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Sample records for qt interval prolongation

  1. Prolonged QT interval in Rett syndrome

    OpenAIRE

    1999-01-01

    Rett syndrome is a severe neurodevelopmental disorder of unknown aetiology. A prolonged QT interval has been described previously in patients with Rett syndrome. To investigate QT prolongation and the presence of cardiac tachyarrhythmias in Rett syndrome electrocardiography and 24 hour Holter monitoring were performed prospectively in a cohort of 34 girls with Rett syndrome. The corrected QT value was prolonged in nine patients. Compared with a group of healthy controls of a...

  2. Safety information on QT-interval prolongation

    DEFF Research Database (Denmark)

    Warnier, Miriam J; Holtkamp, Frank A; Rutten, Frans H;

    2014-01-01

    Prolongation of the QT interval can predispose to fatal ventricular arrhythmias. Differences in QT-labeling language can result in miscommunication and suboptimal risk mitigation. We systematically compared the phraseology used to communicate on QT-prolonging properties of 144 drugs newly approve......) was moderate (kappa 0.434). However, the agreement in expected clinical decisions based on the product labels was much higher (kappa 0.673). The US drug label tends to be more explicit, especially when it considers absence of QT effects....

  3. Multifactorial QT Interval Prolongation and Takotsubo Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Michael Gysel

    2014-01-01

    Full Text Available A 71-year-old woman collapsed while working as a grocery store cashier. CPR was performed and an AED revealed torsades de pointes (TdP. She was subsequently defibrillated resulting in restoration of sinus rhythm with a QTc interval of 544 msec. Further evaluation revealed a diagnosis of Takotsubo Cardiomyopathy (TCM contributing to the development of a multifactorial acquired long QT syndrome (LQTS. The case highlights the role of TCM as a cause of LQTS in the setting of multiple risk factors including old age, female gender, hypokalemia, and treatment with QT prolonging medications. It also highlights the multifactorial nature of acquired LQTS and lends support to growing evidence of an association with TCM.

  4. QT interval prolongation after Premature Ventricular Contractions (PVCs

    Directory of Open Access Journals (Sweden)

    Mohammed Haroon Rashid

    2010-11-01

    Full Text Available Long QT syndrome (LQTS is an inherited ion channelopathy resulting in abnormal ventricular repolarization and abnormal prolongation of QT interval on the ECG. Syncope, fainting, cardiac arrest, and sudden death are common manifestations of LQTS. We present a case report that describes a patient with prolonged QT interval after extrasystoles and a family history of sudden cardiac deaths.

  5. Assessing QT Interval Prolongation and its Associated Risks with Antipsychotics

    DEFF Research Database (Denmark)

    Nielsen, Jimmi; Graff, Claus; Kanters, Jørgen K.

    2011-01-01

    markers for TdP have been developed but none of them is clinically implemented yet and QT interval prolongation is still considered the most valid surrogate marker. Although automated QT interval determination may offer some assistance, QT interval determination is best performed by a cardiologist skilled...

  6. Assessing QT interval prolongation and its associated risks with antipsychotics

    DEFF Research Database (Denmark)

    Nielsen, Jimmi; Graff, Claus; Kanters, Jørgen K.

    2011-01-01

    markers for TdP have been developed but none of them is clinically implemented yet and QT interval prolongation is still considered the most valid surrogate marker. Although automated QT interval determination may offer some assistance, QT interval determination is best performed by a cardiologist skilled...

  7. Quality of drug label information on QT interval prolongation

    DEFF Research Database (Denmark)

    Warnier, Miriam J; Holtkamp, Frank A; Rutten, Frans H;

    2014-01-01

    characteristics (SPC) of recently approved medicinal products. METHODS: Drug labels of products centrally approved in Europe between 2006 and 2012 were screened. Of drugs including the term 'QT' in the SPC, the message on QT-prolongation ('no prolongation'/'unclear drug-QT association'/'possibly QT......-prolongation'/'QT-prolongation') and the advice on cautionary measures pertaining to QT-prolongation in the label were examined, as well as their association. RESULTS: Of the 175 screened products, 44 contained information on QT in the SPC ('no QT-prolongation': 23%, 'unclear drug-QT association': 43%, 'possibly QT-prolongation': 16%, 'QT......-prolongation': 18%). 62% contained advices to act with caution in patients with additional risk factors for QT-prolongation. Products that more likely to have QT-prolonging properties according to the SPC provided more information on QT-prolongation in the SPC ('no prolongation': 10% and for the category 'QT...

  8. Drug induced QT prolongation: the measurement and assessment of the QT interval in clinical practice.

    Science.gov (United States)

    Isbister, Geoffrey K; Page, Colin B

    2013-07-01

    There has been an increasing focus on drug induced QT prolongation including research on drug development and QT prolongation, following the removal of drugs due to torsades de pointes (TdP). Although this has improved our understanding of drug-induced QT prolongation there has been much less research aimed at helping clinicians assess risk in individual patients with drug induced QT prolongation. This review will focus on assessment of drug-induced QT prolongation in clinical practice using a simple risk assessment approach. Accurate measurement of the QT interval is best done manually, and not using the measurement of standard ECG machines. Correction for heart rate (HR) using correction formulae such as Bazett's is often inaccurate. These formulae underestimate and overestimate the duration of cardiac repolarization at low and high heart rates, respectively. Numerous cut-offs have been suggested as an indicator of an abnormal QT, but are problematic in clinical practice. An alternative approach is the QT nomogram which is a plot of QT vs. HR. The nomogram has an 'at risk' line and QT-HR pairs above this line have been shown in a systematic study to be associated with TdP and the line is more sensitive and specific than Bazett's QTc of 440 ms or 500 ms. Plotting the QT-HR pair for patients on drugs suspected or known to cause QT prolongation allows assessment of the QT interval based on normal population QT variability. This risk assessment then allows the safer commencement of drugs therapeutically or management of drug induced effects in overdose. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

  9. Prolonged QT interval in a man with anorexia nervosa

    Science.gov (United States)

    Macías-Robles, María Dolores; Perez-Clemente, Ana María; Maciá-Bobes, Carmen; Alvarez-Rueda, María Asunción; Pozo-Nuevo, Sergio

    2009-01-01

    Anorexia nervosa is an eating disorder characterized by the avoidance of food intake, which usually leads to a weight loss. Cardiac co-morbility is common and we can find sometimes a mass loss from the left ventricle, which can be seen by echocardiography. But the commonest complications are rhythm variations, typically bradycardia with a prolonged QT interval in up to a 40% of the cases, which altogether elevates ventricular tachycardia and sudden death risk. We present the case of a male who was diagnosed with anorexia nervosa and developed asthenia, a long QT interval and also a severe both hypokalaemia and hypomagnesaemia. We intend to discuss the pathogenic paths as well as prophylactic and therapeutic measures to this potentially-lethal pathology. PMID:19646241

  10. Cesium-induced QT-interval prolongation in an adolescent.

    Science.gov (United States)

    O'Brien, Catherine E; Harik, Nada; James, Laura P; Seib, Paul M; Stowe, Cindy D

    2008-08-01

    Alternative medicine is becoming increasingly popular, especially with terminally ill patients. Most alternative remedies have not been adequately studied or proven effective for the diseases for which they are promoted. In the worst cases, these therapies are harmful. We describe a 16-year-old girl with metastatic hepatocellular carcinoma who experienced cesium-induced QT-interval prolongation after the start of a cesium chloride-based alternative treatment regimen. She had received seven courses of chemotherapy, with a cumulative doxorubicin dose of 500 mg/m(2) over 5 months, resulting in minimal tumor regression. Against the advice of her oncologist, she abandoned traditional therapy and started an alternative regimen that included cesium chloride supplements. Two weeks later, the patient went to a local emergency department after experiencing two brief syncopal episodes. An electrocardiogram revealed occasional premature ventricular contractions, a QTc interval of 683 msec (normal range for females 450-460 msec), and R on T phenomenon. She was admitted to the hospital and later experienced monomorphic ventricular tachycardia, which resolved spontaneously. Lidocaine therapy was started, and the patient was transferred to a cardiac intensive care unit at our hospital. Her plasma cesium level was 2400 microg/dl (normal cesium level was 1800 microg/dl, and her QTc interval was 494 msec. According to the Naranjo adverse drug reaction probability scale, cesium was the probable cause of the patient's arrhythmia. In animal models, cesium chloride has induced cardiac arrhythmias, including torsade de pointes. It inhibits delayed rectifier potassium channels in the myocardium, causing delayed repolarization and QT-interval prolongation. Patients with cancer should be aware that alternative remedies may be harmful and ineffective. Because patients may be unlikely to self-report alternative remedies, health care providers should specifically ask their patients about any

  11. [Drug-induced QT interval prolongation: do we know the risks?].

    Science.gov (United States)

    Villamañán, Elena; Armada, Eduardo; Ruano, Margarita

    2015-03-15

    Sudden cardiac death is an important cause of mortality in developed countries, most of them being consequence of acute ventricular arrhythmias. These arrhythmias, in some cases, owe to QT interval prolongation. A major risk factor for this condition is the use of drugs that prolong the QT interval. In fact, in recent years, one of the most common reasons for drug withdrawal or usage restrictions has been drug induced QT interval prolongation that involves both cardiovascular and non-cardiovascular drugs. Taking into account the severity that the occurrence of such an event may have, it is important for clinicians to know the risks of these drugs in certain patients. In this review we analyze the drugs that prolong the QT interval, the risk factors that can enhance QT prolongation and the drug interactions that can increase these risks. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  12. Hypoglycaemia and QT interval prolongation in type 1 diabetes

    DEFF Research Database (Denmark)

    Christensen, Toke Folke; Cichosz, Simon Lebech; Tarnow, L.

    2014-01-01

    hypoglycaemia varies greatly between studies. METHODS: We studied ten adults with type 1 diabetes (age 41±15years) without cardiovascular disease or neuropathy. Single-blinded hypoglycaemia was induced by a subcutaneous insulin bolus followed by a control episode on two occasions separated by 4weeks. QT....... CONCLUSIONS: Hypoglycaemia as experienced after a subcutaneous injection of insulin may cause QTc prolongation in type 1 diabetes. However, the magnitude of prolongation is less than typically reported during glucose clamp studies, possible because of the study design with focus on minimizing unwanted study...

  13. Prolonged QT interval predicts cardiac and all-cause mortality in the elderly. The Rotterdam Study

    NARCIS (Netherlands)

    M.C. de Bruyne (Martine); A.W. Hoes (Arno); J.A. Kors (Jan); J.H. van Bemmel (Jan); D.E. Grobbee (Diederick); A. Hofman (Albert)

    1999-01-01

    textabstractAIMS: To examine the association between heart-rate corrected QT prolongation and cardiac and all-cause mortality in the population-based Rotterdam Study among men and women aged 55 years or older and to compare the prognostic value of the QT interval, using

  14. QT interval prolongation in opioid agonist treatment: analysis of continuous 12-lead electrocardiogram recordings.

    Science.gov (United States)

    Isbister, Geoffrey K; Brown, Amanda L; Gill, Anthony; Scott, Alexander J; Calver, Leonie; Dunlop, Adrian J

    2017-10-01

    Methadone is a widely used opioid agonist treatment associated with QT prolongation and torsades de pointes. We investigated the QT interval in patients treated with methadone or buprenorphine using continuous 12-lead Holter recordings. We prospectively made 24-h Holter recordings in patients prescribed methadone or buprenorphine, compared to controls. After their normal dose a continuous 12-lead Holter recorder was attached for 24 h. Digital electrocardiograms were extracted hourly from the Holter recordings. The QT interval was measured automatically (H-scribe software, Mortara Pty Ltd) and checked manually. The QT interval was plotted against heart rate (HR) on the QT nomogram to determine abnormality. Demographics, dosing, medical history and laboratory investigations were recorded. There were 58 patients (19 methadone, 20 buprenorphine and 19 control); median age 35 years (20-56 years); 33 males. Baseline characteristics were similar. Median dose of methadone was 110 mg day(-1) (70-170 mg day(-1) ) and buprenorphine was 16 mg day(-1) (12-32 mg day(-1) ). Seven participants had abnormal QT intervals. There was a significant difference in the proportion of prescribed methadone with abnormal QT intervals, 7/19 (37%; 95% confidence interval: 17-61%), compared to controls 0/19 (0%; 95% confidence interval: 0-21%; P = 0.008), but no difference between buprenorphine and controls (0/20). QT vs. HR plots showed patients prescribed methadone had higher QT-HR pairs over 24 h compared to controls. There was no difference in dose for patients prescribed methadone with abnormal QT intervals and those without. Methadone is associated with prolonged QT intervals, but there was no association with dose. Buprenorphine did not prolong the QT interval. Twenty four-hour Holter recordings using the QT nomogram is a feasible method to assess the QT interval in patients prescribed methadone. © 2017 The Authors. British Journal of Clinical Pharmacology published by John

  15. QT interval prolongation related to psychoactive drug treatment: a comparison of monotherapy versus polytherapy

    Directory of Open Access Journals (Sweden)

    Piccinelli Marco

    2005-01-01

    Full Text Available Abstract Background Several antipsychotic agents are known to prolong the QT interval in a dose dependent manner. Corrected QT interval (QTc exceeding a threshold value of 450 ms may be associated with an increased risk of life threatening arrhythmias. Antipsychotic agents are often given in combination with other psychotropic drugs, such as antidepressants, that may also contribute to QT prolongation. This observational study compares the effects observed on QT interval between antipsychotic monotherapy and psychoactive polytherapy, which included an additional antidepressant or lithium treatment. Method We examined two groups of hospitalized women with Schizophrenia, Bipolar Disorder and Schizoaffective Disorder in a naturalistic setting. Group 1 was composed of nineteen hospitalized women treated with antipsychotic monotherapy (either haloperidol, olanzapine, risperidone or clozapine and Group 2 was composed of nineteen hospitalized women treated with an antipsychotic (either haloperidol, olanzapine, risperidone or quetiapine with an additional antidepressant (citalopram, escitalopram, sertraline, paroxetine, fluvoxamine, mirtazapine, venlafaxine or clomipramine or lithium. An Electrocardiogram (ECG was carried out before the beginning of the treatment for both groups and at a second time after four days of therapy at full dosage, when blood was also drawn for determination of serum levels of the antipsychotic. Statistical analysis included repeated measures ANOVA, Fisher Exact Test and Indipendent T Test. Results Mean QTc intervals significantly increased in Group 2 (24 ± 21 ms however this was not the case in Group 1 (-1 ± 30 ms (Repeated measures ANOVA p Conclusions No significant prolongation of the QT interval was found following monotherapy with an antipsychotic agent, while combination of these drugs with antidepressants caused a significant QT prolongation. Careful monitoring of the QT interval is suggested in patients taking a

  16. QT interval prolongation in users of selective serotonin reuptake inhibitors in an elderly surgical population

    DEFF Research Database (Denmark)

    van Haelst, Ingrid M M; van Klei, Wilton A; Doodeman, Hieronymus J;

    2014-01-01

    OBJECTIVE: To investigate the association between the use of a selective serotonin reuptake inhibitor (SSRI) and the occurrence of QT interval prolongation in an elderly surgical population. METHOD: A cross-sectional study was conducted among patients (> 60 years) scheduled for outpatient preanes...

  17. The assessment of potential for QT interval prolongation with new pharmaceuticals: impact on drug development.

    Science.gov (United States)

    Gralinski, M R

    2000-01-01

    Few examinations of a single physiological variable can end the development of a putative new pharmaceutical. Prolongation of the electrocardiographic QT interval is one of these tests. Recognizing the removal of several approved and widely used medicines, worldwide regulatory authorities have raised a heightened awareness on the submission of data surrounding the ventricular repolarization process. This review will discuss the anatomy and physiology surrounding the generation of the electrocardiographic QT interval and the consequences of its alteration. In addition, relevant models of preclinical safety and general guidelines for clinical examination in this area are discussed along with the impact of incorporating these assays into the drug development process.

  18. [Patient safety: prescription of drugs that prolong the QT interval].

    Science.gov (United States)

    Hernández-Arroyo, María Jesús; Díaz-Madero, Alfonso; Menacho-Miguel, David

    2015-09-01

    Objetivo: conocer la prescripcion de farmacos con riesgo conocido de prolongar el intervalo QT en un area de salud, informar a los medicos responsables de los factores de riesgo asociados a su aparicion y mejorar la seguridad del paciente. Métodos: estudio descriptivo transversal y observacional de prevalencia. Se incluyeron 4.964 pacientes de un area de salud en tratamiento con farmacos con riesgo conocido en un mes. Se identificaron farmacos de riesgo, interacciones y factores predisponentes. Se proporciono a cada medico los pacientes con farmacos con riesgo conocido, las recomendaciones y la encuesta para conocer mas factores de riesgo, su utilidad y su actitud clinica. Se realizo un analisis estadistico descriptivo. Resultados: el 3,2% de los pacientes del area estaban tratados con farmacos con riesgo conocido. El 64,0% eran mujeres, 57,5% mayores de 65 anos, y el 39,6% presentaban interacciones. El numero medio de factores de riesgo por paciente fue 1,78. Los farmacos con riesgo conocido mas frecuentes fueron antidepresivos (41,2%) y antibioticos (40,4%). El 25,4% de los medicos devolvio la encuesta informando de la actitud clinica en 1.073 pacientes: se retiro el farmaco con riesgo conocido en 289, se redujo la dosis en 113 y se realizo electrocardiograma en 398. Los medicos identificaron otros factores de riesgo: problema cardiaco (17,9%) e hiper/hipotiroidismo (8,8%). Conclusiones: la prevalencia detectada en la prescripcion de farmacos que prolongan el intervalo QT es relevante teniendo en cuenta que los pacientes tenian ademas otros factores de riesgo. Su identificacion permite mejorar la calidad de la atencion y la seguridad del paciente.

  19. Seizures following hippocampal kindling induce QT interval prolongation and increased susceptibility to arrhythmias in rats.

    Science.gov (United States)

    Bealer, Steven L; Little, Jason G

    2013-07-01

    The prolonged seizures of status epilepticus produce chronic arrhythmogenic changes in cardiac function. This study was designed to determine if repeated, self-limiting seizures administered to kindled rats induce similar cardiac dysfunction. Multiple seizures administered to rats following hippocampal kindling resulted in cardiac QT interval prolongation and increased susceptibility to experimental arrhythmias. These data suggest that multiple, self-limiting seizures of intractable epilepsy may have cardiac effects that can contribute to sudden unexpected death in epilepsy (SUDEP).

  20. The effect of arsenic trioxide on QT interval prolongation during APL therapy

    Institute of Scientific and Technical Information of China (English)

    周晋; 孟然; 李晓霞; 吕成芳; 范圣瑾; 杨宝峰

    2003-01-01

    Objective To investigate the cardiac effect of QT interval prolongation in the treatment of acute promyelocytic leukemia (APL) with arsenic trioxide (As2O3), and the relationship between QT and serum arsenic concentration.Methods Blood serum arsenic concentrations of thirty APL patients were determined at 2 hours, 4 hours, 8 hours, and 24 hours after As2O3 injection using atomic fluorophotometry. Cardiac functions were measured simultaneously using a 12-lead body-surface electrocardiogram (ECG). Q-T intervals were manually measured, and then corrected using Bazett ' s formula (QTc). QT dispersion (QTd) was also calculated. In order to assess the effects of arsenic on the symptoms of anemia, twenty-four anemia patients were divided into two groups on the basis hemoglobin concentration: Group1 (Hb≥90 g/L), and Group 2 (60 g/L≤Hb<90 g/L). QTc and QTd of these patients were also manually measured.Results All QT intervals of APL patients treated with As2O3 injection were prolonged [32.2 ms (27, 41 ms); P 0.05]. There was a delay of 2 hours in maximum QTc following peaks in serum arsenic concentration. Changes in QTc and QTd of the two anemic groups were not prominent.Conclusions As2O3 can prolong QTc intervals in APL patients, but the effects are delayed compared to peak serum arsenic concentrations. As2O3 has no prolongation effect on QTd. Mild and moderate anemia do not effect QTc and QTd.

  1. Co-Prescription of QT-Interval Prolonging Drugs: An Analysis in a Large Cohort of Geriatric Patients.

    Directory of Open Access Journals (Sweden)

    Simone Schächtele

    Full Text Available Drug-induced QT-interval prolongation is associated with occurrence of potentially fatal Torsades de Pointes arrhythmias (TdP. So far, data regarding the overall burden of QT-interval prolonging drugs (QT-drugs in geriatric patients are limited.This study was performed to assess the individual burden of QT-interval prolonging drugs (QT-drugs in geriatric polymedicated patients and to identify the most frequent and risky combinations of QT-drugs.In the discharge medication of geriatric patients between July 2009 and June 2013 from the Geriatrics in Bavaria-Database (GiB-DAT (co-prescriptions of QT-drugs were investigated. QT-drugs were classified according to a publicly available reference site (CredibleMeds® as ALL-QT-drugs (associated with any QT-risk or High-risk-QT-drugs (corresponding to QT-drugs with known risk of Torsades de Pointes according to CredibleMeds® and in addition as SmPC-high-risk-QT-drugs (according to the German prescribing information (SmPC contraindicated co-prescription with other QT-drugs.Of a cohort of 130,434 geriatric patients (mean age 81 years, 67% women, prescribed a median of 8 drugs, 76,594 patients (58.7% received at least one ALL-QT-drug. Co-prescriptions of two or more ALL-QT-drugs were observed in 28,768 (22.1% patients. Particularly risky co-prescriptions of High-risk-QT-drugs or SmPC-high-risk-QT-drugs with at least on further QT-drug occurred in 55.9% (N = 12,633 and 54.2% (N = 12,429 of these patients, respectively. Consideration of SmPCs (SmPC-high-risk-QT-drugs allowed the identification of an additional 15% (N = 3,999 patients taking a risky combination that was not covered by the commonly used CredibleMeds® classification. Only 20 drug-drug combinations accounted for more than 90% of these potentially most dangerous co-prescriptions.In a geriatric study population co-prescriptions of two and more QT-drugs were common. A considerable proportion of QT-drugs with higher risk only could be detected by

  2. Metoprolol and diltiazem ameliorate ziprasidone-induced prolonged corrected QT interval in rats.

    Science.gov (United States)

    Erbas, Oytun; Yilmaz, Mustafa

    2015-12-01

    Ziprasidone, an atypical antipsychotic agent, has been shown to increase the corrected QT (QTc) interval in some patients. The aim of this study was to reveal the effects of metoprolol and diltiazem on ziprasidone drug-induced prolonged QTc interval. A total of 24 rats were equally divided into the following four groups: the first group was used as the control and received 1 mL/kg saline; 3 mg/kg ziprasidone and saline were administered to the second group; 3 mg/kg ziprasidone and 1 mg/kg metoprolol were administered to the third group and 3 mg/kg ziprasidone and 2 mg/kg diltiazem were administered to the fourth group. Two hours following application of the drugs, the QTc was calculated by performing electrocardiography in derivation (D)I. The duration of QTc interval was compared among the four groups. The mean QTc intervals were significantly increased in the third and fourth groups compared with the second group (p metoprolol and diltiazem in the prevention of ziprasidone-induced elongation in the QTc interval. Both metoprolol and diltiazem may be considered in the prophylactic therapy of high-risk patients who are using ziprasidone.

  3. Prolonged Tp-e Interval and Tp-e/QT Ratio in Children with Mitral Valve Prolapse.

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    Demirol, Mustafa; Karadeniz, Cem; Ozdemir, Rahmi; Çoban, Şenay; Katipoğlu, Nagehan; Yozgat, Yılmaz; Meşe, Timur; Unal, Nurettin

    2016-08-01

    Although it is considered to be a benign condition, previous studies have shown that a subset of patients with mitral valve prolapse (MVP) may be at risk of ventricular arrhythmia and sudden cardiac death (SCD). Previous studies have suggested that the interval between the peak and the end of the T wave (Tp-e) can be used as a marker for the transmural dispersion of repolarization. Increased Tp-e interval and Tp-e/QT ratio are associated with ventricular arrhythmias and SCD. The aim of this study was to assess alterations in ventricular repolarization by using the Tp-e interval and Tp-e/QT ratio in children with MVP and to investigate their relationships with the degree of valvular regurgitation. This study prospectively investigated 110 children with MVP and 107 age- and sex-matched healthy control subjects. Tp-e interval, Tp-e/QT ratio, and QT and QTc dispersions were measured from a 12-lead electrocardiogram and compared between groups. QT and QTc dispersions, Tp-e interval, and Tp-e/QTc ratio were found to be significantly higher in patients with MVP. A positive correlation was found between Tp-e/QTc ratio and increase in the degree of mitral regurgitation (MR) (p e intervals; QT, QTc, or Tp-e dispersions; or Tp-e/QT ratio (all p values >0.05). Individuals with MVP may be more prone to ventricular arrhythmias due to prolonged QTd, QTcd, and Tp-e interval and increased Tp-e/QT and Tp-e/QTc ratios. Therefore, due to their longer life expectancy, children with MVP should be followed up on regarding life-threatening arrhythmias.

  4. Prolonged corrected QT interval is predictive of future stroke events even in subjects without ECG-diagnosed left ventricular hypertrophy.

    Science.gov (United States)

    Ishikawa, Joji; Ishikawa, Shizukiyo; Kario, Kazuomi

    2015-03-01

    We attempted to evaluate whether subjects who exhibit prolonged corrected QT (QTc) interval (≥440 ms in men and ≥460 ms in women) on ECG, with and without ECG-diagnosed left ventricular hypertrophy (ECG-LVH; Cornell product, ≥244 mV×ms), are at increased risk of stroke. Among the 10 643 subjects, there were a total of 375 stroke events during the follow-up period (128.7±28.1 months; 114 142 person-years). The subjects with prolonged QTc interval (hazard ratio, 2.13; 95% confidence interval, 1.22-3.73) had an increased risk of stroke even after adjustment for ECG-LVH (hazard ratio, 1.71; 95% confidence interval, 1.22-2.40). When we stratified the subjects into those with neither a prolonged QTc interval nor ECG-LVH, those with a prolonged QTc interval but without ECG-LVH, and those with ECG-LVH, multivariate-adjusted Cox proportional hazards analysis demonstrated that the subjects with prolonged QTc intervals but not ECG-LVH (1.2% of all subjects; incidence, 10.7%; hazard ratio, 2.70, 95% confidence interval, 1.48-4.94) and those with ECG-LVH (incidence, 7.9%; hazard ratio, 1.83; 95% confidence interval, 1.31-2.57) had an increased risk of stroke events, compared with those with neither a prolonged QTc interval nor ECG-LVH. In conclusion, prolonged QTc interval was associated with stroke risk even among patients without ECG-LVH in the general population.

  5. The QT and Corrected QT Interval in Recovery After Exercise in Children

    NARCIS (Netherlands)

    Berger, Wouter Rudolph; Gow, Robert M.; Kamberi, Suleman; Cheung, Michael; Smith, Katherine Rose; Davis, Andrew Mark

    2011-01-01

    Background-Prolongation of the QT interval after exercise can be used to help diagnose long-QT syndrome, especially when the resting QT interval is borderline. The aim of this study was to determine the normal ranges for QT and corrected QT in the recovery phase after exercise in children. Methods a

  6. [The QT interval: standardization, limits and interpretation].

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    Ouali, S; Ben Salem, H; Gribaa, R; Kacem, S; Hammas, S; Fradi, S; Neffeti, E; Remedi, F; Boughzela, E

    2012-02-01

    Despite clinical importance of ventricular repolarisation, it remains difficult to analyse. Conventionally, quantification of the electrocardiographic ventricular repolarization is usually performed with reference to axis of the T wave and QT interval duration. A variety of factors can prolong the QT interval, such as drug effects, electrolyte imbalances, and myocardial ischemia. The biggest risk with prolongation of the QT interval is the development of torsades de pointes. Commonly accepted reference ranges for the electrocardiogram (ECG) have been in use, with little change, for many years. Populations throughout the world present several differences: age, ethnic compositions, and are exposed to different environmental factors. Recent studies have reported reference data for QT interval in healthy population and have evaluated the influence of age, gender, QRS duration and heart rate on this interval. In this review, we address several issues relative to the measurement, and interpretation of QT interval and its adjustment for rate, age, gender and QRS duration.

  7. Relation of increased short-term variability of QT interval to congenital long-QT syndrome

    DEFF Research Database (Denmark)

    Hinterseer, Martin; Beckmann, Britt-Maria; Thomsen, Morten B

    2009-01-01

    Apart from clinical symptoms the diagnosis and risk stratification in long-QT syndrome (LQTS) is usually based on the surface electrocardiogram. Studies have indicated that not only prolongation of the QT interval but also an increased short-term variability of QT interval (STV(QT)) is a marker f...

  8. Effect of mood states on QT interval and QT dispersion in eating disorder patients.

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    Takimoto, Yoshiyuki; Yoshiuchi, Kazuhiro; Akabayashi, Akira

    2008-04-01

    Prolonged QT interval and QT dispersion have been reported in patients with eating disorders. Although the factors that cause prolongation remain unclear, mood states such as anxiety have been reported to influence QT interval and dispersion, probably via the autonomic nervous system. Therefore the aim of the present paper was to investigate mood effect on prolonged QT interval and QT dispersion. The subjects were 47 female anorexia nervosa (AN) and 48 female bulimia nervosa (BN) patients. In all of the patients, serum electrolyte levels were normal. QT interval and QT dispersion were measured from 12-lead electrocardiographic recordings. Mood states in each patient were measured using a Profile of Mood States (POMS) evaluation, and the patients were divided into high- and low-score groups for each POMS subscale. The differences in QT variables were compared between the two groups for each subscale. In the BN group, QT interval and QT dispersion in the high depression score group were significantly longer than those in the low depression score group, and QT dispersion was significantly greater in the high anxiety score group than in the low anxiety score group. In addition, QT interval and QT dispersion were significantly correlated with depression scores. In the AN group there were no significant differences in QT interval or QT dispersion between the high- and low-score groups for any POMS subscale. BN patients with worse states of depression or anxiety had longer QT intervals and larger QT dispersion. In BN patients, mood disturbance might increase the risk of arrhythmias.

  9. QT-Interval Duration and Mortality Rate

    Science.gov (United States)

    Zhang, Yiyi; Post, Wendy S.; Dalal, Darshan; Blasco-Colmenares, Elena; Tomaselli, Gordon F.; Guallar, Eliseo

    2012-01-01

    Background Extreme prolongation or reduction of the QT interval predisposes patients to malignant ventricular arrhythmias and sudden cardiac death, but the association of variations in the QT interval within a reference range with mortality end points in the general population is unclear. Methods We included 7828 men and women from the Third National Health and Nutrition Examination Survey. Baseline QT interval was measured via standard 12-lead electrocardiographic readings. Mortality end points were assessed through December 31, 2006 (2291 deaths). Results After an average follow-up of 13.7 years, the association between QT interval and mortality end points was U-shaped. The multivariate-adjusted hazard ratios comparing participants at or above the 95th percentile of age-, sex-, race-, and R-R interval–corrected QT interval (≥439 milliseconds) with participants in the middle quintile (401 to <410 milliseconds) were 2.03 (95% confidence interval, 1.46-2.81) for total mortality, 2.55 (1.59-4.09) for mortality due to cardiovascular disease (CVD), 1.63 (0.96-2.75) for mortality due to coronary heart disease, and 1.65 (1.16-2.35) for non-CVD mortality. The corresponding hazard ratios comparing participants with a corrected QT interval below the fifth percentile (<377 milliseconds) with those in the middle quintile were 1.39 (95% confidence interval, 1.02-1.88) for total mortality, 1.35 (0.77-2.36) for CVD mortality, 1.02 (0.44-2.38) for coronary heart disease mortality, and 1.42 (0.97-2.08) for non-CVD mortality. Increased mortality also was observed with less extreme deviations of QT-interval duration. Similar, albeit weaker, associations also were observed with Bazett-corrected QT intervals. Conclusion Shortened and prolonged QT-interval durations, even within a reference range, are associated with increased mortality risk in the general population. PMID:22025428

  10. International Conference on Harmonisation; guidance on E14 Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs; availability. Notice.

    Science.gov (United States)

    2005-10-20

    The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "E14 Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs." The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance provides recommendations to sponsors concerning clinical studies to assess the potential of a new drug to cause cardiac arrhythmias, focusing on the assessment of changes in the QT/QTc interval on the electrocardiogram as a predictor of risk. The guidance is intended to encourage the assessment of drug effects on the QT/QTc interval as a standard part of drug development and to encourage the early discussion of this assessment with FDA.

  11. Effects of the New Aldose Reductase Inhibitor Benzofuroxane Derivative BF-5m on High Glucose Induced Prolongation of Cardiac QT Interval and Increase of Coronary Perfusion Pressure

    Directory of Open Access Journals (Sweden)

    C. Di Filippo

    2016-01-01

    Full Text Available This study investigated the effects of the new aldose reductase inhibitor benzofuroxane derivative 5(6-(benzo[d]thiazol-2-ylmethoxybenzofuroxane (BF-5m on the prolongation of cardiac QT interval and increase of coronary perfusion pressure (CPP in isolated, high glucose (33.3 mM D-glucose perfused rat hearts. BF-5m was dissolved in the Krebs solution at a final concentration of 0.01 μM, 0.05 μM, and 0.1 μM. 33.3 mM D-glucose caused a prolongation of the QT interval and increase of CPP up to values of 190 ± 12 ms and 110 ± 8 mmHg with respect to the values of hearts perfused with standard Krebs solution (11.1 mM D-glucose. The QT prolongation was reduced by 10%, 32%, and 41%, respectively, for the concentration of BF-5m 0.01 μM, 0.05 μM, and 0.1 μM. Similarly, the CPP was reduced by 20% for BF-5m 0.05 μM and by 32% for BF-5m 0.1 μM. BF-5m also increased the expression levels of sirtuin 1, MnSOD, eNOS, and FOXO-1, into the heart. The beneficial actions of BF-5m were partly abolished by the pretreatment of the rats with the inhibitor of the sirtuin 1 activity EX527 (10 mg/kg/day/7 days i.p. prior to perfusion of the hearts with high glucose + BF-5m (0.1 μM. Therefore, BF-5m supplies cardioprotection from the high glucose induced QT prolongation and increase of CPP.

  12. QT Prolongation due to Graves’ Disease

    Directory of Open Access Journals (Sweden)

    Zain Kulairi

    2017-01-01

    Full Text Available Hyperthyroidism is a highly prevalent disease affecting over 4 million people in the US. The disease is associated with many cardiac complications including atrial fibrillation and also less commonly with ventricular tachycardia and fibrillation. Many cardiac pathologies have been extensively studied; however, the relationship between hyperthyroidism and rate of ventricular repolarization manifesting as a prolonged QTc interval is not well known. Prolonged QTc interval regardless of thyroid status is a risk factor for cardiovascular mortality and life-threatening ventricular arrhythmia. The mechanism regarding the prolongation of the QT interval in a hyperthyroid patient has not been extensively investigated although its clinical implications are relevant. Herein, we describe a case of prolonged QTc in a patient who presented with signs of hyperthyroidism that was corrected with return to euthyroid status.

  13. QT Prolongation due to Graves' Disease

    Science.gov (United States)

    Deol, Nisha; Tolly, Renee; Manocha, Rohan; Naseer, Maliha

    2017-01-01

    Hyperthyroidism is a highly prevalent disease affecting over 4 million people in the US. The disease is associated with many cardiac complications including atrial fibrillation and also less commonly with ventricular tachycardia and fibrillation. Many cardiac pathologies have been extensively studied; however, the relationship between hyperthyroidism and rate of ventricular repolarization manifesting as a prolonged QTc interval is not well known. Prolonged QTc interval regardless of thyroid status is a risk factor for cardiovascular mortality and life-threatening ventricular arrhythmia. The mechanism regarding the prolongation of the QT interval in a hyperthyroid patient has not been extensively investigated although its clinical implications are relevant. Herein, we describe a case of prolonged QTc in a patient who presented with signs of hyperthyroidism that was corrected with return to euthyroid status. PMID:28154763

  14. Analysis of Onset Mechanisms of a Sphingosine 1-Phosphate Receptor Modulator Fingolimod-Induced Atrioventricular Conduction Block and QT-Interval Prolongation

    Energy Technology Data Exchange (ETDEWEB)

    Yagi, Yukihiro [Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143–8540 (Japan); Pharmaceutical Research Center, Meiji Seika Pharma Co., Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama, Kanagawa 222–8567 (Japan); Nakamura, Yuji [Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143–8540 (Japan); Kitahara, Ken [Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143–8540 (Japan); Division of Cardiovascular Medicine, Department of Internal Medicine, Faculty of Medicine, Toho University, 6-11-1 Omori-nishi, Ota-ku, Tokyo 143–8541 (Japan); Harada, Takuma [Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143–8540 (Japan); Kato, Kazuhiko; Ninomiya, Tomohisa [Pharmaceutical Research Center, Meiji Seika Pharma Co., Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama, Kanagawa 222–8567 (Japan); Cao, Xin [Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143–8540 (Japan); Ohara, Hiroshi [Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143–8540 (Japan); Division of Cardiovascular Medicine, Department of Internal Medicine, Faculty of Medicine, Toho University, 6-11-1 Omori-nishi, Ota-ku, Tokyo 143–8541 (Japan); Izumi-Nakaseko, Hiroko [Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143–8540 (Japan); Suzuki, Kokichi [Pharmaceutical Research Center, Meiji Seika Pharma Co., Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama, Kanagawa 222–8567 (Japan); Ando, Kentaro [Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143–8540 (Japan); and others

    2014-11-15

    Fingolimod, a sphingosine 1-phosphate (S1P) receptor subtype 1, 3, 4 and 5 modulator, has been used for the treatment of patients with relapsing forms of multiple sclerosis, but atrioventricular conduction block and/or QT-interval prolongation have been reported in some patients after the first dose. In this study, we directly compared the electropharmacological profiles of fingolimod with those of siponimod, a modulator of sphingosine 1-phosphate receptor subtype 1 and 5, using in vivo guinea-pig model and in vitro human ether-a-go-go-related gene (hERG) assay to better understand the onset mechanisms of the clinically observed adverse events. Fingolimod (0.01 and 0.1 mg/kg) or siponimod (0.001 and 0.01 mg/kg) was intravenously infused over 10 min to the halothane-anaesthetized guinea pigs (n = 4), whereas the effects of fingolimod (1 μmol/L) and siponimod (1 μmol/L) on hERG current were examined (n = 3). The high doses of fingolimod and siponimod induced atrioventricular conduction block, whereas the low dose of siponimod prolonged PR interval, which was not observed by that of fingolimod. The high dose of fingolimod prolonged QT interval, which was not observed by either dose of siponimod. Meanwhile, fingolimod significantly inhibited hERG current, which was not observed by siponimod. These results suggest that S1P receptor subtype 1 in the heart could be one of the candidates for fingolimod- and siponimod-induced atrioventricular conduction block since S1P receptor subtype 5 is localized at the brain, and that direct I{sub Kr} inhibition may play a key role in fingolimod-induced QT-interval prolongation. - Highlights: • Fingolimod and siponimod are S1P{sub 1,3,4,5} and S1P{sub 1,5} receptor modulators, respectively. • Fingolimod and siponimod induced AV block in the halothane-anesthetized guinea pigs. • S1P{sub 1} in the hearts may be the target of fingolimod- and siponimod-induced AV block. • Fingolimod directly inhibited hERG current, which was not

  15. International Conference on Harmonisation; guidance on S7B Nonclinical Evaluation of the Potential for Delayed Ventricular Repolarization (QT Interval Prolongation) by Human Pharmaceuticals; availability. Notice.

    Science.gov (United States)

    2005-10-20

    The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "S7B Nonclinical Evaluation of the Potential for Delayed Ventricular Repolarization (QT Interval Prolongation) by Human Pharmaceuticals." The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance describes a nonclinical testing strategy for assessing the potential of a test substance to delay ventricular repolarization and includes information concerning nonclinical assays and an integrated risk assessment. The guidance is intended to facilitate the nonclinical assessment of the effects of pharmaceuticals on ventricular repolarization and proarrhythmic risk.

  16. QT Interval Prolongation Associated with Intramuscular Ziprasidone in Chinese Patients: A Case Report and a Comprehensive Literature Review with Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Xian-Bin Li

    2014-01-01

    Full Text Available Intramuscular (IM ziprasidone has been associated with QTc interval prolongations in patients with preexisting risk factors. A 23-year-old male Chinese schizophrenia patient experienced an increase of QTc interval of 83 milliseconds (ms after receiving 20 mg IM ziprasidone (baseline and increased QT/QTc were, respectively, 384/418 and 450/501. This was rated as a probable adverse drug reaction (ADR by the Liverpool ADR causality assessment tool. A systematic review including all types of trials reporting the effect of IM ziprasidone on the QTc interval prolongation identified 19 trials with a total of 1428 patients. Mean QTc change from baseline to end of each study was −3.7 to 12.8 ms after IM ziprasidone. Four randomized trials (3 of 4 published in Chinese were used to calculate a meta-analysis of QTc interval prolongation which showed no significant differences between IM ziprasidone and IM haloperidol groups (risk ratio 0.49 to 4.31, 95% confidence interval 0.09 to 19.68, P = 0.06 to 0.41. However, our review included two cases of patients who experienced symptoms probably related to QTc prolongation after IM ziprasidone. Thus, careful screening and close monitoring, including baseline ECG, should be considered in patients receiving IM ziprasidone for the first time.

  17. Electrocardiographic Screening for Prolonged QT Interval to Reduce Sudden Cardiac Death in Psychiatric Patients: A Cost-Effectiveness Analysis.

    Directory of Open Access Journals (Sweden)

    Antoine Poncet

    Full Text Available Sudden cardiac death is a leading cause of mortality in psychiatric patients. Long QT (LQT is common in this population and predisposes to Torsades-de-Pointes (TdP and subsequent mortality.To estimate the cost-effectiveness of electrocardiographic screening to detect LQT in psychiatric inpatients.We built a decision analytic model based on a decision tree to evaluate the cost-effectiveness and utility of LQT screening from a health care perspective. LQT proportion parameters were derived from an in-hospital cross-sectional study. We performed experts' elicitation to estimate the risk of TdP, given extent of QT prolongation. A TdP reduction of 65% after LQT detection was based on positive drug dechallenge rate and through adequate treatment and electrolyte adjustments. The base-case model uncertainty was assessed with one-way and probabilistic sensitivity analyses. Finally, the TdP related mortality and TdP avoidance parameters were varied in a two-way sensitivity analysis to assess their effect on the Incremental Cost-Effectiveness Ratio (ICER.Costs, Quality Ajusted Life Year (QALY, ICER, and probability of cost effectiveness thresholds ($ 10,000, $25,000, and $50,000 per QALY.In the base-case scenario, the numbers of patients needed to screen were 1128 and 2817 to avoid one TdP and one death, respectively. The ICER of systematic ECG screening was $8644 (95%CI, 3144-82 498 per QALY. The probability of cost-effectiveness was 96% at a willingness-to-pay of $50,000 for one QALY. In sensitivity analyses, results were sensitive to the case-fatality of TdP episodes and to the TdP reduction following the diagnosis of LQT.In psychiatric hospitals, performing systematic ECG screening at admission help reduce the number of sudden cardiac deaths in a cost-effective fashion.

  18. 药物致Q-T间期延长的文献分析%Literature Analysis of Drug-induced Q-T Interval Prolongation

    Institute of Scientific and Technical Information of China (English)

    穆维静; 任晓蕾; 张海英

    2013-01-01

    近年来,临床实践有许多药物都会导致Q-T间期延长甚至尖端扭转型室性心律失常(TdP)。本文通过对1979年-2013年国内医药期刊公开报道的药物致Q-T间期延长的个案进行统计和分析,总结了56个病例的一般情况、引起Q-T间期延长的药物、发生时间及转归等,致Q-T间期延长药物中排在前三位的分别为抗心律失常药、抗微生物药、抗组胺药。大部分患者在用药后一个月内出现,停药及对症治疗后好转。临床医师应正确地认识药物致Q-T间期延长发生机制和易感因素,才能保证临床安全有效地使用药物。%Many medications can cause QT prolongation and torsades de pointes ventricular tachycardia (TdP), which were gradually discovered in recent years. Based on year 1979-2013 domestic medical journals and public report about drug-induced QT prolongation were collected and analyzed. Total of 56 cases were collected and summarized in respect of general condition of patients, drugs involved, occurrence times of ADR, outcomes and so on. The top three classes of drugs causing Q-T interval prolongation are antiarrhythmic drugs, antimicrobials and antihistamines. Most ADRs occurred within one month after treatment. ADRs relieved after drug withdrawal and symptomatic treatment. Physicians should pay more attention to the medications’ mechanisms and risk factors of drug-induced Q-T interval prolongation to ensure medication administration safety.

  19. Prolongation of heart rate-corrected QT interval is a predictor of cardiac autonomic dysfunction in patients with systemic lupus erythematosus.

    Science.gov (United States)

    Nomura, Atsushi; Kishimoto, Mitsumasa; Takahashi, Osamu; Deshpande, Gautam A; Yamaguchi, Kenichi; Okada, Masato

    2014-05-01

    Heart rate-corrected QT interval duration (QTc) has been shown to be related to cardiac autonomic dysfunction in patients with diabetes mellitus, although this association has not been previously described in patients with systemic lupus erythematosus (SLE). We retrospectively reviewed the medical records of 91 SLE patients and 144 non-SLE connective tissue disease patients visiting our clinic from November 2010 to April 2011. We compared ambulatory heart rate identified by pulse measured by automated machine in an outpatient waiting area versus resting heart rate identified on prior screening electrocardiogram. Heart rate differences were analyzed in relation to QTc interval and other characteristics. Ambulatory and resting heart rate differences were larger among SLE patients with QTc prolongation (QTc > 430 ms) than those without QTc prolongation (mean difference, 15.9 vs. 9.6, p = 0.001). In multivariate analysis, differences in heart rate were associated with QTc prolongation (OR 1.10, 95 % CI 1.01-1.21; p = 0.038), independent of age, duration of disease, immunosuppressant use, hydroxychloroquine use, diabetes mellitus, cardiac abnormality, anti-Ro/SS-A antibody positivity, or resting heart rate. Cardiac autonomic dysfunction is a common manifestation of SLE and may be related to QTc prolongation.

  20. Beat-to-beat variability of QT intervals is increased in patients with drug-induced long-QT syndrome

    DEFF Research Database (Denmark)

    Hinterseer, Martin; Thomsen, Morten Bækgaard; Beckmann, Britt-Maria

    2008-01-01

    Torsades de pointes arrhythmias (TdP) occur by definition in the setting of prolonged QT intervals. Animal models of drug induced Long-QT syndrome (dLQTS) have shown higher predictive value for proarrhythmia with beat-to-beat variability of repolarization duration (BVR) when compared with QT inte...

  1. Q-T interval (QT(C)) in patients with cirrhosis: relation to vasoactive peptides and heart rate

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Gülberg, V; Fuglsang, S

    2007-01-01

    OBJECTIVE: Prolonged Q-T interval (QT) has been reported in patients with cirrhosis who also exhibit profound abnormalities in vasoactive peptides and often present with elevated heart rate (HR). The aim of this study was to relate QT to the circulating level of endothelins (ET-1 and ET-3) and ca...

  2. The Evaluation of a Borderline Long QT Interval in an Asymptomatic Patient.

    Science.gov (United States)

    Obeyesekere, Manoj N; Leong-Sit, Peter; Gula, Lorne J; Yee, Raymond; Skanes, Allan C; Klein, George J; Krahn, Andrew D

    2012-06-01

    QT prolongation on resting electrocardiography (ECG) is common, and the clinician is often challenged by the dilemma of excluding acquired causes and recognizing potential congenital long QT syndrome (LQTS). The hallmark of LQTS is an abnormally long QT interval. However, a normal or borderline long QT interval may be observed in up to 50% of patients with LQTS because of the intermittent nature of QT prolongation. This review presents an approach to evaluating the asymptomatic patient with a borderline long QT interval, which incorporates a comprehensive clinical assessment, rest and provocative ECG testing, and genetic testing when appropriate.

  3. Long QT interval in Turner syndrome – a high prevalence of LQTS gene mutations

    DEFF Research Database (Denmark)

    Trolle, Christian; Mortensen, Kristian Havmand; Pedersen, Lisbeth Nørum

    Objective: QT interval prolongation of unknown aetiology is common in Turner syndrome (TS). This study set out to explore the presence of known pathogenic long QT (LQT) mutations in TS and to examine the corrected QT interval (QTc) over time and relate the findings to the TS phenotype. Methods...

  4. Electrocardiographic QT interval and mortality: a meta-analysis

    Science.gov (United States)

    Zhang, Yiyi; Post, Wendy S.; Blasco-Colmenares, Elena; Dalal, Darshan; Tomaselli, Gordon F.; Guallar, Eliseo

    2011-01-01

    Background Extremely abnormal prolongation of the electrocardiographic QT interval is associated with malignant ventricular arrhythmias and sudden cardiac death. However, the implications of variations in QT-interval length within normal limits for mortality in the general population are still unclear. Methods We performed a meta-analysis to investigate the relation of QT interval with mortality endpoints. Inverse-variance weighted random-effects models were used to summarize the relative risks across studies. Twenty-three observational studies were included. Results The pooled relative risk estimates comparing the highest with the lowest categories of QT-interval length were 1.35 (95% confidence interval = 1.24–1.46) for total mortality, 1.51 (1.29–1.78) for cardiovascular mortality, 1.71 (1.36–2.15) for coronary heart disease mortality, and 1.44 (1.01–2.04) for sudden cardiac death. A 50 msec increase in QT interval was associated with a relative risk of 1.20 (1.15–1.26) for total mortality, 1.29 (1.15–1.46) for cardiovascular mortality, 1.49 (1.25–1.76) for coronary heart disease mortality, and 1.24 (0.97–1.60) for sudden cardiac death. Conclusions We found consistent associations between prolonged QT interval and increased risk of total, cardiovascular, coronary, and sudden cardiac death. QT-interval length is a determinant of mortality in the general population. PMID:21709561

  5. QT interval prolongation and type I hypersensitivity reaction caused by orally taken moxifloxacin%莫西沙星片致 QT 间期延长和速发型变态反应

    Institute of Scientific and Technical Information of China (English)

    欧登科; 周晓明; 陈愉; 肇丽梅; 赵立

    2014-01-01

    Mezlocillin sodium and sulbactam sodium for injection(2. 5 g,once every 12 hours)and azithromycin injection(0. 5 g,once daily)were given to a 23-year-old female patient due to the community-aquired mycoplasma pneumonia and acute purulent tonsillitis. On the eleventh day,the treatments above mentioned were changed to oral moxifloxacin 0. 4 g once daily because of the improvement of the patient's condition. Thirty minutes after the moxifloxacin administration for the first time,the patient felt chest tightness,palpitation,fever,and generalized flush accompanied by wheal and papula on her limbs and trunk. The electrocardiogram examination showed double directional or inverted T waves in the precordial leads and prolonged QT period with corrected QT interval 462 ms. Laboratory examination showed creatine kinase(CK)239 U/ L,isoenzyme of creatine kinase(CK-MB)35 U/ L. TypeⅠhypersensitivity reaction was diagnosed. Moxifloxacin was stopped and ananaphylaxis and supportive treatments were given immediately. Three days later,her skin symptoms disappeared,ECG examination result returned to normal. The levels of CK and CK-MB were 40 U/ L and 11 U/ L,respectively.%1例23岁女性患者因支原体肺炎合并急性化脓性扁桃体炎给予注射用美洛西林钠舒巴坦钠(2.5 g,1次/12 h)和阿奇霉素(0.5 g,1次/ d)静脉滴注,第11天因病情好转改为莫西沙星0.4 g口服,1次/ d。患者首次服用莫西沙星后约30 min 出现胸闷、心悸、气促、发热,接着出现颜面及全身潮红,四肢及躯干出现风团、红色丘疹伴瘙痒,心电图提示胸前导联 T 波双向、倒置,QT 间期延长,校正的 QT 间期为462 ms。实验室检查示肌酸激酶(CK)239 U/ L,CK 同工酶(CK-MB)35 U/ L。诊断为速发型过敏反应。停用莫西沙星并立即给予抗过敏治疗及对症处理,3 d 后皮肤症状消失,心电图正常,CK 40 U/ L,CK-MB 11 U/ L。

  6. Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization

    NARCIS (Netherlands)

    Arking, Dan E.; Pulit, Sara L.; Crotti, Lia; Van der Harst, Pim; Munroe, Patricia B.; Koopmann, Tamara T.; Sotoodehnia, Nona; Rossin, Elizabeth J.; Morley, Michael; Wang, Xinchen; Johnson, Andrew D.; Lundby, Alicia; Gudbjartsson, Daniel F.; Noseworthy, Peter A.; Eijgelsheim, Mark; Bradford, Yuki; Tarasov, Kirill V.; Dorr, Marcus; Miiller-Nurasyid, Martina; Lahtinen, Annukka M.; Nolte, Ilja M.; Smith, Albert Vernon; Bis, Joshua C.; Isaacs, Aaron; Newhouse, Stephen J.; Evans, Daniel S.; Post, Wendy S.; Waggott, Daryl; Lyytikainen, Leo-Pekka; Hicks, Andrew A.; Eisele, Lewin; Ellinghaus, David; Hayward, Caroline; Navarro, Pau; Ulivi, Sheila; Tanaka, Toshiko; Tester, David J.; Chatel, Stephanie; Gustafsson, Stefan; Kumari, Meena; Morris, Richard W.; Naluai, Asa T.; Padmanabhan, Sandosh; Kluttig, Alexander; Strohmer, Bernhard; Panayiotou, Andrie G.; Torres, Maria; Knoflach, Michael; Hubacek, Jaroslav A.; Slowikowski, Kamil; Raychaudhuri, Soumya; Kumar, Runjun D.; Harris, Tamara B.; Launer, Lenore J.; Shuldiner, Alan R.; Alonso, Alvaro; Bader, Joel S.; EhreT, Georg; Huang, Hailiang; Kao, W. H. Linda; Strait, James B.; Macfarlane, Peter W.; Brown, Morris; Caulfield, Mark J.; Samani, Nilesh J.; Kronenberg, Florian; Willeit, Johann; Smith, J. Gustav; Greiser, Karin H.; Schwabedissen, Henriette Meyer Zu; Werdan, Karl; Carella, Massimo; Zelante, Leopoldo; Heckbert, Susan R.; Psaty, Bruce M.; Rotter, Jerome I.; Kolcic, Ivana; Poagek, Ozren; Wright, Alan F.; Griffin, Maura; Daly, Mark J.; Arnar, David O.; Holm, Hilma; Thorsteinsdottir, Unnur; Denny, Joshua C.; Roden, Dan M.; Zuvich, Rebecca L.; Emilsson, Valur; Plump, Andrew S.; Larson, Martin G.; O'Donnell, Christopher J.; Yin, Xiaoyan; Bobboll, Marco; D'Adamo, Adamo P.; Iorio, Annamaria; Sinagra, Gianfranco; Carracedo, Angel; Cummings, Steven R.; Nalls, Michael A.; Jula, Antti; Kontula, Kimmo K.; Marjamaa, Annukka; Oikarinen, Lasse; Perola, Markus; Porthan, Kimmo; Erbe, Raimund; Hoffmann, Per; Jockel, Karl-Heinz; Kalsch, Hagen; Nothen, Markus M.; Den Hoed, Marcel; Loos, Ruth J. F.; Thelle, Dag S.; Gieger, Christian; Meitinger, Thomas; Perz, Siegfried; Peters, Annette; Pruchal, Hanna; Sinner, Moritz F.; Waldenberger, Melanie; De Boer, Rudolf A.; Franke, Lude; Van der Vleuten, Pieter A.; Beckmann, Britt Maria; Martens, Eimo; Bardail, Abdennasser; Hofman, Nynke; Wilde, Arthur A. M.; Behr, Elijah R.; Dalageorgou, Chrysoula; Giudicessi, John R.; Medeiros-Domingo, Argelia; Barc, Julien; Kyndt, Florence; Probst, Vincent; Ghidoni, Alice; Insolia, Roberto; Hamilton, Robert M.; Scherer, Stephen W.; Brandimarto, Jeffrey; Margulies, Kenneth; Moravec, Christine E.; Del Greco, Fabiola; Fuchsberger, Christian; O'Connell, Jeffrey R.; Lee, Wai K.; Watt, Graham C. M.; Campbell, Harry; Wild, Sarah H.; El Mokhtari, Nour E.; Frey, Norbert; Asselbergs, Folkert W.; Mateo Leach, Irene; Navis, Gerjan; Van den Berg, Maarten P.; Van Veldhuisen, Dirk J.; Kellis, Manolis; Krijthe, Bouwe P.; Franco, Oscar H.; Hofman, Albert; Kors, Jan A.; Uitterlinden, Andre G.; Witteman, Jacqueline C. M.; Kedenko, Lyudmyla; Lamina, Claudia; Oostra, Ben A.; Abecasis, Goncalo R.; Lakatta, Edward G.; Mulas, Antonella; Orru, Marco; Schlessinger, David; Uda, Manuela; Markus, Marcello R. P.; Volker, Uwe; Snieder, Harold; Spector, Timothy D.; Arnlov, Johan; Lind, Lars; Sundstrom, Johan; Syvanen, Ann-Christine; Kivimaki, Mika; Kahonen, Mika; Mononen, Nina; Raitakari, I. T.; Viikari, Jorma S.; Adamkova, Vera; Kiech, Stefan; Brion, Maria; Nicolaides, Andrew N.; Paulweber, Bernhard; Haerting, Johannes; Dominiczak, Anna F.; Nyberg, Fredrik; Whincup, Peter H.; Hingorani, Aroon D.; Schott, Jean-Jacques; Bezzina, Connie R.; Ingelsson, Erik; Ferrucci, Luigi; Gaspariniin, Paolo; Wilson, James F.; Rudan, Igor; Franke, Andre; Miihleisen, Thomas W.; Pramstaller, Peter P.; Lehtimaki, Terho J.; Paterson, Andrew D.; Parsa, Afshin; Liu, Yongmei; Van Duijn, Cornelia M.; Siscovick, David S.; Gudnason, Vilmundur; Jamshidi, Yalda; Salomaa, Veikko; Felix, Stephan B.; Sanna, Serena; Ritchie, Marylyn D.; Stricker, Bruno H.; Stefansson, Karl; Boyer, Laurie A.; Cappola, Thomas P.; Olsen, Jesper V.; Lage, Kasper; Schwartz, Peter J.; Kaab, Stefan; Chakravarti, Aravinda; Ackerman, Michael J.; Pfeufer, Arne; De Bakker, Paul I. W.; Newton-Cheh, Christopher

    2014-01-01

    The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using

  7. Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization

    NARCIS (Netherlands)

    D.E. Arking (Dan); S.L. Pulit (Sara); L. Crotti (Lia); P. van der Harst (Pim); P. Munroe (Patricia); T.T. Koopmann (Tamara); N. Sotoodehnia (Nona); E. Rossin (Elizabeth); M. Morley (Michael); X. Wang (Xinchen); A.D. Johnson (Andrew); A. Lundby (Alicia); D.F. Gudbjartsson (Daniel); P.A. Noseworthy (Peter); M. Eijgelsheim (Mark); Y. Bradford (Yuki); K.V. Tarasov (Kirill); M. Dörr (Marcus); M. Müller-Nurasyid (Martina); A.M. Lahtinen (Annukka); I.M. Nolte (Ilja); G.D. Smith; J.C. Bis (Joshua); A.J. Isaacs (Aaron); S.J. Newhouse (Stephen); D.S. Evans (Daniel); W.S. Post (Wendy S.); D. Waggott (Daryl); L.-P. Lyytikäinen (Leo-Pekka); A.A. Hicks (Andrew); L. Eisele (Lewin); D. Ellinghaus (David); C. Hayward (Caroline); P. Navarro (Pau); S. Ulivi (Shelia); T. Tanaka (Toshiko); D.J. Tester (David); S. Chatel (Stéphanie); S. Gustafsson (Stefan); M. Kumari (Meena); R. Morris (Richard); A.T. Naluai (Asa); S. Padmanabhan (Sandosh); A. Kluttig (Alexander); B. Strohmer (Bernhard); A.G. Panayiotou (Andrie); M. Torres (Maria); M. Knoflach (Michael); J.A. Hubacek (Jaroslav A.); K. Slowikowski (Kamil); S. Raychaudhuri (Soumya); R.D. Kumar (Runjun); T.B. Harris (Tamara); L.J. Launer (Lenore); A.R. Shuldiner (Alan); A. Alonso (Alvaro); J.S. Bader (Joel); G.B. Ehret (Georg); H. Huang (Hailiang); W.H.L. Kao (Wen); J.B. Strait (James); P.W. Macfarlane (Peter); M.J. Brown (Morris); M. Caulfield (Mark); N.J. Samani (Nilesh); F. Kronenberg (Florian); J. Willeit (Johann); J.G. Smith (J. Gustav); K.H. Greiser (Karin Halina); H.M. Zu Schwabedissen (Henriette Meyer); K. Werdan (Karl); C. Carella (Cintia); L. Zelante (Leopoldo); S.R. Heckbert (Susan); B.M. Psaty (Bruce); J.I. Rotter (Jerome); I. Kolcic (Ivana); O. Polasek (Ozren); A.F. Wright (Alan); M. Griffin (Maura); M.J. Daly (Mark); D.O. Arnar (David); H. Hólm (Hilma); U. Thorsteinsdottir (Unnur); J.C. Denny (Joshua); D.M. Roden (Dan); R.L. Zuvich (Rebecca); V. Emilsson (Valur); A.S. Plump (Andrew); M.G. Larson (Martin); C.J. O'Donnell (Christopher); X. Yin (Xiaoyan); M. Bobbo (Marco); P. d' Adamo (Pio); A. Iorio (Annamaria); G. Sinagra (Gianfranco); A. Carracedo (Angel); S.R. Cummings (Steven); M.A. Nalls (Michael); A. Jula (Antti); K.K. Kontula (Kimmo); A. Marjamaa (Annukka); L. Oikarinen (Lasse); M. Perola (Markus); K. Porthan (Kimmo); R. Erbel (Raimund); P. Hoffmann (Per); K.-H. Jöckel (Karl-Heinz); H. Kälsch (Hagen); M.M. Nöthen (Markus); M. den Hoed (Marcel); R.J.F. Loos (Ruth); D.S. Thelle (Dag); C. Gieger (Christian); T. Meitinger (Thomas); S. Perz (Siegfried); A. Peters (Annette); H. Prucha (Hanna); M.F. Sinner (Moritz); M. Waldenberger (Melanie); R.A. de Boer (Rudolf); L. Franke (Lude); P.A. van der Vleuten (Pieter); B.M. Beckmann (Britt); E. Martens (Eimo); A. Bardai (Abdennasser); N. Hofman (Nynke); A.A.M. Wilde (Arthur); E.R. Behr (Elijah ); C. Dalageorgou (Chrysoula); J.R. Giudicessi (John); A. Medeiros-Domingo (Argelia); J. Barc (Julien); F. Kyndt (Florence); V. Probst (Vincent); A. Ghidoni (Alice); R. Insolia (Roberto); R.M. Hamilton (Robert); S.W. Scherer (Stephen); J. Brandimarto (Jeffrey); K. Margulies (Kenneth); C.E. Moravec (Christine); F. Del Greco M (Fabiola); C. Fuchsberger (Christian); J.R. O'Connell (Jeffery); W.K. Lee (Wai); G.C.M. Watt (Graham); H. Campbell (Harry); S.H. Wild (Sarah); N.E. El Mokhtari (Nour); N. Frey (Norbert); F.W. Asselbergs (Folkert); I.M. Leach (Irene Mateo); G. Navis (Gerjan); M.P. van den Berg (Maarten); D.J. van Veldhuisen (Dirk); M. Kellis (Manolis); B.P. Krijthe (Bouwe); O.H. Franco (Oscar); A. Hofman (Albert); J.A. Kors (Jan); A.G. Uitterlinden (André); J.C.M. Witteman (Jacqueline); L. Kedenko (Lyudmyla); C. Lamina (Claudia); B.A. Oostra (Ben); G.R. Abecasis (Gonçalo); E. Lakatta (Edward); A. Mulas (Antonella); M. Orrù (Marco); D. Schlessinger (David); M. Uda (Manuela); M.R.P. Markus (Marcello R. P.); U. Völker (Uwe); H. Snieder (Harold); T.D. Spector (Timothy); J. Ärnlöv (Johan); L. Lind (Lars); J. Sundstrom (Johan); A.C. Syvanen; M. Kivimaki (Mika); M. Kähönen (Mika); K. Mononen (Kari); O. Raitakari (Olli); J. Viikari (Jorma); V. Adamkova (Vera); S. Kiechl (Stefan); M.-J. Brion (Maria); A.N. Nicolaides (Andrew); B. Paulweber (Bernhard); J. Haerting (Johannes); A. Dominiczak (Anna); F. Nyberg (Fredrik); P.H. Whincup (Peter); A. Hingorani (Aroon); J.-J. Schott (Jean-Jacques); C.R. Bezzina (Connie); E. Ingelsson (Erik); L. Ferrucci (Luigi); P. Gasparini (Paolo); J.F. Wilson (James); I. Rudan (Igor); A. Franke (Andre); T.W. Mühleisen (Thomas); P.P. Pramstaller (Peter Paul); T. Lehtimäki (Terho); A.D. Paterson (Andrew); A. Parsa (Afshin); Y. Liu (Yongmei); C.M. van Duijn (Cock); D.S. Siscovick (David); V. Gudnason (Vilmundur); Y. Jamshidi (Yalda); V. Salomaa (Veikko); S.B. Felix (Stephan); S. Sanna (Serena); M.D. Ritchie (Marylyn); B.H.Ch. Stricker (Bruno); J-A. Zwart (John-Anker); L.A. Boyer (Laurie); T.P. Cappola (Thomas); J.V. Olsen (Jesper); P. Lage (Pedro); P.J. Schwartz (Peter); S. Kääb (Stefan); A. Chakravarti (Aravinda); M. Ackerman (Margaret); A. Pfeufer (Arne); P.I.W. de Bakker (Paul); C. Newton-Cheh (Christopher)

    2014-01-01

    textabstractThe QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (L

  8. Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization

    NARCIS (Netherlands)

    D.E. Arking (Dan); S.L. Pulit (Sara); L. Crotti (Lia); P. van der Harst (Pim); P. Munroe (Patricia); T.T. Koopmann (Tamara); N. Sotoodehnia (Nona); E. Rossin (Elizabeth); M. Morley (Michael); X. Wang (Xinchen); A.D. Johnson (Andrew); A. Lundby (Alicia); D.F. Gudbjartsson (Daniel); P.A. Noseworthy (Peter); M. Eijgelsheim (Mark); Y. Bradford (Yuki); K.V. Tarasov (Kirill); M. Dörr (Marcus); M. Müller-Nurasyid (Martina); A.M. Lahtinen (Annukka); I.M. Nolte (Ilja); G.D. Smith; J.C. Bis (Joshua); A.J. Isaacs (Aaron); S.J. Newhouse (Stephen); D.S. Evans (Daniel); W.S. Post (Wendy S.); D. Waggott (Daryl); L.-P. Lyytikäinen (Leo-Pekka); A.A. Hicks (Andrew); L. Eisele (Lewin); D. Ellinghaus (David); C. Hayward (Caroline); P. Navarro (Pau); S. Ulivi (Shelia); T. Tanaka (Toshiko); D.J. Tester (David); S. Chatel (Stéphanie); S. Gustafsson (Stefan); M. Kumari (Meena); R. Morris (Richard); A.T. Naluai (Asa); S. Padmanabhan (Sandosh); A. Kluttig (Alexander); B. Strohmer (Bernhard); A.G. Panayiotou (Andrie); M. Torres (Maria); M. Knoflach (Michael); J.A. Hubacek (Jaroslav A.); K. Slowikowski (Kamil); S. Raychaudhuri (Soumya); R.D. Kumar (Runjun); T.B. Harris (Tamara); L.J. Launer (Lenore); A.R. Shuldiner (Alan); A. Alonso (Alvaro); J.S. Bader (Joel); G.B. Ehret (Georg); H. Huang (Hailiang); W.H.L. Kao (Wen); J.B. Strait (James); P.W. Macfarlane (Peter); M.J. Brown (Morris); M. Caulfield (Mark); N.J. Samani (Nilesh); F. Kronenberg (Florian); J. Willeit (Johann); J.G. Smith (J. Gustav); K.H. Greiser (Karin Halina); H.M. Zu Schwabedissen (Henriette Meyer); K. Werdan (Karl); C. Carella (Cintia); L. Zelante (Leopoldo); S.R. Heckbert (Susan); B.M. Psaty (Bruce); J.I. Rotter (Jerome); I. Kolcic (Ivana); O. Polasek (Ozren); A.F. Wright (Alan); M. Griffin (Maura); M.J. Daly (Mark); D.O. Arnar (David); H. Hólm (Hilma); U. Thorsteinsdottir (Unnur); J.C. Denny (Joshua); D.M. Roden (Dan); R.L. Zuvich (Rebecca); V. Emilsson (Valur); A.S. Plump (Andrew); M.G. Larson (Martin); C.J. O'Donnell (Christopher); X. Yin (Xiaoyan); M. Bobbo (Marco); P. d' Adamo (Pio); A. Iorio (Annamaria); G. Sinagra (Gianfranco); A. Carracedo (Angel); S.R. Cummings (Steven); M.A. Nalls (Michael); A. Jula (Antti); K.K. Kontula (Kimmo); A. Marjamaa (Annukka); L. Oikarinen (Lasse); M. Perola (Markus); K. Porthan (Kimmo); R. Erbel (Raimund); P. Hoffmann (Per); K.-H. Jöckel (Karl-Heinz); H. Kälsch (Hagen); M.M. Nöthen (Markus); M. den Hoed (Marcel); R.J.F. Loos (Ruth); D.S. Thelle (Dag); C. Gieger (Christian); T. Meitinger (Thomas); S. Perz (Siegfried); A. Peters (Annette); H. Prucha (Hanna); M.F. Sinner (Moritz); M. Waldenberger (Melanie); R.A. de Boer (Rudolf); L. Franke (Lude); P.A. van der Vleuten (Pieter); B.M. Beckmann (Britt); E. Martens (Eimo); A. Bardai (Abdennasser); N. Hofman (Nynke); A.A.M. Wilde (Arthur); E.R. Behr (Elijah ); C. Dalageorgou (Chrysoula); J.R. Giudicessi (John); A. Medeiros-Domingo (Argelia); J. Barc (Julien); F. Kyndt (Florence); V. Probst (Vincent); A. Ghidoni (Alice); R. Insolia (Roberto); R.M. Hamilton (Robert); S.W. Scherer (Stephen); J. Brandimarto (Jeffrey); K. Margulies (Kenneth); C.E. Moravec (Christine); F. Del Greco M (Fabiola); C. Fuchsberger (Christian); J.R. O'Connell (Jeffery); W.K. Lee (Wai); G.C.M. Watt (Graham); H. Campbell (Harry); S.H. Wild (Sarah); N.E. El Mokhtari (Nour); N. Frey (Norbert); F.W. Asselbergs (Folkert); I.M. Leach (Irene Mateo); G. Navis (Gerjan); M.P. van den Berg (Maarten); D.J. van Veldhuisen (Dirk); M. Kellis (Manolis); B.P. Krijthe (Bouwe); O.H. Franco (Oscar); A. Hofman (Albert); J.A. Kors (Jan); A.G. Uitterlinden (André); J.C.M. Witteman (Jacqueline); L. Kedenko (Lyudmyla); C. Lamina (Claudia); B.A. Oostra (Ben); G.R. Abecasis (Gonçalo); E. Lakatta (Edward); A. Mulas (Antonella); M. Orrù (Marco); D. Schlessinger (David); M. Uda (Manuela); M.R.P. Markus (Marcello R. P.); U. Völker (Uwe); H. Snieder (Harold); T.D. Spector (Timothy); J. Ärnlöv (Johan); L. Lind (Lars); J. Sundstrom (Johan); A.C. Syvanen; M. Kivimaki (Mika); M. Kähönen (Mika); K. Mononen (Kari); O. Raitakari (Olli); J. Viikari (Jorma); V. Adamkova (Vera); S. Kiechl (Stefan); M.-J. Brion (Maria); A.N. Nicolaides (Andrew); B. Paulweber (Bernhard); J. Haerting (Johannes); A. Dominiczak (Anna); F. Nyberg (Fredrik); P.H. Whincup (Peter); A. Hingorani (Aroon); J.-J. Schott (Jean-Jacques); C.R. Bezzina (Connie); E. Ingelsson (Erik); L. Ferrucci (Luigi); P. Gasparini (Paolo); J.F. Wilson (James); I. Rudan (Igor); A. Franke (Andre)

    2014-01-01

    textabstractThe QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome

  9. Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization

    NARCIS (Netherlands)

    Arking, Dan E.; Pulit, Sara L.; Crotti, Lia; Van der Harst, Pim; Munroe, Patricia B.; Koopmann, Tamara T.; Sotoodehnia, Nona; Rossin, Elizabeth J.; Morley, Michael; Wang, Xinchen; Johnson, Andrew D.; Lundby, Alicia; Gudbjartsson, Daniel F.; Noseworthy, Peter A.; Eijgelsheim, Mark; Bradford, Yuki; Tarasov, Kirill V.; Dorr, Marcus; Miiller-Nurasyid, Martina; Lahtinen, Annukka M.; Nolte, Ilja M.; Smith, Albert Vernon; Bis, Joshua C.; Isaacs, Aaron; Newhouse, Stephen J.; Evans, Daniel S.; Post, Wendy S.; Waggott, Daryl; Lyytikainen, Leo-Pekka; Hicks, Andrew A.; Eisele, Lewin; Ellinghaus, David; Hayward, Caroline; Navarro, Pau; Ulivi, Sheila; Tanaka, Toshiko; Tester, David J.; Chatel, Stephanie; Gustafsson, Stefan; Kumari, Meena; Morris, Richard W.; Naluai, Asa T.; Padmanabhan, Sandosh; Kluttig, Alexander; Strohmer, Bernhard; Panayiotou, Andrie G.; Torres, Maria; Knoflach, Michael; Hubacek, Jaroslav A.; Slowikowski, Kamil; Raychaudhuri, Soumya; Kumar, Runjun D.; Harris, Tamara B.; Launer, Lenore J.; Shuldiner, Alan R.; Alonso, Alvaro; Bader, Joel S.; EhreT, Georg; Huang, Hailiang; Kao, W. H. Linda; Strait, James B.; Macfarlane, Peter W.; Brown, Morris; Caulfield, Mark J.; Samani, Nilesh J.; Kronenberg, Florian; Willeit, Johann; Smith, J. Gustav; Greiser, Karin H.; Schwabedissen, Henriette Meyer Zu; Werdan, Karl; Carella, Massimo; Zelante, Leopoldo; Heckbert, Susan R.; Psaty, Bruce M.; Rotter, Jerome I.; Kolcic, Ivana; Poagek, Ozren; Wright, Alan F.; Griffin, Maura; Daly, Mark J.; Arnar, David O.; Holm, Hilma; Thorsteinsdottir, Unnur; Denny, Joshua C.; Roden, Dan M.; Zuvich, Rebecca L.; Emilsson, Valur; Plump, Andrew S.; Larson, Martin G.; O'Donnell, Christopher J.; Yin, Xiaoyan; Bobboll, Marco; D'Adamo, Adamo P.; Iorio, Annamaria; Sinagra, Gianfranco; Carracedo, Angel; Cummings, Steven R.; Nalls, Michael A.; Jula, Antti; Kontula, Kimmo K.; Marjamaa, Annukka; Oikarinen, Lasse; Perola, Markus; Porthan, Kimmo; Erbe, Raimund; Hoffmann, Per; Jockel, Karl-Heinz; Kalsch, Hagen; Nothen, Markus M.; Den Hoed, Marcel; Loos, Ruth J. F.; Thelle, Dag S.; Gieger, Christian; Meitinger, Thomas; Perz, Siegfried; Peters, Annette; Pruchal, Hanna; Sinner, Moritz F.; Waldenberger, Melanie; De Boer, Rudolf A.; Franke, Lude; Van der Vleuten, Pieter A.; Beckmann, Britt Maria; Martens, Eimo; Bardail, Abdennasser; Hofman, Nynke; Wilde, Arthur A. M.; Behr, Elijah R.; Dalageorgou, Chrysoula; Giudicessi, John R.; Medeiros-Domingo, Argelia; Barc, Julien; Kyndt, Florence; Probst, Vincent; Ghidoni, Alice; Insolia, Roberto; Hamilton, Robert M.; Scherer, Stephen W.; Brandimarto, Jeffrey; Margulies, Kenneth; Moravec, Christine E.; Del Greco, Fabiola; Fuchsberger, Christian; O'Connell, Jeffrey R.; Lee, Wai K.; Watt, Graham C. M.; Campbell, Harry; Wild, Sarah H.; El Mokhtari, Nour E.; Frey, Norbert; Asselbergs, Folkert W.; Mateo Leach, Irene; Navis, Gerjan; Van den Berg, Maarten P.; Van Veldhuisen, Dirk J.; Kellis, Manolis; Krijthe, Bouwe P.; Franco, Oscar H.; Hofman, Albert; Kors, Jan A.; Uitterlinden, Andre G.; Witteman, Jacqueline C. M.; Kedenko, Lyudmyla; Lamina, Claudia; Oostra, Ben A.; Abecasis, Goncalo R.; Lakatta, Edward G.; Mulas, Antonella; Orru, Marco; Schlessinger, David; Uda, Manuela; Markus, Marcello R. P.; Volker, Uwe; Snieder, Harold; Spector, Timothy D.; Arnlov, Johan; Lind, Lars; Sundstrom, Johan; Syvanen, Ann-Christine; Kivimaki, Mika; Kahonen, Mika; Mononen, Nina; Raitakari, I. T.; Viikari, Jorma S.; Adamkova, Vera; Kiech, Stefan; Brion, Maria; Nicolaides, Andrew N.; Paulweber, Bernhard; Haerting, Johannes; Dominiczak, Anna F.; Nyberg, Fredrik; Whincup, Peter H.; Hingorani, Aroon D.; Schott, Jean-Jacques; Bezzina, Connie R.; Ingelsson, Erik; Ferrucci, Luigi; Gaspariniin, Paolo; Wilson, James F.; Rudan, Igor; Franke, Andre; Miihleisen, Thomas W.; Pramstaller, Peter P.; Lehtimaki, Terho J.; Paterson, Andrew D.; Parsa, Afshin; Liu, Yongmei; Van Duijn, Cornelia M.; Siscovick, David S.; Gudnason, Vilmundur; Jamshidi, Yalda; Salomaa, Veikko; Felix, Stephan B.; Sanna, Serena; Ritchie, Marylyn D.; Stricker, Bruno H.; Stefansson, Karl; Boyer, Laurie A.; Cappola, Thomas P.; Olsen, Jesper V.; Lage, Kasper; Schwartz, Peter J.; Kaab, Stefan; Chakravarti, Aravinda; Ackerman, Michael J.; Pfeufer, Arne; De Bakker, Paul I. W.; Newton-Cheh, Christopher

    The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using

  10. Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization

    NARCIS (Netherlands)

    D.E. Arking (Dan); S.L. Pulit (Sara); L. Crotti (Lia); P. van der Harst (Pim); P. Munroe (Patricia); T.T. Koopmann (Tamara); N. Sotoodehnia (Nona); E. Rossin (Elizabeth); M. Morley (Michael); X. Wang (Xinchen); A.D. Johnson (Andrew); A. Lundby (Alicia); D.F. Gudbjartsson (Daniel); P.A. Noseworthy (Peter); M. Eijgelsheim (Mark); Y. Bradford (Yuki); K.V. Tarasov (Kirill); M. Dörr (Marcus); M. Müller-Nurasyid (Martina); A.M. Lahtinen (Annukka); I.M. Nolte (Ilja); G.D. Smith; J.C. Bis (Joshua); A.J. Isaacs (Aaron); S.J. Newhouse (Stephen); D.S. Evans (Daniel); W.S. Post (Wendy S.); D. Waggott (Daryl); L.-P. Lyytikäinen (Leo-Pekka); A.A. Hicks (Andrew); L. Eisele (Lewin); D. Ellinghaus (David); C. Hayward (Caroline); P. Navarro (Pau); S. Ulivi (Shelia); T. Tanaka (Toshiko); D.J. Tester (David); S. Chatel (Stéphanie); S. Gustafsson (Stefan); M. Kumari (Meena); R. Morris (Richard); A.T. Naluai (Asa); S. Padmanabhan (Sandosh); A. Kluttig (Alexander); B. Strohmer (Bernhard); A.G. Panayiotou (Andrie); M. Torres (Maria); M. Knoflach (Michael); J.A. Hubacek (Jaroslav A.); K. Slowikowski (Kamil); S. Raychaudhuri (Soumya); R.D. Kumar (Runjun); T.B. Harris (Tamara); L.J. Launer (Lenore); A.R. Shuldiner (Alan); A. Alonso (Alvaro); J.S. Bader (Joel); G.B. Ehret (Georg); H. Huang (Hailiang); W.H.L. Kao (Wen); J.B. Strait (James); P.W. Macfarlane (Peter); M.J. Brown (Morris); M. Caulfield (Mark); N.J. Samani (Nilesh); F. Kronenberg (Florian); J. Willeit (Johann); J.G. Smith (J. Gustav); K.H. Greiser (Karin Halina); H.M. Zu Schwabedissen (Henriette Meyer); K. Werdan (Karl); C. Carella (Cintia); L. Zelante (Leopoldo); S.R. Heckbert (Susan); B.M. Psaty (Bruce); J.I. Rotter (Jerome); I. Kolcic (Ivana); O. Polasek (Ozren); A.F. Wright (Alan); M. Griffin (Maura); M.J. Daly (Mark); D.O. Arnar (David); H. Hólm (Hilma); U. Thorsteinsdottir (Unnur); J.C. Denny (Joshua); D.M. Roden (Dan); R.L. Zuvich (Rebecca); V. Emilsson (Valur); A.S. Plump (Andrew); M.G. Larson (Martin); C.J. O'Donnell (Christopher); X. Yin (Xiaoyan); M. Bobbo (Marco); P. d' Adamo (Pio); A. Iorio (Annamaria); G. Sinagra (Gianfranco); A. Carracedo (Angel); S.R. Cummings (Steven); M.A. Nalls (Michael); A. Jula (Antti); K.K. Kontula (Kimmo); A. Marjamaa (Annukka); L. Oikarinen (Lasse); M. Perola (Markus); K. Porthan (Kimmo); R. Erbel (Raimund); P. Hoffmann (Per); K.-H. Jöckel (Karl-Heinz); H. Kälsch (Hagen); M.M. Nöthen (Markus); M. den Hoed (Marcel); R.J.F. Loos (Ruth); D.S. Thelle (Dag); C. Gieger (Christian); T. Meitinger (Thomas); S. Perz (Siegfried); A. Peters (Annette); H. Prucha (Hanna); M.F. Sinner (Moritz); M. Waldenberger (Melanie); R.A. de Boer (Rudolf); L. Franke (Lude); P.A. van der Vleuten (Pieter); B.M. Beckmann (Britt); E. Martens (Eimo); A. Bardai (Abdennasser); N. Hofman (Nynke); A.A.M. Wilde (Arthur); E.R. Behr (Elijah ); C. Dalageorgou (Chrysoula); J.R. Giudicessi (John); A. Medeiros-Domingo (Argelia); J. Barc (Julien); F. Kyndt (Florence); V. Probst (Vincent); A. Ghidoni (Alice); R. Insolia (Roberto); R.M. Hamilton (Robert); S.W. Scherer (Stephen); J. Brandimarto (Jeffrey); K. Margulies (Kenneth); C.E. Moravec (Christine); F. Del Greco M (Fabiola); C. Fuchsberger (Christian); J.R. O'Connell (Jeffery); W.K. Lee (Wai); G.C.M. Watt (Graham); H. Campbell (Harry); S.H. Wild (Sarah); N.E. El Mokhtari (Nour); N. Frey (Norbert); F.W. Asselbergs (Folkert); I.M. Leach (Irene Mateo); G. Navis (Gerjan); M.P. van den Berg (Maarten); D.J. van Veldhuisen (Dirk); M. Kellis (Manolis); B.P. Krijthe (Bouwe); O.H. Franco (Oscar); A. Hofman (Albert); J.A. Kors (Jan); A.G. Uitterlinden (André); J.C.M. Witteman (Jacqueline); L. Kedenko (Lyudmyla); C. Lamina (Claudia); B.A. Oostra (Ben); G.R. Abecasis (Gonçalo); E. Lakatta (Edward); A. Mulas (Antonella); M. Orrù (Marco); D. Schlessinger (David); M. Uda (Manuela); M.R.P. Markus (Marcello R. P.); U. Völker (Uwe); H. Snieder (Harold); T.D. Spector (Timothy); J. Ärnlöv (Johan); L. Lind (Lars); J. Sundstrom (Johan); A.C. Syvanen; M. Kivimaki (Mika); M. Kähönen (Mika); K. Mononen (Kari); O. Raitakari (Olli); J. Viikari (Jorma); V. Adamkova (Vera); S. Kiechl (Stefan); M.-J. Brion (Maria); A.N. Nicolaides (Andrew); B. Paulweber (Bernhard); J. Haerting (Johannes); A. Dominiczak (Anna); F. Nyberg (Fredrik); P.H. Whincup (Peter); A. Hingorani (Aroon); J.-J. Schott (Jean-Jacques); C.R. Bezzina (Connie); E. Ingelsson (Erik); L. Ferrucci (Luigi); P. Gasparini (Paolo); J.F. Wilson (James); I. Rudan (Igor); A. Franke (Andre); T.W. Mühleisen (Thomas); P.P. Pramstaller (Peter Paul); T. Lehtimäki (Terho); A.D. Paterson (Andrew); A. Parsa (Afshin); Y. Liu (Yongmei); C.M. van Duijn (Cock); D.S. Siscovick (David); V. Gudnason (Vilmundur); Y. Jamshidi (Yalda); V. Salomaa (Veikko); S.B. Felix (Stephan); S. Sanna (Serena); M.D. Ritchie (Marylyn); B.H.Ch. Stricker (Bruno); J-A. Zwart (John-Anker); L.A. Boyer (Laurie); T.P. Cappola (Thomas); J.V. Olsen (Jesper); P. Lage (Pedro); P.J. Schwartz (Peter); S. Kääb (Stefan); A. Chakravarti (Aravinda); M. Ackerman (Margaret); A. Pfeufer (Arne); P.I.W. de Bakker (Paul); C. Newton-Cheh (Christopher)

    2014-01-01

    textabstractThe QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (L

  11. Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization

    NARCIS (Netherlands)

    Arking, Dan E.; Pulit, Sara L.; Crotti, Lia; Van der Harst, Pim; Munroe, Patricia B.; Koopmann, Tamara T.; Sotoodehnia, Nona; Rossin, Elizabeth J.; Morley, Michael; Wang, Xinchen; Johnson, Andrew D.; Lundby, Alicia; Gudbjartsson, Daniel F.; Noseworthy, Peter A.; Eijgelsheim, Mark; Bradford, Yuki; Tarasov, Kirill V.; Dorr, Marcus; Miiller-Nurasyid, Martina; Lahtinen, Annukka M.; Nolte, Ilja M.; Smith, Albert Vernon; Bis, Joshua C.; Isaacs, Aaron; Newhouse, Stephen J.; Evans, Daniel S.; Post, Wendy S.; Waggott, Daryl; Lyytikainen, Leo-Pekka; Hicks, Andrew A.; Eisele, Lewin; Ellinghaus, David; Hayward, Caroline; Navarro, Pau; Ulivi, Sheila; Tanaka, Toshiko; Tester, David J.; Chatel, Stephanie; Gustafsson, Stefan; Kumari, Meena; Morris, Richard W.; Naluai, Asa T.; Padmanabhan, Sandosh; Kluttig, Alexander; Strohmer, Bernhard; Panayiotou, Andrie G.; Torres, Maria; Knoflach, Michael; Hubacek, Jaroslav A.; Slowikowski, Kamil; Raychaudhuri, Soumya; Kumar, Runjun D.; Harris, Tamara B.; Launer, Lenore J.; Shuldiner, Alan R.; Alonso, Alvaro; Bader, Joel S.; EhreT, Georg; Huang, Hailiang; Kao, W. H. Linda; Strait, James B.; Macfarlane, Peter W.; Brown, Morris; Caulfield, Mark J.; Samani, Nilesh J.; Kronenberg, Florian; Willeit, Johann; Smith, J. Gustav; Greiser, Karin H.; Schwabedissen, Henriette Meyer Zu; Werdan, Karl; Carella, Massimo; Zelante, Leopoldo; Heckbert, Susan R.; Psaty, Bruce M.; Rotter, Jerome I.; Kolcic, Ivana; Poagek, Ozren; Wright, Alan F.; Griffin, Maura; Daly, Mark J.; Arnar, David O.; Holm, Hilma; Thorsteinsdottir, Unnur; Denny, Joshua C.; Roden, Dan M.; Zuvich, Rebecca L.; Emilsson, Valur; Plump, Andrew S.; Larson, Martin G.; O'Donnell, Christopher J.; Yin, Xiaoyan; Bobboll, Marco; D'Adamo, Adamo P.; Iorio, Annamaria; Sinagra, Gianfranco; Carracedo, Angel; Cummings, Steven R.; Nalls, Michael A.; Jula, Antti; Kontula, Kimmo K.; Marjamaa, Annukka; Oikarinen, Lasse; Perola, Markus; Porthan, Kimmo; Erbe, Raimund; Hoffmann, Per; Jockel, Karl-Heinz; Kalsch, Hagen; Nothen, Markus M.; Den Hoed, Marcel; Loos, Ruth J. F.; Thelle, Dag S.; Gieger, Christian; Meitinger, Thomas; Perz, Siegfried; Peters, Annette; Pruchal, Hanna; Sinner, Moritz F.; Waldenberger, Melanie; De Boer, Rudolf A.; Franke, Lude; Van der Vleuten, Pieter A.; Beckmann, Britt Maria; Martens, Eimo; Bardail, Abdennasser; Hofman, Nynke; Wilde, Arthur A. M.; Behr, Elijah R.; Dalageorgou, Chrysoula; Giudicessi, John R.; Medeiros-Domingo, Argelia; Barc, Julien; Kyndt, Florence; Probst, Vincent; Ghidoni, Alice; Insolia, Roberto; Hamilton, Robert M.; Scherer, Stephen W.; Brandimarto, Jeffrey; Margulies, Kenneth; Moravec, Christine E.; Del Greco, Fabiola; Fuchsberger, Christian; O'Connell, Jeffrey R.; Lee, Wai K.; Watt, Graham C. M.; Campbell, Harry; Wild, Sarah H.; El Mokhtari, Nour E.; Frey, Norbert; Asselbergs, Folkert W.; Mateo Leach, Irene; Navis, Gerjan; Van den Berg, Maarten P.; Van Veldhuisen, Dirk J.; Kellis, Manolis; Krijthe, Bouwe P.; Franco, Oscar H.; Hofman, Albert; Kors, Jan A.; Uitterlinden, Andre G.; Witteman, Jacqueline C. M.; Kedenko, Lyudmyla; Lamina, Claudia; Oostra, Ben A.; Abecasis, Goncalo R.; Lakatta, Edward G.; Mulas, Antonella; Orru, Marco; Schlessinger, David; Uda, Manuela; Markus, Marcello R. P.; Volker, Uwe; Snieder, Harold; Spector, Timothy D.; Arnlov, Johan; Lind, Lars; Sundstrom, Johan; Syvanen, Ann-Christine; Kivimaki, Mika; Kahonen, Mika; Mononen, Nina; Raitakari, I. T.; Viikari, Jorma S.; Adamkova, Vera; Kiech, Stefan; Brion, Maria; Nicolaides, Andrew N.; Paulweber, Bernhard; Haerting, Johannes; Dominiczak, Anna F.; Nyberg, Fredrik; Whincup, Peter H.; Hingorani, Aroon D.; Schott, Jean-Jacques; Bezzina, Connie R.; Ingelsson, Erik; Ferrucci, Luigi; Gaspariniin, Paolo; Wilson, James F.; Rudan, Igor; Franke, Andre; Miihleisen, Thomas W.; Pramstaller, Peter P.; Lehtimaki, Terho J.; Paterson, Andrew D.; Parsa, Afshin; Liu, Yongmei; Van Duijn, Cornelia M.; Siscovick, David S.; Gudnason, Vilmundur; Jamshidi, Yalda; Salomaa, Veikko; Felix, Stephan B.; Sanna, Serena; Ritchie, Marylyn D.; Stricker, Bruno H.; Stefansson, Karl; Boyer, Laurie A.; Cappola, Thomas P.; Olsen, Jesper V.; Lage, Kasper; Schwartz, Peter J.; Kaab, Stefan; Chakravarti, Aravinda; Ackerman, Michael J.; Pfeufer, Arne; De Bakker, Paul I. W.; Newton-Cheh, Christopher

    2014-01-01

    The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using

  12. The dark side of the QT interval. The Short QT Syndrome: pathophysiology, clinical presentation and management

    Directory of Open Access Journals (Sweden)

    I. Comelli

    2012-12-01

    Full Text Available A large number of studies has been carried out to investigate the pathophysiology and the clinical implications of QT interval prolongation in the ECG over recent years (1, 2, 3, 4, 5, 6. It was only in the last decade, however, that the scientists have focused on the specular aspects of the long QT syndrome (LQTS, and it is now well established that the abnormal shortening of the QT interval is associated with meaningful clinical consequences and adverse outcomes. The aim of the present article is to summarize knowledge and existing evidence about the Short QT Syndrome (SQTS. SQTS is a rare, albeit largely underdiagnosed, genetically determined disease, which is characterized by a high tendency to develop life-threatening arrhythmias. The two clinical landmarks of SQTS are the presence of a short QT interval (i.e., less than 320 ms in a structurally normal heart. The disease is now classified as a “channellopathy”, and is principally caused by a defective functioning of both potassium and calcium ion channels. The underlying genetic anomalies cause an abnormal ripolarization and a reduced refractoriness of myocardiocites. Pharmacologic treatments are mainly tailored to slow the conduction and to prolong the refractory period of myocardiocites. The implantable cardioverter and defibrillator (ICD is currently considered the therapeutic gold standard (7.

  13. Drug-Induced QT Prolongation as a Result of an Escitalopram Overdose in a Patient with Previously Undiagnosed Congenital Long QT Syndrome

    Directory of Open Access Journals (Sweden)

    Paul Singh

    2014-01-01

    Full Text Available We present a case of drug-induced QT prolongation caused by an escitalopram overdose in a patient with previously undiagnosed congenital LQTS. A 15-year-old Caucasian female presented following a suicide attempt via an escitalopram overdose. The patient was found to have a prolonged QT interval with episodes of torsades de pointes. The patient was admitted to the telemetry unit and treated. Despite the resolution of the torsades de pointes, she continued to demonstrate a persistently prolonged QT interval. She was seen by the cardiology service and diagnosed with congenital long QT syndrome. This case illustrates the potential for an escitalopram overdose to cause an acute QT prolongation in a patient with congenital LQTS and suggests the importance of a screening electrocardiogram prior to the initiation of SSRIs, especially in patients at high risk for QT prolongation.

  14. Circadian profile of QT interval and QT interval variability in 172 healthy volunteers

    DEFF Research Database (Denmark)

    Bonnemeier, Hendrik; Wiegand, Uwe K H; Braasch, Wiebke

    2003-01-01

    of sleep. QT and R-R intervals revealed a characteristic day-night-pattern. Diurnal profiles of QT interval variability exhibited a significant increase in the morning hours (6-9 AM; P ...-to-beat QT interval duration (QT, QTapex [QTa], Tend [Te]), variability (QTSD, QTaSD), and the mean R-R interval were determined from 24-hour ambulatory electrocardiograms after exclusion of artifacts and premature beats. All volunteers were fully active, awoke at approximately 7:00 AM, and had 6-8 hours...... alterations mainly at daytime with normal aging. Furthermore, the diurnal course of the QT interval variability strongly suggests that it is related to cardiac sympathetic activity and to the reported diurnal pattern of malignant ventricular arrhythmias....

  15. Clinical assessment of drug-induced QT prolongation in association with heart rate changes.

    Science.gov (United States)

    Extramiana, Fabrice; Maison-Blanche, Pierre; Cabanis, Marie-José; Ortemann-Renon, Catherine; Beaufils, Philippe; Leenhardt, Antoine

    2005-04-01

    The formulas for heart rate (HR) correction of QT interval have been shown to overcorrect or undercorrect this interval with changes in HR. A Holter-monitoring method avoiding the need for any correction formulas is proposed as a means to assess drug-induced QT interval changes. A thorough QT study included 2 single doses of the alpha1-adrenergic receptor blocker alfuzosin, placebo, and a QT-positive control arm (moxifloxacin) in 48 healthy subjects. Bazett, Fridericia, population-specific (QTcN), and subject-specific (QTcNi) correction formulas were applied to 12-lead electrocardio-graphic recording data. QT1000 (QT at RR = 1000 ms), QT largest bin (at the largest sample size bin), and QT average (average QT of all RR bins) were obtained from Holter recordings by use of custom software to perform rate-independent QT analysis. The 3 Holter end points provided similar results, as follows: Moxifloxacin-induced QT prolongation was 7.0 ms (95% confidence interval [CI], 4.4-9.6 ms) for QT1000, 6.9 ms (95% CI, 4.8-9.1 ms) for QT largest bin, and 6.6 ms (95% CI, 4.6-8.6 ms) for QT average. At the therapeutic dose (10 mg), alfuzosin did not induce significant change in the QT. The 40-mg dose of alfuzosin increased HR by 3.7 beats/min and induced a small QT1000 increase of 2.9 ms (95% CI, 0.3-5.5 ms) (QTcN, +4.6 ms [95% CI, 2.1-7.0 ms]; QTcNi, +4.7 ms [95% CI, 2.2-7.1 ms]). Data corrected by "universal" correction formulas still showed rate dependency and yielded larger QTc change estimations. The Holter method was able to show the drug-induced changes in QT rate dependence. The direct Holter-based QT interval measurement method provides an alternative approach to measure rate-independent estimates of QT interval changes during treatment.

  16. Drug-induced QT-interval shortening following antiepileptic treatment with oral rufinamide.

    Science.gov (United States)

    Schimpf, Rainer; Veltmann, Christian; Papavassiliu, Theano; Rudic, Boris; Göksu, Turgay; Kuschyk, Jürgen; Wolpert, Christian; Antzelevitch, Charles; Ebner, Alois; Borggrefe, Martin; Brandt, Christian

    2012-05-01

    The arrhythmogenic potential of short QT intervals has recently been highlighted in patients with a short QT syndrome. Drug-induced QT-interval prolongation is a known risk factor for ventricular tachyarrhythmias. However, reports on drug-induced QT-interval shortening are rare and proarrhythmic effects remain unclear. Recently, rufinamide, a new antiepileptic drug for the add-on treatment of Lennox-Gastaut syndrome, was approved in the European Union and the United States. Initial trials showed drug-induced QT-interval shortening. The aim of our study was to evaluate the effects of rufinamide on QT intervals in patients with difficult-to-treat epilepsies. Nineteen consecutive patients with Lennox-Gastaut syndrome and other epilepsy syndromes were included (n = 12 men; mean age 41 ± 12 years). QRS, QT, and T(peak)-T(end) intervals were analyzed before and during rufinamide treatment. The mean QT interval shortened significantly following rufinamide administration (QT interval 349 ± 23 ms vs 327 ± 17 ms; corrected QT interval 402 ± 22 ms vs 382 ± 16 ms; P = .002). T(peak)-T(end) intervals were 79 ± 17 ms before and 70 ± 20 ms on treatment (P = .07). The mean reduction of the corrected QT interval was 20 ± 18 ms. During follow-up (3.04 ± 1.09 years), no adverse events including symptomatic cardiac arrhythmias or sudden cardiac deaths were observed. QTc-interval shortening following oral rufinamide administration in a small patient group was not associated with significant clinical adverse effects. These observations notwithstanding, the ability of rufinamide to significantly shorten the QT interval portends a potential arrhythmogenic risk that may best be guarded against by periodic electrocardiographic recordings. Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  17. Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization

    DEFF Research Database (Denmark)

    Arking, Dan E; Pulit, Sara L; Crotti, Lia

    2014-01-01

    The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Usi....... Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD. © 2014 Nature America, Inc....

  18. Greater insulin resistance indicates decreased diurnal variation in the QT interval in patients with type 2 diabetes.

    Science.gov (United States)

    Tanaka, Kotoko; Yodogawa, Kenji; Ono, Takuya; Yana, Kazuo; Miyamoto, Masaaki; Atarashi, Hirotsugu; Kato, Takao; Mizuno, Kyoichi

    2014-03-01

    Circadian variations in the QT interval (QT) and QT dispersion are decreased in patients with type 2 diabetes because of cardioneuropathy. Insulin resistance has been recently identified as an independent determinant of QT prolongation in normoglycemic women. However, the relationship between QT prolongation and the degree of insulin resistance as well as circadian variation remains unclear in diabetic patients. This study was designed to assess the relationship between insulin resistance and the circadian variation in QT measurements in patients with type 2 diabetes. In 14 patients with diabetes, QT, corrected QT (QTc), QT dispersion, QTc dispersion, and RR interval (RR) were analyzed using 12-lead Holter monitoring and commercial software. The degree of diurnal variation in each measurement was defined as the amplitude between the maximum and mean values on curves fitted using the mean cosinor method (A_QT, A_QTc, A_QT dispersion, A_QTc dispersion, and A_RR). The cosine curve was fitted to all measured values in each QT measurement and RR for 24 h. Insulin resistance (glucose infusion rate (GIR)) was measured using the euglycemic hyperinsulinemic glucose clamp method. The maximum QT, QTc, QT dispersion, and QTc dispersion were >450 ms. GIR was significantly correlated with A_QT only (r = 0.59, P < 0.05). GIR was not correlated with other variables, and was dependent only on the circadian variation in QT.

  19. Electrocardiographic corrected QT interval prolongation and its risk factors in patients with clozapine treatment%氯氮平治疗相关心电图校正QT间期延长及其危险因素

    Institute of Scientific and Technical Information of China (English)

    吕建宝; 张向阳; 李娟; 杨甫德

    2014-01-01

    目的:调查精神分裂症患者在氯氮平治疗期间心电图校正QT间期(corrected QT interval,QTc)的变化及其相关因素。方法收集使用氯氮平治疗的210例精神分裂症患者,检测心肌酶等生化指标,检查心电图,按Bazett’s公式计算QTc间期,并以桡动脉搏动次数作为心率。结果 QTc间期延长发生率15.24%,女性QTc间期延长发生率高于男性(29.23%vs.8.98%),差异有统计学意义(P0.05)。多因素线性回归分析示,心率与QTc间期有关联(β=0.719,标准化β=0.691,P=0.027)。结论精神分裂症患者在氯氮平治疗期间QTc间期延长发生率高,心率快可能是其危险因素。%Objective To investigate risk factors of corrected QT (QTc) interval prolongation in schizophrenia pa-tients treated with clozapine. Methods Two hundred and ten schizophrenia patients treated with clozapine were included in the study. Measurement of myocardial enzymes and electrocardiography were performed to determine QTc interval. QTc interval was calculated according to Bazett’s formula. Results QTc prolongation prevalence rate was 15.24%, The QTc prolongation prevalence rate was higher in female than in male (29.23%vs. 8.98%, P0.05). Multi-factors linear regression analysis showed that heart rate was related with QTc interval (β=0.719, standardizedβ=0.691, P=0.027). Conclusions QTc interval prolonga-tion prevalence rate is high in patients treated with clozapine. And increased heart rate might be risk factor of QTc inter-val prolongation.

  20. Relationship between QT interval and ventricular electrical axis: A new suggestion for Lead selection in QT interval measurement

    OpenAIRE

    "Moradman S; Hatamizadeh P "

    2000-01-01

    Exploration of the interlead QT variation (QT dispersion) introduced cardiologists to some new concepts including the deed to define a standard for lead selection in the measurement of QT interval and the reason or factors contributing to QT dispersion. Hoseever, still there dose not exist a generally acceptable standard for lead selection and the reason for the QT dispersion has not been given the importance it deserves. Only a few hypotheses have been suggested, none of which have been seri...

  1. Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization

    Science.gov (United States)

    Arking, Dan E.; Pulit, Sara L.; Crotti, Lia; van der Harst, Pim; Munroe, Patricia B.; Koopmann, Tamara T.; Sotoodehnia, Nona; Rossin, Elizabeth J.; Morley, Michael; Wang, Xinchen; Johnson, Andrew D.; Lundby, Alicia; Gudbjartsson, Daníel F.; Noseworthy, Peter A.; Eijgelsheim, Mark; Bradford, Yuki; Tarasov, Kirill V.; Dörr, Marcus; Müller-Nurasyid, Martina; Lahtinen, Annukka M.; Nolte, Ilja M.; Smith, Albert Vernon; Bis, Joshua C.; Isaacs, Aaron; Newhouse, Stephen J.; Evans, Daniel S.; Post, Wendy S.; Waggott, Daryl; Lyytikäinen, Leo-Pekka; Hicks, Andrew A.; Eisele, Lewin; Ellinghaus, David; Hayward, Caroline; Navarro, Pau; Ulivi, Sheila; Tanaka, Toshiko; Tester, David J.; Chatel, Stéphanie; Gustafsson, Stefan; Kumari, Meena; Morris, Richard W.; Naluai, Åsa T.; Padmanabhan, Sandosh; Kluttig, Alexander; Strohmer, Bernhard; Panayiotou, Andrie G.; Torres, Maria; Knoflach, Michael; Hubacek, Jaroslav A.; Slowikowski, Kamil; Raychaudhuri, Soumya; Kumar, Runjun D.; Harris, Tamara B.; Launer, Lenore J.; Shuldiner, Alan R.; Alonso, Alvaro; Bader, Joel S.; Ehret, Georg; Huang, Hailiang; Kao, W.H. Linda; Strait, James B.; Macfarlane, Peter W.; Brown, Morris; Caulfield, Mark J.; Samani, Nilesh J.; Kronenberg, Florian; Willeit, Johann; Smith, J. Gustav; Greiser, Karin H.; zu Schwabedissen, Henriette Meyer; Werdan, Karl; Carella, Massimo; Zelante, Leopoldo; Heckbert, Susan R.; Psaty, Bruce M.; Rotter, Jerome I.; Kolcic, Ivana; Polašek, Ozren; Wright, Alan F.; Griffin, Maura; Daly, Mark J.; Arnar, David O.; Hólm, Hilma; Thorsteinsdottir, Unnur; Denny, Joshua C.; Roden, Dan M.; Zuvich, Rebecca L.; Emilsson, Valur; Plump, Andrew S.; Larson, Martin G.; O'Donnell, Christopher J.; Yin, Xiaoyan; Bobbo, Marco; D'Adamo, Adamo P.; Iorio, Annamaria; Sinagra, Gianfranco; Carracedo, Angel; Cummings, Steven R.; Nalls, Michael A.; Jula, Antti; Kontula, Kimmo K.; Marjamaa, Annukka; Oikarinen, Lasse; Perola, Markus; Porthan, Kimmo; Erbel, Raimund; Hoffmann, Per; Jöckel, Karl-Heinz; Kälsch, Hagen; Nöthen, Markus M.; consortium, HRGEN; den Hoed, Marcel; Loos, Ruth J.F.; Thelle, Dag S.; Gieger, Christian; Meitinger, Thomas; Perz, Siegfried; Peters, Annette; Prucha, Hanna; Sinner, Moritz F.; Waldenberger, Melanie; de Boer, Rudolf A.; Franke, Lude; van der Vleuten, Pieter A.; Beckmann, Britt Maria; Martens, Eimo; Bardai, Abdennasser; Hofman, Nynke; Wilde, Arthur A.M.; Behr, Elijah R.; Dalageorgou, Chrysoula; Giudicessi, John R.; Medeiros-Domingo, Argelia; Barc, Julien; Kyndt, Florence; Probst, Vincent; Ghidoni, Alice; Insolia, Roberto; Hamilton, Robert M.; Scherer, Stephen W.; Brandimarto, Jeffrey; Margulies, Kenneth; Moravec, Christine E.; Fabiola Del, Greco M.; Fuchsberger, Christian; O'Connell, Jeffrey R.; Lee, Wai K.; Watt, Graham C.M.; Campbell, Harry; Wild, Sarah H.; El Mokhtari, Nour E.; Frey, Norbert; Asselbergs, Folkert W.; Leach, Irene Mateo; Navis, Gerjan; van den Berg, Maarten P.; van Veldhuisen, Dirk J.; Kellis, Manolis; Krijthe, Bouwe P.; Franco, Oscar H.; Hofman, Albert; Kors, Jan A.; Uitterlinden, André G.; Witteman, Jacqueline C.M.; Kedenko, Lyudmyla; Lamina, Claudia; Oostra, Ben A.; Abecasis, Gonçalo R.; Lakatta, Edward G.; Mulas, Antonella; Orrú, Marco; Schlessinger, David; Uda, Manuela; Markus, Marcello R.P.; Völker, Uwe; Snieder, Harold; Spector, Timothy D.; Ärnlöv, Johan; Lind, Lars; Sundström, Johan; Syvänen, Ann-Christine; Kivimaki, Mika; Kähönen, Mika; Mononen, Nina; Raitakari, Olli T.; Viikari, Jorma S.; Adamkova, Vera; Kiechl, Stefan; Brion, Maria; Nicolaides, Andrew N.; Paulweber, Bernhard; Haerting, Johannes; Dominiczak, Anna F.; Nyberg, Fredrik; Whincup, Peter H.; Hingorani, Aroon; Schott, Jean-Jacques; Bezzina, Connie R.; Ingelsson, Erik; Ferrucci, Luigi; Gasparini, Paolo; Wilson, James F.; Rudan, Igor; Franke, Andre; Mühleisen, Thomas W.; Pramstaller, Peter P.; Lehtimäki, Terho J.; Paterson, Andrew D.; Parsa, Afshin; Liu, Yongmei; van Duijn, Cornelia; Siscovick, David S.; Gudnason, Vilmundur; Jamshidi, Yalda; Salomaa, Veikko; Felix, Stephan B.; Sanna, Serena; Ritchie, Marylyn D.; Stricker, Bruno H.; Stefansson, Kari; Boyer, Laurie A.; Cappola, Thomas P.; Olsen, Jesper V.; Lage, Kasper; Schwartz, Peter J.; Kääb, Stefan; Chakravarti, Aravinda; Ackerman, Michael J.; Pfeufer, Arne; de Bakker, Paul I.W.; Newton-Cheh, Christopher

    2014-01-01

    The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal Mendelian Long QT Syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals we identified 35 common variant QT interval loci, that collectively explain ∼8-10% of QT variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 novel QT loci in 298 unrelated LQTS probands identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode for proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies novel candidate genes for ventricular arrhythmias, LQTS,and SCD. PMID:24952745

  2. T(peak)T(end) interval in long QT syndrome

    DEFF Research Database (Denmark)

    Kanters, Jørgen Kim; Haarmark, Christian; Vedel-Larsen, Esben;

    2008-01-01

    to the occurrence of syncope. METHODS: Electrocardiograms were taken in 95 patients with LQTS drawn from the Danish long QT registry (44 patients with KvLQT1, 43 with HERG, and 8 with SCN5A mutations) and manually evaluated for the QT, QT(peak), and RR interval. RESULTS AND CONCLUSION: (1) T(p)T(e) cannot be used...

  3. [Effect of olopatadine hydrochloride, a novel antiallergic agent, on the QT interval in dogs].

    Science.gov (United States)

    Iwamoto, K; Ikeda, J; Nito, M; Kosaka, N; Ichikawa, S; Kobayashi, H; Ohmori, K

    2001-06-01

    Olopatadine hydrochloride (olopatadine), a novel antiallergic agent, is effective in the treatment of allergic rhinitis, chronic urticaria, eczema and dermatitis. It has been reported that terfenadine and astemizole cause side effects on the circulatory system such as QT prolongation followed by serious ventricular arrhythmias (torsades de pointes). To investigate the possibility of QT prolongation, we used both conscious normal dogs and hypokalemia-anesthetized dogs under two conditions: 1) olopatadine used alone and 2) olopatadine used in combination with itraconazole, the CYP3A4-inhibiting antifungal agent, in the present investigation. The group treated with terfenadine alone (30 mg/kg, p.o.) and the group treated with a combination of terfenadine (10 mg/kg, p.o.) and itraconazole (100 mg/kg, p.o.) had a significantly prolonged QT interval. On the other hand, the group treated with olopatadine alone (30 mg/kg, p.o.) and the group treated with a combination of olopatadine (30 mg/kg, p.o.) and itraconazole (100 mg/kg, p.o.) did not show any significant changes in QT interval. Moreover, olopatadine (1 and 5 mg/kg, i.v.) did not influence the QT interval in hypokalemia-anesthetized dogs. These results suggest that there is very little possibility of QT prolongation as a result of clinically used olopatadine.

  4. Randomized, double-blind, placebo-controlled clinical trial of a two-day regimen of dihydroartemisinin-piperaquine for malaria prevention halted for concern over prolonged corrected QT interval.

    Science.gov (United States)

    Manning, Jessica; Vanachayangkul, Pattaraporn; Lon, Chanthap; Spring, Michele; So, Mary; Sea, Darapiseth; Se, Youry; Somethy, Sok; Phann, Sut-Thang; Chann, Soklyda; Sriwichai, Sabaithip; Buathong, Nillawan; Kuntawunginn, Worachet; Mitprasat, Mashamon; Siripokasupkul, Raveewan; Teja-Isavadharm, Paktiya; Soh, Eugene; Timmermans, Ans; Lanteri, Charlotte; Kaewkungwal, Jaranit; Auayporn, Montida; Tang, Douglas; Chour, Char Meng; Prom, Satharath; Haigney, Mark; Cantilena, Louis; Saunders, David

    2014-10-01

    Dihydroartemisinin-piperaquine, the current first-line drug for uncomplicated malaria caused by Plasmodium falciparum and Plasmodium vivax in Cambodia, was previously shown to be of benefit as malaria chemoprophylaxis when administered as a monthly 3-day regimen. We sought to evaluate the protective efficacy of a compressed monthly 2-day treatment course in the Royal Cambodian Armed Forces. The safety and efficacy of a monthly 2-day dosing regimen of dihydroartemisinin-piperaquine were evaluated in a two-arm, randomized, double-blind, placebo-controlled cohort study with 2:1 treatment allocation. Healthy military volunteers in areas along the Thai-Cambodian border where there is a high risk of malaria were administered two consecutive daily doses of 180 mg dihydroartemisinin and 1,440 mg piperaquine within 30 min to 3 h of a meal once per month for a planned 4-month period with periodic electrocardiographic and pharmacokinetic assessment. The study was halted after only 6 weeks (69 of 231 projected volunteers enrolled) when four volunteers met a prespecified cardiac safety endpoint of QTcF (Fridericia's formula for correct QT interval) prolongation of >500 ms. The pharmacodynamic effect on the surface electrocardiogram (ECG) peaked approximately 4 h after piperaquine dosing and lasted 4 to 8 h. Unblinded review by the data safety monitoring board revealed mean QTcF prolongation of 46 ms over placebo at the maximum concentration of drug in serum (Cmax) on day 2. Given that dihydroartemisinin-piperaquine is one of the few remaining effective antimalarial agents in Cambodia, compressed 2-day treatment courses of dihydroartemisinin-piperaquine are best avoided until the clinical significance of these findings are more thoroughly evaluated. Because ECG monitoring is often unavailable in areas where malaria is endemic, repolarization risk could be mitigated by using conventional 3-day regimens, fasting, and avoidance of repeated dosing or coadministration with other QT-prolonging

  5. Abnormalities of the QT interval in primary disorders of autonomic failure

    Science.gov (United States)

    Choy, A. M.; Lang, C. C.; Roden, D. M.; Robertson, D.; Wood, A. J.; Robertson, R. M.; Biaggioni, I.

    1998-01-01

    BACKGROUND: Experimental evidence shows that activation of the autonomic nervous system influences ventricular repolarization and, therefore, the QT interval on the ECG. To test the hypothesis that the QT interval is abnormal in autonomic dysfunction, we examined ECGs in patients with severe primary autonomic failure and in patients with congenital dopamine beta-hydroxylase (DbetaH) deficiency who are unable to synthesize norepinephrine and epinephrine. SUBJECTS AND METHODS: Maximal QT and rate-corrected QT (QTc) intervals and adjusted QTc dispersion [(maximal QTc - minimum QTc on 12 lead ECG)/square root of the number of leads measured] were determined in blinded fashion from ECGs of 67 patients with primary autonomic failure (36 patients with multiple system atrophy [MSA], and 31 patients with pure autonomic failure [PAF]) and 17 age- and sex-matched healthy controls. ECGs of 5 patients with congenital DbetaH deficiency and 6 age- and sex-matched controls were also analyzed. RESULTS: Patients with MSA and PAF had significantly prolonged maximum QTc intervals (492+/-58 ms(1/2) and 502+/-61 ms(1/2) [mean +/- SD]), respectively, compared with controls (450+/-18 ms(1/2), P parasympathetic and sympathetic failure have abnormally prolonged QT interval and increased QT dispersion. However, QT interval in patients with congenital DbetaH deficiency was not significantly different from controls. It is possible, therefore, that QT abnormalities in patients with primary autonomic failure are not solely caused by lesions of the sympathetic nervous system, and that the parasympathetic nervous system is likely to have a modulatory role in ventricular repolarization.

  6. Nomenclature,categorization and usage of formulae to adjust QT interval for heart rate

    Institute of Scientific and Technical Information of China (English)

    Simon; W; Rabkin; Xin; Bo; Cheng

    2015-01-01

    Assessment of the QT interval on a standard 12 lead electrocardiogram is of value in the recognition of a number of conditions. A critical part of its use is the adjustment for the effect of heart rate on QT interval. A systematic search was conducted to identify studiesthat proposed formulae to standardize the QT interval by heart rate. A nomenclature was developed for current and subsequent equations based on whether they are corrective(QTc) or predictive(QTp). QTc formulae attempt to separate the dependence of the length of the QT interval from the length of the RR interval. QTp formulae utilize heart rate and the output QTp is compared to the uncorrected QT interval. The nomenclature consists of the first letter of the first author’s name followed by the next two consonance(whenever possible) in capital letters; with subscripts in lower case alphabetical letter if the first author develops more than one equation. The single exception was the Framingham equation,because this cohort has developed its own "name" amongst cardiovascular studies. Equations were further categorized according to whether they were linear,rational,exponential,logarithmic,or power based. Data show that a person’s QT interval adjusted for heart rate can vary dramatically with the different QTc and QTp formulae depending on the person’s heart rate and QT interval. The differences in the QT interval adjustment equations encompasses values that are considered normal or significant prolonged. To further compare the equations,we considered that the slope of QTc versus heart rate should be zero if there was no correlation between QT and heart rate. Reviewing a sample of 107 patient ECGs from a hospital setting,the rank order of the slope- from best(closest to zero) to worst was QTc DMT,QTc RTHa,QTc HDG,QTc GOT,QTcF RM,QTcF RD,QTcB ZT and QTcM YD. For two recent formulae based on large data sets specifically QTcD MT and QTcR THa,there was no significant deviation of the slope from zero. In

  7. Increased persistent sodium current due to decreased PI3K signaling contributes to QT prolongation in the diabetic heart.

    Science.gov (United States)

    Lu, Zhongju; Jiang, Ya-Ping; Wu, Chia-Yen C; Ballou, Lisa M; Liu, Shengnan; Carpenter, Eileen S; Rosen, Michael R; Cohen, Ira S; Lin, Richard Z

    2013-12-01

    Diabetes is an independent risk factor for sudden cardiac death and ventricular arrhythmia complications of acute coronary syndrome. Prolongation of the QT interval on the electrocardiogram is also a risk factor for arrhythmias and sudden death, and the increased prevalence of QT prolongation is an independent risk factor for cardiovascular death in diabetic patients. The pathophysiological mechanisms responsible for this lethal complication are poorly understood. Diabetes is associated with a reduction in phosphoinositide 3-kinase (PI3K) signaling, which regulates the action potential duration (APD) of individual myocytes and thus the QT interval by altering multiple ion currents, including the persistent sodium current INaP. Here, we report a mechanism for diabetes-induced QT prolongation that involves an increase in INaP caused by defective PI3K signaling. Cardiac myocytes of mice with type 1 or type 2 diabetes exhibited an increase in APD that was reversed by expression of constitutively active PI3K or intracellular infusion of phosphatidylinositol 3,4,5-trisphosphate (PIP3), the second messenger produced by PI3K. The diabetic myocytes also showed an increase in INaP that was reversed by activated PI3K or PIP3. The increases in APD and INaP in myocytes translated into QT interval prolongation for both types of diabetic mice. The long QT interval of type 1 diabetic hearts was shortened by insulin treatment ex vivo, and this effect was blocked by a PI3K inhibitor. Treatment of both types of diabetic mouse hearts with an INaP blocker also shortened the QT interval. These results indicate that downregulation of cardiac PI3K signaling in diabetes prolongs the QT interval at least in part by causing an increase in INaP. This mechanism may explain why the diabetic population has an increased risk of life-threatening arrhythmias.

  8. QT interval changes in term pregnant women living at moderately ...

    African Journals Online (AJOL)

    2015-12-20

    Dec 20, 2015 ... Objective: This study aimed to compare the QT interval changes in women with term pregnancy living at ... as an increase in circulating volume, heart rate, and cardiac ..... exercise before and after an himalayan expedition.

  9. Increased Short-Term Beat-To-Beat Variability of QT Interval in Patients with Acromegaly.

    Science.gov (United States)

    Orosz, Andrea; Csajbók, Éva; Czékus, Csilla; Gavallér, Henriette; Magony, Sándor; Valkusz, Zsuzsanna; Várkonyi, Tamás T; Nemes, Attila; Baczkó, István; Forster, Tamás; Wittmann, Tibor; Papp, Julius Gy; Varró, András; Lengyel, Csaba

    2015-01-01

    Cardiovascular diseases, including ventricular arrhythmias are responsible for increased mortality in patients with acromegaly. Acromegaly may cause repolarization abnormalities such as QT prolongation and impairment of repolarization reserve enhancing liability to arrhythmia. The aim of this study was to determine the short-term beat-to-beat QT variability in patients with acromegaly. Thirty acromegalic patients (23 women and 7 men, mean age±SD: 55.7±10.4 years) were compared with age- and sex-matched volunteers (mean age 51.3±7.6 years). Cardiac repolarization parameters including frequency corrected QT interval, PQ and QRS intervals, duration of terminal part of T waves (Tpeak-Tend) and short-term variability of QT interval were evaluated. All acromegalic patients and controls underwent transthoracic echocardiographic examination. Autonomic function was assessed by means of five standard cardiovascular reflex tests. Comparison of the two groups revealed no significant differences in the conventional ECG parameters of repolarization (QT: 401.1±30.6 ms vs 389.3±16.5 ms, corrected QT interval: 430.1±18.6 ms vs 425.6±17.3 ms, QT dispersion: 38.2±13.2 ms vs 36.6±10.2 ms; acromegaly vs control, respectively). However, short-term beat-to-beat QT variability was significantly increased in acromegalic patients (4.23±1.03 ms vs 3.02±0.80, Pacromegaly in spite of unchanged conventional parameters of ventricular repolarization. This enhanced temporal QT variability may be an early indicator of increased liability to arrhythmia.

  10. Increased Short-Term Beat-To-Beat Variability of QT Interval in Patients with Acromegaly

    Science.gov (United States)

    Orosz, Andrea; Csajbók, Éva; Czékus, Csilla; Gavallér, Henriette; Magony, Sándor; Valkusz, Zsuzsanna; Várkonyi, Tamás T.; Nemes, Attila; Baczkó, István; Forster, Tamás; Wittmann, Tibor; Papp, Julius Gy.; Varró, András; Lengyel, Csaba

    2015-01-01

    Cardiovascular diseases, including ventricular arrhythmias are responsible for increased mortality in patients with acromegaly. Acromegaly may cause repolarization abnormalities such as QT prolongation and impairment of repolarization reserve enhancing liability to arrhythmia. The aim of this study was to determine the short-term beat-to-beat QT variability in patients with acromegaly. Thirty acromegalic patients (23 women and 7 men, mean age±SD: 55.7±10.4 years) were compared with age- and sex-matched volunteers (mean age 51.3±7.6 years). Cardiac repolarization parameters including frequency corrected QT interval, PQ and QRS intervals, duration of terminal part of T waves (Tpeak-Tend) and short-term variability of QT interval were evaluated. All acromegalic patients and controls underwent transthoracic echocardiographic examination. Autonomic function was assessed by means of five standard cardiovascular reflex tests. Comparison of the two groups revealed no significant differences in the conventional ECG parameters of repolarization (QT: 401.1±30.6 ms vs 389.3±16.5 ms, corrected QT interval: 430.1±18.6 ms vs 425.6±17.3 ms, QT dispersion: 38.2±13.2 ms vs 36.6±10.2 ms; acromegaly vs control, respectively). However, short-term beat-to-beat QT variability was significantly increased in acromegalic patients (4.23±1.03 ms vs 3.02±0.80, Pacromegaly in spite of unchanged conventional parameters of ventricular repolarization. This enhanced temporal QT variability may be an early indicator of increased liability to arrhythmia. PMID:25915951

  11. Coupling Data Mining and Laboratory Experiments to Discover Drug Interactions Causing QT Prolongation.

    Science.gov (United States)

    Lorberbaum, Tal; Sampson, Kevin J; Chang, Jeremy B; Iyer, Vivek; Woosley, Raymond L; Kass, Robert S; Tatonetti, Nicholas P

    2016-10-18

    QT interval-prolonging drug-drug interactions (QT-DDIs) may increase the risk of life-threatening arrhythmia. Despite guidelines for testing from regulatory agencies, these interactions are usually discovered after drugs are marketed and may go undiscovered for years. Using a combination of adverse event reports, electronic health records (EHR), and laboratory experiments, the goal of this study was to develop a data-driven pipeline for discovering QT-DDIs. 1.8 million adverse event reports were mined for signals indicating a QT-DDI. Using 1.6 million electrocardiogram results from 380,000 patients in our institutional EHR, these putative interactions were either refuted or corroborated. In the laboratory, we used patch-clamp electrophysiology to measure the human ether-à-go-go-related gene (hERG) channel block (the primary mechanism by which drugs prolong the QT interval) to evaluate our top candidate. Both direct and indirect signals in the adverse event reports provided evidence that the combination of ceftriaxone (a cephalosporin antibiotic) and lansoprazole (a proton-pump inhibitor) will prolong the QT interval. In the EHR, we found that patients taking both ceftriaxone and lansoprazole had significantly longer QTc intervals (up to 12 ms in white men) and were 1.4 times more likely to have a QTc interval above 500 ms. In the laboratory, we found that, in combination and at clinically relevant concentrations, these drugs blocked the hERG channel. As a negative control, we evaluated the combination of lansoprazole and cefuroxime (another cephalosporin), which lacked evidence of an interaction in the adverse event reports. We found no significant effect of this pair in either the EHR or in the electrophysiology experiments. Class effect analyses suggested this interaction was specific to lansoprazole combined with ceftriaxone but not with other cephalosporins. Coupling data mining and laboratory experiments is an efficient method for identifying QT

  12. Multivariate analysis of risk factors for QT prolongation following subarachnoid hemorrhage

    Science.gov (United States)

    Fukui, Shinji; Katoh, Hiroshi; Tsuzuki, Nobusuke; Ishihara, Shoichiro; Otani, Naoki; Ooigawa, Hidetoshi; Toyooka, Terushige; Ohnuki, Akira; Miyazawa, Takahito; Nawashiro, Hiroshi; Shima, Katsuji

    2003-01-01

    Background Subarachnoid hemorrhage (SAH) often causes a prolongation of the corrected QT (QTc) interval during the acute phase. The aim of the present study was to examine independent risk factors for QTc prolongation in patients with SAH by means of multivariate analysis. Method We studied 100 patients who were admitted within 24 hours after onset of SAH. Standard 12-lead electrocardiography (ECG) was performed immediately after admission. QT intervals were measured from the ECG and were corrected for heart rate using the Bazett formula. We measured serum levels of sodium, potassium, calcium, adrenaline (epinephrine), noradrenaline (norepinephrine), dopamine, antidiuretic hormone, and glucose. Results The average QTc interval was 466 ± 46 ms. Patients were categorized into two groups based on the QTc interval, with a cutoff line of 470 ms. Univariate analyses showed significant relations between categories of QTc interval, and sex and serum concentrations of potassium, calcium, or glucose. Multivariate analyses showed that female sex and hypokalemia were independent risk factors for severe QTc prolongation. Hypokalemia (<3.5 mmol/l) was associated with a relative risk of 4.53 for severe QTc prolongation as compared with normokalemia, while the relative risk associated with female sex was 4.45 as compared with male sex. There was a significant inverse correlation between serum potassium levels and QTc intervals among female patients. Conclusion These findings suggest that female sex and hypokalemia are independent risk factors for severe QTc prolongation in patients with SAH. PMID:12793884

  13. Utility of corrected QT interval in orthostatic intolerance.

    Directory of Open Access Journals (Sweden)

    Jung Bin Kim

    Full Text Available We performed this study to determine whether electrocardiographic corrected QT (QTc interval predicts alterations in sympathovagal balance during orthostatic intolerance (OI. We reviewed 1,368 patients presenting with symptoms suggestive of OI who underwent electrocardiography and composite autonomic function tests (AFTs. Patients with a positive response to the head-up tilt test were classified into orthostatic hypotension (OH, neurocardiogenic syncope (NCS, or postural orthostatic tachycardia syndrome (POTS groups. A total of 275 patients (159 OH, 54 NCS, and 62 POTS were included in the final analysis. Between-group comparisons of OI symptom grade, QTc interval, QTc dispersion, and each AFT measure were performed. QTc interval and dispersion were correlated with AFT measures. OH Patients had the most severe OI symptom grade and NCS patients the mildest. Patients with OH showed the longest QTc interval (448.8±33.6 msec, QTc dispersion (59.5±30.3 msec and the lowest values in heart rate response to deep breathing (HRDB (10.3±6.0 beats/min and Valsalva ratio (1.3±0.2. Patients with POTS showed the shortest QTc interval (421.7±28.6 msec, the highest HRDB values (24.5±9.2 beats/min, Valsalva ratio (1.8±0.3, and proximal and distal leg sweat volumes in the quantitative sudomotor axon reflex test. QTc interval correlated negatively with HRDB (r = -0.443, p<0.001 and Valsalva ratio (r = -0.425, p<0.001. We found negative correlations between QTc interval and AFT values representing cardiovagal function in patients with OI. Our findings suggest that prolonged QTc interval may be considered to be a biomarker for detecting alterations in sympathovagal balance, especially cardiovagal dysfunction in OH.

  14. Analysis of Relationship between Levofloxacin and Corrected QT Prolongation Using a Clinical Data Warehouse.

    Science.gov (United States)

    Park, Man Young; Kim, Eun Yeob; Lee, Young Ho; Kim, Woojae; Kim, Ku Sang; Sheen, Seung Soo; Lim, Hong Seok; Park, Rae Woong

    2011-03-01

    The aim of this study was to examine whether or not levofloxacin has any relationship with QT prolongation in a real clinical setting by analyzing a clinical data warehouse of data collected from different hospital information systems. Electronic prescription data and medical charts from 3 different hospitals spanning the past 9 years were reviewed, and a clinical data warehouse was constructed. Patients who were both administrated levofloxacin and given electrocardiograms (ECG) were selected. The correlations between various patient characteristics, concomitant drugs, corrected QT (QTc) prolongation, and the interval difference in QTc before and after levofloxacin administration were analyzed. A total of 2,176 patients from 3 different hospitals were included in the study. QTc prolongation was found in 364 patients (16.7%). The study revealed that age (OR 1.026, p data seem to be essential to adverse drug reaction surveillance in future.

  15. Effect of oxatomide, an antiallergic agent, on QT interval in dogs.

    Science.gov (United States)

    Iwamoto, K; Ikeda, J; Nito, M; Kosaka, N; Ichikawa, S; Ohmori, K; Sakai, K

    2001-01-01

    Oxatomide (CAS 60607-34-3, KW-4354) is an effective antiallergic agent for allergic rhinitis, urticaria, pruritus cutaneous, and eczema/dermatitis, etc. Terfenadine (CAS 50679-08-8) and astemizole (CAS 68844-77-9), antiallergic agents, have been reported to induce QT prolongation leading to serious ventricular arrhythmia (torsades de pointes) as cardiovascular adverse effects. The present study was carried out to determine whether oxatomide and terfenadine have effects on QT interval as a single drug or in combination with itraconazole (CAS 84625-61-6), an antifungal agent with a CYP3A4 inhibitory effect, in conscious dogs. Terfenadine alone induced QT prolongation at the dose of 30 mg/kg p.o. When itraconazole was administered at the dose of 100 mg/kg p.o. 1 h before terfenadine administration, terfenadine induced QT prolongation at the dose of 10 mg/kg p.o. On the other hand, oxatomide did not induce QT prolongation either as a single agent at the dose of 30 mg/kg p.o. or in combination with itraconazole at the dose of 10 mg/kg p.o. The results present no evidence that oxatomide has the potential to provoke ventricular arrhythmia.

  16. Syncope and QT prolongation among patients treated with methadone for heroin dependence in the city of Copenhagen

    DEFF Research Database (Denmark)

    Fanoe, Søren; Hvidt, C; Ege, P

    2007-01-01

    Background: Methadone is prescribed to heroin addicts to decrease illicit opioid use. Prolongation of the QT interval in the ECG of patients with torsade de pointes (TdP) has been reported in methadone users. As heroin addicts sometimes faint while using illicit drugs, doctors might attribute too...... were collected in a population of adult heroin addicts treated with methadone or buprenorphine on a daily basis. Of the patients at the Drug Addiction Service in the municipal of Copenhagen, 450 ( 52%) were included. The QT interval was estimated from 12 lead ECGs. All participants were interviewed...... odds for syncope. Conclusions: Methadone is associated with QT prolongation and higher reporting of syncope in a population of heroin addicts. Abbreviations: HERG, human ether-a-go-go related gene; LQT2, type 2 of the long QT syndrome; TdP, torsade de pointes....

  17. Randomized, Controlled, Thorough QT/QTc Study Shows Absence of QT Prolongation with Luseogliflozin in Healthy Japanese Subjects.

    Directory of Open Access Journals (Sweden)

    Yuji Kumagai

    Full Text Available Luseogliflozin is a selective sodium glucose co-transporter 2 (SGLT2 inhibitor. To evaluate the cardiac safety of luseogliflozin, a thorough QT/QTc study was conducted in healthy Japanese subjects. The effects of moxifloxacin on QT prolongation in Japanese subjects were also evaluated. In this double-blind, placebo- and open-label positive-controlled, 4-way crossover study, 28 male and 28 female subjects received a single dose of luseogliflozin 5 mg (therapeutic dose, luseogliflozin 20 mg (supratherapeutic dose, placebo, and moxifloxacin 400 mg. Serial triplicate digital 12-lead electrocardiograms (ECGs were recorded before and after dosing, and results were analyzed using the Fridericia correction (QTcF method. Serial blood sampling was performed for pharmacokinetic analyses of luseogliflozin and moxifloxacin to analyze the relationship between QTcF interval and plasma concentration. The upper limits of the two-sided 90% confidence intervals (CIs for baseline and placebo-adjusted QTcF intervals (ΔΔQTcF in the 5 mg and 20 mg luseogliflozin groups were less than 10 ms at all time points. No correlation between plasma luseogliflozin concentrations and ΔΔQTcF was observed. In the moxifloxacin group, the lower limits of the two-sided 90% CIs for ΔΔQTcF were greater than 5 ms at all time points. A positive relationship was observed between plasma moxifloxacin concentration and change in ΔΔQTcF. Luseogliflozin was well tolerated at both dose levels. The majority of adverse events were mild in severity, and no serious or life-threatening adverse events occurred. Neither therapeutic (5 mg nor supratherapeutic (20 mg doses of luseogliflozin affected QT prolongation in healthy Japanese subjects.

  18. Modulation of the QT interval duration in hypertension with antihypertensive treatment.

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    Klimas, Jan; Kruzliak, Peter; Rabkin, Simon W

    2015-07-01

    The duration of the QT interval as measured by 12-lead electrocardiography is a measure of myocardial repolarization and is widely used to describe cardiac abnormalities, to determine the presence of cardiac toxicity and to evaluate drug safety. In hypertension, the QT interval is a predictor of the risk of both coronary events and cardiovascular death, after adjusting for the effects of additional risk factors. The mechanism of QT interval prolongation is multifactorial and includes cardiomyocyte hypertrophy and increased left ventricular mass, with accompanying changes in left ventricular transmural dispersion of repolarization, as well as changes in the tone of the autonomic nervous system of some patients with hypertension and mechano-electrical feedback, although this mechanism is less likely. Antihypertensive drugs vary in their effect on QT interval duration. The mechanisms underlying their effect depend on changes in left ventricular mass and autonomic nervous system tone, as well as changes in the activity of cardiac ion channels. Although blood pressure reduction is the primary goal of antihypertensive drug therapy and although the choice of antihypertensive drug treatment regimens varies among different individuals, the data regarding the disparate effects of antihypertensive drugs on the duration of the QT interval warrant consideration when implementing long-term pharmacotherapy for hypertension.

  19. RELATIONSHIP OF SLEEP DURATION AND QT INTERVAL IN OBESE AND NON-OBESE MEDICAL STUDENTS

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    Hariprasad

    2016-02-01

    Full Text Available BACKGROUND Sleep deprivation has become a major concern in the modern era. It is found to have an inverse relation with obesity increasing cardiovascular diseases. This study was done to correlate effects of sleep deprivation & obesity with QT interval. OBJECTIVES 1. To assess sleep deprivation in medical students. 2. To measure QT interval and QTc in obese and normal weight medical students. 3. To correlate these QT interval and QTc values with sleep deprivation and obesity. METHODOLOGY In this cross sectional study by simple random sampling 30 obese and 30 normal weight individuals were selected based on Quetelet Index. They were further sub- grouped into Group A with 2-4 hrs., Group B with 4-6 hrs. and Group C with 6-8 hrs. of sleep duration, respectively. Electrocardiography was recorded and QT & QTc was measured. The mean and standard deviations were calculated and by 2 tailed t-test for equality of means, significance was established. RESULTS The QT interval measured in Group A has a mean 363±25.1 in normal weight whereas 374±31.6 in obese which is increased. In all groups QTc interval was within normal limits though more in obese individuals. But in group A obese 431±31.6 which shows borderline QTc prolongation (≥430-451ms in men. Thus severe sleep deprivation contributes to obesity and prolongs QTc interval to pathologically. CONCLUSIONS Our study concludes that sleep deprivation has significant correlation with QTc interval. Mild to moderate sleep deprivation affects obese more than normal weight & Severe sleep deprivation with obesity may lead to borderline QTc prolongation.

  20. Síndrome del QT largo Syndrome of long Q-T interval

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    Michel Cabrera Ortega

    2011-06-01

    Full Text Available El síndrome del QT largo congénito de tipo Romano-Ward es una canalopatía arritmogénica poco frecuente, caracterizada por una grave alteración en la repolarización ventricular y traducida en el electrocardiograma por un alargamiento del intervalo QTc. Se documenta el caso de una paciente con síndrome del QT largo congénito de tipo 1, asintomática, con antecedentes familiares de muerte súbita y síndrome del QT largo, a quien se le realizó estudio ecocardiográfico, prueba ergométrica, detección de potenciales tardíos y dispersión del QT como complementos diagnósticos y estratificadores de riesgo. Se prescribió tratamiento farmacológico y semanas después se valoró su efectividad.The syndrome of congenital long Q-T interval (Q-T-i of Romano-Ward type is an uncommon arrthymic channel disease, characterized by a severe alteration in ventricular repolarization and translated in the electrocardiogram by a lengthening of QTc interval. This is the case of a female patient presenting with type 1 congenital long Q-T, asymptomatic, with family history of sudden death and syndrome of long Q-T; an echocardiography study, ergometer test, late potentials detection and Q-T dispersion as diagnostic complements and risk stratification. Drug therapy was prescribed and several weeks later its effectiveness was assessed.

  1. Postural Change-associated Alterations in QT/QTc Intervals on Electrocardiograms

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    Yutaka Kubo, MD

    2005-01-01

    Full Text Available In a new drug development, regulatory authorities recommend the “thorough QT/QTc study”, in which the use of a positive control group was recommended for evaluating assay sensitivity that allows the detection of a QT/QTc interval prolongation about 5 msec. The effects of postural change on the QT/QTc intervals were examined to determine its potential usefulness as a nonpharmacological positive control. Standard 12-lead electrocardiograms of 72 healthy male subjects (mean age: 22.6 ± 2.0 years were recorded in the morning and evening in 6 positions (supine, 30-degree semisitting, standing, supine, 90-degree sitting, and standing. The QT-RR relationships during postural changes seemed to be similar in the morning and the evening. The QTc interval calculated by the Fridericia's or Framingham's formula shortened in the sitting (7 to 10 msec and the standing position (11 to 14 msec compared to that in the supine position. On the other hand, the QTc interval calculated by the Bazett's formula prolonged by nearly 4 msec in the sitting position and by nearly 9 msec in the standing position. The results suggest that the difference in QTc interval during postural change, especially from supine to sitting position, could be useful as a nonpharmacological positive control.

  2. Fine-mapping and initial characterization of QT interval loci in African Americans.

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    Christy L Avery

    Full Text Available The QT interval (QT is heritable and its prolongation is a risk factor for ventricular tachyarrhythmias and sudden death. Most genetic studies of QT have examined European ancestral populations; however, the increased genetic diversity in African Americans provides opportunities to narrow association signals and identify population-specific variants. We therefore evaluated 6,670 SNPs spanning eleven previously identified QT loci in 8,644 African American participants from two Population Architecture using Genomics and Epidemiology (PAGE studies: the Atherosclerosis Risk in Communities study and Women's Health Initiative Clinical Trial. Of the fifteen known independent QT variants at the eleven previously identified loci, six were significantly associated with QT in African American populations (P≤1.20×10(-4: ATP1B1, PLN1, KCNQ1, NDRG4, and two NOS1AP independent signals. We also identified three population-specific signals significantly associated with QT in African Americans (P≤1.37×10(-5: one at NOS1AP and two at ATP1B1. Linkage disequilibrium (LD patterns in African Americans assisted in narrowing the region likely to contain the functional variants for several loci. For example, African American LD patterns showed that 0 SNPs were in LD with NOS1AP signal rs12143842, compared with European LD patterns that indicated 87 SNPs, which spanned 114.2 Kb, were in LD with rs12143842. Finally, bioinformatic-based characterization of the nine African American signals pointed to functional candidates located exclusively within non-coding regions, including predicted binding sites for transcription factors such as TBX5, which has been implicated in cardiac structure and conductance. In this detailed evaluation of QT loci, we identified several African Americans SNPs that better define the association with QT and successfully narrowed intervals surrounding established loci. These results demonstrate that the same loci influence variation in QT

  3. Involvement of the autonomic nervous system in diurnal variation of corrected QT intervals in common marmosets.

    Science.gov (United States)

    Honda, Masaki; Komatsu, Ryuichi; Isobe, Takehito; Tabo, Mitsuyasu; Ishikawa, Tomohisa

    2013-01-01

    Our previous study has shown that the corrected QT (QTc) interval of the electrocardiogram is longer during the dark period than during the light period in telemetered common marmosets. In the present study, we investigated the involvement of sympathetic and parasympathetic nervous activities in the changes of QTc interval associated with the light-dark cycle.Telemetry transmitters were implanted in six common marmosets to continuously record the electrocardiogram. The QT intervals obtained were corrected for the RR interval by applying individual probabilistic QT-rate correction formulae. Power spectral analysis of heart rate variability was performed to quantify each autonomic nervous function. Changes in QTc intervals and autonomic nervous tones were associated with the light-dark cycle. Parasympathetic nervous activity and QTc intervals significantly increased by approximately 10 ms during the dark period.Atropine, a muscarinic receptor antagonist, suppressed the increased parasympathetic tone and QTc prolongation during the dark period. In contrast, propranolol, a β-adrenoceptor antagonist, decreased the sympathetic activity and increased QTc intervals during the light period. These results suggest that the parasympathetic nerve functions prolong QTc intervals during the dark period, while the sympathetic nerve functions shorten them during the light period in common marmosets.

  4. Disease-associated QT-shortage versus quinine associated QT-prolongation: age dependent ECG-effects in Ghanaian children with severe malaria

    Science.gov (United States)

    2014-01-01

    Background While several anti-malarials are known to affect the electric conduction system of the heart, less is known on the direct effects of Plasmodium falciparum infection. Some earlier studies point to a direct impact of Plasmodium falciparum infection on the electric conduction system of the heart. The aim of this study was to analyse infection- and drug-induced effects on the electric conduction system. Methods Children aged 12 months to 108 months with severe malaria were included in Kumasi, Ghana. In addition to basic demographic, clinical, biochemical and parasitological, biochemical data were measured data upon hospitalization (day 0) and 12-lead electrocardiograms were recorded before (day 0) and after (day 1) initiation of quinine therapy as well as after 42 (±3) days. Results A total of 180 children were included. Most children were tachycardic on day 0 but heart rate declined on day 1 and during follow up. The corrected QT intervals were longest on day 1 and shortest on day 0. Comparison of QT intervals with day 42 (healthy status) after stratification for age demonstrated that in the youngest (<24 months) this was mainly due to a QT shortage on day 0 while a QT prolongation on day 1 was most pronounced in the oldest (≥48 months). Nearly one third of the participating children had measurable 4-aminoquinoline levels upon admission, but no direct effect on the corrected QT intervals could be shown. Conclusion Severe P. falciparum infection itself can provoke changes in the electrophysiology of the heart, independent of anti-malarial therapy. Especially in young - thus non immune - children the effect of acute disease associated pre-treatment QT-shortage is more pronounced than quinine associated QT-prolongation after therapy. Nevertheless, neither malaria nor anti-malarial induced effects on the electrophysiology of the heart were associated with clinically relevant arrhythmias in the present study population. PMID:24902591

  5. [Effect of pazufloxacin mesilate, a new quinolone antibacterial agent, for intravenous use on QT interval].

    Science.gov (United States)

    Fukuda, Hitoshi; Morita, Yukie; Shiotani, Norio; Mizuo, Midori; Komae, Norihisa

    2004-08-01

    The potential for QT interval prolongation of pazufloxacin mesilate (PZFX mesilate), a new quinolone antibacterial agent for intravenous use, was investigated by in vitro and in vivo electrophysiology studies. Following results were obtained. In vitro electrophysiology study using guinea pig papillary muscles: PZFX mesilate (30-300 microM) had no effects on resting membrane potential (RMP), action potential amplitude (APA) and action potential duration (APD). Reference quinolones, sparfloxacin (3-30 microM) and moxifloxacin (10-100 microM), had no effects on RMP and APA, but significantly prolonged APD at more than 3 and 10 microM, respectively, while ciprofloxacin (10-100 microM) had no effect on each parameter. In vivo electrophysiology study using anesthetized dogs: PZFX mesilate had no effects on electrocardiograph parameter (PR interval, QRS interval, QT interval and QTc) after intravenous administration of 3-30 mg/kg. These results suggest that PZFX mesilate has low potential for QT interval prolongation.

  6. Long QT interval in Turner syndrome--a high prevalence of LQTS gene mutations.

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    Christian Trolle

    Full Text Available OBJECTIVES: QT-interval prolongation of unknown aetiology is common in Turner syndrome. This study set out to explore the presence of known long QT mutations in Turner syndrome and to examine the corrected QT-interval (QTc over time and relate the findings to the Turner syndrome phenotype. METHODS: Adult women with Turner syndrome (n = 88 were examined thrice and 68 age-matched healthy controls were examined once. QTc was measured by one blinded reader (intra-reader variability: 0.7%, and adjusted for influence of heart rate by Bazett's (bQTc and Hodges's formula (hQTc. The prevalence of mutations in genes related to Long QT syndrome was determined in women with Turner syndrome and a QTc >432.0 milliseconds (ms. Echocardiographic assessment of aortic valve morphology, 24-hour blood pressures and blood samples were done. RESULTS: The mean hQTc in women with Turner syndrome (414.0 ± 25.5 ms compared to controls (390.4 ± 17.8 ms was prolonged (p432 ms, 7 had mutations in major Long QT syndrome genes (SCN5A and KCNH2 and one in a minor Long QT syndrome gene (KCNE2. CONCLUSION: There is a high prevalence of mutations in the major LQTS genes in women with TS and prolonged QTc. It remains to be settled, whether these findings are related to the unexplained excess mortality in Turner women. CLINICAL TRIAL REGISTRATION: NCT00624949. https://register.clinicaltrials.gov/prs/app/action/SelectProtocol/sid/S0001FLI/selectaction/View/ts/3/uid/U000099E.

  7. Increased Short-Term Beat-To-Beat Variability of QT Interval in Patients with Acromegaly.

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    Andrea Orosz

    Full Text Available Cardiovascular diseases, including ventricular arrhythmias are responsible for increased mortality in patients with acromegaly. Acromegaly may cause repolarization abnormalities such as QT prolongation and impairment of repolarization reserve enhancing liability to arrhythmia. The aim of this study was to determine the short-term beat-to-beat QT variability in patients with acromegaly. Thirty acromegalic patients (23 women and 7 men, mean age±SD: 55.7±10.4 years were compared with age- and sex-matched volunteers (mean age 51.3±7.6 years. Cardiac repolarization parameters including frequency corrected QT interval, PQ and QRS intervals, duration of terminal part of T waves (Tpeak-Tend and short-term variability of QT interval were evaluated. All acromegalic patients and controls underwent transthoracic echocardiographic examination. Autonomic function was assessed by means of five standard cardiovascular reflex tests. Comparison of the two groups revealed no significant differences in the conventional ECG parameters of repolarization (QT: 401.1±30.6 ms vs 389.3±16.5 ms, corrected QT interval: 430.1±18.6 ms vs 425.6±17.3 ms, QT dispersion: 38.2±13.2 ms vs 36.6±10.2 ms; acromegaly vs control, respectively. However, short-term beat-to-beat QT variability was significantly increased in acromegalic patients (4.23±1.03 ms vs 3.02±0.80, P<0.0001. There were significant differences between the two groups in the echocardiographic dimensions (left ventricular end diastolic diameter: 52.6±5.4 mm vs 48.0±3.9 mm, left ventricular end systolic diameter: 32.3±5.2 mm vs 29.1±4.4 mm, interventricular septum: 11.1±2.2 mm vs 8.8±0.7 mm, posterior wall of left ventricle: 10.8±1.4 mm vs 8.9±0.7 mm, P<0.05, respectively. Short-term beat-to-beat QT variability was elevated in patients with acromegaly in spite of unchanged conventional parameters of ventricular repolarization. This enhanced temporal QT variability may be an early indicator of increased

  8. [Torsade de pointes (TdP) observed during general anesthesia for cerebral aneurysm clipping in a patient with QT prolongation].

    Science.gov (United States)

    Tajiri, Osamu; Ito, Hiroyuki; Yago, Yasuko; Masumori, Yasushi

    2011-09-01

    A 55-year-old woman underwent emergency cerebral aneurysm clipping for subarachnoid hemorrhage (SAH). Her past and family history was unremarkable. Preoperative blood examinations were within normal ranges except for a slight decrease in serum potassium level. ECG showed a prolonged QTc interval (0.54 sec). General anesthesia was induced with propofol, fentanyl and vecuronium, and maintained with 1-1.5% sevoflurane, 50% nitrous oxide in oxygen and intermitted doses of fentanyl. About three hours after starting the operation, bigeminal pulse appeared followed by torsade de pointes. This arrhythmia returned to sinus rhythm by continuous infusion of lidocaine, and operation was performed completely. At the end of the operation, prolonged QT interval (QTc 0.71 sec) was noted. Her postoperative course was unremarkable and she was discharged on postoperative day 44. QT prolongation is a frequently seen ECG abnormality in a patient with SAH. In anesthetic management in this situation, it is important to monitor QT interval closely as well as to use anesthetics that would not exacerbate QT interval prolongation.

  9. Availability of human induced pluripotent stem cell-derived cardiomyocytes in assessment of drug potential for QT prolongation

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    Nozaki, Yumiko, E-mail: yumiko-nozaki@ds-pharma.co.jp [Preclinical Research Laboratories, Dainippon Sumitomo Pharma. Co., Ltd., Suita, Osaka 564-0053 (Japan); Honda, Yayoi, E-mail: yayoi-honda@ds-pharma.co.jp [Preclinical Research Laboratories, Dainippon Sumitomo Pharma. Co., Ltd., Suita, Osaka 564-0053 (Japan); Tsujimoto, Shinji, E-mail: shinji-tsujimoto@ds-pharma.co.jp [Regenerative and Cellular Medicine Office, Dainippon Sumitomo Pharma. Co., Ltd., Chuo-ku, Tokyo 104-0031 (Japan); Watanabe, Hitoshi, E-mail: hitoshi-1-watanabe@ds-pharma.co.jp [Preclinical Research Laboratories, Dainippon Sumitomo Pharma. Co., Ltd., Suita, Osaka 564-0053 (Japan); Kunimatsu, Takeshi, E-mail: takeshi-kunimatsu@ds-pharma.co.jp [Preclinical Research Laboratories, Dainippon Sumitomo Pharma. Co., Ltd., Suita, Osaka 564-0053 (Japan); Funabashi, Hitoshi, E-mail: hitoshi-funabashi@ds-pharma.co.jp [Preclinical Research Laboratories, Dainippon Sumitomo Pharma. Co., Ltd., Suita, Osaka 564-0053 (Japan)

    2014-07-01

    Field potential duration (FPD) in human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs), which can express QT interval in an electrocardiogram, is reported to be a useful tool to predict K{sup +} channel and Ca{sup 2+} channel blocker effects on QT interval. However, there is no report showing that this technique can be used to predict multichannel blocker potential for QT prolongation. The aim of this study is to show that FPD from MEA (Multielectrode array) of hiPS-CMs can detect QT prolongation induced by multichannel blockers. hiPS-CMs were seeded onto MEA and FPD was measured for 2 min every 10 min for 30 min after drug exposure for the vehicle and each drug concentration. I{sub Kr} and I{sub Ks} blockers concentration-dependently prolonged corrected FPD (FPDc), whereas Ca{sup 2+} channel blockers concentration-dependently shortened FPDc. Also, the multichannel blockers Amiodarone, Paroxetine, Terfenadine and Citalopram prolonged FPDc in a concentration dependent manner. Finally, the I{sub Kr} blockers, Terfenadine and Citalopram, which are reported to cause Torsade de Pointes (TdP) in clinical practice, produced early afterdepolarization (EAD). hiPS-CMs using MEA system and FPDc can predict the effects of drug candidates on QT interval. This study also shows that this assay can help detect EAD for drugs with TdP potential. - Highlights: • We focused on hiPS-CMs to replace in vitro assays in preclinical screening studies. • hiPS-CMs FPD is useful as an indicator to predict drug potential for QT prolongation. • MEA assay can help detect EAD for drugs with TdP potentials. • MEA assay in hiPS-CMs is useful for accurately predicting drug TdP risk in humans.

  10. Lesson Twenty-five Prevalence and Prognostic significance of Short QT Interval

    Institute of Scientific and Technical Information of China (English)

    鲁端; 王劲

    2008-01-01

    @@ Background-Short-QT syndrome is an inherited disorder characterized by a short QT interval and an increased risk of sudden cardiac death.The clinical significance of a short OT interval observed in a randomly recorded ECG is not known.Therefore,we assessed the prevalence and prognostic significance of a short QT interval in a general population.

  11. The effect of esmolol on corrected-QT interval, corrected-QT interval dispersion changes seen during anesthesia induction in hypertensive patients taking an angiotensin-converting enzyme inhibitor

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    Zahit Çeker

    2015-02-01

    Full Text Available BACKGROUND AND OBJECTIVES: The importance of minimizing the exaggerated sympatho-adrenergic responses and QT interval and QT interval dispersion changes that may develop due to laryngoscopy and tracheal intubation during anesthesia induction in the hypertensive patients is clear. Esmolol decreases the hemodynamic response to laryngoscopy and intubation. However, the effect of esmolol in decreasing the prolonged QT interval and QT interval dispersion as induced by laryngoscopy and intubation is controversial. We investigated the effect of esmolol on the hemodynamic, and corrected-QT interval and corrected-QT interval dispersion changes seen during anesthesia induction in hypertensive patients using angiotensin converting enzyme inhibitors. METHODS: 60 ASA I-II patients, with essential hypertension using angiotensin converting enzyme inhibitors were included in the study. The esmolol group received esmolol at a bolus dose of 500 mcg/kg followed by a 100 mcg/kg/min infusion which continued until the 4th min after intubation. The control group received 0.9% saline similar to the esmolol group. The mean blood pressure, heart rate values and the electrocardiogram records were obtained as baseline values before the anesthesia, 5 min after esmolol and saline administration, 3 min after the induction and 30 s, 2 min and 4 min after intubation. RESULTS: The corrected-QT interval was shorter in the esmolol group (p = 0.012, the corrected-QT interval dispersion interval was longer in the control group (p = 0.034 and the mean heart rate was higher in the control group (p = 0.022 30 s after intubation. The risk of arrhythmia frequency was higher in the control group in the 4-min period following intubation (p = 0.038. CONCLUSION: Endotracheal intubation was found to prolong corrected-QT interval and corrected-QT interval dispersion, and increase the heart rate during anesthesia induction with propofol in hypertensive patients using angiotensin converting

  12. Effects of changes in frequency on guinea pig ventricular action potential duration and on QT interval under different experimental conditions.

    Science.gov (United States)

    von Savigny, L; Hohnloser, S; Antoni, H

    1981-01-01

    Isolated perfused guinea pig hearts (Langendorff preparation) were arrested by carbachol (0.1-0.2 mg/l) and electrically stimulated in the region of the av-conducting system. The QT interval was determined by means of extracellular electrodes at different driving frequencies. Separate experiments were performed on papillary muscles from the right ventricle to measure the duration of the transmembrane action potential under comparable conditions. At 35 degrees C (Ke+ 5.4 mmol/l) increasing the frequency of stimulation (range 12-120/min) caused the action potential duration (APD) to decrease to a greater extent than the QT interval. Stepwise rising of the external K+ concentration up to 16.2 mmol/l produced a nearly parallel shift to the APD-frequency relation to lower values. Again, the QT interval was less affected by increasing the external K+ concentration than the APD. Stepwise reduction of the temperature down to 20 degrees C prolonged the APD as well as the QT interval, the effects being more pronounced at lower than at higher stimulation frequencies. Under all examined experimental conditions, the APD proved to be markedly shorter than the QT interval even when the latter is diminished by the duration of QRS. The results suggest that no close relation exists between the APD and the QT interval. The observed divergencies may be due to functional differences among various parts of the ventricles.

  13. A RELATIONSHIP BETWEEN QT INTERVAL AND CARDIOVASCULAR RISK FACTORS IN WOMEN WITH RHEUMATOID ARTHRITIS

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    D. S. Novikova

    2014-07-01

    Full Text Available Objective: to study a relationship of QT interval to cardiovascular risk factors in women with rheumatoid arthritis (RA.Subjects and methods. 291 female patients aged less than 60 years with a valid diagnosis of RA were examined. A control group consisted of125 women without rheumatic diseases. In addition to the clinical manifestations, acidity, and severity of RA, the authors assessed traditional risk factors (TRF of cardiovascular diseases (CVD, performed Holter ECG monitoring, common carotid artery duplex scanning, transthoracic echocardiographic study, and determined the levels of serum inflammatory markers.Results. The patients with RA differ from the control group in a longer adjusted QT interval, corrected for TRF of CVD. The major factorsassociated with a daily prolonged QTc interval in the women with RA are arterial hypertension, systolic, diastolic, pulse blood pressure level s, body mass index, subclinical target organ damage (carotid artery atherosclerosis, left ventricular (LV diastolic dysfunction, LV hypertrophyand remodeling, and the duration of RA. Leflunomide therapy is an additional factor associated with a prolonged nocturnal QT interval.Conclusion. The RA patients with a prolonged QTc interval and no clinical signs of cardiac lesion need meticulous examination aimed to identify CVD.

  14. A RELATIONSHIP BETWEEN QT INTERVAL AND CARDIOVASCULAR RISK FACTORS IN WOMEN WITH RHEUMATOID ARTHRITIS

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    D. S. Novikova

    2013-01-01

    Full Text Available Objective: to study a relationship of QT interval to cardiovascular risk factors in women with rheumatoid arthritis (RA.Subjects and methods. 291 female patients aged less than 60 years with a valid diagnosis of RA were examined. A control group consisted of125 women without rheumatic diseases. In addition to the clinical manifestations, acidity, and severity of RA, the authors assessed traditional risk factors (TRF of cardiovascular diseases (CVD, performed Holter ECG monitoring, common carotid artery duplex scanning, transthoracic echocardiographic study, and determined the levels of serum inflammatory markers.Results. The patients with RA differ from the control group in a longer adjusted QT interval, corrected for TRF of CVD. The major factorsassociated with a daily prolonged QTc interval in the women with RA are arterial hypertension, systolic, diastolic, pulse blood pressure level s, body mass index, subclinical target organ damage (carotid artery atherosclerosis, left ventricular (LV diastolic dysfunction, LV hypertrophyand remodeling, and the duration of RA. Leflunomide therapy is an additional factor associated with a prolonged nocturnal QT interval.Conclusion. The RA patients with a prolonged QTc interval and no clinical signs of cardiac lesion need meticulous examination aimed to identify CVD.

  15. QT Interval and QT Dispersion in Patients Undergoing Hemodialysis: Revisiting the Old Theory

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    Mohamed A. Alabd

    2011-07-01

    Full Text Available Aims: We sought to explore the response of the corrected QT (QTc interval duration and QT dispersion (QTD to hemodialysis. Methods: We enrolled 50 patients with end-stage renal disease undergoing regular hemodialysis. Blood samples were drawn for measurement of serum electrolytes, and a 12-lead ECG was performed to measure the QTc interval duration and QTD, immediately before and just after dialysis sessions. Results: The mean age of the cohort was 42.8 ± 12.2 years (58% males. Both the QTc duration and QTD showed marked variability after hemodialysis. A significant correlation was found between the decrease of both serum potassium and magnesium levels after dialysis and the post-dialysis QTc interval duration, with Pearson’s correlation coefficients r = –0.43 and r = –0.34, p = 0.002 and p = 0.01, respectively. Patients with a post-dialysis increase of QTc interval duration had a significantly higher percentage of reduction of serum potassium (p = 0.029, whereas patients with a post-dialysis increase of QTD had a significantly higher percentage of reduction of serum magnesium (p = 0.03. Conclusion: Our findings suggest a highly variable response of the QTc interval duration and QTD to hemodialysis. The post-dialysis QTc interval duration inversely correlated with the decrease of both serum potassium and magnesium levels after dialysis.

  16. QT Interval and QT Dispersion in Patients Undergoing Hemodialysis: Revisiting the Old Theory

    Science.gov (United States)

    Alabd, Mohamed A.; El-Hammady, Walid; Shawky, Ahmed; Nammas, Wail; El-Tayeb, Mohamed

    2011-01-01

    Aims We sought to explore the response of the corrected QT (QTc) interval duration and QT dispersion (QTD) to hemodialysis. Methods We enrolled 50 patients with end-stage renal disease undergoing regular hemodialysis. Blood samples were drawn for measurement of serum electrolytes, and a 12-lead ECG was performed to measure the QTc interval duration and QTD, immediately before and just after dialysis sessions. Results The mean age of the cohort was 42.8 ± 12.2 years (58% males). Both the QTc duration and QTD showed marked variability after hemodialysis. A significant correlation was found between the decrease of both serum potassium and magnesium levels after dialysis and the post-dialysis QTc interval duration, with Pearson's correlation coefficients r = −0.43 and r = −0.34, p = 0.002 and p = 0.01, respectively. Patients with a post-dialysis increase of QTc interval duration had a significantly higher percentage of reduction of serum potassium (p = 0.029), whereas patients with a post-dialysis increase of QTD had a significantly higher percentage of reduction of serum magnesium (p = 0.03). Conclusion Our findings suggest a highly variable response of the QTc interval duration and QTD to hemodialysis. The post-dialysis QTc interval duration inversely correlated with the decrease of both serum potassium and magnesium levels after dialysis. PMID:22470374

  17. Recapitulation of Clinical Individual Susceptibility to Drug-Induced QT Prolongation in Healthy Subjects Using iPSC-Derived Cardiomyocytes

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    Tadahiro Shinozawa

    2017-02-01

    Full Text Available To predict drug-induced serious adverse events (SAE in clinical trials, a model using a panel of cells derived from human induced pluripotent stem cells (hiPSCs of individuals with different susceptibilities could facilitate major advancements in translational research in terms of safety and pharmaco-economics. However, it is unclear whether hiPSC-derived cells can recapitulate interindividual differences in drug-induced SAE susceptibility in populations not having genetic disorders such as healthy subjects. Here, we evaluated individual differences in SAE susceptibility based on an in vitro model using hiPSC-derived cardiomyocytes (hiPSC-CMs as a pilot study. hiPSCs were generated from blood samples of ten healthy volunteers with different susceptibilities to moxifloxacin (Mox-induced QT prolongation. Different Mox-induced field potential duration (FPD prolongation values were observed in the hiPSC-CMs from each individual. Interestingly, the QT interval was significantly positively correlated with FPD at clinically relevant concentrations (r > 0.66 in multiple analyses including concentration-QT analysis. Genomic analysis showed no interindividual significant differences in known target-binding sites for Mox and other drugs such as the hERG channel subunit, and baseline QT ranges were normal. The results suggest that hiPSC-CMs from healthy subjects recapitulate susceptibility to Mox-induced QT prolongation and provide proof of concept for in vitro preclinical trials.

  18. Cellular mechanism of the QT prolongation induced by sulpiride.

    Science.gov (United States)

    Lee, Hyang-Ae; Kim, Ki-Suk; Park, Sang-Joon; Kim, Eun-Joo

    2009-01-01

    In this study, the authors investigated the electrophysiological effect of sulpiride on cardiac repolarization using conventional microelectrode recording techniques in isolated canine Purkinje fibers and a whole-cell patch clamp technique in transiently transfected cells with the hERG, KCNQ1/KCNE1, KCNJ2, and SCN5A cDNA and in rat cardiac myocytes for I(Ca). In studies of action potential duration, 10 microM, 100 microM, 300 microM, and 1 mM sulpiride prolonged action potential duration in a concentration-dependent manner. In studies of cardiac ion channels, sulpiride did not significantly affect I(Na), I(Ca), I(Ks), I(K1), except for I(Kr). Sulpiride dose-dependently decreased the hERG tail current. It is considered that the prolonged action potential duration by sulpiride was mainly the result of inhibition of the hERG channel. The data suggest that the clinical use of sulpiride is reasonable within therapeutic plasma concentrations, but all patients taking this drug should be cautiously monitored for clinical signs of long-QT syndrome and severe arrhythmia.

  19. A Common Genetic Variant Risk Score is Associated with Drug-Induced QT Prolongation and Torsade de Pointes Risk: A Pilot Study.

    Science.gov (United States)

    Strauss, David G; Vicente, Jose; Johannesen, Lars; Blinova, Ksenia; Mason, Jay W; Weeke, Peter; Behr, Elijah R; Roden, Dan M; Woosley, Raymond; Kosova, Gulum; Rosenberg, Michael A; Newton-Cheh, Christopher

    2017-02-17

    Background -Drug-induced QT interval prolongation, a risk factor for life-threatening ventricular arrhythmias, is a potential side effect of many marketed and withdrawn medications. The contribution of common genetic variants previously associated with baseline QT interval to drug-induced QT prolongation and arrhythmias is not known. Methods -We tested the hypothesis that a weighted combination of common genetic variants contributing to QT interval at baseline, identified through genome-wide association studies, can predict individual response to multiple QT-prolonging drugs. Genetic analysis of 22 subjects was performed in a secondary analysis of a randomized, double-blind, placebo-controlled, cross-over trial of 3 QT-prolonging drugs with 15 time-matched QT and plasma drug concentration measurements. Subjects received single doses of dofetilide, quinidine, ranolazine and placebo. The outcome was the correlation between a genetic QT score comprising 61 common genetic variants and the slope of an individual subject's drug-induced increase in heart rate corrected QT (QTc) vs. drug concentration. Results -The genetic QT score was correlated with drug-induced QTc prolongation. Among white subjects, genetic QT score explained 30% of the variability in response to dofetilide (r = 0.55 [95% CI, 0.09-0.81], P = 0.02), 23% in response to quinidine (r = 0.48 [95% CI, -0.03 to 0.79], P = 0.06) and 27% in response to ranolazine (r = 0.52 [95% CI, 0.05 to 0.80], P = 0.03). Furthermore, the genetic QT score was a significant predictor of drug-induced torsade de pointes in an independent sample of 216 cases compared to 771 controls (r(2) = 12%, P = 1x10(-7)). Conclusions -We demonstrate that a genetic QT score comprising 61 common genetic variants explains a significant proportion of the variability in drug-induced QT prolongation and is a significant predictor of drug-induced torsade de pointes. These findings highlight an opportunity for recent genetic discoveries to improve

  20. Adaptation of the QT interval to heart rate changes in isolated perfused guinea pig heart: influence of amiodarone and D-sotalol.

    Science.gov (United States)

    Padrini, R; Speranza, G; Nollo, G; Bova, S; Piovan, D; Antolini, R; Ferrari, M

    1997-05-01

    The inadequacy of the QT interval to shorten following heart rate increase is a feature of the inherited long QT syndrome and may have a role in the genesis of the typical arrhythmias associated with this syndrome (torsade des pointes). The aim of our study was to evaluate whether drugs that prolong the QT interval, such as amiodarone and D-sotalol, may also impair the ability of the QT interval to adapt to sudden heart rate changes. Experiments were carried out on isolated perfused guinea pig hearts (Langendorff preparation). Driving frequency was changed, in steps, every two minutes (Hz: 2.5-3-2.5-3.75-2.5-5-2.5), while epicardial ECG was continuously recorded on magnetic tape. QT interval was automatically measured by means of a beat-by-beat analysis program. D-sotalol was added to the perfusion medium at a concentration of 4 micrograms ml-1, while amiodarone was administered, before in vitro evaluation, for seven days (50 mg kg-1 per day, intraperitoneally). In control experiments two phases of QT adaptation were identified: an abrupt QT shortening at the first beat after frequency change (QT1), followed by a gradual, exponential QT shortening that reached a new steady state in about 1 min (half life: 13 sec). The electrical restitution curve (the relation between QT1 and the corresponding diastolic interval) had a rate constant of 57 +/- 8 ms. Neither drug changed the slow component of QT adaptation. However, both drugs increased the ability of QT to shorten upon premature stimulation: D-sotalol by increasing the rate constant of the restitution curve and amiodarone by decreasing the y-intercept. Our results indicate that D-sotalol and amiodarone do not impair QT shortening during tachycardia but, on the contrary, they may favour QT adaptation, thus reducing the likelihood of the potentially lethal 'R on T phenomenon'. This may be an additional mechanism by which these drugs can exert their antifibrillatory action.

  1. The prognostic value of the QT interval and QT interval dispersion in all-cause and cardiac mortality and morbidity in a population of Danish citizens

    DEFF Research Database (Denmark)

    Elming, H; Holm, E; Jun, L

    1998-01-01

    of 1658 women and 1797 men aged 30-60 years. QT interval dispersion was calculated from the maximal difference between QT intervals in any two leads. All cause mortality over 13 years, and cardiovascular mortality as well as cardiac morbidity over 11 years, were the main outcome parameters. Subjects...... of cardiovascular mortality and cardiac fatal and non-fatal morbidity in a general population over 11 years.......AIMS: To evaluate the prognostic value of the QT interval and QT interval dispersion in total and in cardiovascular mortality, as well as in cardiac morbidity, in a general population. METHODS AND RESULTS: The QT interval was measured in all leads from a standard 12-lead ECG in a random sample...

  2. QT interval in healthy dogs: which method of correcting the QT interval in dogs is appropriate for use in small animal clinics?

    Directory of Open Access Journals (Sweden)

    Maira S. Oliveira

    2014-05-01

    Full Text Available The electrocardiography (ECG QT interval is influenced by fluctuations in heart rate (HR what may lead to misinterpretation of its length. Considering that alterations in QT interval length reflect abnormalities of the ventricular repolarisation which predispose to occurrence of arrhythmias, this variable must be properly evaluated. The aim of this work is to determine which method of correcting the QT interval is the most appropriate for dogs regarding different ranges of normal HR (different breeds. Healthy adult dogs (n=130; German Shepherd, Boxer, Pit Bull Terrier, and Poodle were submitted to ECG examination and QT intervals were determined in triplicates from the bipolar limb II lead and corrected for the effects of HR through the application of three published formulae involving quadratic, cubic or linear regression. The mean corrected QT values (QTc obtained using the diverse formulae were significantly different (ρ<0.05, while those derived according to the equation QTcV = QT + 0.087(1- RR were the most consistent (linear regression. QTcV values were strongly correlated (r=0.83 with the QT interval and showed a coefficient of variation of 8.37% and a 95% confidence interval of 0.22-0.23 s. Owing to its simplicity and reliability, the QTcV was considered the most appropriate to be used for the correction of QT interval in dogs.

  3. Asociación de la neuropatía autonómica cardiovascular y el intervalo QT prolongado con la morbimortalidad cardiovascular en pacientes con diabetes mellitus tipo 2 Association of cardiovascular autonomic neuropathy and prolonged QT interval with cardiovascular morbidity and mortality in patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Ray Ticse Aguirre

    2011-03-01

    Full Text Available Con el objetivo de evaluar la relación entre la neuropatía autonómica cardiovascular (NACV y el intervalo QT corregido (QTc con la morbimortalidad cardiovascular en pacientes con diabetes mellitus tipo 2, se realizó el seguimiento a 5 años de 67 pacientes que acudieron a consulta externa del Servicio de Endocrinología. Se presentaron eventos cardiovasculares en 16 pacientes; el 82% completó el seguimiento y se encontró que el intervalo QTc prolongado fue la única variable que se asoció de forma significativa a morbimortalidad cardiovascular en el análisis de regresión logística múltiple (RR: 13,56; IC 95%: 2,01-91,36 (p=0,0074.In order to evaluate the relationship between cardiovascular autonomic neuropathy and corrected QT interval (QTc with cardiovascular morbidity and mortality in patients with type 2 diabetes mellitus, we followed up for 5 years 67 patients attending the outpatient Endocrinology Service. 82% completed follow-up and cardiovascular events occurred in 16 patients. We found that long QTc interval was the only variable significantly associated with cardiovascular morbidity and mortality in the multiple logistic regression analysis (RR: 13.56, 95% CI: 2.01-91.36 (p = 0.0074.

  4. QT prolongation in a child with thyroid storm

    Science.gov (United States)

    Albert, Benjamin B; Eckersley, Luke Gerard; Skinner, Jonathan Robert; Jefferies, Craig

    2014-01-01

    Summary A 12-year-old girl presented with an acute confusional state and a 2-year history of weight loss, anxiety, agitation and recurrent fever. Thyroid function tests confirmed severe hyperthyroidism, and a diagnosis of thyroid storm was made (Burch and Wartofsky score=75). ECG showed a prolonged QTc interval of 506 ms. Acute treatment for thyroid storm consisted of Lugol's iodine, prednisolone, carbimazole and propranolol. She made a steady recovery and by 3 months her thyroid function had normalised; a repeat ECG showed a QTc within the normal range (430 ms). There was no relevant family history. This is a case of QTc prolongation with hyperthyroidism and normalisation with euthyroidism. It is not commonly recognised that hyperthyroidism in children may be associated with QTc prolongation. QTc measurement should be incorporated into management protocols for hyperthyroidism. PMID:24729112

  5. QT Interval Variability Index and QT Interval Duration in Different Sleep Stages: Analysis of Polysomnographic Recordings in Nonapneic Male Patients

    Directory of Open Access Journals (Sweden)

    Moonika Viigimae

    2015-01-01

    Full Text Available The aim of the study was to determine whether different sleep stages, especially REM sleep, affect QT interval duration and variability in male patients without obstructive sleep apnea (OSA. Polysomnographic recordings of 30 patients were analyzed. Beat-to-beat QT interval variability was calculated using QTV index (QTVI formula. For QTc interval calculation, in addition to Bazett’s formula, linear and parabolic heart rate correction formulas with two separate α values were used. QTVI and QTc values were calculated as means of 2 awake, 3 NREM, and 3 REM sleep episodes; the duration of each episode was 300 sec. Mean QTVI values were not statistically different between sleep stages. Therefore, elevated QTVI values found in patients with OSA cannot be interpreted as physiological sympathetic impact during REM sleep and should be considered as a risk factor for potentially life-threatening ventricular arrhythmias. The absence of difference of the mean QTc interval values between NREM and REM stages seems to confirm our conclusion that sympathetic surges during REM stage do not induce repolarization variability. In patients without notable structural and electrical remodeling of myocardium, physiological elevation in sympathetic activity during REM sleep remains subthreshold concerning clinically significant increase of myocardial electrical instability.

  6. Antipsychotic Polypharmacy and Corrected QT Interval: A Systematic Review.

    Science.gov (United States)

    Takeuchi, Hiroyoshi; Suzuki, Takefumi; Remington, Gary; Uchida, Hiroyuki

    2015-05-01

    It remains unclear whether antipsychotic polypharmacy, a common clinical practice, is related to an increased risk of corrected time between start of Q wave and end of T wave (QTc) interval prolongation. We conducted a systematic review of the literature to address this important issue. A systematic literature search was conducted in October 2014, using MEDLINE, Embase, and PsycINFO. Studies and case reports were included if they reported QTc intervals or QTc interval changes before and after antipsychotic polypharmacy or QTc intervals in both antipsychotic polypharmacy and monotherapy groups. A total of 21 articles (10 clinical trials, 4 observational studies, and 7 case reports) met inclusion criteria. The clinical trials have shown that a combination treatment with risperidone or pimozide is not obviously related to an increase in QTc interval, whereas ziprasidone or sertindole combined with clozapine may prolong QTc interval. Among the 4 observational studies, antipsychotic polypharmacy was not clearly associated with QTc prolongation in 3 studies, each cross-sectional. In contrast, one prospective study showed a significant increase in QTc interval following antipsychotic coadministration. The case reports indicated an increased risk of QTc prolongation in at least some patients receiving antipsychotic polypharmacy. Currently available evidence fails to confirm that antipsychotic polypharmacy worsens QTc prolongation in general, although the evidence is scarce and inconsistent. Clinicians are advised to remain conservative in resorting to antipsychotic polypharmacy, as a combination of some QTc-prolongation liable antipsychotics may further prolong QTc interval, and efficacy supporting the clinical benefits of antipsychotic polypharmacy is equivocal, at best.

  7. RELATIONSHIP OF SLEEP DURATION AND QT INTERVAL IN OBESE AND NON-OBESE MEDICAL STUDENTS

    OpenAIRE

    Hariprasad; Chandrakala

    2016-01-01

    BACKGROUND Sleep deprivation has become a major concern in the modern era. It is found to have an inverse relation with obesity increasing cardiovascular diseases. This study was done to correlate effects of sleep deprivation & obesity with QT interval. OBJECTIVES 1. To assess sleep deprivation in medical students. 2. To measure QT interval and QTc in obese and normal weight medical students. 3. To correlate these QT interval and QTc values with sleep deprivation ...

  8. Drowsiness discrimination in an overnight driving simulation on the basis of RR and QT intervals

    Directory of Open Access Journals (Sweden)

    Heinze Christian

    2017-09-01

    Full Text Available We examined if ECG-based features are discrimi-native towards drowsiness. Twenty-five volunteers (19–32 years completed 7×40 minutes of monotonous overnight driving simulation, designed to induce drowsiness. ECG (512 s-1 was recorded continuously; subjective ratings of drowsiness on the Karolinska sleepiness scale (KSS were polled every five minutes. ECG recordings were divided into 5-min segments, each associated with the mean of one self- and two observer-KSS ratings. Those mean KSS values were binarized to obtain two classes not drowsy and drowsy. The Q-, R- and T-waves in the recordings were detected; R-peak positions were manually reviewed; the Q- and T-detection method was tested against the manual annotations of Physio-net’s QT database. Power spectral densities of RR intervals (RR-PSD and quantiles of the empirical distribution of heart-rate corrected QTc intervals were estimated. Support-vector machines and random-holdout cross-validation were used for the estimation of the classification error. Using either RR-PSD or QTc features yielded mean test errors of 79.3 ± 0.3 % and 82.7 ± 0.5 %, respectively. Merging RR and QTc features improved the accuracy to 88.3 ± 0.2 %. QTc intervals of the class drowsy were generally prolonged com-pared to not drowsy. Our findings indicate that the inclusion of QT intervals contribute to the discrimination of driver sleepiness.

  9. Food and Insulin Effect on QT/QTC Interval of ECG

    Science.gov (United States)

    2014-08-19

    Effects of Different Meals on the QT/QTc Interval; Insulin and Oral Hypoglycemic [Antidiabetic] Drugs Causing Adverse Effects in Therapeutic Use; C-Peptide Effects on the QT/QTc Interval; Moxifloxacin ECG Profile in Fed and Fasted State; Japanese vs. Caucasian TQT Comparison

  10. Assessment of the QT interval in the electroencephalography (EEG) of children with syncope, epilepsy, and attention-deficit hyperactivity disorder (ADHD).

    Science.gov (United States)

    Jha, Om P; Khurana, Divya S; Carvalho, Karen S; Melvin, Joseph J; Legido, Agustin; O'Riordan, Anna C; Valencia, Ignacio

    2010-03-01

    The interpretation of QT interval is often neglected during electroencephalography (EEG) reading. We compared the incidence of prolonged QT interval, as seen in the electrocardiography (ECG) recording lead of the EEG, in children presenting with seizure, syncope, or attention-deficit hyperactivity disorder (ADHD). Abnormal QT was defined as >460 ms. The incidence of prolonged QT in the seizure, syncope, and ADHD groups was 1/50 (2%), 7/50 (14%), and 2/50 (4%), respectively (P = .036, chi-square). The mean +/- SD of QT were 405 +/- 34, 424 +/- 39, and 414 +/- 36, respectively (P = .035, analysis of variance [ANOVA], syncope group, compared with seizure group). The incidence of prolonged QT as measured in the EEG was unexpectedly high in children presenting with seizure, syncope, or ADHD. These data support the concept that QT evaluation should be emphasized during routine EEG reading, as it may aid in identifying cases of undiagnosed cardiac conduction abnormalities. Prospective studies comparing EEG-ECG tracings with 12-lead ECG are warranted.

  11. Syncope and QT prolongation among patients treated with methadone for heroin dependence in the city of Copenhagen

    DEFF Research Database (Denmark)

    Fanoe, Søren; Hvidt, C; Ege, P

    2007-01-01

    Background: Methadone is prescribed to heroin addicts to decrease illicit opioid use. Prolongation of the QT interval in the ECG of patients with torsade de pointes (TdP) has been reported in methadone users. As heroin addicts sometimes faint while using illicit drugs, doctors might attribute too...... many episodes of syncope to illicit drug use and thereby underestimate the incidence of TdP in this special population, and the high mortality in this population may, in part, be caused by the proarrhythmic effect of methadone. Methods: In this cross-sectional study interview, ECGs and blood samples...... were collected in a population of adult heroin addicts treated with methadone or buprenorphine on a daily basis. Of the patients at the Drug Addiction Service in the municipal of Copenhagen, 450 ( 52%) were included. The QT interval was estimated from 12 lead ECGs. All participants were interviewed...

  12. Heart block and prolonged Q-Tc interval following muscle relaxant reversal: a case report.

    Science.gov (United States)

    Shields, John A

    2008-02-01

    Heart block and Q-Tc interval prolongation have been reported with several agents used in anesthesia, and the US Food and Drug Administration mandates evaluation of the Q-T interval with new drugs. Drug-induced Q-T interval prolongation may precipitate life-threatening arrhythmias, is considered a precursor for torsades de pointes, and may predict cardiovascular complications. In the patient described in this article, heart block occurred and the Q-Tc interval became prolonged after muscle relaxant reversal with neostigmine; both were considered to be related to the combination of agents used in the case, as well as to other predisposing factors such as morbid obesity. The agents used that affected cardiac conduction were neostigmine, desflurane, droperidol, dolasetron, and dexmedetomidine. Although the heart block was resolved after 2 doses of atropine, prolonged P-R and Q-Tc intervals persisted into the immediate postoperative period but returned to baseline within 4 hours. Clinical implications of this report include increasing awareness of the multitude of factors affecting Q-T interval prolongation during anesthesia.

  13. Poisoning severity score, Glasgow coma scale, corrected QT interval in acute organophosphate poisoning.

    Science.gov (United States)

    Akdur, Okhan; Durukan, Polat; Ozkan, Seda; Avsarogullari, Levent; Vardar, Alper; Kavalci, Cemil; Ikizceli, Ibrahim

    2010-05-01

    The aim of this study was to investigate effectiveness of the poisoning severity score (PSS), Glasgow coma scale (GCS), and corrected QT (QTc) interval in predicting outcomes in acute organophosphates (OP) poisoning. Over a period of 2 years, 62 patients with OP poisoning were admitted to emergency department (ED) of Erciyes University Medical School Hospital. The age, sex, cause of contact, compound involved, time elapsed between exposure and admission to the ED, duration of hospital stay, and cardiac manifestations at the time of presentation were recorded. GCS and poisoning severity score (PSS) was calculated for each patient. Electrocardiogram (ECG) analysis included the rate, rhythm, ST-T abnormalities, conduction defects, and measurement of PR and QT intervals. Sixty-two patients with OP poisoning presented to our ED from January 2007 to December 2008 from which 54 patients were included in the study. The mean age was 34.1 +/- 14.8 years. Of the cases, 53.7% were female. Twenty-six patients had a prolonged QTc interval. Mean PSS of men and women was 1.8 +/- 1.0. No statistically significant correlation was found between the PSS and QTc intervals of the cases. A significant correlation was determined between the GCS and PSS of grade 3 and grade 4 cases. GCS is a parameter that helps clinician to identify advanced grade OP poisoning patients in the initial assessment in the ED. However, ECG findings, such as prolonged QTc interval, are not effective in determination of short-term prognosis and show no relationship with PSS.

  14. Diurnal variation and dispersion in QT interval in cirrhosis: relation to haemodynamic changes

    DEFF Research Database (Denmark)

    Hansen, Stig; Møller, Søren; Bendtsen, Flemming

    2007-01-01

    with cirrhosis, undergoing a haemodynamic investigation. 24-h 12 lead Holter monitoring provided information on QT and heart rate variability. RESULTS: Mean QT(C) was above upper normal limit (440 ms(1/2)) in eleven patients (47%) and significantly higher than in controls (441 vs 400 ms(1/2), p...=0.03-0.001). No diurnal variation of QT(disp) was found in cirrhosis. Heart rate variability was reduced with a significant relation to central hypovolaemia (r=0.55, p=0.01). CONCLUSIONS: Twenty-four hours QT(C) is prolonged in a substantial fraction of patients with cirrhosis, but with normal...... diurnal variation. The combination of long QT(C) and normal QT(disp) suggests delayed myocyte repolarisation on the cellular level, rather than temporal and spatial heterogeneity in the myocardial wall....

  15. Prevalence and Risk Factors Associated with Use of QT-Prolonging Drugs in Hospitalized Older People.

    Science.gov (United States)

    Franchi, C; Ardoino, I; Rossio, R; Nobili, A; Biganzoli, E M; Marengoni, A; Marcucci, M; Pasina, L; Tettamanti, M; Corrao, S; Mannucci, P M

    2016-01-01

    The objective of this study was to evaluate the prevalence of the prescription of QT-prolonging drugs at hospital admission and discharge and the risk factors associated with their use in older people (aged 65 years and older). Data were obtained from the REPOSI (REgistro POliterapie SIMI [Società Italiana di Medicina Interna]) registry, which enrolled 4035 patients in 2008 (n = 1332), 2010 (n = 1380), and 2012 (n = 1323). Multivariable logistic regression was performed to determine the risk factors independently associated with QT-prolonging drug use. QT-prolonging drugs were classified by the risk of Torsades de Pointes (TdP) (definite, possible, or conditional) according to the Arizona Center for Education and Research on Therapeutics (AzCERT) classification. Specific drug combinations were also assessed. Among 3906 patients prescribed at least one drug at admission, 2156 (55.2%) were taking at least one QT-prolonging drug. Risk factors independently associated with the use of any QT-prolonging drugs were increasing age (odds ratio [OR] 1.02, 95% CI 1.01-1.03), multimorbidity (OR 2.69, 95% CI 2.33-3.10), hypokalemia (OR 2.79, 95% CI 1.32-5.89), atrial fibrillation (OR 1.66, 95% CI 1.40-1.98), and heart failure (OR 3.17, 95% CI 2.49-4.05). Furosemide, alone or in combination, was the most prescribed drug. Amiodarone was the most prescribed drug with a definite risk of TdP. Both the absolute number of QT-prolonging drugs (2890 vs. 3549) and the number of patients treated with them (2456 vs. 2156) increased at discharge. Among 1808 patients not prescribed QT-prolonging drugs at admission, 35.8% were prescribed them at discharge. Despite their risk, QT-prolonging drugs are widely prescribed to hospitalized older persons. The curriculum for both practicing physicians and medical students should be strengthened to provide more education on the appropriate use of drugs in order to improve the management of hospitalized older people.

  16. Long QT syndrome genotyping by electrocardiography: fact, fiction, or something in between?

    DEFF Research Database (Denmark)

    Kanters, Jørgen K.; Graff, Claus; Andersen, Mads Peter;

    2006-01-01

    Diagnosis of long QT syndrome (LQTS) is difficult. A prolonged QT interval is easily overlooked, and in 10% of all patients with LQTS, the QT interval is normal. Genotyping is unfortunately not able to detect all patients and healthy subjects correctly. Although QT prolongation is the most used...

  17. Heart rate-corrected QT interval helps predict mortality after intentional organophosphate poisoning.

    Directory of Open Access Journals (Sweden)

    Shou-Hsuan Liu

    Full Text Available INTRODUCTION: In this study, we investigated the outcomes for patients with intentional organophosphate poisoning. Previous reports indicate that in contrast to normal heart rate-corrected QT intervals (QTc, QTc prolongation might be indicative of a poor prognosis for patients exposed to organophosphates. METHODS: We analyzed the records of 118 patients who were referred to Chang Gung Memorial Hospital for management of organophosphate poisoning between 2000 and 2011. Patients were grouped according to their initial QTc interval, i.e., normal (0.44 s. Demographic, clinical, laboratory, and mortality data were obtained for analysis. RESULTS: The incidence of hypotension in patients with prolonged QTc intervals was higher than that in the patients with normal QTc intervals (P = 0.019. By the end of the study, 18 of 118 (15.2% patients had died, including 3 of 75 (4.0% patients with normal QTc intervals and 15 of 43 (34.9% patients with prolonged QTc intervals. Using multivariate-Cox-regression analysis, we found that hypotension (OR = 10.930, 95% CI = 2.961-40.345, P = 0.000, respiratory failure (OR = 4.867, 95% CI = 1.062-22.301, P = 0.042, coma (OR = 3.482, 95% CI = 1.184-10.238, P = 0.023, and QTc prolongation (OR = 7.459, 95% CI = 2.053-27.099, P = 0.002 were significant risk factors for mortality. Furthermore, it was revealed that non-survivors not only had longer QTc interval (503.00±41.56 versus 432.71±51.21 ms, P = 0.002, but also suffered higher incidences of hypotension (83.3 versus 12.0%, P = 0.000, shortness of breath (64 versus 94.4%, P = 0.010, bronchorrhea (55 versus 94.4%, P = 0.002, bronchospasm (50.0 versus 94.4%, P = 0.000, respiratory failure (94.4 versus 43.0%, P = 0.000 and coma (66.7 versus 11.0%, P = 0.000 than survivors. Finally, Kaplan-Meier analysis demonstrated that cumulative mortality was higher among patients with prolonged QTc

  18. Short QT interval is unreliable marker of anabolic androgenic steroid abuse in competitive athletes

    Directory of Open Access Journals (Sweden)

    Đorđević Vitomir

    2012-01-01

    Full Text Available Introduction. Previous animal and human studies provided the evidence that testosterone may affect ventricular repolarization by shortening of the QT interval. Synthetic derivatives of testosterone, modified to enhance its anabolic properties, are occasionally abused by some competitive athletes. Objective. We assessed whether the QT interval duration could discriminate androgenic anabolic steroids (AAS-using strength athletes (SA from drug-free endurance athletes (EA, by comparing 25 formulas for QT interval correction. Methods. We recruited 22 elite male athletes involved in long-term strength or endurance training and 20 sedentary controls. All elite

  19. Identification and Functional Characterization of a Novel CACNA1C-Mediated Cardiac Disorder Characterized by Prolonged QT Intervals with Hypertrophic Cardiomyopathy, Congenital Heart Defects, and Sudden Cardiac Death

    Science.gov (United States)

    Boczek, Nicole J.; Ye, Dan; Jin, Fang; Tester, David J.; Huseby, April; Bos, J. Martijn; Johnson, Aaron J.; Kanter, Ronald; Ackerman, Michael J.

    2016-01-01

    Background A portion of sudden cardiac deaths (SCD) can be attributed to structural heart diseases such as hypertrophic cardiomyopathy (HCM) or cardiac channelopathies such as long QT syndrome (LQTS); however, the underlying molecular mechanisms are quite distinct. Here, we identify a novel CACNA1C missense mutation with mixed loss-of-function/gain-of-function responsible for a complex phenotype of LQTS, HCM, SCD, and congenital heart defects (CHDs). Methods and Results Whole exome sequencing (WES) in combination with Ingenuity Variant Analysis was completed on three affected individuals and one unaffected individual from a large pedigree with concomitant LQTS, HCM, and CHDs and identified a novel CACNA1C mutation, p.Arg518Cys, as the most likely candidate mutation. Mutational analysis of exon 12 of CACNA1C was completed on 5 additional patients with a similar phenotype of LQTS plus a personal or family history of HCM-like phenotypes, and identified two additional pedigrees with mutations at the same position, p.Arg518Cys/His. Whole cell patch clamp technique was used to assess the electrophysiological effects of the identified mutations in CaV1.2, and revealed a complex phenotype, including loss of current density and inactivation in combination with increased window and late current. Conclusions Through WES and expanded cohort screening, we identified a novel genetic substrate p.Arg518Cys/His-CACNA1C, in patients with a complex phenotype including LQTS, HCM, and CHDs annotated as cardiac-only Timothy syndrome. Our electrophysiological studies, identification of mutations at the same amino acid position in multiple pedigrees, and co-segregation with disease in these pedigrees provides evidence that p.Arg518Cys/His is the pathogenic substrate for the observed phenotype. PMID:26253506

  20. Syncope and QT prolongation among patients treated with methadone for heroin dependence in the city of Copenhagen

    DEFF Research Database (Denmark)

    Fanoe, Søren; Hvidt, Christian; Ege, Peter Preben

    2007-01-01

    Methadone is prescribed to heroin addicts to decrease illicit opioid use. Prolongation of the QT interval in the ECG of patients with torsade de pointes (TdP) has been reported in methadone users. As heroin addicts sometimes faint while using illicit drugs, doctors might attribute too many episodes...... of syncope to illicit drug use and thereby underestimate the incidence of TdP in this special population, and the high mortality in this population may, in part, be caused by the proarrhythmic effect of methadone....

  1. PK/PD Modelling of the QT Interval: a Step Towards Defining the Translational Relationship Between In Vitro, Awake Beagle Dogs, and Humans.

    Science.gov (United States)

    Marostica, Eleonora; Van Ammel, Karel; Teisman, Ard; Gallacher, David; Van Bocxlaer, Jan; De Ridder, Filip; Boussery, Koen; Vermeulen, An

    2016-07-01

    Inhibiting the human ether-a-go-go-related gene (hERG)-encoded potassium ion channel is positively correlated with QT-interval prolongation in vivo, which is considered a risk factor for the occurrence of Torsades de Pointes (TdP). A pharmacokinetic/pharmacodynamic model was developed for four compounds that reached the clinic, to relate drug-induced QT-interval change in awake dogs and humans and to derive a translational scaling factor a 1. Overall, dogs were more sensitive than humans to QT-interval change, an a 1 of 1.5 was found, and a 10% current inhibition in vitro produced a higher percent QT-interval change in dogs as compared to humans. The QT-interval changes in dogs were predictive for humans. In vitro and in vivo information could reliably describe the effects in humans. Robust translational knowledge is likely to reduce the need for expensive thorough QT studies; therefore, expanding this work to more compounds is recommended.

  2. Circadian rhythm in QT interval is preserved in mice deficient of potassium channel interacting protein 2

    DEFF Research Database (Denmark)

    Gottlieb, Lisa A; Lubberding, Anniek; Larsen, Anders Peter;

    2016-01-01

    Potassium Channel Interacting Protein 2 (KChIP2) is suggested to be responsible for the circadian rhythm in repolarization duration, ventricular arrhythmias, and sudden cardiac death. We investigated the hypothesis that there is no circadian rhythm in QT interval in the absence of KChIP2. Implanted...... telemetric devices recorded electrocardiogram continuously for 5 days in conscious wild-type mice (WT, n = 9) and KChIP2(-/-) mice (n = 9) in light:dark periods and in complete darkness. QT intervals were determined from all RR intervals and corrected for heart rate (QT100 = QT/(RR/100)(1/2)). Moreover, QT...... intervals were determined from complexes within the RR range of mean-RR ± 1% in the individual mouse (QTmean-RR). We find that RR intervals are 125 ± 5 ms in WT and 123 ± 4 ms in KChIP2(-/-) (p = 0.81), and QT intervals are 52 ± 1 and 52 ± 1 ms, respectively(p = 0.89). No ventricular arrhythmias or sudden...

  3. Drugs that enlarge the QT interval of the electrocardiogram. Fármacos que prolongan el intervalo QT del electrocardiograma.

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    Antonio L. Moreno Otero

    2006-12-01

    Full Text Available In this article the main causes of the enlargement of the electrocardiogram QT interval are commented, making emphasis in the main cause: drugs. Some of the drugs are mentioned that produce this clinical situation, as well as the possible mechanisms that produce it. Besides, some recommendations, related with the prescription of drugs that enlarge this electrocardiogram interval, are given.
    En este artículo se comentan las principales causas de la prolongación del intervalo QT del electrocardiograma, enfatizando en la principal causa: los medicamentos. Se mencionan algunos de los medicamentos que producen esta situación médica, así como los posibles mecanismos que la producen. Además, se ofrecen algunas recomendaciones relacionadas con la prescripción de fármacos que prolongan este intervalo del electrocardiograma.

  4. QT interval changes in term pregnant women living at moderately high altitude.

    Science.gov (United States)

    Batmaz, G; Aksoy, A N; Aydın, S; Ay, N K; Dane, B

    2016-01-01

    This study aimed to compare the QT interval changes in women with term pregnancy living at moderately high altitude (1890 m in Erzurum, Turkey) with those of women living at sea level (31 m in İstanbul, Turkey). One-hundred ten women (n = 55, for each group) with full-term and single child pregnancies. Two different locations in that state were selected: İstanbul, Turkey, which is at 31 m above sea level (Group 1) and Erzurum, Turkey, at 1890 m above sea level (Group 2). Physicians from the two locations participated in the study. We estimated QTc, QTc Max, QTc Min, QT, and QTcd intervals. Moderately high altitude group had significantly longer QT parameters (QTc, QTc Max, QTc Min, QT, and QTcd intervals) compared with sea level group (P anges occur in term pregnant women living moderately high altitude. These changes may be associated with pregnancy-related cardiovascular complications in moderately high altitude.

  5. Os efeitos da metformina sobre a dispersão do intervalo QT e QTc de ratos diabéticos Effects of metformin on QT and QTc interval dispersion of diabetic rats

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    Eunice Cristina da Silva Costa

    2008-04-01

    Full Text Available FUNDAMENTO: Diversos fármacos podem causar aumento do intervalo QT, bem como da sua dispersão (QTd em registros eletrocardiográficos (ECG. O QTd pode ser um marcador potencialmente sensível ao aumento do risco de arritmias cardíacas e morte súbita cardíaca. Metformina é uma substância de eficácia anti-hiperglicêmica utilizada no tratamento do diabete. Entretanto, estudos têm relacionado efeitos dose-dependentes da metformina sobre a glicemia e marcadores de riscos cardiovasculares. OBJETIVO: Avaliar os efeitos dose-resposta da metformina sobre o QT e QTd de ratos diabéticos. MÉTODOS: Ratos Wistar machos foram distribuídos em cinco grupos: controle não-tratado (C, diabético não-tratado (D, diabéticos tratados com metformina nas doses 3,5, 30 e 74 µg/kg/pc (DM 3,5, DM 30 e DM 74. O diabete foi induzido por uma injeção de aloxana (40 mg/kg, i.v.. O ECG foi registrado (1º, 15º e 30º dias através de quatro eletrodos inseridos na camada subcutânea das patas. Ambos os intervalos, RR e QT, foram medidos, e então os valores do QT corrigido e da dispersão de QT foram calculados. RESULTADOS: Os grupos DM 3,5 e DM 30 mostraram significativa redução da glicemia (pBACKGROUND: Several drugs can cause prolonged QT interval, as well as prolonged QT dispersion (QTd in electrocardiographic (EKG recordings. QTd may be a potentially sensitive marker of increased risk of cardiac arrhythmias and sudden cardiac death. Metformin is an effective antihyperglycemic agent used in the treatment of diabetes. However, studies have correlated dose-dependent effects of metformin on glycemia and cardiovascular risk markers. OBJECTIVE: To evaluate the dose-response effects of metformin on QT and QTd of diabetic rats. METHODS: Male Wistar rats were distributed in five groups: non-treated control (C, non-treated diabetics (D, diabetics treated with metmorfin at the doses of 3.5, 30 and 74 µg/kg/bw (DM 3.5, DM 30 and DM 74. Diabetes was induced by an

  6. Pannexin-1 Deficient Mice Have an Increased Susceptibility for Atrial Fibrillation and Show a QT-Prolongation Phenotype

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    Stella Petric

    2016-02-01

    Full Text Available Background/Aims: Pannexin-1 (Panx1 is an ATP release channel that is ubiquitously expressed and coupled to several ligand-gated receptors. In isolated cardiac myocytes, Panx1 forms large conductance channels that can be activated by Ca2+ release from the sarcoplasmic reticulum. Here we characterized the electrophysiological function of these channels in the heart in vivo, taking recourse to mice with Panx1 ablation. Methods: Cardiac phenotyping of Panx1 knock-out mice (Panx1-/- was performed by employing a molecular, cellular and functional approach, including echocardiography, surface and telemetric ECG recordings with QT analysis, physical stress testing and quantification of heart rate variability. In addition, an in vivo electrophysiological study entailed programmed electrical stimulation using an intracardiac octapolar catheter. Results: Panx1 deficiency results in a higher incidence of AV-block, delayed ventricular depolarisation, significant prolongation of QT- and rate corrected QT-interval and a higher incidence of atrial fibrillation after intraatrial burst stimulation. Conclusion: Panx1 seems to play an important role in murine cardiac electrophysiology and warrants further consideration in the context of hereditary forms of atrial fibrillation.

  7. Antipsychotic Dose Mediates the Association between Polypharmacy and Corrected QT Interval.

    Science.gov (United States)

    Barbui, Corrado; Bighelli, Irene; Carrà, Giuseppe; Castellazzi, Mariasole; Lucii, Claudio; Martinotti, Giovanni; Nosè, Michela; Ostuzzi, Giovanni

    2016-01-01

    Antipsychotic (AP) drugs have the potential to cause prolongation of the QT interval corrected for heart rate (QTc). As this risk is dose-dependent, it may be associated with the number of AP drugs concurrently prescribed, which is known to be associated with increased cumulative equivalent AP dosage. This study analysed whether AP dose mediates the relationship between polypharmacy and QTc interval. We used data from a cross-sectional survey that investigated the prevalence of QTc lengthening among people with psychiatric illnesses in Italy. AP polypharmacy was tested for evidence of association with AP dose and QTc interval using the Baron and Kenny mediational model. A total of 725 patients were included in this analysis. Of these, 186 (26%) were treated with two or more AP drugs (AP polypharmacy). The mean cumulative AP dose was significantly higher in those receiving AP polypharmacy (prescribed daily dose/defined daily dose = 2.93, standard deviation 1.31) than monotherapy (prescribed daily dose/defined daily dose = 0.82, standard deviation 0.77) (z = -12.62, p polypharmacy (mean = 420.86 milliseconds, standard deviation 27.16) than monotherapy (mean = 413.42 milliseconds, standard deviation 31.54) (z = -2.70, p = 0.006). The Baron and Kenny mediational analysis showed that, after adjustment for confounding variables, AP dose mediates the association between polypharmacy and QTc interval. The present study found that AP polypharmacy is associated with QTc interval, and this effect is mediated by AP dose. Given the high prevalence of AP polypharmacy in real-world clinical practice, clinicians should consider not only the myriad risk factors for QTc prolongation in their patients, but also that adding a second AP drug may further increase risk as compared with monotherapy.

  8. Common Variation in the NOS1AP Gene Is Associated With Drug-Induced QT Prolongation and Ventricular Arrhythmia

    NARCIS (Netherlands)

    Jamshidi, Yalda; Nolte, Ilja M.; Dalageorgou, Chrysoula; Zheng, Dongling; Johnson, Toby; Bastiaenen, Rachel; Ruddy, Suzanne; Talbott, Daniel; Norris, Kris J.; Snieder, Harold; George, Alfred L.; Marshall, Vanessa; Shakir, Saad; Kannankeril, Prince J.; Munroe, Patricia B.; Camm, A. John; Jeffery, Steve; Roden, Dan M.; Behr, Elijah R.

    2012-01-01

    Objectives This study sought to determine whether variations in NOS1AP affect drug-induced long QT syndrome (LQTS). Background Use of antiarrhythmic drugs is limited by the high incidence of serious adverse events including QT prolongation and torsades de pointes. NOS1AP gene variants play a role in

  9. Comparison of QT dispersion during atrial fibrillation and sinus rhythm in the same patients, at normal and prolonged ventricular repolarization

    NARCIS (Netherlands)

    Houltz, B; Darpo, B; Swedberg, K; Blomstrom, P; Crijns, HJGM; Jensen, SM; Svernhage, E; Edvardsson, N

    Aims Drug-induced increase in QT dispersion has been associated with increased risk of ventricular proarrhythmia. The aim of the present study was to compare QT dispersion during atrial fibrillation and sinus rhythm in the same patients at normal and prolonged ventricular repolarization. Methods and

  10. Dispersion durations of P-wave and QT interval in children treated with a ketogenic diet.

    Science.gov (United States)

    Doksöz, Önder; Güzel, Orkide; Yılmaz, Ünsal; Işgüder, Rana; Çeleğen, Kübra; Meşe, Timur

    2014-04-01

    Limited data are available on the effects of a ketogenic diet on dispersion duration of P-wave and QT-interval measures in children. We searched for the changes in these measures with serial electrocardiograms in patients treated with a ketogenic diet. Twenty-five drug-resistant patients with epilepsy treated with a ketogenic diet were enrolled in this study. Electrocardiography was performed in all patients before the beginning and at the sixth month after implementation of the ketogenic diet. Heart rate, maximum and minimum P-wave duration, P-wave dispersion, and maximum and minimum corrected QT interval and QT dispersion were manually measured from the 12-lead surface electrocardiogram. Minimum and maximum corrected QT and QT dispersion measurements showed nonsignificant increase at month 6 compared with baseline values. Other previously mentioned electrocardiogram parameters also showed no significant changes. A ketogenic diet of 6 months' duration has no significant effect on electrocardiogram parameters in children. Further studies with larger samples and longer duration of follow-up are needed to clarify the effects of ketogenic diet on P-wave dispersion and corrected QT and QT dispersion. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Tp-e interval and Tp-e/QT ratio in patients with Human Immunodeficiency Virus.

    Science.gov (United States)

    Ünal, Sefa; Yayla, Çağrı; Açar, Burak; Ertem, Ahmet G; Akboğa, Mehmet K; Gökaslan, Serkan; Erdöl, Mehmet A; Sönmezer, Meliha Ç; Kaya Kiliç, Esra; Ataman Hatipoğlu, Çiğdem; Aydoğdu, Sinan; Temizhan, Ahmet

    2017-03-09

    Human Immunodeficiency Virus (HIV) infection and AIDS are known to cause cardiovascular diseases such as premature coronary artery disease, cardiomyopathy, and arrhythmias. Recently, Tp-e interval and Tp-e/QT ratio has been shown as a novel marker of ventricular repolarization. We aimed to evaluate the ventricular repolarization using Tp-e interval and Tp-e/QT ratio in patients with Human Immunodeficiency Virus (HIV) infection. Totally 48 patients with HIV and 60 control subjects were enrolled to the study. Tp-e interval, Tp-e/QT and Tp-e/QTc ratio were measured from the 12-lead electrocardiogram. Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio were significantly higher in patients with HIV than control subjects (all pe interval and disease duration (r=0.298, p=0.048). and inverse correlation between Tp-e interval and CD4 count(r=-0.303, p=0.036). Our study showed that Tp-e interval, Tp-e/QT and Tp-e/QTc ratios were increased in patients with HIV than control subjects.

  12. Prolonged P-Wave and QT Dispersion in Children with Inflammatory Bowel Disease in Remission

    Science.gov (United States)

    Yılmaz, Nuh; Kutluk, Günsel; Dedeoğlu, Reyhan; Öztarhan, Kazım; Tulunoğlu, Aras; Şap, Fatih

    2017-01-01

    Objectives. Ulcerative colitis (UC) and Crohn's disease (CD) are chronic inflammatory bowel diseases (IBD) with unclear underlying aetiologies. Severe cardiac arrhythmias have been emphasised in a few studies on adult IBD patients. This study aimed to investigate the alteration of the P-wave and QT interval dispersion parameters to assess the risk of atrial conduction and ventricular repolarisation abnormalities in pediatric IBD patients. Patients and Methods. Thirty-six IBD patients in remission (UC: 20, CD: 16) aged 3–18 years and 36 age- and sex-matched control patients were enrolled in the study. Twelve-lead electrocardiograms were used to determine durations of P-wave, QT, and corrected QT (QTc) interval dispersion. Transthoracic echocardiograms and 24-hour rhythm Holter recordings were obtained for both groups. Results. The P-wave dispersion, QT dispersion, and QTc interval dispersion (Pdisp, QTdisp, and QTcdisp) were significantly longer in the patient group. The mean values of Pminimum, Pmaximum, and QTcminimum were significantly different between the two groups. The echocardiography and Holter monitoring results were not significantly different between the groups. Furthermore, no differences in these parameters were detected between the CD and UC groups. Conclusion. Results suggest that paediatric IBD patients may carry potential risks for serious atrial and ventricular arrhythmias over time even during remission.

  13. Tramadol Induced QTc-Interval Prolongation: Prevalence, Clinical Factors and Correlation to Plasma Concentrations.

    Science.gov (United States)

    Keller, Guillermo A; Etchegoyen, María C V; Fernandez, Nicolás; Olivera, Nancy M; Quiroga, Patricia N; Belloso, Waldo H; Diez, Roberto A; Di Girolamo, Guillermo

    2016-01-01

    In recent years, several cases of torsade de pointes have been associated with many opioids. However, to present no cases have been reported with tramadol. To evaluate the effect of tramadol on QT-interval in the clinical setting. Medical history and comorbidities predisposing to QT interval prolongation were registered for patients requiring medical assistance that involved tramadol administration. Ionograms and ECGs were performed at baseline and intratreatment; QT interval was analyzed after correction with Bazzet, Fridericia, Framinghan and Hogdes formula. 115 patients were studied (50.4% males) All patients had received tramadol 150-400 mg/day during 3.0-5.0 days at the moment of intratreatment control. Plasma concentrations of tramadol were 201-1613 ng/mL. Intratreatment electrocardiographic control, as mean ± SD (range), showed QTcB 372±32 (305 to 433), QTcFri 356±37 (281 to 429), QTcFra 363±33 (299 to 429), QTcH 362±30 (304 to 427), ΔQTcB 26±40 (-73 to 110), ΔQTcFri 24±48 (-97 to 121), ΔQTcFra 22±42 (-81 to 109) and .QTcH 22±38 (-68 to 110) ms. QTc interval presents high correlation with plasma tramadol concentrations (for .QTc, R>0.77). Renal failure was associated with a relative risk for ΔQTc > 30 ms of 1.90 (IC95% 1.31-2.74) and for ΔQTc > 60 ms of 4.74 (IC95% 2.57-8.74). No patient had evidence of arrhythmia during the present study. Tramadol produces QTc interval prolongation in good correlation with plasma drug concentrations; renal failure is a risk factor for higher concentration and QT prolongation by tramadol.

  14. Optimisation of embryonic and larval ECG measurement in zebrafish for quantifying the effect of QT prolonging drugs.

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    Sundeep Singh Dhillon

    Full Text Available Effective chemical compound toxicity screening is of paramount importance for safe cardiac drug development. Using mammals in preliminary screening for detection of cardiac dysfunction by electrocardiography (ECG is costly and requires a large number of animals. Alternatively, zebrafish embryos can be used as the ECG waveform is similar to mammals, a minimal amount of chemical is necessary for drug testing, while embryos are abundant, inexpensive and represent replacement in animal research with reduced bioethical concerns. We demonstrate here the utility of pre-feeding stage zebrafish larvae in detection of cardiac dysfunction by electrocardiography. We have optimised an ECG recording system by addressing key parameters such as the form of immobilization, recording temperature, electrode positioning and developmental age. Furthermore, analysis of 3 days post fertilization (dpf zebrafish embryos treated with known QT prolonging drugs such as terfenadine, verapamil and haloperidol led to reproducible detection of QT prolongation as previously shown for adult zebrafish. In addition, calculation of Z-factor scores revealed that the assay was sensitive and specific enough to detect large drug-induced changes in QTc intervals. Thus, the ECG recording system is a useful drug-screening tool to detect alteration to cardiac cycle components and secondary effects such as heart block and arrhythmias in zebrafish larvae before free feeding stage, and thus provides a suitable replacement for mammalian experimentation.

  15. Entropy Analysis of RR and QT Interval Variability during Orthostatic and Mental Stress in Healthy Subjects

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    Mathias Baumert

    2014-12-01

    Full Text Available Autonomic activity affects beat-to-beat variability of heart rate and QT interval. The aim of this study was to explore whether entropy measures are suitable to detect changes in neural outflow to the heart elicited by two different stress paradigms. We recorded short-term ECG in 11 normal subjects during an experimental protocol that involved head-up tilt and mental arithmetic stress and computed sample entropy, cross-sample entropy and causal interactions based on conditional entropy from RR and QT interval time series. Head-up tilt resulted in a significant reduction in sample entropy of RR intervals and cross-sample entropy, while mental arithmetic stress resulted in a significant reduction in coupling directed from RR to QT. In conclusion, measures of entropy are suitable to detect changes in neural outflow to the heart and decoupling of repolarisation variability from heart rate variability elicited by orthostatic or mental arithmetic stress.

  16. Differences in the electrocardiographic QT interval of various breeds of athletic horses during rest and exercise

    DEFF Research Database (Denmark)

    Pedersen, Philip Juul; Karlsson, Madeleine; Madsen, Mette Flethøj

    2016-01-01

    linear regression model. The breed of horse had a significant effect on the model. There was no systematic effect of BW or estimated exercise intensity, but a high inter-horse variability was observed. CONCLUSIONS: The equine QT interval should preferably be corrected for heart rate according to breed...... is influenced to some extent by heart rate, age, body weight (BW), sex, autonomic tone, and environment. In horses, there is substantial inter-breed variation in size and training, and the aims of this study were therefore to determine the best model describing the QT to RR relationship in breeds of various...... to peak exercise level and plotted against RR intervals. Data points were fitted with relevant regression models, and the effect of breed, BW, and estimated exercise intensity was examined. RESULTS: For all breeds in this study, the QT interval was best described as a function of RR by the piecewise...

  17. Are ECG monitoring recommendations before prescription of QT-prolonging drugs applied in daily practice?

    DEFF Research Database (Denmark)

    Warnier, Miriam Jacoba; Rutten, Frans Hendrik; Souverein, Patrick Cyriel

    2015-01-01

    PURPOSE: Monitoring of the QT duration by electrocardiography (ECG) prior to treatment is frequently recommended in the label of QT-prolonging drugs. It is, however, unknown how often general practitioners in daily clinical practice are adhering to these risk-minimization measures. We assessed...... the frequency of ECG measurements in patients where haloperidol was initiated in primary care. METHODS: Patients (≥18 years) with a first prescription of haloperidol in the UK Clinical Practice Research Datalink (2009-2013) were included. The proportion of ECGs made was determined in two blocks of 4 weeks......: during the exposure period when haloperidol was initiated, and during the control period, 1 year before. Conditional logistic regression analysis was applied to calculate the relative risk of having an ECG in the exposure period compared with the control period. Subgroup analyses were performed to assess...

  18. ARRITMIAS VENTRICULARES Y NUEVO SÍNDROME CORONARIO AGUDO EN PACIENTES CON INFARTO Y DISPERSIÓN DEL INTERVALO QT PROLONGADO / Ventricular arrhythmias and new acute coronary syndrome in patients with infarction and prolonged QT dispersion

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    Luis M. Reyes Hernández

    2013-01-01

    and Objectives: Myocardial ischemia increases QT dispersion in the electrocardiogram because, in these circumstances, the action potential duration decreases in the ischemic insult area by creating a dispersion of repolarization. The rapid succession of local metabolic and ionic alterations creates favorable situations in the genesis of ventricular arrhythmias during ischemia. The objective was to determine the association of the prolonged QTc dispersion, in the acute coronary syndrome, with ventricular arrhythmias and the recurrence of acute coronary disease. Method: A total of 194 patients with acute myocardial infarction were studied. The QT interval duration was measured in a 12-lead electrocardiogram and it was corrected for heart rate in each of these leads. The dispersion of the interval was also assessed. It was taken into account the electrocardiographic evolution of these patients in relation to the occurrence of ventricular arrhythmias and a new acute coronary syndrome in a 30-day follow-up. Results: Among the patients who had a prolonged QT dispersion, there was a prevalence of the deceased due to ventricular fibrillation (7 cases for 7.5%, and only 2 patients (2.2% who suffered from this arrhythmia were discharged alive. A new acute coronary syndrome was found in 17 patients with prolonged QT dispersion, versus 8 patients with normal QT dispersion. Conclusions: Ventricular extrasystoles was the most common arrhythmia in patients with normal QT dispersion, and ventricular fibrillation was the most common in patients with prolonged QT dispersion. Most patients who had a new acute coronary syndrome had a prolonged QTc.

  19. Cardiac hypertrophy: a risk factor for QT-prolongation and cardiac sudden death.

    Science.gov (United States)

    Kang, Y James

    2006-01-01

    Cardiac hypertrophy was viewed as a compensatory response to hemodynamic stress. However, cumulative evidence obtained from studies using more advanced technologies in human patients and animal models suggests that cardiac hypertrophy is a maladaptive process of the heart in response to intrinsic and extrinsic stimuli. Although hypertrophy can normalize wall tension, it is a risk factor for QT-prolongation and cardiac sudden death. Studies using molecular biology techniques such as transgenic and knockout mice have revealed many important molecules that are involved in the development of heart hypertrophy and have demonstrated signaling pathways leading to the pathogenesis. With the same approach, the consequence of heart hypertrophy has been examined. The significance of hypertrophy in the development of overt heart failure has been demonstrated and several critical molecular pathways involved in the process were revealed. A comprehensive understanding of the threats of heart hypertrophy to patients has helped to develop novel treatment strategies. The recognition of hypertrophy as a major risk factor for QT-prolongation and cardiac sudden death is an important advance in cardiac medicine. Cellular and molecular mechanisms of this risk aspect are currently under extensively exploring. These studies would lead to more comprehensive approaches to prevention of potential life threatening arrhythmia and cardiac sudden death. The adaptation of new approaches such as functional genomics and proteomics will further advance our knowledge of heart hypertrophy.

  20. The genetic basis of long QT and short QT syndromes: a mutation update

    DEFF Research Database (Denmark)

    Hedley, Paula L; Jørgensen, Poul; Schlamowitz, Sarah;

    2009-01-01

    Long QT and short QT syndromes (LQTS and SQTS) are cardiac repolarization abnormalities that are characterized by length perturbations of the QT interval as measured on electrocardiogram (ECG). Prolonged QT interval and a propensity for ventricular tachycardia of the torsades de pointes (TdP) type...... are characteristic of LQTS, while SQTS is characterized by shortened QT interval with tall peaked T-waves and a propensity for atrial fibrillation. Both syndromes represent a high risk for syncope and sudden death. LQTS exists as a congenital genetic disease (cLQTS) with more than 700 mutations described in 12 genes...

  1. Inflammation and prolonged QT time: results from the Cardiovascular Disease, Living and Ageing in Halle (CARLA study.

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    Daniel Medenwald

    Full Text Available BACKGROUND: Previous research found an association of CRP with QT time in population based samples. Even more, there is evidence of a substantial involvement of the tumor necrosis factor-alpha system in the pathophysiology of cardiac arrhythmia, while the role of Interleukin 6 remains inconclusive. OBJECTIVE: To determine the association between inflammation with an abnormally prolonged QT-time (APQT in men and women of the elderly general population. METHODS: Data descend from the baseline examination of the prospective, population-based Cardiovascular Disease, Living and Ageing in Halle (CARLA Study. After exclusion of subjects with atrial fibrillation and missing ECG recording the final study cohort consisted of 919 men and 797 women. Blood parameters of inflammation were the soluble TNF-Receptor 1 (sTNF-R1, the high-sensitive C-reactive protein (hsCRP, and Interleukin 6 (IL-6. In accordance with major cardiologic societies we defined an APQT above a QT time of 460 ms in women and 450 ms in men. Effect sizes and the corresponding 95% confidence intervals (CI were estimated by performing multiple linear and logistic regression analyses including the analysis of sex differences by interaction terms. RESULTS: After covariate adjustment we found an odds ratio (OR of 1.89 (95% CI: 1.13, 3.17 per 1000 pg/mL increase of sTNF-R1 in women, and 0.74 (95% CI: 0.48, 1.15 in men. In the covariate adjusted linear regression sTNF-R1 was again positively associated with QT time in women (5.75 ms per 1000 pg/mL, 95% CI: 1.32, 10.18, but not in men. Taking possible confounders into account IL-6 and hsCRP were not significantly related to APQT in both sexes. CONCLUSION: Our findings from cross-sectional analyses give evidence for an involvement of TNF-alpha in the pathology of APQT in women.

  2. QT variability during initial exposure to sotalol

    DEFF Research Database (Denmark)

    Weeke, Peter; Delaney, Jessica; Mosley, Jonathan D

    2013-01-01

    A prolonged QT interval is associated with increased risk of Torsades de pointes (TdP) and may be fatal. We sought to investigate the extent to which clinical covariates affect the change in QT interval among 'real-world' patients treated with sotalol and followed in an electronic medical record...

  3. Effect of Age and Sex on the QTc Interval in Children and Adolescents With Type 1 and 2 Long-QT Syndrome.

    Science.gov (United States)

    Vink, Arja S; Clur, Sally-Ann B; Geskus, Ronald B; Blank, Andreas C; De Kezel, Charlotte C A; Yoshinaga, Masao; Hofman, Nynke; Wilde, Arthur A M; Blom, Nico A

    2017-04-01

    In congenital long-QT syndrome, age, sex, and genotype have been associated with cardiac events, but their effect on the trend in QTc interval has never been established. We, therefore, aimed to assess the effect of age and sex on the QTc interval in children and adolescents with type 1 (LQT1) and type 2 (LQT2) long-QT syndrome. QTc intervals of 12-lead resting electrocardiograms were determined, and trends over time were analyzed using a linear mixed-effects model. The study included 278 patients with a median follow-up of 4 years (interquartile range, 1-9) and a median number of 6 (interquartile range, 2-10) electrocardiograms per patient. Both LQT1 and LQT2 male patients showed QTc interval shortening after the onset of puberty. In LQT2 male patients, this was preceded by a progressive QTc interval prolongation. In LQT1, after the age of 12 years, male patients had a significantly shorter QTc interval than female patients. In LQT2, during the first years of life and from 14 to 26 years, male patients had a significantly shorter QTc interval than female patients. On the contrary, between 5 and 14 years, LQT2 male patients had significantly longer QTc interval than LQT2 female patients. There is a significant effect of age and sex on the QTc interval in long-QT syndrome, with a unique pattern per genotype. The age of 12 to 14 years is an important transitional period. In the risk stratification and management of long-QT syndrome patients, clinicians should be aware of these age-, sex-, and genotype-related trends in QTc interval and especially the important role of the onset of puberty. © 2017 American Heart Association, Inc.

  4. High Resolution ECG for Evaluation of QT Interval Variability during Exposure to Acute Hypoxia

    Science.gov (United States)

    Zupet, P.; Finderle, Z.; Schlegel, Todd T.; Starc, V.

    2010-01-01

    Ventricular repolarization instability as quantified by the index of QT interval variability (QTVI) is one of the best predictors for risk of malignant ventricular arrhythmias and sudden cardiac death. Because it is difficult to appropriately monitor early signs of organ dysfunction at high altitude, we investigated whether high resolution advanced ECG (HR-ECG) analysis might be helpful as a non-invasive and easy-to-use tool for evaluating the risk of cardiac arrhythmias during exposure to acute hypoxia. 19 non-acclimatized healthy trained alpinists (age 37, 8 plus or minus 4,7 years) participated in the study. Five-minute high-resolution 12-lead electrocardiograms (ECGs) were recorded (Cardiosoft) in each subject at rest in the supine position breathing room air and then after breathing 12.5% oxygen for 30 min. For beat-to-beat RR and QT variability, the program of Starc was utilized to derive standard time domain measures such as root mean square of the successive interval difference (rMSSD) of RRV and QTV, the corrected QT interval (QTc) and the QTVI in lead II. Changes were evaluated with paired-samples t-test with p-values less than 0.05 considered statistically significant. As expected, the RR interval and its variability both decreased with increasing altitude, with p = 0.000 and p = 0.005, respectively. Significant increases were found in both the rMSSDQT and the QTVI in lead II, with p = 0.002 and p = 0.003, respectively. There was no change in QTc interval length (p = non significant). QT variability parameters may be useful for evaluating changes in ventricular repolarization caused by hypoxia. These changes might be driven by increases in sympathetic nervous system activity at ventricular level.

  5. Recurrent takotsubo with prolonged QT and torsade de pointes and left ventricular thrombus.

    Science.gov (United States)

    Ahmed, Alaa Eldin K; Serafi, Abdulhalim; Sunni, Nadia S; Younes, Hussein; Hassan, Walid

    2017-01-01

    Takotsubo cardiomyopathy, also known as "takotsubo syndrome," refers to transient apical ballooning syndrome, stress cardiomyopathy, or broken heart syndrome and is a recently recognized syndrome typically characterized by transient and reversible left ventricular dysfunction that develops in the setting of acute severe emotional or physical stress. Increased catecholamine levels have been proposed to play a central role in the pathogenesis of the disease, although the specific pathophysiology of this condition remains to be fully determined. At present, there have been very few reports of recurrent takotsubo cardiomyopathy. In this case report, we present a patient with multiple recurrences of takotsubo syndrome triggered by severe emotional stress that presented with recurrent loss of consciousness, QT prolongation, and polymorphic ventricular tachycardia (torsade de pointes) and left ventricular apical thrombus.

  6. Evaluation of the fetal QT interval using non-invasive fetal ECG technology.

    Science.gov (United States)

    Behar, Joachim; Zhu, Tingting; Oster, Julien; Niksch, Alisa; Mah, Douglas Y; Chun, Terrence; Greenberg, James; Tanner, Cassandre; Harrop, Jessica; Sameni, Reza; Ward, Jay; Wolfberg, Adam J; Clifford, Gari D

    2016-09-01

    Non-invasive fetal electrocardiography (NI-FECG) is a promising alternative continuous fetal monitoring method that has the potential to allow morphological analysis of the FECG. However, there are a number of challenges associated with the evaluation of morphological parameters from the NI-FECG, including low signal to noise ratio of the NI-FECG and methodological challenges for getting reference annotations and evaluating the accuracy of segmentation algorithms. This work aims to validate the measurement of the fetal QT interval in term laboring women using a NI-FECG electrocardiogram monitor. Fetal electrocardiogram data were recorded from 22 laboring women at term using the NI-FECG and an invasive fetal scalp electrode simultaneously. A total of 105 one-minute epochs were selected for analysis. Three pediatric electrophysiologists independently annotated individual waveforms and averaged waveforms from each epoch. The intervals measured on the averaged cycles taken from the NI-FECG and the fetal scalp electrode showed a close agreement; the root mean square error between all corresponding averaged NI-FECG and fetal scalp electrode beats was 13.6 ms, which is lower than the lowest adult root mean square error of 16.1 ms observed in related adult QT studies. These results provide evidence that NI-FECG technology enables accurate extraction of the fetal QT interval.

  7. Relationships between QT interval and heart rate variability at rest and the covariates in healthy young adults.

    Science.gov (United States)

    Arai, Kaori; Nakagawa, Yui; Iwata, Toyoto; Horiguchi, Hyogo; Murata, Katsuyuki

    2013-01-01

    To clarify the links between ECG QT-related parameters and heart rate variability (HRV) and the covariates possibly distorting them, the averaged RR and QT intervals in a single lead ECG were measured for 64 male and 86 female subjects aged 18-26. The QT index, defined by Rautaharju et al., in the young adults was not significantly related to any HRV parameters nor heart rate, but the Bazett's corrected QT (QTc) interval was associated negatively with the parasympathetic activity and positively with heart rate. No significant differences in the QTc interval, QT index or heart rate were seen between the men and women, but they significantly differed between both sexes after adjustment for possible covariates such as age and body mass index (BMI). Significant sex differences in parasympathetic parameters of the HRV were unchanged before and after the adjustment, but significant differences observed in the unadjusted sympathetic parameters disappeared after adjusting for covariates. Age, BMI and body fat percentage also were significant covariates affecting these ECG parameters. Consequently, QT index, unaffected by heart rate and HRV parameters, appears to be a more useful indicator than the QTc interval. Instead, the QT index and HRV parameters are recommended to be simultaneously measured in epidemiological research because they are probably complementary in assessing autonomic nervous function. Also, these parameters should be analyzed in men and women separately. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Association between maximal oxygen uptake and the heart rate corrected-QT interval in postmenopausal overweight women.

    Science.gov (United States)

    Michishita, Ryoma; Shono, Naoko; Kasahara, Takaki; Tsuruta, Toshiyuki

    2009-08-01

    Increased aerobic capacity can reduce the incidence of cardiovascular disease and the mortality rate. On the other hand, a prolonged heart rate corrected-QT (QTc) interval is associated with an increased risk of arrhythmias, cardiac sudden death and coronary artery disease. The association of the aerobic capacity and coronary risk factors with QTc interval was investigated in postmenopausal overweight women. The subjects included 84 postmenopausal overweight women [age: 58.7+/-6.4 years, body mass index (BMI): 27.9+/-3.3] with coronary risk factors. Electrocardiogram (ECG) was recorded with a standard resting 12-lead ECG after more than 5 minutes of rest. The QTc interval was automatically calculated according to Bazett's formula. A multistage graded submaximal exercise test was performed on an electric bicycle ergometer to determine the estimated maximal oxygen uptake (VO(2)max). Single correlation analysis showed the QTc interval to be positively associated with hemoglobin A(1)c (HbA(1)c), fasting glucose, fasting insulin, BMI, waist circumference, serum potassium and the number of coronary risk factors, while negatively correlated with VO(2)max. Stepwise multiple regression analysis demonstrated the strong association of the QTc interval with HbA(1)c and VO(2)max (r(2)=0.244, p<0.0001). In both patients with and without metabolic syndrome (n=15, n=69, respectively), the QTc interval was independently associated with the HbA(1)c (r(2)=0.318, p<0.05, r(2)= 0.115, p<0.05, respectively). These results suggest that decreased aerobic capacity and glucose intolerance may be independent risk factors for a prolonged QTc interval, while demonstrating no relationship with metabolic syndrome.

  9. Heart Rate-Corrected QT and JT Intervals in Electrocardiograms in Physically Fit Students and Student Athletes.

    Science.gov (United States)

    Misigoj-Durakovic, Marjeta; Durakovic, Zijad; Prskalo, Ivan

    2016-11-01

    In literature, data on the prevalence of prolonged and shortened corrected QT (QTc) have shown considerable variability. The aim of the study was to compare QTc and JTc intervals of competitive student athletes and noncompetitive sport participants to QTc cutoff points used in athletes. A group of 485 physically fit candidates for the study of kinesiology (139 female and 346 male candidates) aged 18-20 participated in the study. Basic anthropometry, field fitness test, cardiovascular, electrocardiograms measurements, and blood sampling for lipid profile were conducted. The prolonged QTc according to European Society of Cardiology criteria was found in 2.9% of female and 4.3% of male students. When the "Seattle criteria" were used, the proportion of prolonged QTc was 1.44% in female and 0.29% in male students. The shortened QTc according to the Seattle cutoff points was presented in 0.7% of female and 2.0% of male students. The JTc over 400 ms was found in 0.72% of female and 0.29% of male students. The JTc shorter than 320 ms was presented in 0.7% of female and 1.1% of male students. No significant differences were found between students involved in competitive sport and those involved in recreational sporting activities. Female students had lower body mass index and blood pressure values, better blood lipid profile, and lower uric acid concentrations. In conclusion, the Seattle criteria markedly decreased the proportion of prolonged QTc in student athletes, particularly in male students. It seems that the JTc interval could be a better parameter than the QTc interval for the estimation of specific repolarization time in physically fit university students.

  10. Uremic retention solute indoxyl sulfate level is associated with prolonged QTc interval in early CKD patients.

    Science.gov (United States)

    Tang, Wei-Hua; Wang, Chao-Ping; Chung, Fu-Mei; Huang, Lynn L H; Yu, Teng-Hung; Hung, Wei-Chin; Lu, Li-Fen; Chen, Po-Yuan; Luo, Ching-Hsing; Lee, Kun-Tai; Lee, Yau-Jiunn; Lai, Wen-Ter

    2015-01-01

    Total mortality and sudden cardiac death is highly prevalent in patients with chronic kidney disease (CKD). In CKD patients, the protein-bound uremic retention solute indoxyl sulfate (IS) is independently associated with cardiovascular disease. However, the underlying mechanisms of this association have yet to be elucidated. The relationship between IS and cardiac electrocardiographic parameters was investigated in a prospective observational study among early CKD patients. IS arrhythmogenic effect was evaluated by in vitro cardiomyocyte electrophysiological study and mathematical computer simulation. In a cohort of 100 early CKD patients, patients with corrected QT (QTc) prolongation had higher IS levels. Furthermore, serum IS level was independently associated with prolonged QTc interval. In vitro, the delay rectifier potassium current (IK) was found to be significantly decreased after the treatment of IS in a dose-dependent manner. The modulation of IS to the IK was through the regulation of the major potassium ion channel protein Kv 2.1 phosphorylation. In a computer simulation, the decrease of IK by IS could prolong the action potential duration (APD) and induce early afterdepolarization, which is known to be a trigger mechanism of lethal ventricular arrhythmias. In conclusion, serum IS level is independently associated with the prolonged QTc interval in early CKD patients. IS down-regulated IK channel protein phosphorylation and the IK current activity that in turn increased the cardiomyocyte APD and QTc interval in vitro and in the computer ORd model. These findings suggest that IS may play a role in the development of arrhythmogenesis in CKD patients.

  11. Coffee, Alcohol, Smoking, Physical Activity and QT Interval Duration: Results from the Third National Health and Nutrition Examination Survey

    Science.gov (United States)

    Zhang, Yiyi; Post, Wendy S.; Dalal, Darshan; Blasco-Colmenares, Elena; Tomaselli, Gordon F.; Guallar, Eliseo

    2011-01-01

    Background Abnormalities in the electrocardiographic QT interval duration have been associated with an increased risk of ventricular arrhythmias and sudden cardiac death. However, there is substantial uncertainty about the effect of modifiable factors such as coffee intake, cigarette smoking, alcohol consumption, and physical activity on QT interval duration. Methods We studied 7795 men and women from the Third National Health and Nutrition Survey (NHANES III, 1988–1994). Baseline QT interval was measured from the standard 12-lead electrocardiogram. Coffee and tea intake, alcohol consumption, leisure-time physical activities over the past month, and lifetime smoking habits were determined using validated questionnaires during the home interview. Results In the fully adjusted model, the average differences in QT interval comparing participants drinking ≥6 cups/day to those who did not drink any were −1.2 ms (95% CI −4.4 to 2.0) for coffee, and −2.0 ms (−11.2 to 7.3) for tea, respectively. The average differences in QT interval duration comparing current to never smokers was 1.2 ms (−0.6 to 2.9) while the average difference in QT interval duration comparing participants drinking ≥7 drinks/week to non-drinkers was 1.8 ms (−0.5 to 4.0). The age, race/ethnicity, and RR-interval adjusted differences in average QT interval duration comparing men with binge drinking episodes to non-drinkers or drinkers without binge drinking were 2.8 ms (0.4 to 5.3) and 4.0 ms (1.6 to 6.4), respectively. The corresponding differences in women were 1.1 (−2.9 to 5.2) and 1.7 ms (−2.3 to 5.7). Finally, the average differences in QT interval comparing the highest vs. the lowest categories of total physical activity was −0.8 ms (−3.0 to 1.4). Conclusion Binge drinking was associated with longer QT interval in men but not in women. QT interval duration was not associated with other modifiable factors including coffee and tea intake, smoking, and physical activity. PMID

  12. Coffee, alcohol, smoking, physical activity and QT interval duration: results from the Third National Health and Nutrition Examination Survey.

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    Yiyi Zhang

    Full Text Available BACKGROUND: Abnormalities in the electrocardiographic QT interval duration have been associated with an increased risk of ventricular arrhythmias and sudden cardiac death. However, there is substantial uncertainty about the effect of modifiable factors such as coffee intake, cigarette smoking, alcohol consumption, and physical activity on QT interval duration. METHODS: We studied 7795 men and women from the Third National Health and Nutrition Survey (NHANES III, 1988-1994. Baseline QT interval was measured from the standard 12-lead electrocardiogram. Coffee and tea intake, alcohol consumption, leisure-time physical activities over the past month, and lifetime smoking habits were determined using validated questionnaires during the home interview. RESULTS: In the fully adjusted model, the average differences in QT interval comparing participants drinking ≥6 cups/day to those who did not drink any were -1.2 ms (95% CI -4.4 to 2.0 for coffee, and -2.0 ms (-11.2 to 7.3 for tea, respectively. The average differences in QT interval duration comparing current to never smokers was 1.2 ms (-0.6 to 2.9 while the average difference in QT interval duration comparing participants drinking ≥7 drinks/week to non-drinkers was 1.8 ms (-0.5 to 4.0. The age, race/ethnicity, and RR-interval adjusted differences in average QT interval duration comparing men with binge drinking episodes to non-drinkers or drinkers without binge drinking were 2.8 ms (0.4 to 5.3 and 4.0 ms (1.6 to 6.4, respectively. The corresponding differences in women were 1.1 (-2.9 to 5.2 and 1.7 ms (-2.3 to 5.7. Finally, the average differences in QT interval comparing the highest vs. the lowest categories of total physical activity was -0.8 ms (-3.0 to 1.4. CONCLUSION: Binge drinking was associated with longer QT interval in men but not in women. QT interval duration was not associated with other modifiable factors including coffee and tea intake, smoking, and physical activity.

  13. Influence of Dietary Sodium and Potassium Intake on the Heart Rate Corrected-QT Interval in Elderly Subjects.

    Science.gov (United States)

    Michishita, Ryoma; Ishikawa-Takata, Kazuko; Yoshimura, Eiichi; Mihara, Rikako; Ikenaga, Masahiro; Morimura, Kazuhiro; Takeda, Noriko; Yamada, Yosuke; Higaki, Yasuki; Tanaka, Hiroaki; Kiyonaga, Akira

    2015-01-01

    It is well known that imbalances in the dietary electrolytes are associated with a significantly higher incidence of cardiovascular disease (CVD). On the other hand, a prolonged heart rate corrected-QT (QTc) interval is associated with an increased risk of cardiac autonomic nervous system dysfunction, the incidence of CVD and sudden cardiac death. This study was designed to clarify the association between the nutritional status and the QTc interval in elderly subjects. The subjects included 119 elderly subjects (46 males and 73 females, age; 72.9±4.8 y) without a history of CVD, who were taking cardioactive drugs. Resting 12-lead electrocardiography was performed, while the QTc interval was calculated according to Bazett's formula. The nutritional status was assessed using a brief self-administered diet history questionnaire. The subjects were divided into three categories, which were defined as equally trisected distributions of the body mass index (BMI). The QTc interval was significantly longer in both the low and high BMI groups than in the moderate BMI group in both genders (pintake in the low BMI group and the sodium intake in the high BMI group in both genders (psodium and potassium intake, depending on the body mass.

  14. Using simulated noise to define optimal QT intervals for computer analysis of ambulatory ECG.

    Science.gov (United States)

    Tikkanen, P E; Sellin, L C; Kinnunen, H O; Huikuri, H V

    1999-01-01

    The ambulatory electrocardiogram (ECG) is an important medical tool, not only for diagnosis of adverse cardiac events, but also to predict the risk of such events occurring. The 24-hour ambulatory ECG has certain problems and drawbacks because the signal is corrupted by noise from various sources and also several other conditions which may alter the ECG morphology. We have developed a Windows based program for the computer analysis of ambulatory ECG which attempts to address these problems. The software includes options for importing ECG data, different methods of waveform analysis, data-viewing, and exporting the extracted time series. In addition, the modular structure allows for flexible maintenance and expansion of the software. The ECG was recorded using a Holter device and oversampled to enhance the fidelity of the low sampling rate of the ambulatory ECG. The influence of different sampling rates on the interval variability were studied. The noise sensitivity of the implemented algorithm was tested with several types of simulated noise and the precision of the interval measurement was reported with SD values. Our simulations showed that, in most of the cases, defining the end of QT interval at the maximum of the T wave gave the most precise measurement. The definition of the onset of the ventricular repolarization duration is most precisely made on the maximum or descending maximal slope of the R wave. We also analyzed some examples of time series from patients using power spectrum estimates in order to validate the low level QT interval variability.

  15. Management of ventricular fibrillation or unstable ventricular tachycardia in patients with congenital long-QT syndrome: a suggested modification to ACLS guidelines.

    Science.gov (United States)

    Homme, Jason H; White, Roger D; Ackerman, Michael J

    2003-10-01

    Prolongation of the QT interval is a known risk factor for syncope, seizures and sudden cardiac death. Most patients with QT prolongation have an acquired cause, but congenital forms of QT prolongation are being increasingly recognized. However, existing advanced cardiac life support (ACLS) treatment algorithms for prolonged QT mediated ventricular fibrillation pertains to acquired long-QT syndrome (LQTS). Here, a young patient with out-of-hospital cardiac arrest secondary to congenital LQTS illustrates critical exceptions to the current ACLS treatment algorithms for ventricular fibrillation and unstable ventricular tachycardia when QT prolongation is congenital in origin. A clarified ACLS algorithm is proposed.

  16. [Effects of tilt test and beta-adrenergic stimulation on the QT interval in normal children and pediatric patients with unexplained syncope].

    Science.gov (United States)

    Arnaiz, Pilar; Dumas, Eduardo; Heusser, Felipe; González, Rolando; Jalil, Jorge

    2004-02-01

    In normal children, any procedure that increases heart rate, such as the tilt test, may shorten the QT interval. The effect of the tilt test on QT interval in children with syncope remains unknown. We analyzed the response of RR and QT intervals during a tilt test in 3 groups of children: 28 healthy children (group 1), 26 with syncope of unknown etiology and negative tilt test results (group 2), and 17 with vasovagal syncope (group 3). During the tilt test, RR and QT intervals were significantly shortened in groups 1 and 2. In group 3, RR interval was lengthened during syncope whereas the QT interval remained constant. QT interval lengthening during the tilt test is not a characteristic finding in normal children or in children with vasovagal syncope.

  17. Remote ischaemic preconditioning shortens QT intervals during exercise in healthy subjects.

    Science.gov (United States)

    Caru, Maxime; Lalonde, François; Gravel, Hugo; Daigle, Chantal; Tournoux, François; Jacquemet, Vincent; Curnier, Daniel

    2016-11-01

    The protective action of remote ischaemic preconditioning (RIPC) has been demonstrated in the context of surgical interventions in cardiology. Application of RIPC to sports performance has been proposed, but its effect on the electrocardiogram (ECG) during exercise remains unknown. This exploratory study aims to measure the changes in ventricular repolarization observed during exercise following RIPC in healthy subjects. In an experimental randomized crossover study, 17 subjects underwent two bouts of constant load exercise tests at 75% and 115% of gas exchange threshold (GET). Prior to exercise, they were allocated to either control or RIPC intervention with four cycles of 5 min of ischaemia followed by 5 min of reperfusion. ECG was continuously recorded during the protocol. QT and RR intervals were measured every 30 s (on an average tracing of the preceding 10 s). Although the time course of RR intervals did not differ between the two interventions (p = .56 at 75% GET and p = .74 at 115% GET), a significant shortening of QT intervals (measured from Q onset to T end) was observed during exercise (mean ± standard deviation of RIPC vs. -32 ± 19 ms at 75% GET (p exercise.

  18. Tp-e interval and Tp-e/QT ratio in patients with celiac disease.

    Science.gov (United States)

    Demirtaş, K; Yayla, Ç; Yüksel, M; Açar, B; Ünal, S; Ertem, A G; Kaplan, M; Akpinar, M Y; Kiliç, Z M Y; Kayaçetin, E

    2017-10-07

    Celiac disease is a chronic immune-mediated disease of the small intestine. It has been known that dilated cardiomyopathy and ischemic coronary artery disease have become more frequent in patients with celiac disease. The aim of the study was to assess Tp-e interval and Tp-e/QT ratio in patients with celiac disease. This study was conducted at a single center in collaboration with gastroenterology and cardiology clinics. Between January 2014 and June 2015, a total of 76 consecutive patients were enrolled (38 patients with celiac disease and 38 control subjects). Tp-e interval, Tp-e/QT and Tp-e/QTc ratio were measured from the 12-lead electrocardiogram. Tp-e interval (64.2±11.0 vs. 44.5±6.0; pceliac disease than control subjects. There was a significant positive correlation between Tp-e/QTc ratio and disease duration in patients with celiac disease (r=0.480, p=0.003) and also there was a significant positive correlation between Tp-e/QTc ratio and erythrocyte sedimentation rate (r=0.434, pceliac disease. Whether these changes increase the risk of ventricular arrhythmia deserve further studies. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  19. Evaluation of baseline corrected QT interval and azithromycin prescriptions in an academic medical center.

    Science.gov (United States)

    Lee, Rachael A; Guyton, Allison; Kunz, Danielle; Cutter, Gary R; Hoesley, Craig J

    2016-01-01

    Azithromycin is used in the inpatient setting for a variety of conditions. In 2013, the US Food and Drug Administration released a warning regarding risk for corrected QT (QTc) prolongation and subsequent arrhythmias. Knowledge of inpatient prescribing patterns of QTc prolonging medications with respect to patient risk factors for adverse cardiovascular events can help recognize safe use in light of these new warnings. To assess inpatient prescribing patterns, risk factors for QTc prolongation, and relationship between drug-drug interactions and cardiac monitoring in patients receiving azithromycin. Retrospective cohort study. One hundred inpatients ≥ 19 years of age were randomly selected from 1610 patient encounters between October 2012 and April 2013 who were administered at least 1 dose of azithromycin. Length of stay, reason for use, therapy duration, and concomitant medications were recorded. Telemetry charges and baseline electrocardiogram (ECG) prior to administration were assessed. Seventy-nine percent of azithromycin use was empiric. Sixty-five percent of patients received a baseline ECG prior to prescribing azithromycin, of which 60% had borderline or abnormal QTc prolongation. Seventy-six percent of patients were prescribed 2 or more QTc prolonging medications, of which there were more abnormal ECGs at baseline (P = 0.03) despite having telemetry ordered less than half of the time. In a cohort of hospitalized patients, azithromycin was prescribed despite risk factors for QTc prolongation and administration of interacting medications. Selection of azithromycin by providers appears to be independent from these risk factors, and education and vigilance to drug-drug interactions may be useful in limiting cardiac events with prescribing azithromycin. © 2015 Society of Hospital Medicine.

  20. Hyperpyrexia associated with congenital Long QT Syndrome

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    Nuriye Tarakci

    2014-08-01

    Full Text Available Congenital long QT syndrome (CLQTS is a genetic disorder presented with prolonged QT interval. In these patients, risk of sudden cardiac death due to ventricular tachyarrhythmias is high. Bradycardia may exhibit as a result of intrauterine fetal atrioventricular block, sinus bradycardia, tachycardia in these patient. Prolonged QT interval and multisystem involvement such as sensorineural hearing loss, muscle paralysis, immune deficiency, syndactyly have been reported in these patient . We have detected hyperpyrexia without clinical immunodeficiency and infection in our patient. To our knowledge, our patient is the first case in the literature . [Cukurova Med J 2014; 39(4.000: 909-903

  1. QT hysteresis in long-QT syndrome children with exercise testing

    Institute of Scientific and Technical Information of China (English)

    GAO Dong-sheng; FANG Wei-yi; Christine Chiu-Man; Joel Kirsh; Gil Gross; Robert M.Hamilton

    2007-01-01

    Background Congenital long QT syndrome (LQTS) is an inherited ion channel disorder resulting in abnormal cardiac repolarization that can cause syncope and sudden death associated with a prolonged rate-corrected QT interval and polymorphic ventricular tachycardia. Several studies in adults showed that LQTS patients have altered QT adaptation to heart rate changes compared with normal subjects which forming a "hysteresis loop" in the QT-circle length plot. This study was to observe the QT interval changing during exercise testing in children long QT syndrome (LQTS) patients,explore the new diagnosis methods of LQTS.Methods The subjects were divided into 3 groups according to 1993 LQTS diagnostic criteria. Group 1: LQTS group(n=17) who scored > or = 4 points indicating definite LQTS. Group 2: Middle group (n=16), patients who have prolonged QT interval but scored 1.5 to 3.5. Group 3: Normal control group (n=18). The average age of all study population is (12.3±5.8) years. No case had beta-adrenergic antagonists administration before exercise testing. All subjects were underwent tread mill exercise testing and electrocardiograph in whole exercise testing and recovery were recorded. QT and heart rate changing during whole exercise testing period were recorded. △QT, the QT interval at 1, 2, 4, 6 minutes into recovery subtract from the QT interval at a similar heart rate during exercise, were calculated.Results In all three groups, QT intervals were shortening with the increasing of heart rate, but QTc had no significant change. △QT at 1 minute ((45±11) ms), 2 minutes ((37±15) ms), 4 minutes ((23±12) ms) into recovery in LQTS group were significantly greater than that of the other two groups (P<0.05, P<0.01, P<0.01, respectively). There was no△QT significant difference between middle group and normal control group at recovery time. During the recovery phase in LQTS group, the QT interval remained shortened despite a decelerating heart rate, forming a

  2. Literature review and pilot studies of the effect of QT correction formulas on reported beta2-agonist-induced QTc prolongation.

    Science.gov (United States)

    Milic, Milos; Bao, Xuping; Rizos, Demetri; Liu, Fujun; Ziegler, Michael G

    2006-04-01

    Drugs that stimulate the beta2-adrenergic receptor have been reported to prolong the QT interval corrected for heart rate (QTc interval), a potential mechanism for cardiac toxicity. This study evaluated whether beta2-adrenergic agonist drugs prolong the QTc interval when different correction formulas for the effect of heart rate are used. Healthy subjects of both sexes aged 19 to 33 years were recruited with advertisements. In pilot studies, subjects took a preparation containing the beta2-agonist ephedrine, or they participated in a postural study of the effect of endogenous beta-agonists. The study-drug group took 3 pills of the ephedra preparation per day for 2 days and then 6 pills per day for the next 2 days. Electrocardiograms (ECGs) were recorded before and at 1, 3, and 82 hours after the first study-drug dose and both before and after standing in the standing-up group. QT intervals obtained by automatic measurement were corrected for heart rate with 3 formulas: Bazett (QTc[B]), Framingham (QTc[F]), and Fridericia (QTc[Fr]). For the literature review, PubMed was searched using the search terms beta2-agonist drugs, QT, QTc, EKG, ECG, or electrocardiogram for studies that reported prolongation of the QTc by beta2-agonist drugs. We analyzed the method by which 11 different studies corrected QT interval for heart rate after the use of formoterol, salmeterol, terbutaline, salbutamol, and fenoterol. The ephedra study included 20 healthy subjects (35% men; mean [SD] age, 25 [4] years). Two hours after the last dose, QTc[B] had increased significantly from baseline by 19 ms (P=0.02). QTc[F] and QTc[Fr] did not change significantly. In the postural study, 19 healthy subjects (68% men; mean [SD] age, 32 [8] years) stood up and QTc[B] increased by a mean (SD) of 8 (15) ms (P=0.03). In these subjects, the QTc[B]/RR regression slope was significantly different from 0 (r=0.60, P=0.002), and the Bazett formula did not eliminate the dependence of QTc on heart rate. However

  3. Comparison between QT Interval Parameters in Type 2 Diabetic and Nondiabetic Patients with Non-ST Elevation Myocardial Infarction

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    HamidReza Bonakdar

    2015-10-01

    Full Text Available Background: QT interval parameters have been suggested as a predictor of lethal arrhythmia and mortality in patients with myocardial infarction. The aim of the present study was to compare the value of QT interval indices in patients presenting with non-ST-segment elevation myocardial infarction (NSTEMI between a group of patients with type 2 diabetes mellitus and a nondiabetic group of patients.Methods: This case-control study evaluated QT interval parameters in 115 patients (47 diabetic and 68 nondiabetic patients diagnosed with NSTEMI between September 2011 and July 2012. The following QT interval indices were analyzed: maximum (max and minimum (min QT interval; max and min corrected QT interval (QTc; QT dispersion (QTd; and corrected QT dispersion (QTcd. All the patients were observed for ventricular arrhythmia during their hospital course and underwent coronary angiography. They were selected to undergo coronary artery bypass surgery (CABG or percutaneous coronary angioplasty (PCI based on their coronary anatomy.Results: The mean age of the patients was 60.8 ± 11.4 years. The patients were 40.0% female and 60.0% male. There were no significant differences in clinical characters between type 2 diabetic and nondiabetic patients with NSTEMI. Compared with post-myocardial infarction patients without diabetes, those with type 2 diabetes had higher QTc max , QTd and QTcd (p value < 0.05. There was a significant difference in QTd and QTcd in the patients needing coronary revascularization with diabetes as opposed to the nondiabetics (p value = 0.035 and p value = 0.025, respectively as well as those who had ventricular arrhythmia with diabetes (p value = 0.018 and p value = 0.003, respectively. QTcd was higher in the patients who had higher in-hospital mortality (p value = 0.047. The QTc max, QTd and QTcd were significantly (all p values < 0.05 associated with ventricular arrhythmia, QTcd with need for revascularization and QTc max with in

  4. Nifekalant hydrochloride terminating sustained ventricular tachycardia accompanied with QT dispersion prolongation

    Institute of Scientific and Technical Information of China (English)

    WANG Jing; HUA Wei; ZHU Jun; YANG Yan-min; WANG Fang-zheng; PU Jie-lin; CHEN Ke-ping; ZHANG Shu

    2010-01-01

    Background Ventricular tachycardia (VT) and ventricular fibrillation are the main reasons causing sudden cardiac death.This study aimed to investigate the effects of nifekalant hydrochloride (NIF) on QT dispersion (QTd) in treating VT.Methods A total of 16 consecutive patients suffered sustained VT was included and then randomly divided into two groups according to the administration duration of NIF.In long-time group (group L), patients were injected with NIF continuously for at least 12 hours after a bolus dose.The patients in short-time group (group S) were injected with NIF just for 1 hour.Results There were 7 of all 10 episodes of VT which were terminated by NIF, including 4 episodes in group L were stopped over 1 hour after continuous infusion of NIF.One patient suffered from torsade de pointes.Electrocardiography analysis indicated that QTd was significantly decreased 12 hours after stopping of infusing NIF compared with that when VT stopped ((45.4±22.1) ms vs.(73.4±33.2) ms, P <0.01), and the corrected QTd (QTcd) decreased too ((47.8±22.9) ms vs.(78.3±36.5) ms, P <0.01 ).There was a positive correlation between the increase in QTd and dose of administrating NIF (P <0.01), so was QTcd (P <0.01).Conclusions More administration of NIF indicates higher terminating rate of VT and more QTd prolongation.However,the safety is acceptable if several important issues were noticed in using NIF, such as serum potassium concentration,stopping side-effect related agents, and carefully observing clinical responses.

  5. Comparative usefulness of beat-to-beat QT dispersion and QT interval fluctuations for identifying patients with organic heart disease at risk for ventricular arrhythmias.

    Science.gov (United States)

    Galeano, Erdulfo J; Yoshida, Akihiro; Ohnishi, Yoshio; Okajima, Katsunori; Ishida, Akihiko; Kitamura, Hidetsuna; Kubo, Shinya; Yokoyama, Mitsuhiro

    2003-02-01

    The comparative usefulness of 10 min of beat-to-beat 12-lead QT dispersion (QTd) and QT interval variability index (QTVI) analysis for identifying patients with organic heart disease (OHD) at risk for ventricular arrhythmias was assessed in 86 subjects: 54 had OHD without a history of ventricular arrhythmias, 15 had OHD with documented ventricular tachycardia, and there were 17 controls. The following parameters were analyzed among the groups: (1) the average QTd (mean QTd), (2) the difference between the maximum and minimum QTd observed over the recording time (QTd variation), (3) the maximum difference of QTd between consecutive beats (QTd maximum), (4) the QTd standard deviation (QTd variability), and (5) QTVI, calculated in lead I or II according to an established formula: log 10 [(QTv/QTm2) / (HRv/HRm2)]. All the analyzed parameters were significantly increased in the patients with and without ventricular tachycardia when compared with the controls. QTd variation, QTd maximum and QTd variability were the only variables that remained significantly increased in the group of patients with documented ventricular tachycardia, compared with those without arrhythmia. Thus, beat-to-beat fluctuations of both the QT interval and QTd may be markers of temporal electrical instability in patients with OHD.

  6. Ventricular ectopy and QTc-interval prolongation associated with dronedarone therapy.

    Science.gov (United States)

    Gonzalez, Jaime E; Sauer, William H; Krantz, Mori J

    2013-10-01

    Amiodarone is an effective treatment for atrial and ventricular arrhythmias, but its use is limited by a toxic adverse-effect profile. Although dronedarone has been touted as an antiarrhythmic agent devoid of both solid organ toxicity and proarrhythmic properties, its potential for prolonging ventricular repolarization may augment triggered ectopy. We describe a 66-year-old man who began dronedarone 400 mg twice/day for new-onset paroxysmal atrial fibrillation; he had no left ventricular dysfunction or clinical heart failure. Three months after starting the drug, he complained of malaise, fatigue, and rare palpitations. Twenty four-hour Holter monitoring revealed increased premature ventricular complexes, and the rate-corrected QT (QTc) interval was prolonged (range 525-760 msec). Dronedarone was discontinued and the patient's symptoms gradually resolved over the next 3 weeks. Holter monitoring revealed a marked reduction in ventricular ectopy burden, and the QTc interval decreased to his baseline values. Even in the absence of documented symptomatic torsade de pointes, this case suggests that caution should be exercised when prescribing dronedarone and that serial QTc interval monitoring may be appropriate. In addition, clinicians should have a low threshold to perform Holter monitoring if symptoms develop during dronedarone therapy.

  7. Abnormal vascular function in PR-interval prolongation.

    Science.gov (United States)

    Chan, Yap-Hang; Siu, Chung-Wah; Yiu, Kai-Hang; Li, Sheung-Wai; Lau, Kui-Kai; Lam, Tai-Hing; Lau, Chu-Pak; Tse, Hung-Fat

    2011-10-01

    Underlying mechanisms of PR-interval prolongation leading to increased risk of adverse cardiovascular outcomes, including atrial fibrillation, are unclear. This study aims to investigate the relation between PR interval and changes in vascular function. We hypothesize that there exists an intermediate pathological stage between electrocardiographic PR prolongation and adverse cardiovascular outcomes, which could be reflected by changes in surrogate measurements of vascular function. We recruited 88 healthy subjects (mean age 57.5 ± 9.8 y, 46% male) from a community-based health screening program who had no history of cardiovascular disease or diabetes mellitus. PR interval was determined from a resting 12-lead electrocardiogram. Vascular function was noninvasively assessed by flow-mediated dilation (FMD) using high-resolution ultrasound and brachial-ankle pulse wave velocity (PWV) using a vascular profiling system. Only 3 subjects had a PR-interval length longer than the conventional cutoff of 200 ms. The PR-interval length was associated inversely with FMD (Pearson r = -0.30, P = 0.004) and positively with PWV (r = 0.40, P PR-interval length by each 25 ms was independently associated with reduced FMD by -1 unit (absolute %, B = -0.04 [95% confidence interval: -0.080 to -0.002, P = 0.040)] and increased PWV by +103 cm/second (B = +4.1 [95% confidence interval: 0.6-7.6, P = 0.023]). This study shows that PR-interval length, even in the conventionally normal range, is independently associated with endothelial dysfunction and increased arterial stiffness in healthy subjects free of atherosclerotic disease. This suggests the presence of a systemic, intermediate pathologic stage of the vasculature in PR prolongation before clinically manifest cardiovascular events, and could represent a mediating mechanism. © 2011 Wiley Periodicals, Inc.

  8. Uremic retention solute indoxyl sulfate level is associated with prolonged QTc interval in early CKD patients.

    Directory of Open Access Journals (Sweden)

    Wei-Hua Tang

    Full Text Available Total mortality and sudden cardiac death is highly prevalent in patients with chronic kidney disease (CKD. In CKD patients, the protein-bound uremic retention solute indoxyl sulfate (IS is independently associated with cardiovascular disease. However, the underlying mechanisms of this association have yet to be elucidated. The relationship between IS and cardiac electrocardiographic parameters was investigated in a prospective observational study among early CKD patients. IS arrhythmogenic effect was evaluated by in vitro cardiomyocyte electrophysiological study and mathematical computer simulation. In a cohort of 100 early CKD patients, patients with corrected QT (QTc prolongation had higher IS levels. Furthermore, serum IS level was independently associated with prolonged QTc interval. In vitro, the delay rectifier potassium current (IK was found to be significantly decreased after the treatment of IS in a dose-dependent manner. The modulation of IS to the IK was through the regulation of the major potassium ion channel protein Kv 2.1 phosphorylation. In a computer simulation, the decrease of IK by IS could prolong the action potential duration (APD and induce early afterdepolarization, which is known to be a trigger mechanism of lethal ventricular arrhythmias. In conclusion, serum IS level is independently associated with the prolonged QTc interval in early CKD patients. IS down-regulated IK channel protein phosphorylation and the IK current activity that in turn increased the cardiomyocyte APD and QTc interval in vitro and in the computer ORd model. These findings suggest that IS may play a role in the development of arrhythmogenesis in CKD patients.

  9. Normal electrocardiographic QT interval in race-fit Standardbred horses at rest and its rate dependence during exercise

    DEFF Research Database (Denmark)

    Pedersen, Philip J; Kanters, Jørgen K.; Buhl, Rikke

    2013-01-01

    Cardiac repolarization, measured as QT and Tpeak to Tend (TpTe) intervals on the ECG, is important, as irregularities caused by diseases, ventricular hypertrophy, drugs and genetic defects can trigger arrhythmias which predispose human patients to syncope and sudden cardiac death. In horses, repo...

  10. Serum 25-Hydroxyvitamin D, Calcium, Phosphorus, and Electrocardiographic QT Interval Duration: Findings from NHANES III and ARIC

    Science.gov (United States)

    Zhang, Yiyi; Post, Wendy S.; Dalal, Darshan; Bansal, Sandeep; Blasco-Colmenares, Elena; Jan De Beur, Suzanne; Alonso, Alvaro; Soliman, Elsayed Z.; Whitsel, Eric A.; Brugada, Ramón; Tomaselli, Gordon F.

    2011-01-01

    Context: Disturbances in 25-hydroxyvitamin D, calcium, and phosphorus concentrations have been associated with increased risks of total and cardiovascular mortality. It is possible that changes in electrocardiographic QT interval duration may mediate these effects, but the association of 25-hydroxyvitamin D, phosphorus, and calcium concentrations with QT interval duration has not been evaluated in general population samples. Objective: The objective of the study was to evaluate the association of 25-hydroxyvitamin D, phosphorus, and calcium concentrations with QT interval duration in two large samples of the U.S. general population. Design: This study included cross-sectional analyses the Third National Health and Nutrition Survey (NHANES III) and the Atherosclerosis Risk in Communities (ARIC) study. Setting: The study was conducted in the general community. Patients or Other Participants: Patients included 7,312 men and women from NHANES III and 14,825 men and women from the ARIC study. Interventions: Serum 25-hydroxyvitamin D, total and ionized calcium, and inorganic phosphorus were measured in NHANES III, and serum total calcium and inorganic phosphorus were measured in ARIC. Main Outcome Measure: QT interval duration was obtained from standard 12-lead electrocardiograms. Results: In NHANES III, the multivariate adjusted differences in average QT interval duration comparing the highest vs. the lowest quartiles of serum total calcium, ionized calcium, and phosphorus were −3.6 msec (−5.8 to −1.3; P for trend = 0.005), −5.4 msec (−7.4 to −3.5; P for trend <0.001), and 3.9 msec (2.0–5.9; P for trend <0.001), respectively. The corresponding differences in ARIC were −3.1 msec (−4.3 to −2.0; P for trend <0.001), −2.9 msec (−3.8 to −1.9; P for trend <0.001), and 2.3 msec (1.3–3.3; P for trend <0.001). No association was found between 25-hydroxyvitamin D concentrations and QT interval duration. Conclusions: In two large samples of the general

  11. The evaluation of QT intervals during diagnosis and after follow-up in acromegaly patients.

    Science.gov (United States)

    Baser, Husniye; Akar Bayram, Nihal; Polat, Burcak; Evranos, Berna; Ersoy, Reyhan; Bozkurt, Engin; Cakir, Bekir

    2014-01-01

    Introdução: O estudo teve como objectivo a determinação do intervalo QT em doentes com acromegália e a análise da correlação entre o intervalo QT e a concentração de hormona do crescimento e de IGF-1 (insulin-like growth factor-1). Material e Métodos: O estudo englobou 41 doentes com acromegália. O grupo de controlo englobou 41 indivíduos com características semelhantes no que se refere a comorbilidades, idade e género. A electrocardiografia de doentes com acromegália foi obtida no início do estudo e após o follow-up. Foi apenas obtido um electrocardiograma no grupo de controlo. Foram calculados o QT máximo, QT mínimo, dispersão do intervalo QT, QT máximo corrigido, QT mínimo corrigido e dispersão do intervalo QT corrigido. Resultados: Os valores do QT máximo basal, dispersão do intervalo QT, QT máximo corrigido e dispersão do QT corrigido foram significativamente mais prolongados no grupo de doentes com acromegália do que nos controlos. O QT máximo corrigido e a dispersão do QT corrigido foram significativamente mais curtos durante o seguimento clínico, quando comparados com os valores basais dos doentes. O QT máximo, dispersão do QT, QT máximo corrigido e dispersão do QT corrigido durante o seguimento clínico não foram estatisticamente diferentes dos valores obtidos nos controlos. Com excepção de uma correlação negativa entre os valores da hormona do crescimento e a dispersão do QT corrigido em doentes durante o seguimento clínico, nenhuma outra correlação foi assinalada entre os valores do intervalo QT e as concentrações de hormona do crescimento e de IGF-1. Concluiu-se que a dispersão do intervalo QT está correlacionada com a duração da doença nos doentes com acromegália. Discussão: Em doentes com acromegália, é importante a detecção de preditores clínicos de arritmia cardíaca. A dispersão do intervalo QT é considerada um preditor relevante de arritmias ventriculares. Os doentes com acromeg

  12. Lesson Forty-Four Evaluation of Toxicity for Heart Failure Therapeutics:Studying Effects on the QT Interval

    Institute of Scientific and Technical Information of China (English)

    童鸿

    2011-01-01

    @@ Introduction One of the most feared complications in medicine is sudden death caused by drug-induced proarrhythmia.Accordingly, concerted efforts have been made to define a drug's proarrhythmic potential before regulatory approval.Monitoring for QT prolongation is one such method.Patients with heart failure represent a particularly high-risk population for torsade de pointes because of structural and electric remodeling that impair repolarization reserve1.

  13. Quantification of 16 QT-prolonging Drugs and Metabolites in Human Postmortem Blood and Cardiac Tissue Using UPLC–MS-MS

    DEFF Research Database (Denmark)

    Mikkelsen, Christian Reuss; Jornil, Jakob; Vukelic Andersen, Ljubica;

    2016-01-01

    QT-prolonging compounds present a treatment risk in mentally ill patients. Knowledge of the concentration in the heart compared with blood is necessary to assess the cardiac toxicity of QT-prolonging compounds. To address this issue, this article presents a validated analytical method for the qua......QT-prolonging compounds present a treatment risk in mentally ill patients. Knowledge of the concentration in the heart compared with blood is necessary to assess the cardiac toxicity of QT-prolonging compounds. To address this issue, this article presents a validated analytical method...... for the quantification of 16 QT-prolonging drugs (QTD) and metabolites in postmortem whole blood and postmortem cardiac tissue. Samples were prepared by protein precipitation and quantified using ultra-performance liquid chromatography coupled with tandem mass spectrometry. Deuterated internal standards were used...... concentrations of the prescription drugs. No noteworthy degradation during storage of the extracts was detected. The method was applied in five authentic cases of mentally ill patients. In conclusion, an analytical method was successfully developed and validated for the quantification of QTD in postmortem whole...

  14. QT interval variability in body surface ECG : measurement, physiological basis, and clinical value: position statement and consensus guidance endorsed by the European Heart Rhythm Association jointly with the ESC Working Group on Cardiac Cellular Electrophysiology

    NARCIS (Netherlands)

    Baumert, Mathias; Porta, Alberto; Vos, Marc A; Malik, Marek; Couderc, Jean-Philippe; Laguna, Pablo; Piccirillo, Gianfranco; Smith, Godfrey L; Tereshchenko, Larisa G; Volders, Paul G A

    2016-01-01

    This consensus guideline discusses the electrocardiographic phenomenon of beat-to-beat QT interval variability (QTV) on surface electrocardiograms. The text covers measurement principles, physiological basis, and clinical value of QTV. Technical considerations include QT interval measurement and the

  15. Short QT syndrome.

    Science.gov (United States)

    Schimpf, Rainer; Wolpert, Christian; Gaita, Fiorenzo; Giustetto, Carla; Borggrefe, Martin

    2005-08-15

    The short QT syndrome constitutes a new clinical entity that is associated with a high incidence of sudden cardiac death, syncope, and/or atrial fibrillation even in young patients and newborns. Patients with this congenital electrical abnormality are characterized by rate-corrected QT intervalsdelayed-rectifier current I(Kr) have been identified in the first two reported families with familial sudden cardiac death. Recently, two further gain-of-function mutations in the KCNQ1 gene encoding the alpha-subunit of the KvLQT1 (I(Ks)) channel and in the KCNJ2 gene encoding the strong inwardly rectifying channel protein Kir2.1 confirmed a genetically heterogeneous disease. The possible substrate for the development of ventricular tachyarrhythmias may be a significant transmural dispersion of the repolarisation due to a heterogeneous abbreviation of the action potential duration. The implantable cardioverter defibrillator is the therapy of choice in patients with syncope and a positive family history of sudden cardiac death. However, ICD therapy in patients with a short QT syndrome has an increased risk for inappropriate shock therapies due to possible T wave oversensing. The impact of sotalol, ibutilide, flecainide, and quinidine on QT prolongation has been evaluated, but only quinidine effectively suppressed gain-of-function in I(Kr) with prolongation of the QT interval. In patients with a mutation in HERG, it rendered ventricular tachycardias/ventricular fibrillation non-inducible and restored the QT interval/heart rate relationship towards a normal range. It may serve as an adjunct to ICD therapy or as a possible alternative treatment, especially for children and newborns.

  16. Comparison of two methods of estimating reader variability in QT interval measurements in thorough QT/QTc studies.

    Science.gov (United States)

    Salvi, Vaibhav; Karnad, Dilip R; Kerkar, Vaibhav; Panicker, Gopi Krishna; Natekar, Mili; Kothari, Snehal

    2014-03-01

    Two methods of estimating reader variability (RV) in QT measurements between 12 readers were compared. Using data from 500 electrocardiograms (ECGs) analyzed twice by 12 readers, we bootstrapped 1000 datasets each for both methods. In grouped analysis design (GAD), the same 40 ECGs were read twice by all readers. In pairwise analysis design (PAD), 40 ECGs analyzed by each reader in a clinical trial were reanalyzed by the same reader (intra-RV) and also by another reader (inter-RV); thus, variability between each pair of readers was estimated using different ECGs. Inter-RV (mean [95% CI]) between pairs of readers by GAD and PAD was 3.9 ms (2.1-5.5 ms) and 4.1 ms (2.6-5.4 ms), respectively, using ANOVA, 0 ms (-0.0 to 0.4 ms), and 0 ms (-0.7 to 0.6 ms), respectively, by actual difference between readers and 7.7 ms (6.2-9.8 ms) and 7.7 ms (6.6-9.1 ms), respectively, by absolute difference between readers. Intra-RV too was comparable. RV estimates by the grouped- and pairwise analysis designs are comparable. © 2014 Wiley Periodicals, Inc.

  17. Usefulness of short-term variability of QT intervals as a predictor for electrical remodeling and proarrhythmia in patients with nonischemic heart failure

    DEFF Research Database (Denmark)

    Hinterseer, Martin; Beckmann, Britt-Maria; Thomsen, Morten Bækgaard;

    2010-01-01

    The high incidence of sudden cardiac death in heart failure (HF) reflects electrophysiologic changes in response to myocardial failure. We previously showed that short-term variability of QT intervals (STV(QT)) identifies latent repolarization disorders in patients with drug-induced or congenital...

  18. QT measurement and heart rate correction during hypoglycemia

    DEFF Research Database (Denmark)

    Christensen, Toke Folke; Randløv, Jette; Christensen, Leif Engmann;

    2010-01-01

    Introduction. Several studies show that hypoglycemia causes QT interval prolongation. The aim of this study was to investigate the effect of QT measurement methodology, heart rate correction, and insulin types during hypoglycemia. Methods. Ten adult subjects with type 1 diabetes had hypoglycemia...... induced by intravenous injection of two insulin types in a cross-over design. QT measurements were done using the slope-intersect (SI) and manual annotation (MA) methods. Heart rate correction was done using Bazett's (QTcB) and Fridericia's (QTcF) formulas. Results. The SI method showed significant...... a significant impact on the prolongation of QT during hypoglycemia. Heart rate correction may also influence the QT during hypoglycemia while the type of insulin is insignificant. Prolongation of QTc in this study did not reach pathologic values suggesting that QTc prolongation cannot fully explain the dead...

  19. Prognostic 2.0: software tool for heart rate variability analysis and QT interval dispersion

    Science.gov (United States)

    Mendoza, Alfonso; Rueda, Oscar L.; Bautista, Lola X.; Martinez, Víctor E.; Lopez, Eddie R.; Gomez, Mario F.; Alvarez, Alexander

    2007-09-01

    Cardiovascular diseases, in particular Acute Myocardial Infarction (AMI) are the first cause of death in industrialized countries. Measurements of indicators of the behavior of the autonomic nervous system, such as the Heart Rate Variability (HRV) and the QT Interval Dispersion (QTD) in the acute phase of the AMI (first 48 hours after the event) give a good estimation of the subsequent cardiac events that could present a person who had suffered an AMI. This paper describes the implementation of the second version of Prognostic-AMI, a software tool that automate the calculation of such indicators. It uses the Discrete Wavelet Transform (DWT) to de-noise the signals an to detect the QRS complex and the T-wave from a conventional electrocardiogram of 12 leads. Indicators are measured in both time and frequency domain. A pilot trial performed on a sample population of 76 patients shows that people who had had cardiac complications in the acute phase of the AMI have low values in the indicators of HRV and QTD.

  20. Quantification of 16 QT-prolonging Drugs and Metabolites in Human Postmortem Blood and Cardiac Tissue Using UPLC-MS-MS

    DEFF Research Database (Denmark)

    Mikkelsen, Christian R; Jornil, Jakob; Andersen, Ljubica V;

    2016-01-01

    QT-prolonging compounds present a treatment risk in mentally ill patients. Knowledge of the concentration in the heart compared with blood is necessary to assess the cardiac toxicity of QT-prolonging compounds. To address this issue, this article presents a validated analytical method for the qua......QT-prolonging compounds present a treatment risk in mentally ill patients. Knowledge of the concentration in the heart compared with blood is necessary to assess the cardiac toxicity of QT-prolonging compounds. To address this issue, this article presents a validated analytical method....... Validation results showed that the bias was ±15% and precision was ≤15% for all compounds in both matrices. The recovery ranged from 78.8 to 127.4%, and the matrix effect ranged from 61.0 to 128.7% across both matrices. The limit of detection and the lower limit of quantification were below the therapeutic...... concentrations of the prescription drugs. No noteworthy degradation during storage of the extracts was detected. The method was applied in five authentic cases of mentally ill patients. In conclusion, an analytical method was successfully developed and validated for the quantification of QTD in postmortem whole...

  1. Short-term beat-to-beat variability of the QT interval is increased and correlates with parameters of left ventricular hypertrophy in patients with hypertrophic cardiomyopathy.

    Science.gov (United States)

    Orosz, Andrea; Baczkó, István; Nagy, Viktória; Gavallér, Henriette; Csanády, Miklós; Forster, Tamás; Papp, Julius Gy; Varró, András; Lengyel, Csaba; Sepp, Róbert

    2015-09-01

    Stratification models for the prediction of sudden cardiac death (SCD) are inappropriate in patients with hypertrophic cardiomyopathy (HCM). We investigated conventional electrocardiogram (ECG) repolarization parameters and the beat-to-beat short-term QT interval variability (QT-STV), a new parameter of proarrhythmic risk, in 37 patients with HCM (21 males, average age 48 ± 15 years). Resting ECGs were recorded for 5 min and the frequency corrected QT interval (QTc), QT dispersion (QTd), beat-to-beat short-term variability of QT interval (QT-STV), and the duration of terminal part of T waves (Tpeak-Tend) were calculated. While all repolarization parameters were significantly increased in patients with HCM compared with the controls (QTc, 488 ± 61 vs. 434 ± 23 ms, p < 0.0001; QT-STV, 4.5 ± 2 vs. 3.2 ± 1 ms, p = 0.0002; Tpeak-Tend duration, 107 ± 27 vs. 91 ± 10 ms, p = 0.0015; QTd, 47 ± 17 vs. 34 ± 9 ms, p = 0.0002), QT-STV had the highest relative increase (+41%). QT-STV also showed the best correlation with indices of left ventricular (LV) hypertrophy, i.e., maximal LV wall thickness normalized for body surface area (BSA; r = 0.461, p = 0.004) or LV mass (determined by cardiac magnetic resonance imaging) normalized for BSA (r = 0.455, p = 0.015). In summary, beat-to-beat QT-STV showed the most marked increase in patients with HCM and may represent a novel marker that merits further testing for increased SCD risk in HCM.

  2. Overexpression of KCNJ2 in induced pluripotent stem cell-derived cardiomyocytes for the assessment of QT-prolonging drugs

    Directory of Open Access Journals (Sweden)

    Min Li

    2017-06-01

    Full Text Available Human induced pluripotent stem cell (hiPSC-derived cardiomyocytes hold great potentials to predict pro-arrhythmic risks in preclinical cardiac safety screening, although the hiPSC cardiomyocytes exhibit rather immature functional and structural characteristics, including spontaneous activity. Our physiological characterization and mathematical simulation showed that low expression of the inward-rectifier potassium (IK1 channel is a determinant of spontaneous activity. To understand impact of the low IK1 expression on the pharmacological properties, we tested if transduction of hiPSC-derived cardiomyocytes with KCNJ2, which encodes the IK1 channel, alters pharmacological response to cardiac repolarization processes. The transduction of KCNJ2 resulted in quiescent hiPSC-derived cardiomyocytes, which need pacing to elicit action potentials. Significant prolongation of paced action potential duration in KCNJ2-transduced hiPSC-derived cardiomyocytes was stably measured at 0.1 μM E-4031, although the same concentration of E-4031 ablated firing of non-treated hiPSC-derived cardiomyocytes. These results in single cells were confirmed by mathematical simulations. Using the hiPSC-derived cardiac sheets with KCNJ2-transduction, we also investigated effects of a range of drugs on field potential duration recorded at 1 Hz. The KCNJ2 overexpression in hiPSC-derived cardiomyocytes may contribute to evaluate a part of QT-prolonging drugs at toxicological concentrations with high accuracy.

  3. No effect on QT intervals of mipomersen, a 2'-O-methoxyethyl modified antisense oligonucleotide targeting ApoB-100 mRNA, in a phase I dose escalation placebo-controlled study, and confirmed by a thorough QT (tQT) study, in healthy subjects.

    Science.gov (United States)

    Yu, Rosie Z; Gunawan, Rudy; Li, Zhaoyang; Mittleman, Robert S; Mahmood, Asif; Grundy, John S; Singleton, Walter; Geary, Richard; Wang, Yanfeng

    2016-03-01

    The aim of this study to evaluate the effect of mipomersen on QT intervals in a phase I dose escalation, placebo-controlled study, and a thorough QT (tQT) study in healthy subjects. In the initial phase I study, 29 healthy subjects received either single or multiple (for 4 weeks) ascending doses of mipomersen (50-400 mg) administered subcutaneously (SC) or via a 2-h intravenous (IV) infusion, and 7 subjects received placebo. In the confirmative tQT study, 58 healthy subjects received placebo, 400 mg IV moxifloxacin, 200 mg SC, or 200 mg IV of mipomersen in a double-blind, 4-way crossover design with a minimum 5-day washout between treatments. ECG measurements were performed at baseline and selected time points (including Tmax). The correlation between QTcF intervals corrected for baseline and time-matched placebo when available with PK plasma exposure was evaluated by linear regression analysis. In the phase I study, no positive correlation between the PK exposure and ∆QTcF or ∆∆QTcF was observed within the wide dose or exposure range tested. Similar results were observed in the tQT study, where the predicted ΔΔQTcF and its upper bound of the 90% CI at Cmax of therapeutic and supratherapeutic dose were approximately -1.7 and 2.9 ms, respectively. Mipomersen showed no effect on QT intervals in both the phase I dose escalation study and the tQT study. These results support the proposal that QT assessment can be made in a phase I dose escalation study, and no tQT study may be necessary if the phase I dose escalation study showed a negative QT effect.

  4. CHANGES IN HEART RATE, HEART RATE VARIABILITY AND QT INTERVAL IN WOMEN WITH RHEUMATOID ARTHRITIS DURING RITUXIMAB TREATMENT

    Directory of Open Access Journals (Sweden)

    D. S. Novikova

    2014-01-01

    Full Text Available Rheumatoid arthritis (RA is a proven high cardiovascular risk disease. High heart rate (HR, lower heart rate variabil- ity (HRV, and increased QT interval are considered as predictors of cardiovascular events in patients with coronary heart disease, chronic heart failure, and diabetes mellitus. In RA, there is a pronounced rise in HR, a reduction in HRV, and an increase in QT interval mainly due to the factors reflecting the severity of the disease. Rituximab (RTM is successfully used to treat patients with high RA activity. At the same time there are only a few pieces of evidence for the effect of the drug on the cardiovascular system. Objective: to study changes in HR, HRV, and QT interval values obtained during electrocardiography (ECG Holter monitoring (ECG HM in RTM-treated women during a 6-month follow-up. Subjects and methods: The investigation enrolled 55 women (mean age 50 years with a definite diagnosis of RA and its high activity. The patients were examined 6 months after administration of RTM. The latter was infused intra- venously twice (500 and 1000 mg in 22% and 78% of the patients, respectively during therapy with disease-modifying antirheumatic and non-steroidal anti-inflammatory drugs and glucocorticoids. The RA patients were divided into two groups: 1 a satisfactory/good effect of RTM according to the EULAR criteria (n = 41; 2 no effect (n = 14. Analysis of 24-hour ECG HM yielded the values of HR and mean duration of corrected QT interval (QTc. The tim- ing HRV values obtained at ECG HM were standardized from age and mean HR (SDNNn, RMSSDn, and pNN50n. Results. The baseline HRmin and HRmean values were higher and SDNNn was lower in the RA patients in Group 1 than those in Group 2 (p < 0.05. In Group 1, RTM therapy was accompanied by a reduction in HRmean and HRmin by 8% and by an increase in SDNNn by 3%, RMSSDn by 26%, and pNN50n by 33% whereas no significant changes in HR and HRV were found in Group 2. The RTM therapy

  5. Increased Short-Term Beat-to-Beat QT Interval Variability in Patients with Impaired Glucose Tolerance

    Directory of Open Access Journals (Sweden)

    Andrea Orosz

    2017-06-01

    Full Text Available Prediabetic states and diabetes are important risk factors for cardiovascular morbidity and mortality. Determination of short-term QT interval variability (STVQT is a non-invasive method for assessment of proarrhythmic risk. The aim of the study was to evaluate the STVQT in patients with impaired glucose tolerance (IGT. 18 IGT patients [age: 63 ± 11 years, body mass index (BMI: 31 ± 6 kg/m2, fasting glucose: 6.0 ± 0.4 mmol/l, 120 min postload glucose: 9.0 ± 1.0 mmol/l, hemoglobin A1c (HbA1c: 5.9 ± 0.4%; mean ± SD] and 18 healthy controls (age: 56 ± 9 years, BMI: 27 ± 5 kg/m2, fasting glucose: 5.2 ± 0.4 mmol/l, 120 min postload glucose: 5.5 ± 1.3 mmol/l, HbA1c: 5.4 ± 0.3% were enrolled into the study. ECGs were recorded, processed, and analyzed off-line. The RR and QT intervals were expressed as the average of 30 consecutive beats, the temporal instability of beat-to-beat repolarization was characterized by calculating STVQT as follows: STVQT = Σ|QTn + 1 − QTn| (30x√2−1. Autonomic function was assessed by means of standard cardiovascular reflex tests. There were no differences between IGT and control groups in QT (411 ± 43 vs 402 ± 39 ms and QTc (431 ± 25 vs 424 ± 19 ms intervals or QT dispersion (44 ± 13 vs 42 ± 17 ms. However, STVQT was significantly higher in IGT patients (5.0 ± 0.7 vs 3.7 ± 0.7, P < 0.0001. The elevated temporal STVQT in patients with IGT may be an early indicator of increased instability of cardiac repolarization during prediabetic conditions.

  6. Effects of long-term hormone replacement therapy on QT and corrected QT dispersion during resting and peak exercise electrocardiography in post-menopausal women.

    Science.gov (United States)

    Altunkeser, Bülent B; Ozdemir, Kurtulus; Içli, Abdullah; Celik, Cetin; Akyürek, Cemalettin; Gök, Hasan

    2002-01-01

    It is known that the QT interval is longer in women than men. Estrogen is reported to account for the QT interval prolongation in several studies conducted with hormone replacement therapy (HRT) in postmenopausal women. Along with this, there are conflicting data as regards the effects of HRT on QT interval and dispersion. Moreover, there is no evidence about the effect of HRT on exercise QT parameters. We compared QT parameters obtained from surface electrocardiograms during resting and peak exercise before and after 6 months of HRT consisting of estrogen plus progesterone in healthy postmenopausal women. Twenty-four healthy postmenopausal women were given 0.625 mg/day conjugated estrogens and 2.5 mg/day medroxyprogesterone acetate for 6 months. Exercise stress testing using the Bruce protocol was performed before and after HRT. QT maximum, minimum, dispersion and corrected QT maximum, minimum and dispersion were calculated during resting and peak exercise. HRT resulted in a significant increase in estradiol plasma levels from 24+/-10 pg/mL to 117+/-66 pg/mL (Pexercise (20+/-7 versus 25+/-10 ms; Pexercise QT parameters were unchanged. The resting QT parameters are not affected by long term HRT consisting of estrogen plus progesterone, which leads to an increase in QT dispersion and corrected QT dispersion during peak exercise.

  7. Congenital Short QT Syndrome

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    Charles Antzelevitch

    2004-04-01

    Full Text Available Long QT intervals in the ECG have long been associated with sudden cardiac death. The congenital long QT syndrome was first described in individuals with structurally normal hearts in 1957.1 Little was known about the significance of a short QT interval. In 1993, after analyzing 6693 consecutive Holter recordings Algra et al concluded that an increased risk of sudden death was present not only in patients with long QT interval, but also in patients with short QT interval (<400 ms.2 Because this was a retrospective analysis, further evaluation of the data was not possible. It was not until 2000 that a short-QT syndrome (SQTS was proposed as a new inherited clinical syndrome by Gussak et al.3 The initial report was of two siblings and their mother all of whom displayed persistently short QT interval. The youngest was a 17 year old female presenting with several episodes of paroxysmal atrial fibrillation requiring electrical cardioversion.3 Her QT interval measured 280 msec at a heart rate of 69. Her 21 year old brother displayed a QT interval of 272 msec at a heart rate of 58, whereas the 51 year old mother showed a QT of 260 msec at a heart rate of 74. The authors also noted similar ECG findings in another unrelated 37 year old patient associated with sudden cardiac death.

  8. Accuracy of popular automatic QT Interval algorithms assessed by a 'Gold Standard' and comparison with a Novel method: computer simulation study

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    Hunt Anthony

    2005-09-01

    Full Text Available Abstract Background Accurate measurement of the QT interval is very important from a clinical and pharmaceutical drug safety screening perspective. Expert manual measurement is both imprecise and imperfectly reproducible, yet it is used as the reference standard to assess the accuracy of current automatic computer algorithms, which thus produce reproducible but incorrect measurements of the QT interval. There is a scientific imperative to evaluate the most commonly used algorithms with an accurate and objective 'gold standard' and investigate novel automatic algorithms if the commonly used algorithms are found to be deficient. Methods This study uses a validated computer simulation of 8 different noise contaminated ECG waveforms (with known QT intervals of 461 and 495 ms, generated from a cell array using Luo-Rudy membrane kinetics and the Crank-Nicholson method, as a reference standard to assess the accuracy of commonly used QT measurement algorithms. Each ECG contaminated with 39 mixtures of noise at 3 levels of intensity was first filtered then subjected to three threshold methods (T1, T2, T3, two T wave slope methods (S1, S2 and a Novel method. The reproducibility and accuracy of each algorithm was compared for each ECG. Results The coefficient of variation for methods T1, T2, T3, S1, S2 and Novel were 0.36, 0.23, 1.9, 0.93, 0.92 and 0.62 respectively. For ECGs of real QT interval 461 ms the methods T1, T2, T3, S1, S2 and Novel calculated the mean QT intervals(standard deviations to be 379.4(1.29, 368.5(0.8, 401.3(8.4, 358.9(4.8, 381.5(4.6 and 464(4.9 ms respectively. For ECGs of real QT interval 495 ms the methods T1, T2, T3, S1, S2 and Novel calculated the mean QT intervals(standard deviations to be 396.9(1.7, 387.2(0.97, 424.9(8.7, 386.7(2.2, 396.8(2.8 and 493(0.97 ms respectively. These results showed significant differences between means at >95% confidence level. Shifting ECG baselines caused large errors of QT interval with T1 and T2

  9. Sex-Steroid Hormones and Electrocardiographic QT-Interval Duration: Findings From the Third National Health and Nutrition Examination Survey and the Multi-Ethnic Study of Atherosclerosis

    Science.gov (United States)

    Zhang, Yiyi; Ouyang, Pamela; Post, Wendy S.; Dalal, Darshan; Vaidya, Dhananjay; Blasco-Colmenares, Elena; Soliman, Elsayed Z.; Tomaselli, Gordon F.; Guallar, Eliseo

    2011-01-01

    The association between physiologic levels of sex hormones and QT-interval duration in humans was evaluated using data from 727 men enrolled in the Third National Health and Nutrition Examination Survey and 2,942 men and 1,885 postmenopausal women enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA). Testosterone, estradiol, and sex hormone-binding globulin levels were measured in serum and free testosterone was calculated from those values. QT interval was measured using a standard 12-lead electrocardiogram. In men from the Third National Health and Nutrition Survey, the multivariate adjusted differences in average QT-interval duration comparing the highest quartiles with the lowest quartiles of total testosterone and free testosterone were −8.5 ms (95% confidence interval (CI): −15.5, −1.4) and −8.0 ms (95% CI: −13.2, −2.8), respectively. The corresponding differences were −1.8 ms (95% CI: −3.8, −0.2), and −4.7 ms (95% CI: −6.7, −2.6), respectively, in men from MESA and −0.6 ms (95% CI: −3.0, 1.8) and 0.8 ms (95% CI: −1.6, 3.3), respectively, in postmenopausal women from MESA. Estradiol levels were not associated with QT-interval duration in men, but there was a marginally significant positive association in postmenopausal women. The findings suggest that testosterone levels may explain differences in QT-interval duration between men and women and could be a contributor to population variability in QT-interval duration among men. PMID:21768401

  10. Short QT syndrome

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    Fiorenzo Gaita

    2011-12-01

    Full Text Available The short QT syndrome (SQTS is a recently described genetic arrhythmogenic disorder, characterized by abnormally short QT intervals on surface electrocardiogram (ECG and a high incidence of sudden death (SD during life, including the first months of life. The inheritance of SQTS is autosomal dominant, with genetic heterogeneity. Gain-of-function mutations in 3 genes encoding potassium channels have been associated to the disease: KCNH2 encoding IKr (SQT1, KCNQ1 encoding IKs (SQT2, and KCNJ2 encoding IK1 (SQT3. Loss-of-function mutations in 3 genes encoding the cardiac L-type calcium channel, CACNA1C, CACNB2b and CACNA2D1 may underlie a mixed phenotype of Brugada pattern ECG (or non-specific repolarization changes in case of CACNA2D1 and shorter than normal QT intervals. Clinical presentation is often severe, as cardiac arrest represents the first clinical presentation in most subjects. Moreover, often a noticeable family history of cardiac SD is present. Atrial fibrillation may be observed, also in young individuals. At electrophysiological study, short atrial and ventricular refractory periods are found, and atrial and ventricular fibrillation are easily induced by programmed electrical stimulation. The outcome of patients with SQTS becomes relatively safe when they are identified and treated. Currently, the suggested therapeutic strategy is an implantable cardioverter- defibrillator (ICD in patients with personal history of aborted SD or syncope. In asymptomatic adult patients from highly symptomatic families and in newborn children pharmacological treatment with hydroquinidine, which has been shown to prolong the QT interval and reduce the inducibility of ventricular arrhythmias, may be proposed.

  11. Anaesthesia Application for Cardiac Denervation in a Patient with Long QT Syndrome and Cardiomyopathy

    Science.gov (United States)

    Karadeniz, Ümit; Demir, Aslı; Koçulu, Rabia

    2016-01-01

    Long QT syndrome is a congenital disorder that is characterized by a prolongation of the QT interval on electrocardiograms and a propensity to ventricular tachyarrhythmias, which may lead to syncope, cardiac arrest or sudden death. Cardiomyopathy and pulmonary hypertension diseases have additional risks in anaesthesia management. In this study, we emphasize on one lung ventilation, pacemaker-implantable cardioverter–defibrillator and the anaesthesia management process in a patient with long QT syndrome, cardiomyopathy and pulmonary hypertension who underwent thoracic sympathectomy. PMID:27366557

  12. Effects of propofol and sevoflurane for induction in general anesthesia on QT interval1%丙泊酚和七氟醚全麻诱导对心电图QT间期的影响

    Institute of Scientific and Technical Information of China (English)

    庄上英; 欧阳葆怡; 黄焕森; 庄小雪梁荣丰

    2014-01-01

    目的::观测丙泊酚静脉诱导、七氟醚吸入诱导、丙泊酚与七氟醚静吸复合诱导对QT间期的影响。方法:选择2013年1月至2014年1月在广州医科大学附属第一医院择期气管插管全麻下行手术治疗的中青年患者45例为研究对象,根据数字表法随机将患者分为3组:单纯丙泊酚静脉诱导组( P 组)、单纯七氟醚吸入诱导组( S组)和丙泊酚七氟醚静吸复合诱导组( PS组),每组各15例。分别于诱导前和诱导后行心电图检查,记录心率、血压、QT间期变化,计算QTc-F。结果:与诱导前相比,P组、S组和PS组诱导后的QTc-F显著延长(P0.05)。结论:3种诱导方法均有使QT间期延长的趋势,均需谨慎用于术前QT间期延长的患者。%Objective:To observe the effects of propofol intravenous induction, sevoflurane inhalation induction,and propofol intravenous induction combined with sevoflurane inhalation induction on QT interval. Methods: Forty-five young patients, who underwent elective operation with endotracheally intubated general anesthesia in the First Affiliated Hospital of Guangzhou Medical University between January 2013 and January 2014, were included and randomized into single propofol intravenous induction group ( Group P ) , single sevoflurane inhalation induction group ( Group S) ,and propofol intravenous induction combined with sevoflurane inhalation induction group (Group PS),with 15 cases in each group.Electrocardiography was taken before and after induction. The changes in heart rate, blood pressure, and QT interval were recorded, and the QTc-F was calculated.Results:Compared with the pre-induction, the QTc-F of group P, group S and group PS prolonged significantly after induction ( P0.05).Conclusion:All the three induction methods tend to prolong QT interval, which should be cautiously used for patients who have QT interval prolongation before operation.

  13. Drug-induced long QT syndrome increases the risk of drowning.

    Science.gov (United States)

    Vincenzi, Frank F

    2016-02-01

    There is strong evidence linking inherited long QT syndromes with an increased risk of drowning due to fatal arrhythmias in the water. Drug-induced long QT syndrome (DILQTS) is hypothesized to increase the risk of drowning by similar mechanisms. It is suggested that QT prolongation caused by a drug or drugs, when combined with the autonomic conflict associated with the mammalian dive reflex and/or the cold shock reflex, sets up conditions that may result in a sudden fatal arrhythmia while in water - thus an increased risk of drowning related to a drug-induced prolongation of the QT interval. Many widely used drugs prolong the QT interval thus raising a drug safety issue that needs confirmation or refutation.

  14. Management of prolonged QT interval and torsades de pointes in the intoxicated patient

    NARCIS (Netherlands)

    Kan, A. A.; de Lange, D. W.; Donker, D. W.; Meulenbelt, J.

    2014-01-01

    Many drugs can significantly inf luence cardiac repolarisation causing an increased duration of this repolarisation phase, challenging the repolarisation reserve. This may set the stage for life-threatening ventricular arrhythmias such as torsades de pointes (TdP). TdP generally occurs in

  15. Selective acquired long QT syndrome (saLQTS upon risperidone treatment

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    Lazarczyk Maciej

    2012-12-01

    Full Text Available Abstract Background Numerous structurally unrelated drugs, including antipsychotics, can prolong QT interval and trigger the acquired long QT syndrome (aLQTS. All of them are thought to act at the level of KCNH2, a subunit of the potassium channel. Although the QT-prolonging drugs are proscribed in the subjects with aLQTS, the individual response to diverse QT-prolonging drugs may vary substantially. Case presentation We report here a case of aLQTS in response to small doses of risperidone that was confirmed at three independent drug challenges in the absence of other QT-prolonging drugs. On the other hand, the patient did not respond with QT prolongation to some other antipsychotics. In particular, the administration of clozapine, known to be associated with higher QT-prolongation risk than risperidone, had no effect on QT-length. A detailed genetic analysis revealed no mutations or polymorphisms in KCNH2, KCNE1, KCNE2, SCN5A and KCNQ1 genes. Conclusions Our observation suggests that some patients may display a selective aLQTS to a single antipsychotic, without a potassium channel-related genetic substrate. Contrasting with the idea of a common target of the aLQTS-triggerring drugs, our data suggests existence of an alternative target protein, which unlike the KCNH2 would be drug-selective.

  16. Diagnostic performance of various QTc interval formulas in a large family with long QT syndrome type 3 : Bazett's formula not so bad after all

    NARCIS (Netherlands)

    Brouwer, J; van den Berg, MP; Grobbee, DE; Haaksma, J; Wilde, AAM

    2003-01-01

    Background: Recently, we identified a novel mutation of SCN5A (1795insD) in a large family with LQTS(3). The aim of this study was to assess whether the various proposed corrections of the QT interval to heart rate help to improve the identification of carriers of the mutant gene. Methods: The study

  17. Diagnostic performance of various QTc interval formulas in a large family with long QT syndrome type 3 : Bazett's formula not so bad after all

    NARCIS (Netherlands)

    Brouwer, J; van den Berg, MP; Grobbee, DE; Haaksma, J; Wilde, AAM

    2003-01-01

    Background: Recently, we identified a novel mutation of SCN5A (1795insD) in a large family with LQTS(3). The aim of this study was to assess whether the various proposed corrections of the QT interval to heart rate help to improve the identification of carriers of the mutant gene. Methods: The study

  18. 常用麻醉药物对QT间期的影响%The effect of the commonly used anesthetic on the QT interval

    Institute of Scientific and Technical Information of China (English)

    张巧云; 滕金亮

    2012-01-01

    背景 迄今为止,临床资料显示有近30多种药物会对QT间期(QT interval,QTc)产生影响,其中包括某些麻醉药物.目的 了解各种常用麻醉药物对QTc的不同影响,有助于临床合理选择麻醉用药.内容 常用的麻醉药及麻醉辅助用药对QTc的不同影响.趋向 通过了解常用麻醉药物对QTc的不同影响,有助于麻醉医师针对不同患者选择合适的麻醉药物,从而有效预防一些可能发生的不良症状.%Background According to the clinical data,more than 30 kinds of drugs,including some commonly used anesthetics,could affect the QT interval.Objective With better understanding the effects of different anesthetics on the QT interval,anesthetists can choose anesthetics for clinical use rationally.Content Different effects of the commonly used anesthetics and the adjuvant drugs on the QT interval are compared.Trend It is better for the anesthetists to choose the proper anesthetics for different patients with the understanding different anesthetics affecting on the QT interval as some adverse symptom can be prevented efficiently.

  19. Ventricular Cycle Length Characteristics Estimative of Prolonged RR Interval during Atrial Fibrillation

    Science.gov (United States)

    CIACCIO, EDWARD J.; BIVIANO, ANGELO B.; GAMBHIR, ALOK; EINSTEIN, ANDREW J.; GARAN, HASAN

    2014-01-01

    Background When atrial fibrillation (AF) is incessant, imaging during a prolonged ventricular RR interval may improve image quality. It was hypothesized that long RR intervals could be predicted from preceding RR values. Methods From the PhysioNet database, electrocardiogram RR intervals were obtained from 74 persistent AF patients. An RR interval lengthened by at least 250 ms beyond the immediately preceding RR interval (termed T0 and T1, respectively) was considered prolonged. A two-parameter scatterplot was used to predict the occurrence of a prolonged interval T0. The scatterplot parameters were: (1) RR variability (RRv) estimated as the average second derivative from 10 previous pairs of RR differences, T13–T2, and (2) Tm–T1, the difference between Tm, the mean from T13 to T2, and T1. For each patient, scatterplots were constructed using preliminary data from the first hour. The ranges of parameters 1 and 2 were adjusted to maximize the proportion of prolonged RR intervals within range. These constraints were used for prediction of prolonged RR in test data collected during the second hour. Results The mean prolonged event was 1.0 seconds in duration. Actual prolonged events were identified with a mean positive predictive value (PPV) of 80% in the test set. PPV was >80% in 36 of 74 patients. An average of 10.8 prolonged RR intervals per 60 minutes was correctly identified. Conclusions A method was developed to predict prolonged RR intervals using two parameters and prior statistical sampling for each patient. This or similar methodology may help improve cardiac imaging in many longstanding persistent AF patients. PMID:23998759

  20. Relationship Between Angiotensin-converting Enzyme Gene Polymorphism and QT Dispersion in Hemodialysis Patients.

    Science.gov (United States)

    Toraman, Aysun; Colak, Hulya; Tekce, Hikmet; Cam, Sirri; Kursat, Seyhun

    2017-05-01

    The angiotensin-converting enzyme (ACE) gene insertion or deletion in long-term hemodialysis patients may be associated with corrected QT interval prolongation, leading to fatal arrhythmias. The ACE D allele is known to increase the risk of malignant ventricular arrhythmias and is also associated with increased QT dispersion after myocardial infarction and hypertension. This study aimed to evaluate the relationship between ACE gene polymorphism and QT dispersion in hemodialysis patients. In 70 hemodialysis patients, electrocardiography was performed and QT dispersion was calculated. Corrected QT interval was calculated using Bazett Formula. The ACE gene polymorphism was determined by polymerase chain reaction. The mean age of the patients was 60 ± 12 years. The mean QT dispersion and corrected QT dispersion were 61.71 ± 21.99 and 73.18 ± 25.51, respectively. QT dispersion inversely correlated with serum calcium and potassium levels and positively correlated with ACE gene polymorphism and residual urine. Calcium level was the predictor factor for QT dispersion. The ACE genotype correlated with QT dispersion, corrected QT dispersion, hemoglobin, and residual urine, and inversely correlated with serum potassium. Corrected QT dispersion correlated with ACE gene polymorphism and residual urine. The DD genotype of ACE had significally greater QT dispersion and corrected QT dispersion than the II and ID genotypes. Our study showed that the most important parameter affecting corrected QT dispersion was ACE gene polymorphism on the background of D allelle. Patients carrying this allelle need special attention regarding optimal suppression of renin-angiotensin-aldosteron system activity.

  1. Dose-Dependent Effects of Methadone on QT interval in Patients under Methadone Maintenance Treatment

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    Farzad Gheshlaghi

    2013-03-01

    Full Text Available Background: The role of methadone in QTc prolongation, Torsades de Pointes (TdP arrhythmia and sudden cardiac death has been debated. Because of widespread use of methadone in methadone maintenance treatment (MMT centers, we aimed to study dose-related effects of methadone on QTc prolongation. Methods: In a comparative observational study, 90 patients who were under MMT were evaluated. Patients were divided into three groups according to methadone daily dose (G1: 0-59 mg, G2: 60-109 mg, G3: 110-150 mg. Twelve-lead electrocardiograms (ECG were performed at baseline and two months later, after reaching the maximum daily dose of methadone. The QTc were calculated for each patient. Comparison of mean QTc and mean QTc prolongation between baseline and follow up ECGs were analyzed. Results: In total, mean (SD age was 32.4 (8.5. TdP was not detected in any patients. Mean QTc was 405.2 (17.0 and 418.5 (23.1 msec before and two months after MMT respectively. There was a significant difference between mean QTc in each group before and after treatment (P

  2. Characterization of QT and RR interval series during acute myocardial ischemia by means of recurrence quantification analysis.

    Science.gov (United States)

    Peng, Yi; Sun, Zhongwei

    2011-01-01

    This study is aimed to investigate the nonlinear dynamic properties of the fluctuations in ventricular repolarization, heart rate and their correlation during acute myocardial ischemia. From 13 ECG records in long-term ST-T database, 170 ischemic episodes were selected with the duration of 34 s to 23 min 18 s, and two 5-min episodes immediately before and after each ischemic episode as non-ischemic ones for comparison. QT interval (QTI) and RR interval (RRI) were extracted and the ectopic beats were removed. Recurrence quantification analysis (RQA) was performed on QTI and RRI series, respectively, and cross recurrence quantification analysis (CRQA) on paired normalized QTI and RRI series. Wilcoxon signed-rank test was used for statistical analysis. Results revealed that the RQA indexes for QTI and HRI series had the same changing trend during ischemia with more significantly changed indexes in QTI series. In the CRQA, indexes related to the vertical and horizontal structures in recurrence plot significantly increased, representing decreased dependency of QTI on RRI. Both QTI and RRI series showed reduced complexity during ischemia with higher sensitivity in ventricular repolarization. The weakened coupling between QTI and RRI suggests the decreased influence of sinoatrial node on QTI modulation during ischemia.

  3. Computer quantitation of Q-T and terminal T wave (aT-eT) intervals during exercise: methodology and results in normal men.

    Science.gov (United States)

    O'Donnell, J; Knoebel, S B; Lovelace, D E; McHenry, P L

    1981-05-01

    Computer-quantitated measurements of the Q-T intervals, the Q-T/Q-Tc ratio (Q-T/corrected Q-T) and the terminal T wave (apex to end of T [aT-eT] interval) were evaluated in resting and exercise electrocardiograms of 130 normal men with a mean age of 40 years. Pseudo-orthogonal, bipolar X, Y and Z axis leads were recorded during treadmill exercise testing, and 25 consecutive QRS-T complexes from standing rest and three exercise stages were computer-averaged. The Q-T intervals, Q-T/Q-Tc ratio and aT-eT interval measurements were then computed in the X and Z axis leads only, because the Y lead proved to be too noisy for accurate interpretation. A correlation coefficient of 0.9830 resulted between measurements made manually from the plotted, composite QRS-T complexes and those made by computer. No significant differences , in the paired sense, were found between any of the measurements. Measurements made on the Z axis lead; however, the differences in the measurements remained constant across all stages of exercise. A Q-T/Q-Tc ratio of greater than 1.08, previously reported to be a reliable indicator of coronary disease, was observed in the majority of our normal subjects during exercise. Although the Q-T interval is substantially influenced by many factors, the aT-eT interval proved not to be age- or heart rate-dependent. It appears that the aT-eT interval can be measured with a high degree of reliability during exercise and it may prove to be a relatively specific indicator of repolarization alterations that occur with myocardial ischemia.

  4. Effect of nalmefene 20 and 80 mg on the corrected QT interval and T-wave morphology

    DEFF Research Database (Denmark)

    Matz, Jørgen; Graff, Claus; Vainio, Petri J.

    2011-01-01

    Nalmefene is an orally administered competitive opioid receptor antagonist targeted at reducing alcohol consumption in alcohol-dependent patients. As part of the regulatory requirements for drug approval, the potential of novel compounds for causing unwanted proarrhythmia should be studied...... in a thoroughly designed clinical QT/corrected QT (QTc) study (International Conference on Harmonisation [ICH] E14 guideline)....

  5. Effects of bepridil and CERM 4205 (ORG 30701) on the relation between cardiac cycle length and QT duration in healthy volunteers.

    Science.gov (United States)

    Lecocq, B; Lecocq, V; Prost, P L; Fleurot, O; Boisson, P; Jaillon, P

    1990-09-01

    Bepridil is a calcium antagonist that prolongs the duration of ventricular repolarization, whereas CERM 4205, another calcium antagonist, seems to be devoid of any effect on QT interval. The aim of this study was to compare the effects of bepridil and CERM 4205 on the QT-RR relation at different heart rates during rest and exercise and the results of pharmacologic tests designed to vary neurovegetative tone. Twelve healthy men (21 to 37 years) participated in a placebo-controlled, randomized, crossover, double-blind study and received either bepridil (200 mg/day twice daily) or CERM 4205 (200 mg/day twice daily), or matching placebo during three 14-day treatment periods at 2-week intervals. Bepridil, but not CERM 4205, caused a significant prolongation of resting QT interval. The RR-QT relation was monoexponential for all subjects during resting and exercising physiologic conditions and remained unchanged after 14 days with placebo or CERM 4205. Bepridil significantly shifted the relation upward, resulting in a rate-dependent QT prolongation that predominated during bradycardia. After isoprenaline, QT no longer adapted to changes in heart rate, whereas atropine resulted in a rate-dependent shortening in QT. These results suggest that bepridil and CERM 4205 exert different effects on ventricular repolarization, since only bepridil significantly prolonged QT duration. Bepridil-induced prolongation of QT increased at slow heart rates, which could explain the greater incidence of torsades de pointes in bradycardia.

  6. Pulsed flows observed during an interval of prolonged northward IMF

    Directory of Open Access Journals (Sweden)

    G. Provan

    2005-06-01

    Full Text Available On the 22 December 2002 the interplanetary magnetic field (IMF was directed northwards for more than 12h. The Northern and Southern Hemisphere SuperDARN radars were used to study global high-latitude convection during this interval, complemented by data from the ACE and DMSP F13 spacecraft. The relative magnitudes of the IMF By and Bz components varied during this period. When the magnitude of the By component was comparable with or dominated the Bz component, signatures of simultaneous low-latitude and lobe reconnection were observed. Specifically two "standard" merging cells were observed in both hemispheres. In the Northern Hemisphere a high-latitude lobe cell was observed within the dusk merging cell, and there was also evidence of a narrow viscous cell located equatorward of this lobe cell. We observed the ionospheric signatures of flux transfer events (FTEs in both the Northern and Southern Hemispheres, occurring with a periodicity of ~15min. In the Northern Hemisphere the FTEs were associated with a stepwise equatorward progression of the equatorward boundary of radar backscatter on the dayside. When the IMF Bz component was predominantly greater than the IMF By component, we observed a four-cell convection pattern in the Northern Hemisphere, with pulses of reverse reconnection and an associated stepwise poleward retraction of the equatorward boundary of radar backscatter occurring every ~25min. These observations are consistent with pulsed lobe reconnection occurring in both hemispheres, closing open flux and adding closed flux to the dayside magnetopause. So, during this northward IMF interval the location of the sites of reconnection between the IMF and the Earth's magnetosphere, and thus the form of reconnection process, varied with changing IMF conditions. However, the reconnection remained pulsed, with lobe-only reconnection having a significantly longer

  7. Long QT in children with congenital deafness: a brief report

    Directory of Open Access Journals (Sweden)

    Naseraldin Akbari Asbagh

    2013-08-01

    Full Text Available Background: Long QT syndromes (LQT are genetic abnormalities of ventricular repo-larization, with an estimated incidence of about one per 10000 births. It is characterized by prolongation of the QT interval in electrocardiogram (EKG and associated with a high risk for syncope and sudden death in patients. Type of this syndrome is association with congenital deafness. Our objective was to evaluate QT interval in children with congenital deafness.Methods: For 219 patients referred to Imam Khomeini Hospital audiometric clinic in 2011, questionnaire were completed. A total of 23 congenitally deaf children were incl-uded. All patients’ examinations were done by a pediatric cardiologist. Electrocardio-gram is conducted in all children (23 patients with sever and deep congenital deafness. Then the QT interval was measured based on Bazett’s formula. Echocardiography was also performed in these children to assess left ventricular function and the presence of mitral valve prolapse.Results: The overall patients were two hundred and nineteen children. A total of twenty three congenitally deaf children were included and electrocardiogram was obtained. Three children had obviously prolonged QTc (0.48±0.02 second. The median age of them was 6.1±5 year, the median weight was 18±11.3 kilogram and the median of QT interval was 0.48±0.02 second.Conclusion: The QT interval obtained 0.48±0.02 second. In the present study we found prolonged QT in congenital deafness, thus we recommend to evaluate the electrocardio-gram of children with congenital deafness.

  8. Low-Pass Filtering Approach via Empirical Mode Decomposition Improves Short-Scale Entropy-Based Complexity Estimation of QT Interval Variability in Long QT Syndrome Type 1 Patients

    Directory of Open Access Journals (Sweden)

    Vlasta Bari

    2014-09-01

    Full Text Available Entropy-based complexity of cardiovascular variability at short time scales is largely dependent on the noise and/or action of neural circuits operating at high frequencies. This study proposes a technique for canceling fast variations from cardiovascular variability, thus limiting the effect of these overwhelming influences on entropy-based complexity. The low-pass filtering approach is based on the computation of the fastest intrinsic mode function via empirical mode decomposition (EMD and its subtraction from the original variability. Sample entropy was exploited to estimate complexity. The procedure was applied to heart period (HP and QT (interval from Q-wave onset to T-wave end variability derived from 24-hour Holter recordings in 14 non-mutation carriers (NMCs and 34 mutation carriers (MCs subdivided into 11 asymptomatic MCs (AMCs and 23 symptomatic MCs (SMCs. All individuals belonged to the same family developing long QT syndrome type 1 (LQT1 via KCNQ1-A341V mutation. We found that complexity indexes computed over EMD-filtered QT variability differentiated AMCs from NMCs and detected the effect of beta-blocker therapy, while complexity indexes calculated over EMD-filtered HP variability separated AMCs from SMCs. The EMD-based filtering method enhanced features of the cardiovascular control that otherwise would have remained hidden by the dominant presence of noise and/or fast physiological variations, thus improving classification in LQT1.

  9. QT dispersion in HIV-infected patients receiving combined antiretroviral therapy.

    Science.gov (United States)

    Wongcharoen, Wanwarang; Suaklin, Somkhuan; Tantisirivit, Nualnit; Phrommintikul, Arintaya; Chattipakorn, Nipon

    2014-11-01

    A higher prevalence of QT prolongation has been reported among human immunodeficiency virus (HIV)-infected patients. Previous studies have demonstrated that QT dispersion is a better predictor of serious ventricular tachyarrhythmia and cardiac mortality than corrected QT (QTc) interval. However, data of QT dispersion in HIV-infected patients receiving a combined antiretroviral therapy (cART) is limited. We sought to assess QTc interval and QT dispersion in HIV-infected patients receiving cART. The association between QT parameters and heart rate variability (HRV) was also examined. Ninety-one HIV-infected patients receiving cART (male = 33, mean age = 44 ± 10 years) and 70 HIV-seronegative subjects (male = 25, mean age = 44 ± 8 years) were enrolled in the study. In a resting 12-lead electrocardiogram, QT interval was measured by the tangent method in all leads with well-defined T waves. The QT dispersion was defined as the difference between maximum and minimum QTc intervals in any of 12 leads. The baseline characteristics were not different between the two groups. We demonstrated the significantly longer mean QTc interval (420 ± 21 vs. 409 ± 21 ms, P dispersion in HIV-infected group compared to the control group (85 ± 29 vs. 55 ± 23 ms, P dispersion (92 ± 28 vs. 81 ± 29 ms, P = 0.098). There were no associations between QT parameters and either HRV or cART regimens. HIV-infected patients receiving cART were associated with prolonged QTc interval and increased QT dispersion, independent of autonomic dysfunction and antiretroviral drugs, which may have led to the potentially higher risk of ventricular arrhythmia and cardiac mortality. © 2014 Wiley Periodicals, Inc.

  10. Associations between changes in city and address specific temperature and QT interval--the VA Normative Aging Study.

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    Amar J Mehta

    Full Text Available BACKGROUND: The underlying mechanisms of the association between ambient temperature and cardiovascular morbidity and mortality are not well understood, particularly for daily temperature variability. We evaluated if daily mean temperature and standard deviation of temperature was associated with heart rate-corrected QT interval (QTc duration, a marker of ventricular repolarization in a prospective cohort of older men. METHODS: This longitudinal analysis included 487 older men participating in the VA Normative Aging Study with up to three visits between 2000-2008 (n = 743. We analyzed associations between QTc and moving averages (1-7, 14, 21, and 28 days of the 24-hour mean and standard deviation of temperature as measured from a local weather monitor, and the 24-hour mean temperature estimated from a spatiotemporal prediction model, in time-varying linear mixed-effect regression. Effect modification by season, diabetes, coronary heart disease, obesity, and age was also evaluated. RESULTS: Higher mean temperature as measured from the local monitor, and estimated from the prediction model, was associated with longer QTc at moving averages of 21 and 28 days. Increased 24-hr standard deviation of temperature was associated with longer QTc at moving averages from 4 and up to 28 days; a 1.9°C interquartile range increase in 4-day moving average standard deviation of temperature was associated with a 2.8 msec (95%CI: 0.4, 5.2 longer QTc. Associations between 24-hr standard deviation of temperature and QTc were stronger in colder months, and in participants with diabetes and coronary heart disease. CONCLUSION/SIGNIFICANCE: In this sample of older men, elevated mean temperature was associated with longer QTc, and increased variability of temperature was associated with longer QTc, particularly during colder months and among individuals with diabetes and coronary heart disease. These findings may offer insight of an important underlying mechanism of

  11. Assessment of Atrial Fibrillation and Ventricular Arrhythmia Risk after Bariatric Surgery by P Wave/QT Interval Dispersion.

    Science.gov (United States)

    Yılmaz, Mustafa; Altın, Cihan; Tekin, Abdullah; Erol, Tansel; Arer, İlker; Nursal, Tarık Zafer; Törer, Nurkan; Erol, Varlık; Müderrisoğlu, Haldun

    2017-09-13

    The association of obesity with atrial fibrillation (AF) and with ventricular arrhythmias is well documented. The aim of this study was to investigate whether weight reduction by a laparoscopic sleeve gastrectomy has any effect on P wave dispersion (PWD), a predictor of AF, and corrected QT interval dispersion (CQTD), a marker of ventricular arrhythmias, in obese individuals. In a prospective study, a total of 114 patients (79 females, 35 males) who underwent laparoscopic sleeve gastrectomy were examined. The patients were followed 1 year. PWD and CQTD values before and 3rd, 6th, and 12th months after the surgery were calculated and compared. There was a statistically significant decline in body mass index (BMI), PWD, and CQTD values among baseline, 3rd, 6th, and 12th months (p p p = 0.002), ΔPWD and Δleft atrial diameter (LAD) (r = 0.65, p p = 0.004), ΔCQTD and ΔLVEDD (r = 0.35, p p = 0.002). In multiple linear regression analysis, there was a statistically significant relationship between ΔPWD and ΔBMI (β = 0.713, p p = 0.016), ΔPWD and ΔLAD (β = 0.619, p p = 0.011), ΔCQTD and ΔLVEDD (β = 0.304, p p = 0.009). PWD and CQTD values of patients were shown to be attenuated after bariatric surgery. These results indirectly offer that there may be a reduction in risk of AF, ventricular arrhythmia, and sudden cardiac death after obesity surgery.

  12. Quetiapine, QTc interval prolongation, and torsade de pointes: a review of case reports.

    Science.gov (United States)

    Hasnain, Mehrul; Vieweg, W Victor R; Howland, Robert H; Kogut, Christopher; Breden Crouse, Ericka L; Koneru, Jayanthi N; Hancox, Jules C; Digby, Geneviève C; Baranchuk, Adrian; Deshmukh, Anand; Pandurangi, Ananda K

    2014-06-01

    Recently, both the manufacturer of quetiapine and the US Food and Drug Administration warned healthcare providers and patients about quetiapine-induced QTc interval prolongation and torsade de pointes (TdP) when using this drug within the approved labeling.  We reviewed the case-report literature and found 12 case reports of QTc interval prolongation in the setting of quetiapine administration. There were no cases of quetiapine-induced TdP or sudden cardiac death (SCD) among patients using quetiapine appropriately and free of additional risk factors for QTc interval prolongation and TdP. Among the 12 case reports risk factors included female sex (nine cases), coadministration of a drug associated with QTc interval prolongation (eight cases), hypokalemia or hypomagnesemia (six cases) quetiapine overdose (five cases), cardiac problems (four cases), and coadministration of cytochrome P450 3A4 inhibitors (two cases). There were four cases of TdP. As drug-induced TdP is a rare event, prospective studies to evaluate the risk factors associated with QTc prolongation and TdP are difficult to design, would be very costly, and would require very large samples to capture TdP rather than its surrogate markers. Furthermore, conventional statistical methods may not apply to studies of TdP, which is rare and an 'outlier' manifestation of QTc prolongation. We urge drug manufacturers and regulatory agencies to periodically publish full case reports of psychotropic drug-induced QTc interval prolongation, TdP, and SCD so that clinicians and investigators may better understand the clinical implications of prescribing such drugs as quetiapine.

  13. High incidence of functional ion-channel abnormalities in a consecutive Long QT cohort with novel missense genetic variants of unknown significance

    DEFF Research Database (Denmark)

    Steffensen, Annette Buur; Refaat, Marwan M; David, Jens-Peter

    2015-01-01

    The Long QT syndrome (LQTS) is a disorder characterized by a prolongation of the QT interval and a propensity to ventricular tachyarrhythmias, which may lead to syncope, cardiac arrest, or sudden death. Our objective was to (1) determine the incidence of variants with unknown significance (VUS) i...

  14. A Thorough QTc Study Confirms Early Pharmacokinetics/QTc Modeling: A Supratherapeutic Dose of Omarigliptin, a Once-Weekly DPP-4 Inhibitor, Does Not Prolong the QTc Interval.

    Science.gov (United States)

    Tatosian, Daniel A; Cardillo Marricco, Nadia; Glasgow, Xiaoli Shirley; DeGroot, Bruce; Dunnington, Katherine; George, Laura; Gendrano, Isaias Noel; Johnson-Levonas, Amy O; Swearingen, Dennis; Kauh, Eunkyung

    2016-09-01

    Omarigliptin is a dipeptidyl peptidase-4 inhibitor being developed as a once-weekly treatment for type 2 diabetes. This double-blind, double-dummy, randomized, 3-period balanced crossover study definitively evaluated the effects of a supratherapeutic omarigliptin dose on QTc interval. Population-specific correction of QT interval (QTcP) was used for the primary analysis. Healthy subjects (n = 60) were enrolled and received treatments separated by a ≥4-week washout: (1) single-dose 25 mg omarigliptin (day 1), single-dose 175 mg omarigliptin (day 2); (2) placebo (day 1) followed by single-dose 400 mg moxifloxacin (day 2); (3) placebo (days 1 and 2). Day 2 QTcP intervals were analyzed. The primary hypothesis was supported if the 90%CIs for the least-squares mean differences between omarigliptin 175 mg and placebo in QTcP interval change from baseline were all < 10 milliseconds at every postdose point on day 2. The upper bounds of the 90%CIs for the differences (omarigliptin-placebo) in QTcP change from baseline for omarigliptin 175 mg were < 10 milliseconds at all postdose times on day 2. In conclusion, a supratherapeutic dose of omarigliptin does not prolong the QTcP interval to a clinically meaningful degree relative to placebo, confirming the results of the earlier concentration-QTc analysis.

  15. LATE POTENTIALS, QTC PROLONGATION, AND PREDICTION OF ARRHYTHMIC EVENTS AFTER MYOCARDIAL-INFARCTION

    NARCIS (Netherlands)

    TOBE, TJM; DELANGEN, CDJ; CRIJNS, HJGM; WIESFELD, ACP; VANGILST, WH; FABER, KG; LIE, KI; WESSELING, H

    1994-01-01

    In a series of 171 consecutive survivors of acute myocardial infarction, the predictive value of late potentials and QTc prolongation was prospectively assessed. QT intervals were measured in lead V-2, corrected QT (QTc) was calculated using Bazett's equation (cut-off value 440 ms). Late potentials

  16. Prolonged Q-T(c) interval in mild portal hypertensive cirrhosis

    DEFF Research Database (Denmark)

    Ytting, Henriette; Henriksen, Jens H; Fuglsang, Stefan

    2005-01-01

    BACKGROUND/AIMS: The Q-T(c) interval is prolonged in a substantial fraction of patients with cirrhosis, thus indicating delayed repolarisation. However, no information is available in mild portal hypertensive patients. We therefore determined the Q-T(c) interval in cirrhotic patients with hepatic...... venous pressure gradient (HVPG) portal hypertension (HVPG> or = 12 mmHg) and controls without liver disease. RESULTS......), values which are significantly above that of the controls (0.410 s(1/2), P portal hypertensive group, the Q-T(c) interval was inversely related to indicators of liver function, such as indocyanine green clearance (r = -0.34, P

  17. Prolonged Q-T(c) interval in mild portal hypertensive cirrhosis

    DEFF Research Database (Denmark)

    Ytting, Henriette; Henriksen, Jens Henrik; Fuglsang, Stefan

    2005-01-01

    BACKGROUND/AIMS: The Q-T(c) interval is prolonged in a substantial fraction of patients with cirrhosis, thus indicating delayed repolarisation. However, no information is available in mild portal hypertensive patients. We therefore determined the Q-T(c) interval in cirrhotic patients with hepatic...... venous pressure gradient (HVPG) portal hypertension (HVPG> or = 12 mmHg) and controls without liver disease. RESULTS......), values which are significantly above that of the controls (0.410 s(1/2), P portal hypertensive group, the Q-T(c) interval was inversely related to indicators of liver function, such as indocyanine green clearance (r = -0.34, P

  18. The T-peak–T-end Interval as a Marker of Repolarization Abnormality

    DEFF Research Database (Denmark)

    Bhuiyan, Tanveer A.; Graff, Claus; Kanters, Jørgen K.;

    2015-01-01

    a significant increase of both TpTe and QT from baseline is apparent with QT-prolonging drugs, the TpTe/QT ratio remained the same at baseline and after drug administration, thus indicating that prolongation of TpTe is just a fractional part of total QT prolongation. In the presence of notched or flattened T......-waves, the uncertainty associated with measurement of the TpTe interval increases. The errors in TpTe for individual subjects may be substantial, thus complicating the use of TpTe for follow-up of individuals. CONCLUSIONS: The duration of the QT interval and TpTe are closely related. Drugs appear to prolong the Tp...

  19. A mouse model to study the link between hypoxia, long QT interval and sudden infant death syndrome.

    Science.gov (United States)

    Neary, Marianne T; Mohun, Timothy J; Breckenridge, Ross A

    2013-03-01

    The pathology of sudden infant death syndrome (SIDS) is poorly understood. Many risk factors, including hypoxia, have been identified. Prolongation of the ECG QTc interval is associated with elevated risk of SIDS but its aetiology in most cases remains unknown. We have characterised ECG changes in the newborn mouse in the hours and days following birth. There was a steady increase in heart rate alongside significant decreases in QTc interval, QRS duration and QTc dispersion over the first 10 postnatal days. Birth into hypoxia (10% FiO2) prevented electrocardiac maturation, downregulated cardiac ion-channel expression and led to neonatal death. We found that risk of death decreased with increasing age of exposure to hypoxia. Genetic elevation of cardiac hypoxia-signalling after birth in αMHC-Cre::VHL(fl/fl) mice also prevented electrocardiographic maturation, leading to arrhythmia and death before weaning. Immunohistochemistry and western blotting revealed internalisation and dephosphorylation of Connexin43. We conclude that increased ambient oxygen concentration after birth drives maturation of the cardiac electrical conduction system, failure of which leads to aberrant ion channel and Connexin43 expression and predisposes to arrhythmia and sudden death. This is consistent with known risk factors of SIDS and provides a link between neonatal hypoxia, ECG abnormalities and sudden death.

  20. IS THERE ANY RELATIONSHIP BETWEEN LITHIUM-INDUCED QT PROLONGATION AND PLASMA OR ERYTHROCYTE CONCENTRATION OF LITHIUM?

    Directory of Open Access Journals (Sweden)

    SIMIN DASHTI-KHAVIDAKI

    2006-06-01

    Full Text Available This study was designed to find possible relationship between QTc prolongation and erythrocyte or plasma lithium concentrations. Fifty-six patients with bipolar disorder entered this case- control study. Subjects were between 17 to 63 years of age and were receiving lithium alone, or lithium plus haloperidol or lithium plus thioridazine. The exclusion criteria were past history of cardiovascular, hepatic, renal or metabolic disorders or using other medications known to cause rhythm disturbances. The case group included males with QTc 450ms and females with QTc470ms while the control group included males and females with QTc<450 and QTc< 470ms, respectively. Serum sodium and potassium levels, erythrocyte and plasma lithium concentrations as well as lithium ratio were determined for all subjects and compared between the case and control groups by independent sample t-test. The mean of these levels were not different between the case and control groups. Additionally, no correlations were found between QTc and erythrocyte or plasma lithium concentration, lithium ratio, serum sodium or potassium levels. Analyzing the data for patients treated with lithium alone showed no significant correlations between QTc prolongation and erythrocyte or plasma lithium concentration, lithium ratio or serum potassium level. However, a significant correlation was found between serum sodium concentration and QTc prolongation. It should be noted that QTc prolongation occurred six times more in patients who were taking thioridazine and lithium concomitantly. This study noted no influence of sex or co-administration of haloperidol with lithium on QTc prolongation. It is concluded that plasma or erythrocyte lithium levels may not be able to predict QTc prolongation and its consequences.

  1. Rare genetic variants previously associated with congenital forms of long QT syndrome have little or no effect on the QT interval

    DEFF Research Database (Denmark)

    Ghouse, Jonas; Have, Christian Theil; Weeke, Peter

    2015-01-01

    ) and genotype array data (n = 6161) for putative cLQTS genetic variants. In total, 33 of 1358 variants previously reported to associate with cLQTS were identified. Of these, 10 variants were found in 8 or more individuals. Electrocardiogram results showed normal mean QTc intervals in carriers compared with non...

  2. Reference intervals for glucose, beta-cell polypeptides, and counterregulatory factors during prolonged fasting

    DEFF Research Database (Denmark)

    Højlund, Kurt; Wildner-Christensen, M; Eshøj, O

    2001-01-01

    To establish reference intervals for the pancreatic beta-cell response and the counterregulatory hormone response to prolonged fasting, we studied 33 healthy subjects (16 males, 17 females) during a 72-h fast. Glucose, insulin, C-peptide, and proinsulin levels decreased (P ... of counterregulatory factors increased during the fast [P fasting (P ... decreased from the second to third day of fasting (P = 0.03). Males had higher glucose and glucagon levels and lower FFA levels during the fast (P

  3. Assessment of drug-induced torsade de pointes risk for hospitalized high-risk patients receiving QT-prolonging agents.

    Science.gov (United States)

    Jardin, Carla G M; Putney, David; Michaud, Stephen

    2014-02-01

    Although risk factors for torsade de pointes (TdP) are known, identifying hospitalized patients at greatest risk for QTcP who should receive cardiac monitoring is poorly defined. Describe the prevalence of risk for TdP in patients and associations between risk factors and QTc prolongation (QTcP) at a tertiary teaching hospital. This retrospective analysis assessed physiological and pharmacological risk factors for TdP of adult patients receiving ≥1 QTc-prolonging medications (QTcMed) during hospitalization. The QTcMeds were stratified by risk for causing TdP (probable, possible, and conditional). Baseline electrocardiograms (ECGs) were assessed for QTcP associated with risk for TdP. During a 6-month period, 12,401 (51%) hospitalizations received ≥1 QTcMed. A baseline ECG was obtained for 2381 (19%) patients. A total of 386 (16%) patients with a baseline ECG were found to have QTcP. Significant associations for QTcP were found with the following physiological risk factors: female (P = .021), left-ventricular ejection fraction <40% (P < .0001), cardiac arrest (P < .0001), and cardioversion (P = .007). Significantly more patients with QTcP (n = 209, 54%) received probable-risk QTcMeds than those without QTcP (n = 542, 27%; P < .0001). Probable-risk QTcMeds administered alone or concomitantly with other QTcMeds were more frequently associated with QTcP. No documented cases of TdP were identified. Of the population receiving QTcMeds, only a small portion had a baseline ECG, identifying a large population at risk of QTcP without appropriate monitoring. Patients with cardiac disease receiving probable-risk QTcMeds were associated with the highest risk of QTcP and should be monitored closely.

  4. Duodenal myotomy blocks reduction of meal size and prolongation of intermeal interval by cholecystokinin.

    Science.gov (United States)

    Lateef, Dalya M; Washington, Martha C; Raboin, Shannon J; Roberson, Allison E; Mansour, Mahmoud M; Williams, Carol S; Sayegh, Ayman I

    2012-02-01

    We have shown that vagotomy (VGX) attenuates the reduction of meal size (MS) produced by cholecystokinin (CCK) -8 and -33 and that celiaco-mesenteric ganglionectomy (CMGX) attenuates the prolongation of the intermeal interval (IMI) produced by CCK-33. Here, we report the following novel data. First, by determining the distribution of CCK(1) receptor messenger RNA, which mediates reduction of MS and prolongation of IMI by CCK, in seven regions of the gastrointestinal tract in the adult rat we found that the duodenum contains the highest concentration of this receptor in the gut. Second, based on the previous finding we performed a unique surgical technique known as duodenal myotomy (MYO), which severs all the nerves of the gut wall in the duodenum including vagus, splanchnic and enteric nerves. Third, we determined MS and IMI in duodenal MYO rats in responses to endogenous CCK-58 released by the non-nutrient, trypsin inhibitor, camostat and CCK-8 to test the possibility that the duodenum is the site of action for reduction of MS and prolongation of IMI. We found that, similar to the previous work reported by using CCK-8 and MS, duodenal MYO also blocked reduction of MS by camostat. Forth, duodenal MYO blocked prolongation of IMI by camostat. As such, our current results suggest that the duodenum is the gut site that communicates both feeding signals of endogenous CCK, MS and IMI, with the brain through vagal and splanchnic afferents.

  5. Anestesia e síndrome do QT longo Anestesia e síndrome del QT largo Anesthesia and the long QT syndrome

    Directory of Open Access Journals (Sweden)

    Michelle Nacur Lorentz

    2007-10-01

    la operación.BACKGROUND AND OBJECTIVES: Cardiac arrhythmias are important factors of perioperative morbidity and mortality. Among the causes of arrhythmias, the long QT syndrome, both in the genetic and acquired types, should be remembered since several drugs used in anesthesia, as well as in the perioperative period, can prolong the QT interval and trigger potentially malignant arrhythmias. CONTENTS: A review of the long QT syndrome (LQTS, discussing its causes and definition, as well as the mechanisms of the disease. Besides mentioning several drugs implicated in prolonging the QT interval, and the most adequate anesthetic approaches to affected patients are recommended. CONCLUSION: The long QT syndrome, possible cause of intra- and postoperative morbidity and mortality, can be related to drugs used during anesthesia. The anesthesiologist should have knowledge of this syndrome, in order to avoid an unfavorable outcome.

  6. Distribution of reference range of QT interval based on the artificial neural networks%基于人工神经网络的中国人心电图QT间期参考值的地理分布

    Institute of Scientific and Technical Information of China (English)

    张雯; 岑敏仪; 葛淼; 何进伟; 路春爱; 张莹; 杨绍芳; 姜吉琳; 许金辉; 刘新蕾

    2015-01-01

    目的:为制定中国人心电图 QT 间期参考值的统一标准提供依据。方法收集中国84个市(县)级医院、研究单位及高等院校测定的15164例健康成年人心电图 QT 间期参考值。运用相关分析、主成分分析、人工神经网络、GIS 空间分析等方法研究其与经度、纬度、海拔、年平均气温、年平均相对湿度、年降水量、气温年较差、表土粉粒百分率、表土阳离子交换量(黏土)、表土阳离子交换量(潜育土)、表土碱度的关系。结果通过五层人工神经网络模拟健康中国人心电图 QT 间期的参考值范围,并通过克里格插值法精确地内插出中国人心电图 QT 间期参考值范围的地理分布图。结论知道中国某地的地理要素,就可用此模型估算该地区成年人心电图 QT 间期参考值,同时也可用空间分布图直观得到中国任何地方的成年人心电图 QT 间期参考值。%Objective To supply a scientific basis for unifying the reference value standard of QT interval of Chinese people .Meth-ods The QT interval reference values were collected from 15 164 healthy people in 84 areas of China.The correlations between the measured values of QT interval and the 11 geographical factors were analyzed .Results After 5 layers′Neural Networks and self-study about building the analogue rules for 60 times, the relationship between the normal reference value of QT interval and geographic factors had be limitated with the methods of BP neural networks and Spatial analysis of GIS .The geography distribution map of the reference range of QT interval was inserted exactly with the method of Kriging .Conclusions If geographical factors of a particular area are obtained ,the QT interval reference value of Chinese people in this area could be calculated using this model and the normal QT interval reference values of Chinese men any -where in China could be obtained from geography distribution

  7. Carbon monoxide poisoning mimicking long-QT induced syncope

    NARCIS (Netherlands)

    I.M. Onvlee-Dekker (Irene); A.C.H. de Vries (Andrica); A.D.J. ten Harkel (Arend)

    2007-01-01

    textabstractCarbon monoxide (CO)poisoning is a rare cause of QT prolongation, and is therefore easily missed. The case of a patient with unexplained syncope and QT prologation on the electrocardiogram that turned out to be related to CO poisoning is reported here. In patients with QT prolongation,

  8. Study on the relationship between QT interval and the compement of antipsychotic-induced metabolic syndrome%抗精神病药物致代谢综合征及其组分与心电图QT间期的关系

    Institute of Scientific and Technical Information of China (English)

    王相立; 麻爱华

    2009-01-01

    目的 探讨抗精神病药物致代谢综合征(metabolic syndrome,MS)及其组分与心电图QT间期的关系.方法 对460例服用抗精神病药物的精神分裂症患者进行流行病学调查、身体测量、血生化指标测定及MS诊断,记录标准12导联心电图,用Bazett公式计算校正的QT间期(QTC).采用稳态模式评估法计算胰岛素抵抗指数(HOMA-IR).结果 抗精神病药物致代谢综合征人群心电图QT间期延长者124例,占27.0%,男女心电图QT间期延长检出率分别为21.7%、32.7%,差异有显著性(χ2=7.13,P<0.01).MS、HOMA-IR、中心性肥胖、高血压、高血糖、高TG、低HDL-C的检出率分别为39.3%,38.7%,35.4%,34.1%,31.3%,29.8%,27.0%.心电图QT间期延长与中心性肥胖、高血糖、高TG、胰岛素抵抗(IR)、MS及异常组分聚集有相关关系(χ2=4.95~13.63,P<0.05).结论 心电图QT间期延长与抗精神病药物所致多项代谢异常组分、代谢异常聚集及代谢综合征相关联.%Objective To study the relationship between QT interval and the compements of antipsychotic-induced metabolic syndrome in schizophrenic patients. Methods Totally 460 schizophrenic patients(240 men and 220 women)aged 19~60 from the study cohort of the schizophrenic patients in treatment with antipsychotant were recruited in the study for epidemiologic examinations,involving anthropometry and measurements of blood pressure,fasting ang 2hr plasma levels of glucose and insulin and serum levels of lipid.A standard 12-lead ECG was recorded and the corrected QT (QTc)was calculated accordingly by Bazett formula.HOMA-IR index was calculated for estimating individual insulin resistance.Metabolic syndrome(MS)was diagnosed according to the definition issued by the International Diabetes Federation(IDF)in 2005.Results The prolonged QT interval was found in 124 of the 460 cases(27.0%),and the rates of prolonged QT interval being 21.7% and 32.7% in men and women respectively (χ2=7.13,P<0.01).The

  9. Symbolic dynamics to discriminate healthy and ischaemic dilated cardiomyopathy populations: an application to the variability of heart period and QT interval

    Science.gov (United States)

    Valencia, José Fernando; Vallverdu, Montserrat; Rivero, Isidre; Voss, Andreas; de Luna, Antonio Bayes; Porta, Alberto; Caminal, Pere

    2015-01-01

    Myocardial ischaemia is hypothesized to stimulate the cardiac sympathetic excitatory afferents and, therefore, the spontaneous changes of heart period (approximated as the RR interval), and the QT interval in ischaemic dilated cardiomyopathy (IDC) patients might reflect this sympathetic activation. Symbolic analysis is a nonlinear and powerful tool for the extraction and classification of patterns in time-series analysis, which implies a transformation of the original series into symbols and the construction of patterns with the symbols. The aim of this work was to investigate whether symbolic transformations of RR and QT cardiac series can provide a better separation between IDC patients and healthy control (HC) subjects compared with traditional linear measures. The variability of these cardiac series was studied during daytime and night-time periods and also during the complete 24 h recording over windows of short data sequences of approximately 5 min. The IDC group was characterized by an increase in the occurrence rate of patterns without variations (0 V%) and a reduction in the occurrence rate of patterns with one variation (1 V%) and two variations (2 V%). Concerning the RR variability during the daytime, the highest number of patterns had 0 V%, whereas the rates of 1 V% and 2 V% were lower. During the night, 1 V% and 2 V% increased at the expense of diminishing 0 V%. Patterns with and without variations between consecutive symbols were able to increase the separation between the IDC and HC groups, allowing accuracies higher than 80%. With regard to entropy measures, an increase in RR regularity was associated with cardiac disease described by accuracy >70% in the RR series and by accuracy >60% in the QTc series. These results could be associated with an increase in the sympathetic tone in IDC patients. PMID:25548268

  10. Cardiac safety evaluation of pharmaceuticals and thorough QT/QTc study%药物心脏安全性评估与全面QT/QTc研究

    Institute of Scientific and Technical Information of China (English)

    佘飞; 李海燕

    2011-01-01

    许多非抗心律失常药物可以导致心电图QT间期延长,甚至引发尖端扭转型室性心动过速.因此在新药上市前,进行的心脏安全性评估,应该包括药物对QT间期影响的特点.全面QT/QTC研究旨在通过测量QT间期,明确药物是否具有延长QT间期的作用,判断其引发恶性心律失常的风险,并为决定药物是否进入下一步研发提供数据支持.%Many non -antiarrhythmic drugs could induce QT interval prolongation on the surface electrocardiogram, or even result in ventricular tachycardia, especially torsades de pointes. Therefore, an adequate pre -marketing cardiac safety evaluation of a new pharmaceutical agent should include rigorous characterization of its effects on the QT/QTc interval. Thorough QT/QTc study is designed to detect drug- induced QT interval prolongation, assess the risk of inducing malignant arrhythmia caused by research drags, and provide data to decide whether to enter the next step of drug development.

  11. CCK-58 prolongs the intermeal interval, whereas CCK-8 reduces this interval: not all forms of cholecystokinin have equal bioactivity.

    Science.gov (United States)

    Sayegh, Ayman I; Washington, Martha C; Raboin, Shannon J; Aglan, Amnah H; Reeve, Joseph R

    2014-05-01

    It has been accepted for decades that "all forms of cholecystokinin (CCK) have equal bioactivity," despite accumulating evidence to the contrary. To challenge this concept, we compared two feeding responses, meal size (MS, 10% sucrose) and intermeal interval (IMI), in response to CCK-58, which is the major endocrine form of CCK, and CCK-8, which is the most abundantly utilized form. Doses (0, 0.1, 0.5, 0.75, 1, 3 and 5 nmol/kg) were administered intraperitoneally over a 210-min test to Sprague Dawley rats that had been food-deprived overnight. We found that (1) all doses of CCK-58, except the lowest dose, and all doses of CCK-8, except the lowest two doses, reduced food intake more than vehicle did; (2) at two doses, 0.75 and 3 nmol/kg, CCK-58 increased the IMI, while CCK-8 failed to alter this feeding response; and (3) CCK-58, at all but the lowest two doses, increased the satiety ratio (IMI between first and second meals (min) divided by first MS (ml)) relative to vehicle, while CCK-8 did not affect this value. These findings demonstrate that the only circulating form of CCK in rats, CCK-58, prolongs the IMI more than CCK-8, the peptide generally utilized in feeding studies. Taken together, these results add to a growing list of functions where CCK-8 and CCK-58 express qualitatively different bioactivities. In conclusion, the hypothesis that "all forms of cholecystokinin (CCK) have equal bioactivity" is not supported.

  12. Study of heart-rate corrected QT interval and QT dispersion in patients with pulmonary hypertension%肺动脉高压患者心率校正QT间期和QT离散度的研究

    Institute of Scientific and Technical Information of China (English)

    张洪亮; 王勇; 罗勤; 柳志红; 赵智慧; 熊长明; 倪新海; 何建国

    2010-01-01

    目的:检测肺动脉高压(pulmonary hypertension,PH)患者的心率校正的QT间期(heart rate-corrected QT interval,QTc)和QTc离散度(QTc dispersion,QTcd),并评价其与肺动脉压力的关系.方法:入选2003年12月至2008年7月因初步诊断为PH而进行有心导管术的患者.记录静息12导联心电图,手工测量QT间期并用Bazett公式进行校正.根据平均肺动脉压,将患者分为对照组,轻-中度PH 组和重度PH组.结果:共入选201例患者.男性患者的QTc和QTcd在3组间差异无统计学意义.女性患者中,重度PH组的QTc比对照组高[(436.1±39.4)ms vs.(407.6±24.8)ms,P=0.037],重度PH组的QTcd(68.5 ±20.9)ms高于对照组(45.1 ±12.6)ms和轻-中度组(58.6 ±14.7)ms(P=0.002;P=0.003).此外,女性患者的QTc和QTcd与平均肺动脉压正相关(r=0.207,P=0.03;r=0.236,P=0.012).结论:本组资料中女性PH患者的QTc和QTcd与平均肺动脉压正相关,且在重度PH患者中显著增高,有待于进一步探讨.

  13. QT Dispersion: Does It Change after Percutaneous Coronary Intervention?

    Directory of Open Access Journals (Sweden)

    Mahsa Asadi Moghaddam

    2011-02-01

    Full Text Available Background: Myocardial ischemia is one of several causes of prolonged QT dispersion. The aim of this study was to evaluate the effect that percutaneous coronary intervention has on the depolarization and repolarization parameters of surface electrocardiography in patients with chronic stable angina.Methods: We assessed the effects of full revascularization in patients with chronic stable angina and single-vessel disease who underwent percutaneous coronary intervention. Twelve-lead electrocardiograms were recorded before intervention and 24 hours subsequently. We measured parameters including QRS duration, QT and corrected QT durations, and JT and corrected JT duration in both electrocardiograms and compared the values.Results: There were significant differences between the mean QRS interval (0.086 ± 0.01sec vs. 0.082 ± 0.01 second; p value = 0.01, mean corrected QT dispersion (0.080 ± 0.04 sec vs. 0.068 ± 0.04 sec; p value = 0.001, and mean corrected JT dispersion (0.074 ± 0.04 sec vs. 0.063 ± 0.04 sec; p value = 0.001 before and after percutaneous coronary intervention. No significant differences were found between the other ECG parameters.Conclusion: Our data indicate that the shortening of corrected QT dispersion and corrected JT dispersion in patients undergoing percutaneous coronary intervention is prominent.

  14. QTc interval prolongation in HIV-infected patients: a case–control study by 24-hour Holter ECG recording

    Directory of Open Access Journals (Sweden)

    Fiorentini Alessandra

    2012-12-01

    Full Text Available Abstract Background Aim of the study was to assess QTc interval by a 24-hour ECG recording in a group of HIV-infected individuals with a basal prolonged QTc. The risk factors associated with QTc prolongation and the indices of cardiovascular autonomic control were also evaluated. Methods A case–control study was performed using as cases 32 HIV-infected patients with prolonged (>440 msec QTc interval as assessed by Holter ECG, and as controls 64 HIV-infected subjects with normal QTc interval. Autonomic function was evaluated by heart rate variability analysis during 24-hour recording. Results Duration of HIV disease was significantly longer among cases than among controls (p=0.04. Waist/hip ratio was also higher among cases than among controls (p=0.05. Frequency domain analysis showed the absence of physiologic decrease of low frequency (LF in the night period in both cases and controls. The LF night in cases showed a statistically significant reduction when compared with controls (p=0.007. Conclusions In our study group, QTc interval prolongation was associated with a longer duration of HIV infection and with a greater waist/hip ratio. HIV patients with QTc interval prolongation and with a longer duration of HIV infection were more likely to have an impairment of parasympathetic and sympathetic cardiac component.

  15. Congenital long QT syndrome in children

    Directory of Open Access Journals (Sweden)

    Cerović Ivana

    2016-01-01

    Full Text Available Long QT syndrome (LQTS is a cardiac repolarization disorder characterized by prolonged QT interval on the electrocardiogram (ECG and increased propensity to ventricular tachyarrhythmias and cardiac events. LQTS might be acquired or congenital, which presents a group of channelopathies that occur due to mutation in one of 15 so far identified genes. The most frequent types of congenital LTQS are LQT1, LQT2 and LQT3. Prolonged or delayed repolarization leads to the increase of action potential duration which predisposes early afterdepolarization, as well as the amplification of transmural dispersion of repolarization, both contributing to the development of Torsades de Pointes ventricular tachycardia. Clinical manifestations of LQTS are palpitations, syncope, aborted cardiac arrest or sudden cardiac death, but it can also be asymptomatic. Trigger factors for symptoms are specific for certain genotype. LQTS examination includes thorough clinical and family history focused on distinctive data (repeated syncopes, cases of sudden cardiac death in the family, hereditary arrhythmias, resting ECG, exercise stress testing and genetic analysis, with additional methods (serial ECG records, 24h ECG Holter, epinephrine test. Clinical LQTS diagnosis is based on Schwartz's scoring system, while the criteria for final diagnosis of LQTS depend on Schwartz's score, QT interval duration, presence of pathogenic mutation and clinical symptoms. Treatment approach begins with lifestyle modifications and β-blockers therapy, while other options include implantable cardioverter- defibrillator, permanent pacemaker or surgical sympathectomy. Sudden cardiac death is the reason of 90% of sudden deaths in young athletes, while LQTS is one of its causes. Recommendations for physical activities in children with congenital LQTS arise from the ones for adults and they presume very strict limitations. Further researches are expected to advance the understanding of genotype

  16. Incidence and risk of QTc interval prolongation among cancer patients treated with vandetanib: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Jiajie Zang

    Full Text Available BACKGROUND: Vandetanib is a multikinase inhibitor that is under assessment for the treatment of various cancers. QTc interval prolongation is one of the major adverse effects of this drug, but the reported incidence varies substantially among clinical trials. We performed a systematic review and meta-analysis to obtain a better understanding in the risk of QTc interval prolongation among cancer patients administered vandetanib. METHODOLOGY AND PRINCIPAL FINDINGS: Eligible studies were phase II and III prospective clinical trials that involved cancer patients who were prescribed vandetanib 300 mg/d and that included data on QTc interval prolongation. The overall incidence and risk of QTc interval prolongation were calculated using random-effects or fixed-effects models, depending on the heterogeneity of the included studies. Nine trials with 2,188 patients were included for the meta-analysis. The overall incidence of all-grade and high-grade QTc interval prolongation was 16.4% (95% CI, 8.1-30.4% and 3.7% (8.1-30.4%, respectively, among non-thyroid cancer patients, and 18.0% (10.7-28.6% and 12.0% (4.5-28.0%, respectively, among thyroid cancer patients. Patients with thyroid cancer who had longer treatment duration also had a higher incidence of high-grade events, with a relative risk of 3.24 (1.57-6.71, than patients who had non-thyroid cancer. Vandetanib was associated with a significantly increased risk of all-grade QTc interval prolongation with overall Peto odds ratios of 7.26 (4.36-12.09 and 5.70 (3.09-10.53 among patients with non-thyroid cancer and thyroid cancer, respectively, compared to the controls. CONCLUSIONS/SIGNIFICANCE: Treatment with vandetanib is associated with a significant increase in the overall incidence and risk of QTc interval prolongation. Different cancer types and treatment durations may affect the risk of developing high-grade QTc interval prolongation.

  17. Van gen naar ziekte; Ionkanaaleiwitten en het lange-QT-intervalsyndroom

    NARCIS (Netherlands)

    Wilde, A.A.M.; Van Langen, I.M.

    2000-01-01

    The long QT syndrome is characterised by QT prolongation on the ECG, repeated syncope and sudden cardiac death. QT prolongation is the result of delayed repolarisation at the cellular level, secondary to dysfunctioning ion channels. Ventricular arrhythmias underlie syncope and death. At least six ge

  18. Unintended consequences of reducing QT-alert overload in a computerized physician order entry system

    NARCIS (Netherlands)

    I.H. van der Sijs (Heleen); R. Kowlesar (Ravi); J.E.C.M. Aarts (Jos); M. Berg (Marc); A.G. Vulto (Arnold); T. van Gelder (Teun)

    2009-01-01

    textabstractPurpose: After complaints of too many low-specificity drug-drug interaction (DDI) alerts on QT prolongation, the rules for QT alerting in the Dutch national drug database were restricted in 2007 to obviously QT-prolonging drugs. The aim of this virtual study was to investigate whether

  19. Drug-induced Inhibition and Trafficking Disruption of ion Channels: Pathogenesis of QT Abnormalities and Drug-induced Fatal Arrhythmias.

    Science.gov (United States)

    Cubeddu, Luigi X

    2016-01-01

    Risk of severe and fatal ventricular arrhythmias, presenting as Torsade de Pointes (TdP), is increased in congenital and acquired forms of long QT syndromes (LQTS). Drug-induced inhibition of K+ currents, IKs, IKr, IK1, and/or Ito, delay repolarization, prolong QT, and increase the risk of TdP. Drug-induced interference with IKr is the most common cause of acquired LQTS/TdP. Multiple drugs bind to KNCH2-hERG-K+ channels affecting IKr, including antiarrythmics, antibiotics, antivirals, azole-antifungals, antimalarials, anticancer, antiemetics, prokinetics, antipsychotics, and antidepressants. Azithromycin has been recently added to this list. In addition to direct channel inhibition, some drugs interfere with the traffic of channels from the endoplasmic reticulum to the cell membrane, decreasing mature channel membrane density; e.g., pentamidine, geldalamicin, arsenic trioxide, digoxin, and probucol. Other drugs, such as ketoconazole, fluoxetine, norfluoxetine, citalopram, escitalopram, donepezil, tamoxifen, endoxifen, atazanavir, and roxitromycin, induce both direct channel inhibition and impaired channel trafficking. Although many drugs prolong the QT interval, TdP is a rare event. The following conditions increase the risk of drug-induced TdP: a) Disease states/electrolyte levels (heart failure, structural cardiac disease, bradycardia, hypokalemia); b) Pharmacogenomic variables (presence of congenital LQTS, subclinical ion-channel mutations, history of or having a relative with history of drug-induced long QT/TdP); c) Pharmacodynamic and kinetic factors (high doses, women, elderly, metabolism inhibitors, combining two or more QT prolonging drugs, drugs that prolong the QT and increase QT dispersion, and drugs with multiple actions on ion channels). Because most of these conditions are preventable, careful evaluation of risk factors and increased knowledge of drug use associated with repolarization abnormalities are strongly recommended.

  20. Methadone, QTc interval prolongation and torsade de pointes: Case reports offer the best understanding of this problem.

    Science.gov (United States)

    Vieweg, W Victor R; Hasnain, Mehrul; Howland, Robert H; Clausen, Thomas; Koneru, Jayanthi N; Kogut, Christopher; Crouse, Ericka L Breden; Hancox, Jules C; Fernandez, Antony; Pandurangi, Ananda K

    2013-08-01

    We reviewed the literature and found 31 adult cases and 1 newborn case of methadone-associated QTc interval prolongation and/or torsade de pointes (TdP). Parametric statistics may not be useful in studying this issue because methadone-associated TdP is a very rare event and, hence, "an extreme outlier" consistent with scalable randomness. We may have to rely upon narrative medicine in the form of case reports with all its limitations and hazards to provide our best understanding. We report risk factors for methadone-associated QTc interval prolongation and TdP based on review of published case reports. We believe both drug manufacturers and the FDA would better serve our patients and inform clinicians if they more readily reported drug-induced outliers such as methadone-associated TdP using a case report format.

  1. Prolongation of PR interval is associated with endothelial dysfunction and activation of vascular repair in high-risk cardiovascular patients.

    Science.gov (United States)

    Chan, Yap-Hang; Siu, Chung-Wah; Yiu, Kai-Hang; Yiu, Yuen-Fung; Lau, Kui-Kai; Lam, Tai-Hing; Lau, Chu-Pak; Tse, Hung-Fat

    2013-06-01

    Epidemiological studies showed that PR prolongation is associated with increased risk of adverse cardiovascular outcomes. We investigated the relations of PR interval with indices of vascular function and endothelial repair as the underlying mechanisms. The study comprised 348 high-risk patients with prior coronary artery disease, ischemic stroke, and/or diabetes mellitus recruited from medical outpatient clinics and 150 healthy subjects without such a history. PR interval was considered prolonged if >200 ms, as determined from resting 12-lead electrocardiogram. Vascular function was assessed by brachial flow-meditated dilatation (FMD) using high-resolution ultrasound. Circulating CD133(+)/KDR(+) endothelial progenitor cell (EPC) levels were measured by flow cytometry. Among healthy subjects, PR interval was inversely associated with FMD (R = -0.20, P = 0.015), but not with the level of circulating CD133(+)/KDR(+) EPC (R = 0.05, P = 0.58). Among high-risk cardiovascular patients, PR prolongation >200 ms was more common compared with healthy subjects (45/348 (13 %) versus 4/150 (3 %), P PR interval was associated inversely with FMD (R = -0.14, P = 0.01) and positively with circulating CD133(+)/KDR(+) EPC level (R = +0.14, P = 0.009). Circulating CD133(+)/KDR(+) EPC level was significantly increased in patients with PR prolongation >200 ms (0.87 ± 0.37 versus 0.68 ± 0.42 (log, ×10(-3)/ml), P = 0.005). Adjusted for potential confounders, increased PR interval remained independently associated with increased CD133(+)/KDR(+) EPC by +0.002 (95 % confidence interval (CI) 0.000 to 0.004 (log, ×10(-3)/ml), P = 0.011) and depressed FMD (B = -0.014 %, 95 % CI -0.027 to -0.002, P = 0.026). PR prolongation is associated with endothelial dysfunction and evidence of endothelial repair activation in patients with high cardiovascular risk.

  2. Survival after withdrawal of dofetilide in patients with congestive heart failure and a short baseline QTc interval; a follow-up on the Diamond-CHF QT substudy

    DEFF Research Database (Denmark)

    Brendorp, B; Torp-Pedersen, C; Elming, H;

    2003-01-01

    withdrawal of dofetilide. METHODS: Patients with congestive heart failure (CHF) and reduced left ventricular function enrolled in the Diamond-CHF (Danish Investigations of Arrhythmia and Mortality on Dofetilide-CHF) study were eligible for our QT substudy provided they were in sinus rhythm and had...

  3. A new biomarker--index of cardiac electrophysiological balance (iCEB)--plays an important role in drug-induced cardiac arrhythmias: beyond QT-prolongation and Torsades de Pointes (TdPs).

    Science.gov (United States)

    Lu, Hua Rong; Yan, Gan-Xin; Gallacher, David J

    2013-01-01

    In the present study, we investigated whether a new biomarker - index of cardiac electrophysiological balance (iCEB=QT/QRS) - could predict drug-induced cardiac arrhythmias (CAs), including ventricular tachycardia/ventricular fibrillation (VT/VF) and Torsades de Pointes (TdPs). The rabbit left ventricular arterially-perfused-wedge was used to investigate whether the simple iCEB measured from the ECG is reflective of the more difficult measurement of λ (effective refractory period×conduction velocity) for predicting CAs induced by a number of drugs. Dofetilide concentration-dependently increased iCEB and λ, predicting potential risk of drug-induced incidence of early afterdepolarizations (EADs) starting at 0.01μM. Digoxin (1 and 5μM), encainide (5 and 20μM) and propoxyphene (10 and 100μM) markedly reduced both iCEB and λ, predicting their ability to induce non-TdP-like VT/VF. At 10μM, both NS1643 and levcromakalim significantly decreased λ and iCEB, which was preceded with presence of non-TdP-like VT/VF. Isoprenaline (0.05 to 0.5μM) significantly reduced both λ and iCEB, which was associated with a high incidence of non-TdP-like VT/VF in most preparations. Other biomarkers (i.e. transmural dispersion of T-wave and instability of the QT interval) predicted only dofetilide-induced long QT and EADs, but did not predict drug-induced risk of non-TdP-like VT/VF. Our data from 7 reference drugs of known pro-arrhythmic effects suggests that 1) this non-invasive iCEB predicts potential risk of drug-induced CAs beyond long QT and TdP; 2) iCEB is more useful than the current biomarkers (i.e. transmural dispersion and instability) in predicting potential risks for drug-induced non-TdP-like VT/VF. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Analysis of heart rate variability and QT interval dispersion in hyperthyroidism patients%甲亢患者心率变异性及QT间期离散度分析

    Institute of Scientific and Technical Information of China (English)

    杜琼颖; 井艳

    2015-01-01

    ObjectiveTo research the changes of heart rate variability and QT interval dispersion (QTd) in hyperthyroidism patients.MethodsThere were 52 hyperthyroidism patients as hyperthyroidism group and 49 healthy people as control group. A retrospective analysis was made on their 24 h dynamic electrocardiogram and conventional standard 12-lead electrocardiogram. Minimum heart rate, maximum heart rate, and average heart rate values, standard deviation in all sinus cardiac RR interphase (NN interval) (SDNN) in heart rate variability, standard deviation average in RR interphase (SDANN), proportion of adjacent NN difference >50 ms in total number of sinus heart beat (PNN50), adjacent RR interphase root-mean-square (RMSSD), maximum QT interval (QTmax), minimum QT interval (QTmin), QT interval dispersion (QTmax-QTmin) were analyzed and compared in the two groups.ResultsThe hyperthyroidism group had higher minimum heart rate, maximum heart rate, and average heart rate than the control group, and their difference had statistical significance (P50 ms的个数占总窦性心搏个数的百分比(PNN50)、相邻RR间期差值的均方根(RMSSD)以及最大QT间期(QTmax)、最小QT间期(QTmin)、QT间期离散度(QTmax-QTmin).结果 甲亢组患者的最小心率、最大心率、平均心率均较对照组增高, 差异具有统计学意义(P<0.05);SDNN、PNN50、SDANN、RMSSD均较对照组降低, 差异具有统计学意义(P<0.05);QTd较对照组增大, 差异具有统计学意义(P<0.05).结论 甲亢患者心率变异性及QT离散度异常率较高, 自主神经对心脏的调节能力降低, 易发生恶性心律失常及心源性猝死, 临床上应对该类患者给予高度重视, 减少猝死的发生.

  5. QT response after a test dose and during maintenance therapy with AZD1305 in patients with atrial fibrillation: a double-blind, randomized, placebo-controlled trial

    DEFF Research Database (Denmark)

    Egstrup, Kenneth; Bergfeldt, Lennart; Duris, Tibor

    2011-01-01

    AZD1305 is an investigational antiarrhythmic agent that prolongs refractoriness through combined potassium and sodium channel inhibition. This study aimed to explore the utility of a test dose in predicting QT interval corrected according to Fridericia's formula (QTcF) during subsequent maintenan...

  6. Long QT Syndrome - A case report

    Directory of Open Access Journals (Sweden)

    Erwan Martanto

    2003-06-01

    Full Text Available Long QT syndrome (LQTS is an uncommon disease due to genetic defect and responsible for polymorphic VT (torsade-de pointes-TdP and sudden cardiac death. A case of 25 year-old woman with palpitation, severe headache and recurrent syncopal episode since 16 year-old is reported. The ECG showed bigeminy ventricular premaure contraction (VPC , prolonged QTc interval and abnormal T wave. Peripartal cardiomyopathy was diagnosed recently after the first delivery. In July 2002, she was hospitalized due to recurrent syncope, seizure proceeded by TdP and VF. On admission she need several times DC shock and temporary pacemaker with relatively high rate. Beta-blocker and implantation of dual chamber permanent pacemaker finally could control the malignant arrhythmias. During follow-up for 4 months, she was doing well and no syncopal episode occurred. (Med J Indones 2003; 12: 109-13 Keywords: LQTS, arrhythmia, pacemaker, beta-blocker

  7. QT dynamics during treatment with sertindole

    DEFF Research Database (Denmark)

    Nielsen, Jimmi; Wang, Fang; Graff, Claus

    2015-01-01

    were excluded from further analysis due to low amplitude of the T-wave. When patients were shifted to sertindole, the VR increased from 0.192 (SD 0.045) to 0.223 (SD 0.061), p = 0.02. The QTcF interval increased from 388 (SD 16) to 403 ms (SD 14), p = 0.002. There was no difference in heart rate 78 bpm...... (SD 8) versus 80 bpm (SD 10), p = 0.3 or heart rate variability (SDNN) 127 (SD 40) versus 115 ms (SD 45), p = 0.4. CONCLUSION: Sertindole was associated with 19 ms QTc prolongation and an increased ratio of QT variability to heart rate variability. Both measures may contribute to the increased...

  8. PR interval prolongation in coronary patients or risk equivalent: excess risk of ischemic stroke and vascular pathophysiological insights.

    Science.gov (United States)

    Chan, Yap-Hang; Hai, Jo Jo; Lau, Kui-Kai; Li, Sheung-Wai; Lau, Chu-Pak; Siu, Chung-Wah; Yiu, Kai-Hang; Tse, Hung-Fat

    2017-08-24

    Whether PR prolongation independently predicts new-onset ischemic events of myocardial infarction and stroke was unclear. Underlying pathophysiological mechanisms of PR prolongation leading to adverse cardiovascular events were poorly understood. We investigated the role of PR prolongation in pathophysiologically-related adverse cardiovascular events and underlying mechanisms. We prospectively investigated 597 high-risk cardiovascular outpatients (mean age 66 ± 11 yrs.; male 67%; coronary disease 55%, stroke 22%, diabetes 52%) for new-onset ischemic stroke, myocardial infarction (MI), congestive heart failure (CHF), and cardiovascular death. Vascular phenotype was determined by carotid intima-media thickness (IMT). PR prolongation >200 ms was present in 79 patients (13%) at baseline. PR prolongation >200 ms was associated with significantly higher mean carotid IMT (1.05 ± 0.37 mm vs 0.94 ± 0.28 mm, P = 0.010). After mean study period of 63 ± 11 months, increased PR interval significantly predicted new-onset ischemic stroke (P = 0.006), CHF (P = 0.040), cardiovascular death (P 200 ms. Using multivariable Cox regression, PR prolongation >200 ms independently predicted new-onset ischemic stroke (HR 8.6, 95% CI: 1.9-37.8, P = 0.005), cardiovascular death (HR 14.1, 95% CI: 3.8-51.4, P PR interval predicts new-onset MI at the exploratory cut-off >162 ms (C-statistic 0.70, P = 0.001; HR: 8.0, 95% CI: 1.65-38.85, P = 0.010). PR prolongation strongly predicts new-onset ischemic stroke, MI, cardiovascular death, and combined cardiovascular endpoint including CHF in coronary patients or risk equivalent. Adverse vascular function may implicate an intermediate pathophysiological phenotype or mediating mechanism.

  9. Antiarrhythmic properties of a rapid delayed-rectifier current activator in rabbit models of acquired long QT syndrome

    DEFF Research Database (Denmark)

    Diness, Thomas G; Yeh, Yung-Hsin; Qi, Xiao Yan;

    2008-01-01

    effect of a novel compound (NS1643) that activates the rapid delayed-rectifier K+ current, I(Kr), in two rabbit models of acquired LQTS. METHODS AND RESULTS: We used two clinically relevant in vivo rabbit models of TdP in which we infused NS1643 or vehicle: (i) three-week atrioventricular block...... with ventricular bradypacing; (ii) dofetilide-induced I(Kr) inhibition in methoxamine-sensitized rabbits. In addition, we studied effects on ionic currents in cardiomyocytes with I(Kr) suppressed by bradycardia remodelling or dofetilide exposure. Bradypaced rabbits developed QT interval prolongation, spontaneous...... ventricular ectopy, and TdP. Infusion of NS1643 completely suppressed arrhythmic activity and shortened the QT interval; vehicle had no effect. NS1643 also suppressed ventricular tachyarrhythmias caused by infusion of dofetilide to methoxamine-sensitized rabbits, and reversed dofetilide-induced QT...

  10. Medicamentos que podem induzir prolongamento do intervalo QT utilizados por idosos em domicílio

    Directory of Open Access Journals (Sweden)

    Josiane Macêdo Martins

    2015-10-01

    cardiac death. The objective of this study was to identify drugs used by elderly at home which may induce QTi prolongation. This is a quantitative, retrospective, descriptive, exploratory study conducted in a teaching hospital. A total of 190 elderly with information on the use of medications at home available in medical records were included in the study. The median age was 69.5 years, and 99 (52.1 % were female. The median number of medications used per patient at home was 4.0. A variety of 159 drugs were identified including 23(14.5% that may induce QTi prolongation. Among the 39 elderly (20.5% using drugs that may induce QTi prolongation, the most frequent were: amiodarone, amitriptyline, nortriptyline, citalopram and fluoxetine. Hypertension was the most frequent risk factor for QTi prolongation. The use of these drugs and the presence of risk factors place the elderly at increased risk for developing torsade de pointes. The identification of drugs that may induce QTi prolongation, drug-drug interactions and clinical conditions that may lead to this adverse effect reinforces the need for actions to ensure the drug safety in the elderly population and to avoid serious adverse events.Keywords: QT interval prolongation. Drugs. Elderly. Torsades de pointes.

  11. Prolonged QTc interval and risk of sudden cardiac death in a population of older adults

    DEFF Research Database (Denmark)

    Straus, Sabine M J M; Kors, Jan A; De Bruin, Marie L

    2006-01-01

    , >470 ms in women) was associated with a three-fold increased risk of sudden cardiac death (hazard ratio, 2.5; 95% confidence interval, 1.3 to 4.7), after adjustment for age, gender, body mass index, hypertension, cholesterol/high-density lipoprotein ratio, diabetes mellitus, myocardial infarction...

  12. Qt for Symbian

    CERN Document Server

    Fitzek, Frank H P; Torp, Tony

    2009-01-01

    Qt for Symbian takes a unique look at this cutting-edge programming environment. Step-by-step it explains Qt in an easy to access fashion, using simple examples throughout. A bible for all beginners it covers topics such as: Installing the developer platform / SDK; Explaining the basic Qt environment; The extension of Qt for Symbian modules. o Communication. o Sensors. o Etc; Simple examples for Qt for Symbian. This Nokia-endorsed primer written by developers involved in the new release of Qt will ultimately save you costs, development resources, and will help you get to market faster!.

  13. KCNE1 D85N polymorphism — a sex-specific modifier in type 1 long QT syndrome?

    Directory of Open Access Journals (Sweden)

    Marjamaa Annukka

    2011-01-01

    Full Text Available Abstract Background Long QT syndrome (LQTS is an inherited ion channel disorder manifesting with prolongation of the cardiac repolarization phase and severe ventricular arrhythmias. The common KCNE1 D85N potassium channel variant prolongs QT interval by inhibiting IKs (KCNQ1 and IKr (KCNH2 currents and is therefore a suitable candidate for a modifier gene in LQTS. Methods We studied the effect of D85N on age-, sex-, and heart rate-adjusted QT-interval duration by linear regression in LQTS patients carrying the Finnish founder mutations KCNQ1 G589D (n = 492, KCNQ1 IVS7-2A>G (n = 66, KCNH2 L552S (n = 73, and KCNH2 R176W (n = 88. We also investigated the association between D85N and clinical variables reflecting the severity of the disease. Results D85N was associated with a QT prolongation by 26 ms (SE 8.6, p = 0.003 in males with KCNQ1 G589D (n = 213, but not in females with G589D (n = 279. In linear regression, the interaction between D85N genotype and sex was significant (p = 0.028. Within the KCNQ1 G589D mutation group, KCNE1 D85N carriers were more often probands of the family (p = 0.042 and were more likely to use beta blocker medication (p = 0.010 than non-carriers. The number of D85N carriers in other founder mutation groups was too small to assess its effects. Conclusions We propose that KCNE1 D85N is a sex-specific QT-interval modifier in type 1 LQTS and may also associate with increased severity of disease. Our data warrant additional studies on the role of KCNE1 D85N in other genetically homogeneous groups of LQTS patients.

  14. Epileptic Patients are at Risk of Cardiac Arrhythmias: A Novel Approach using QT-nomogram, Tachogram, and Cardiac Restitution Plots

    Science.gov (United States)

    Al-Nimer, Marwan S.; Al-Mahdawi, Sura A.; Abdullah, Namir M.; Al-Mahdawi, Akram

    2017-01-01

    Background: Sudden death is reported in patients who had a history of epilepsy and some authors believed that is due to cardiac arrhythmias. Objectives: This study aimed to predict that the epileptic patients are at risk of serious cardiac arrhythmias by QT-nomogram, tachogram (Lorenz), and cardiac restitution plots. Methods: A total number of 71 healthy subjects (Group I) and 64 newly diagnosed epileptic patients (Group II) were recruited from Al-Yarmouk and Baghdad Teaching hospitals in Baghdad from March 2015 to July 2015 and included in this study. The diagnosis of epilepsy achieved clinically, electroencephalograph record and radio-images including computerized tomography and magnetic image resonance. At the time of entry into the study, an electrocardiography (ECG) was done, and the determinants of each ECG record were calculated. The QT-nomogram, tachogram, and cardiac restitution plots were used to identify the patients at risk of cardiac arrhythmias. Results: Significant prolonged corrected QT corrected (QTc) and JT corrected intervals were observed in female compared with male at age ≥50 years while the TQ interval was significantly prolonged in males of Group II. Eight patients of Group II had a significant pathological prolonged QTc interval compared with undetectable finding in Group I. QT nomogram did not disclose significant findings while the plots of Lorenz and restitution steepness disclose that the patients of Group II were vulnerable to cardiac arrhythmias. Abnormal ECG findings were observed in the age extremities (≤18 years and ≥50 years) in Group II compared with Group I. Conclusion: Utilization of QT-nomogram, restitution steepness, and tachogram plots is useful tools for detection subclinical vulnerable epileptic patient with cardiac arrhythmias. PMID:28149075

  15. Epileptic patients are at risk of cardiac arrhythmias: A novel approach using QT-nomogram, tachogram, and cardiac restitution plots

    Directory of Open Access Journals (Sweden)

    Marwan S Al-Nimer

    2017-01-01

    Full Text Available Background: Sudden death is reported in patients who had a history of epilepsy and some authors believed that is due to cardiac arrhythmias. Objectives: This study aimed to predict that the epileptic patients are at risk of serious cardiac arrhythmias by QT-nomogram, tachogram (Lorenz, and cardiac restitution plots. Methods: A total number of 71 healthy subjects (Group I and 64 newly diagnosed epileptic patients (Group II were recruited from Al-Yarmouk and Baghdad Teaching hospitals in Baghdad from March 2015 to July 2015 and included in this study. The diagnosis of epilepsy achieved clinically, electroencephalograph record and radio-images including computerized tomography and magnetic image resonance. At the time of entry into the study, an electrocardiography (ECG was done, and the determinants of each ECG record were calculated. The QT-nomogram, tachogram, and cardiac restitution plots were used to identify the patients at risk of cardiac arrhythmias. Results: Significant prolonged corrected QT corrected (QTc and JT corrected intervals were observed in female compared with male at age ≥50 years while the TQ interval was significantly prolonged in males of Group II. Eight patients of Group II had a significant pathological prolonged QTc interval compared with undetectable finding in Group I. QT nomogram did not disclose significant findings while the plots of Lorenz and restitution steepness disclose that the patients of Group II were vulnerable to cardiac arrhythmias. Abnormal ECG findings were observed in the age extremities (≤18 years and ≥50 years in Group II compared with Group I. Conclusion: Utilization of QT-nomogram, restitution steepness, and tachogram plots is useful tools for detection subclinical vulnerable epileptic patient with cardiac arrhythmias.

  16. Cigarette Smoking Is Associated with Prolongation of the QTc Interval Duration in Patients with Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Petros Thomakos

    2013-01-01

    Full Text Available Aims. Aim of the study was to evaluate the effect of smoking on autonomic nervous system (ANS activity and QTc interval duration in patients with Type 2 diabetes mellitus (T2DM. Methods. A total of 70 patients with T2DM (35 chronic smokers, 35 nonsmokers treated with oral antidiabetic medications underwent continuous ECG Holter monitoring for 24 hours and analysis of time- and frequency-domain measures of heart rate variability (HRV. HRV over short time was also assessed using the deep breathing test. In addition, baroreflex sensitivity (BRS was evaluated using the spontaneous sequence method. The mean QTc interval was measured from the 24-hour ECG recordings. Results. Smokers had lower body mass index (BMI and exhibited higher 24-hour mean heart rate. There was no difference regarding all measures of ANS activity between the two groups. Smokers showed increased mean QTc duration during the 24 hours (439.25±26.95 versus 425.05±23.03 ms, P=0.021 as well as in both day (439.14±24.31 ms, P=0.042 and night periods (440.91±32.30 versus 425.51±24.98 ms, P=0.033. The association between smoking status and mean QTc interval persisted after adjusting for BMI. Conclusions. Cigarette smoking is associated with prolongation of the QTc interval in patients with T2DM by a mechanism independent of ANS dysfunction.

  17. Programming with Qt

    CERN Document Server

    Dalheimer, Matthias Kalle

    2002-01-01

    The popular open source KDE desktop environment for Unix was built with Qt, a C++ class library for writing GUI applications that run on Unix, Linux, Windows 95/98, Windows 2000, and Windows NT platforms. Qt emulates the look and feel of Motif, but is much easier to use. Best of all, after you have written an application with Qt, all you have to do is recompile it to have a version that works on Windows. Qt also emulates the look and feel of Windows, so your users get native-looking interfaces. Platform independence is not the only benefit. Qt is flexible and highly optimized. You'll find th

  18. Repolarization analysis in children with the long QT syndrome.

    Science.gov (United States)

    Brockmeier, Konrad; Khalil, Markus; Sreeram, Narayanswami; Ulmer, Herbert E

    2003-01-01

    QT duration changes were analysed in 26 children with long QT syndrome (median age 9 years). With 12-lead Holter recordings, we found that macroscopically QT adaptation to heart rate changes was slow and only 3 of 26 patients showed abrupt changes in QT interval duration. These changes in the time domain were always accompanied by changes of STT morphology in the 3 of 26 patients. Application of Bazett's heart rate correction algorithm was inappropriate to show true QT changes in this young patient group due to temporary typical large cycle length variations, where moreover an overcorrection of the heart rate impact resulted in reflection of RR interval changes rather than true QT duration changes.

  19. Boosted protease inhibitors and the electrocardiographic measures of QT and PR durations

    DEFF Research Database (Denmark)

    Soliman, Elsayed Z; Lundgren, Jens D; Roediger, Mollie P;

    2011-01-01

    There are contradictory reports regarding the effects of protease inhibitors on the ECG measures of QT and PR interval durations. The effect of interrupting use of protease inhibitors on QT and PR progression is also unknown.......There are contradictory reports regarding the effects of protease inhibitors on the ECG measures of QT and PR interval durations. The effect of interrupting use of protease inhibitors on QT and PR progression is also unknown....

  20. Peripartum cardiomyopathy presenting with syncope due to Torsades de pointes: a case of long QT syndrome with a novel KCNH2 mutation.

    Science.gov (United States)

    Nishimoto, Orie; Matsuda, Morihiro; Nakamoto, Kei; Nishiyama, Hirohiko; Kuraoka, Kazuya; Taniyama, Kiyomi; Tamura, Ritsu; Shimizu, Wataru; Kawamoto, Toshiharu

    2012-01-01

    Peripartum cardiomyopathy (PPCM) is a cardiomyopathy of unknown cause that occurs in the peripartum period. We report a case of PPCM presenting with syncope 1 month after an uncomplicated delivery. Electrocardiography showed Torsades de pointes (TdP) and QT interval prolongation. Echocardiography showed left ventricular systolic dysfunction and endomyocardial biopsy showed myocyte degeneration and fibrosis. Administration of magnesium sulfate and temporary pacing eliminated recurrent TdP. Genetic analyses revealed that recurrent TdP occurred via electrolyte disturbance and cardiac failure due to PPCM on the basis of a novel mutation in KCNH2, a gene responsible for inherited type 2 long QT syndrome.

  1. Predictive value of QT interval dynamicity for sudden death in patients with idiopathic dilated cardiomyopathy%QT间期动态性在扩张型心肌病猝死风险预测中的价值

    Institute of Scientific and Technical Information of China (English)

    包明威; 谭团团; 于胜波; 陈葵; 黄从新

    2010-01-01

    目的 研究QT间期频率依赖性在原发性扩张型心肌病(扩心病)患者猝死风险预测中的作用.方法 选取55例原发性扩心病患者和27例健康志愿者(对照组).询问病史并行心脏超声、心电图和动态心电图检查.检测左室舒张末期内径(LVEDD)、左室射血分数(LVEF)、QT间期离散度(QTd)、心率变异性(SDNN)、QT/RR相关直线的斜率、24 h室性早搏(VPB)和非持续性室性心动过速(NSVT)的次数.随访扩心病患者,随访终点为全因死亡.结果 扩心病组的LVEDD、QTd、VPB、NSVT、QTe/RR(QTe为Q波起始至T波终点的间期)和QTp/RR(QTp为Q波起始至T波顶点的间期)斜率显著高于对照组;LVEF和SDNN显著低于对照组.扩心病猝死组、非猝死组和对照组相比,LVEDD、LVEF、QTd、SDNN、QTe/RR和QTp/RR斜率的差异有统计学意义.扩心病猝死组和非猝死组比较,LVEF、SDNN、QTe/RR和QTp/RR斜率的差异有统计学意义.扩心病NSVT阳性组和NSVT阴性组比较,LVEF、QTd、VPB、QTe/RR和QTp/RR斜率的差异有统计学意义.扩心病患者的猝死率,QTe/RR斜率≥0.210者显著高于<0.210者(54.5%与21.1%,P<0.05);QTp/RR斜率≥0.190者显著高于<0.190者(52.2%与21.9%,P<0.05);在LVEF≤35%和NSVT阳性的基础上结合应用QTe/RR≥0.210或QTp/RR≥0.190,猝死率显著提高.结论 扩心病猝死组QT/RR斜率显著高于非猝死组和对照组,QT频率依赖性对扩心病患者猝死有较高的预测价值,并可进一步提高NSVT和LVEF的预测价值.%Objective To explore the predictive value of QT interval dynamicity for sudden death in patients with idiopathic dilated cardiomyopathy ( DCM ). Methods Fifty-five patients with DCM ( DCM group) and 27 healthy subjects (Control group, Con) were enrolled. Investigations included history collection, clinical examination, echocardiography, electrocardiogram and 24 h ambulatory electrocardiogram. Following indexes were determined: left ventricle end diastolic

  2. Application development with Qt creator

    CERN Document Server

    Rischpater, Ray

    2014-01-01

    This book is great for developers who are new to Qt and Qt Creator and who are interested in harnessing the power of Qt for cross-platform development. If you have basic experience programming in C++, you have what it takes to create engaging cross-platform applications using Qt and Qt Creator!

  3. A detailed description and assessment of outcomes of patients with hospital recorded QTc prolongation.

    Science.gov (United States)

    Laksman, Zachary; Momciu, Bogdan; Seong, You Won; Burrows, Patricia; Conacher, Susan; Manlucu, Jaimie; Leong-Sit, Peter; Gula, Lorne J; Skanes, Allan C; Yee, Raymond; Klein, George J; Krahn, Andrew D

    2015-04-01

    Corrected QT (QTc) interval prolongation has been shown to be an independent predictor of mortality in many clinical settings and is a common finding in hospitalized patients. The causes and outcomes of patients with extreme QTc interval prolongation during a hospital admission are poorly described. The aim of this study was to prospectively identify patients with automated readings of QTc intervals >550 ms at 1 academic tertiary hospital. One hundred seventy-two patients with dramatic QTc interval prolongation (574 ± 53 ms) were identified (mean age 67.6 ± 15.1 years, 48% women). Most patients had underlying heart disease (60%), predominantly ischemic cardiomyopathy (43%). At lease 1 credible and presumed reversible cause associated with QTc interval prolongation was identified in 98% of patients. The most common culprits were QTc interval-prolonging medications, which were deemed most responsible in 48% of patients, with 25% of these patients taking ≥2 offending drugs. Two patients were diagnosed with congenital long-QT syndrome. Patients with electrocardiograms available before and after hospital admission demonstrated significantly lower preadmission and postdischarge QTc intervals compared with the QTc intervals recorded in the hospital. In conclusion, in-hospital mortality was high in the study population (29%), with only 4% of patients experiencing arrhythmic deaths, all of which were attributed to secondary causes.

  4. The application of root mean square electrocardiography (RMS ECG for the detection of acquired and congenital long QT syndrome.

    Directory of Open Access Journals (Sweden)

    Robert L Lux

    Full Text Available BACKGROUND: Precise measurement of the QT interval is often hampered by difficulty determining the end of the low amplitude T wave. Root mean square electrocardiography (RMS ECG provides a novel alternative measure of ventricular repolarization. Experimental data have shown that the interval between the RMS ECG QRS and T wave peaks (RTPK closely reflects the mean ventricular action potential duration while the RMS T wave width (TW tracks the dispersion of repolarization timing. Here, we tested the precision of RMS ECG to assess ventricular repolarization in humans in the setting of drug-induced and congenital Long QT Syndrome (LQTS. METHODS: RMS ECG signals were derived from high-resolution 24 hour Holter monitor recordings from 68 subjects after receiving placebo and moxifloxacin and from standard 12 lead ECGs obtained in 97 subjects with LQTS and 97 age- and sex-matched controls. RTPK, QTRMS and RMS TW intervals were automatically measured using custom software and compared to traditional QT measures using lead II. RESULTS: All measures of repolarization were prolonged during moxifloxacin administration and in LQTS subjects, but the variance of RMS intervals was significantly smaller than traditional lead II measurements. TW was prolonged during moxifloxacin and in subjects with LQT-2, but not LQT-1 or LQT-3. CONCLUSION: These data validate the application of RMS ECG for the detection of drug-induced and congenital LQTS. RMS ECG measurements are more precise than the current standard of care lead II measurements.

  5. The application of root mean square electrocardiography (RMS ECG) for the detection of acquired and congenital long QT syndrome.

    Science.gov (United States)

    Lux, Robert L; Sower, Christopher Todd; Allen, Nancy; Etheridge, Susan P; Tristani-Firouzi, Martin; Saarel, Elizabeth V

    2014-01-01

    Precise measurement of the QT interval is often hampered by difficulty determining the end of the low amplitude T wave. Root mean square electrocardiography (RMS ECG) provides a novel alternative measure of ventricular repolarization. Experimental data have shown that the interval between the RMS ECG QRS and T wave peaks (RTPK) closely reflects the mean ventricular action potential duration while the RMS T wave width (TW) tracks the dispersion of repolarization timing. Here, we tested the precision of RMS ECG to assess ventricular repolarization in humans in the setting of drug-induced and congenital Long QT Syndrome (LQTS). RMS ECG signals were derived from high-resolution 24 hour Holter monitor recordings from 68 subjects after receiving placebo and moxifloxacin and from standard 12 lead ECGs obtained in 97 subjects with LQTS and 97 age- and sex-matched controls. RTPK, QTRMS and RMS TW intervals were automatically measured using custom software and compared to traditional QT measures using lead II. All measures of repolarization were prolonged during moxifloxacin administration and in LQTS subjects, but the variance of RMS intervals was significantly smaller than traditional lead II measurements. TW was prolonged during moxifloxacin and in subjects with LQT-2, but not LQT-1 or LQT-3. These data validate the application of RMS ECG for the detection of drug-induced and congenital LQTS. RMS ECG measurements are more precise than the current standard of care lead II measurements.

  6. [Long QT syndrome: a brief review of the electrocardiographical diagnosis including Viskin's test].

    Science.gov (United States)

    Márquez, Manlio F

    2012-01-01

    The QT interval measures both repolarization and depolarization. Learning to measure the QT interval and know how to correct (QTc) for heart rate (HR) is essential for the diagnosis of long QT syndrome (LQTS). The QTc interval changes in duration and even morphology depending on the time of the day and on a day-to-day basis. A diminished adaptive response of the QTc interval to changes in HR is known as QT hysteresis. Viskin has introduced a very simple clinical test to confirm the diagnosis of LQTS based on the "hypoadaptation" of the QT when standing. This phenomenon gives the appearance of a "stretching of the QT" on the surface ECG. Likewise, he has coined the term "QT stunning" to refer to the phenomenon that the QTc interval does not return to baseline despite recovery of baseline HR after standing. This article shows some examples of the Viskin's test.

  7. Therapeutic hypothermia after cardiac arrest in Long QT syndrome: Could it be an adjunctive treatment to prevent dysrhythmias?

    Directory of Open Access Journals (Sweden)

    Kumar Jatti

    2015-06-01

    Full Text Available Therapeutic hypothermia has been used for neuroprotection following cardiac arrest presenting with ventricular tachycardia or ventricular fibrillation regardless of underlying cause. Long QT syndrome is a cause for polymorphic ventricular tachycardia, and we know that therapeutic hypothermia increases the QT interval. We managed a 27-year-old woman, who was 10 weeks post-partum, who collapsed secondary to ventricular fibrillation at home. Bystander cardiopulmonary resuscitation was started with successful resuscitation after a rescue shock from paramedics. On hospital admission, her computerised tomography head, computerised tomography pulmonary angiogram and echocardiography did not show any abnormality. Her baseline electrocardiogram showed prolonged QTc interval of 504 ms without ischaemic changes. After intubation and ventilation, she was treated with therapeutic hypothermia for 48 h. She had a further episode of polymorphic ventricular tachycardia requiring rescue shock just prior to starting therapeutic hypothermia in hospital. No dysrhythmias occurred during therapeutic hypothermia, although the QTc further increased. After stopping the therapeutic hypothermia, she had two further ventricular tachycardia episodes. After commencement of beta blockers, she remained free of arrhythmias, and an implantable cardioverter defibrillator was implanted, she has recovered without any neurological deficit. Ventricular dysrhythmias caused by prolongation of the QT interval during or after therapeutic hypothermia are not well understood. There has been a report of a patient also having ventricular dysrhythmia 2 h after re-warming post therapeutic hypothermia and also a report of arrhythmia free period during therapeutic hypothermia in a long QT syndrome patient; both these features are present in our patient. Re-warming is not usually known to cause any arrhythmias; however, it could be a problem in those with long QT syndrome. Whether

  8. DESARROLLO PROGRESIVO DE ONDA J GIGANTE Y PROLONGACIÓN EXTREMA DEL INTERVALO QT EN LA HIPOTERMIA INDUCIDA / Progressive development of giant J wave and extreme prolongation of QT interval in induced hypothermia

    Directory of Open Access Journals (Sweden)

    Yaniel Castro Torres

    2013-07-01

    Full Text Available Resumen: La aparición de ondas J es el suceso más común observado en el electrocardiograma de un paciente con hipotermia. Se presenta el caso de un hombre de 47 años, que le fue inducido un paro cardíaco mediante hipotermia para una cirugía cardíaca. En el trazo electrocardiográfico se evidencia el desarrollo progresivo de una onda J exuberante. Estas ondas pueden simular un infarto agudo de miocardio y se consideran una variable predictora de arritmogénesis. / Abstract: The appearance of J waves is the most common event observed in the electrocardiogram of a patient with hypothermia. We report the case of 47 years-old man, who underwent cardiac arrest using hypothermia for cardiac surgery. In the electrocardiographic tracing the progressive development of giant J waves is evident. These waves can mimic acute myocardial infarction and are considered a predictor of arrhythmogenesis.

  9. A single prolonged milking interval of 24h compromises the well-being and health of dairy Holstein cows.

    Science.gov (United States)

    Kohler, P; Alsaaod, M; Dolf, G; O'Brien, R; Beer, G; Steiner, A

    2016-11-01

    Cows are often shown at dairy shows with overfilled udders to achieve a better show placing. However, it is unclear to what degree "over-bagging" affects the health and well-being of show cows. The goal of this study was to assess the effect of a single prolonged milking interval (PMI) of 24h on the measurable signs of health and well-being in dairy cows in early and mid-lactation and to assess the effect of a nonsteroidal anti-inflammatory drug (NSAID) on well-being during a PMI. Fifteen Holstein cows were studied in early lactation (89.5±2.7d in milk) and were given an NSAID or physiological saline in a crossover design. Ten cows were studied again in mid-lactation (151.6±4.0d in milk). Data on clinical signs of cows' health, behavior, and well-being were collected at 1 or 2h intervals before and during a PMI of 24h. Data from the last 6h of a 12h milking interval were compared with the last 6h of the PMI. Compared with that of a cow in the last 6h of a 12-h milking interval, the behavior of cows in early lactation (saline group) changed during the last 6h of the PMI: we observed decreased eating time (22.4 vs. 16.2min/h), increased ruminating time (13.3 vs. 25.0min/h), and increased hind limb abduction while walking (score 41.7 vs. 62.6) and standing (31.2 vs. 38.9cm). Udder firmness was increased (2.9 vs. 4.5kg) during this period and more weight was placed on the hind limbs (46.4 vs. 47.0%). We also found pathological signs at the end of the PMI: all cows showed milk leaking, and 10 of 15 cows developed edema in the subcutaneous udder tissue. Somatic cell count was significantly increased from 12h to 72h after the PMI. Administration of an NSAID had no influence on measured variables, except that the occurrence of edema was not significantly increased during PMI in the flunixin group (10 of 15 and 6 of 15 cows for the saline and flunixin groups, respectively). In the cows in mid-lactation, different variables were not significantly changed in the PMI

  10. Qt 5 blueprints

    CERN Document Server

    Huang, Symeon

    2015-01-01

    If you are a programmer looking for a truly cross-platform GUI framework to help you save your time by side-stepping the incompatibility between different platforms and building applications using Qt 5 for multiple targets, then this book is most certainly intended for you. It is assumed that you have a basic programming experience of C++ and fundamental knowledge about Qt.

  11. A combined abnormality in heart rate variation and QT corrected interval is a strong predictor of cardiovascular death in type 1 diabetes

    DEFF Research Database (Denmark)

    Lykke, J A; Tarnow, Lise; Parving, H H;

    2008-01-01

    Long-term diabetes is associated with excess morbidity and mortality, and cardiovascular autonomic neuropathy and QTc interval abnormalities are both predictive of early cardiovascular death in diabetes. We aimed to investigate the effect of these risk factors in a large cohort of type 1 diabetic...

  12. Síndrome de QT prolongado congénito y embarazo: reporte de dos casos Congenital long QT syndrome and pregnancy: report of two cases

    Directory of Open Access Journals (Sweden)

    Julián M Aristizábal

    2010-04-01

    Full Text Available El síndrome de QT prolongado congénito, es una entidad clínica que se caracteriza por la alteración en la repolarización miocárdica dada por una prolongación significativa del intervalo QT con riesgo aumentado de síncope, taquicardia ventricular polimórfica y muerte súbita. Se produce por la alteración en la función de canales iónicos responsables del potencial de acción de las células cardíacas, como consecuencia de múltiples mutaciones, de las cuales las más frecuentes se dan en los canales de sodio y potasio. La relación con el embarazo y principalmente la presencia de eventos en el posparto, está determinada por arritmias ventriculares o episodios de muerte súbita, lo cual debe llevar a una evaluación exhaustiva de QTc prolongado y sus factores desencadenantes o enfermedades concomitantes. Se muestran los casos clínicos de dos pacientes que presentaron muerte súbita en el posparto en las cuales se diagnosticó síndrome de QT largo congénito.Congenital long QT syndrome is a clinical entity characterized by impairment of myocardial repolarization given by significant prolongation of the corrected QT interval with an increased risk of syncope, polymorphic ventricular tachycardia and sudden death. This is produced by an alteration in the function of ion channels responsible for the action potential of cardiac cells as a consequence of multiple mutations, the most common of which are in the sodium and potassium channels. The relationship with pregnancy and especially the presence of events in the postpartum period is clearly determined by the presence of ventricular arrhythmias or episodes of sudden death, that should lead to a thorough evaluation of prolonged QTc and its triggers or concomitant diseases. We present the clinical records of two patients who had sudden death during the postpartum and were diagnosed as congenital long QT Syndrome.

  13. Creation of a knowledge management system for QT analyses.

    Science.gov (United States)

    Tornøe, Christoffer W; Garnett, Christine E; Wang, Yaning; Florian, Jeffry; Li, Michael; Gobburu, Jogarao V

    2011-07-01

    An increasing number of thorough QT (TQT) reports are being submitted to the US Food and Drug Administration's interdisciplinary review team for QT (IRT-QT), requiring time-intensive quantitative analyses by a multidisciplinary review team within 45 days. This calls for systematic learning to guide future trials and policies by standardizing and automating the QT analyses to improve review efficiency, provide consistent advice, and enable pooled data analyses to answer key regulatory questions. The QT interval represents the time from initiation of ventricular depolarization to completion of ventricular repolarization recorded by electrocardiograph (ECG) and is used in the proarrhythmic risk assessment. The developed QT knowledge management system is implemented in the R package "QT." Data from 11 crossover TQT studies including time-matched ECGs and pharmacokinetic measurements following single doses of 400 to 1200 mg moxifloxacin were used for the QT analysis example. The automated workflow was divided into 3 components (data management, analysis, and archival). The generated data sets, scripts, tables, and graphs are automatically stored in a queryable repository and summarized in an analysis report. More than 100 TQT studies have been analyzed using the system since 2007. This has dramatically reduced the time needed to review TQT studies and has made the IRT-QT reviews consistent across reviewers. Furthermore, the system enables leveraging prior knowledge through pooled data analyses to answer policy-related questions and to understand the various effects that influence study results.

  14. Automated QT analysis that learns from cardiologist annotations.

    Science.gov (United States)

    Strachan, Iain Guy David; Hughes, Nicholas Peter; Poonawala, Mustafa Hashim; Mason, Jay W; Tarassenko, Lionel

    2009-01-01

    Reliable, automated QT analysis would allow the use of all the ECG data recorded during continuous Holter monitoring, rather than just intermittent 10-second ECGs. BioQT is an automated ECG analysis system based on a Hidden Markov Model, which is trained to segment ECG signals using a database of thousands of annotated waveforms. Each sample of the ECG signal is encoded by its wavelet transform coefficients. BioQT also produces a confidence measure which can be used to identify unreliable segmentations. The automatic generation of templates based on shape descriptors allows an entire 24 hours of QT data to be rapidly reviewed by a human expert, after which the template annotations can automatically be applied to all beats in the recording. The BioQT software has been used to show that drug-related perturbation of the T wave is greater in subjects receiving sotalol than in those receiving moxifloxacin. Chronological dissociation of T-wave morphology changes from the QT prolonging effect of the drug was observed with sotalol. In a definitive QT study, the percentage increase of standard deviation of QT(c) for the standard manual method with respect to that obtained with BioQT analysis was shown to be 44% and 30% for the placebo and moxifloxacin treatments, respectively. BioQT provides fully automated analysis, with confidence values for self-checking, on very large data sets such as Holter recordings. Automatic templating and expert reannotation of a small number of templates lead to a reduction in the sample size requirements for definitive QT studies.

  15. 房颤合并RR间期延长的动态心电图分析%Analysis of Dynamic Electrocardiogram RR Interval Prolonged Combine Atrial Fibrillation

    Institute of Scientific and Technical Information of China (English)

    郑守景; 陈伟玲

    2014-01-01

    目的:总结分析房颤合并有RR间期延长的动态心电图特点,以有效的指导临床治疗。方法:对60例房颤合并有RR间期延长患者的动态心电图进行回顾性分析,根据RR间期延长发作时间将所有患者分为睡眠组(仅在22∶00-7∶00发作,患者27例)及非睡眠组(24 h内均有发作,患者33例)。对两组患者的平均心室率(HR)、RR间期延长次数、RR间期延长平均时间及黑矇晕厥发生频率进行统计,并对两组以上资料进行对比分析。结果:睡眠组HR明显高于非睡眠组(P<0.05);而RR间期延长次数、RR间期延长平均时间及黑矇晕厥发生频率方面均明显低于非睡眠组(P<0.05)。结论:与睡眠无关的房颤合并有RR间期延长患者其病情重于仅于睡眠时发作房颤合并有RR间期延长患者,临床更应重视。%Objective:To analysis the characteristics of dynamic electrocardiogram of atrial fibrillation with RR interval prolongation,to guide the clinical treatment.Method:Retrospective analysis dynamic electrocardiogram of 60 patients atrial fibrillation with RR interval prolongation.Accorded to the prolongation of the RR interval time of onset of all patients were divided into sleep group(only in 22∶00 to 7∶00 attack,27 cases)and non sleep group(24 hours had seizures,33 cases).Analyzed the average heart rate (HR),RR interval prolonged prolongation of the RR interval number,average time and black mask or syncope statistical frequency of two groups.Result:The HR of sleep group was significantly higher than that in non sleep group(P<0.05);and prolonged RR interval prolongation of the RR interval number,average time and black mask syncope occurred frequency of sleep group were significantly lower than those in non sleep group(P<0.05). Conclusion:Atrial fibrillation with RR interval prolongation in non sleep group is severe illness than sleep group,more attention shall be paid to the clinical.

  16. [Progress in research on defective protein trafficking and functional restoration in HERG-associated long QT syndrome].

    Science.gov (United States)

    Fang, Peiliang; Lian, Jiangfang

    2016-02-01

    The human ether-a-go-go related gene (HERG) encodes the α -subunit of the rapid component of the delayed rectifier K(+) channel, which is essential for the third repolarization of the action potential of human myocardial cells. Mutations of the HERG gene can cause type II hereditary long QT syndrome (LQT2), characterized by prolongation of the QT interval, abnormal T wave, torsade de pointes, syncope and sudden cardiac death. So far more than 300 HERG mutations have been identified, the majority of which can cause LQT2 due to HERG protein trafficking defect. It has been reported that certain drugs can induce acquired long QT syndrome through directly blocking the pore and/or affecting the HERG trafficking. The trafficking defects and K(+) currents can be restored with low temperature and certain drugs. However, the mechanisms underlying defective trafficking caused by HERG mutations and the inhibition/restoration of HERG trafficking by drugs are still unknown. This review summarizes the current understanding of the molecular mechanisms including HERG trafficking under physiological and pathological conditions, and the effects of drugs on the HERG trafficking, in order to provide theoretical evidence for the diagnosis and treatment of long QT syndrome.

  17. Application development with Qt creator

    CERN Document Server

    Rischpater, Ray

    2013-01-01

    Written in a concise and easy-to-follow approach, this book will guide you to develop your first application with Qt with illustrated examples and screenshots.If you are a developer who is new to Qt and Qt Creator and is interested in harnessing the power of Qt for cross-platform development, this book is great for you. If you have basic experience programming in C++, you have what it takes to create great cross-platform applications using Qt and Qt Creator!

  18. LATE POTENTIALS IN A BRADYCARDIA-DEPENDENT LONG QT-SYNDROME ASSOCIATED WITH SUDDEN-DEATH DURING SLEEP

    NARCIS (Netherlands)

    TOBE, TJM; DELANGEN, CDJ; BINKBOELKENS, MTE; MOOK, PH; VIERSMA, JW; LIE, KI; WESSELING, H

    1992-01-01

    The purpose of this study was to determine the incidence of late potentials and their relation to QT prolongation in a family with a high incidence of sudden death during sleep at a young age and bradycardia-dependent QT prolongation (n = 9) and to compare the findings with those in consanguineous f

  19. QT dispersion and P wave dispersion in patients with fibromyalgia.

    Science.gov (United States)

    Yolbaş, Servet; Yıldırım, Ahmet; Düzenci, Deccane; Karakaya, Bülent; Dağlı, Mustafa Necati; Koca, Süleyman Serdar

    2016-12-01

    Fibromyalgia (FM) is a chronic disease characterized by widespread pain. Somatic complaints associated with the cardiovascular system, such as chest pain and palpitations, are frequently seen in FM patients. P and QT dispersions are simple and inexpensive measurements reflecting the regional heterogeneity of atrial and ventricular repolarization, respectively. QT dispersion can cause serious ventricular arrhythmias. The aim of the present study was to evaluate QT dispersion and P wave dispersion in patients with FM. The study involved 48 FM patients who fulfilled the established criteria and 32 healthy controls (HC). A standard 12-lead electrocardiogram was performed on all participants. QT dispersion was defined as the difference between the longest and the shortest QT intervals. Similarly, the differences between the shortest and longest P waves were defined as P wave dispersion. The QT dispersion and corrected QT dispersion were shorter in the FM group compared with the HC group (pdispersion value, there was no significant difference between the FM and HC groups (p=0.088). Longer QT and P wave dispersions are not problems in patients with FM. Therefore, it may be concluded that fibromyalgia does not include an increased risk of atrial and/or ventricular arrhythmias.

  20. Prolongation of injection interval after switching therapy from ranibizumab to aflibercept in Japanese patients with macular edema secondary to branch retinal vein occlusion

    Science.gov (United States)

    Tagami, Mizuki; Sai, Ryuto; Fukuda, Masahide; Azumi, Atsushi

    2017-01-01

    Purpose This study was conducted to investigate the outcome of switching therapy from ranibizumab to aflibercept in Japanese patients with macular edema (ME) secondary to branch retinal vein occlusion (BRVO) in daily practice. Materials and methods This retrospective study enrolled 15 eyes in 15 Japanese patients with ME secondary to BRVO who had been receiving a pro re nata regimen of ranibizumab and had provided written informed consent to switch to aflibercept therapy. The intravitreal injection interval, central retinal thickness, and visual acuity were evaluated before and after switching. Results The mean period of ranibizumab treatment was 11.8±4.2 months. The mean observation period after switching to aflibercept was 10.6±3.4 months, and seven patients were observed for more than 12 months after switching. The mean intravitreal injection interval was prolonged by 23.6 days with aflibercept (68.2±26.4 days with ranibizumab vs 91.8±33.2 days with aflibercept; P=0.0011). The mean intravitreal injection interval just before the switch was 81.3±35.6 days and was significantly prolonged to 100.8±34.2 days just after the switch to aflibercept (P=0.0309). The mean central retinal thickness did not change before or after the switch to aflibercept (295±55 μm with ranibizumab vs 276±25 μm with aflibercept; P=0.12). The mean visual acuity also remained at an improved level after the switch. No systemic or ocular side effects were evident during the study period. Conclusion Switching therapy from ranibizumab to aflibercept in Japanese patients with ME secondary to BRVO prolonged the intravitreal injection interval without anatomical or functional degradation.

  1. Prolongation of injection interval after switching therapy from ranibizumab to aflibercept in Japanese patients with macular edema secondary to branch retinal vein occlusion

    Directory of Open Access Journals (Sweden)

    Tagami M

    2017-02-01

    Full Text Available Mizuki Tagami, Ryuto Sai, Masahide Fukuda, Atsushi Azumi Ophthalmology Department, Eye Center, Kobe Kaisei Hospital, Kobe, Hyogo, Japan Purpose: This study was conducted to investigate the outcome of switching therapy from ranibizumab to aflibercept in Japanese patients with macular edema (ME secondary to branch retinal vein occlusion (BRVO in daily practice. Materials and methods: This retrospective study enrolled 15 eyes in 15 Japanese patients with ME secondary to BRVO who had been receiving a pro re nata regimen of ranibizumab and had provided written informed consent to switch to aflibercept therapy. The intravitreal injection interval, central retinal thickness, and visual acuity were evaluated before and after switching. Results: The mean period of ranibizumab treatment was 11.8±4.2 months. The mean observation period after switching to aflibercept was 10.6±3.4 months, and seven patients were observed for more than 12 months after switching. The mean intravitreal injection interval was prolonged by 23.6 days with aflibercept (68.2±26.4 days with ranibizumab vs 91.8±33.2 days with aflibercept; P=0.0011. The mean intravitreal injection interval just before the switch was 81.3±35.6 days and was significantly prolonged to 100.8±34.2 days just after the switch to aflibercept (P=0.0309. The mean central retinal thickness did not change before or after the switch to aflibercept (295±55 µm with ranibizumab vs 276±25 µm with aflibercept; P=0.12. The mean visual acuity also remained at an improved level after the switch. No systemic or ocular side effects were evident during the study period. Conclusion: Switching therapy from ranibizumab to aflibercept in Japanese patients with ME secondary to BRVO prolonged the intravitreal injection interval without anatomical or functional degradation. Keywords: branch retinal vein occlusion, macular edema, ranibizumab, aflibercept

  2. QT-Syndrome

    Directory of Open Access Journals (Sweden)

    Haverkamp W

    2001-01-01

    Full Text Available QT-Syndrome sind durch eine im Oberflächen-EKG nachweisbare abnorme Verlängerung der QT-Intervall-Dauer und das spontane Auftreten ventrikulärer Tachyarrhythmien vom Typ der Torsade de Pointes (TdP charakterisiert. Die Rhythmusstörungen führen typischerweise zu rezidivierend auftretenden Synkopen, bei Degeneration von TdP in Kammerflimmern kann ein plötzlicher Herztod resultieren. Es ist zu unterscheiden zwischen einer kongenitalen und einer sog. erworbenen Form der Erkrankung. Während wir heute wissen, daß es sich beim kongenitalen QT-Syndrom (Romano-Ward-Syndrom, Jervell-und-Lange-Nielsen-Syndrom um eine genetisch bedingte Ionenkanalerkrankung handelt, sind die Mechanismen, die zu einer erworbenen abnormen, mit TdP einhergehenden QT-Verlängerung führen, bisher weitgehend unbekannt; nur in wenigen Fällen scheinen, wie bei den angeborenen Formen, Mutationen von Genen, die für Ionenkanäle kodieren, zugrundezuliegen. QT-Syndrome sind zwar relativ seltene Erkrankungen, im Spannungsfeld zwischen Klinik, traditioneller und molekulargenetischer Diagnostik sowie herkömmlichen Therapieverfahren und zukünftig anstehender genspezifischer Therapie kommt ihnen jedoch Modellcharakter zu.

  3. Late sodium current block for drug-induced long QT syndrome: Results from a prospective clinical trial.

    Science.gov (United States)

    Johannesen, L; Vicente, J; Mason, J W; Erato, C; Sanabria, C; Waite-Labott, K; Hong, M; Lin, J; Guo, P; Mutlib, A; Wang, J; Crumb, W J; Blinova, K; Chan, D; Stohlman, J; Florian, J; Ugander, M; Stockbridge, N; Strauss, D G

    2016-02-01

    Drug-induced long QT syndrome has resulted in many drugs being withdrawn from the market. At the same time, the current regulatory paradigm for screening new drugs causing long QT syndrome is preventing drugs from reaching the market, sometimes inappropriately. In this study, we report the results of a first-of-a-kind clinical trial studying late sodium (mexiletine and lidocaine) and calcium (diltiazem) current blocking drugs to counteract the effects of hERG potassium channel blocking drugs (dofetilide and moxifloxacin). We demonstrate that both mexiletine and lidocaine substantially reduce heart-rate corrected QT (QTc) prolongation from dofetilide by 20 ms. Furthermore, all QTc shortening occurs in the heart-rate corrected J-Tpeak (J-Tpeak c) interval, the biomarker we identified as a sign of late sodium current block. This clinical trial demonstrates that late sodium blocking drugs can substantially reduce QTc prolongation from hERG potassium channel block and assessment of J-Tpeak c may add value beyond only assessing QTc.

  4. Hypokalemia: a potent risk for QTc prolongation in clarithromycin treated rats.

    Science.gov (United States)

    Karmakar, Sanmoy; Padman, Aswathi; Swamy Mane, Naga; Sen, Tuhinadri

    2013-06-05

    Clarithromycin belongs to macrolide group of antibiotics commonly known for their proarrhythmic potency. Besides agents interfering with CYP 3A, electrolyte imbalance might influence repolarization problems of clarithromycin. The proarrhythmic tendency of clarithromycin particularly in association with hypokalemia manifested a change in QT interval in rat electrocardiogram (ECG). Varying degree of hypokalemia was induced by intraperitoneal injection of furosemide (50, 30, and 10 mg/kg, for seven days). The serum electrolyte levels confirmed that hypokalemia was established in the groups receiving furosemide. Simultaneously, clarithromycin was orally administered in the doses of 100 and 80 mg/kg for seven days. ECG was measured for 5 min in anaesthetised rat before and after 2 h of treatment. The QT interval was corrected for heart rate and reported as corrected QT (QTc). Distinct QTc interval prolongation was observed in groups receiving furosemide (50 and 30 mg/kg) alone and in all the groups receiving clarithromycin alongside furosemide. Neither, clarithromycin (80 mg/kg) nor furosemide (10 mg/kg) exhibited any significant change in the QTc interval but in combination these drugs led to a significant increase in the QTc interval. Most interestingly, potassium supplementation was found to reduce QTc interval in the group presenting with maximum QTc prolongation. These results suggest that hypokalemic condition potentiates the clarithromycin induced QTc prolongation, thereby indicating the importance of monitoring serum electrolyte during clarithromycin therapy. Although, selection of rat for examination of proarrhythmic liability is controversial, this report may be considered as an evidence of hypokalemia potentiating clarithromycin induced QTc prolongation.

  5. Population-based beat-to-beat QT analysis from Holter recordings in the long QT syndrome.

    Science.gov (United States)

    Page, Alex; McNitt, Scott; Xia, Xiaojuan; Zareba, Wojciech; Couderc, Jean-Philippe

    2017-08-10

    The increasing dissemination of wearable ECG recorders (e.g. Holter, patches, and strap sensors) enables the acquisition of large amounts of data during long periods of time. However, the clinical value of these long-term continuous recordings is hindered by the lack of automatic tools to extract clinically relevant information (other than non-sinus and life-threatening rhythms) from such long-term data, particularly when targeting population-based research. In this work, we propose and test a new tool for analyzing beat-to-beat interval measurements and extracting features from Holter ECGs. Specifically, we assess the adaptation of the QT interval following sudden changes in heart rate in the primary long QT types (1 & 2). We find that in long QT syndrome type 2, certain QT adaptation patterns can indicate a higher risk for cardiac events. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. QTc interval in patients with schizophrenia receiving antipsychotic treatment as monotherapy or polypharmacy

    DEFF Research Database (Denmark)

    Elliott, Anja Friis; Johan Mørk, Thibault; Højlund, Mikkel

    2017-01-01

    Objective: Antipsychotics are associated with a polymorphic ventricular tachycardia, torsades de pointes, which, in the worst case, can lead to sudden cardiac death. The QT interval corrected for heart rate (QTc) is used as a clinical proxy for torsades de pointes. The QTc interval can be prolong...... on monitoring the QTc interval in women with schizophrenia receiving antipsychotics as polypharmacy....... by antipsychotic monotherapy, but it is unknown if the QTc interval is prolonged further with antipsychotic polypharmaceutical treatment. Therefore, this study investigated the associations between QTc interval and antipsychotic monotherapy and antipsychotic polypharmaceutical treatment in schizophrenia......, and measured the frequency of QTc prolongation among patients. Methods: We carried out an observational cohort study of unselected patients with schizophrenia visiting outpatient facilities in the region of Central Jutland, Denmark. Patients were enrolled from January of 2013 to June of 2015, with follow...

  7. Anthracyclines and Acquired Long QT Syndrome. A Case Report

    Directory of Open Access Journals (Sweden)

    Carlos Rodríguez Armada

    2014-12-01

    Full Text Available Acquired long QT syndrome results from secondary causes and can be caused by more than 100 non-antiarrhythmic drugs. Cardiac arrest due to Torsades de pointes induced by drugs causing prolonged QT syndrome is a rare but potentially fatal event, even in hospitals. The case of a 47-year-old patient diagnosed with non-Hodgkin lymphoma admitted to the hematology department of the Dr. Gustavo Aldereguía Lima University General Hospital in Cienfuegos is presented. The patient had been previously treated with anthracyclines and developed episodes of palpitations and syncope later. The treatment included monitoring the patient, avoiding other QT prolonging agents and administrating magnesium sulfate and potassium chloride with a proper maintenance of the fluid and acid-base balance. The presentation of this case aims at motivating interest in new reports on the subject and establishing a direct causal relationship through the evidence provided by new experiences.

  8. Normal QT dispersion in colchicine-resistant familial Mediterranean fever (FMF).

    Science.gov (United States)

    Nussinovitch, Udi; Livneh, Avi; Volovitz, Benjamin; Nussinovitch, Moshe; Ben-Zvi, Ilan; Lidar, Merav; Nussinovitch, Naomi

    2012-07-01

    The association between familial Mediterranean fever (FMF) and subclinical cardiac disease remains controversial. The aim of the current study was to evaluate whether FMF patients, who do not respond to colchicine treatment, and thereby endure persistent inflammation, have increased QT dispersion (QTd) values. Twenty-two FMF patients and 22 age- and sex-matched control subjects were included in the study. Repolarization and QT dispersion parameters were computed from 12-lead ECG recording using designated computer software, and results of five beats were subsequently averaged. Both FMF patients and controls had similar comorbidities, similar values of average QT, average corrected QT interval length, average QTd interval, average QT corrected dispersion, QT dispersion ratio, JT dispersion (JTd), and JT corrected dispersion. In conclusion, FMF patients who were unresponsive to colchicine treatment and did not develop amyloidosis had normal QTd and JTd parameters, indicating a non-increased risk for repolarization-associated ventricular arrhythmias.

  9. Does KCNE5 play a role in long QT syndrome?

    DEFF Research Database (Denmark)

    Hofman-Bang, Jacob; Jespersen, Thomas; Grunnet, Morten

    2004-01-01

    BACKGROUND: Long QT syndrome [LQTS] is a congenital cardiac disease characterised by prolonged QTC-time, syncopes and sudden cardiac death. LQTS is caused by mutations in genes coding for ion channels involved in the action potential. KCNE5 codes for a novel beta-subunit of the ion channel...

  10. Q-Tcd对乳腺癌表阿霉素化疗致心肌损伤的早期预测价值%EARLY PREDICTION VALUE OF Q-T INTERVAL DISPERSION FOR MYOCARDIAL INJURY INDUCED BY EPIRUBICIN IN BREAST CANCER PATIENTS

    Institute of Scientific and Technical Information of China (English)

    张英; 李青山; 刘兰芳; 吕喜英; 白璐

    2015-01-01

    Objective:To investigate the predictive value of Q-T interval dispersion (Q-Tcd) for early myocardial injury induced by epirubicin. Methods:44 breast cancer patients were all treated with epirubicin for 1-5 cycles with the dose was 75mg/m2. The patients were divided into myocardial injury group and non-myocardial injury group according to the troponinⅠlevel;The Q-T interval dispersion and echocardiographic results of patients in 2 groups were compared. Results:44 breast cancer patients, myocardial injury group had 16 patients, non-myocardial injury group had 28 patients. The Q-T interval dispersion of patients in myocardial injury group was obviously higher than that of patients in non-myocardial injury group (P0.05). Conclusions:Compared with left ventricular end diastolic diameter and left ventricular ejection fraction, Q-T interval dispersion is more sensitive for forecasting early myocardial injury induced by epirubicin.%目的::探讨Q-T 间期离散度(Q-Tcd)预测表阿霉素导致早期心肌损伤的应用价值。方法:44例乳腺癌患者均采用含表阿霉素的方案化疗,使用剂量为75mg/m2,治疗1-5个周期。根据肌钙蛋白Ⅰ水平将患者分为心肌损伤组和未发生心肌损伤组,比较患者的Q-T间期离散度和心脏超声结果。结果:44例患者中心肌损伤组16例、未发生心肌损伤组28例。心肌损伤组患者Q-T间期离散度明显高于未发生心肌损伤组(P0.05)。结论:表阿霉素对心肌损伤的评价指标中,Q-T间期离散度较左室舒张末期前后径和射血分数更为敏感,对表阿霉素致心肌病具有预测价值。

  11. Newer QT Correction Formulae to Correct QT for Heart Rate Changes During Exercise.

    Science.gov (United States)

    Rabkin, Simon W; Cheng, XinBo Justin

    2016-02-01

    The QT interval is a marker for drug-induced cardiac toxicity, electrolyte abnormalities and genetic mutations with a high risk of sudden death. The objective was to determine the optimal QT-heart rate correction when heart rate is increased. A total of 40 persons had QT interval measured before at the end of each stage of a Bruce protocol. Currently used heart rate correction formulae (QTc) were compared to recently proposed QTc formulae derived from large population studies. Comparing the data at each stage of exercise found that QTc using the Bazett formula (QTcBZT) increased with exercise while the QTc proposed by Fridericia (QTcFRD) and by Framingham (QTcFRM) decreased with exercise. In contrast QTc proposed by Dmitrienko (QTcDMT) and Rautaharju (QTcRTHa) were relatively constant despite the increase in heart rate during exercise, whereas QTc proposed by Hodges (QTcHDG) was more variable. With exercise, the differences between QTcBZT or QTcFRD and the other correction formulae became greater and highly significant. Next, the slope of QTc or RR regression was calculated for each individual during the exercise test. The rank order of the slopes (from the smallest to largest absolute value) was QTcRTHa, QTcDMT, QTcBZT, QTcHDG, QTcFRD and QTcFRM. Furthermore the slope of the QT/heart rate relationship was significantly (P heart rate correction formula should be used when evaluating QT interval at faster heart rates especially those associated with exercise. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  12. Long QT syndrome: A therapeutic challenge

    Directory of Open Access Journals (Sweden)

    Shah Maully

    2008-01-01

    Full Text Available Congenital long QT syndrome (LQTS is one of the most common cardiac channelopathies and is characterized by prolonged ventricular repolarization and life-threatening arrhythmias. The mortality is high among untreated patients. The identification of several LQTS genes has had a major impact on the management strategy for both patients and family members. An impressive genotype-phenotype correlation has been noted and genotype identification has enabled genotype specific therapies. Beta blockers continue to be the primary treatment for prevention of life threatening arrhythmias in the majority of patients. Other therapeutic options include pacemakers, implantable cardioverter defibrillators, left cardiac sympathetic denervation, sodium channel blocking medications and lifestyle modification.

  13. Thorough QT study of the effect of fesoterodine on cardiac repolarization.

    Science.gov (United States)

    Malhotra, B; Wood, N; Sachse, R; Gandelman, K

    2010-05-01

    Fesoterodine 4 mg and 8 mg once daily are indicated for the treatment of overactive bladder. A thorough QT study was conducted to investigate the effects of fesoterodine on cardiac repolarization. In this parallel-group study, subjects were randomly assigned to receive double-blind fesoterodine 4 mg, fesoterodine 28 mg, or placebo or open-label moxifloxacin 400 mg (positive control) for 3 days. Electrocardiograms (ECGs) were obtained on Days -1 (baseline), 1, and 3. The primary analysis was the time-averaged changes from baseline for Fridericia's-corrected QT interval (QTcF) on Day 3. Among 261 subjects randomized to fesoterodine 4 mg (n = 64), fesoterodine 28 mg (n = 68), placebo (n = 65), or moxifloxacin 400 mg (n = 64), 256 completed the trial. The least squares mean changes in QTcF from baseline were 21.1, 20.5, 18.5, and 31.3 ms (maximum), and -5.1, -4.2, -5.2, and 7.6 ms (time-averaged at Day 3) for placebo, fesoterodine 4 mg, fesoterodine 28 mg, and moxifloxacin, respectively. The lower limit of the 95% confidence interval exceeded 5 ms for moxifloxacin. The results indicate that fesoterodine is not associated with QTc prolongation or other ECG abnormalities at either therapeutic or supratherapeutic doses.

  14. Circadian variation in QT dispersion determined from a 12-lead Holter recording

    DEFF Research Database (Denmark)

    Hansen, Stig; Rasmussen, Verner; Larsen, Klaus;

    2007-01-01

    Background: QT dispersion is considered to reflect inhomogeneity of myocardial repolarization. Method: The circadian variation of QT interval dispersion was examined in 95 healthy subjects using 24-hour Holter monitoring. Three different methods of lead selection were applied: all 12 leads (QTdisp...

  15. Circadian variation in QT dispersion determined from a 12-lead Holter recording

    DEFF Research Database (Denmark)

    Hansen, S; Rasmussen, Verner; Larsen, Klaus

    2007-01-01

    Background: QT dispersion is considered to reflect inhomogeneity of myocardial repolarization. Method: The circadian variation of QT interval dispersion was examined in 95 healthy subjects using 24-hour Holter monitoring. Three different methods of lead selection were applied: all 12 leads (QTdis...

  16. Circadian variation in QT dispersion determined from a 12-lead Holter recording

    DEFF Research Database (Denmark)

    Hansen, S; Rasmussen, Verner; Larsen, Klaus

    2007-01-01

    Background: QT dispersion is considered to reflect inhomogeneity of myocardial repolarization. Method: The circadian variation of QT interval dispersion was examined in 95 healthy subjects using 24-hour Holter monitoring. Three different methods of lead selection were applied: all 12 leads (QTdisp...

  17. Cardiac Safety Research Consortium: can the thorough QT/QTc study be replaced by early QT assessment in routine clinical pharmacology studies? Scientific update and a research proposal for a path forward.

    Science.gov (United States)

    Darpo, Borje; Garnett, Christine; Benson, Charles T; Keirns, James; Leishman, Derek; Malik, Marek; Mehrotra, Nitin; Prasad, Krishna; Riley, Steve; Rodriguez, Ignacio; Sager, Philip; Sarapa, Nenad; Wallis, Robert

    2014-09-01

    The International Conference on Harmonization E14 guidance for the clinical evaluation of QT/QTc interval prolongation requires almost all new drugs to undergo a dedicated clinical study, primarily in healthy volunteers, the so-called TQT study. Since 2005, when the E14 guidance was implemented in United States and Europe, close to 400 TQT studies have been conducted. In February 2012, the Cardiac Safety Research Consortium held a think tank meeting at Food and Drug Administration's White Oak campus to discuss whether "QT assessment" can be performed as part of routine phase 1 studies. Based on these discussions, a group of experts convened to discuss how to improve the confidence in QT data from early clinical studies, for example, the First-Time-in-Human trial, through collection of serial electrocardiograms and pharmacokinetic samples and the use of exposure response analysis. Recommendations are given on how to design such "early electrocardiogram assessment," and the limitation of not having a pharmacologic-positive control in these studies is discussed. A research path is identified toward collecting evidence to replace or provide an alternative to the dedicated TQT study.

  18. Factors that prolong the 'postmortem interval until finding' (PMI-f) among community-dwelling elderly individuals in Japan: analysis of registration data.

    Science.gov (United States)

    Ito, Tomoko; Tamiya, Nanako; Takahashi, Hideto; Yamazaki, Kentaro; Yamamoto, Hideki; Sakano, Shoji; Kashiwagi, Masayo; Miyaishi, Satoru

    2012-01-01

    To clarify the factors affecting 'postmortem interval until finding' (PMI-f) among elderly unexpected death cases. Cross-sectional study. All area of Yamagata prefecture in Japan. Entering subjects were 5675 elderly cases with age of ≥65 years selected from all 9002 cases of unexpected death from 2002 to 2007 in Yamagata prefecture between 2002 and 2007. Our final study subjects consisted of 3387 cases sampled with several criteria to assess the factors to prolong PMI-f. The outcome was the postmortem interval until finding (PMI-f) as the time from death until finding the body which we defined in this study. 'Living alone' showed the highest adjusted HR (3.73, 95% CI 3.37 to 4.13), also 'unnatural death' (1.50, 1.28 to 1.75), 'found at own home' (1.37, 1.22 to 1.55) and 'younger subjects' (0.99, 0.98 to 0.99). In the model including interactions with the household situation, we found 'male subjects living alone' and 'female subjects living with family' tended to be found later. PMI-f is an effective outcome for quantitative analyses of risk of bodies left. To prevent the elderly dead bodies left for long time, it is necessary to keep regular home-based contact with elderly individuals living alone.

  19. Cardiac safety of indacaterol in healthy subjects: a randomized, multidose, placebo- and positive-controlled, parallel-group thorough QT study

    Directory of Open Access Journals (Sweden)

    Woessner Ralph

    2011-05-01

    Full Text Available Abstract Background Indacaterol is a novel once-daily ultra long-acting β2-agonist for the treatment of chronic obstructive pulmonary disease. It is known that β2-agonists, like other adrenergic compounds, can prolong the QT-interval. This thorough QT/QTc study (as per ICH E14 guideline evaluated the effect of indacaterol on the QT interval in healthy subjects. Methods In this randomized, double-blind, parallel-group, placebo- and positive-controlled (open-label moxifloxacin study, non-smoking healthy subjects (18-55 years, body mass index: 18.5-32.0 kg/m2 were randomized (4:4:2:4:1 to 14-day treatment with once-daily indacaterol (150 μg, 300 μg, or 600 μg, placebo, or placebo/moxifloxacin (double-blind 14-day treatment with placebo and a single open-label dose of 400 mg moxifloxacin on Day 14. The primary endpoint was the change from baseline on Day 14 in QTcF (QT interval corrected for heart rate using Fridericia's formula. Results In total, 404 subjects were randomized to receive indacaterol (150 [n = 108], 300 [n = 108], 600 μg [n = 54], placebo (n = 107, or placebo/moxifloxacin (n = 27; 388 subjects completed the study. Maximal time-matched mean (90% confidence intervals treatment differences from placebo in QTcF change from baseline on Day 14 were 2.66 (0.55, 4.77, 2.98 (1.02, 4.93 and 3.34 (0.86, 5.82 ms for indacaterol 150 μg, 300 μg and 600 μg, respectively. Study sensitivity was confirmed with moxifloxacin demonstrating a significant maximal time-matched QTcF prolongation of 13.90 (10.58, 17.22 ms compared to placebo. All indacaterol doses were well tolerated. Conclusion Indacaterol, at doses up to 600 μg once daily (2-4 times the therapeutic dose does not have any clinically relevant effect on the QT interval. Trial Registration ClinicalTrials.gov: NCT01263808

  20. Cardiac safety of indacaterol in healthy subjects: a randomized, multidose, placebo- and positive-controlled, parallel-group thorough QT study.

    Science.gov (United States)

    Khindri, Sanjeev; Sabo, Ronald; Harris, Stuart; Woessner, Ralph; Jennings, Simon; Drollmann, Anton F

    2011-05-26

    Indacaterol is a novel once-daily ultra long-acting β2-agonist for the treatment of chronic obstructive pulmonary disease. It is known that β2-agonists, like other adrenergic compounds, can prolong the QT-interval. This thorough QT/QTc study (as per ICH E14 guideline) evaluated the effect of indacaterol on the QT interval in healthy subjects. In this randomized, double-blind, parallel-group, placebo- and positive-controlled (open-label moxifloxacin) study, non-smoking healthy subjects (18-55 years, body mass index: 18.5-32.0 kg/m2) were randomized (4:4:2:4:1) to 14-day treatment with once-daily indacaterol (150 μg, 300 μg, or 600 μg), placebo, or placebo/moxifloxacin (double-blind 14-day treatment with placebo and a single open-label dose of 400 mg moxifloxacin on Day 14). The primary endpoint was the change from baseline on Day 14 in QTcF (QT interval corrected for heart rate using Fridericia's formula). In total, 404 subjects were randomized to receive indacaterol (150 [n = 108], 300 [n = 108], 600 μg [n = 54]), placebo (n = 107), or placebo/moxifloxacin (n = 27); 388 subjects completed the study. Maximal time-matched mean (90% confidence intervals) treatment differences from placebo in QTcF change from baseline on Day 14 were 2.66 (0.55, 4.77), 2.98 (1.02, 4.93) and 3.34 (0.86, 5.82) ms for indacaterol 150 μg, 300 μg and 600 μg, respectively. Study sensitivity was confirmed with moxifloxacin demonstrating a significant maximal time-matched QTcF prolongation of 13.90 (10.58, 17.22) ms compared to placebo. All indacaterol doses were well tolerated. Indacaterol, at doses up to 600 μg once daily (2-4 times the therapeutic dose) does not have any clinically relevant effect on the QT interval.

  1. Comparable Effects of High-Intensity Interval Training and Prolonged Continuous Exercise Training on Abdominal Visceral Fat Reduction in Obese Young Women

    Directory of Open Access Journals (Sweden)

    Haifeng Zhang

    2017-01-01

    Full Text Available This study compared the effect of prolonged moderate-intensity continuous training (MICT on reducing abdominal visceral fat in obese young women with that of work-equivalent (300 kJ/training session high-intensity interval training (HIIT. Forty-three participants received either HIIT (n=15, MICT (n=15, or no training (CON, n=13 for 12 weeks. The abdominal visceral fat area (AVFA and abdominal subcutaneous fat area (ASFA of the participants were measured through computed tomography scans preintervention and postintervention. Total fat mass and the fat mass of the android, gynoid, and trunk regions were assessed through dual-energy X-ray absorptiometry. Following HIIT and MICT, comparable reductions in AVFA (−9.1, −9.2 cm2, ASFA (−35, −28.3 cm2, and combined AVFA and ASFA (−44.7, −37.5 cm2, p>0.05 were observed. Similarly, reductions in fat percentage (−2.5%, −2.4%, total fat mass (−2.8, −2.8 kg, and fat mass of the android (−0.3, −0.3 kg, gynoid (−0.5, −0.7 kg, and trunk (−1.6, −1.2 kg, p>0.05 regions did not differ between HIIT and MICT. No variable changed in CON. In conclusion, MICT consisting of prolonged sessions has no quantitative advantage, compared with that resulting from HIIT, in abdominal visceral fat reduction. HIIT appears to be the predominant strategy for controlling obesity because of its time efficiency.

  2. Comparable Effects of High-Intensity Interval Training and Prolonged Continuous Exercise Training on Abdominal Visceral Fat Reduction in Obese Young Women

    Science.gov (United States)

    Zhang, Haifeng; Tong, Tom K.; Qiu, Weifeng; Zhang, Xu; Zhou, Shi

    2017-01-01

    This study compared the effect of prolonged moderate-intensity continuous training (MICT) on reducing abdominal visceral fat in obese young women with that of work-equivalent (300 kJ/training session) high-intensity interval training (HIIT). Forty-three participants received either HIIT (n = 15), MICT (n = 15), or no training (CON, n = 13) for 12 weeks. The abdominal visceral fat area (AVFA) and abdominal subcutaneous fat area (ASFA) of the participants were measured through computed tomography scans preintervention and postintervention. Total fat mass and the fat mass of the android, gynoid, and trunk regions were assessed through dual-energy X-ray absorptiometry. Following HIIT and MICT, comparable reductions in AVFA (−9.1, −9.2 cm2), ASFA (−35, −28.3 cm2), and combined AVFA and ASFA (−44.7, −37.5 cm2, p > 0.05) were observed. Similarly, reductions in fat percentage (−2.5%, −2.4%), total fat mass (−2.8, −2.8 kg), and fat mass of the android (−0.3, −0.3 kg), gynoid (−0.5, −0.7 kg), and trunk (−1.6, −1.2 kg, p > 0.05) regions did not differ between HIIT and MICT. No variable changed in CON. In conclusion, MICT consisting of prolonged sessions has no quantitative advantage, compared with that resulting from HIIT, in abdominal visceral fat reduction. HIIT appears to be the predominant strategy for controlling obesity because of its time efficiency. PMID:28116314

  3. Evaluation of five QT correction formulas using a software-assisted method of continuous QT measurement from 24-hour Holter recordings.

    Science.gov (United States)

    Molnar, J; Weiss, J; Zhang, F; Rosenthal, J E

    1996-10-15

    To evaluate and compare QT correction formulas in healthy subjects, we used 24-hour Holter monitoring because it allows the assessment of QT intervals over a large range of rates. Computer-assisted QT-interval measurements were obtained from 21 subjects. QT-RR relations for individuals and the group were fitted by regression analysis to 5 QT prediction formulas: simple Bazett's, modified Bazett's, linear (Framingham), modified Fridericia's and exponential (Sarma's). There were no significant differences in mean squared residuals between formulas. When using individually calculated regression parameters, each formula gave good or acceptable QT correction over the entire range of RR intervals. Simple Bazett's formula (which uses no regression parameters) was unreliable at high rates. Akaike information criteria rank was: Sarma's, Framingham, modified Bazett's, Fridericia's, and simple Bazett's. When group-based regression parameters were applied to individuals, no formula had a clear advantage over simple Bazett's. We conclude that any formula that invokes regression parameters unique to each individual provides satisfactory QT correction. Determination of these parameters requires long-term recording to obtain an adequate range of rates. Group-based regression parameters give poor correction. When individual parameters cannot be determined, as in a 12-lead electrocardiogram, no formula provides an advantage over the familiar simple Bazett's.

  4. Functional assessment of compound mutations in the KCNQ1 and KCNH2 genes associated with long QT syndrome

    DEFF Research Database (Denmark)

    Grunnet, Morten; Behr, Elijah Raphael; Calloe, Kirstine

    2005-01-01

    BACKGROUND: Long QT syndrome (LQTS) is a cardiovascular disorder characterized by prolonged QTc time, syncope, or sudden death caused by torsades de pointes and ventricular fibrillation. We investigated the clinical and electrophysiologic phenotype of individual mutations and the compound mutations...

  5. Factors that prolong the ‘postmortem interval until finding’ (PMI-f) among community-dwelling elderly individuals in Japan: analysis of registration data

    Science.gov (United States)

    Ito, Tomoko; Tamiya, Nanako; Takahashi, Hideto; Yamazaki, Kentaro; Yamamoto, Hideki; Sakano, Shoji; Kashiwagi, Masayo; Miyaishi, Satoru

    2012-01-01

    Objectives To clarify the factors affecting ‘postmortem interval until finding’ (PMI-f) among elderly unexpected death cases. Design Cross-sectional study. Setting All area of Yamagata prefecture in Japan. Participants Entering subjects were 5675 elderly cases with age of ≥65 years selected from all 9002 cases of unexpected death from 2002 to 2007 in Yamagata prefecture between 2002 and 2007. Our final study subjects consisted of 3387 cases sampled with several criteria to assess the factors to prolong PMI-f. Primary outcome measures The outcome was the postmortem interval until finding (PMI-f) as the time from death until finding the body which we defined in this study. Results ‘Living alone’ showed the highest adjusted HR (3.73, 95% CI 3.37 to 4.13), also ‘unnatural death’ (1.50, 1.28 to 1.75), ‘found at own home’ (1.37, 1.22 to 1.55) and ‘younger subjects’ (0.99, 0.98 to 0.99). In the model including interactions with the household situation, we found ‘male subjects living alone’ and ‘female subjects living with family’ tended to be found later. Conclusions PMI-f is an effective outcome for quantitative analyses of risk of bodies left. To prevent the elderly dead bodies left for long time, it is necessary to keep regular home-based contact with elderly individuals living alone. PMID:23024252

  6. Composition analysis of A, C, G, T nucleotides in genes responsible for the Long QT Syndrome

    Directory of Open Access Journals (Sweden)

    Vamsidhar Enireddy,

    2010-06-01

    Full Text Available Long QT syndrome (LQTS is a congenital disorder characterized by a prolongation of the QT interval on ECG and a propensity to ventricular tachyarrhythmia, which may lead to syncope, cardiac arrest, or sudden death. LQTS is caused by mutations of the genes for cardiac potassium and sodium or calcium ion channels. 8 genes have been identified.LQT1 (KCNQ1, LQT2 (KCNH2, and LQT3 (SCN5A account for most cases of LQTS, with estimated prevalence of 45%, 45%, and 7%, respectively. We have used the analogy of genome analysis and VIRUS (vital information recourse under siege and analyzed Since KCNQ1, KCNH2 and SCN5A genes are playing an important role in LQTS disease, we have taken their nucleotide sequences in FASTA format and submitted them in Geneboy(www.dnai.org.And studied their composition of nucleic acids (A,C,T,G,and we have received results for genes KCNQ1,KCNH2 such that their nucleic acid composition approximately same, being their prevalence percentage is same.

  7. Q -T间期离散度和心脏超声对蒽环类药物早期心肌损伤的预测价值%Predictive value of QT interval dispersion and echocardiography in early myocardium injury induced by anthracycline

    Institute of Scientific and Technical Information of China (English)

    张英; 张海峰; 李青山; 赵景新

    2014-01-01

    目的:探讨Q-T间期离散度和心脏超声对预测蒽环类药物引起的早期心肌损伤的敏感性及应用价值。方法入选29例乳腺癌患者,且均采用含蒽环类药物的方案化疗,应用表阿霉素剂量为75 mg /m2,进行2~6个周期,随化疗进行体内蒽环类药物累积剂量不同,动态监测心电图Q-T间期离散度及心脏超声变化,并进行分析与评价。结果化疗后Q-T间期离散度较化疗前明显延长,差异有显著性意义,P<0.001。化疗后左室舒张末期前后径较化疗前轻度增大、左室射血分数较化疗前轻度下降,但差异无显著性意义, P>0.05。结论化疗药物对心肌损伤的评价指标中,心电图Q-T间期离散度较心脏超声的左室舒张末期前后径和左室射血分数更为敏感,具有对蒽环类药物引起的心肌损伤的早期预测价值,通过监测心电图Q-T间期离散度变化,能及早在心肌损伤亚临床阶段发现其心脏毒性的发生与进展。%Objective To discuss the application value and sensitivity of QT interval dispersion and echocardiography in early myocardium injury induced by anthracycline .Methods The study included 29 breast cancer patients , who received chemotherapy with anthracycline ,The dosage of epidoxorubicina was 75 mg/m2 for 2-6 cycles.QT interval dispersion by ECG and echocardiography were analyzed in accordance with the accumulation of anthracycline by chemotherapy .Results Q-T interval dispersion became longer after chemotherapy compared to that before chemotherapy .The differences were sta-tistically significant (P0.05). Conclusion Among the indexes of myocardium injury induced by chemotherapy drugs , Q-T interval dispersion is more sensitive than left ventricular end -diastolic diameter and LVEF by echocardiography , and can be a useful marker for early prediction of anthracycline -induced myocardium injury .We can discover the early occurrence and progress of

  8. Prevention of Pazopanib-Induced Prolonged Cardiac Repolarization and Proarrhythmic Effects

    Directory of Open Access Journals (Sweden)

    Tulay Akman

    2014-11-01

    Full Text Available Background: Pazopanib (PZP may induce prolonged cardiac repolarization and proarrhythmic effects, similarly to other tyrosine kinase inhibitors. Objectives: To demonstrate PZP-induced prolonged cardiac repolarization and proarrhythmic electrophysiological effects and to investigate possible preventive effects of metoprolol and diltiazem on ECG changes (prolonged QT in an experimental rat model. Methods: Twenty-four Sprague-Dawley adult male rats were randomly assigned to 4 groups (n = 6. The first group (normal group received 4 mL of tap water and the other groups received 100 mg/kg of PZP (Votrient® tablet perorally, via orogastric tubes. After 3 hours, the following solutions were intraperitoneally administered to the animals: physiological saline solution (SP, to the normal group and to the second group (control-PZP+SP group; 1 mg/kg metoprolol (Beloc, Ampule, AstraZeneca, to the third group (PZP+metoprolol group; and 1mg/kg diltiazem (Diltiazem, Mustafa Nevzat, to the fourth group (PZP+diltiazem group. One hour after, and under anesthesia, QTc was calculated by recording ECG on lead I. Results: The mean QTc interval values were as follows: normal group, 99.93 ± 3.62 ms; control-PZP+SP group, 131.23 ± 12.21 ms; PZP+metoprolol group, 89.36 ± 3.61 ms; and PZP+diltiazem group, 88.86 ± 4.04 ms. Both PZP+metoprolol and PZP+diltiazem groups had significantly shorter QTc intervals compared to the control-PZP+SP group (p < 0.001. Conclusion: Both metoprolol and diltiazem prevented PZP-induced QT interval prolongation. These drugs may provide a promising prophylactic strategy for the prolonged QTc interval associated with tyrosine kinase inhibitor use.

  9. QT dispersion in patients with acromegaly.

    Science.gov (United States)

    Unubol, Mustafa; Eryilmaz, Ufuk; Guney, Engin; Ture, Mevlut; Akgullu, Cagdas

    2013-04-01

    Acromegaly is a rare condition caused by a pituitary adenoma that secretes growth hormone. The mortality rate is 72 % higher in patients with acromegaly than in the general population according to meta-analyses. Mortality analysis has shown as many as 60 % of acromegalic patients die due to cardiovascular disease. Sudden cardiac death may occur in patients with acromegaly and malignant ventricular arrhythmia may play an important role in this fatal complication; however, the precise mechanism is not fully known. QT dispersion (dQT) is an electrophysiological factor known to be associated with a tendency for ventricular arrhythmia and sudden cardiac death. This study aimed to evaluate dQT as an early predictor of ventricular tachyarrhythmia, as sudden cardiac death commonly occurs in acromegalic patients. This cross-sectional case-control study enrolled 20 patients (10 female and 10 male) with acromegaly and 20 healthy controls (11 female and 9 male) after exclusion criteria were applied. Each participant underwent 12-lead electrocardiography, including ≥3 QRS complexes, at a speed of 25 mm/s after a 15-min rest. In each participant, the QT interval (beginning of the Q wave to the end of the T wave) was corrected (QTc) for heart rate using Bazett's formula [Formula: see text] QTc dispersion (dQTc) (QTc max - QTc min) was also calculated. There was no significant difference in median dQTc between the acromegalic patients (0.79 s) and the controls (0.45 s) (p > 0.05). Active acromegalic patients (n = 14) were estimated to have a median dQTc of 0.82 s, after excluding from the analysis six patients that were under full biochemical control, and that had randomly obtained growth hormone levels acromegaly might have an elevated risk for ventricular arrhythmia. We think that a non-invasive, simple and inexpensive marker-measurement of dQT-as part of cardiac monitoring could be valuable for screening complications in acromegalic patients.

  10. Cardiovascular Effects of Energy Drinks in Familial Long QT Syndrome: A Randomized Cross-Over Study.

    Science.gov (United States)

    Gray, Belinda; Ingles, Jodie; Medi, Caroline; Driscoll, Timothy; Semsarian, Christopher

    2017-03-15

    Caffeinated energy drinks may trigger serious cardiac effects. The aim of this study was to determine the cardiovascular effects of caffeinated energy drink consumption in patients with familial long QT syndrome (LQTS). From 2014-2016, 24 LQTS patients aged 16-50 years were recruited to a randomized, double-blind, cross-over study of energy drink (ED) versus control (CD) with participants acting as their own controls (one week washout). The primary study outcome was an increase in corrected QT interval (QTc) by >20ms. Secondary outcomes were changes in systolic and diastolic blood pressure. In 24 patients with LQTS (no dropout), mean age was 29±9 years, 13/24 (54%) were female, and 8/24 (33%) were probands. Intention to treat analysis revealed no significant change in QTc with ED compared with CD (12±28ms vs 16±27ms, 3% vs 4%, p=0.71). The systolic and diastolic blood pressure significantly increased with ED compared to CD (peak change 7±16mmHg vs 1±16mmHg, 6% vs 0.8%, p=0.046 and 8±10 vs 2±9mmHg, 11% vs 3% p=0.01 respectively). These changes correlated with significant increases in serum caffeine (14.6±11.3 vs 0.5±0.1μmol/L, p<0.001) and serum taurine (737±199 vs -59±22μmol/L, p<0.001). There were three patients with dangerous QTc prolongation of ≥50ms following energy drink consumption. Caffeinated energy drinks have significant haemodynamic effects in patients with LQTS, especifically an acute increase in blood pressure. Since dangerous QTc prolongation was seen in some LQTS patients, we recommend caution in young patients with LQTS consuming energy drinks. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. HERG block, QT liability and sudden cardiac death.

    Science.gov (United States)

    Brown, Arthur M

    2005-01-01

    Non-cardiac drugs may prolong action potential duration (APD) and QT leading to Torsade de Pointes (TdP) and sudden cardiac death. TdP is rare and QT is used as a surrogate marker in the clinic. For non-cardiac drugs, APD/QT liability is always associated with a reduction in hERG current produced by either direct channel block or inhibition of trafficking. hERG and APD liabilities correlate better when APDs are measured in rabbit versus canine Purkinje fibres. hERG and APD/QT liabilities may be dissociated when hERG block is offset by block of calcium or sodium currents. hERG liability may be placed in context by calculating a safety margin (SM) from the IC50 for inhibition of hERG current measured by patch clamp divided by the effective therapeutic plasma concentration of the drug. The SM is uncertain because literature values for IC50 may vary by 50-fold and small differences in plasma protein binding have large effects. With quality control, the IC50 95% confidence limits vary less than twofold. Ideally, hERG liability should be determined during lead optimization. Patch damp has insufficient throughput for this purpose. A novel high-throughput screen has been developed to detect drugs that block hERG directly and/or inhibit hERG trafficking.

  12. 非抗心律失常药物致QT延长和尖端扭转型室性心动过速的机理和相关危险因素%QT Prolongation and Torsades de Pointes Induced by Non-Antiarrhythmia Drugs: the Mechanism and Related Risk Factors

    Institute of Scientific and Technical Information of China (English)

    侯静波

    2011-01-01

    临床上常用的一些非抗心律失常药物如抗菌素和抗组胺类药物也可导致QT间期延长甚至尖端扭转型室性心动过速.主要机理与抑制心肌细胞快速激活延迟整流钾电流相关.正常情况下发生概率极低,但当存在各种危险因素时发生率明显增高.主要的危险因素包括基因的易感性如存在亚临床型先天性QT延长综合征或基因的变异、合并用药、老年、女性、低血钾、严重心动过缓、基础心脏疾病和肝肾功能异常等.正确认识其发生机理和相关危险因素,可保证临床医师有效而安全地使用药物.%Some of the non-antiarrhythmia drugs, like antibiotics and antihistamines, can cause QT prolongation and torsades de pointes. It is rare but potentially fatal. The blockade of the rapid component of the delayed rectifier potassium current ( /Kr) of the cardiac cell is responsible for the cellular mechanisms of this action. The underlying risk factors include genetic susceptibility ( /atent congenital LQTS, genetic polymorphisms) , drugs and drug combinations, advanced age, female sex, low serum potassium concentration, bradycardia, pre-existing cardiac disease, kidney and hepatic malfunction. Recognition of the related risk factors and exacerbating conditions can prevent the occurrence of the fatal side effect of these drugs.

  13. Radiotherapy for patients with isolated local recurrence of primary resected pancreatic cancer. Prolonged disease-free interval associated with favorable prognosis

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Akira; Itasaka, Satoshi; Yoshimura, Michio; Matsuo, Yukinori; Mizowaki, Takashi; Hiraoka, Masahiro [Kyoto University, Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto (Japan); Takaori, Kyoichi; Kawaguchi, Yoshiya; Uemoto, Shinji [Kyoto University, Department of Surgery, Graduate School of Medicine, Kyoto (Japan); Shibuya, Keiko [Yamaguchi University Graduate School of Medicine, Department of Therapeutic Radiology, Yamaguchi (Japan)

    2014-05-15

    To evaluate the treatment outcomes of radiotherapy and prognostic factors for recurrent pancreatic cancer. The study comprised 30 patients who developed a locoregional recurrence of primarily resected pancreatic cancer and received radiotherapy between 2000 and 2013 with a median dose of 54 Gy (range, 39-60 Gy). Concurrent chemotherapy included gemcitabine for 18 patients and S-1 for seven patients. The treatment outcomes and prognostic factors were retrospectively analyzed. The median follow-up after radiotherapy was 14.6 months. The 1-year overall survival, local control, and progression-free survival rates were 69 %, 67 %, and 32 %, respectively. The median overall survival and progression-free survival rates were 15.9 and 6.9 months, respectively. Tumor marker reduction and ≥ 50 % reduction were observed in 18 and two patients, respectively. Of the seven patients who exhibited pain symptoms, four and two patients were partly and completely relieved, respectively. Late grade 3 ileus and gastroduodenal bleeding were observed in one patient each. Among the clinicopathological factors evaluated, only a disease-free interval of greater than 18.9 months exhibited a significant association with improved overall survival (p = 0.017). Radiotherapy for isolated locally recurrent pancreatic cancer resulted in encouraging local control, overall survival, and palliative effects with mild toxicity, particularly in patients with a prolonged disease-free interval. This treatment strategy should be prospectively evaluated. (orig.) [German] Beurteilung strahlentherapeutischer Behandlungsergebnisse und prognostischer Faktoren bei rezidivierendem Pankreaskrebs. In dieser Studie wurden 30 Patienten aufgenommen, bei denen es nach primaer reseziertem Pankreaskrebs zu lokoregionaeren Rezidiven kam und die zwischen 2000 und 2013 strahlentherapeutisch mit einer mittleren Dosis von 54 Gy (Bereich 39-60 Gy) behandelt wurden. Im Rahmen der gleichzeitig durchgefuehrten Chemotherapie wurde

  14. Research and Development of Seismic Data Processing System Based on Constrained Inversion for Interval Velocity by Utilizing Qt Graphic User Interface Library%约束层速度反演方法及其处理系统的Qt研发

    Institute of Scientific and Technical Information of China (English)

    周洪生; 程冰洁; 张薇; 高妍; 梁群

    2012-01-01

    三维约束层速度反演技术是建立在指数渐进边界形式速度趋势模型之上,结合了井资料、旁道数据,以阻尼因子全局约束计算层速度的方法.能有效识别层速度异常区域,适用于大倾角低幅构造,少井无井区的速度资料处理.在充分利用Windows操作系统的广泛应用及运行稳定的基础上,结合跨平台的c++图形用户界面库Qt,使用c/c++和fortran语言混合编程,完成了三维约束层速度反演处理系统的研发.该处理系统运用于南海琼东南BD地区实际资料表明:方法能较好的解决纵向连续及横向变速的问题,计算得到的剖面分层贴合层位曲线,能更清晰的描绘构造细节,为储层预测提供依据.%The constrained inversion for interval velocity is based on exponential asymptotically bounded velocity mode, combined with well data, bypath data and damping factor to compute the global restriction interval velocity. It can identify anomaly interval velocity area and finish the processing of the seismic data in high inclination angle and low amplitude structure area. The processing system is developed by utilizing the stable and high efficient features of Windows operating system, combined with a cross-platform Qt graphical user interface software library, written by mixed programming languages including c/c-H- and FORTRAN, and designed by the multi-tread and object-oriented programming, etc. The technologies obtain good application results in actual seismic data from South-Sea BD target area, it can resolve the question about vertical continuous and horizontal variation, the horizon in computed profile next to the actual horizon curve, and describe the structure detail clearly. Above all, the processing system provides a solution for the development of other seismic data processing software, and contributes to the reservoir prediction.

  15. Identification of a novel KCNQ1 mutation associated with both Jervell and Lange-Nielsen and Romano-Ward forms of long QT syndrome in a Chinese family

    Directory of Open Access Journals (Sweden)

    Liu Jing

    2008-04-01

    Full Text Available Abstract Background Long QT syndrome (LQTS is a cardiac disorder characterized by prolonged QT intervals on electrocardiograms (ECG, ventricular arrhythmias, and sudden death. Clinically, two inherited forms of LQTS have been defined: autosomal dominant LQTS or Romano-Ward syndrome (RWS not associated with deafness and autosomal recessive LQTS or Jervell and Lange-Nielsen syndrome (JLNS associated with deafness. Methods A Chinese family with both RWS and JLNS was identified. Family members were diagnosed based on the presence of a prolonged QT interval as seen on a 12-lead ECG and a medical history of syncope, palpitation, and deafness. Mutational studies in the KCNQ1 potassium channel gene were performed using direct DNA sequence analysis and restriction length polymorphism analysis. Results The proband in the Chinese family and her brother had previously been diagnosed with JLNS, and two other members were affected with RWS. The proband was also affected with atrial fibrillation. A single nucleotide substitution of C to T at nucleotide 965 of KCNQ1 was identified, and the mutation resulted in the substitution of a threonine residue at codon 322 by a methionine residue (T322M. The novel heterozygous T322M mutation was identified in two patients with RWS, one member with borderline QTc, and two normal family members. The two JLNS patients in the family carried the homozygous T322M mutation. The T322M mutation was not found in 200 Chinese normal controls. Conclusion Our results suggest that T322M is a novel mutation that caused RWS with high intrafamilial variability in the heterozygous carriers and typical JLNS in the homozygous carriers within this Chinese family. The T322M mutation is the first mutation identified for JLNS in the Chinese population.

  16. Effects of Cardiac Resynchronization Therapy on the Arrhythmic Substrate in a Patient with Long QT and Torsades de pointes

    Directory of Open Access Journals (Sweden)

    Masayasu Ikutomi, MD

    2011-01-01

    Full Text Available We describe a patient with torsades de pointes (TdP who was implanted with cardiac resynchronization therapy defibrillator (CRT-D. At the time of CRT-D implantation, left ventricular (LV epicardial pacing exacerbated TdPs and developed into electrical storm, which was triggered even by biventricular pacing. We needed to inactivate the LV lead for 2 weeks. At the next device check testing of LV pacing still induced TdPs, whe reas biventricular pacing did not. After starting the continuous biventricular pacing no ventricular arrhythmias happened, and furthermore the QT intervals prolonged by LV pacing were obviously shortened only after 2 weeks as ventricular systolic function recovered. Then even continuous LV alone pacing induced no TdP. These findings indicate novel electrical effects of cardiac resynchronization therapy.

  17. ICH E14-compatible holter bin method and its equivalence to individual heart rate correction in the assessment of drug-induced QT changes.

    Science.gov (United States)

    Malik, Marek; Hnatkova, Katerina; Kowalski, Donna; Keirns, James J; Van Gelderen, E Marcel

    2014-11-01

    The Holter bin method evaluates QT interval changes in the presence of heart rate changes without correcting the QT interval. However, the method does not allow time-matched comparisons, thus contradicting available guidance and good practice. We report a modification of the methods that allows time-matched comparisons without any heart rate correction. The modified Holter bin method (a) finds matching baseline heart rates for each QT reading on treatment and (b) calculates ΔQT values from the QT intervals on baseline and on treatment that match in heart rates. The difference between ΔQT values on active treatment and placebo provides the ΔΔQT value. The method was compared with the individual correction method in the data of the mirabegron thorough QT study in which supratherapeutic doses of this β3-adrenoceptor agonist led to substantial heart rate changes. The modified Holter bin method reproduced closely the results obtained with the individual heart rate correction. At all time points of the mirabegron study, the differences between the mean ΔΔQT values by the Holter bin method and the individual correction method were below 1 millisecond. Compared to the individual correction, the Holter bin method led to slight increases in the standard deviations of ΔΔQT values, but these were on average below 0.25 millisecond. The Holter bin methodology can be modified to make it compatible with the available guidance and with good practice of clinical investigations. The results obtained with the modified Holter bin method are practically the same as with individualized heart rate corrected QT intervals. The close correspondence between the 2 methods demonstrates that the present possibilities of comparing QT interval duration in the presence of experiment-induced heart rate differences are not influenced by methodological artifacts. © 2014 Wiley Periodicals, Inc.

  18. [Citalopram, escitalopram and prolonged QT: warning or alarm?].

    Science.gov (United States)

    Alvarez, Enric; Vieira, Sara; Garcia-Moll, Xavier

    2014-01-01

    The alerts issued by regulatory agencies on the potential cardiac toxicity of citalopram and escitalopram have caused alarm among clinicians. A review of the data concerning this topic shows that the alarm should be limited to patients with a history of syncope or poisoning. As a precautionary measure, an electrocardiogram should be performed on elderly patients.

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

    Science.gov (United States)

    Leong, I U S; Skinner, J R; Shelling, A N; Love, D R

    2010-07-01

    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.

  20. Ventricular dysfunction in a family with long QT syndrome type 3

    NARCIS (Netherlands)

    Hummel, Yoran M.; Wilde, Arthur A. M.; Voors, Adriaan A.; Bugatti, Silvia; Hillege, Hans L.; van den Berg, Maarten P.

    2013-01-01

    Long QT syndrome (LQTS) type 3 is characterized by prolonged ventricular repolarization due to persistent sodium inward current secondary to a mutation in SCN5a, the gene encoding for the -subunit of the sodium channel. We speculated that by disrupting calcium homeostasis the persistent inward sodiu

  1. Biophysical Properties of 9 KCNQ1 Mutations Associated with Long QT Syndrome (LQTS)

    Science.gov (United States)

    Yang, Tao; Chung, Seo-Kyung; Zhang, Wei; Mullins, Jonathan G.L.; McCulley, Caroline H.; Crawford, Jackie; MacCormick, Judith; Eddy, Carey-Anne; Shelling, Andrew N.; French, John K.; Yang, Ping; Skinner, Jonathan R.; Roden, Dan M.; Rees, Mark I.

    2009-01-01

    Background Inherited long QT syndrome (LQTS) is characterized by prolonged QT interval on the EKG, syncope and sudden death due to ventricular arrhythmia. Causative mutations occur mostly in cardiac potassium and sodium channel subunit genes. Confidence in mutation pathogenicity is usually reached through family genotype-phenotype tracking, control population studies, molecular modelling and phylogenetic alignments, however, biophysical testing offers a higher degree of validating evidence. Methods and Results By using in-vitro electrophysiological testing of transfected mutant and wild-type LQTS constructs into Chinese Hamster Ovary cells, we investigated the biophysical properties of 9 KCNQ1 missense mutations (A46T, T265I, F269S, A302V, G316E, F339S, R360G, H455Y, and S546L) identified in a New Zealand based LQTS screening programme. We demonstrate through electrophysiology and molecular modeling that seven of the missense mutations have profound pathological dominant negative loss-of-function properties confirming their likely disease-causing nature. This supports the use of these mutations in diagnostic family screening. Two mutations (A46T, T265I) show suggestive evidence of pathogenicity within the experimental limits of biophysical testing, indicating that these variants are disease-causing via delayed or fast activation kinetics. Further investigation of the A46T family has revealed an inconsistent co-segregation of the variant with the clinical phenotype. Conclusions Electrophysiological characterisation should be used to validate LQTS pathogenicity of novel missense channelopathies. When such results are inconclusive, great care should be taken with genetic counselling and screening of such families, and alternative disease causing mechanisms should be considered. PMID:19808498

  2. Evaluation of repolarization dynamics using the QT-RR regression line slope and intercept relationship during 24-h Holter ECG.

    Science.gov (United States)

    Fujiki, Akira; Yoshioka, Ryozo; Sakabe, Masao

    2015-03-01

    QT-RR linear regression consists of two parameters, slope and intercept, and the aim of this study was to evaluate repolarization dynamics using the QT-RR linear regression slope and intercept relationship during 24-h Holter ECG. This study included 466 healthy subjects (54.6 ± 14.6 years; 200 men and 266 women) and 17 patients with ventricular arrhythmias, consisted of 10 patients with idiopathic ventricular fibrillation (IVF) and 7 patients with torsades de pointes (TDP). QT and RR intervals were measured from ECG waves based on a 15-s averaged ECG during 24-h Holter recording using an automatic QT analyzing system. The QT interval dependence on the RR interval was analyzed using a linear regression line for each subject ([QT] = A[RR] + B; where A is the slope and B is the y-intercept). The slope of the QT-RR regression line in healthy subjects was significantly greater in women than in men (0.185 ± 0.036 vs. 0.161 ± 0.033, p Holter ECG may become a simple useful marker for abnormality of ventricular repolarization dynamics.

  3. Oxycodone is associated with dose-dependent QTc prolongation in patients and low-affinity inhibiting of hERG activity in vitro

    DEFF Research Database (Denmark)

    Fanoe, Søren; Jensen, Gorm Boje; Sjøgren, Per

    2008-01-01

    with the use of these drugs. WHAT THIS PAPER ADDS: This study is the first to show that oxycodone dose is associated with QT prolongation and in vitro blockade of hERG channels expressed in HEK293. Neither morphine nor tramadol doses are associated with the QT interval length. AIMS: During recent years some...... patients treated with methadone, oxycodone, morphine or tramadol were recruited in a cross-sectional study. The QTc was estimated from a 12-lead ECG. To examine hERG activity in the presence of oxycodone, electrophysiological testing was conducted using Xenopus laevis oocytes and HEK293 cells expressing h...... dose was associated with a 10 ms(1/2) (95% CI 2-19) longer QTc. Neither morphine nor tramadol dose was associated with the QTc. Electrophysiological testing revealed low-affinity inhibition of the potassium current through hERG channels expressed in HEK293 cells (IC(50) = 171 microM oxycodone...

  4. QT wave dispersion in patients with panic disorder

    Institute of Scientific and Technical Information of China (English)

    Murad Atmaca; Mustafa Yavuzkir; Filiz Izci; M. Gurkan Gurok; Sahin Adiyaman

    2012-01-01

    [Objective] QT dispersion (QTd),defined as the maximal inter-lead difference in QT intervals on 12 leads of the surface electrocardiogram (ECG),reflects the regional heterogeneity of ventricular repolarization and has been suggested as an important marker for risk of arrhythmia in addition to the QT interval.Some investigators proposed that it might be a predisposing factor for arrhythmic events and sudden death.Thus,we aimed to investigate whether QTd differs in patients with panic disorder from that in healthy controls.[Methods] In 40 panic disorder patients and 40 healthy controls,Qmax,Qmin,and QTd values were measured.In addition,the Hamilton depression rating scale and the panic agoraphobia scale were scored for both patients and healthy volunteers.[Results] Qmax and Qmin values in the panic disorder patients were significantly higher than those in healthy controls.The mean corrected QTd was significantly greater in the patients than in the controls.One-way analysis of covariance (ANCOVA,using left atrial size,age and heart rate as covariates) also corrected the significant difference.In addition,ANCOVA revealed a significant main effect for the diagnosis,indicating a significantly higher QTd for patients compared with controls.[Conclusion]QTd might be associated with panic disorder.Future studies in larger samples evaluating the effects of treatment are required.

  5. Relation of early changes of QT dispersion to changes in left ventricular systolic and diastolic function after a first acute myocardial infarction

    DEFF Research Database (Denmark)

    Møller, Jacob E; Husic, Mirza; Søndergaard, Eva

    2002-01-01

    OBJECTIVE: To describe the relation between changes of left ventricular systolic and diastolic function and changes of QT dispersion (difference in duration between longest and shortest QT interval) following acute myocardial infarction. DESIGN: QT dispersion was determined at admission, hospital...... normalized QT dispersion was associated with a significant decrease of ventricular volumes. After 1 year end-systolic (70 +/- 32 ml vs 49 +/- 16 ml, p = 0.006) and end-diastolic volumes (138 +/- 41 ml vs 105 +/- 22 ml, p = 0.001) were higher in Group B. In a multivariate model Group B was significantly...

  6. Prolonged interval between fusion and activation impairs embryonic development by inducing chromosome scattering and nuclear aneuploidy in pig somatic cell nuclear transfer.

    Science.gov (United States)

    You, Jinyoung; Song, Kilyoung; Lee, Eunsong

    2010-01-01

    The aim of the present study was to examine the effect of various intervals between electrofusion and activation (FA interval) on the nuclear remodelling and development of somatic cell nuclear transfer (SCNT) embryos in pigs. Reconstructed oocytes were activated at 0 (simultaneous fusion and activation; SFA), 1, 2 and 3 h (delayed activation) after electrofusion; these groups were designated as DA1, DA2 and DA3, respectively. When oocyte nuclear status was examined at 0.5, 1, 2 and 3 h after electrofusion, the incidence of chromosome scattering was increased (P or=3) pseudopronuclei (PPN) (0.0% of SFA; 5.3% of DA1; 21.7% of DA2; and 33.5% of DA3). The development of SCNT embryos to the blastocyst stage was decreased (P nuclear aneuploidy.

  7. Investigação de variantes gênicas de canais iônicos em pacientes com síndrome do QT longo Investigación de variantes génicas de canales iónicos en pacientes con síndrome del QT largo Investigation of ion channel gene variants in patients with long QT syndrome

    Directory of Open Access Journals (Sweden)

    Ernesto Curty

    2011-03-01

    their family members were sequenced and analyzed using Geneious ProTM software. RESULTS: Two families with clinical criteria for LQTS were investigated. The proband of Family A had QTC = 562 ms, Schwartz Score = 5.5. The genotyping identified the G1714A mutation in the KCNH2 gene. QTC = 521 ± 42 ms was observed in family members carrying the mutation against QTC = 391 ± 21 ms for non-carriers. The proband of Family B had QTc = 551 ms, Schwartz Score = 5.5. The genotyping identified the G1600T mutation, in the same gene. The analysis of family members revealed QTC = 497 ± 42 ms in mutation carriers, compared with QTC = 404 ± 29 ms in non-carriers. CONCLUSION: Two gene variants previously associated with LQTS were found in two families clinically diagnosed with LQTS. The prolongation of the QT interval was observed in all family members carrying the mutations. A strategy was developed to identify variants of genes KCNQ1, KCNH2 and SCN5A, making it possible to train technical staff for future application to diagnosis routine.

  8. Graphical representation of QT rate correction formulae: an aid facilitating the use of a given formula and providing a visual comparison of the impact of different formulae.

    Science.gov (United States)

    Rowlands, Derek J

    2012-01-01

    The QT interval on the electrocardiogram is an increasingly important measurement, especially in relation to drug action and interaction. The QT interval varies inversely as the heart rate and numerous rate correction formulae have been proposed. It is difficult to compare the effect of applying different formulae at different heart rates and for different measured QT intervals. A simple graphical display of the results from different formulae is proposed. This display is dependent on the concept of the absolute correction factor. This graphical presentation is useful (a) in comparing the effect of the application of different formulae and (b) in directly reading the correction produced by any individual formula.

  9. Molecular biology and cellular mechanisms of Brugada and long QT syndromes in infants and young children.

    Science.gov (United States)

    Antzelevitch, C

    2001-01-01

    Sudden cardiac death accounts for 19% of sudden deaths in children between 1 and 13 years of age and 30% of sudden deaths that occur between 14 and 21 years of age. The incidence of sudden cardiac death displays 2 peaks: one between 45 and 75 years of age, as a result of coronary artery disease, and the other between birth and 6 months of age, caused by sudden infant death syndrome. The role of cardiac arrhythmias in sudden infant death syndrome has long been a matter of debate and the role of cardiac arrhythmias in children in general is not well defined. Recent findings point to a contribution of primary electrical diseases of the heart including the Brugada and long QT syndromes to sudden death in infants and children. Mutations in SCN5A and HERG and KvLQT1 have been shown to be associated with life-threatening arrhythmias and long QT intervals in young infants. These mutations cause changes in sodium and potassium currents that amplify intrinsic electrical heterogeneities within the heart, thus providing a substrate as well as a trigger for the development of reentrant arrhythmias, including Torsade de Pointes (TdP), commonly associated with the long QT syndrome (LQTS). Mutations in SCN5A have also been shown to cause the sodium channel to turn off prematurely and thus to set the stage for the development of a rapid polymorphic ventricular tachycardia/ventricular fibrillation in patients with the Brugada Syndrome. In LQTS, ion channel mutations cause a preferential prolongation of the M cell action potential that contributes to the development of long QT intervals, wide-based or notched T waves, and a large transmural dispersion of repolarization, which provides the substrate for the development of TdP. An early afterdepolarization-induced triggered beat is thought to provide the extrasystole that precipitates TdP. In the Brugada syndrome, mutations in SCN5A reduce sodium current density, causing premature repolarization of the epicardial action potential due

  10. Sources of Variation in the QT Readings: What should you be Aware of?

    Directory of Open Access Journals (Sweden)

    Iana Simova

    2007-03-01

    Full Text Available The QT interval is measured manually or automatically. In comparison with manual methods, the automated ones offer advantages in terms of absolute repeatability of measurements, immunity from errors related to observer fatigue, lack of attention, as well as efficiency and cost effectiveness that permits either more extensive and rigorous testing for the same cost as manual methods, or more rapid testing at lower cost. But a question arises: 'Can the QT interval be measured by fully automated methods with accuracy acceptable for clinical evaluations?' We created a dataset of manually measured Q-onsets and T-ends for the PTB Diagnostic ECG Database. Further on we developed a fully automated method for QT measurements and forwarded it to PhysioNet/Computers in Cardiology Challenge, 2006. The manually measured dataset was then used as a 'gold standard' for assessment of the accuracy of the automated method. The current lecture notes summarize all our up to date publications on the QT measurements topic. Sources of variation in the QT readings are for the first time discussed by the authors.

  11. J-shaped association between QTc interval duration and the risk of atrial fibrillation

    DEFF Research Database (Denmark)

    Nielsen, Jonas Bille; Graff, Claus; Pietersen, Adrian;

    2013-01-01

    The aim of this study was to investigate whether the heart rate-corrected QT (QTc) interval on the electrocardiogram (ECG) is associated with the onset of atrial fibrillation (AF).......The aim of this study was to investigate whether the heart rate-corrected QT (QTc) interval on the electrocardiogram (ECG) is associated with the onset of atrial fibrillation (AF)....

  12. Corticosteroid treatment normalizes QTc prolongation and improves heart block in an elderly patient with anti-Ro-positive systemic lupus erythematosus.

    Science.gov (United States)

    Saribayev, Maksat; Tufan, Fatih; Oz, Fahrettin; Erer, Burak; Ozpolat, Tahsin; Ozturk, Gulistan Bahat; Akin, Sibel; Saka, Bulent; Erten, Nilgun; Tascioglu, Cemil; Karan, Akif

    2014-06-01

    Systemic lupus erythematosus (SLE) is a multisystemic disease which potentially involves various organs including the skin, joints, kidneys, liver, hematopoetic system, and serous membranes. It is rarely seen in elderly males. The most common cardiovascular involvement type is pericarditis. Anti-Ro antibodies may be associated with neonatal lupus which causes heart blocks. Recent literature indicates that anti-Ro antibodies may be associated with various rhythm and conduction disturbances in the adulthood. The most common finding associated with anti-Ro antibodies is prolonged corrected QT (QTc) interval. Herein, we present an elderly male patient with anti-Ro-positive SLE associated with prolonged QTc interval and AV blocks that significantly improved after corticosteroid treatment.

  13. Concentration-Response Modeling of ECG Data From Early-Phase Clinical Studies as an Alternative Clinical and Regulatory Approach to Assessing QT Risk - Experience From the Development Program of Lemborexant.

    Science.gov (United States)

    Murphy, Patricia J; Yasuda, Sanae; Nakai, Kenya; Yoshinaga, Takashi; Hall, Nancy; Zhou, Meijian; Aluri, Jagadeesh; Rege, Bhaskar; Moline, Margaret; Ferry, Jim; Darpo, Borje

    2017-01-01

    Lemborexant is a novel dual orexin receptor antagonist being developed to treat insomnia. Its potential to cause QT prolongation was evaluated using plasma concentration-response (CR) modeling applied to data from 2 multiple ascending-dose (MAD) studies. In the primary MAD study, placebo or lemborexant (2.5 to 75 mg) was administered for 14 consecutive nights. In another MAD study designed to "bridge" pharmacokinetic and safety data between Japanese and non-Japanese subjects (J-MAD), placebo or lemborexant (2.5, 10, or 25 mg) was administered for 14 consecutive nights. QT intervals were estimated using a high-precision measurement technique and evaluated using a linear mixed-effects CR model, for each study separately and for the pooled data set. When each study was analyzed separately, the slopes of the CR relationship were shallow and not statistically significant. In the pooled analysis, the slope of the CR relationship was -0.00002 milliseconds per ng/mL (90%CI, -0.01019 to 0.01014 milliseconds). The highest observed Cmax was 400 ng/mL, representing a margin 8-fold above exposures expected for the highest planned clinical dose. The model-predicted QTc effect at 400 ng/mL was 1.1 milliseconds (90%CI, -3.49 to 5.78 milliseconds). In neither the J-MAD study nor the pooled analysis was an effect of race identified. CR modeling of data from early-phase clinical studies, including plasma levels far exceeding those anticipated clinically, indicated that a QT effect >10 milliseconds could be excluded. Regulatory agreement with this methodology demonstrates the effectiveness of a CR modeling approach as an alternative to thorough QT studies. © 2016, The American College of Clinical Pharmacology.

  14. A novel deletion-frameshift mutation in the S1 region of HERG gene in a Chinese family with long QT syndrome

    Institute of Scientific and Technical Information of China (English)

    GAO Ying; ZHANG Ping; LI Xue-bin; WU Cun-cao; GUO Ji-hong

    2013-01-01

    Background The congenital Long QT syndrome (LQTS) is a hereditary cardiac channelopathy that is characterized by a prolonged QT interval,syncope,ventricular arrhythmias,and sudden death.The chromosome 7-linked type 2 congenital LQTS (LQT2) is caused by gene mutations in the human ether-a-go-go-related gene (HERG).Methods A Chinese family diagnosed with LQTS were screened for KCNQ1,HERG and SCN5A,using polymerase chain reaction (PCR),direct sequencing,and clong sequencing.We also investigated the mRNA expression of the HERG gene.Results We identified a novel i414fs+98X mutation in the HERG gene.The deletion mutation of 14-bp in the first transmembrane segment (S1) introduced premature termination codons (PTCs) at the end of exon 6.This mutation would result in a serious phenotype if the truncated proteins co-assembled with normal subunit to form the defective channels.But only the proband was symptomatic.Conclusions We found that the mRNA level of the HERG gene was significantly lower in 1414fs+98X carriers than in noncarriers.We found a novel 1414fs+98X mutation.The mRNA level supports that NMD mechanism might regulate the novel mutation.

  15. The Calcium/Calmodulin/Kinase System and Arrhythmogenic Afterdepolarizations in Bradycardia-Related Acquired Long-QT Syndrome

    NARCIS (Netherlands)

    Qi, XiaoYan; Yeh, Yung-Hsin; Chartier, Denis; Xiao, Ling; Tsuji, Yukiomi; Brundel, Bianca J. J. M.; Kodama, Itsuo; Nattel, Stanley

    2009-01-01

    Background-Sustained bradycardia is associated with long-QT syndrome in human beings and causes spontaneous torsades de pointes in rabbits with chronic atrioventricular block (CAVB), at least partly by downregulating delayed-rectifier K(+)-current to cause action potential (AP) prolongation. We addr

  16. Use of mutant-specific ion channel characteristics for risk stratification of long QT syndrome patients

    DEFF Research Database (Denmark)

    Jons, Christian; O-Uchi, Jin; Moss, Arthur J;

    2011-01-01

    Inherited long QT syndrome (LQTS) is caused by mutations in ion channels that delay cardiac repolarization, increasing the risk of sudden death from ventricular arrhythmias. Currently, the risk of sudden death in individuals with LQTS is estimated from clinical parameters such as age, gender...... predictor for cardiac events (syncope, aborted cardiac arrest, and sudden death) (hazard ratio = 2.10), whereas the length of the QT interval itself was not. Our results indicate that genotype and biophysical phenotype analysis may be useful for risk stratification of LQT1 patients and suggest that slow...

  17. The impact of recent advances in genetics in understanding disease mechanisms underlying the long QT syndromes.

    Science.gov (United States)

    Harmer, Stephen C; Tinker, Andrew

    2016-07-01

    Long QT syndrome refers to a characteristic abnormality of the electrocardiogram and it is associated with a form of ventricular tachycardia known as torsade-de-pointes and sudden arrhythmic death. It can occur as part of a hereditary syndrome or can be acquired usually because of drug administration. Here we review recent genetic, molecular and cellular discoveries and outline how they have furthered our understanding of this disease. Specifically we focus on compound mutations, genome wide association studies of QT interval, modifier genes and the therapeutic implications of this recent work.

  18. Semiconductor Whole Exome Sequencing for the Identification of Genetic Variants in Colombian Patients Clinically Diagnosed with Long QT Syndrome.

    Science.gov (United States)

    Burgos, Mariana; Arenas, Alvaro; Cabrera, Rodrigo

    2016-08-01

    Inherited long QT syndrome (LQTS) is a cardiac channelopathy characterized by a prolongation of QT interval and the risk of syncope, cardiac arrest, and sudden cardiac death. Genetic diagnosis of LQTS is critical in medical practice as results can guide adequate management of patients and distinguish phenocopies such as catecholaminergic polymorphic ventricular tachycardia (CPVT). However, extensive screening of large genomic regions is required in order to reliably identify genetic causes. Semiconductor whole exome sequencing (WES) is a promising approach for the identification of variants in the coding regions of most human genes. DNA samples from 21 Colombian patients clinically diagnosed with LQTS were enriched for coding regions using multiplex polymerase chain reaction (PCR) and subjected to WES using a semiconductor sequencer. Semiconductor WES showed mean coverage of 93.6 % for all coding regions relevant to LQTS at >10× depth with high intra- and inter-assay depth heterogeneity. Fifteen variants were detected in 12 patients in genes associated with LQTS. Three variants were identified in three patients in genes associated with CPVT. Co-segregation analysis was performed when possible. All variants were analyzed with two pathogenicity prediction algorithms. The overall prevalence of LQTS and CPVT variants in our cohort was 71.4 %. All LQTS variants previously identified through commercial genetic testing were identified. Standardized WES assays can be easily implemented, often at a lower cost than sequencing panels. Our results show that WES can identify LQTS-causing mutations and permits differential diagnosis of related conditions in a real-world clinical setting. However, high heterogeneity in sequencing depth and low coverage in the most relevant genes is expected to be associated with reduced analytical sensitivity.

  19. Heterogeneous Phenotype of Long QT Syndrome Caused by the KCNH2-H562R Mutation: Importance of Familial Genetic Testing.

    Science.gov (United States)

    Muñoz-Esparza, Carmen; García-Molina, Esperanza; Salar-Alcaraz, Mariela; Peñafiel-Verdú, Pablo; Sánchez-Muñoz, Juan J; Martínez Sánchez, Juan; Cabañas-Perianes, Valentín; Valdés Chávarri, Mariano; García Alberola, Arcadio; Gimeno-Blanes, Juan R

    2015-10-01

    Long QT syndrome is an inherited ion channelopathy that leads to syncope and sudden death. Because of the heterogeneous phenotype of this disease, genetic testing is fundamental to detect individuals with concealed long QT syndrome. In this study, we determined the features of a family with 13 carriers of the KCNH2-H562R missense mutation, which affects the pore region of the HERG channel. We identified the KCNH2-H562R mutation in a 65-year-old man with a prolonged QTc interval who had experienced an episode of torsade de pointes. Subsequently, a total of 13 mutation carriers were identified in the family. Carriers (age 48 [26] years; 46% males) underwent clinical evaluation, electrocardiography and echocardiography. The mean (standard deviation) QTc in carriers was 493 (42) ms (3 [23%] showed normal QTc); 6 (46%) had symptoms (4, syncope; 1, sudden death; 1, aborted sudden death [proband]). While under treatment with beta-blockers, 11 of 12 carriers (92%) remained asymptomatic at 5 years of follow-up (1 patient required left cardiac sympathectomy). The QTc shortening with beta-blockers was 50 (37) ms. There was 1 sudden death in a patient who refused treatment. Family study is essential in the interpretation of a genetic testing result. This article describes the heterogeneous and variable phenotype of a large family with the KCNH2-H562R mutation and highlights the role of genetic study for the appropriate identification of at-risk individuals who would benefit from treatment. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  20. New echocardiographic insights in short QT syndrome: More than a channelopathy?

    Science.gov (United States)

    Frea, Simone; Giustetto, Carla; Capriolo, Michele; Scrocco, Chiara; Fornengo, Cristina; Benedetto, Sara; Bianchi, Francesca; Pidello, Stefano; Morello, Mara; Gaita, Fiorenzo

    2015-10-01

    Short QT syndrome (SQTS) is a congenital ion channel disease characterized by an increased risk of sudden cardiac death. Little is known about the possibility that accelerated repolarization alters mechanical function in SQTS. The study investigated the presence of left ventricular dysfunction and mechanical dispersion, assessed by tissue Doppler imaging (TDI) and speckle tracking echocardiography (STE), and their correlation with QT interval duration and genetics. Fifteen SQTS patients (7 with HERG and 3 with KCNQ1 mutation) were studied. Electrocardiographic and echocardiographic parameters were compared with age- and sex-matched healthy controls. When compared to the control group, SQTS patients showed reduced left ventricular contraction (global longitudinal strain: -16.0% ± 3.4% vs -22.6% ± 1.7%, P < .001; myocardial performance index 0.59 ± 0.17 vs 0.34 ± 0.08, P < .001) and a higher incidence of ejection fraction <55% (odds ratio 11, 95% confidence interval 1.045-374, P = .04). Mechanical dispersion assessed by TDI (P < .01) and STE (P < .001) was higher in the SQTS group than in controls; each parameter showed a significant inverse correlation with QT interval but not with QT dispersion. This study showed that in SQTS systolic function may also be affected. SQTS patients presented a significant dispersion of myocardial contraction. TDI and STE could become part of the evaluation of this rare disease. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  1. Acute resistance exercise reduces heart rate complexity and increases QTc interval.

    Science.gov (United States)

    Heffernan, K S; Sosnoff, J J; Jae, S Y; Gates, G J; Fernhall, B

    2008-04-01

    Acute resistance exercise (RE) has been shown to reduce cardiac vagal control. Whether this would in turn affect QTc interval (an index of ventricular depolarization/repolarization) or heart rate complexity is not known. Heart rate variability (HRV), heart rate complexity (SampEn), and QT interval (rate corrected using Bazett, Fridericia, Hodges, and Framingham) were measured before and 5 min after an acute RE bout in twelve healthy young men. Normalized high frequency power of HRV (an index of cardiac parasympathetic modulation; HF (nu)), and SampEn were reduced following RE (p heart rate complexity and increased QTc length. Thus, during recovery from acute RE, there is prolongation of depolarization and repolarization of the ventricles concomitant with reduced cardiac irregularity, and this may be related to a reduction in cardiac vagal control.

  2. Effects of bilastine on T-wave morphology and the QTc interval

    DEFF Research Database (Denmark)

    Graff, Claus; Struijk, Johannes; Kanters, Jørgen K.;

    2012-01-01

    The International Conference of Harmonisation (ICH) E14 guideline for thorough QT studies requires assessing the propensity of new non-antiarrhythmic drugs to affect cardiac repolarization. The present study investigates whether a composite ECG measure of T-wave morphology (Morphology Combination...... Score [MCS]) can be used together with the heart rate corrected QT interval (QTc) in a fully ICH E14-compliant thorough QT study to exclude clinically relevant repolarization effects of bilastine, a novel antihistamine....

  3. Prediction and modeling of effects on the QTc interval for clinical safety margin assessment, based on single-ascending-dose study data with AZD3839.

    Science.gov (United States)

    Sparve, Erik; Quartino, Angelica L; Lüttgen, Maria; Tunblad, Karin; Gårdlund, Anna Teiling; Fälting, Johanna; Alexander, Robert; Kågström, Jens; Sjödin, Linnea; Bulgak, Alexander; Al-Saffar, Ahmad; Bridgland-Taylor, Matthew; Pollard, Chris; Swedberg, Michael D B; Vik, Torbjörn; Paulsson, Björn

    2014-08-01

    Corrected QT interval (QTc) prolongation in humans is usually predictable based on results from preclinical findings. This study confirms the signal from preclinical cardiac repolarization models (human ether-a-go-go-related gene, guinea pig monophasic action potential, and dog telemetry) on the clinical effects on the QTc interval. A thorough QT/QTc study is generally required for bioavailable pharmaceutical compounds to determine whether or not a drug shows a QTc effect above a threshold of regulatory interest. However, as demonstrated in this AZD3839 [(S)-1-(2-(difluoromethyl)pyridin-4-yl)-4-fluoro-1-(3-(pyrimidin-5-yl)phenyl)-1H-isoindol-3-amine hemifumarate] single-ascending-dose (SAD) study, high-resolution digital electrocardiogram data, in combination with adequate efficacy biomarker and pharmacokinetic data and nonlinear mixed effects modeling, can provide the basis to safely explore the margins to allow for robust modeling of clinical effect versus the electrophysiological risk marker. We also conclude that a carefully conducted SAD study may provide reliable data for effective early strategic decision making ahead of the thorough QT/QTc study.

  4. Efeitos de esmolol, lidocaína e fentanil nos intervalos dispersão da onda P, QT, QTc e respostas hemodinâmicas à intubação endotraqueal durante indução com propofol: um estudo comparativo Efectos del esmolol, de la lidocaína y del fentanilo en los intervalos dispersión de la onda, QT, QTc y respuestas hemodinámicas a la intubación endotraqueal durante inducción con propofol: un estudio comparativo Effects of esmolol, lidocaine and fentanyl on P wave dispersion, QT, QTc intervals and hemodynamic responses to endotracheal intubation during propofol induction: a comparative study

    Directory of Open Access Journals (Sweden)

    Volkan Hancı

    2013-06-01

    control electrocardiograms (ECGs done before anesthesia induction. The patients were randomised into four equal groups. The control group (Group C received saline 5 mL, the esmolol group (Group E received esmolol 0.5 mg.kg-1, the fentanyl group (Group F received fentanyl 2 µg.kg-1 and the lidocaine group (Group L received lidocaine 1.5 mg.kg-1 before anesthesia induction. Anesthesia was induced with intravenous propofol. ECGs for all patients were performed during the 1st and 3rd minutes of induction, 3 minutes after administration of muscle relaxant, and at 5 minutes and 10 minutes after intubation. Pwd and QT intervals were measured on all ECGs. QTc intervals were determined using the Bazett formula. Heart rate (HR and mean arterial pressure (MAP were recorded before and after induction of anesthesia, immediately after intubation, and 1, 3, 5, 7 and 10 minutes after intubation. RESULTS: Compared with control, HR significantly increased in Group C, Group L and Group F after intubation. However, in Group E, there was no significant difference in HR values between control and after intubation. Compared with control, MAP significantly increased in Group C and Group L after the intubation. However, in Group E and Group F, there was no significant difference in MAP values between control and after the intubation. Compared with control, Pwd significantly increased in Group C after intubation. In Group L, Group F and Group E, there was no significant difference in Pwd values between control and after the intubation. Compared with control, QTc duration significantly increased in Group C and L after the intubation. In Group F and Group E, there was no significant difference in QTc durations between control and after the intubation. CONCLUSION: We concluded that administration of esmolol before intubation prevents tachycardia and an increase in MAP, Pwd and QTc duration caused by laryngoscopy and tracheal intubation.

  5. Effects of phenobarbital and levetiracetam on PR and QTc intervals in patients with post-stroke seizure.

    Science.gov (United States)

    Siniscalchi, Antonio; Scaglione, Francesco; Sanzaro, Enzo; Iemolo, Francesco; Albertini, Giorgio; Quirino, Gianluca; Manes, Maria Teresa; Gratteri, Santo; Mercuri, Nicola Biagio; De Sarro, Giovambattista; Gallelli, Luca

    2014-12-01

    Sudden unexplained/unexpected death (SUDEP) is related to high mortality in patients with epilepsy. The prolongation of QT interval, involved in cardiac arrhythmia-related SUDEP, may be precipitated by antiepileptic drugs (AEDs). In this study, we evaluated the effects of phenobarbital and levetiracetam on PR-QTc intervals in patients with post-stroke seizures. We performed an open-label, parallel group, prospective, multicenter study between June 2009 and December 2013 in patients older than 18 years of age with a clinical diagnosis of post-stroke seizure and treated with phenobarbital or levetiracetam. In order to exclude a role of cerebral post-stroke injury on modulation of PR and QTc intervals, patients with cerebral post-stroke injury and without seizures were also enrolled as controls. Interictal electrocardiography analysis revealed no significant difference in PR interval between patients treated with an AED (n = 49) and control patients (n = 50) (181.25 ± 12.05 vs. 182.4 ± 10.3 ms; p > 0.05). In contrast, a significantly longer QTc interval was recorded in patients treated with an AED compared with control patients (441.2 ± 56.6 vs. 396.8 ± 49.3 ms; p phenobarbital showed a significantly longer QTc interval than patients treated with levetiracetam (460.0 ± 57.2 vs. 421.5 ± 50.1 ms; p phenobarbital prolonged QTc interval more so than levetiracetam.

  6. Evaluation of QT and P Wave Dispersion and Mean Platelet Volume among Inflammatory Bowel Disease Patients

    Directory of Open Access Journals (Sweden)

    Yuksel DOGAN, Aliye SOYLU, Gulay A. EREN, Sule POTUROGLU, Can DOLAPCIOGLU, Kenan SONMEZ, Habibe DUMAN, Isa SEVINDIR

    2011-01-01

    Full Text Available Background: In inflammatory bowel disease (IBD number of thromboembolic events are increased due to hypercoagulupathy and platelet activation. Increases in mean platelet volume (MPV can lead to platelet activation, this leads to thromboembolic events and can cause acute coronary syndromes. In IBD patients, QT-dispersion and P-wave dispersion are predictors of ventricular arrhythmias and atrial fibrilation; MPV is accepted as a risk factor for acute coronary syndromes, we aimed at evaluating the correlations of these with the duration of disease, its localization and activity.Methods: The study group consisted of 69 IBD (Ulcerative colitis n: 54, Crohn's Disease n:15 patients and the control group included 38 healthy individuals. Disease activity was evaluated both endoscopically and clinically. Patients with existing cardiac conditions, those using QT prolonging medications and having systemic diseases, anemia and electrolyte imbalances were excluded from the study. QT-dispersion, P-wave dispersion and MPV values of both groups were compared with disease activity, its localization, duration of disease and the antibiotics used.Results: The P-wave dispersion values of the study group were significantly higher than those of the control group. Duration of the disease was not associated with QT-dispersion, and MPV levels. QT-dispersion, P-wave dispersion, MPV and platelet count levels were similar between the active and in mild ulcerative colitis patients. QT-dispersion levels were similar between IBD patients and the control group. No difference was observed between P-wave dispersion, QT-dispersion and MPV values; with regards to disease duration, disease activity, and localization in the study group (p>0.05.Conclusions: P-wave dispersion which is accepted as a risk factor for the development of atrial fibirilation was found to be high in our IBD patients. This demonstrates us that the risk of developing atrial fibrillation may be high in patients

  7. QT correction formulas and laboratory analysis on patients with metabolic syndrome and diabetes

    Science.gov (United States)

    Wong, Sara; Rivera, Pedro; Rodríguez, María. G.; Severeyn, Érika; Altuve, Miguel

    2013-11-01

    This article presents a study of ventricular repolarization in diabetic and metabolic syndrome subjects. The corrected QT interval (QTc) was estimated using four correction formulas commonly employed in the literature: Bazett, Fridericia, Framingham and Hodges. After extracting the Q, R and T waves from the electrocardiogram of 52 subjects (19 diabetic, 15 with metabolic syndrome and 18 control), using a wavelet-based approach, the RR interval and QT interval were determined. Then, QTc interval was computed using the formulas previously mentioned. Additionally, laboratory test (fasting glucose, cholesterol, triglycerides) were also evaluated. Results show that metabolic syndrome subjects have normal QTc. However, a longer QTc in this population may be a sign of future complication. The corrected QT interval by Fridericia's formula seems to be the most appropriated for metabolic syndrome subjects (low correlation coefficient between RR and QTc). Significant differences were obtained in the blood glucose and triglyceride levels, principally due to the abnormal sugar metabolization of metabolic syndrome and diabetic subjects. Further studies are focused on the acquisition of a larger database of metabolic syndrome and diabetics subjects and the repetition of this study using other populations, like high performance athletes.

  8. Hysteresis of electrocardiographic depolarization-repolarization intervals during dynamic physical exercise and subsequent recovery.

    Science.gov (United States)

    Lewis, M J; Short, A L

    2006-02-01

    The post-exercise electrocardiographic QT interval is shortened relative to that at similar heart rates during exercise or pre-exercise rest. This lag in QT adaptation to the recovering heart rate is described as "hysteresis". No previous studies have quantified the influence of ECG electrode placement on hysteresis following physical exercise. Six males and six females of similar age, mass and aerobic fitness undertook progressive sub-maximal bicycle exercise. A three-channel ECG was recorded continuously during pre-exercise, exercise and recovery. Beat-to-beat NN (cardiac interval) and QT(a) interval (Q wave onset to T wave apex) data were measured for each sinus heart beat. QT(a)-NN hysteresis was calculated as the difference in QT(a) magnitude at identical heart rates during the rest/exercise and post-exercise recovery periods. There were some significant (p ECG electrode placement in future investigations.

  9. Is there a relationship between the blood cholinesterase and QTc interval in the patients with acute organophosphate poisoning?

    Science.gov (United States)

    Baydin, A; Aygun, D; Yazici, M; Karatas, A; Deniz, T; Yardan, T

    2007-06-01

    Organophosphates cause poisoning as a result of the excessive accumulation of acetylcholine at the cholinergic synapses due to inhibition of acetylcholinesterase (ChE). In the literature, it has been reported that there have been electrocardiographic abnormalities, including QT-interval prolongation in most patients with acute organophosphate poisoning (OPP), and a relation between blood ChE level and clinical severity in acute OPP. The aim of this study is to assess the relationship between blood ChE level and QTc interval in the patients with acute OPP. This retrospective study consists of 20 patients admitted to the emergency intensive care unit. A total of 93 QTc interval and blood ChE measures obtained on the same day from 20 cases were compared for their correlation. There were prolonged QTc intervals in 35.4% of the ECGs. There was a negative correlation between QTc interval and blood ChE measures. In following up the patients with acute OPP, QTc interval may be useful when blood ChE levels are low and may provide complementary information concerning the severity of poisoning. However, further prospective studies, supporting the present results, are needed.

  10. Design Scheme of Remote Monitoring System Based on Qt

    Directory of Open Access Journals (Sweden)

    Xu Dawei

    2015-01-01

    Full Text Available This paper introduces a design scheme of remote monitoring system based on Qt, the scheme of remote monitoring system based on S3C2410 and Qt, with the aid of cross platform development tools Qt and powerful ARM platform design and implementation. The development of remote video surveillance system based on embedded terminal has practical significance and value.

  11. Phase-contrast magnet resonance imaging reveals regional, transmural, and base-to-apex dispersion of mechanical dysfunction in patients with long QT syndrome.

    Science.gov (United States)

    Brado, Johannes; Dechant, Markus J; Menza, Marius; Komancsek, Adriana; Lang, Corinna N; Bugger, Heiko; Foell, Daniela; Jung, Bernd A; Stiller, Brigitte; Bode, Christoph; Odening, Katja E

    2017-09-01

    Regional dispersion of prolonged repolarization is a hallmark of long QT syndrome (LQTS). We have also revealed regional heterogeneities in mechanical dysfunction in transgenic rabbit models of LQTS. In this clinical pilot study, we investigated whether patients with LQTS exhibit dispersion of mechanical/diastolic dysfunction. Nine pediatric patients with genotyped LQTS (12.2 ± 3.3 years) and 9 age- and sex-matched healthy controls (10.6 ± 1.5 years) were subjected to phase-contrast magnetic resonance imaging to analyze radial (Vr) and longitudinal (Vz) myocardial velocities during systole and diastole in the left ventricle (LV) base, mid, and apex. Twelve-lead electrocardiograms were recorded to assess the heart rate-corrected QT (QTc) interval. The QTc interval was longer in patients with LQTS than in controls (469.1 ± 39.4 ms vs 417.8 ± 24.4 ms; P dispersion of contraction duration was increased in the LV apex (TTPVz_max-min: 38.9 ± 25.5 ms vs 20.2 ± 14.7 ms; P = .07; TTPVz-Vr: -21.7 ± 14.5 ms vs -8.7 ± 11.3 ms; P dispersion is increased in LQTS with an increased regional and transmural dispersion of contraction duration and altered apicobasal longitudinal relaxation sequence. LQTS is an electromechanical disorder, and phase-contrast magnetic resonance imaging Heterogeneity in mechanical dysfunction enables a detailed assessment of mechanical consequences of LQTS. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  12. Effects of Single Dose Energy Drink on QT and P-Wave Dispersion

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    Huseyin Arinc

    2013-12-01

    Full Text Available INTRODUCTION: Aim of this study is to evaluate the cardiac electrophysiological effects of energy drink (Red Bull on QT and P duration and dispersion on surface electrocardiogram. METHODS: Twenty healthy volunteers older than 17 years of age were included the study. Subjects with a cardiac rhythm except sinus rhythm, history of atrial or ventricular arrhythmia, family history of premature sudden cardiac death, palpitations, T-wave abnormalities, QTc interval greater than 440 milliseconds, or those P-waves and QT intervals unavailable in at least eight ECG leads were excluded. Subjects having insomnia, lactose intolerance, caffeine allergy, recurrent headaches, depression, any psychiatric condition, and history of alcohol or drug abuse, pregnant or lactating women were also excluded from participation. 12 lead ECG was obtained before and after consumption of 250 cc enegry drink. QT and P-wave dispersion was calculated. RESULTS: No significant difference have occurred in heart rate (79 ± 14 vs.81 ±13, p=0.68, systolic pressure (114 ± 14 vs.118 ± 16,p=0.38, diastolic blood pressure (74 ± 12 vs.76 ± 14, p=0.64, QT dispersion (58 ± 12 vs. 57 ± 22, p= 0.785 and P-wave dispersion (37 ± 7 vs. 36 ± 13, p= 0.755 between before and 2 hours after consumption of energy drink. DISCUSSION AND CONCLUSION: Consumption of single dose energy drink doesn't affect QT dispersion and P-wave dispersion, heart rate and blood pressure in healthy adults.

  13. Kort QT-syndrom som arvelig sygdom

    DEFF Research Database (Denmark)

    Møller, Daniel Vega; Hedley, Paula L; Olesen, Morten;

    2011-01-01

    Inherited ion-channel disorders can lead to life-threatening cardiac arrhythmias. A recent, rare entity has been discovered and termed short QT syndrome due to its electrocardiac features in conjunction with atrial and ventricular tachyarrhythmias as well as syncope and sudden cardiac death...

  14. Het lange-QT-tijdsyndroom bij kinderen

    NARCIS (Netherlands)

    Ten Harkel, A.D.J.; Lubbers, L.J.; Hoorntje, Th.; Blom, N.A.; Van Langen, I.M.; Sreeram, N.; Wilde, A.A.M.

    2002-01-01

    We examined 29 pediatric patients with long-Qt-syndrome in three academic hospitals. The mean age was 10 years (3-17). Of these patients 22 used betablocker therapy, in three combined with pacemaker. Genotyping has been performed in 22 children. LQTSI (mutation in the KCNQ1 gene) was found in twelve

  15. Síndrome del QT largo

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    Michel Cabrera Ortega

    2011-06-01

    Full Text Available El síndrome del QT largo congénito de tipo Romano-Ward es una canalopatía arritmogénica poco frecuente, caracterizada por una grave alteración en la repolarización ventricular y traducida en el electrocardiograma por un alargamiento del intervalo QTc. Se documenta el caso de una paciente con síndrome del QT largo congénito de tipo 1, asintomática, con antecedentes familiares de muerte súbita y síndrome del QT largo, a quien se le realizó estudio ecocardiográfico, prueba ergométrica, detección de potenciales tardíos y dispersión del QT como complementos diagnósticos y estratificadores de riesgo. Se prescribió tratamiento farmacológico y semanas después se valoró su efectividad.

  16. Influence of antenatal physical exercise on heart rate variability and QT variability.

    Science.gov (United States)

    Carpenter, R E; Emery, S J; Uzun, O; Rassi, D; Lewis, M J

    2017-01-01

    We sought to characterise the influence of an antenatal exercise programme on ECG-derived cardiac variables. Fifity-one healthy pregnant women were recruited and randomly assigned (2 × 2×2 design) to an exercise group or a control group. Exercising groups attended weekly classes from the 20th week of pregnancy onwards. Cardiovascular assessments (heart rate variabiliy (HRV), QT, and the QT variability index (QTVI)) were performed at 12-16, 26-28, 34-36 weeks and 12 weeks following birth, during supine rest and exercise conditions. Advancing gestation was associated with an increased maternal heart rate (p = 0.001), shorter QT interval (p = 0.003), diminished HRV (p = 0.002) and increased QTVI (p = 0.002). Each of these changes was reversed within 12 weeks postpartum (p Exercise group displayed exaggerated changes for all variables (except QT) but only during supine rest in the third trimester (p exercise programme undertaken between mid and late pregnancy exaggerated these changes during rest in the third trimester of pregnancy.

  17. Update on the Diagnosis and Management of Familial Long QT Syndrome.

    Science.gov (United States)

    Waddell-Smith, Kathryn E; Skinner, Jonathan R

    2016-08-01

    This update was reviewed by the CSANZ Continuing Education and Recertification Committee and ratified by the CSANZ board in August 2015. Since the CSANZ 2011 guidelines, adjunctive clinical tests have proven useful in the diagnosis of LQTS and are discussed in this update. Understanding of the diagnostic and risk stratifying role of LQTS genetics is also discussed. At least 14 LQTS genes are now thought to be responsible for the disease. High-risk individuals may have multiple mutations, large gene rearrangements, C-loop mutations in KCNQ1, transmembrane mutations in KCNH2, or have certain gene modifiers present, particularly NOS1AP polymorphisms. In regards to treatment, nadolol is preferred, particularly for long QT type 2, and short acting metoprolol should not be used. Thoracoscopic left cardiac sympathectomy is valuable in those who cannot adhere to beta blocker therapy, particularly in long QT type 1. Indications for ICD therapies have been refined; and a primary indication for ICD in post-pubertal females with long QT type 2 and a very long QT interval is emerging.

  18. Long QT syndrome-associated mutations in the S4-S5 linker of KvLQT1 potassium channels modify gating and interaction with minK subunits.

    Science.gov (United States)

    Franqueza, L; Lin, M; Shen, J; Splawski, I; Keating, M T; Sanguinetti, M C

    1999-07-23

    Long QT syndrome is an inherited disorder of cardiac repolarization caused by mutations in cardiac ion channel genes, including KVLQT1. In this study, the functional consequences of three long QT-associated missense mutations in KvLQT1 (R243C, W248R, E261K) were characterized using the Xenopus oocyte heterologous expression system and two-microelectrode voltage clamp techniques. These mutations are located in or near the intracellular linker between the S4 and S5 transmembrane domains, a region implicated in activation gating of potassium channels. The E261K mutation caused loss of function and did not interact with wild-type KvLQT1 subunits. R243C or W248R KvLQT1 subunits formed functional channels, but compared with wild-type KvLQT1 current, the rate of activation was slower, and the voltage dependence of activation and inactivation was shifted to more positive potentials. Co expression of minK and KvLQT1 channel subunits induces a slow delayed rectifier K(+) current, I(Ks), characterized by slow activation and a markedly increased magnitude compared with current induced by KvLQT1 subunits alone. Coexpression of minK with R243C or W248R KvLQT1 subunits suppressed current, suggesting that coassembly of mutant subunits with minK prevented normal channel gating. The decrease in I(Ks) caused by loss of function or altered gating properties explains the prolonged QT interval and increased risk of arrhythmia and sudden death associated with these mutations in KVLQT1.

  19. Anti-addiction Drug Ibogaine Prolongs the Action Potential in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

    Science.gov (United States)

    Rubi, Lena; Eckert, Daniel; Boehm, Stefan; Hilber, Karlheinz; Koenig, Xaver

    2017-04-01

    Ibogaine is a plant alkaloid used as anti-addiction drug in dozens of alternative medicine clinics worldwide. Recently, alarming reports of life-threatening cardiac arrhythmias and cases of sudden death associated with the ingestion of ibogaine have accumulated. Using whole-cell patch clamp recordings, we assessed the effects of ibogaine and its main metabolite noribogaine on action potentials in human ventricular-like cardiomyocytes derived from induced pluripotent stem cells. Therapeutic concentrations of ibogaine and its long-lived active metabolite noribogaine significantly retarded action potential repolarization in human cardiomyocytes. These findings represent the first experimental proof that ibogaine application entails a cardiac arrhythmia risk for humans. In addition, they explain the clinically observed delayed incidence of cardiac adverse events several days after ibogaine intake. We conclude that therapeutic concentrations of ibogaine retard action potential repolarization in the human heart. This may give rise to a prolongation of the QT interval in the electrocardiogram and cardiac arrhythmias.

  20. Differences in the Slope of the QT-RR Relation Based on 24-Hour Holter ECG Recordings between Cardioembolic and Atherosclerotic Stroke.

    Science.gov (United States)

    Fujiki, Akira; Sakabe, Masao

    Objective Detecting paroxysmal atrial fibrillation in patients with ischemic stroke presenting in sinus rhythm is difficult because such episodes are often short, and they are also frequently asymptomatic. It is possible that the ventricular repolarization dynamics may reflect atrial vulnerability and cardioembolic stroke. Hence, we compared the QT-RR relation between cardioembolic stroke and atherosclerotic stroke during sinus rhythm. Methods The subjects comprised 62 consecutive ischemic stroke patients including 31 with cardioembolic strokes (71.8±12.7 years, 17 men) and 31 with atherosclerotic strokes (74.8±10.8 years, 23 men). The QT and RR intervals were measured from ECG waves based on a 15-sec averaged ECG during 24-hour Holter recording using an automatic QT analyzing system. The QT interval dependence on the RR interval was analyzed using a linear regression line for each subject ([QT]=A[RR]+B; where A is the slope and B is the y-intercept). Results The mean slope of the QT-RR relation was significantly greater in cardioembolic stroke than in atherosclerotic stroke (0.187±0.044 vs. 0.142±0.045, pHolter recordings did not differ between them. An increased slope (≥0.14) of the QT-RR regression line could predict cardioembolic stroke with 97% sensitivity, 55% specificity and a positive predictive value of 64%. Conclusion The increased slope of the QT-RR linear regression line based on 24-hour Holter ECG in patients with ischemic stroke presenting in sinus rhythm may therefore be a simple and useful marker for cardioembolic stroke.

  1. H558R polymorphism in SCN5A is associated with Keshan disease and QRS prolongation in Keshan disease patients.

    Science.gov (United States)

    Jiang, S; Li, F L; Dong, Q; Liu, H W; Fang, C F; Shu, C; Cheng, H; Cui, J; Ma, H X; Chen, D Q; Li, H

    2014-08-28

    Keshan disease (KSD), a potentially fatal cardiomyopathy, has very high incidence in some selenium-poor regions of China. KSD may be accompanied with a variety of arrhythmia, which is associated with mutations in the gene coding for cardiac voltage-gated sodium channel (SCN5A). The molecular mechanism of KSD is still largely obscure. We aimed to determine the association between the H558R polymorphism of SCN5A and KSD. We recruited 71 patients with KSD and 80 geographical region-matched control subjects in our study. Vital sign and electrocardiographic (ECG) measurements were performed for heart rate, systolic pressure, diastolic pressure, PR interval, QT interval, QRS duration, ST-T changes and complete right bundle branch block (CRBBB), and H558R polymorphism was genotyped using the polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) method and sequencing. A significant association was found between the H558R polymorphism of exon 12 and KSD. Allele C carriers had a decreased risk for KSD with an odds ratio of 0.332 [95% confidence interval (CI), 0.160-0.692] as well as for QRS prolongation in KSD patients with an odds ratio of 0.089 (95%CI, 0.022-0.361). Our results provide support to the association between H558R polymorphism and the decreased risk for KSD. H558R polymorphism might increase susceptibility to KSD, and SCN5A containing the polymorphism might be a predisposing gene for QRS prolongation.

  2. Carvedilol versus metoprolol in patients undergoing direct percutaneous coronary interventions for myocardial infarction: effects on QT dynamicity.

    Science.gov (United States)

    Bonnemeier, Hendrik; Ortak, Jasmin; Tölg, Ralph; Witt, Maren; Schmidt, Jörg; Wiegand, Uwe K H; Bode, Frank; Schunkert, Heribert; Richardt, Gert

    2005-01-01

    Beta-adrenergic blockers exert significant antiarrhythmic activity during ischemia and reperfusion. To further explore the beneficial effects conferred by alpha-1-adrenoceptor blockade on ventricular repolarization dynamicity in the acute phase of myocardial infarction (AMI), we compared carvedilol with metoprolol in the setting of primary percutaneous coronary intervention (PCI). In a prospective study, 100 consecutive patients undergoing primary PCI for AMI were randomized to metoprolol 200 mg/day versus carvedilol 25 mg/day. The first oral dose of study drug was administered and a 24-hour ambulatory electrocardiogram recorded upon hospital admission. Slopes of the linear QT/RR regression were determined before and after reperfusion. A total of 38 recordings of patients treated with metoprolol and 34 recordings of patients with carvedilol were eligible for analysis of QT/RR slopes. The two study groups were similar with respect to age, gender, TIMI perfusion grades, ventricular function, duration of ischemia, and site and size of infarction. Mean RR- and QT-intervals were similar to the metoprolol and carvedilol groups, before and after PCI. Likewise, there was no significant difference in QT/RR slopes between the metoprolol and carvedilol groups before PCI. In contrast, after PCI, there was a trend toward lower QT/RR slopes in the metoprolol group (from 0.18 +/- 0.07 to 0.17 +/- 0.08), and a significant decrease in QT/RR slopes in the carvedilol group (from 0.17 +/- 0.07 to 0.14 +/- 0.09). In patients undergoing successful direct PCI for AMI, treatment with carvedilol, in contrast to metoprolol, was associated with a significant decrease in QT-RR slopes, suggesting greater cardiac electrical stability.

  3. Modulation of hERG potassium channel gating normalizes action potential duration prolonged by dysfunctional KCNQ1 potassium channel

    Science.gov (United States)

    Zhang, Hongkang; Zou, Beiyan; Yu, Haibo; Moretti, Alessandra; Wang, Xiaoying; Yan, Wei; Babcock, Joseph J.; Bellin, Milena; McManus, Owen B.; Tomaselli, Gordon; Nan, Fajun; Laugwitz, Karl-Ludwig; Li, Min

    2012-01-01

    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 KCNQ1 or human ether-a-go-go related genes (hERG), which encode two repolarizing potassium currents known as IKs and IKr. 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 cardiomyocytes to match the experimental waveforms of both healthy control and LQT syndrome type 1 (LQT1) action potentials. The quantitative evaluation suggests that elevation of IKr by reducing voltage sensitivity of inactivation, not via slowing of deactivation, could more effectively restore normal QT duration if IKs is reduced. Using a unique specific chemical activator for IKr 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 IKr 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. PMID:22745159

  4. Acquired long QT syndrome and monomorphic ventricular tachycardia after alternative treatment with cesium chloride for brain cancer.

    Science.gov (United States)

    Dalal, Anuj K; Harding, John D; Verdino, Ralph J

    2004-08-01

    Individuals searching for symptomatic relief or a potential cure are increasingly seeking and using nontraditional therapies for their various diseases. Little is known about the potential adverse effects that patients may encounter while undergoing these alternative treatments. Cesium chloride is an unregulated agent that has been reported to have antineoplastic properties. Cesium chloride is advertised as an alternative agent for many different types of cancers and can be purchased easily on the Internet. Recently, QT prolongation and polymorphic ventricular tachycardia were reported in several patients taking cesium chloride as alternative treatment for cancer. We report acquired QT prolongation and sustained monomorphic ventricular tachycardia in a patient who self-initiated and completed a course of cesium chloride as adjunctive treatment for brain cancer.

  5. QT dispersion and ventricular arrhythmias in children with primary mitral valve prolapse

    Science.gov (United States)

    İmamoğlu, Ebru Yalın; Eroğlu, Ayşe Güler

    2016-01-01

    Aim: To investigate ventricular arrhythmias in children with primary mitral valve prolapse and to evaluate its relation with QT length, QT dispersion, autonomic function tests and heart rate variability measurements. Material and Methods: Fourty two children with mitral valve prolapse and 32 healthy children were enrolled into the study. Twelve-lead electrocardiograms, autonomic function tests, echocardiography and 24-hour rhythm Holter tests were performed. Electrocardiograms were magnified digitally. The QT length was corrected according to heart rate. The patients were grouped according to the number of premature ventricular contractions and presence of complex ventricular arhythmia in the 24-hour rhythm Holter monitor test. Heart rate variability measurements were calculated automatically from the 24-hour rhythm Holter monitor test. Orthostatic hypotension and resting heart rate were used as autonomic function tests. Results: The mean age was 13.9±3.3 years in the patient group and 14.6±3.1 years in the control group (p>0.05). Thirty four of the patients (81%) were female and eight (19%) were male. Twenty five of the control subjects (78%) were female and seven (22%) were male. The QT dispersion and heart rate corrected QT interval were found to be significantly increased in the children with primary mitral valve prolapse when compared with the control group (56±16 ms vs. 43±11 ms, p=0.001; 426±25 ms vs. 407±26 ms, p=0.002, respectively). In 24-hour rhythm Holter monitor tests, ventricular arrhythmias were found in 21 out of 42 patients (50%) and 6 out of 32 control subjects (18.8%) (p=0.006). QT dispersion was found to be significantly increased in patients with premature ventricular contractions ≥ 10/day and/or complex ventricular arrhythmias compared to the control group without ventricular premature beats (p=0.002). There was no significant difference in autonomic function tests and heart rate variability measurements between the patient and control

  6. The disease-specific phenotype in cardiomyocytes derived from induced pluripotent stem cells of two long QT syndrome type 3 patients.

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    Azra Fatima

    Full Text Available Long QT syndromes (LQTS are heritable diseases characterized by prolongation of the QT interval on an electrocardiogram, which often leads to syncope and sudden cardiac death. Here we report the generation of induced pluripotent stems (iPS cells from two patients with LQTS type 3 carrying a different point mutation in a sodium channel Nav1.5 (p.V240M and p.R535Q and functional characterization of cardiomyocytes (CM derived from them. The iPS cells exhibited all characteristic properties of pluripotent stem cells, maintained the disease-specific mutation and readily differentiated to CM. The duration of action potentials at 50% and 90% repolarization was longer in LQTS-3 CM as compared to control CM but this difference did not reach statistical significance due to high variations among cells. Sodium current recordings demonstrated longer time to peak and longer time to 90% of inactivation of the Na(+ channel in the LQTS-3 CM. This hints at a defective Na(+ channel caused by deficiency in open-state inactivation of the Na(+ channel that is characteristic of LQTS-3. These analyses suggest that the effect of channel mutation in the diseased CM is demonstrated in vitro and that the iPS cell-derived CM can serve as a model system for studying the pathophysiology of LQTS-3, toxicity testing and design of novel therapeutics. However, further improvements in the model are still required to reduce cell-to-cell and cell line-to-cell line variability.

  7. Quinine and the ABCs of Long QT: A Patient's Misfortune with Arthritis, (Alcoholic) Beverages, and Cramps.

    Science.gov (United States)

    Sheehan, Elyce T; Frizzell, Jarrod D; Gabaldon, Jude; West, Michael B

    2016-10-01

    A 91-year-old woman presented to the emergency department by ambulance after her family found her minimally responsive. Telemetry monitoring demonstrated episodes of non-sustained polymorphic ventricular tachycardia (PMVT) associated with significantly prolonged repolarization. Her medical history revealed that she was taking quinine or a derivative in three different forms: hydroxychloroquine, quinine sulfate (for leg cramps), and her gin mixed with tonic water (containing quinine). The present case is illustrative of classic etiologies and findings of acquired long QT syndrome, and serves as an important reminder for providers to take a complete medication history, including use of duplicative and alternative medicines and type of alcohol consumption.

  8. The clinical factors′ prediction of increased intradialytic qt dispersion on the electrocardiograms of chronic hemodialysis patients

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    Dina Oktavia

    2013-01-01

    Full Text Available Ventricular arrhythmias and sudden death are common in patients on maintenance hemodialysis (HD. The increase in QT dispersion (QTd on the electrocardiogram (ECG reflects increased tendency for ventricular repolarization that predisposes to arrhythmias. The purpose of the study was to identify the clinical factors that may predict the increased intradialytic QTd and to assess differences in QTd before and after HD. Each of 61 chronic HD patients underwent 12-lead ECG and blood pressure (BP measurement before and every 1 h during a single HD session. The QT intervals were corrected for heart rate using Bazett′s formula. Intradialytic QTd increased in 30 (49% patients. There was no correlation between the increased QTd and the clinical factors including hypertension, pulse pressure, intradialytic hypotension, left ventricular hypertrophy, old myocardial infarct, diabetes mellitus, and nutritional status. The means of QT interval and QTd increased after HD session (from 382 ± 29 to 444 ± 26 ms, P <0.05; and from 74 ± 21 to 114 ± 53 ms, respectively, P <0.05. We conclude that the increased intradialytic QTd could not be predicted by any of the clinical factors evaluated in this study. There was significant difference in the means of QTd before and after HD session.

  9. Review and management of the dental patient with Long QT syndrome (LQTS).

    Science.gov (United States)

    Rochford, Christopher; Seldin, R David

    2009-01-01

    Long QT syndrome (LQTS) is a unique cardiovascular condition, with both congenital and acquired forms that afflict patients. These patients show a lengthening of the repolarization phase of the cardiac cycle, which can be best visualized on an electrocardiogram (ECG). The ECG changes can include QT interval (the time between the start of the Q wave and the end of the T wave, as seen on an ECG) and T wave abnormalities, as well as progression to torsades de pointes and ventricular fibrillation. The ECG changes are most commonly elicited by physical activity, emotional stress, and certain medications. This condition represents a challenge for the oral and maxillofacial surgeon. Patients with LQTS must receive proper medical management and a controlled and anxiety-free surgical environment. The purpose of this article was to present a review of LQTS and provide recommendations for effective surgical management. Additionally, a case report of a patient with LQTS, treated by one of the authors, has been included.

  10. Design and Application of Qt/Embedded Serial Port Class%Qt/Embedded串口类的设计及应用

    Institute of Scientific and Technical Information of China (English)

    陈旭红; 高文学

    2010-01-01

    针对Qt/Embedded类中没有提供串口基础类的现状,研究了Qt/Embedded与串口信息交互的方法,并给出了Qt/Embedded串口类的实现及Qt/Embedded串口类在工业控制中的应用实例.

  11. Founder mutations characterise the mutation panorama in 200 Swedish index cases referred for Long QT syndrome genetic testing

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    Stattin Eva-Lena

    2012-10-01

    Full Text Available Abstract Background Long QT syndrome (LQTS is an inherited arrhythmic disorder characterised by prolongation of the QT interval on ECG, presence of syncope and sudden death. The symptoms in LQTS patients are highly variable, and genotype influences the clinical course. This study aims to report the spectrum of LQTS mutations in a Swedish cohort. Methods Between March 2006 and October 2009, two hundred, unrelated index cases were referred to the Department of Clinical Genetics, Umeå University Hospital, Sweden, for LQTS genetic testing. We scanned five of the LQTS-susceptibility genes (KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 for mutations by DHPLC and/or sequencing. We applied MLPA to detect large deletions or duplications in the KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 genes. Furthermore, the gene RYR2 was screened in 36 selected LQTS genotype-negative patients to detect cases with the clinically overlapping disease catecholaminergic polymorphic ventricular tachycardia (CPVT. Results In total, a disease-causing mutation was identified in 103 of the 200 (52% index cases. Of these, altered exon copy numbers in the KCNH2 gene accounted for 2% of the mutations, whereas a RYR2 mutation accounted for 3% of the mutations. The genotype-positive cases stemmed from 64 distinct mutations, of which 28% were novel to this cohort. The majority of the distinct mutations were found in a single case (80%, whereas 20% of the mutations were observed more than once. Two founder mutations, KCNQ1 p.Y111C and KCNQ1 p.R518*, accounted for 25% of the genotype-positive index cases. Genetic cascade screening of 481 relatives to the 103 index cases with an identified mutation revealed 41% mutation carriers who were at risk of cardiac events such as syncope or sudden unexpected death. Conclusion In this cohort of Swedish index cases with suspected LQTS, a disease-causing mutation was identified in 52% of the referred patients. Copy number variations explained 2% of the

  12. Anestesia e síndrome do QT longo Anestesia e síndrome del QT largo Anesthesia and the long QT syndrome

    OpenAIRE

    Michelle Nacur Lorentz; Flávio Gouveia Camelo Ramiro

    2007-01-01

    JUSTIFICATIVA E OBJETIVOS: As disritmias cardíacas são fatores importantes de morbimortalidade no período perioperatório. Dentre as causas de disritmias, a síndrome do QT longo, tanto em sua forma genética como adquirida deve ser lembrada, já que muitos fármacos usados em anestesia, bem como ocorrências no período perioperatório podem prolongar o intervalo QT e precipitar disritmias cardíacas potencialmente malignas. CONTEÚDO: Revisão da síndrome do QT longo (LQTS), abordando suas causas e su...

  13. Solving the TTC 2013 Flowgraphs Case with FunnyQT

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    Tassilo Horn

    2013-11-01

    Full Text Available FunnyQT is a model querying and model transformation library for the functional Lisp-dialect Clojure providing a rich and efficient querying and transformation API. This paper describes the FunnyQT solution to the TTC 2013 Flowgraphs Transformation Case. It solves all four tasks, and it has won the best efficiency award for this case.

  14. Long QT syndrome in a patient with allergic rhinoconjunctivitis and auto-immune diabetes: focus on the choice of anti-H1 drugs.

    Science.gov (United States)

    Moneret-Vautrin, D A; de Chillou, C; Codreanu, A

    2006-12-01

    The long QT syndrome is a rare disease. The prevalence is estimated at 1/5 000 to 1/20,000. Numerous drugs are contra-indicated because they can lengthen the QT interval. A case of pollen allergy in an adolescent with LQTS is described. The possibility to prescribe anti-H1 drugs is reviewed since cases of torsades de pointe and even deaths have been reported for terfenadine and astemizole. Diphenhydramine, orphenadrine and hydroxyzine are contra-indicated. No accidents and no effects on the QT interval have been published for ebastine, fexofenadine, desloratadine and levocetirizine. These anti-H1 drugs could be used with great care, without any association with drugs resulting in low serum potassium level. Azelastine eye drops have been authorized and a routine protection by inhaled corticosteroids during the pollinic period has been advised in this adolescent treated by betablockers.

  15. Long QT syndrome and anaesthesia%QT间期延长综合征与麻醉

    Institute of Scientific and Technical Information of China (English)

    温莉; 陈国忠

    2009-01-01

    Long QT syndrome (LQTS) is an arrhythmogenic cardiovascular disorder resulting from mutations in cardiac ion channels. The perioperative period is a time of high risk for patients with LQTS. This review summarizes the effect of various drugs on the QT interval and perioperative management in patients with known LQTS. The anesthesiologist is faced with difficult decisions on the best way to conduct anaesthesia. In order to improve scientific rationale in the anaesthetic management of LQTS patients, future investigations should focus on perioperative physiological and pharmacological influences on transmural dispersion of repolarization.%QT间期延长综合征(long QT syndrome,LQTS)是由于离子通道变异,可引起致死性心律失常的一类疾病.围术期是LQTS的高危时期.此文总结了各种麻醉药物对QT间期的影响,以及LQTS患者围术期处理的注意事项,但尚不能确定最合理的麻醉方法,未来的研究应着重于手术期间的生理和药理对跨壁复极离散度的影响.

  16. Progress in research on defective protein trafficking and functional restoration in HERG-associated long QT syndrome%HERG钾通道蛋白质转运异常和功能恢复与LQTS的研究进展

    Institute of Scientific and Technical Information of China (English)

    方培亮; 廉姜芳

    2016-01-01

    The human ether-a-go-go related gene (HERG) encodes the α-subunit of the rapid component of the delayed rectifier K+ channel,which is essential for the third repolarization of the action potential of human myocardial cells.Mutations of the HERG gene can cause type Ⅱ hereditary long QT syndrome (LQT2),characterized by prolongation of the QT interval,abnormal T wave,torsade de pointes,syncope and sudden cardiac death.So far more than 300 HERG mutations have been identified,the majority of which can cause LQT2 due to HERG protein trafficking defect.It has been reported that certain drugs can induce acquired long QT syndrome through directly blocking the pore and/or affecting the HERG trafficking.The trafficking defects and K+ currents can be restored with low temperature and certain drugs.However,the mechanisms underlying defective trafficking caused by HERG mutations and the inhibition/ restoration of HERG trafficking by drugs are still unknown.This review summarizes the current understanding of the molecular mechanisms including HERG trafficking under physiological and pathological conditions,and the effects of drugs on the HERG trafficking,in order to provide theoretical evidence for the diagnosis and treatment of long QT syndrome.%HERG基因编码快速激活延迟整流钾电流(rapidly activated delayed rectifier potassuim current,Ikr)的α亚单位,而Ikr在人类心脏动作电位3期复极化过程中起着重要的作用.HERG基因突变引起遗传性2型长QT综合征(hereditary long QT syndrome 2,hLQT2),表现为心电图QT间期延长、T波异常,易于发生尖端扭转型室速、晕厥及心源性猝死.截至目前,已发现300多个HERG基因突变位点,而其中多数突变导致LQT2机制为蛋白质转运异常.近年报道很多药物可致获得性长QT综合征(acquired long QT syndrome,aLQTS),机制除药物直接阻滞HERG通道外,亦伴随对HERG蛋白转运的抑制从而使细胞膜Ikr电流减少.很多体外实验又证明,低温

  17. A fatal combination in an old lady: Tako-Tsubo cardiomyopathy, long QT syndrome, and cardiac hypertrophy.

    Science.gov (United States)

    Wedekind, Horst; Müller, Joachim G; Ribbing, Michael; Skurzewski, Paul; Bozzetti, Christoph; Meyer-Krahmer, Hans-Joachim; Böcker, Dirk

    2009-06-01

    Tako-Tsubo cardiomyopathy (TT-CM), also called stress-induced cardiomyopathy or transient left ventricular (LV) apical ballooning syndrome, is characterized by transient apical or midventricular LV dysfunction that mimics myocardial infarction, but in the absence of significant coronary artery disease. The onset of TT-CM is typically triggered by an acute medical illness or by intense emotional, psychological, or physical stress. During the acute phase, a disturbed repolarization with QT prolongation in the surface ECG is frequently obvious. Despite the generally good prognosis of TT-CM, severe clinical courses have been reported due to the depressed LV function with cardiogenic shock or malignant tachyarrhythmias. We report an unusual presentation of a patient with TT-CM and recurrent episodes of torsades de pointes tachyarrhythmias. In this patient, we identified pre- and coexisting congenital long QT syndrome and severe cardiac hypertrophy--all of them associated with disturbed myocardial repolarization and predisposed the patient to malignant tachyarrhythmias.

  18. Modeling tissue- and mutation- specific electrophysiological effects in the long QT syndrome: role of the Purkinje fiber.

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    Vivek Iyer

    Full Text Available Congenital long QT syndrome is a heritable family of arrhythmias caused by mutations in 13 genes encoding ion channel complex proteins. Mounting evidence has implicated the Purkinje fiber network in the genesis of ventricular arrhythmias. In this study, we explore the hypothesis that long QT mutations can demonstrate different phenotypes depending on the tissue type of expression. Using computational models of the human ventricular myocyte and the Purkinje fiber cell, the biophysical alteration in channel function in LQT1, LQT2, LQT3, and LQT7 are modeled. We identified that the plateau potential was important in LQT1 and LQT2, in which mutation led to minimal action potential prolongation in Purkinje fiber cells. The phenotype of LQT3 mutation was dependent on the biophysical alteration induced as well as tissue type. The canonical ΔKPQ mutation causes severe action potential prolongation in both tissue types. For LQT3 mutation F1473C, characterized by shifted channel availability, a more severe phenotype was seen in Purkinje fiber cells with action potential prolongation and early afterdepolarizations. The LQT3 mutation S1904L demonstrated striking effects on action potential duration restitution and more severe action potential prolongation in Purkinje fiber cells at higher heart rates. Voltage clamp simulations highlight the mechanism of effect of these mutations in different tissue types, and impact of drug therapy is explored. We conclude that arrhythmia formation in long QT syndrome may depend not only on the basis of mutation and biophysical alteration, but also upon tissue of expression. The Purkinje fiber network may represent an important therapeutic target in the management of patients with heritable channelopathies.

  19. Síndrome de QT largo congénito: revisión de las diferentes variantes y tratamientos

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    Carlos Escobar Cervantes

    2005-01-01

    Full Text Available El síndrome de QT largo es una entidad clínica y genéticamente heterogénea, caracterizada por la prolongación del intervalo QT en el electrocardiograma de superficie junto con una dispersión aumentada de la repolarización ventricular que asocia una predisposición a la aparición de arritmias ventriculares malignas, torsade de pointes y fibrilación ventricular, que pueden conducir a una muerte súbita cardíaca. El síndrome de QT largo afecta predominantemente a adolescentes y adultos jóvenes con corazones estructural y funcionalmente normales pero que subyace una alteración en los canales de potasio o de sodio. Se han utilizado diferentes tratamientos en el síndrome de QT largo que incluyen la corrección de la causa subyacente y de los factores precipitantes, el tratamiento antiadrenérgico (beta-bloqueantes, simpatectomía cervicotorácica izquierda, sulfato de magnesio, isoproterenol, marcapasos, desfibrilador automático implantable. A pesar de estos tratamientos, la proporción de eventos cardíacos todavía es elevada. Otros tratamientos potenciales incluyen bloqueadores de los canales de sodio, suplementos de potasio, activadores de los canales de potasio, bloqueadores alfa-adrenérgicos, bloqueadores de los canales de calcio, atropina e inhibidores de la proteincinasa. El objetivo de este artículo es revisar las diferentes variantes conocidas hasta ahora del síndrome de QT largo congénito así como de los distintos tratamientos utilizados hasta la fecha y de los nuevos avances y posibles futuras estrategias en el síndrome de QT largo y en las torsade de pointes.Long-QT syndrome is a clinically and genetically heterogeneous syndrome characterized by lengthening of the QT interval and increased dispersion of the ventricular repolarization on the surface electrocardiogram and a propensity to malignant ventricular arrhythmias, torsade de pointes and ventricular fibrillation, which may lead to sudden cardiac death. Long-QT

  20. Supratherapeutic dose evaluation and effect of lesinurad on cardiac repolarization: a thorough QT/QTc study

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    Shen Z

    2016-10-01

    Full Text Available Zancong Shen,1 Michael Gillen,2 Kathy Tieu,1 Mai Nguyen,1 Erin Harmon,1 David M Wilson,1 Bradley Kerr,1 Caroline A Lee1 1Ardea Biosciences, Inc., San Diego, CA, 2AstraZeneca LP, Gaithersburg, MD, USA Introduction: Lesinurad is a selective uric acid reabsorption inhibitor approved in the United States and Europe for treatment of gout in combination with a xanthine oxidase inhibitor. A maximum tolerated dose study was conducted to determine the lesinurad supratherapeutic dose, followed by a thorough QTc study to characterize the effect of lesinurad on cardiac repolarization.Methods: The maximum tolerated dose study was a randomized, double-blind, placebo-controlled, single-ascending dose study that enrolled 35 healthy men and women. Lesinurad plasma exposure (maximum observed plasma concentration and area under the plasma concentration versus time curve was determined at doses of 800 mg, 1,200 mg, and 1,600 mg. The thorough QTc study was a double-blind, four-period, placebo-controlled crossover study with 54 healthy men and women who received single doses of lesinurad 1,600 mg (supratherapeutic dose, lesinurad 400 mg, moxifloxacin 400 mg, and placebo in randomized sequence. Digital 12-lead electrocardiograms were recorded at eleven time points over 24 hours in each treatment period. QT intervals were corrected for heart rate using an individual-specific correction factor (QTcI.Results: The upper bound of the one-sided 95% confidence interval for time-matched, placebo-subtracted, baseline-adjusted QTcI intervals (ΔΔQTcI was <10 ms for both the lesinurad 400 mg and 1,600 mg doses. ΔΔQTcI was independent of lesinurad concentrations. No QTcI thresholds >480 ms or QTcI increases >30 ms were observed. Moxifloxacin mean QTcI intervals were >5 ms, and the lower bounds of the 90% confidence interval were >5 ms at 2 hours, 3 hours, and 4 hours, confirming assay sensitivity.Conclusion: Lesinurad, at supratherapeutic doses, does not

  1. The clinical manifestation and electrocardiograph characteristics of a LQT13 pedigree%长QT13家系的临床表现和心电学特征研究

    Institute of Scientific and Technical Information of China (English)

    洪丽; 刘金秋; 王莹琦; 潘晓杰; 夏云龙; 张树龙; 高连君; 杨延宗

    2014-01-01

    Objective To investigate the relationship between the genotype and phenotype in LQT13.Methods A larger long QT syndrome(LQTS) family pedigree including 49 cases in four generations was evaluated.Clinical investigations,electrocardiograph (ECG),ultrasound cardiograph (UCG) were delivered to all family members.Blood samples were taken for the gene screen in 44 members.The digital ECG and dynamic ECG data were collected from LQT13 patients and matched healthy individuals compared.Results Seven cases were diagnosed as LQTS based on clinical evaluation.The KIR3.4-Gly387Arg mutation was found in 9 affected family members,including the 7 cases with positive clinical diagnosis and 2 suspected clinical cases,6 in female,and 3 male.The QT interval of female patients was relatively longer with frequent syncope.The syncope was easily induced by emotional stress.It may occur during night.Patients with shorter QT interval (450-460 ms) experienced only once or none syncope.The first syncope occurred after their twenties and occurred frequently from twenties to fifties.It seldom occurred after fifties.Pacemaker was implanted in 2 cases.β-blocker was effective in LQT13.Compared to healthy individuals,the mutation carriers were found to have prolonged QT peak interval with a significantly higher T-wave morphology combination score.Low frequency/high frequency ratio of heart rate variability was reduced in LQT13 patients.Conclusion The Kir3.4-Gly387Arg mutation leads to LQT13.Most of LQT13 patients are female.The first syncope attack occurs at their twenties.The QT interval is prolonged slightly with the first part of T wave prolongation.The prognosis of the LQT13 family members is relatively benign.No one experienced sudden cardiac death during the 9 years follow-up.%目的 探讨长QT13 (LQT13)家系临床表现、心电学特点和基因型之间的关系.方法 研究入选了大连医科大学附属第一医院心内科1个LQT13家系,4代人,共有家族成员49例.家族调

  2. Congenital short QT syndrome: landmarks of the newest arrhythmogenic cardiac channelopathy.

    Science.gov (United States)

    Pérez Riera, Andrés Ricardo; Paixão-Almeida, Adail; Barbosa-Barros, Raimundo; Yanowitz, Frank G; Baranchuk, Adrian; Dubner, Sergio; Palandri Chagas, Antônio Carlos

    2013-01-01

    Congenital or familial short QT syndrome is a genetically heterogeneous cardiac channelopathy without structural heart disease that has a dominant autosomal or sporadic pattern of transmission affecting the electric system of the heart. Patients present clinically with a spectrum of signs and symptoms including irregular palpitations due to episodes of paroxysmal atrialfibrillation, dizziness and fainting (syncope) and/or sudden cardiac death due to polymorphic ventricular tachycardia and ventricular fibrillation. Electrocardiographic (ECG) findings include extremely short QTc intervals (QTc interval ≤330 ms) not significantly modified with heart rate changes and T waves of great voltage witha narrow base. Electrophysiologic studies are characterized by significant shortening of atrial and ventricular refractory periods and arrhythmias induced by programmed stimulation. A few families have been identified with specific genotypes: 3 with mutations in potassium channels called SQT1 (Iks), SQT2 (Ikr) and SQT3 (Ik1). These 3 potassium channel variants are the "genetic mirror image" of long QT syndrome type 2, type 1 and Andersen-Tawil syndrome respectively because they exert opposite gain-of-function effects on the potassium channels in contrast to the loss-of-function of the potassium channels in the long QT syndromes. Three new variants with overlapping phenotypes affecting the slow inward calcium channels havealso been described. Finally, another variant with mixed phenotype affecting the sodium channel was reported. This review focuses the landmarks of this newest arrhythmogenic cardiac channelopathy on the main clinical, genetic, and proposed ECG mechanisms. In addition therapeutic options and the molecular autopsy of this fascinating primary electrical heart disease are discussed.

  3. Efeito de levobupivacaína e bupivacaína nas dispersões da onda P, QT e QT corrigido (QTc em cesariana Efecto de la levobupivacaína y la bupivacaína en las dispersiones de la onda P, QT y QT corregido (QTc en cesárea The Effect of levobupivacaine and bupivacaine on QT, corrected QT (Qtc, and P wave dispersions in cesarean section

    Directory of Open Access Journals (Sweden)

    Yeliz Deniz

    2013-04-01

    the patients were obtained in the operation room. Heart rate (HR, non-invasive blood pressure (NIBP, peripheral oxygen saturation (SpO2 and respiration rates (RR were recorded. Venous cannulation was performed with 18G cannula and fluid preload made with 10 mL.kg-1. Lactated Ringer solution. After fluid preload, second ECG recordings were taken and the patients were randomly separated into two groups. Group B (n = 30 received 10 mg of bupivacaine and Group L (n = 30 received 10 mg of levobupivacaine for spinal anesthesia. ECG recordings were repeated at 1, 5 and 10 minutes after spinal block. HR, NIBP, SpO2 , RR and sensory block levels were also recorded at the same time intervals. At predetermined time intervals of spinal anesthesia, P wave dispersion (Pwd, QT dispersion (QTd, and QTc dispersion (QTcd durations were measured from ECG records. QT and QTc durations are calculated with Bazzett formula. RESULTS: There was no difference between two groups according to block levels, hemodynamic parameters, Pwd, QTd, QTc and QTcd durations. CONCLUSION: Bupivacaine and levobupivacaine may be preferred in spinal anesthesia in pregnant patients who have extended Pwd and QTcd preoperatively.

  4. 基于Qt/Embedded的嵌入式控制界面开发%The development of embedded control interface based on Qt/Embedded

    Institute of Scientific and Technical Information of China (English)

    赵莹; 徐大平; 吕跃刚

    2009-01-01

    作者通过结合Qt/Embedded的特性和优点,提出用Qt/Embedded实现风力发电控制系统的图形界面的思路和设计原则,重点介绍了在嵌入式Linux内核基础上Qt/Embedded的安装和编程过程.

  5. Review of Current Research of Inherited Long-QT Syndrome%遗传性长QT综合征的研究进展

    Institute of Scientific and Technical Information of China (English)

    范新荣

    2012-01-01

    Hereditary long-QT syndrome is the first ionic channelopathy with increased propensity to syncope, torsades de pointes, ventricular fibrillation and sudden arrhythmic death. This inherited cardiac disease is characterized by a prolongation of the QT interval and abnormality of the T wave at basal ECG. Some researches showed mutations in the genes, encoded cardiac ion channel { K+ , Na+ and Ca + ) subunits or proteins involved in modulating ionic currents, could cause repolarization abnormality. LQTS with more than 1 700 mutations are classified to 13 genotypes ( LQTS 1-13). Clinical evidences on significant correlation between genotype and phenotype have been reported. To date, several therapies play an important role in primary and secondary prevention of hereditary LQTS, including beta-adrenergic receptor blockers, heart pacing, implantable cardioverter defibrillator and left cervicothoracic sympathectomy.%遗传性长QT综合征是第一个被发现的离子通道病,其心电图特征性表现为QT间期延长,T波异常,易诱发尖端扭转型室性心动过速和心室颤动,临床表现为反复的晕厥及心脏猝死.实验研究指出各种编码钾通道、钠通道、钙通道亚基蛋白或调控蛋白的基因突变导致心脏复极异常.遗传性长QT综合征按突变基因类型共分为13型,且特异的基因型与患者临床表型之间也存在着显著的关联性.目前对长QT综合征的治疗方法包括:β受体阻滞剂、心脏起搏、埋藏式心脏复律除颤器、左颈胸交感神经切除术及其他治疗策略,这些治疗方法在遗传性长QT综合征的一级及二级预防中起着重要的作用.

  6. Thorough QT Studies: Questions and Quandaries.

    Science.gov (United States)

    Malik, Marek; Garnett, Christine E; Zhang, Joanne

    2010-01-01

    The International Conference on Harmonisation E14 Guidance was successful in largely standardizing the conduct of the so-called thorough QT/QTc studies (TQTS). Nevertheless, there is still a spectrum of frequently encountered problems with details of design, conduct and interpretation of TQTS. Several of these challenges are reviewed here, starting with explaining that the TQTS goal is only to identify drugs for which the proarrhythmic risk might be considered excluded for the purposes of regulatory benefit-risk assessment. Suggestions are made on how to categorize and quantify or exclude proarrhythmic risk if the TQTS is positive. There is a conceptual need for TQTS, and this is discussed, together with reasons why restricted clinical registries cannot prove the absence of proarrhythmic liability of any drug. Appropriate drug doses investigated in TQTS should be derived from the maximum clinically tolerable dose rather than from the known or expected therapeutic dose. With the help of concentration-QTc modelling, the standard therapeutic dose can be omitted from TQTS, especially if the study is expected to be negative. Conditions for single-dose TQTS acceptability are reviewed. The role of the so-called positive control is assessed, contrasting the role of a same-class comparator for the investigated drug. A single 400 mg dose of moxifloxacin is advocated as the present 'gold standard' assay sensitivity test. The necessity of careful placebo control is explained and the frequency of ECG assessments is considered. The central tendency and outlier analyses are discussed, together with the correct approaches to baseline adjustment. The review concludes that the design and interpretation of TQTS must not be approached with mechanistic stereotypes, and highlights the importance of relating the QTc changes to drug plasma levels.

  7. [Dopplerometry at prolonged pregnancy].

    Science.gov (United States)

    Salii-Prenichi, L; Milchev, N; Markova, D; Apiosjan, Zh

    2010-01-01

    Prolonged pregnancy, associated with low amniotic fluid is a reason for the increase of fetal mortality and morbidity. There is no a define test at prolonged pregnancy which can determine which pregnancy are at a risk for adverse outcome and complications. Dopplerometry as a noninvasive method for examination of blood circulation, and especially a. cerebri media and a. umbilicalis can be used for the prediction of the outcome of prolonged pregnancy.

  8. Female predominance and transmission distortion in the long-QT syndrome

    NARCIS (Netherlands)

    Imboden, Medea; Swan, Heikki; Denjoy, Isabelle; Van Langen, Irene Marijke; Latinen-Forsblom, Päivi Johanna; Napolitano, Carlo; Fressart, Véronique; Breithardt, Guenter; Berthet, Myriam; Priori, Silvia; Hainque, Bernard; Wilde, Arthur Arnold Maria; Schulze-Bahr, Eric; Feingold, Josué; Guicheney, Pascale

    2006-01-01

    BACKGROUND: Congenital long-QT syndrome is a disorder resulting in ventricular arrhythmias and sudden death. The most common forms of the long-QT syndrome, types 1 and 2, are caused by mutations in the potassium-channel genes KCNQ1 and KCNH2, respectively. Although inheritance of the long-QT syndrom

  9. Treating an Adolescent with Long QT Syndrome for Bipolar Disorder: A Case Presentation.

    Science.gov (United States)

    Önen, Özlem; Kutlu, Ayşe; Erkuran, Handan Özek

    2017-01-26

    Long QT syndrome (LQTS) is described as the development of sudden syncope attacks or death as a result of ventricular tachycardia (VT) episodes that might be observed as elongated QT interval in electrocardiography (ECG). Implantable Cardioverter Defibrillator (ICD) is recommended as first-line treatment for the condition in guidelines. We aimed to present an adolescent recently diagnosed with Bipolar Disorder (BD) who had LQTS that was treated with ICD, discussing her follow up and treatment along with relevant literature. Psychiatric assessment of the case that applied to our child psychiatry unit due to manic symptoms were carried out by using Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) criteria. Symptom severity was monitored via Young Mania Rating Scale scores (YMRSS). The case met criteria for Bipolar Disorder Type I (BD-I). She had improvement in her mood symptoms with treatment regimen as risperidone 3 mg/day, valproate 1000 mg/day and lorazepam 1 mg/dayi after her 2-week follow up as well as no reported ICD activity, reflecting fine cardiac functions and rhythm. LQTS is a serious health issue for children and adolescents diagnosed with BD. This condition should be kept in mind especially in cases where familial risk factors are present and precautions need to be maintained upon required assessments. These cases need to be closely monitored due to risk factors related to both BD and LQTS, in a multidisciplinary fashion, involving both psychiatry and cardiology divisions.

  10. A novel splice mutation of HERG in a Chinese family with long QT syndrome

    Institute of Scientific and Technical Information of China (English)

    SHANG Yun-peng; XIE Xu-dong; WANG Xing-xiang; CHEN Jun-zhu; ZHU Jian-hua; TAO Qian-min; ZHENG Liang-rong

    2005-01-01

    Congenital long QT syndrome (LQTS) is a genetically heterogeneous disease in which six ion-channel genes have been identified. The phenotype-genotype relationships of the HERG (human ether-a-go-go-related gene) mutations are not fully understood. The objective of this study is to identify the underlying genetic basis of a Chinese family with LQTS and to characterize the clinical manifestations properties of the mutation. Single strand conformation polymorphism (SSCP) analyses were conducted on DNA fragments amplified by polymerase chain reaction from five LQT-related genes. Aberrant conformers were analyzed by DNA sequencing. A novel splice mutation in C-terminus of HERG was identified in this Chinese LQTS family,leading to the deletion of 11-bp at the acceptor splice site of Exon9 [Exon9 IVS del (-12→-2)]. The mutation might affect,through deficient splicing, the putative cyclic nucleotide binding domain (CNBD) of the HERG K+ channel. This mutation resulted in a mildly affected phenotype. Only the proband had a history of syncopes, while the other three individuals with long QT interval had no symptoms. Two other mutation carriers displayed normal phenotype. No sudden death occurred in the family. The 4 affected individuals and the two silent mutation carriers were all heterozygous for the mutation. It is the first splice mutation of HERG reported in Chinese LQTS families. Clinical data suggest that the CNBD mutation may be less malignant than mutations occurring in the pore region and be partially dominant over wild-type function.

  11. Risk of atrial fibrillation as a function of the electrocardiographic PR interval

    DEFF Research Database (Denmark)

    Nielsen, Jonas Bille; Pietersen, Adrian; Graff, Claus;

    2013-01-01

    Prolongation of the PR interval has been associated with an increased risk of incident atrial fibrillation (AF).......Prolongation of the PR interval has been associated with an increased risk of incident atrial fibrillation (AF)....

  12. Mitoxantrone and acquired Long-QT Syndrome. Case presentation. Mitoxantrone y síndrome QT prolongado adquirido. Presentación de un caso.

    Directory of Open Access Journals (Sweden)

    Lázaro Enrique De la Cruz Aviléz

    2009-05-01

    Full Text Available The acquired Long-QT Syndrome can be caused by more than 100 non anti-arrhythmic drugs. These drugs block potassium channels; particularly the IKr which extends the ventricular repolarization beyond 450 ms. This syndrome is associated with ventricular helical tachycardia that could potentially cause immediate death. We report a patient with diagnosis of leukaemia who was treated with mitoxantrone and presented syncope. The electrocardiogram showed an interval QTc of 576 ms. After an exclusion diagnosis we concluded that there could be an association with the use of this drug caused by its toxic effects for the cardiac system. Mitoxantrone interferes in ionic transportation through cellular membrane, delays the exit of potassium from the cells and acts in the functioning of ATP asa Na/K altering the ventricular repolarization; however, it is not on the list of drugs that enlarge the QT interval. Our objective with this work is to raise the interest on new reports on this subject, and to establish a more direct causal relation through the evidence derived from new experiences. El síndrome QT largo adquirido puede ser producido entre otros aspectos por más de 100 fármacos no antiarrítmicos. Estos tienen la capacidad de bloquear los canales de potasio; fundamentalmente los IKr, prolongan la repolarización ventricular más allá de los 450 ms. Este síndrome se asocia a taquicardias ventriculares helicoidales con potencial para producir una muerte súbita. Se reporta un paciente con diagnóstico de leucemia tratado con mitoxantrone, que presentó un síncope. Además, en el electrocardiograma se constató el hallazgo de un intervalo QTc de 576 ms. Después de realizar un diagnóstico de exclusión, se concluyó que podía haber una asociación con el uso del fármaco, por sus efectos tóxicos para el sistema cardiaco. El mitoxantrone, entre otras cosas, interfiere en el trasporte de iones a través de la membrana celular, retarda la salida de

  13. The Transplantation and Application of Embedded GUI Based on Qt/Embedded and Qtopia%基于Qt/Embedded和Qtopia的嵌入式GUI移植开发

    Institute of Scientific and Technical Information of China (English)

    张亚军; 孔帅

    2010-01-01

    基于Qt/Embedded和Qtopia在UP-NetARM2410-S平台上进行交叉编译与安装过程的应用设计.通过对Qt/Embedded的GUI研究,并且给出了Qt/Embedded下应用程序的开发以及如何将应用程序添加到Qtopia的实例.

  14. Long QT, alteration of calcium-phosphate product, prevalence of ventricular arrhythmias and sudden death in peritoneal dialysis patients: a Holter study

    Directory of Open Access Journals (Sweden)

    Pierluigi Di Loreto

    2013-03-01

    Full Text Available Materials and methods We studied 79 patients on peritoneal dialysis. Each underwent 24-h electrocardiography (Holter monitoring and measurement of the rate-corrected QT interval (QTc. We analyzed the correlation between QTc and plasma levels of Ca++, PO4−, K+, Na+, Mg++, and parathyroid hormone (PTH. Results The mean QTc was 0.445 ± 0.04 s. In 55 patients, the QTc was prolonged (> 0.45 s. Mean laboratory values for the group were: PTH 344 ± 25 pg/mL, Ca++ 9.27 ± 0.11 mg/dL, PO4− 5.5 ± 1.5 mg/dL, Na+ 139.6 ± 3.4 mmol/L, K+ 4.04 ± 0.64 mmol/L, and Mg++ 2.52 ± 0.43 mg/dL. Holter monitoring revealed complex premature ventricular contractions in 44 patients, monomorphic premature ventricular contractions in 16, and nonsustained ventricular tachycardia (NSVT in 10. The QTc was significantly correlated with plasma levels of PO4− (r = 0.045, p < 0.05, PTH (r = 0.077, p < 0.02, and Ca++ (r = 0.076, p < 0.02. Eleven patients had Lown class 4a or 4b ventricular arrhythmias, and their mean QTc was 465 ± 0.02 ms. Ten had NSVT and their QTc was 464 ± 0.03 ms. Eleven patients died suddenly (mean QTc 465 ± 0.03 ms; all 11 had either NSTV or Lown class 4 ventricular arrhythmias. Conclusions Long QTc seems to be associated with an increased prevalence of ventricular arrhythmias that may be the cause of sudden cardiac death.

  15. QT dispersion in patients with arrhythmogenic right ventricular dysplasia

    DEFF Research Database (Denmark)

    Benn, Marianne; Hansen, P S; Pedersen, A K

    1999-01-01

    , of electrical instability. The present study was conducted to assess the occurrence of QT dispersion and its modulation during treatment with sotalol. Methods Twenty-five patients with the diagnosis of arrhythmogenic right ventricular dysplasia were studied retrospectively. Fourteen patients were considered low...

  16. Beat-to-beat T-wave amplitude variability in the long QT syndrome.

    Science.gov (United States)

    Extramiana, Fabrice; Tatar, Charif; Maison-Blanche, Pierre; Denjoy, Isabelle; Messali, Anne; Dejode, Patrick; Iserin, Frank; Leenhardt, Antoine

    2010-09-01

    Long QT syndrome (LQTS) is a primary electrical disease characterized by QT prolongation and increased repolarization dispersion leading to T-wave amplitude beat-to-beat changes. We aimed to quantify beat-to-beat T-wave amplitude variability from ambulatory Holter recordings in genotyped LQTS patients. Seventy genotyped LQTS patients (mean age 23 +/- 15 years, 42 males, 50% LQT1, 39% LQT2, and 11% LQT3) and 70 normal matched control subjects underwent a 24-h digital Holter recording. Using the Tvar software (Ela Medical, Sorin group), the beat-to-beat variance of the T-wave amplitude (TAV in microV) [corrected] was assessed on 50-ms consecutive clusters during three 1-h periods: one with around average diurnal heart rate (Day Fast), one nocturnal period (Night), and one diurnal period with around average nocturnal heart rate (Day Slow). TAV was increased in LQTS patients during the two diurnal periods but not at night (during the Day Fast period, mean TAV was 34 +/- 20 microV [corrected] in LQTS patients vs. 27 +/- 10 microV [corrected] in controls, P < 0.05). This effect depended on the genotype. In LQT1, TAV was larger when compared with controls for both Day Fast and Slow periods, but in LQT2 only Day Fast shows higher TAV. Oppositely, in LQT3 the TAV was higher than in the control group during the Day slow period (mean TAV = 34 +/- 20 vs. 25 +/- 8 microV [corrected] in controls, P < 0.05). In genotyped LQTS patients beat-to-beat T-wave amplitude variability was increased when compared with control subjects. That pattern was modulated by circadian influences in a gene-dependent manner.

  17. Effect of anthracyclines and isoflurane on QTc interval

    Directory of Open Access Journals (Sweden)

    A. Venugopal

    2014-01-01

    Conclusions: Anthracycline chemotherapy can produce significant prolongation of QTc interval. In addition, use of 0.5% end tidal concentration of isoflurane can further augment the QTc interval significantly.

  18. Evaluation of the effect on cardiac repolarization (QTc interval) of oncologic drugs.

    Science.gov (United States)

    Morganroth, J

    2007-01-01

    The 12-lead electrocardiograph (ECG) is the standard safety measurement used in clinical trials to identify drug-induced cardiac adverse effects. Drug-induced prolongation of the QTc interval (the measure of cardiac repolarization change), when excessive and in conjunction with the right risk factors, can degenerate into a polymorphic ventricular tachycardia called torsades de pointes and has become a new focus for new drug development. The assessment of an ECG in clinical practice using machine-defined QTc duration is intrinsically unreliable. Current regulatory concepts have focused on the need for measuring ECG intervals using manual techniques using digital processing in a central ECG laboratory. The QT interval is subject to a large degree of spontaneous variability requiring attention to basic clinical trial design issues such as sample size (use as large a cohort as possible), frequency of measurements taken (at least three to six ECGs at baseline and at many time points on therapy with pharmacokinetic samples if possible), and their accuracy. Since most oncologic products are cytotoxic, a Thorough or Dedicated ECG Trial cannot be conducted and in the usual trail, especially in phase I, all changes seen on the ECG will be attributed to the new oncology drug. For most nononcologic drugs, there is regulatory guidance on how much an effect on QTc duration might be related to the risk of cardiac toxicity. For oncology products, the central tendency magnitude and proportion of outliers needs to be well defined to construct a label if the risk-benefit analysis leads to marketing approval. Clinical cardiac findings such as syncope, ventricular tachyarrhythmias, and other cardiac effects will be important in this analysis.

  19. interval functions

    Directory of Open Access Journals (Sweden)

    J. A. Chatfield

    1978-01-01

    Full Text Available Suppose N is a Banach space of norm |•| and R is the set of real numbers. All integrals used are of the subdivision-refinement type. The main theorem [Theorem 3] gives a representation of TH where H is a function from R×R to N such that H(p+,p+, H(p,p+, H(p−,p−, and H(p−,p each exist for each p and T is a bounded linear operator on the space of all such functions H. In particular we show that TH=(I∫abfHdα+∑i=1∞[H(xi−1,xi−1+−H(xi−1+,xi−1+]β(xi−1+∑i=1∞[H(xi−,xi−H(xi−,xi−]Θ(xi−1,xiwhere each of α, β, and Θ depend only on T, α is of bounded variation, β and Θ are 0 except at a countable number of points, fH is a function from R to N depending on H and {xi}i=1∞ denotes the points P in [a,b]. for which [H(p,p+−H(p+,p+]≠0 or [H(p−,p−H(p−,p−]≠0. We also define an interior interval function integral and give a relationship between it and the standard interval function integral.

  20. 基于Qt/Embedded的车载GUI的研究与实现%Research and Implement of Vehicle GUI Based on Qt/Embedded

    Institute of Scientific and Technical Information of China (English)

    周超杰; 孔繁虹

    2012-01-01

    开发具有友好的人机交互界面和现场可操作性的嵌入式系统是开发智能车载终端的重要环节.使用嵌入式Linux操作系统作为底层软件平台,并使用嵌入式Qt/Embedded (Qt/E)图形用户界面库作为开发工具,设计一种友好的车载人机交互界面.重点介绍了Qt/E开发平台的搭建和Qt/E的绘图机制,并给出车载GUI中关键模块的实现过程.%Developing friendly interactive interface and on-site operational embedded systems is an important part of development of intelligent vehicle terminal. This paper uses an embedded Linux operating system as the underlying software platform and the embedded Qt/Embedded ( Qt/E) as a graphical user interface library development tools to design a car-friendly interactive interface. Focuses on the building of Qt/E development platform and Qt/E drawing mechanism and describes the implementation process of the key module in vehicle GUI.

  1. Sheehan Syndrome with Acquired Long QT Syndrome Complicated by Torsade de Pointes: Report of One Case and Literature Analysis%席汉综合征并长QT综合征伴发尖端扭转型室性心动过速一例报道并文献分析

    Institute of Scientific and Technical Information of China (English)

    王创畅; 吴伟; 马培; 卿立金

    2013-01-01

    One case of 48 - year - old Sheehan syndrome patients with hypothyroidism hy laboratory examination were given isoprenaline and thyroxin. No recurrence was noted after 2 - week follow - ups. Sheehan syndrome, probably leading to deficiency of sex hormones, thyroid hormones, adrenal hormones and other endocrine hormone, is related, to some extent, to acquired long QT syndrome. Its specific mechanisms may be associated with heart myxedema, gender difference in sex hormones, sinus bradycardia and other factors. For patients with unexplained prolonged QT intervals, thyroid, gonads, adrenal function should examined to prevent missed diagnoses and misdiagnoses.%本文报道1例48岁席汉综合征患者,实验室检查提示甲状腺功能低下,给予异丙肾上腺素,补充甲状腺素等治疗后随访2周无再发.席汉综合征患者可导致性激素、甲状腺激素、肾上腺激素等各种内分泌激素缺乏,与获得性长QT综合征具有一定关系,具体机制可能与心脏黏液性水肿、性激素的性别差异、窦性心动过缓等因素有关.对原因不明的QT间期延长患者应注意查甲状腺、性腺、肾上腺功能,以防漏诊误诊.

  2. Síťová hra v Nokia Qt SDK

    OpenAIRE

    Pramuka, Tomáš

    2012-01-01

    Práce se zaobírá návrhem aplikace, síťové hry v Nokia Qt SDK pro mobilní zařízení Nokia N900. Aplikace umožňuje hrát hru dvěma hráčům proti sobě v reálném čase. Práce obsahuje informace o mobilním zařízení Nokia N900, o jeho hardwarové a softwarové části, informace o vývoji aplikací v Nokia Qt SDK a o jednotlivých častech a nástrojích SDK. Součástí práce je návrh aplikace. This work is about application design of network game, developed in Nokia Qt SDK for the mobile device Nokia N900. App...

  3. Exhaustion from prolonged gambling

    Directory of Open Access Journals (Sweden)

    Fatimah Lateef

    2013-01-01

    Full Text Available Complaints of fatigue and physical exhaustion are frequently seen in the acute medical setting, especially amongst athletes, army recruits and persons involved in strenuous and exertional physical activities. Stress-induced exhaustion, on the other hand, is less often seen, but can present with very similar symptoms to physical exhaustion. Recently, three patients were seen at the Department of Emergency Medicine, presenting with exhaustion from prolonged involvement in gambling activities. The cases serve to highlight some of the physical consequences of prolonged gambling.

  4. Exhaustion from prolonged gambling

    Institute of Scientific and Technical Information of China (English)

    Fatimah Lateef

    2013-01-01

    Complaints of fatigue and physical exhaustion are frequently seen in the acute medical setting, especially amongst athletes, army recruits and persons involved in strenuous and exertional physical activities.Stress-induced exhaustion, on the other hand, is less often seen, but can present with very similar symptoms to physical exhaustion.Recently, three patients were seen at theDepartment ofEmergencyMedicine, presenting with exhaustion from prolonged involvement in gambling activities.The cases serve to highlight some of the physical consequences of prolonged gambling.

  5. Deciding about treatments that prolong life

    Science.gov (United States)

    Palliative care - treatments that prolong life; Palliative care - life support; End-of-life-treatments that prolong life; Ventilator - treatments that prolong life; Respirator - treatments that prolong life; ...

  6. Heart rate dependency of JT interval sections.

    Science.gov (United States)

    Hnatkova, Katerina; Johannesen, Lars; Vicente, Jose; Malik, Marek

    2017-08-09

    Little experience exists with the heart rate correction of J-Tpeak and Tpeak-Tend intervals. In a population of 176 female and 176 male healthy subjects aged 32.3±9.8 and 33.1±8.4years, respectively, curve-linear and linear relationship to heart rate was investigated for different sections of the JT interval defined by the proportions of the area under the vector magnitude of the reconstructed 3D vectorcardiographic loop. The duration of the JT sub-section between approximately just before the T peak and almost the T end was found heart rate independent. Most of the JT heart rate dependency relates to the beginning of the interval. The duration of the terminal T wave tail is only weakly heart rate dependent. The Tpeak-Tend is only minimally heart rate dependent and in studies not showing substantial heart rate changes does not need to be heart rate corrected. For any correction formula that has linear additive properties, heart rate correction of JT and JTpeak intervals is practically the same as of the QT interval. However, this does not apply to the formulas in the form of Int/RR(a) since they do not have linear additive properties. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Purkinje Cells as Sources of Arrhythmias in Long QT Syndrome Type 3.

    Science.gov (United States)

    Iyer, Vivek; Roman-Campos, Danilo; Sampson, Kevin J; Kang, Guoxin; Fishman, Glenn I; Kass, Robert S

    2015-08-20

    Long QT syndrome (LQTS) is characterized by ventricular arrhythmias and sudden cardiac death. Purkinje cells (PC) within the specialized cardiac conduction system have unique electrophysiological properties that we hypothesize may produce the primary sources of arrhythmia in heritable LQTS. LQTS type 3 (LQT3) transgenic mice harboring the ΔKPQ(+/-) mutation were crossed with Contactin2-EGFP BAC transgenic mice, which express a fluorescent reporter gene within the Purkinje fiber network. Isolated ventricular myocytes (VMs) (EGFP(-)) and PCs (EGFP(+)) from wild type and ΔKPQ mutant hearts were compared using the whole-cell patch clamp technique and microfluorimetry of calcium transients. Increased late sodium current was seen in ΔKPQ-PCs and ΔKPQ-VMs, with larger density in ΔKPQ-PCs. Marked prolongation of action potential duration of ΔKPQ-PCs was seen compared to ΔKPQ-VMs. ΔKPQ-PCs, but not ΔKPQ-VMs, exhibited frequent early afterdepolarizations, which corresponded to repetitive oscillations of intracellular calcium. Abnormalities in cell repolarization were reversed with exposure to mexiletine. We present the first direct experimental evidence that PCs are uniquely sensitive to LQT3 mutations, displaying electrophysiological behavior that is highly pro-arrhythmic.

  8. Prolonged labour : women's experiences

    OpenAIRE

    Nystedt, Astrid

    2005-01-01

    Aim: The overall aim of this thesis was to illuminate, describe, and promote understanding of women’s experiences of prolonged labour. The thesis compromises four studies. Methods: Paper I describes a case-referent study that recruited women (n = 255) giving singleton live birth to their first child by spontaneous labour after more than 37 completed weeks’ pregnancy. Participants completed a questionnaire that investigated childbirth experiences, previous family relationships, and childhood e...

  9. Lack of significant effect of bilastine administered at therapeutic and supratherapeutic doses and concomitantly with ketoconazole on ventricular repolarization: results of a thorough QT study (TQTS) with QT-concentration analysis.

    Science.gov (United States)

    Tyl, Benoît; Kabbaj, Meriam; Azzam, Sara; Sologuren, Ander; Valiente, Román; Reinbolt, Elizabeth; Roupe, Kathryn; Blanco, Nathalie; Wheeler, William

    2012-06-01

    The effect of bilastine on cardiac repolarization was studied in 30 healthy participants during a multiple-dose, triple-dummy, crossover, thorough QT study that included 5 arms: placebo, active control (400 mg moxifloxacin), bilastine at therapeutic and supratherapeutic doses (20 mg and 100 mg once daily, respectively), and bilastine 20 mg administered with ketoconazole 400 mg. Time-matched, triplicate electrocardiograms (ECGs) were recorded with 13 time points extracted predose and 16 extracted over 72 hours post day 4 dosing. Four QT/RR corrections were implemented: QTcB; QTcF; a linear individual correction (QTcNi), the primary correction; and a nonlinear one (QTcNnl). Moxifloxacin was associated with a significant increase in QTcNi at all time points between 1 and 12 hours, inclusively. Bilastine administration at 20 mg and 100 mg had no clinically significant impact on QTc (maximum increase in QTcNi, 5.02 ms; upper confidence limit [UCL] of the 1-sided, 95% confidence interval, 7.87 ms). Concomitant administration of ketoconazole and bilastine 20 mg induced a clinically relevant increase in QTc (maximum increase in QTcNi, 9.3 ms; UCL, 12.16 ms). This result was most likely related to the cardiac effect of ketoconazole because for all time points, bilastine plasma concentrations were lower than those observed following the supratherapeutic dose.

  10. Left thoracic sympathectomy in a premature infant with long QT syndrome and heart failure.

    Science.gov (United States)

    Surendran, Sushitha; Kumar, Thittamaranahalli K S; Knott-Craig, Christopher J

    2017-01-01

    Left thoracic sympathectomy has been shown to be an effective treatment for adults with long QT syndrome who are refractory to medical therapy. We report the successful use of left thoracic sympathectomy for the management of a 10-week-old premature baby with long QT syndrome and heart failure from a large ventricular septal defect and patent ductus arteriosus.

  11. Association of a congenital long QT syndrome type 1 with Takotsubo cardiomyopathy

    OpenAIRE

    El?Battrawy, Ibrahim; Behnes, Michael; Borggrefe, Martin; Akin, Ibrahim

    2016-01-01

    Key Clinical Message The occurrence of takotsubo cardiomyopathy in a patient with congenital long QT syndrome has rarely been described. This case report discusses the occurrence of a clinically overt takotsubo cardiomyopathy accompanied by congenital long QT syndrome type 1 in a female patient.

  12. Solving the Class Diagram Restructuring Transformation Case with FunnyQT

    Directory of Open Access Journals (Sweden)

    Tassilo Horn

    2013-11-01

    Full Text Available FunnyQT is a model querying and model transformation library for the functional Lisp-dialect Clojure providing a rich and efficient querying and transformation API. This paper describes the FunnyQT solution to the TTC 2013 Class Diagram Restructuring Transformation Case. This solution and the GROOVE solution share the best overall solution award for this case.

  13. Combining $Q_T$ and small-$x$ resummations

    CERN Document Server

    Marzani, Simone

    2015-01-01

    We analyze transverse momentum ($Q_T$) resummation of a colorless final state, e.g. Higgs production in gluon fusion or the production of a lepton pair via the Drell-Yan mechanism, in the limit where the invariant mass of the final state is much less then the center-of-mass energy, i.e. $Q^2\\ll s$. We show how the traditional resummation of logarithms of $Q_T/Q$ can be supplemented with the resummation of the leading logarithmic contributions at small $x=Q^2/s$ and we compute the necessary ingredients to perform such joint resummation.

  14. Research of a Message Delivery Model Based on QT Quick%基于QT Quick的消息分发模型研究

    Institute of Scientific and Technical Information of China (English)

    熊萱; 杜祝; 谭钦文

    2012-01-01

    QT Quick是一项新技术,用于动态设计和描述图形用户界面。文章基于QT Quick技术,提出了一种消息分发模型,并结合工程实际应用,对该模型实现的关键技术、消息分发流程进行了研究。%QT Quick is a new technology used for dynamic design and description of graphical user interface(GUI).Based on QT Quick,a message delivery model is proposed in this paper.Considering engineering practice,research on key technologies to achieve the model and the message delivery flow is presented.

  15. Effect of dofetilide on QT dispersion and the prognostic implications of changes in QT dispersion for patients with congestive heart failure

    DEFF Research Database (Denmark)

    Brendorp, Bente; Elming, Hanne; Jun, Li;

    2002-01-01

    AIMS: Drug-induced changes in QT dispersion may be a way of detecting harmful repolarisation abnormalities for patients receiving antiarrhythmic drugs affecting ventricular repolarisation. METHODS AND RESULTS: In 463 congestive heart failure (CHF) patients enrolled in the Danish Investigations...

  16. 基于Qt/Embedded嵌入式控制界面的设计%Design of Qt/Embedded-based Control Interface

    Institute of Scientific and Technical Information of China (English)

    陈曦; 刘增强

    2011-01-01

    介绍了一种基于嵌入式Linux操作系统的小型通用智能控制器的图形用户界面的设计,着重阐述了使用跨平台开发工具Qt/Embedded的开发过程.%The graphical user interface( GUI) design for small general-purpose intelligent controllers was introduced, including the development process of employing Qt/Embedded in the design.

  17. Prolonged pain and disability are common after rib fractures.

    Science.gov (United States)

    Fabricant, Loic; Ham, Bruce; Mullins, Richard; Mayberry, John

    2013-05-01

    The contribution of rib fractures to prolonged pain and disability may be underappreciated and undertreated. Clinicians are traditionally taught that the pain and disability of rib fractures resolves in 6 to 8 weeks. This study was a prospective observation of 203 patients with rib fractures at a level 1 trauma center. Chest wall pain was evaluated by the McGill Pain Questionnaire (MPQ) pain rating index (PRI) and present pain intensity (PPI). Prolonged pain was defined as a PRI of 8 or more at 2 months after injury. Prolonged disability was defined as a decrease in 1 or more levels of work or functional status at 2 months after injury. Predictors of prolonged pain and disability were determined by multivariate analysis. One hundred forty-five male patients and 58 female patients with a mean injury severity score (ISS) of 20 (range, 1 to 59) had a mean of 5.4 rib fractures (range, 1 to 29). Forty-four (22%) patients had bilateral fractures, 15 (7%) had flail chest, and 92 (45%) had associated injury. One hundred eighty-seven patients were followed 2 months or more. One hundred ten (59%) patients had prolonged chest wall pain and 142 (76%) had prolonged disability. Among 111 patients with isolated rib fractures, 67 (64%) had prolonged chest wall pain and 69 (66%) had prolonged disability. MPQ PPI was predictive of prolonged pain (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.4 to 2.5), and prolonged disability (OR, 2.2; 95% CI, 1.5 to 3.4). The presence of significant associated injuries was predictive of prolonged disability (OR, 5.9; 95% CI, 1.4 to 29). Prolonged chest wall pain is common, and the contribution of rib fractures to disability is greater than traditionally expected. Further investigation into more effective therapies that prevent prolonged pain and disability after rib fractures is needed. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Genetic variants for long QT syndrome among infants and children from a statewide newborn hearing screening program cohort.

    Science.gov (United States)

    Chang, Ruey-Kang R; Lan, Yueh-Tze; Silka, Michael J; Morrow, Hallie; Kwong, Alan; Smith-Lang, Janna; Wallerstein, Robert; Lin, Henry J

    2014-03-01

    Autosomal recessive long QT syndrome (LQTS), or Jervell and Lange-Nielsen syndrome (JLNS), can be associated with sensorineural hearing loss. We aimed to explore newborn hearing screening combined with electrocardiograms (ECGs) for early JLNS detection. In California, we conducted statewide, prospective ECG screening of children ≤ 6 years of age with unilateral or bilateral, severe or profound, sensorineural or mixed hearing loss. Families were identified through newborn hearing screening and interviewed about medical and family histories. Twelve-lead ECGs were obtained. Those with positive histories or heart rate corrected QT (QTc) intervals ≥ 450 ms had repeat ECGs. DNA sequencing of 12 LQTS genes was performed for repeat QTc intervals ≥ 450 ms. We screened 707 subjects by ECGs (number screened/number of responses = 91%; number of responses/number of families who were mailed invitations = 54%). Of these, 73 had repeat ECGs, and 19 underwent gene testing. No subject had homozygous or compound heterozygous LQTS mutations, as in JLNS. However, 3 individuals (with QTc intervals of 472, 457, and 456 ms, respectively) were heterozygous for variants that cause truncation or missplicing: 2 in KCNQ1 (c.1343dupC or p.Glu449Argfs*14; c.1590+1G>A or p.Glu530sp) and 1 in SCN5A (c.5872C>T or p.Arg1958*). In contrast to reports of JLNS in up to 4% of children with sensorineural hearing loss, we found no examples of JLNS. Because the 3 variants identified were unrelated to hearing, they likely represent the prevalence of potential LQTS mutations in the general population. Further studies are needed to define consequences of such mutations and assess the overall prevalence. Published by Mosby, Inc.

  19. Application of Open Source Scientific Numerical Calculation Software QtOctave%开源科学数值计算软件QtOctave的应用

    Institute of Scientific and Technical Information of China (English)

    关东; 岳云娟; 邹晨

    2012-01-01

    QtOctave is a Linux operating system based on graphical interface on the integrated development environment of scientific numerical calculation software. It is a Matlab-like software by the GNU project support, and its Octave language is compatible with Matlab m language. QtOctave can be easily applied to a lorentz attractor numerical simulation experiment. It shows that QtOctave has the same advantages as Matalb: easy to use, easy to learn and powerful. QtOctave has a high val- ue of popularization in the numerical simulation experiment and teaching activities.%QtOctave是一个Linux操作系统之上的基于图形界面的集成开发环境的科学数值计算软件。它是一个由GNU项目支持的类Matlab软件,其使用的Octave语言兼容Matlab的m语言。以使用QtOctave进行洛伦兹吸引子的数值模拟实验为例,说明该软件和Matlab同样具有易使用、易学习、功能强大的优点,在数值模拟实验和教学活动中具备较好的推广价值。

  20. QT intervals and QT dispersion determined from a 12-lead 24-hour Holter recording in patients with coronary artery disease and patients with heart failure

    DEFF Research Database (Denmark)

    Hansen, S.; Rasmussen, V.; Torp-Pedersen, C.;

    2008-01-01

    modes of lead selection was used: all 12-leads (QTdisp 12), only precordial leads (QTdisp 6), and one pair of preselected leads (QTdisp 2) in a 24-hour Holter recording every fourth hour each comprising 10 consecutive measurements in 54 healthy subjects, 29 patients with coronary artery disease (CAD......), and 29 patients with heart failure (HF). RESULTS: A significant circadian variation was observed in healthy subjects when modes QTdisp 12 and QTdisp 6 were used (Mean +/- SD 35.58 +/- 16.48 ms; P ... in QTdisp 12 (Mean +/- SD 33.13 +/- 14.86 ms; P detected in healthy subjects and in patients with uncomplicated CAD, but not in those who...

  1. QT variability index on 24-hour Holter independently predicts mortality in patients with heart failure: analysis of Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca (GISSI-HF) trial.

    Science.gov (United States)

    Dobson, Craig P; La Rovere, Maria Teresa; Pinna, Gian Domenico; Goldstein, Robert; Olsen, Cara; Bernardinangeli, Marino; Veniani, Marco; Midi, Paolo; Tavazzi, Luigi; Haigney, Mark

    2011-08-01

    Increased temporal variability of repolarization, as reflected by QT interval variability measured over 10-15 minutes, predicted spontaneous ventricular arrhythmias and death in implantable cardioverter-defibrillator patients in mild to moderate heart failure (HF). The purpose of this study was to test our hypothesis that increased mean QT variability over 24 hours would be associated with increased cardiovascular (CV) mortality in a heterogeneous HF population. The Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca-Heart Failure trial prospectively enrolled subjects with HF of any cause. Twenty-four-hour Holter recordings from 268 subjects were analyzed using a template-matching, semiautomatic algorithm to measure QT and heart rate time series in sequential 5-minute epochs over 24 hours. The QT variability index (QTVI) was expressed as the log ratio of the normalized QT variance over normalized heart rate variance. Total and CV mortality were assessed as a function of continuous and dichotomous QTVI (>-0.84) in univariate and multivariable Cox proportional hazards models, adjusting for significant clinical predictors. After a median of 47 months, there were 53 deaths, of which 44 were from CV causes. A significant association with the outcome was found for QTVI both as continuous and dichotomous variables after adjustment for clinical covariates (age >70, New York Heart Association class III-IV, left ventricular ejection fraction, nonsustained ventricular tachycardia, creatinine): QTVI hazard ratio (HR) 4.0 (confidence interval [CI] 1.8-88; P = .008) for total and 4.4 (CI 1.9-10.1; P = .0006) for CV mortality; QTVI >-0.84 HR 2.0 (CI 1.1-3.6; P = .02) for total and 2.1 (CI 1.1-3.8; P = .02) for CV mortality. Increased repolarization lability, as reflected in QTVI measured over 24 hours, is associated with increased risk for total and CV mortality in a heterogeneous population with chronic HF. Published by Elsevier Inc.

  2. Effect of Loss of Heart Rate Variability on T-Wave Heterogeneity and QT Variability in Heart Failure Patients: Implications in Ventricular Arrhythmogenesis.

    Science.gov (United States)

    Nayyar, Sachin; Hasan, Muhammad A; Roberts-Thomson, Kurt C; Sullivan, Thomas; Baumert, Mathias

    2017-03-03

    Heart rate variability (HRV) modulates dynamics of ventricular repolarization. A diminishing value of HRV is associated with increased vulnerability to life-threatening ventricular arrhythmias, however the causal relationship is not well-defined. We evaluated if fixed-rate atrial pacing that abolishes the effect of physiological HRV, will alter ventricular repolarization wavefronts and is relevant to ventricular arrhythmogenesis. The study was performed in 16 subjects: 8 heart failure patients with spontaneous ventricular tachycardia [HFVT], and 8 subjects with structurally normal hearts (H Norm). The T-wave heterogeneity descriptors [total cosine angle between QRS and T-wave loop vectors (TCRT, negative value corresponds to large difference in the 2 loops), T-wave morphology dispersion, T-wave loop dispersion] and QT intervals were analyzed in a beat-to-beat manner on 3-min records of 12-lead surface ECG at baseline and during atrial pacing at 80 and 100 bpm. The global T-wave heterogeneity was expressed as mean values of each of the T-wave morphology descriptors and variability in QT intervals (QTV) as standard deviation of QT intervals. Baseline T-wave morphology dispersion and QTV were higher in HFVT compared to H Norm subjects (p ≤ 0.02). While group differences in T-wave morphology dispersion and T-wave loop dispersion remained unaltered with atrial pacing, TCRT tended to fall more in HFVT patients compared to H Norm subjects (interaction p value = 0.086). Atrial pacing failed to reduce QTV in both groups, however group differences were augmented (p < 0.0001). Atrial pacing and consequent loss of HRV appears to introduce unfavorable changes in ventricular repolarization in HFVT subjects. It widens the spatial relationship between wavefronts of ventricular depolarization and repolarization. This may partly explain the concerning relation between poorer HRV and the risk of ventricular arrhythmias.

  3. Porting and Implementation of phoneME Feature Based on Qt/Embedded%基于Qt/Embedded的phoneME Feature移植与实现

    Institute of Scientific and Technical Information of China (English)

    高攀; 杨斌; 刘建敏

    2011-01-01

    phoneME Feature is a high-performance Java Virtual Machine,however Qt/Embedded is a C + + GUI library for the embedded system.In order to make phoneME Feature run the ARM-Linux target platform with the Qt/Embedded graphics, it' s necessary to study the relationship between phoneME Feature and the Qt/Embedded graphics library, the method and procedure of porting of phoneME Feature to the target platform based on Qt/Embedded deeply.The setps of porting mainly contains setting up the build environment,building PCSL( Portable Common Services Library) ,building CLDC (Connected Limited Device Configuration), building MI DP( Mobile Information Device Profile) and downloading the Java Virtual Machine.%phoneME Feature是一个高性能的Java虚拟机,而Qt/Embedded是一个面向嵌入式系统的C++图形界面库.为了使phoneME Feature在带有Qt/Embedded图形库的ARM-Linux目标平台上运行,就必须深入研究phoneME Feature与Q∥Embedded图形库的关系,以及在目标平台下编译和移植带有Qt/Embedded图形接口的phoneME Feature的方法和步骤.移植过程主要包括编译环境的搭建、PCSL(Portable Common Services Library)的编译、CLDC(Connected Limited Device Configuration)的编译、MIDP(Mobile Information Device Profile)的编译和Java虚拟机的下载.

  4. Impaired cardiac sympathetic innervation in symptomatic patients with long QT syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Kies, Peter; Stegger, Lars; Schober, Otmar [University Hospital Muenster, Department of Nuclear Medicine, Muenster (Germany); Paul, Matthias; Moennig, Gerold [University Hospital Muenster, Department for Cardiology and Angiology, Muenster (Germany); Gerss, Joachim [University of Muenster, Institute of Biostatistics and Clinical Research, Muenster (Germany); Wichter, Thomas [Marienhospital Osnabrueck, Department of Cardiology, Niels-Stensen-Kliniken, Osnabrueck (Germany); Schaefers, Michael [University of Muenster, European Institute of Molecular Imaging - EIMI, Muenster (Germany); Schulze-Bahr, Eric [University Hospital Muenster, Department for Cardiology and Angiology, Muenster (Germany); University Hospital Muenster, Institute for Genetics of Heart Diseases, Muenster (Germany)

    2011-10-15

    Increased sympathetic activation is a key modifier for arrhythmogenesis in patients with long QT syndrome (LQTS), a congenital channelopathy. Therefore, we investigated cardiac sympathetic function using {sup 123}I-metaiodobenzylguanidine (MIBG) single photon emission computed tomography (SPECT) in a cohort of symptomatic LQTS patients and correlated these findings with the underlying genotype. [{sup 123}I]MIBG SPECT was performed in 28 LQTS patients. Among these, 18 patients (64%) had a previous syncope and 10 patients (36%) survived sudden cardiac arrest. Patients were characterized in terms of genetic subtypes and QTc interval on surface ECGs. SPECT images were analysed for regional [{sup 123}I]MIBG uptake in a 33-segment bullseye scheme and compared to those obtained from 10 age-matched healthy control subjects (43 {+-} 12 years). An abnormal {sup 123}I-MIBG scan was found in 17 of 28 LQTS patients (61%) with a tracer reduction mainly located in the anteroseptal segments of the left ventricle. This finding was independent of the genetic LQTS subtype. In addition, no differences were found between LQTS patients with a QTc >500 ms vs <500 ms or those suffering from syncope vs VF (p > 0.05). A distinct regional pattern of impaired cardiac sympathetic function was identified in the majority of symptomatic LQTS patients. This innervation defect was independent of the underlying genotype and clinical disease expression. (orig.)

  5. P-wave and QT dispersion in patients with conversion disorder.

    Science.gov (United States)

    Izci, Filiz; Hocagil, Hilal; Izci, Servet; Izci, Vedat; Koc, Merve Iris; Acar, Rezzan Deniz

    2015-01-01

    The aim of this study was to investigate QT dispersion (QTd), which is the noninvasive marker of ventricular arrhythmia and sudden cardiac death, and P-wave dispersion, which is the noninvasive marker of atrial arrhythmia, in patients with conversion disorder (CD). A total of 60 patients with no known organic disease who were admitted to outpatient emergency clinic and were diagnosed with CD after psychiatric consultation were included in this study along with 60 healthy control subjects. Beck Anxiety Inventory and Beck Depression Scale were administered to patients and 12-lead electrocardiogram measurements were obtained. Pd and QTd were calculated by a single blinded cardiologist. There was no statistically significant difference in terms of age, sex, education level, socioeconomic status, weight, height, and body mass index between CD patients and controls. Beck Anxiety Inventory scores (25.2±10.8 and 3.8±3.2, respectively, Pconversion patients and control group (46±5.7 vs 44±5.5, respectively, P=0.156). Regarding QTc and QTd, there was a statistically significant increase in all intervals in conversion patients (416±10 vs 398±12, Pdisorders was also observed in CD patients. QTc and QTd were significantly increased compared to the control group in patients with CD. These results suggest a possibility of increased risk of ventricular arrhythmia resulting from QTd in CD patients. Larger samples are needed to evaluate the clinical course and prognosis in terms of arrhythmia risk in CD patients.

  6. Risk prediction of cardiovascular death based on the QTc interval

    DEFF Research Database (Denmark)

    Nielsen, Jonas B; Graff, Claus; Rasmussen, Peter V

    2014-01-01

    .1 years, 6647 persons died from cardiovascular causes. Long-term risks of CVD were estimated for subgroups defined by age, gender, cardiovascular disease, and QTc interval categories. In general, we observed an increased risk of CVD for both very short and long QTc intervals. Prolongation of the QTc......AIMS: Using a large, contemporary primary care population we aimed to provide absolute long-term risks of cardiovascular death (CVD) based on the QTc interval and to test whether the QTc interval is of value in risk prediction of CVD on an individual level. METHODS AND RESULTS: Digital...... interval resulted in the worst prognosis for men whereas in women, a very short QTc interval was equivalent in risk to a borderline prolonged QTc interval. The effect of the QTc interval on the absolute risk of CVD was most pronounced in the elderly and in those with cardiovascular disease whereas...

  7. Isolation of avian bornaviruses from psittacine birds using QT6 quail cells in Japan.

    Science.gov (United States)

    Horie, Masayuki; Sassa, Yukiko; Iki, Haruko; Ebisawa, Kazumasa; Fukushi, Hideto; Yanai, Tokuma; Tomonaga, Keizo

    2016-02-01

    Avian bornaviruses (ABVs) were recently discovered as the causative agents of proventricular dilatation disease (PDD). Although molecular epidemiological studies revealed that ABVs exist in Japan, no Japanese isolate has been reported thus far. In this study, we isolated four strains of Psittaciform 1 bornavirus from psittacine birds affected by PDD using QT6 quail cells. To our knowledge, this is the first report to isolate ABVs in Japan and to show that QT6 cells are available for ABV isolation. These isolates and QT6 cells would be powerful tools for elucidating the fundamental biology and pathogenicity of ABVs.

  8. Qt-sovelluksen uudelleenkirjoittaminen Android-käyttöjärjestelmälle

    OpenAIRE

    Lehtonen, Joonas

    2012-01-01

    Tässä opinnäytetyössä selvitettiin, millaisia haasteita ja mahdollisuuksia Android-alusta tarjoaa Qt-sovelluskehittäjälle. Näkokulmaksi otettiin tilanne, jossa olemassa oleva Symbianille tehty Qt-sovellus kirjoitetaan alusta alkaen uudelleen Androidille. Qt on sovelluskehyksenä menettänyt merkitystään sen jälkeen, kun Nokia ilmoitti aloittaneensa yhteistyön Microsoftin kanssa ja samalla hylkäävänsä hiljalleen Symbian-alustan. Samaan aikaan Android on parissa vuodessa kasvanut merkittäväk...

  9. QT-Based Monitoring System of Multi-Functional Laboratory

    Directory of Open Access Journals (Sweden)

    Li Xiaoling

    2012-11-01

    Full Text Available Regarding the embedded processor as the core, this study utilizes various cutting-edge technologies such as wireless LAN, USB interface, Bluetooth, multimedia, etc., to propose the design program of QT-based security monitoring system. Taking the lab environment in school as an example, this system has achieved the security monitoring, information transmission and control of certain equipment. Besides, it has cut the Linux kernel module reasonably and explored the touch screen, serial port, wireless LAN, Bluetooth, USB and other resources, thus realizing various functions, such as collection and processing of audio, video and security information and wireless communication. Thereby, users can carry out real-time monitoring for multiple locations through the wireless LAN.

  10. Optimisation of Embryonic and Larval ECG Measurement in Zebrafish for Quantifying the Effect of QT Prolonging Drugs: e60552

    National Research Council Canada - National Science Library

    Sundeep Singh Dhillon; Éva Dóró; István Magyary; Stuart Egginton; Attila Sík; Ferenc Müller

    2013-01-01

    ... and represent replacement in animal research with reduced bioethical concerns. We demonstrate here the utility of pre-feeding stage zebrafish larvae in detection of cardiac dysfunction by electrocardiography...

  11. Optimisation of embryonic and larval ECG measurement in zebrafish for quantifying the effect of QT prolonging drugs

    National Research Council Canada - National Science Library

    Dhillon, Sundeep Singh; Dóró, Eva; Magyary, István; Egginton, Stuart; Sík, Attila; Müller, Ferenc

    2013-01-01

    ... and represent replacement in animal research with reduced bioethical concerns. We demonstrate here the utility of pre-feeding stage zebrafish larvae in detection of cardiac dysfunction by electrocardiography...

  12. Optimal weighted combinatorial forecasting model of QT dispersion of ECGs in Chinese adults.

    Science.gov (United States)

    Wen, Zhang; Miao, Ge; Xinlei, Liu; Minyi, Cen

    2016-07-01

    This study aims to provide a scientific basis for unifying the reference value standard of QT dispersion of ECGs in Chinese adults. Three predictive models including regression model, principal component model, and artificial neural network model are combined to establish the optimal weighted combination model. The optimal weighted combination model and single model are verified and compared. Optimal weighted combinatorial model can reduce predicting risk of single model and improve the predicting precision. The reference value of geographical distribution of Chinese adults' QT dispersion was precisely made by using kriging methods. When geographical factors of a particular area are obtained, the reference value of QT dispersion of Chinese adults in this area can be estimated by using optimal weighted combinatorial model and reference value of the QT dispersion of Chinese adults anywhere in China can be obtained by using geographical distribution figure as well.

  13. Solving the Petri-Nets to Statecharts Transformation Case with FunnyQT

    Directory of Open Access Journals (Sweden)

    Tassilo Horn

    2013-11-01

    Full Text Available FunnyQT is a model querying and model transformation library for the functional Lisp-dialect Clojure providing a rich and efficient querying and transformation API. This paper describes the FunnyQT solution to the TTC 2013 Petri-Nets to Statcharts Transformation Case. This solution has won the best overall solution award and the best efficiency award for this case.

  14. PENGARUH MODEL PEMBELAJARAN QUANTUM TEACHING BERBANTUAN MODUL QT-BILINGUAL TERHADAP HASIL BELAJAR SISWA

    Directory of Open Access Journals (Sweden)

    Husna Amalana

    2015-11-01

    Full Text Available Quantum teaching learning model supported by QT(Quantum Teaching-bilingual module emphasize optimization all multiple intelligences and learning style of students in learning activities with TANDUR frame. This research aimed to find out the effect of quantum teaching learning model supported by QT-bilingual module to the achievement of X grade students of SMA in Kedungwuni, how much the effect magnitude, and how student response. This research uses true experimental design with X.1 and X.8 classes as reasearch samples which determined by cluster random sampling technique. Data were collected through documentation, test, observation and questionnaire method. The results of hypothesis test analysis showed correlation and determination coefficient are 0.54 and 29.16%. The results of questionnaire stated that the students’ response is very good to quantum teaching learning model assisted by QT-bilingual module. Based on the analysis, it can be concluded that quantum teaching learning model assisted by QT-bilingual module effects on student learning outcomes by achieving the medium level of effect with contribution is 29.16%. Students’ response is very good actually to quantum teaching learning model supported by QT-bilingual module.Keywords: Quantum Teaching, QT-Bilingual Module 

  15. Qt/Embedded在嵌入式Linux系统中的应用%Application of Qt/Embedded in Embedded Linux System

    Institute of Scientific and Technical Information of China (English)

    徐广毅; 张晓林; 崔迎炜; 蒋文军

    2004-01-01

    分析和讨论Qt/Embedded的主流版本3.x系列的底层实现技术;结合2.x版本系列和3.x版本系列,在两种不同的硬件平台(Intel PXA255开发系统与笔者自行设计的Motorola MC9328 MX1开发系统)上的移植过程,讨论Qt/Embedded的底层设备接口与应用移植技术.

  16. Evaluation of Electrocardiographic T-peak to T-end Interval in Subjects with Increased Epicardial Fat Tissue Thickness

    Directory of Open Access Journals (Sweden)

    Ozgur Kaplan

    2015-01-01

    Full Text Available AbstractBackground:The association between periatrial adiposity and atrial arrhythmias has been shown in previous studies. However, there are not enough available data on the association between epicardial fat tissue (EFT thickness and parameters of ventricular repolarization. Thus, we aimed to evaluate the association of EFT thickness with indices of ventricular repolarization by using T-peak to T-end (Tp-e interval and Tp-e/QT ratio.Methods:The present study included 50 patients whose EFT thickness ≥ 9 mm (group 1 and 40 control subjects with EFT thickness < 9 mm (group 2. Transthoracic echocardiographic examination was performed in all participants. QT parameters, Tp-e intervals and Tp-e/QT ratio were measured from the 12-lead electrocardiogram.Results:QTd (41.1 ± 2.5 vs 38.6 ± 3.2, p < 0.001 and corrected QTd (46.7 ± 4.7 vs 43.7 ± 4, p = 0.002 were significantly higher in group 1 when compared to group 2. The Tp-e interval (76.5 ± 6.3, 70.3 ± 6.8, p < 0.001, cTp-e interval (83.1 ± 4.3 vs. 76±4.9, p < 0.001, Tp-e/QT (0.20 ± 0.02 vs. 0.2 ± 0.02, p < 0.001 and Tp-e/QTc ratios (0.2 ± 0.01 vs. 0.18 ± 0.01, p < 0.001 were increased in group 1 in comparison to group 2. Significant positive correlations were found between EFT thickness and Tp-e interval (r = 0.548, p < 0.001, cTp-e interval (r = 0.259, p = 0.01, and Tp-e/QT (r = 0.662, p < 0.001 and Tp-e/QTc ratios (r = 0.560, p < 0.001.Conclusion:The present study shows that Tp-e and cTp-e interval, Tp-e/QT and Tp-e/QTc ratios were increased in subjects with increased EFT, which may suggest an increased risk of ventricular arrhythmia.

  17. Increased vulnerability of human ventricle to re-entrant excitation in hERG-linked variant 1 short QT syndrome.

    Directory of Open Access Journals (Sweden)

    Ismail Adeniran

    2011-12-01

    Full Text Available The short QT syndrome (SQTS is a genetically heterogeneous condition characterized by abbreviated QT intervals and an increased susceptibility to arrhythmia and sudden death. This simulation study identifies arrhythmogenic mechanisms in the rapid-delayed rectifier K(+ current (I(Kr-linked SQT1 variant of the SQTS. Markov chain (MC models were found to be superior to Hodgkin-Huxley (HH models in reproducing experimental data regarding effects of the N588K mutation on KCNH2-encoded hERG. These ionic channel models were then incorporated into human ventricular action potential (AP models and into 1D and 2D idealised and realistic transmural ventricular tissue simulations and into a 3D anatomical model. In single cell models, the N588K mutation abbreviated ventricular cell AP duration at 90% repolarization (APD(90 and decreased the maximal transmural voltage heterogeneity (δV during APs. This resulted in decreased transmural heterogeneity of APD(90 and of the effective refractory period (ERP: effects that are anticipated to be anti-arrhythmic rather than pro-arrhythmic. However, with consideration of transmural heterogeneity of I(Kr density in the intact tissue model based on the ten Tusscher-Noble-Noble-Panfilov ventricular model, not only did the N588K mutation lead to QT-shortening and increases in T-wave amplitude, but δV was found to be augmented in some local regions of ventricle tissue, resulting in increased tissue vulnerability for uni-directional conduction block and predisposing to formation of re-entrant excitation waves. In 2D and 3D tissue models, the N588K mutation facilitated and maintained re-entrant excitation waves due to the reduced substrate size necessary for sustaining re-entry. Thus, in SQT1 the N588K-hERG mutation facilitates initiation and maintenance of ventricular re-entry, increasing the lifespan of re-entrant spiral waves and the stability of scroll waves in 3D tissue.

  18. Identifying drug-induced repolarization abnormalities from distinct ECG patterns in congenital long QT syndrome: a study of sotalol effects on T-wave morphology

    DEFF Research Database (Denmark)

    Graff, Claus; Andersen, Mads P; Xue, Joel Q

    2009-01-01

    BACKGROUND: The electrocardiographic QT interval is used to identify drugs with potential harmful effects on cardiac repolarization in drug trials, but the variability of the measurement can mask drug-induced ECG changes. The use of complementary electrocardiographic indices of abnormal repolariz......BACKGROUND: The electrocardiographic QT interval is used to identify drugs with potential harmful effects on cardiac repolarization in drug trials, but the variability of the measurement can mask drug-induced ECG changes. The use of complementary electrocardiographic indices of abnormal...... are typical ECG patterns in LQT2. Blinded to labels, the new morphology measures were tested in a third group of 39 healthy subjects receiving sotalol. Over 3 days the sotalol group received 0, 160 and 320 mg doses, respectively, and a 12-lead Holter ECG was recorded for 22.5 hours each day. Drug...... with QTcF, p ECG patterns in LQT2 carriers effectively quantified repolarization changes induced by sotalol. Further studies are needed to validate whether this measure has...

  19. Electrophysiological effects of cetirizine, astemizole and D-sotalol in a canine model of long QT syndrome.

    Science.gov (United States)

    Weissenburger, J; Noyer, M; Cheymol, G; Jaillon, P

    1999-07-01

    Observations of torsades de pointes during therapy with terfenadine and astemizole has raised concern about the cardiac safety of non-sedating H1-antagonist agents. We compared cetirizine, another compound of that class, to D-sotalol and to astemizole in a model of acquired long QT syndrome. Open-chest surgery was performed in adult beagle dogs anaesthetized with halothane and thiopental. Bradycardia was produced with beta-adrenergic blockade and sinus node crush. Four left ventricular intramyocardial unipolar monophasic action potentials (MAP) were recorded during atrial pacing at basic cycle lengths (BCL) 400-1500 msec, before and during three successive 1-h drug infusions (0.14, 0.45 and 1.4 mg/kg/h for astemizole and cetirizine and 1.1, 2.2 and 4.5 mg/kg/h for D-sotalol). Dose- and bradycardia-dependent prolongations of MAP duration (MAPD) were produced by D-sotalol (P < 0.001) and astemizole (P < 0.001) but not by cetirizine. At BCL 1500 ms, the three infusions of astemizole prolonged endocardial MAPD from 323 +/- 8 msec (mean +/- SE) at baseline to 343 +/- 10, 379 +/- 13 and 468 +/- 26 msec, respectively (n = 9). Sotalol prolonged that MAPD from 339 +/- 6 msec to 377 +/- 7, 444 +/- 15 and 485 +/- 24 msec (n = 7). In contrast, cetirizine did not prolong MAPD: 341 +/- 8 msec at baseline Vs 330 +/- 8, 324 +/- 9 and 323 +/- 11 msec (n = 9). Drug-induced increase in transmural dispersion reached +79 +/- 19 msec after astemizole, +59 +/- 21 msec after D-sotalol and only +7 +/- 11 msec after cetirizine. Runs of ventricular tachycardias and torsades de pointes occurred during dose three of astemizole (5/9 dogs) and D-sotalol (4/7 dogs) but never during cetirizine. In the present model, astemizole and D-sotalol but not cetirizine prolonged MAPD and transmural dispersions of repolarization and produced torsades de pointes. These results suggest that the halothane-anaesthetized bradycardic dog could be a valuable model to discriminate drugs for their class III effects

  20. Interval arithmetic in calculations

    Science.gov (United States)

    Bairbekova, Gaziza; Mazakov, Talgat; Djomartova, Sholpan; Nugmanova, Salima

    2016-10-01

    Interval arithmetic is the mathematical structure, which for real intervals defines operations analogous to ordinary arithmetic ones. This field of mathematics is also called interval analysis or interval calculations. The given math model is convenient for investigating various applied objects: the quantities, the approximate values of which are known; the quantities obtained during calculations, the values of which are not exact because of rounding errors; random quantities. As a whole, the idea of interval calculations is the use of intervals as basic data objects. In this paper, we considered the definition of interval mathematics, investigated its properties, proved a theorem, and showed the efficiency of the new interval arithmetic. Besides, we briefly reviewed the works devoted to interval analysis and observed basic tendencies of development of integral analysis and interval calculations.

  1. Systolic time intervals after a seven-day orbital flight

    Science.gov (United States)

    Groza, P.; Vrâncianu, R.; Lazǎr, M.; Baevski, R. M.; Funtova, V. L.

    Heart rate, systolic time intervals (pre-ejection period, left ventricular ejection time), ejection fraction, stroke volume and QT interval of two cosmonauts (Leonid Popov - L.P. and Dumitru Prunariu - D.P.) were studied before, during, and after an ergometric bicycle exercise test performed before and after the seven-day Soviet-Romanian orbital flight on the Soyuz 40 - Salyut 6 Complex in May 1981. For this purpose one precordial electrocardiogram (ecg) and the ear photodensitogram (den) were recorded stimulaneously. The method used permitted recording even during exercise, Ecg and den signals were stored on magnetic tape, processed in an analogue device and in a digital computer. The data obtained after landing suggest a slight cardiac deconditioning in L.P., demonstrated especially by augmentation of the pre-ejection period, which was unchanged in D.P. corresponding to a sympathoadrenergic hypertonia. The seven-day orbital flight has not produced important cardiovascular changes.

  2. Comparison of QT dispersion between subclinical hypothyroid and euthyroid patients

    Directory of Open Access Journals (Sweden)

    Muharrem Kıskaç

    2010-06-01

    Full Text Available Objectives: The aim of this study was to investigate the relationship between subclinical hypothyroid and QTc dispersionindicating local heterogeneity in repolarization of myocardium, which is well known as independent cardiac risk factor for sudden death and ventricular arrhythmia.Materials and Methods: We compared QTc dispersion of subclinical hypothyroid patients, after treatment and healthy control group. We included a total of 50 patients with 41 women and 9 men in the study group. Electrocardiographywith 12 derivations, thyroid hormones, serum electrolytes and basic biochemical parameters were measured.The control group consisted of 25 healthy individuals.QT distances were calculated by using Bazet formula. The difference between the longest QTc and the shortest QTc distance was accepted as QTc dispersion (QTcd.Results: Comparison of subclinical hypothyroid patients, their euthyroidic period after treatment and healthy controlgroup, gave no significant differences in age, body weight, body mass index and free thyroxin values. However,significant difference was found in durations of QTd and QTcd between the subclinical hypothyroid, the control and the euthyroidic groups (p0.05.Conclusion: Our results suggested that subclinical hypothyroidpatients had longer QTc dispersion compared to euthyroidic period and healthy subjects. However there was no QTcd difference between the euthyroidic period and healthy control group.

  3. Long QT syndrome: an emerging role for inflammation and immunity

    Directory of Open Access Journals (Sweden)

    Pietro Enea eLazzerini

    2015-05-01

    Full Text Available The Long QT Syndrome (LQTS, classified as congenital or acquired, is a multi-factorial disorder of myocardial repolarization predisposing to life-threatening ventricular arrhythmias, particularly torsades de pointes. In the latest years inflammation and immunity have been increasingly recognized as novel factors crucially involved in modulating ventricular repolarization. In the present paper we critically review the available information on this topic, also analyzing putative mechanisms and potential interplays with the other etiologic factors, either acquired and inherited.Accumulating data indicate inflammatory activation as a potential cause of acquired LQTS. The putative underlying mechanisms are complex but essentially cytokine-mediated, including both direct actions on cardiomyocyte ion channels expression and function, and indirect effects resulting from an increased central nervous system sympathetic drive on the heart. Autoimmunity represents another recently arising cause of acquired LQTS. Indeed, increasing evidence demonstrates that autoantibodies may affect myocardial electric properties by directly cross-reacting with the cardiomyocyte and interfering with specific ion currents as a result of molecular mimicry mechanisms. Intriguingly, recent data suggest that inflammation and immunity may be also involved in modulating the clinical expression of congenital forms of LQTS, possibly triggering or enhancing electrical instability in patients who already are genetically predisposed to arrhythmias. In this view, targeting immuno-inflammatory pathways may in the future represent an attractive therapeutic approach in a number of LQTS patients, thus opening new exciting avenues in antiarrhythmic therapy.

  4. Long QT syndrome mutation detection by SNaPshot technique.

    Science.gov (United States)

    Edelmann, Jeanett; Schumann, Stefanie; Nastainczyk, Marina; Husser-Bollmann, Daniela; Lessig, Rüdiger

    2012-11-01

    Long QT syndrome (LQTS) is a cardiac disorder with an abnormality of cardiac rhythm associated with sudden death especially in younger, apparently healthy individuals. If there is no clear cause of death detectable during comprehensive coroner's inquest (autopsy-negative cases), you have to consider LQTS and other heritable arrhythmia syndromes. A molecular genetic screening regarding mutations in associated genes can help to ensure the cause of death and to protect affected family members. Genetic testing of LQTS, currently performed mainly by sequencing, is still very expensive and time consuming. With this study we present a rapid and reasonable method for the simultaneously screening of some of the most common mutations associated with LQTS, focused on the KCNQ1 and KCNH2 genes. With the method of SNaPshot minisequencing, a total of 58 mutations were analyzed in four multiplex assays which were successfully established and optimized. The comparison with samples previously analyzed by direct sequencing showed concordance. Furthermore, autopsy-negative cases were tested but no mutations could be observed in any of the specimen. The presented method is well suitable for LQTS mutation screening. An enhancement to further mutations and population-based investigations regarding mutation frequencies should be the aim of prospective studies.

  5. Probing cardiac repolarization reserve in drug safety assessment

    NARCIS (Netherlands)

    Nalos, L.

    2011-01-01

    Excessive prolongation of cardiac repolarization, manifested as QT prolongation on ECG, is common unwanted side effect of many drugs and drug candidates. Prolongation of QT interval may lead to life threatening cardiac arrhythmia – Torsade de Point (TdP). Number of drugs was withdrawn from the marke

  6. Qt/Embedded Transplant Supporting Touch Screen on the Linux Platform%Linux平台下支持触摸屏的Qt/Embedded移植

    Institute of Scientific and Technical Information of China (English)

    张敏; 张井岗

    2011-01-01

    随着嵌入式的发展,触摸屏以友善的人机交互性、操作简单灵活、输入速度快,已逐渐取代键盘,成为嵌入式系统的主流输入设备;而Qt作为跨平台的图形用户界面工具包诞生以后,已经扩展到了包括便携式设备在内的几乎当今程序设计的所有领域.以S3C2416为例,介绍了在Linux平台下支持触摸屏的Qt/Embedded移植的详细过程,包括系统环境介绍、带触摸屏库的Qt/Embedded的编译、Linux文件系统设置等,并挑选了一个demo程序对移植情况进行了检验.最后对支持触摸屏的嵌入式系统作了初步展望.%Along with the fast development of embedded system, touch screen has gradually replaced the keyboard and becomes the main input device in embedded systems. QT invented as a cross-platform GUI (graphical user interface) toolkit has extended to many fields of program design including portable devices. In this paper S3C2416 is exemplified to introduce the process of Qt / Embedded transplant supporting touch screen, which includes the system environment introduction, Qt / Embedded compiler with touch screen library, file system settings and so on. Then a demo program is selected to test the transplant. At last an outlook is made for the embedded system supporting touch screen.

  7. Corrected QT changes during antipsychotic treatment of children and adolescents

    DEFF Research Database (Denmark)

    Jensen, Karsten Gjessing; Juul, Klaus; Fink-Jensen, Anders

    2015-01-01

    -regression analyses evaluated the effect of age, sex, dose, and study duration on QTc. Incidences of study-defined QTc prolongation (>440-470 milliseconds), QTc >500 milliseconds, and QTc change >60 milliseconds were also evaluated. RESULTS: A total of 55 studies were meta-analyzed, evaluating 108 treatment arms...

  8. Calcium Transients Closely Reflect Prolonged Action Potentials in iPSC Models of Inherited Cardiac Arrhythmia

    Directory of Open Access Journals (Sweden)

    C. Ian Spencer

    2014-08-01

    Full Text Available Long-QT syndrome mutations can cause syncope and sudden death by prolonging the cardiac action potential (AP. Ion channels affected by mutations are various, and the influences of cellular calcium cycling on LQTS cardiac events are unknown. To better understand LQTS arrhythmias, we performed current-clamp and intracellular calcium ([Ca2+]i measurements on cardiomyocytes differentiated from patient-derived induced pluripotent stem cells (iPS-CM. In myocytes carrying an LQT2 mutation (HERG-A422T, APs and [Ca2+]i transients were prolonged in parallel. APs were abbreviated by nifedipine exposure and further lengthened upon releasing intracellularly stored Ca2+. Validating this model, control iPS-CM treated with HERG-blocking drugs recapitulated the LQT2 phenotype. In LQT3 iPS-CM, expressing NaV1.5-N406K, APs and [Ca2+]i transients were markedly prolonged. AP prolongation was sensitive to tetrodotoxin and to inhibiting Na+-Ca2+ exchange. These results suggest that LQTS mutations act partly on cytosolic Ca2+ cycling, potentially providing a basis for functionally targeted interventions regardless of the specific mutation site.

  9. Model for long QT syndrome type 2 using human iPS cells demonstrates arrhythmogenic characteristics in cell culture

    Directory of Open Access Journals (Sweden)

    Anna L. Lahti

    2012-03-01

    Long QT syndrome (LQTS is caused by functional alterations in cardiac ion channels and is associated with prolonged cardiac repolarization time and increased risk of ventricular arrhythmias. Inherited type 2 LQTS (LQT2 and drug-induced LQTS both result from altered function of the hERG channel. We investigated whether the electrophysiological characteristics of LQT2 can be recapitulated in vitro using induced pluripotent stem cell (iPSC technology. Spontaneously beating cardiomyocytes were differentiated from two iPSC lines derived from an individual with LQT2 carrying the R176W mutation in the KCNH2 (HERG gene. The individual had been asymptomatic except for occasional palpitations, but his sister and father had died suddenly at an early age. Electrophysiological properties of LQT2-specific cardiomyocytes were studied using microelectrode array and patch-clamp, and were compared with those of cardiomyocytes derived from control cells. The action potential duration of LQT2-specific cardiomyocytes was significantly longer than that of control cardiomyocytes, and the rapid delayed potassium channel (IKr density of the LQT2 cardiomyocytes was significantly reduced. Additionally, LQT2-derived cardiac cells were more sensitive than controls to potentially arrhythmogenic drugs, including sotalol, and demonstrated arrhythmogenic electrical activity. Consistent with clinical observations, the LQT2 cardiomyocytes demonstrated a more pronounced inverse correlation between the beating rate and repolarization time compared with control cells. Prolonged action potential is present in LQT2-specific cardiomyocytes derived from a mutation carrier and arrhythmias can be triggered by a commonly used drug. Thus, the iPSC-derived, disease-specific cardiomyocytes could serve as an important platform to study pathophysiological mechanisms and drug sensitivity in LQT2.

  10. Influence of olanzapine on QT variability and complexity measures of heart rate in patients with schizophrenia.

    Science.gov (United States)

    Bär, Karl-Jürgen; Koschke, Mandy; Berger, Sandy; Schulz, Steffen; Tancer, Manuel; Voss, Andreas; Yeragani, Vikram K

    2008-12-01

    Previous studies have shown that untreated patients with acute schizophrenia present with reduced heart rate variability and complexity as well as increased QT variability. This autonomic dysregulation might contribute to increased cardiac morbidity and mortality in these patients. However, the additional effects of newer antipsychotics on autonomic dysfunction have not been investigated, applying these new cardiac parameters to gain information about the regulation at sinus node level as well as the susceptibility to arrhythmias. We have investigated 15 patients with acute schizophrenia before and after established olanzapine treatment and compared them with matched controls. New nonlinear parameters (approximate entropy, compression entropy, fractal dimension) of heart rate variability and also the QT-variability index were calculated. In accordance with previous results, we have observed reduced complexity of heart rate regulation in untreated patients. Furthermore, the QT-variability index was significantly increased in unmedicated patients, indicating increased repolarization lability. Reduction of the heart rate regulation complexity after olanzapine treatment was seen, as measured by compression entropy of heart rate. No change in QT variability was observed after treatment. This study shows that unmedicated patients with acute schizophrenia experience autonomic dysfunction. Olanzapine treatment seems to have very little additional impact in regard to the QT variability. However, the decrease in heart rate complexity after olanzapine treatment suggests decreased cardiac vagal function, which may increase the risk for cardiac mortality. Further studies are warranted to gain more insight into cardiac regulation in schizophrenia and the effect of novel antipsychotics.

  11. Changes in heart rate variability and QT variability during the first trimester of pregnancy.

    Science.gov (United States)

    Carpenter, R E; D'Silva, L A; Emery, S J; Uzun, O; Rassi, D; Lewis, M J

    2015-03-01

    The risk of new-onset arrhythmia during pregnancy is high, presumably relating to changes in both haemodynamic and cardiac autonomic function. The ability to non-invasively assess an individual's risk of developing arrhythmia during pregnancy would therefore be clinically significant. We aimed to quantify electrocardiographic temporal characteristics during the first trimester of pregnancy and to compare these with non-pregnant controls. Ninety-nine pregnant women and sixty-three non-pregnant women underwent non-invasive cardiovascular and haemodynamic assessment during a protocol consisting of various physiological states (postural manoeurvres, light exercise and metronomic breathing). Variables measured included stroke volume, cardiac output, heart rate, heart rate variability, QT and QT variability and QTVI (a measure of the variability of QT relative to that of RR). Heart rate (p variability (p heart rate variability was reduced in pregnancy in all states (p heart rate variability, reflecting a reduction in parasympathetic tone and an increase in sympathetic activity. QTVI shifted to a less favourable value, reflecting a greater than normal amount of QT variability. QTVI appears to be a useful method for quantifying changes in QT variability relative to RR (or heart rate) variability, being sensitive not only to physiological state but also to gestational age. We support the use of non-invasive markers of cardiac electrical variability to evaluate the risk of arrhythmic events in pregnancy, and we recommend the use of multiple physiological states during the assessment protocol.

  12. Diurnal variation of ventricular repolarization in a large family with LQT3-Brugada syndrome characterized by nocturnal sudden death

    NARCIS (Netherlands)

    van den Berg, MP; Haaksma, J; Veeger, NJGM; Wilde, AAM

    BACKGROUND In patients with long-QT syndrome type 3 (LQT3), symptoms occur particularly at rest or during sleep. As to the underlying mechanism, excessive prolongation of the QT interval at slow heart rates probably plays a role. OBJECTIVES The purpose of the present study was to investigate QT

  13. The novel C-terminal KCNQ1 mutation M520R alters protein trafficking

    DEFF Research Database (Denmark)

    Schmitt, Nicole; Calloe, Kirstine; Nielsen, Nathalie Hélix

    2007-01-01

    The long QT-syndrome is characterized by a prolongation of the QT-interval and tachyarrhythmias causing syncopes and sudden death. We identified the missense mutation M520R in the calmodulin binding domain of the Kv7.1 channel from a German family with long QT-syndrome. Heterologous expression of...

  14. Rosuvastatin blocks hERG current and prolongs cardiac repolarization.

    Science.gov (United States)

    Plante, Isabelle; Vigneault, Patrick; Drolet, Benoît; Turgeon, Jacques

    2012-02-01

    Blocking of the potassium current I(Kr) [human ether-a-go-go related gene (hERG)] is generally associated with an increased risk of long QT syndrome (LQTS). The 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor, rosuvastatin, is a methanesulfonamide derivative, which shows structural similarities with several I(Kr) blockers. Hence, we assessed the effects of rosuvastatin on cardiac repolarization by using in vitro, ex vivo, and in vivo models. Patch clamp experiments on hERG-transfected human embryonic kidney (HEK) 293 cells established the potency of rosuvastatin to block hERG [half maximal inhibitory concentration (IC(50) ) = 195 nM]. We showed in isolated guinea pig hearts that 195 nM rosuvastatin prolonged (basic cycle length of 250 ms; p cancer resistance protein (BCRP), multidrug resistance gene (MDR1)] and influx [organic anion transporting polypeptide (OATP) 2B1] transporters involved in the disposition and cardiac distribution of the drug. Genetic polymorphisms observed for BCRP, MDR1, and OATP2B1, and IC(50) determined for hERG blocking lead us to propose that some patients may be at risk of rosuvastatin-induced LQTS.

  15. Big Boss Interval Games

    NARCIS (Netherlands)

    Alparslan-Gok, S.Z.; Brânzei, R.; Tijs, S.H.

    2008-01-01

    In this paper big boss interval games are introduced and various characterizations are given. The structure of the core of a big boss interval game is explicitly described and plays an important role relative to interval-type bi-monotonic allocation schemes for such games. Specifically, each element

  16. Factors influencing uptake of familial long QT syndrome genetic testing.

    Science.gov (United States)

    Burns, Charlotte; McGaughran, Julie; Davis, Andrew; Semsarian, Christopher; Ingles, Jodie

    2016-02-01

    Ongoing challenges of clinical assessment of long QT syndrome (LQTS) highlight the importance of genetic testing in the diagnosis of asymptomatic at-risk family members. Effective access, uptake, and communication of genetic testing are critical for comprehensive cascade family screening and prevention of disease complications such as sudden cardiac death. The aim of this study was to describe factors influencing uptake of LQTS genetic testing, including those relating to access and family communication. We show those who access genetic testing are overrepresented by the socioeconomically advantaged, and that although overall family communication is good, there are some important barriers to be addressed. There were 75 participants (aged 18 years or more, with a clinical and/or genetic diagnosis of LQTS; response rate 71%) who completed a survey including a number of validated scales; demographics; and questions about access, uptake, and communication. Mean age of participants was 46 ± 16 years, 20 (27%) were males and 60 (80%) had genetic testing with a causative gene mutation in 42 (70%). Overall uptake of cascade testing within families was 60% after 4 years from proband genetic diagnosis. All participants reported at least one first-degree relative had been informed of their risk, whereas six (10%) reported at least one first-degree relative had not been informed. Those who were anxious or depressed were more likely to perceive barriers to communicating. Genetic testing is a key aspect of care in LQTS families and intervention strategies that aim to improve equity in access and facilitate effective family communication are needed.

  17. Holter monitoring in the evaluation of congenital long QT syndrome.

    Science.gov (United States)

    Mauriello, Daniel A; Johnson, Jonathan N; Ackerman, Michael J

    2011-09-01

    Long QT syndrome (LQTS) is a potentially lethal cardiac channelopathy that affects one in 2,000 persons; causes syncope, seizures, and sudden death; and is both under- and overdiagnosed. LQTS diagnostic miscues have stemmed from assessment of ambulatory electrocardiographic monitoring (Holter) results. We sought to determine the prevalence of positive Holter monitor tests and its diagnostic significance in evaluating LQTS. We performed an institutional review board-approved review of patients evaluated in our LQTS clinic from 2000 to 2009 who had Holter testing during their evaluation. Included patients (N = 473) were diagnosed with LQTS or dismissed as otherwise normal. Holters classified as positive had an episode of nonsustained ventricular tachycardia, supraventricular tachycardia, ≥4 couplets/day, ≥10 premature ventricular contractions/hour, or >5-second sinus pause. Among 209 patients dismissed as normal (128 females, average age 21 ± 15 years, average QTc 424 ± 39 ms), 27 (12.9%) had a positive Holter, while among 264 patients with LQTS (149 females, average age 22 ± 16 years, average QTc 472 ± 41 ms), 30 (11.3%) had a positive Holter (P = NS). Patients with LQT3 (5/23, 21%) and genotype-negative LQTS (5/19, 26%) had a higher rate of positive Holter testing compared to LQT1 patients (7/124, 6%, P Holters, only one (0.2%) impacted clinical decision making. Routine Holter monitoring appears to be of minimal clinical utility from a diagnostic and prognostic perspective in evaluating LQTS, and may not be cost effective. Whether Holter monitoring aids in therapeutic decisions such as dosing or whether ambulatory QTc measurements, provided by some newer devices, might help in the diagnostic evaluation warrants further scrutiny. ©2011, The Authors. Journal compilation ©2011 Wiley Periodicals, Inc.

  18. Cyamemazine metabolites: effects on human cardiac ion channels in-vitro and on the QTc interval in guinea pigs.

    Science.gov (United States)

    Crumb, William; Benyamina, Amine; Arbus, Christophe; Thomas, George P; Garay, Ricardo P; Hameg, Ahcène

    2008-11-01

    Monodesmethyl cyamemazine and cyamemazine sulfoxide, the two main metabolites of the antipsychotic and anxiolytic phenothiazine cyamemazine, were investigated for their effects on the human ether-à-go-go related gene (hERG) channel expressed in HEK 293 cells and on native I(Na), I(Ca), I(to), I(sus) or I(K1) of human atrial myocytes. Additionally, cyamemazine metabolites were compared with terfenadine for their effects on the QT interval in anaesthetized guinea pigs. Monodesmethyl cyamemazine and cyamemazine sulfoxide reduced hERG current amplitude, with IC50 values of 0.70 and 1.53 microM, respectively. By contrast, at a concentration of 1 microM, cyamemazine metabolites failed to significantly affect I(Na), I(to), I(sus) or I(K1) current amplitudes. Cyamemazine sulfoxide had no effect on I(Ca) at 1 microM, while at this concentration, monodesmethyl cyamemazine only slightly (17%), albeit significantly, inhibited I(Ca) current. Finally, cyamemazine metabolites (5 mg kg(-1) i v.) were unable to significantly prolong QTc values in the guinea pig. Conversely, terfenadine (5 mg kg(-1) i.v.) significantly increased QTc values. In conclusion, cyamemazine metabolite concentrations required to inhibit hERG current substantially exceed those necessary to achieve therapeutic activity of the parent compound in humans. Moreover, cyamemazine metabolites, in contrast to terfenadine, do not delay cardiac repolarization in the anaesthetized guinea pig. These non-clinical findings explain the excellent cardiac safety records of cyamemazine during its 30 years of extensive therapeutic use.

  19. Assessing common classification methods for the identification of abnormal repolarization using indicators of T-wave morphology and QT interval

    DEFF Research Database (Denmark)

    Shakibfar, Saeed; Graff, Claus; Ehlers, Lars Holger;

    2012-01-01

    volunteers and LQT2 carriers were used to train classification algorithms using measures of T-wave morphology and QTc. The ability to correctly classify a third group of test subjects before and after receiving d,l-sotalol was evaluated using classification rules derived from training. As a single......Various parameters based on QTc and T-wave morphology have been shown to be useful discriminators for drug induced I(Kr)-blocking. Using different classification methods this study compares the potential of these two features for identifying abnormal repolarization on the ECG. A group of healthy...

  20. Reader variability in QT measurement due to measurement error and variability in leads selection: a simulation study comparing 2-way vs. 3-way interaction ANOVA model.

    Science.gov (United States)

    Natekar, Mili; Karnad, Dilip R; Salvi, Vaibhav; Ramasamy, Arumugam; Kerkar, Vaibhav; Panicker, Gopi Krishna; Kothari, Snehal

    2014-01-01

    Reader variability (RV) results from measurement differences or variability in lead used for QT measurements; the latter is not reflected in conventional methods for estimating RV. Mean and SD of QT intervals in 12 leads of 100 ECGs measured twice were used to simulate data sets with inter-RV of 5, 10, 15, 20, and 25 ms and intra-RV of 3, 6, 9, 12, and 15 ms. Six hundred twenty-five data sets were simulated such that different leads were used in Read1 and Read2 in 0, 10%, 20%, 30%, 40% of ECGs by 25 readers. RV was estimated using ANOVA interaction models: three-way model using Reader, ECG and lead as factors, and 2-way model using reader and ECG as factors. Estimates from three-way model accurately matched inter- and intra-RV that were introduced during simulation regardless of percent of ECGs with lead selection variability. The two-way model provides identical estimates when both reads are in same leads, but higher, more realistically estimates when measurements are made in different leads. © 2013.