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QT Syndrome (qt + syndrome)
Kinds of QT Syndrome Selected AbstractsAge- and Genotype-Specific Triggers for Life-Threatening Arrhythmia in the Genotyped Long QT SyndromeJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 8 2008TOMOKO SAKAGUCHI M.D. Introduction: Patients with long QT syndrome (LQTS) become symptomatic in adolescence, but some become at age of ,20 years. Since it remains unknown whether clinical features of symptomatic LQTS patients differ depending on the age of onset, we aimed to examine whether triggers for cardiac events are different depending on the age in genotyped and symptomatic LQTS patients. Methods and Results: We identified 145 symptomatic LQTS patients, divided them into three groups according to the age of first onset of symptoms (young <20, intermediate 20,39, and older ,40 years), and analyzed triggers of cardiac events (ventricular tachycardia, syncope, or cardiac arrest). The triggers were divided into three categories: (1) adrenergically mediated triggers: exercise, emotional stress, loud noise, and arousal; (2) vagally mediated triggers: rest/sleep; and (3) secondary triggers: drugs, hypokalemia, and atrioventricular (AV) block. In the young group, 78% of the cardiac events were initiated by adrenergically mediated triggers and 22% were vagally mediated, but none by secondary triggers. In contrast, the adrenergically mediated triggers were significantly lower in the intermediate group. The percentage of secondary triggers was significantly larger in the older group than in the other two groups (0% in young vs 23% in intermediate vs 72% in older; P < 0.0001). Concerning the subdivision of secondary triggers on the basis of genotype, hypokalemia was only observed in LQT1, drugs mainly in LQT2, and AV block only in LQT2. Conclusion: Arrhythmic triggers in LQTS differ depending on the age of the patients, stressing the importance of age-related therapy for genotyped LQTS patients. [source] The Effect of Antihistamine Cetirizine on Ventricular Repolarization in Congenital Long QT SyndromeJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 7 2007ANNA-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] The Normal Effects of Epinephrine and Isoproterenol on Heart Rate and QT Interval: Role in Unmasking the Long QT SyndromeJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 9 2006DAVID M. FITZGERALD M.D., F.H.R.S.Article first published online: 26 JUL 200 No abstract is available for this article. [source] The Mechanism of Pause-Induced Torsade de Pointes in Long QT SyndromeJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 9 2005JINQIU LIU M.D. Introduction: Torsade de pointes (TdP), is often preceded by a short-long cycle length sequence. However, the causal relationship between the pause associated with a short-long cycle length sequence and TdP is not completely understood. This study tests the hypothesis that a pause enhances both dispersion of repolarization and EAD formation; however, EADs that form where APD is longest will be less likely to initiate TdP. Methods and Results: We used optical mapping to measure transmural action potentials from the canine left ventricular wedge preparation. D-sotalol and ATX-II were used to mimic LQT2 and LQT3, respectively. The pause significantly enhanced mean APD (from 356 ± 20 to 381 ± 25 msec in LQT2, P < 0.05; from 609 ± 92 to 675 ± 98 msec in LQT3, P < 0.05) and transmural dispersion (from 35 ± 9 to 46 ± 11 msec in LQT2, P < 0.05; from 121 ± 85 to 171 ± 98 msec in LQT3, P < 0.05) compared to steady state pacing. Under LQT3 condition EADs, EAD-induced triggered activity, and TdP were more likely to occur following a pause. Interestingly, the triggered beat following a pause always broke through at the region of maximum local repolarization gradient. Conclusion: These data suggest that a pause accentuates transmural repolarization gradients and facilitates the formation of EADs and EAD-induced triggered activity. In contrast to our hypothesis, the findings of this study support the concept that M-cells (where APD is longest) can play an important role in both the origination of EAD-induced triggered activity and unidirectional block associated with TdP. [source] Congenital Short QT Syndrome and Implantable Cardioverter Defibrillator Treatment:JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 12 2003Inherent Risk for Inappropriate Shock Delivery Introduction: A congenital short QT interval constitutes a new primary electrical abnormality associated with syncope and/or sudden cardiac death. We report on the initial use of implantable cardioverter defibrillator (ICD) therapy in patients with inherited short QT interval and discuss sensing abnormalities and detection issues. Methods and Results: In five consecutive patients from two unrelated European families who had structurally normal hearts, excessively shortened QT intervals, and a strong positive family history of sudden cardiac death, ICDs were placed for primary and secondary prevention. Mean QT intervals were 252 ± 13 ms (QTc 287 ± 13 ms). Despite normal sensing behavior during intraoperative and postoperative device testing, 3 of 5 patients experienced inappropriate shock therapies for T wave oversensing 30 ± 26 days after implantation. Programming lower sensitivities and decay delays prevented further inappropriate discharges. Conclusion: The congenital short QT syndrome constitutes a new clinical entity with an increased risk for sudden cardiac death. Currently, ICD treatment is the only therapeutic option. In patients with short QT interval and implanted ICD, increased risk for inappropriate therapy is inherent due to the detection of short-coupled and prominent T waves. Careful testing of ICD function and adaptation of sensing levels and decay delays without sacrificing correct arrhythmia detection are essential. (J Cardiovasc Electrophysiol, Vol. 14, pp. 1273-1277, December 2003) [source] Location of Mutation in the KCNQ1 and Phenotypic Presentation of Long QT SyndromeJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 11 2003Ph.D., WOJCIECH ZAREBA M.D. Introduction: Recent data showed that long QT syndrome (LQTS) patients with mutations in the pore region of the HERG (LQT2) gene have significantly higher risk of cardiac events than subjects with mutations in the non-pore region. The aim of this study was to determine whether there is an association between the location of mutations in the KCNQ1 gene and cardiac events in LQT1 patients. Methods and Results: The study population consisted of 294 LQT1 patients with KCNQ1 gene mutations. Demographic, clinical, and follow-up information was compared among subjects with different locations of KCNQ1 mutations defined as pre-pore region including N-terminus (1,278), pore region (279,354), and post-pore region including C-terminus (>354). Cardiac events observed during follow-up from birth until age of last contact or age 40 years were defined as syncope, cardiac arrest, or sudden death. There were 164 (56%) LQT1 patients with pre-pore mutations, 101 (34%) with pore mutations, and 29 (10%) with post-pore mutations. QTc duration did not differ significantly among the three subgroups (mean QTc = 494, 487, and 501 ms, respectively). There was no significant difference between groups with regard to the risk of cardiac events by age 40 years. Conclusion: There are no significant differences in clinical presentation, ECG parameters, and cardiac events among LQT1 patients with different locations of KCNQ1 mutations. These findings indicate that factors other than location of mutation influence clinical phenotype in patients with LQT1 mutations. (J Cardiovasc Electrophysiol, Vol. 14, pp. 1149-1153, November 2003) [source] Prolonged Atrial Action Potential Durations and Polymorphic Atrial Tachyarrhythmias in Patients with Long QT SyndromeJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 10 2003PAULUS 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] Restitution Properties and Occurrence of Ventricular Arrhythmia in LQT2 Type of Long QT SyndromeJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 9 2002SOU YAMAUCHI M.D. Mechanisms of Ventricular Arrhythmia in LQT2 Heart.Introduction: The aim of this study was to clarify the ventricular tachyarrhythmia mechanism induced by the IKr -blocking agent E4031, simulating the LQT2 form. Electrophysiologic properties were examined in 13 canines before and after administration of E4031. Method and Results: Thirty-six needle electrodes were inserted into the anterior left ventricular wall. From each needle, local unipolar electrograms were obtained from four intramural sites. Activation time (AT) and activation-recovery interval (ARI) were measured. To evaluate the susceptibility to ventricular arrhythmia, intramural ARI dispersions and the restitution relationship between ARI and diastolic interval were calculated. After E4031 administration, ARI prolonged uniformly in each myocardial layer. However, ARI dispersion was not augmented compared with control. The slope of the ARI restitution curve after E4031 was significantly steeper than control. A steep slope may result from augmented ARI alternans. In 11 of the 13 canines, ventricular tachyarrhythmia was induced by programmed stimulation after E4031, whereas no arrhythmia was induced by the same protocol in control. Conclusion: Steepness of electrical restitution may play a major role in arrhythmogenicity in LQT2 hearts. [source] Long QT Syndrome: More QuestionsJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 4 2001ARTHUR J. MOSS M.D. [source] Inappropriate ICD Discharge Due to T-Wave Oversensing in a Patient with Short QT SyndromePACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 1 2010YAXUN SUN M.D. A 45-year-old man with diagnosis of short QT syndrome underwent successful implantation of dual-chamber implantable cardioverter-defibrillator (ICD) to prevent sudden cardiac death. Ten days after implantation, the patient was treated by inappropriate ICD discharges for frequent T-wave oversensing. After careful reprogramming of the ICD, the T-wave oversensing was eliminated and no T-wave oversensing or inappropriate discharge was documented during 6-month follow-up period. (PACE 2010; 113,116) [source] QT Interval Variability and Adaptation to Heart Rate Changes in Patients with Long QT SyndromePACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 1 2009JAN 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] Clinical Value of Electrocardiographic Parameters in Genotyped Individuals with Familial Long QT SyndromePACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 4 2001GEROLD MOENNIG MOENNIG, G., et al.: Clinical Value of Electrocardiographic Parameters in Genotyped Individuals with Familial Long QT Syndrome. Rate corrected QT interval (QTc) and QT dispersion (QTd) have been suggested as markers of an increased propensity to arrhythmic events and efficacy of therapy in patients with long QT syndrome (LQTS). To evaluate whether QTc and QTd correlate to genetic status and clinical symptoms in LQTS patients and their relatives, ECGs of 116 genotyped individuals were analyzed. JTc and QTc were longest in symptomatic patients (n = 28). Both QTd and JTd were significantly higher in symptomatic patients than in asymptomatic (n = 29) or unaffected family members (n = 59). The product of QTd/JTd and QTc/JTc was significantly different among all three groups. Both dispersion and product put additional and independent power on identification of mutation carriers when adjusted for sex and age in a logistic regression analysis. Thus, symptomatic patients with LQTS show marked inhomogenity of repolarization in the surface ECG. QT dispersion and QT product might be helpful in finding LQTS mutation carriers and might serve as additional ECG tools to identify asymptomatic LQTS patients. [source] Long QT Syndrome in African-AmericansANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 1 2010Thomas Fugate II B.S. Background: We evaluated the risk factors and clinical course of Long QT syndrome (LQTS) in African-American patients. Methods: The study involved 41 African-Americans and 3456 Caucasians with a QTc , 450 ms from the U.S. portion of the International LQTS Registry. Data included information about the medical history and clinical course of the LQTS patients with end points relating to the occurrence of syncope, aborted cardiac arrest, or LQTS-related sudden cardiac death from birth through age 40 years. The statistical analyses involved Kaplan-Meier time to event graphs and Cox regression models for multivariable risk factor evaluation. Results: The QTc was 29 ms longer in African-Americans than Caucasians. Multivarite Cox analyses with adjustment for decade of birth revealed that the cardiac event rate was similar in African-Americans and Caucasians with LQTS and that beta-blockers were equally effective in reducing cardiac events in the two racial groups. Conclusions: The clinical course of LQTS in African-Americans is similar to that of Caucasians with comparable risk factors and benefit from beta-blocker therapy in the two racial groups. Ann Noninvasive Electrocardiol 2010;15(1):73,76 [source] T-Wave Morphology in Short QT SyndromeANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 3 2009Olli Anttonen M.D. Background: Short QT syndrome (SQTS) is an inherited disorder characterized by a short QT interval and vulnerability to ventricular tachyarrhythmias. The diagnostic criteria for this syndrome are not well defined, since there is uncertainty about the lowest normal limits for the corrected QT (QTc) interval. Objective: The aim of this study was to determine whether T-wave morphology parameters are abnormal in short QT subjects and whether those parameters can help in the diagnosis of SQTS. Methods and Results: We describe three families (10 patients) with short QT intervals (QTc 310 ± 32 ms). Seven subjects had suffered serious arrhythmic events and three were asymptomatic. T-wave morphology was assessed using the principal component analysis (PCA). QTc was significantly shorter and T-wave amplitude in lead V2 higher in the short QT subjects compared to healthy controls (n = 149), (P < 0.001 for both). The total cosine of the angle between the main vectors of the QRS and T-wave loops (TCRT) was markedly abnormal among the symptomatic patients with short QT syndrome (n = 7) (TCRT ,0.14 ± 0.55 vs 0.36 ± 0.51, P = 0.019). None of the three asymptomatic patients with short QT but without a history of arrhythmic events had an abnormally low TCRT. Conclusion: Our observations suggest that patients with a short QT interval and a history of arrhythmic events have abnormal T-wave loop parameters. These electrocardiogram (ECG) features may help in the diagnosis of SQTS in addition to the measurement of the duration of QT interval from the 12-lead ECG. [source] Happiness and Stress Alter Susceptibility to Cardiac Events in Long QT SyndromeANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 2 2009Ph.D., Richard D. Lane M.D. Objective: We sought to determine whether the circumstances preceding an arrhythmic event differed from those preceding a prior control occasion in patients with Long QT Syndrome (LQTS), a well-characterized genetic disorder that puts affected individuals at risk for sudden cardiac death. Methods: Thirty-eight patients (89% female) with LQTS completed a "case-crossover interview" in which each patient served as his/her own control by reporting on circumstances preceding an arrhythmic event (syncope, aborted cardiac arrest, or defibrillator discharge) and preceding a control occasion (the next-to-last birthday). On average the interview was conducted 17 months after the cardiac event and control occasion. Results: During the 24-hour period preceding the cardiac event compared to the day before the control occasion, psychological stress was elevated, peak happiness was reduced, and peak exertion was not significantly different. Rated for the 6-month intervals preceding the event and control occasions, none of these three variables was significantly associated with events. Conclusions: Happiness is associated with a reduction in the 24-hour risk of cardiac events in patients with LQTS, with stress having an opposite effect. To our knowledge, this is the first report indicating that positive emotion may have a protective effect on life-threatening ventricular arrhythmias. This study lends further support to the role of emotions in influencing cardiac events in arrhythmia-prone patients. [source] Long QT Syndrome in Patients over 40 Years of Age: Increased Risk for LQTS-Related Cardiac Events in Patients with Coronary DiseaseANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 4 2008Edward Sze B.A. Background: Previous studies of long QT syndrome (LQTS) have focused primarily on the clinical course of affected patients up to 40 years of age to avoid the confounding influence of acquired heart disease on LQTS-related cardiac events in this genetic disorder. Methods: Patients were identified as having coronary disease if they had a history of hospitalization for myocardial infarction, coronary angioplasty, coronary artery bypass graft surgery, or were treated with medication for angina. LQTS-related cardiac events included the first occurrence of syncope, aborted cardiac arrest, or sudden cardiac death without evidence suggestive of an acute coronary event. Cox proportional hazards regression modeling was used to analyze the independent contribution of coronary disease to LQTS-related cardiac events. Results: Time-dependent coronary disease was associated with an increased risk of LQTS-related cardiac events (hazard ratio 2.24, 95% confidence interval 1.23,4.07, P = 0.008) after adjustment for syncopal history before age 40, QTc, and gender. Factors such as diabetes and hypertension that increase the risk for coronary disease were not associated with an increased risk for LQTS-related cardiac events. Conclusions: This is the first study to demonstrate that coronary disease augments the risk for LQTS-related cardiac events in LQTS. The findings highlight the need for more focused preventive therapy in LQTS patients above the age of 40. [source] Electrocardiographic Transmural Dispersion of Repolarization in Patients with Inherited Short QT SyndromeANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 3 2008Olli Anttonen M.D. Background: Short QT syndrome (SQTS) carries an increased risk for sudden cardiac death. However, only a short QT interval does not express the risk of ventricular arrhythmias. Thus, additional evaluation of the repolarization abnormality in SQTS patients is essential. In experimental models of SQTS, increased transmural dispersion of repolarization (TDR) and its electrocardiographic counterpart T-wave peak to T-wave end interval (TPE) appeared critical for induction of polymorphic ventricular tachycardia (PMVT). In a clinical study with acquired long QT syndrome patients, TPE/QT ratio > 0.28 indicated arrhythmia risk. We hypothesized that the TPE/QT ratio would be greater in SQTS patients than in control subjects. Methods and Results: We compared the behavior of the electrocardiographic TDR in three seriously symptomatic SQTS patients of unknown genotype presenting baseline QTc values <320 ms and in nine healthy age-matched control subjects. We determined QT and TPE intervals as well as TPE/QT ratio from 24-hour ECG recordings using a computer-assisted program. Diurnal average of TPE/QT ratio was 0.28 ± 0.03 in SQTS patients and 0.21 ± 0.02 in control subjects (P = 0.01). SQTS patients had also lesser capacity to change TPE intervals from steady-state conditions to abrupt maximal values than control subjects. Conclusion: SQTS patients have increased and autonomically uncontrolled electrocardiographic TDR. According to experimental SQTS models, the present results may in part explain increased vulnerability of SQTS patients to ventricular arrhythmias. [source] Familial And Acquired Long QT Syndrome And The Cardiac Rapid Delayed Rectifier Potassium CurrentCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 10 2000Harry J Witchel SUMMARY 1. Long QT syndrome (LQTS) is a cardiac disorder characterized by syncope, seizures and sudden death; it can be congenital, idiopathic, or iatrogenic. 2. Long QT syndrome is so-named because of the connection observed between the distinctive polymorphic ventricular tachycardia torsade de pointes and prolongation of the QT interval of the electrocardiogram, reflecting abnormally slowed ventricular action potential (AP) repolarization. Acquired LQTS has many similar clinical features to congenital LQTS, but typically affects older individuals and is often associated with specific pharmacological agents. 3. A growing number of drugs associated with QT prolongation and its concomitant risks of arrhythmia and sudden death have been shown to block the ,rapid' cardiac delayed rectifier potassium current (IKr) or cloned channels encoded by the human ether-a-go-go -related gene (HERG; the gene believed to encode native IKr). Because IKr plays an important role in ventricular AP repolarization, its inhibition would be expected to result in prolongation of both the AP and QT interval of the electrocardiogram. 4. The drugs that produce acquired LQTS are structurally heterogeneous, including anti-arrhythmics, such as quinidine, non-sedating antihistamines, such as terfenadine, and psychiatric drugs, such as haloperidol. In addition to heterogeneity in their structure, the electrophysiological characteristics of HERG/IKr inhibition differ between agents. 5. Here, clinical observations are associated with cellular data to correlate acquired LQTS with the IKr/HERG potassium (K+) channel. One strategy for developing improved compounds in those drug classes that are currently associated with LQTS could be to design drug structures that preserve clinical efficacy but are modified to avoid pharmacological interactions with IKr. Until such time, awareness of the QT-prolongation risk of particular agents is important for the clinician. [source] Video-Assisted Thoracoscopic Sympathectomy for Congenital Long QT SyndromesPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 4p1 2003JIANFENG 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 expressionACTA PHYSIOLOGICA, Issue 3 2010I. 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] Repolarization of the cardiac action potential.ACTA PHYSIOLOGICA, Issue 2010Does an increase in repolarization capacity constitute a new anti-arrhythmic principle? Abstract The cardiac action potential can be divided into five distinct phases designated phases 0,4. The exact shape of the action potential comes about primarily as an orchestrated function of ion channels. The present review will give an overview of ion channels involved in generating the cardiac action potential with special emphasis on potassium channels involved in phase 3 repolarization. In humans, these channels are primarily Kv11.1 (hERG1), Kv7.1 (KCNQ1) and Kir2.1 (KCNJ2) being the responsible ,-subunits for conducting IKr, IKs and IK1. An account will be given about molecular components, biophysical properties, regulation, interaction with other proteins and involvement in diseases. Both loss and gain of function of these currents are associated with different arrhythmogenic diseases. The second part of this review will therefore elucidate arrhythmias and subsequently focus on newly developed chemical entities having the ability to increase the activity of IKr, IKs and IK1. An evaluation will be given addressing the possibility that this novel class of compounds have the ability to constitute a new anti-arrhythmic principle. Experimental evidence from in vitro, ex vivo and in vivo settings will be included. Furthermore, conceptual differences between the short QT syndrome and IKr activation will be accounted for. [source] What Is the mechanism of SIDS?DEVELOPMENTAL PSYCHOBIOLOGY, Issue 3 2009Clues from epidemiology Abstract The cause of sudden infant death syndrome (SIDS) is unknown. Many mechanisms have been postulated, although thermal stress, rebreathing of expired gases and infection/inflammation seem the most viable hypotheses for the causation of SIDS. Deaths from SIDS have reduced dramatically following the recommendation not to place infants to sleep prone. Epidemiological data have shown that prone sleeping position is more risky in winter, colder latitudes, higher altitudes, if the infant is unwell or has excessive bedding or clothing. This suggests prone sleeping position involves either directly or indirectly a thermal mechanism. SIDS caused by an infective/inflammatory mechanism might be associated with deaths occurring during the night. Rebreathing of expired gases, airway obstruction, long QT syndrome and other genetic conditions may explain a small number of sudden unexpected deaths in infancy. © 2009 Wiley Periodicals, Inc. Dev Psychobiol 51: 215,222, 2009 [source] A new approach to long QT syndrome mutation detection by Sequenom MassARRAY® systemELECTROPHORESIS, Issue 10 2010Catarina 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] Automated mutation screening using dideoxy fingerprinting and capillary array electrophoresisHUMAN MUTATION, Issue 5 2001Lars Allan Larsen Abstract The rapid progress in the isolation of genes associated with human disease has resulted in an increasing demand for mutation screening methods. The molecular diagnosis of the long QT syndrome (LQTS), a cardiac disorder characterized by prolongation of the QTc interval in the ECG, syncopes, and sudden death, requires mutation screening of all exons in at least five genes, encoding cardiac Na+ and K+ channel subunits. A method for automated dideoxy fingerprinting (ddF) using capillary array electrophoresis (CAE) was developed and the efficiency of the method was tested by analyzing 24 DNA samples with mutations in one of the genes KCNQ1 and KCNH2, which are involved in 50% of LQTS cases. One of these mutations, 362insQK in KCNQ1, is novel. The sensitivity was 100% using a single electrophoresis temperature of 18°C or 25°C. However, analysis of the samples in both the sense and anti-sense direction were required for high sensitivity. Analysis in a single direction resulted in a decrease of the sensitivity to 74% and 70%, respectively. The throughput of the ddF method, if performed with a 16 capillary CAE instrument, is 288 samples per seven hr if each sample is analyzed on both strands. Hum Mutat 18:451,457, 2001. © 2001 Wiley-Liss, Inc. [source] Collation, assessment and analysis of literature in vitro data on hERG receptor blocking potency for subsequent modeling of drugs' cardiotoxic propertiesJOURNAL OF APPLIED TOXICOLOGY, Issue 3 2009Sebastian Polak Abstract The assessment of the torsadogenic potency of a new chemical entity is a crucial issue during lead optimization and the drug development process. It is required by the regulatory agencies during the registration process. In recent years, there has been a considerable interest in developing in silico models, which allow prediction of drug,hERG channel interaction at the early stage of a drug development process. The main mechanism underlying an acquired QT syndrome and a potentially fatal arrhythmia called torsades de pointes is the inhibition of potassium channel encoded by hERG (the human ether-a-go-go-related gene). The concentration producing half-maximal block of the hERG potassium current (IC50) is a surrogate marker for proarrhythmic properties of compounds and is considered a test for cardiac safety of drugs or drug candidates. The IC50 values, obtained from data collected during electrophysiological studies, are highly dependent on experimental conditions (i.e. model, temperature, voltage protocol). For the in silico models' quality and performance, the data quality and consistency is a crucial issue. Therefore the main objective of our work was to collect and assess the hERG IC50 data available in accessible scientific literature to provide a high-quality data set for further studies. Copyright © 2008 John Wiley & Sons, Ltd. [source] Blockade of HERG K+ channel by an antihistamine drug brompheniramine requires the channel binding within the S6 residue Y652 and F656JOURNAL OF APPLIED TOXICOLOGY, Issue 2 2008Sang-Joon Park Abstract A number of clinically used drugs block delayed rectifier K+ channels and prolong the duration of cardiac action potentials associated with long QT syndrome. This study investigated the molecular mechanisms of voltage-dependent inhibition of human ether- a-go-go -related gene (HERG) delayed rectifier K+ channels expressed in HEK-293 cells by brompheniramine, an antihistamine. Brompheniramine inhibited HERG current in a concentration-dependent manner with the half-maximal inhibitory concentration (IC50) value of 1.7 µm at 0 mV. A block of HERG current by brompheniramine was enhanced by progressive membrane depolarization and showed significantly negative shift in voltage-dependence of channel activation. Inhibition of HERG current by brompheniramine showed time-dependence. The S6 residue HERG mutant Y652A and F656C largely reduced the blocking potency of HERG current. These results indicate that brompheniramine mainly inhibited the HERG potassium channel through the residue Y652 and F656 and these residues may be an obligatory determinant in inhibition of HERG current for brompheniramine. Copyright © 2007 John Wiley & Sons, Ltd. [source] Age- and Genotype-Specific Triggers for Life-Threatening Arrhythmia in the Genotyped Long QT SyndromeJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 8 2008TOMOKO SAKAGUCHI M.D. Introduction: Patients with long QT syndrome (LQTS) become symptomatic in adolescence, but some become at age of ,20 years. Since it remains unknown whether clinical features of symptomatic LQTS patients differ depending on the age of onset, we aimed to examine whether triggers for cardiac events are different depending on the age in genotyped and symptomatic LQTS patients. Methods and Results: We identified 145 symptomatic LQTS patients, divided them into three groups according to the age of first onset of symptoms (young <20, intermediate 20,39, and older ,40 years), and analyzed triggers of cardiac events (ventricular tachycardia, syncope, or cardiac arrest). The triggers were divided into three categories: (1) adrenergically mediated triggers: exercise, emotional stress, loud noise, and arousal; (2) vagally mediated triggers: rest/sleep; and (3) secondary triggers: drugs, hypokalemia, and atrioventricular (AV) block. In the young group, 78% of the cardiac events were initiated by adrenergically mediated triggers and 22% were vagally mediated, but none by secondary triggers. In contrast, the adrenergically mediated triggers were significantly lower in the intermediate group. The percentage of secondary triggers was significantly larger in the older group than in the other two groups (0% in young vs 23% in intermediate vs 72% in older; P < 0.0001). Concerning the subdivision of secondary triggers on the basis of genotype, hypokalemia was only observed in LQT1, drugs mainly in LQT2, and AV block only in LQT2. Conclusion: Arrhythmic triggers in LQTS differ depending on the age of the patients, stressing the importance of age-related therapy for genotyped LQTS patients. [source] The Effect of Antihistamine Cetirizine on Ventricular Repolarization in Congenital Long QT SyndromeJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 7 2007ANNA-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] Sudden Cardiac Death and Inherited Arrhythmia SyndromesJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 2005ANDREA SARKOZY M.D. Sudden cardiac death (SCD) at youth is rare and is often caused by inherited cardiac disorders. This review focuses on the genetic background of inherited primary electrical diseases, the so-called "channelopathies." Following a short clinical description of each syndrome, the recent findings in the genetics of long QT syndrome, short QT syndrome, isolated cardiac conduction defect, familial sick sinus syndrome, familial atrial fibrillation, cathecholaminergic polymorphic ventricular tachycardia, familial Wolff-Parkinson-White (WPW) syndrome, and Brugada syndrome are discussed. The currently proposed theoretical model of overlapping phenotypes in SCN5A sodium channel mutations is presented. The recent data indicate that advances in molecular genetics, experimental and clinical electrophysiology shed some light on the genetic background of primary electrical diseases. However, it is also becoming clear that the process from a mutation of a gene to the clinical presentation of a patient is currently only partially understood and extremely complex. [source] Sex Modulates the Arrhythmogenic Substrate in Prepubertal Rabbit Hearts with Long QT 2JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 5 2005Ph.D., TONG LIU M.D. Females have a greater susceptibility to Torsade de Pointes in congenital and drug-induced long QT syndrome (LQTS) that has been attributed to the modulation of ion channel expression by sex hormones. However, little is known regarding sex differences in pre-puberty, that is, before the surge of sexual hormones. In patients with congenital LQTS types 1 and 2, male children tend to have a greater occurrence of adverse events, especially in 10,15 year olds, than their female counterpart. To evaluate whether the rabbit model of drug-acquired LQTS exhibits similar age dependences, hearts of prepubertal rabbits were perfused, mapped optically to record action potentials (APs) and treated with an IKr blocker, E4031 to elicit LQTS2. As expected, AP durations (APD) were significantly longer in female (n = 18) than male hearts (n = 10), at long cycle length. Surprisingly, E4031 (50,250 nM) induced a greater prolongation of APDs in male than in female hearts, and in both genders reversed the direction of repolarization (apex , base to base , apex), enhancing dispersions of repolarization. Furthermore, in male hearts, E4031 (0.5 ,M) elicited early afterdepolarizations (EADs) that progressed to polymorphic ventricular tachycardia (PVT) (n = 7/10) and were interrupted by isoproterenol (40 nM) and prevented by propranolol (0.5,2.5 ,M). In female hearts, E4031 (0.5 ,M) produced marked prolongations of APDs yet few EADs with no progression to PVT (n = 16/18). Thus, sex differences are opposite in prepubertal versus adult rabbits with respect to E4031-induced APD prolongation, EADs and PVT, underscoring the fact that APD prolongation alone is insufficient to predict arrhythmia susceptibility. 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