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Long QT syndrome is a genetic disorder associated with life threatening ventricular arrhythmias and sudden death. This inherited arrhythmic disorder exhibits genetic heterogeneity, incomplete penetrance, and variable expressivity. During the past two decades there have been major advancements in understanding the genotype-phenotype correlations in LQTS. This genotype-phenotype relationship can lead to improved management of LQTS. However, development of genotype-specific or mutation-specific management strategies is very challenging. This review describes the pathophysiology of LQTS, genotype-phenotype correlations, and focuses on the management of LQTS. In general, the treatment of LQTS consists of lifestyle modifications, medical therapy with beta-blockers, device and surgical therapy. We further summarize current data on the efficacy of pharmacological treatment options for the three most prevalent LQTS variants including beta-blockers in LQT1, LQT2 and LQT3, sodium channel blockers and ranolazine for LQT3, potassium supplementation and spironolactone for LQT2, and possibly sex hormone-based therapy for LQT2. [ABSTRACT FROM AUTHOR]

The mechanisms underlying drug induced QT prolongation and the immediate treatment of torsade de pointes have been extensively studied but the post-acute management of the Acquired Long QT Syndrome (ALQTS) remains to be addressed. We aimed to review the state of the art data regarding risk stratification, arrhythmic prevention and treatment of patients with ALQTS. A comprehensive review of the scientific data collectable from MEDLINE, EMBASE and COCHRANE (from inception to April 2013) was performed, and descriptive and qualitative information was extracted from the most relevant manuscripts. QT prolonging drugs are widely used in hospital clinical practice, and several studies have shown a high prevalence of QT interval prolongation in patients admitted to hospital and a high rate of prescription of QT interval prolonging drugs to patients presenting with QT interval prolongation. Therefore, the acute and post-acute management of ALQTS is of the utmost importance. Avoidance of offending triggers, electrocardiographic screening, pacing at a relatively fast lower rate limit and using pause prevention programming (preferably with concomitant β blocker treatment), implantable defibrillators in the highest risk patients, genetic testing and counselling in selected cases, and family screening are among the potentially applicable strategies. The latter is justifiable by the fact that some studies unveiled a surprisingly similar positive mutation rate in drug induced LQTS compared with congenital LQTS, supporting the hypothesis that the former can be regarded as a latent form of the latter. Drug challenge with D,L-sotalol in suspected LQTS and treatment with a carvedilol analogue, verapamil or an Ikr activating drug are still in need of further investigation. The post-acute management of patients with ALQTS has received scarce attention in the past, probably due to the fact that it is considered a reversible phenomenon in most cases. Considering the relatively high risk of arrhythmic recurrence in the highest risk ALQTS patients, effective preventive and treatment strategies are warranted, and further research is needed. [ABSTRACT FROM AUTHOR]

Abstract: Andersen–Tawil syndrome (ATS) is a rare hereditary multisystem disorder. Ventricular arrhythmias, periodic paralysis and dysmorphic features constitute the classic triad of ATS symptoms. The expressivity of these symptoms is, however, extremely variable, even within single ATS affected families, and not all ATS patients present with the full triad of symptoms. ATS patients may show a prolongation of the QT interval, which explains the classification as long QT syndrome type 7 (LQT7), and specific neurological or neurocognitive defects. In ATS type 1 (ATS1), the syndrome is associated with a loss-of-function mutation in the KCNJ2 gene, which encodes the Kir2.1 inward rectifier potassium channel. In ATS type 2 (ATS2), which does not differ from ATS1 in its clinical symptoms, the genetic defect is unknown. Consequently, ATS2 comprises all cases of ATS in which genetic testing did not reveal a mutation in KCNJ2. The loss-of-function mutations in KCNJ2 in ATS1 affect the excitability of both skeletal and cardiac muscle, which underlies the cardiac arrhythmias and periodic paralysis associated with ATS. Thus far, the molecular mechanism of the dysmorphic features is only poorly understood. In this review, we summarize the clinical symptoms, the underlying genetic and molecular defects, and the management and treatment of ATS. [Copyright &y& Elsevier]

The author discusses the developments in the treatment of ventricular tachycardia and long QT syndrome (LQTS). Also cited are the study which examined the effectiveness of intentional permanent atrial pacing (IPAP), how IPAP reduce breakthrough cardiac events (BCE) in both adult and child patients, and the results in high-risk patients with Andersen-Tawil syndrome and Jervell and Lange-Nielsen syndrome.

Abstract: Impaired ventricular repolarization can lead to long QT syndrome (LQT), a proarrhythmic disease with high risk of developing lethal ventricular tachyarrhythmias. The compound ICA-105574 is a recently developed hERG activator and it enhances I Kr current with very high potency by removing the channel inactivation. The present study was designed to investigate antiarrhythmic properties of ICA-105574. For comparison, the effects of another compound NS1643 was in-parallel assessed, which also acts primarily to attenuate channel inactivation with moderate potency. We found that both ICA-105574 and NS1643 concentration-dependently shortened action potential duration (APD) in ventricular myocytes, and QT/QTc intervals in isolated guinea-pig hearts. ICA-105574, but not NS1643, completely prevented ventricular arrhythmias in intact guinea-pig hearts caused by I Kr and I Ks inhibitors, although both ICA-105574 and NS1643 could reverse the drug-induced prolongation of APD in ventricular myocytes. Reversing prolongation of QT/QTc intervals and antagonizing the increases in transmural dispersion of repolarization and instability of the QT interval induced by I Kr and I Ks inhibitors contributed to antiarrhythmic effect of ICA-105574. Meanwhile, ICA-105574 at higher concentrations showed a potential proarrhythmic risk in normal hearts. Our results suggest that ICA-105574 has more efficient antiarrhythmic activity than NS1643. However, its potential proarrhythmic risk implies that benefits and risks should be seriously taken into consideration for further developing this type of hERG activators. [Copyright &y& Elsevier]

Background and Purpose Zolpidem, a short-acting hypnotic drug prescribed to treat insomnia, has been clinically associated with acquired long QT syndrome ( LQTS) and torsade de pointes ( TdP) tachyarrhythmia. LQTS is primarily attributed to reduction of cardiac human ether-a-go-go-related gene ( hERG)/ IKr currents. We hypothesized that zolpidem prolongs the cardiac action potential through inhibition of hERG K+ channels. Experimental Approach Two-electrode voltage clamp and whole-cell patch clamp electrophysiology was used to record hERG currents from Xenopus oocytes and from HEK 293 cells. In addition, hERG protein trafficking was evaluated in HEK 293 cells by Western blot analysis, and action potential duration ( APD) was assessed in human-induced pluripotent stem cell ( hiPSC)-derived cardiomyocytes. Key Results Zolpidem caused acute hERG channel blockade in oocytes ( IC50 = 61.5 μM) and in HEK 293 cells (IC50 = 65.5 μM). Mutation of residues Y652 and F656 attenuated hERG inhibition, suggesting drug binding to a receptor site inside the channel pore. Channels were blocked in open and inactivated states in a voltage- and frequency-independent manner. Zolpidem accelerated hERG channel inactivation but did not affect I- V relationships of steady-state activation and inactivation. In contrast to the majority of hERG inhibitors, hERG cell surface trafficking was not impaired by zolpidem. Finally, acute zolpidem exposure resulted in APD prolongation in hiPSC-derived cardiomyocytes. Conclusions and Implications Zolpidem inhibits cardiac hERG K+ channels. Despite a relatively low affinity of zolpidem to hERG channels, APD prolongation may lead to acquired LQTS and TdP in cases of reduced repolarization reserve or zolpidem overdose. [ABSTRACT FROM AUTHOR]

QTc interval prolongation is a side effect of several antipsychotic drugs, with associated risks of torsade de pointes arrhythmias and sudden cardiac death. There is an ongoing debate of whether or not electrocardiogram (ECG) assessments should be mandatory in patients starting antipsychotic drugs. To investigate QTc prolongation in a clinically relevant patient group 171 adult patients acutely admitted to an emergency ward for psychosis were consecutively recruited. ECGs were recorded at baseline and then at discharge or after 6 weeks at the latest (discharge/6 weeks), thus reflecting the acute phase treatment period. Themean QTc interval was 421.1 (30.4)ms at baseline and there was a positive association between the QTc interval and the agitation score whereas the QTc interval was inversely associated with the serum calciumlevel. A total of 11.6%had abnormally prolongedQTc intervals and another 14.3% had borderline prolongation. At discharge/6 weeks, the corresponding proportions were reduced to 4.2% and 5.3%, respectively. The reduction of the proportion with prolonged QTc intervals reached statistical significance (chi-square exact test: ?? = 0.046). The finding of about one-quarter of the patients with borderline or prolonged QTc intervals could indicate mandatory ECG recordings in this population. This trial is registered with ClinicalTrials.gov ID: NCT00932529. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to compare the efficacy of beta-blockers in congenital long QT syndrome (LQTS). Background: Beta-blockers are the mainstay in managing LQTS. Studies comparing the efficacy of commonly used beta-blockers are lacking, and clinicians generally assume they are equally effective. Methods: Electrocardiographic and clinical parameters of 382 LQT1/LQT2 patients initiated on propranolol (n = 134), metoprolol (n = 147), and nadolol (n = 101) were analyzed, excluding patients <1 year of age at beta-blocker initiation. Symptoms before therapy and the first breakthrough cardiac events (BCEs) were documented. Results: Patients (56% female, 27% symptomatic, heart rate 76 ± 16 beats/min, QTc 472 ± 46 ms) were started on beta-blocker therapy at a median age of 14 years (interquartile range: 8 to 32 years). The QTc shortening with propranolol was significantly greater than with other beta-blockers in the total cohort and in the subset with QTc >480 ms. None of the asymptomatic patients had BCEs. Among symptomatic patients (n = 101), 15 had BCEs (all syncopes). The QTc shortening was significantly less pronounced among patients with BCEs. There was a greater risk of BCEs for symptomatic patients initiated on metoprolol compared to users of the other 2 beta-blockers combined, after adjustment for genotype (odds ratio: 3.95, 95% confidence interval: 1.2 to 13.1, p = 0.025). Kaplan-Meier analysis showed a significantly lower event-free survival for symptomatic patients receiving metoprolol compared to propranolol/nadolol. Conclusions: Propranolol has a significantly better QTc shortening effect compared to metoprolol and nadolol, especially in patients with prolonged QTc. Propranolol and nadolol are equally effective, whereas symptomatic patients started on metoprolol are at a significantly higher risk for BCEs. Metoprolol should not be used for symptomatic LQT1 and LQT2 patients. [Copyright &y& Elsevier]

Long QT syndrome (LQTS) is a genetic disease characterized by a prolonged QT interval in an electrocardiogram (ECG), leading to higher risk of sudden cardiac death. Among the 12 identified genes causal to heritable LQTS, ∼90% of affected individuals harbor mutations in either KCNQI or human ether-a-go-go related genes (hERG), which encode two repolarizing potassium currents known as lKS and lKr- The ability to quantitatively assess contributions of different current components is therefore important for investigating disease phenotypes and testing effectiveness of pharmacological modulation. Here we report a quantitative analysis by simulating cardiac action potentials of cultured human cardiomyo-cytes to match the experimental waveforms of both healthy control and LQT syndrome type 1 (LQT1) action potentials. The quantitative evaluation suggests that elevation of lKr by reducing voltage sensitivity of inactivation, not via slowing of deactivation, could more effectively restore normal QT duration if lks is reduced. Using a unique specific chemical activator lkr that has a primary effect of causing a right shift of V1/2 for inactivation, we then examined the duration changes of autonomous action potentials from differentiated human cardiomyocytes. Indeed, this activator causes dose-dependent shortening of the action potential durations and is able to normalize action potentials of cells of patients with LQT1. In contrast, an lkr chemical activator of primary effects in slowing channel deactivation was not effective in modulating action potential durations. Our studies provide both the theoretical basis and experimental support for compensatory normalization of action potential duration by a pharmacological agent. [ABSTRACT FROM AUTHOR]

Abstract: Patients with psychiatric illness have an increased cardiovascular mortality, partly due to sudden death and increased by taking certain antipsychotics and other psychotropic drugs. Poor cardiac safety of these drugs is associated with prolongation of the QT interval of the electrocardiogram (ECG), causing an arrhythmia called Torsade de Pointes (TdP). Units for Difficult Patients receive patients whose care is complicated in a usual psychiatric ward, due to agitation or violence. There are currently five of these psychiatric units in France. These units therefore welcome the chemo-resistant patients, that is to say, resistant to many neuroleptics, or associations of major psychotropic drugs. They also accommodate patients whose condition is not compatible with care in prisons. The hospitalization lasts for 10 months on average. The distinctive feature of these units is that they treat patients with reinforced human resources, psychotherapies, and above all psychotropic drugs. Objectives: A study was conducted at the unit in Villejuif, Paris, to measure the prevalence of long QT syndrome and its risk factors in connection with drug prescription. Material and method: An ECG and serum electrolytes were made in the same time for each patient. The data collected are: QT, heart rate, QTc by the formulas of Bazett and Fridericia, QTc given by the device. Conduction disorders were sought for exclusion. Prescriptions were analyzed, sorted by drug therapeutic class, according to the risk of QT prolongation, and dosage levels. Patients: The analysis results of 63 patients aged 19 to 64 years. The average age is 33 years and the sex ratio is 11 women (17%) and 52 men (83%). The most frequent diagnosis was paranoid schizophrenia, representing over 50% of the patients. It is followed by specific disorders of personality. The mood disorders are less frequent. The pervasive developmental disorders are absent. Some patients also have comorbid psychiatric diagnoses. Results: These results show: prevalence of long QT syndrome by 40% according to the formula of Bazett (including 6 %>500ms, major risk of TdP); the preponderance of medicinal risk factor, present in all patients. Other risk factors for QT prolongation are rare (hypokalaemia and bradycardia: 1.6%, female: 17%). The risk factors for TdP are frequent (hypomagnesemia: 8%, hypocalcemia: 46%, renal dysfonction 11%), some of which can be corrected; a measurement variability of the QT interval with significant differences (p <0.001) by the operator and the method of calculation used (Bazett, Fridericia…); increase in the number and average values of long QTc with the number of drugs associated with QT lengthening; lastly, an increase of number and average values of long QTc with high doses. Conclusions: The prevalence of long QT syndrome in our study is higher than that usually found in the literature. The associations of psychotropic drugs are many, evidence that drug resistance is present. These treatments involve many molecules presented as lengthening the QT. Patients with the longest QT, are those having most associated drugs and higher doses. However, despite the proven toxicity of these treatments, it must be remembered that the QT prolongation does not necessarily a negative risk-benefit balance. This is assessed on a case-by-case basis to determine the right practice. These results emphasize the need for increased surveillance of risk associated with long QT patients on psychotropic associations. They now have awareness of carers and the establishment of a protocol for enhanced surveillance in the service. [Copyright &y& Elsevier]

Background--ß-Adrenergic stimulation is the main trigger for cardiac events in type I long-QT syndrome (LQTl). We evaluated a possible association between ion channel response to ß-adrenergic stimulation and clinical response to ß-blocker therapy according to mutation location. Methods and Results--The study sample comprised 860 patients with genetically confirmed mutations in the KCNQ1 channel. Patients were categorized into carriers of missense mutations located in the cytoplasmic loops (C loops), membrane-spanning domain, C/N terminus, and nonmissense mutations. There were 27 aborted cardiac arrest and 78 sudden cardiac death events from birth through 40 years of age. After multivariable adjustment for clinical factors, the presence of C-loop mutations was associated with the highest risk for aborted cardiac arrest or sudden cardiac death (hazard ratio versus nonmissense mutations=2.75; 95% confidence interval, 1.29-5.86; P=0.009). ß-Blocker therapy was associated with a significantly greater reduction in the risk of aborted cardiac arrest or sudden cardiac death among patients with C-loop mutations than among all other patients (hazard ratio=0.12; 95% confidence interval, 0.02-0.73; P=0.02; and hazard ratio=0.82; 95% confidence interval, 0.31-2.13; P=0.68, respectively; P for interaction=0.04). Cellular expression studies showed that membrane spanning and C-loop mutations produced a similar decrease in current, but only C-loop mutations showed a pronounced reduction in channel activation in response to ß-adrenergic stimulation. Conclusions--Patients with C-loop missense mutations in the KCNQ1 channel exhibit a high risk for life-threatening events and derive a pronounced benefit from treatment with ß-blockers. Reduced channel activation after sympathetic activation can explain the increased clinical risk and response to therapy in patients with C-loop mutations. INSET: CLINICAL PERSPECTIVE. [ABSTRACT FROM AUTHOR]

Long-QT syndrome is a potentially lethal cardiac channelopathy that can be mistaken for palpitations, neurocardiogenic syncope, and epilepsy. Delayed diagnosis of long QT syndrome is frequent. Symptoms are often attributed to alternative diagnoses, most commonly seizure disorders. Long QT syndrome has significant mortality, which is reduced with appropriate management. We aim to underline the importance of clinical awareness and correct management to reduce the fatal cases of this syndrome. [ABSTRACT FROM AUTHOR]

We report a case of torsade de pointes after intravenous amiodarone and concurrent hypokalemia. Despite treatment cessation and correction of electrolyte abnormalities, excessive QTc prolongation was noted, which persisted for 14 days. This prolonged course for QTc normalization may be attributed to the high rate of amiodarone loading and concurrent electrolyte disturbances coupled with possible underlying individual variability in pharmacokinetics. [ABSTRACT FROM AUTHOR]

We present the case of a 49-year-old male patient with prosthetic mitral valve endocarditis associated with QT prolongation and torsades de pointes. He was asymptomatic until the end of January 2012, when he was admitted to our hospital emergency unit because of syncope, fever, and suspicion of endocarditis. Cardiologic evaluation was requested and the transthoracic (TTE) and transesophageal (TEE) echocardiograms revealed vegetations on the prosthetic mitral valve. All cultures were positive for methicillin-sensitive Staphylococcus aureus. The corrected QT (QTc) interval was markedly prolonged upon admission (QTc 540 ms). He experienced torsades de pointes (TdP) several times and he was recovered after bystander cardiopulmonary resuscitation. The clinical course and the long QTc interval with deep inverted T wave were completely normalized 4 weeks after. He continued on triple antibiotic therapy for 45 days with a good revolution. The clinical features and the possible mechanisms of QT prolongation (inflammation, infection) of this patient are discussed. [ABSTRACT FROM AUTHOR]

Background: Electrocardiographic and molecular studies have clarified an association between sudden infant death syndrome (SIDS) and long QT syndrome (LQTS), and few data are available for the QT interval in infancy from birth to 1 year of age. Appropriate time of electrocardiographic screening is not clarified. Medical examinations during infancy are mandatory in Japan. Methods and Results: The study population included 1,058 infants. Electrocardiograms were collected with information of infants at birth and at examination. The QT intervals of three consecutive beats were measured in lead V5. Statistical analysis revealed that the following formula was appropriate to minimize the effect of heart rate for infants: corrected QT interval; QTc = QT interval/RR interval 0.43. Subjects were divided into four groups as follows: 0–2, 3–6, 6–11, and 12–52 weeks of age. Tukey''s multiple comparison showed that the QTc intervals were longest (p < 0:0001) in subjects who were 6–11 weeks of age. Conclusions: The QTc interval showed the highest peak at 6-11 weeks of age in infancy. The peak period of occurrence of SIDS is at approximately 2 months of age. An appropriate time of electrocardiographic screening for QT prolongation will be one month of age, and follow-up studies are needed. [Copyright &y& Elsevier]

Long QT syndrome type 3 (LQT3) has been traced to mutations of the cardiac Na+ channel (Nav1.5) that produce persistent Na+ currents leading to delayed ventricular repolarization and torsades de pointes. We performed mutational analyses of patients suffering from LQTS and characterized the biophysical properties of the mutations that we uncovered. One LQT3 patient carried a mutation in the SCN5A gene in which the cysteine was substituted for a highly conserved tyrosine (Y1767C) located near the cytoplasmic entrance of the Nav1.5 channel pore. The wild-type and mutant channels were transiently expressed in tsA201 cells, and Na+ currents were recorded using the patch-clamp technique. The Y1767C channel produced a persistent Na+ current, more rapid inactivation, faster recovery from inactivation, and an increased window current. The persistent Na+ current of the Y1767C channel was blocked by ranolazine but not by many class I antiarrhythmic drugs. The incomplete inactivation, along with the persistent activation of Na+ channels caused by an overlap of voltage-dependent activation and inactivation, known as window currents, appeared to contribute to the LQTS phenotype in this patient. The blocking effect of ranolazine on the persistent Na+ current suggested that ranolazine may be an effective therapeutic treatment for patients with this mutation. Our data also revealed the unique role for the Y1767 residue in inactivating and forming the intracellular pore of the Nav1.5 channel. [ABSTRACT FROM AUTHOR]

Objective: Women during labor may be susceptible to torsades de pointes (TdP), which may cause the fetal condition to deteriorate. The aim of the present investigation was to analyze maternal and fetal outcomes during labor when long QT syndrome (LQTS) was present.Methods: We examined the maternal and neonatal outcomes of 25 pregnancies (18 women) with LQT between 1995 and 2012 at the Department of Perinatology, National Cardiovascular Center, Japan. Maternal and neonatal outcomes including cardiovascular events, cardiovascular events within a week after delivery, caesarean delivery rate, still births, preterm births, and non-reassuring fetal heart rate pattern (NRFHR) during labor were investigated.Results: All the mothers survived, and no cardiovascular events occurred in labor or postpartum due to LQTS in either vaginal delivery or caesarean delivery. A total of 23 women (92%) had used beta blockers in this study. Caesarean delivery was performed due to NRFHR during labor in 5 pregnancies (20%).Conclusion: Delivery when LQTS is present has a low likelihood of cardiovascular events, but pregnancy with LQTS had a higher caesarean delivery rate due to NRFHR in labor. Most women used beta blockers in this study, and it is possible that beta blocker use prevents cardiovascular events during labor. NRFHR during labor may be related with inherited LQT through the mother. [ABSTRACT FROM AUTHOR]

Prolongation of QT/QTc interval during medical treatment can occur not only with cardiovascular drugs but also with non-cardiovascular drugs. It may result in ventricular tachyarrhythmia, a high-risk condition which may trigger sudden cardiac death. Thus, to avoid drug-induced long QT syndrome and serious complications careful attention should be paid in the clinical setting. Moreover, in the last several years objective evaluation by strictly applying electrocardiogram (ECG) data has been strongly recommended for the development of all new drugs in discussions held at the International Conference on Harmonization (ICH). This recommendation has already been adopted in the USA and the EU and is expected to be announced shortly in our country. Not only the drugs but a variety of patient background factors may influence ECG parameters, especially the QT/QTc interval. It is necessary to introduce an appropriate study protocol that can evaluate the risk for QT/QTc prolongation related to the drug. Additionally, an adequate system to record, measure, and evaluate ECG with high objectivity must be applied to all clinical trials. [Copyright &y& Elsevier]

The article reports on the evaluation of the relevant genotype-phenotype features of long-QT syndrome (LQTS) and the strategies explored to develop novel therapeutic approaches. The identification of genetic defects in LQTS has allowed the use of molecular data that are applied to risk stratification. It is possible to envision that future LQTS therapy will include agents that counteract the molecular abnormalities.

Long-QT syndromes (LQTSs) have been described in all ages and are a significant cause of cardiovascular mortality, especially in structurally normal hearts. Abnormalities in transmembrane ion conduction channels and structural proteins produce these clinical syndromes, labeled LQT1-LQT12; however, genotype-positive patients still represent only about 70% of LQTSs. Future research will determine the etiology of the remaining cases, further risk-stratify the known genetic defects, improve current treatment options for these syndromes, and uncover novel therapies. [ABSTRACT FROM AUTHOR]

Recently, the effects of QT interval prolongation have received more attention among clinicians, industry, and official regulatory agencies. Some have advocated the total elimination or discontinuing development of drugs which prolong the QT interval. In this review, we will give a brief overview of the pathophysiology and the dynamic variability and morphology of the QT interval. From the view point of arrhythmogenesis, QT interval prolongation with increased heterogeneity of ventricular repolarization is critical. The problem is how to detect such an abnormal repolarization. To detect heterogeneity, a new index should be developed and validated, and it must incorporate QT variability and morphology of the T wave. The heart rate correction of the QT interval is also an important issue, and disclosing conflict-corrected QT intervals depend on the formulae used. Not just QT interval prolongation is important; what also matters is the heterogeneity of ventricular repolarization. [Copyright &y& Elsevier]

Objective: To develop guidelines for the management of QT prolongation after citalopram overdose, including decontamination with single-dose activated charcoal (SDAC) and cardiac monitoring.Design: Simulation study using a previously developed pharmacokinetic-pharmacodynamic (PKPD) model which predicted the time-course of QT prolongation and the effect of citalopram dose and use of SDAC on QT prolongation.Main Measures and Results: The previously developed PKPD model was used to address the following in patients following citalopram overdose: (1) Above what dose should patients be decontaminated? (2) Above what dose should patients have cardiac monitoring? (3) For what period of time should patients be monitored? The primary outcome was QT,RR combinations above an abnormal threshold as a surrogate predictor of torsades de pointes. Simulations were performed using MATLAB for an overdose patient with typical demographics: 30-year-old female with a heart rate of 79 bpm taking citalopram therapeutically. The simulations showed: (1) There was significant benefit associated with the administration of SDAC to patients following citalopram overdose ingesting >600 mg; (2) With citalopram overdoses >1,000mg it was advisable to give SDAC and cardiac monitor the patient; (3) The risk of developing future abnormal QT,RR combinations was less than 1% in patients with normal QT,RR combinations up to 13 h post-dose, so the minimum monitoring time for citalopram overdoses >1,000mg should be 13h. Recommended dose levels for intervention should be lowered in older patients and patients with tachycardia, while men are less sensitive to QT prolongation.Conclusions: Guidelines for the management of QT prolongation after citalopram overdose were developed. We believe the model will help clinicians to decide which patients to decontaminate and monitor. [ABSTRACT FROM AUTHOR]

Background: LQTS may cause sudden cardiac death (SCD), but the mechanisms linking gene mutations to ventricular fibrillation (VF) are unclear.Objective: To determine whether ventricular activation delays in congenital long QT syndrome (LQTS) are associated with VF and to describe these delays clinically by measuring activation through ventricular myocardium after a premature extrastimulus.Methods: Forty-six patients with LQTS, including 16 with VF (LQTS VF) were investigated, and the results were compared with those from 24 patients with hypertrophic cardiomyopathy and VF (HCM VF). Electrograms in response to premature stimuli were analyzed for increases in electrogram duration (DeltaED) and the S1S2 coupling intervals at which electrogram latency starts to increase (S1S2(delay)). Two piecewise continuous straight line segments were fitted to the last electrogram deflection as a function of S1S2 interval in the LQTS and HCM VF populations, and the difference in their gradient (alpha) was taken as an index of the abruptness of the onset of this delay.Results: Thirteen LQTS VF and six LQTS non-VF patients had values of DeltaED and S1S2(delay) comparable to those in HCM VF patients, while the remainder (three LQTS VF and 24 LQTS non-VF) had lower values (P<.001). There was only a weak correlation between delay and the corrected QT interval. The HCM and LQTS VF patients could be separated by the value of alpha (P<.01), with the LQTS patients having a more abrupt onset of delay.Conclusions: Large delays in ventricular activation after an extrastimulus occur in patients with the LQTS, especially those with VF. The change in delay is abrupt in the LQTS, indicating sudden block to activation creating a dynamic substrate for arrhythmogenesis. [ABSTRACT FROM AUTHOR]

Background: Biventricular pacing is useful for patients with congestive heart failure but has the disadvantage of being a long, user-dependent, highly technical procedure.Objectives: The purpose of this study was to simplify the procedure. The simplified technique consists of sinus (CS) venography prior to implantation, direct coronary access for the left ventricular (LV) lead without use of a left-heart delivery system, and triple-guide/one introducer cephalic vein access as the first approach in patients presenting in sinus rhythm.Methods: A cephalic cutdown was performed, and a steerable hydrophilic guidewire was introduced in the cephalic vein. A 9Fr introducer was advanced over the guidewire, and two other guides were inserted through the introducer. This technique allowed for insertion of a right ventricular lead, an LV lead, and an atrial lead.Results: One hundred three patients were evaluated from January 2002 to September 2004. Four implants failed (3.9%). The 7Fr LV lead was successfully placed in 99 of 103 patients (96.1%) directly via the 9Fr introducer, without use of a dedicated left-heart delivery system. The final position was lateral in 59 patients, posterolateral in 33, posterior in 4, and anterolateral in 3. Sixty patients were in sinus rhythm, 13 were in atrial fibrillation, and 26 had a previous pacemaker (n = 21) or defibrillator (n = 5). Triple cephalic vein access was possible in 48 of the patients in sinus rhythm (80%). Procedure parameters were as follows: LV threshold 0.9 +/- 0.7 V, LV wave amplitude 15 +/- 8 mV, LV impedance 790 +/- 232 Omega, skin-to-skin procedure time 76 +/- 33 minutes, and fluoroscopy time 23 +/- 19 minutes. Ten complications (10.1%) occurred: 7 lead dislodgments (3 within 48 hours and 4 within 6 months) requiring repositioning (7.1%), 1 subacute local infection requiring explantation (1%), 1 phrenic nerve stimulation (1%), and 1 pneumothorax (1%). The long-term success of biventricular pacing was 93.1%.Conclusions: This study demonstrates that cardiac resynchronization therapy implantation can be simplified with the combined use of a steerable hydrophilic guidewire, three guides, and one introducer via a right cephalic vein, without use of a left-heart delivery system. The triple cephalic vein approach yields an 80% implant success rate for patients in sinus rhythm. The long-term success of biventricular pacing was 93.1%. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to evaluate retrospectively a single-center experience with the use of ICDs in patients with long QT syndrome (LQTS) concerning outcome, complications, and optimal programming.Background: Use of implantable cardioverter-defibrillator (ICD) in patients with congenital LQTS is controversial but is generally accepted in high-risk patients.Methods: We enrolled 27 symptomatic patients with LQTS undergoing ICD therapy (QTc 540 +/- 64 ms(1/2); 85% female, 63% cardiac arrest; 33% syncope despite beta-blockers; 4% with severe phenotype) and 81 genotyped patients with LQTS undergoing conventional drug therapy (28 LQT1, 39 LQT2, 1 LQT3, 13 LQT5). During a mean follow-up of 65 +/- 34 months, one death occurred in the ICD group that was not LQTS related. A total of 178 appropriate shocks were observed in 10/27 patients (37%), mostly in survivors of cardiac arrest (in 58% of cardiac arrest patients vs. in 20% of non-cardiac arrest patients).Results: In a logistic regression analysis, only QTc interval (121/178 shocks (68%) for QTc > 500 ms(1/2)) and "survived cardiac arrest" were prognostic for ICD shocks. In 30% of patients in the ICD group, multiple shocks occurred and could be reduced after increase of antibradycardia pacing rate, adding beta-blocker therapy, or starting the rate-smoothing algorithm (average 7.1 shocks before to 0.75 shocks after additional intervention annually).Conclusion: ICD therapy is a safe and useful tool in high-risk patients with LQTS. QTc interval and cardiac arrest survivors were prognostic factors for appropriate ICD shocks. The results of this large single-center experience suggest that beta-blockers should always be added to ICD therapy. In addition, some patients might benefit from additional antibradycardia pacing, prolonged detection time, and a rate-smoothing algorithm to prevent recurrent episodes. [ABSTRACT FROM AUTHOR]

Background: Nicorandil, a potassium channel opener, is used for the treatment of angina pectoris and has a pharmacologic preconditioning effect. This study evaluated whether intravenous nicorandil reduces QT dispersion and prevents bradyarrhythmia during percutaneous transluminal coronary angioplasty (PTCA) of the right coronary artery.Methods: A historical cohort study on the effect of nicorandil on QT dispersion and bradyarrhythmia was conducted. Fifty patients who underwent PTCA of the right coronary artery were enrolled. The patients were divided into a nicorandil (n = 25) group and control group (n = 25). Nicorandil was injected at 4 mg/h continuously 1 hour before PTCA in the nicorandil group. QT dispersion was measured at 1 hour before PTCA (baseline), immediately before PTCA, and 1 minute after the initiation of the first balloon inflation.Results: QT dispersion at 1 minute after the initiation of the first balloon inflation in the control group increased significantly (QT dispersion: 37.1 +/- 17.8 msec and 21.7 +/- 12.2 msec, respectively, P < .001 vs baseline in the control group), and this was larger than at 1 minute after the initiation of the first balloon inflation in the nicorandil group (QT dispersion: 37.1 +/- 17.8 msec and 20.8 +/- 9.4 msec, respectively, P < .001). By two-way repeated measures analysis of variance, there were significant interactions between the time factor and the grouping factor in QT dispersion (P < .001). Bradyarrhythmia was observed in 6 patients in the control group, but none was observed in the nicorandil group.Conclusions: Intravenous nicorandil reduces QT dispersion and prevents bradyarrhythmia during PTCA of the right coronary artery. [ABSTRACT FROM AUTHOR]

Brugada and long QT-3 syndromes are two allelic diseases caused by different mutations in SCN5A gene inherited by an autosomal dominant pattern with variable penetrance. Both of these syndromes are ion channel diseases of the heart manifest on surface electrocardiogram by ST-segment elevation in the right precordial leads and prolonged QT(c) interval, respectively, with predilection for polymorphic ventricular tachycardia and sudden death, which may be the first manifestation of the disease. Brugada syndrome usually manifests during adulthood with male preponderance, whereas long QT3 syndrome usually manifests in teenage years, although it can also manifest in adulthood. Class IA and IC antiarrhythmic drugs increase ST-segment elevation and predilection for polymorphic ventricular tachycardia and ventricular fibrillation in Brugada syndrome, whereas these agents shorten the repolarization and QT(c) interval, and thus may be beneficial in long QT-3 syndrome. Beta-blockade also increases the ST-segment elevation in Brugada syndrome but decreases the dispersion of repolarization in long QT-3 syndrome. Mexiletine, a class IB sodium channel blocker decreases QT(c) interval as well as dispersion of repolarization in long QT-3 syndrome but has no effect on Brugada syndrome. The only effective treatment available at this time for Brugada syndrome is implantable cardioverter defibrillator, although repeated episodes of polymorphic ventricular tachycardia can be treated with isoproterenol. In symptomatic patients of long QT-3 syndrome in whom the torsade de pointes is bradycardia-dependent or pause-dependent, a pacemaker could be used to avoid bradycardia and pauses and an implantable cardioverter defibrillator is indicated where arrhythmia is not controlled with pacemaker and beta-blockade. However, the combination of new devices with pacemaker and cardioverter-defibrillator capabilities appear promising in these patients warranting further study. [ABSTRACT FROM AUTHOR]

The article focuses on the cardiovascular risks associated with stimulant medications for the treatment of attention deficit hyperactivity disorder (ADHD). It discusses the study conducted by C. Zhang and colleagues to analyse the occurrence of cardiac events in patients receiving stimulant therapy, and presents the mild side effects associated with the stimulant therapy, such as increased heart rate and blood pressure.

The long QT syndrome (LQTS) is a cause of syncope and sudden death. Jervell and Lange-Nielson syndrome (JLNS) is an uncommon form of LQTS, having autosomal recessive transmission, and is associated with congenital deafness. We report a case of JLNS in a child who presented to us with refractory epilepsy. The cardiac cause of seizures was suspected as the child was hypotensive and pulseless during the episode of seizures. The child was diagnosed as JLNS based on Schwartz diagnostic criteria for LQTS and congenital sensorineural deafness. The child responded well to â?blocker therapy. Antiepileptic drugs were stopped. The screening of family members with ECG revealed a QT interval more than required for diagnosis of LQTS but they were asymptomatic. All asymptomatic family members were also put on metoprolol. All of them showed great improvement with the reduction of the QT interval on ECG. The patient was doing well on immediate follow?up. [ABSTRACT FROM AUTHOR]

The article presents a case study of atrial fibrillation which was seen in a 14 year old boy with congenital long QT syndrome type 1 who had had a defibrillator implanted which was programmed for managed ventricular pacing. A discussion of the factors that could have led to the fibrillation in the patient despite the fact that he had a defibrillator is presented.

About 10-20% of patients dying suddenly and unexpectedly do not have structural heart disease. The major causes of sudden death in this population are acute ischemia, the syndrome of right bundle branch block, and ST-elevation from V1 to V3, the long QT-syndrome, and the Wolff-Parkinson-While syndrome. In some patients, none of these syndromes can be recognized and ventricular fibrillation is classified as idiopathic. There are good preventive and therapeutic methods against acute ischemia and there are also curative treatments for the Wolff-Parkinson-White syndrome. Patients with idiopathic ventricular fibrillation cannot be recognized beforehand. However, there are electrocardiographic and genetic markers for the Brugada syndrome and the long QT syndrome. It is, therefore, justified to discuss the possible role of the prophylactic defibrillator to prevent sudden death in these 2 syndromes for which no effective treatment exists. Patients with Brugada syndrome have a high incidence of sudden death, and prophylactic defibrillators are indicated in patients with inducible arrhythmias at electrophysiologic study, irrespective of symptoms. On the contrary, the incidence of sudden death in the long QT syndrome is very low, making prophylactic defibrillator implantation not cost-effective. [ABSTRACT FROM AUTHOR]

The authors comment on a study published within the issue which described a semiempiric formula that allows estimation of the true QT interval in left bundle brunch block (LBBB) on a per patient basis. Topics covered include the need to have a reliable and simple technique to assess QT interval in LBBB in the practice of clinical electrophysiology, and questions that need to be answered before the QT derived in the study become a surrogate and a sub-stitute for the manually measured QT.

Introduction: This study aimed to determine the effects of the interaction between intravenous anesthetics and desflurane on the QT interval.Methods: Fifty patients who underwent lumbar spine surgery were included. The patients received 3 μg/kg fentanyl and were randomly divided into two groups: group P patients received 1.5 mg/kg propofol and group T patients received 5 mg/kg thiamylal 2 min after fentanyl injection. All patients received rocuronium and desflurane (6% inhaled concentration) after loss of consciousness. Tracheal intubation was performed 3 min after rocuronium injection. Heart rate (HR), mean arterial pressure (MAP), bispectral index score (BIS), and the heart rate-corrected QT (QTc) interval on a 12-lead electrocardiograms were recorded before fentanyl injection (T1), 2 min after fentanyl injection (T2), 1 min after propofol or thiamylal injection (T3), immediately before intubation (T4), and 2 min after intubation (T5).Results: There were no significant intergroup differences in patient characteristics. BIS and MAP decreased after anesthesia induction in both groups. MAP values at T3, T4, and T5 in group T were higher than those in group P. HR did not change over time or differ between the groups. The QTc intervals at T4 and T5 in group T were longer than those at T1. In group P, the QTc interval at T3 was significantly shorter than that at T1. The QTc intervals at T3, T4, and T5 in group T were significantly longer than those in group P.Conclusions: A propofol injection could counteract the QTc interval prolongation during desflurane anesthesia induction.Trial registration: UMIN Clinical Trials Registry database reference number: UMIN000023707. This study was registered on August 21, 2016. [ABSTRACT FROM AUTHOR]

The article presents case study of a 30-year-old woman, with a medical history of genotype positive long-QT syndrome, who was admitted after recurrent shocks from her implantable cardioverter defibrillator (ICD). It states that medical examination of the patient revealed signs and symptoms of acute alcohol withdrawal, and mentions that electrocardiogram (ECG) of the patient was studied to find out the patient's atrial rhythm.

A letter to the editor is presented which is concerned with the case study of a 72 year old male patient with gastric cancer who developed oxaliplatin-induced Torsades de pointes and long QT syndrome.

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A picture quiz about radiograph of right wrist of a young man, a statistical question based on proportional quota sampling, and a question on case of a 23-year-old woman who slumped and fell from her horse while show jumping are presented.