo, Japan; and Cardiovascular Research Institute, Newark, NY, USA). A cardiac sodium channel mutation identified in Brugada syndrome associated with atrial standstill (Case Report). J Intern Med 2004; 255: 137,142. Mutations in the cardiac Na+ channel gene SCN5A are responsible for multiple lethal ventricular arrhythmias including Brugada syndrome and congenital long QT syndrome. Here we report a case of Brugada syndrome with ST elevation in the right precordial and inferior leads accompanied by atrial standstill and spontaneous ventricular fibrillation. Atrial standstill and J wave elevation were provoked by procainamide. Genetic analysis revealed a missense mutation (R367H) in SCN5A. The resultant mutant Na+ channel was nonfunctional when expressed heterologously in Xenopus oocytes. Our study suggests that genetic defects in SCN5A may be associated with atrial standstill in combination with ventricular arrhythmias. [source]

QT Interval Variability and Adaptation to Heart Rate Changes in Patients with Long QT Syndrome

PACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 1 2009
JAN N, MEC M.D.
Background: Increased QT variability (QTV) has been reported in conditions associated with ventricular arrhythmias. Data on QTV in patients with congenital long QT syndrome (LQTS) are limited. Methods: Ambulatory electrocardiogram recordings were analyzed in 23 genotyped LQTS patients and in 16 healthy subjects (C). Short-term QTV was compared between C and LQTS. The dependence of QT duration on heart rate was evaluated with three different linear models, based either on the RR interval preceding the QT interval (RR0), the RR interval preceding RR0 (RR -1), or the average RR interval in the 60-second period before QT interval (mRR). Results: Short-term QTV was significantly higher in LQTS than in C subjects (14.94 ± 9.33 vs 7.31 ± 1.29 ms; P < 0.001). It was also higher in the non-LQT1 than in LQT1 patients (23.00 ± 9.05 vs 8.74 ± 1.56 ms; P < 0.001) and correlated positively with QTc in LQTS (r = 0.623, P < 0.002). In the C subjects, the linear model based on mRR predicted QT duration significantly better than models based on RR0 and RR -1. It also provided better fit than any nonlinear model based on RR0. This was also true for LQT1 patients. For non-LQT1 patients, all models provided poor prediction of QT interval. Conclusions: QTV is elevated in LQTS patients and is correlated with QTc in LQTS. Significant differences with respect to QTV exist among different genotypes. QT interval duration is strongly affected by noninstantaneous heart rate in both C and LQT1 subjects. These findings could improve formulas for QT interval correction and provide insight on cellular mechanisms of QT adaptation. [source]

Video-Assisted Thoracoscopic Sympathectomy for Congenital Long QT Syndromes

Levofloxacin Induced Polymorphic Ventricular Tachycardia with Normal QT Interval

PACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 5 2001
BRENDON PALTOO
PALTOO, B., et al.: Levofloxacin Induced Polymorphic Ventricular Tachycardia with Normal QT Interval. Polymorphic ventricular tachycardia (PVT) is a form of ventricular tachycardia characterized by QRS complexes that seem to change direction during the tachycardia. If associated with a prolonged QT interval, it is called torsades de pointes. In the absence of a congenital long QT syndrome, torsades is seen with certain drugs such as antiarrythmic agents (Class IA, IC, III), psychotropic medications, antidepressants, antihistamines, and electrolyte disturbances. We report the first case of polymorphic ventricular tachycardia with normal QT interval associated with the oral use of levofloxacin in the absence of other etiologies known to cause these arrhythmias. [source]