WorldWideScience

Sample records for prolonged qt intervals

  1. 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...

  2. QT interval prolongation associated with sibutramine treatment

    Science.gov (United States)

    Harrison-Woolrych, Mira; Clark, David W J; Hill, Geraldine R; Rees, Mark I; Skinner, Jonathan R

    2006-01-01

    Aims To investigate a possible association of sibutramine with QT interval prolongation. Methods Post-marketing surveillance using prescription event monitoring in the New Zealand Intensive Medicines Monitoring Programme (IMMP) identified a case of QT prolongation and associated cardiac arrest in a patient taking sibutramine for 25 days. This patient was further investigated, including genotyping for long QT syndrome. Other IMMP case reports suggesting arrhythmias associated with sibutramine were assessed and further reports were obtained from the World Health Organisation (WHO) adverse drug reactions database. Results The index case displayed a novel mutation in a cardiac potassium channel subunit gene, KCNQ1, which is likely to prolong cardiac membrane depolarization and increase susceptibility to long QT intervals. Assessment of further IMMP reports identified five additional patients who experienced palpitations associated with syncope or presyncopal symptoms, one of whom had a QTc at the upper limit of normal. Assessment of reports from the WHO database identified three reports of QT prolongation and one fatal case of torsade de pointes in a patient also taking cisapride. Conclusions This case series suggests that sibutramine may be associated with QT prolongation and related dysrhythmias. Further studies are required, but in the meantime we would recommend that sibutramine should be avoided in patients with long QT syndrome and in patients taking other medicines that may prolong the QT interval. PMID:16542208

  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. 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...

  5. 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

    BACKGROUND: Information regarding QT-prolongation in the drug label may vary between products. This could lead to suboptimal risk minimization strategies. OBJECTIVE: To systematically assess the variation in the extent and content of information on QT prolongation in the summary of product......-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...

  6. Prognostic Significance Of QT Interval Prolongation In Adult ...

    African Journals Online (AJOL)

    Prognostic survival studies for heart-rate corrected QT interval in patients with chronic heart failure are few; although these patients are known to have a high risk of sudden cardiac death. This study was aimed at determining the mortality risk associated with prolonged QTc in Nigerians with heart failure. Ninety-six ...

  7. Translating QT interval prolongation from conscious dogs to humans.

    Science.gov (United States)

    Dubois, Vincent F S; Smania, Giovanni; Yu, Huixin; Graf, Ramona; Chain, Anne S Y; Danhof, Meindert; Della Pasqua, Oscar

    2017-02-01

    In spite of screening procedures in early drug development, uncertainty remains about the propensity of new chemical entities (NCEs) to prolong the QT/QTc interval. The evaluation of proarrhythmic activity using a comprehensive in vitro proarrhythmia assay does not fully account for pharmacokinetic-pharmacodynamic (PKPD) differences in vivo. In the present study, we evaluated the correlation between drug-specific parameters describing QT interval prolongation in dogs and in humans. Using estimates of the drug-specific parameter, data on the slopes of the PKPD relationships of nine compounds with varying QT-prolonging effects (cisapride, sotalol, moxifloxacin, carabersat, GSK945237, SB237376 and GSK618334, and two anonymized NCEs) were analysed. Mean slope estimates varied between -0.98 ms μM -1 and 6.1 ms μM -1 in dogs and -10 ms μM -1 and 90 ms μM -1 in humans, indicating a wide range of effects on the QT interval. Linear regression techniques were then applied to characterize the correlation between the parameter estimates across species. For compounds without a mixed ion channel block, a correlation was observed between the drug-specific parameter in dogs and humans (y = -1.709 + 11.6x; R 2  = 0.989). These results show that per unit concentration, the drug effect on the QT interval in humans is 11.6-fold larger than in dogs. Together with information about the expected therapeutic exposure, the evidence of a correlation between the compound-specific parameter in dogs and in humans represents an opportunity for translating preclinical safety data before progression into the clinic. Whereas further investigation is required to establish the generalizability of our findings, this approach can be used with clinical trial simulations to predict the probability of QT prolongation in humans. © 2016 The British Pharmacological Society.

  8. Safety information on QT-interval prolongation : comparison of European Union and United States drug labeling

    NARCIS (Netherlands)

    Warnier, Miriam J.; Holtkamp, Frank A.; Rutten, Frans H.; Hoes, Arno W.; de Boer, Anthonius; Mol, Peter G M; De Bruin, Marie L.

    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 approved

  9. Safety information on QT-interval prolongation : Comparison of European Union and United States drug labeling

    NARCIS (Netherlands)

    Warnier, Miriam J.; Holtkamp, Frank A.; Rutten, Frans H.; Hoes, Arno W.; de Boer, Anthonius; Mol, Peter G. M.; De Bruin, Marie L.

    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 approved

  10. QT Interval Prolongation as a Biomarker for Torsades de Pointes and Sudden Death in Drug Development

    Directory of Open Access Journals (Sweden)

    Gregory D. Sides

    2002-01-01

    Full Text Available Prolongation of the QT interval on the surface 12-lead electrocardiogram is widely accepted as a biomarker for the potential of a drug to produce torsades de pointes and/or sudden death. Detection of drug-induced prolongation of the QT interval in animals and man is frequently confounded by extrinsic and intrinsic factors that limit the ability to detect a true drug effect. In particular drugs that increase heart rate show an apparent increase in QT interval that confounds assessment of a true drug effect on cardiac ventricular repolarization. The basis for the use of the QT interval as a biomarker will be examined.

  11. Correlation of prolonged QT interval and severity of cirrhosis of liver

    International Nuclear Information System (INIS)

    Tarique, S.; Sarwar, S.

    2011-01-01

    To determine correlation between prolonged QT interval and severity of disease in patients of cirrhosis of liver. Study Design: Descriptive cross sectional study. Patients and Methods: One hundred and seventeen patients of cirrhosis were included. Baseline haematological and biochemical parameters were determined. Model for end stage liver disease (MELD) score was determined for all patients to document stage of liver disease. Corrected QT interval was determined from electrocardiography of each patient using QT cirrhosis formula. Correlation between QT interval and MELD score was determined using Pearson correlation and Receiver Operating Characteristic (ROC) curve. Results: One hundred and seventeen included patients had mean age of 53.58 (+- 12.11) while male to female ratio was 1.78/1 (75 / 42). Mean MELD score was 17.08 (+- 6.54) in study patients varying between 6 and 37 while mean corrected QT interval was 0.44 seconds (+- 0.06). Pearson correlation revealed no significant relation between severity of liver disease as determined with MELD score and prolonged QT interval (p value 0.18) Area under curve with ROC curve for correlation between prolonged QT interval and severity of liver disease was 0.42. Conclusion: Prolonged QT interval is not an indicator of severity of disease in cirrhosis of liver. (author)

  12. 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...... preanesthesia evaluation in the period 2007 until 2012. The index group included elderly users of an SSRI. The reference group of nonusers of antidepressants was matched to the index group on sex and year of scheduled surgery (ratio, 1:1). The primary outcome was the occurrence of QT interval prolongation shown...... on electrocardiogram. The QT interval was corrected for heart rate (QTc interval). The secondary outcome was the duration of the QTc interval. The outcomes were adjusted for confounding by using regression techniques. RESULTS: The index and reference groups included 397 users of an SSRI and 397 nonusers, respectively...

  13. 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

  14. An Integrative Data Science Pipeline to Identify Novel Drug Interactions that Prolong the QT Interval.

    Science.gov (United States)

    Lorberbaum, Tal; Sampson, Kevin J; Woosley, Raymond L; Kass, Robert S; Tatonetti, Nicholas P

    2016-05-01

    Drug-induced prolongation of the QT interval on the electrocardiogram (long QT syndrome, LQTS) can lead to a potentially fatal ventricular arrhythmia known as torsades de pointes (TdP). Over 40 drugs with both cardiac and non-cardiac indications are associated with increased risk of TdP, but drug-drug interactions contributing to LQTS (QT-DDIs) remain poorly characterized. Traditional methods for mining observational healthcare data are poorly equipped to detect QT-DDI signals due to low reporting numbers and lack of direct evidence for LQTS. We hypothesized that LQTS could be identified latently using an adverse event (AE) fingerprint of more commonly reported AEs. We aimed to generate an integrated data science pipeline that addresses current limitations by identifying latent signals for QT-DDIs in the US FDA's Adverse Event Reporting System (FAERS) and retrospectively validating these predictions using electrocardiogram data in electronic health records (EHRs). We trained a model to identify an AE fingerprint for risk of TdP for single drugs and applied this model to drug pair data to predict novel DDIs. In the EHR at Columbia University Medical Center, we compared the QTc intervals of patients prescribed the flagged drug pairs with patients prescribed either drug individually. We created an AE fingerprint consisting of 13 latently detected side effects. This model significantly outperformed a direct evidence control model in the detection of established interactions (p = 1.62E-3) and significantly enriched for validated QT-DDIs in the EHR (p = 0.01). Of 889 pairs flagged in FAERS, eight novel QT-DDIs were significantly associated with prolonged QTc intervals in the EHR and were not due to co-prescribed medications. Latent signal detection in FAERS validated using the EHR presents an automated and data-driven approach for systematically identifying novel QT-DDIs. The high-confidence hypotheses flagged using this method warrant further investigation.

  15. Strategies to reduce the risk of drug-induced QT interval prolongation: a pharmaceutical company perspective.

    Science.gov (United States)

    Pollard, C E; Valentin, J-P; Hammond, T G

    2008-08-01

    Drug-induced prolongation of the QT interval is having a significant impact on the ability of the pharmaceutical industry to develop new drugs. The development implications for a compound causing a significant effect in the 'Thorough QT/QTc Study' -- as defined in the clinical regulatory guidance (ICH E14) -- are substantial. In view of this, and the fact that QT interval prolongation is linked to direct inhibition of the hERG channel, in the early stages of drug discovery the focus is on testing for and screening out hERG activity. This has led to understanding of how to produce low potency hERG blockers whilst retaining desirable properties. Despite this, a number of factors mean that when an integrated risk assessment is generated towards the end of the discovery phase (by conducting at least an in vivo QT assessment) a QT interval prolongation risk is still often apparent; inhibition of hERG channel trafficking and partitioning into cardiac tissue are just two confounding factors. However, emerging information suggests that hERG safety margins have high predictive value and that when hERG and in vivo non-clinical data are combined, their predictive value to man, whilst not perfect, is >80%. Although understanding the anomalies is important and is being addressed, of greater importance is developing a better understanding of TdP, with the aim of being able to predict TdP rather than using an imperfect surrogate marker (QT interval prolongation). Without an understanding of how to predict TdP risk, high-benefit drugs for serious indications may never be marketed.

  16. 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

  17. Qt interval prolongation and ventricular arrhythmias in patients with chronic heart failure

    International Nuclear Information System (INIS)

    Sarwar, M.; Majeed, S.M.I.; Khan, M.A.; Majeed, S.M.

    2014-01-01

    To determine the association of QTc interval prolongation with ventricular arrhythmias in patients with chronic heart failure. Study Design: Descriptive study. Place and Duration of Study: This study was conducted at Armed Forces Institute of Cardiology/National Institute of Heart Diseases, Rawalpindi, Pakistan from April 2013 to August 2013. Patients and Methods: Fifty three heart failure patients were monitored for 48 hours using ambulatory holter electrocardiography recorders. Digital ECG data was analyzed for QTc interval along with frequency and severity of arrhythmias. Association of prolonged QTc interval with ventricular arrhythmias and severity of arrhythmias was analyzed. Results: Cardiac arrhythmias were observed in 79.2% patients. QT analysis revealed that 69.8% patients had prolonged QTc interval, 86.4% patients with prolonged QTc had ventricular arrhythmias. Of these 66% patients were found to have severe ventricular arrhythmias. Comparison of mean QTc interval of our study population with a reference value showed significantly higher QTc interval of our study group than the test value. Conclusion: Arrhythmia frequency and severity significantly increases with an increase in QTc interval in heart failure demonstrating association of prolonged QTc interval with high risk of severe ventricular arrhythmias and sudden cardiac death in chronic heart failure. (author)

  18. Ibrutinib does not prolong the corrected QT interval in healthy subjects: results from a thorough QT study.

    Science.gov (United States)

    de Jong, Jan; Hellemans, Peter; Jiao, James Juhui; Huang, Yuhan; Mesens, Sofie; Sukbuntherng, Juthamas; Ouellet, Daniele

    2017-12-01

    Ibrutinib is an orally administered, irreversible Bruton's tyrosine kinase inhibitor for treatment of B-cell malignancy. This study evaluated the effects of single-dose ibrutinib at therapeutic and supratherapeutic exposures on cardiac repolarization in healthy subjects. Part 1 used an open-label, two-period sequential design to assess the safety and pharmacokinetics of single doses of ibrutinib 840 and 1680 mg in eight subjects. Part 2 was a randomized, placebo- and positive (moxifloxacin)-controlled, double-blind, single dose, four-way cross-over study to assess the effect of ibrutinib (840 and 1680 mg) on QT/QTc interval. 64 healthy subjects were planned to be enrolled. Baseline-adjusted QT (QTc) intervals for ibrutinib and moxifloxacin (assay sensitivity) were compared to placebo using linear mixed-effect model. A concentration-QTc analysis was also conducted. No clinically relevant safety observations were noted in Part 1. During Part 2, one subject experienced Grade 4 ALT/AST elevations with ibrutinib 1680 mg, leading to study termination and limiting the enrollment to 20 subjects. Ibrutinib demonstrated dose-dependent increases in exposure. The upper bounds of the 90% CIs for the mean difference in change from baseline in QTc between ibrutinib and placebo were Ibrutinib caused a concentration-dependent mild shortening of QTc and mild PR prolongation, but these effects were not considered clinically meaningful. Therapeutic and supratherapeutic concentrations of ibrutinib do not prolong the QTc interval. CLINICALTRIALS.GOV: NCT02271438.

  19. Mitigating prolonged QT interval in cancer nanodrug development for accelerated clinical translation.

    Science.gov (United States)

    Ranjan, Amalendu P; Mukerjee, Anindita; Helson, Lawrence; Vishwanatha, Jamboor K

    2013-12-14

    Cardiac toxicity is the foremost reason for drug discontinuation from development to clinical evaluation and post market surveillance [Fung 35:293-317, 2001; Piccini 158:317-326 2009]. The Food and Drug Administration (FDA) has rejected many potential pharmaceutical agents due to QT prolongation effects. Since drug development and FDA approval takes an enormous amount of time, money and effort with high failure rates, there is an increased focus on rescuing drugs that cause QT prolongation. If these otherwise safe and potent drugs were formulated in a unique way so as to mitigate the QT prolongation associated with them, these potent drugs may get FDA approval for clinical use. Rescuing these compounds not only benefit the patients who need them but also require much less time and money thus leading to faster clinical translation. In this study, we chose curcumin as our drug of choice since it has been shown to posses anti-tumor properties against various cancers with limited toxicity. The major limitations with this pharmacologically active drug are (a) its ability to prolong QT by inhibiting the hERG channel and (b) its low bioavailability. In our previous studies, we found that lipids have protective actions against hERG channel inhibition and therefore QT prolongation. Results of the manual patch clamp assay of HEK 293 cells clearly illustrated that our hybrid nanocurcumin formulation prevented the curcumin induced inhibition of hERG K+ channel at concentrations higher than the therapeutic concentrations of curcumin. Comparing the percent inhibition, the hybrid nanocurcumin limited inhibition to 24.8% at a high curcumin equivalent concentration of 18 μM. Liposomal curcumin could only decrease this inhibition upto 30% only at lower curcumin concentration of 6 μM but not at 18 μM concentration. Here we show a curcumin encapsulated lipopolymeric hybrid nanoparticle formulation which could protect against QT prolongation and also render increased

  20. Hypoglycaemia and QT interval prolongation in type 1 diabetes - bridging the gap between clamp studies and spontaneous episodes

    DEFF Research Database (Denmark)

    Christensen, Toke F.; Cichosz, Simon Lebech; Tarnow, Lise

    2014-01-01

    AIMS: We propose a study design with controlled hypoglycaemia induced by subcutaneous injection of insulin and matched control episodes to bridge the gap between clamp studies and studies of spontaneous hypoglycaemia. The observed prolongation of the heart rate corrected QT interval (QTc) during...... 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...

  1. 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. © 2014 American Heart Association, Inc.

  2. The Half RR Rule: A Poor Rule of Thumb and Not a Risk Assessment Tool for QT Interval Prolongation.

    Science.gov (United States)

    Berling, Ingrid; Isbister, Geoffrey K

    2015-10-01

    Measuring the QT interval on an electrocardiogram (ECG) is integral to risk assessment of Torsade de Pointes (TdP). This study aimed to investigate the accuracy of the 1/2 RR rule as a risk assessment tool for drug-induced TdP, comparing it to the QT nomogram, Bazett's corrected QT (QTcB), and Fridericia's corrected QT (QTcF). The authors calculated sensitivity and specificity of the 1/2 RR rule using a published data set of 129 cases of drug-induced TdP and 316 controls (noncardiotoxic overdoses), compared to the QT nomogram, QTcB > 500 msec and QTcF > 500 msec. To further determine the value of the 1/2 RR rule, its observed positive, and negative agreement were calculated when compared to the QT nomogram for determining an abnormal QT in eight samples of different drugs in overdose. The sensitivity and specificity of the 1/2 RR rule were 88% (95% confidence interval [CI] = 80% to 93%) and 53% (95% CI = 47% to 58%), respectively, compared to the QT nomogram (sensitivity = 97%, 95% CI = 92% to 99%; specificity = 99%, 95% CI = 97% to 100%). It was also less sensitive than QTcB > 500 msec and had a lower specificity than QTcB > 500 msec and QTcF > 500 msec. In drug overdose patients, the 1/2 RR rule had poor observed agreement averaging 41%, which was mainly due to poor positive agreement, except for amisulpride where there was good agreement. The 1/2 RR rule was not as sensitive as the QT nomogram or QTcB > 500 msec for drug-induced TdP. It had poor positive agreement in almost all overdose patients, resulting in over half of patients receiving unnecessary cardiac monitoring and repeat ECGs. © 2015 by the Society for Academic Emergency Medicine.

  3. 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

    with a prolonged QT interval (430 ms or more) or prolonged QT interval dispersion (80 ms or more) were at higher risk of cardiovascular death and cardiac morbidity than subjects whose QT interval was less than 360 ms, or whose QT interval dispersion was less than 30 ms. Cardiovascular death relative risk ratios...

  4. 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...... that an STV(QT) of 4.9 ms was the optimal cut-off value to predict mutation carriers. When incorporating an STV(QT) >4.9 ms for those whose QTc interval was within the normal limits, sensitivity to distinguish mutation carriers increased to 83% with a specificity of 68%, so that another 15 mutation carriers...

  5. Prolonged Tp-e Interval, Tp-e/QT Ratio and Tp-e/QTc Ratio in Patients with Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Alptug Tokatli

    2016-03-01

    Full Text Available BackgroundType 2 diabetes mellitus (T2DM is associated with increased risk of malignant ventricular arrhythmias. Cardiac electrical inhomogeneity may be the leading cause of the increased arrhythmic risk in patients with T2DM. The peak and the end of the T wave (Tp-e interval and associated Tp-e/QT ratio are promising measures of ventricular repolarization indicating transmural dispersion of repolarization. The aim of this study was to assess ventricular repolarization in patients with T2DM by using Tp-e interval, Tp-e/QT ratio and Tp-e/corrected QT interval (QTc ratio.MethodsForty-three patients with T2DM and 43 healthy control subjects, matched by gender and age, were studied. All participants underwent electrocardiography (ECG recording. PR, RR and QT intervals represents the ECG intervals. These are not abbreviations. In all literature these ECG intervals are written like in this text. Tp-e intervals were measured from 12-lead ECG. Rate QTc was calculated by using the Bazett's formula. Tp-e/QT ratio and Tp-e/QTc ratio were also calculated.ResultsMean Tp-e interval was significantly prolonged in patients with T2DM compared to controls (79.4±10.3, 66.4±8.1 ms, respectively; P<0.001. We also found significantly higher values of Tp-e/QT ratio and Tp-e/QTc ratio in patients with diabetes than controls (0.21±0.03, 0.17±0.02 and 0.19±0.02, 0.16±0.02, respectively; P<0.001. There was no difference in terms of the other ECG parameters between the groups.ConclusionTp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio were prolonged in patients with T2DM. We concluded that T2DM leads to augmentation of transmural dispersion of repolarization suggesting increased risk for ventricular arrhythmogenesis.

  6. 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.

  7. Effect of intravenous ondansetron on QT interval prolongation in patients with cardiovascular disease and additional risk factors for torsades: a prospective, observational study

    Directory of Open Access Journals (Sweden)

    Hafermann MJ

    2011-10-01

    Full Text Available Matthew J Hafermann1, Rocsanna Namdar2, Gretchen E Seibold2,3, Robert Lee Page 2nd2,31University of Washington Medical Center, Department of Pharmacy, Seattle, WA; 2University of Colorado Anschutz Medical Campus, School of Pharmacy, Aurora, CO; 3University of Colorado Hospital, Department of Pharmacy, Aurora, CO USABackground: The 5-hydroxytryptamine type 3 antagonists, or setrons (eg, ondansetron, are commonly used for nausea and vomiting in the hospital setting. In 2001, droperidol was given a black box warning because it was found to prolong the QT interval and induce arrhythmias. The setrons share with droperidol the same potential proarrhythmic mechanisms, but limited data exist concerning their effects on the QT interval in individuals at high risk for torsades de pointes.Methods: Forty hospitalized patients admitted for heart failure or acute coronary syndromes with one or more risk factors for torsades de pointes and an order for intravenous ondansetron 4 mg were enrolled in this prospective, observational study. The QT interval corrected for heart rate (QTc was obtained via a 12-lead electrocardiogram on admission and again 120 minutes after the first dose of ondansetron in order to determine the mean change in QTc following ondansetron exposure.Results: The mean time interval between obtaining the baseline electrocardiogram and the second electrocardiogram following ondansetron administration was 3.5 ± 2.14 hours. In the total population, the QTc interval was prolonged by 19.3 ± 18 msec (P < 0.0001 120 minutes after ondansetron administration. For patients with an acute coronary syndrome and those with heart failure, QTc was prolonged by 18.3 ± 20 msec (P < 0.0001 and 20.6 ± 20 msec (P < 0.0012, respectively. Following ondansetron exposure, 31% and 46% in the heart failure and acute coronary syndromes groups, respectively, met gender-related thresholds for a prolonged QTc.Conclusion: Our study found QTc prolongation due to

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

    International Nuclear Information System (INIS)

    Yagi, Yukihiro; Nakamura, Yuji; Kitahara, Ken; Harada, Takuma; Kato, Kazuhiko; Ninomiya, Tomohisa; Cao, Xin; Ohara, Hiroshi; Izumi-Nakaseko, Hiroko; Suzuki, Kokichi; Ando, Kentaro

    2014-01-01

    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 Kr inhibition may play a key role in fingolimod-induced QT-interval prolongation. - Highlights: • Fingolimod and siponimod are S1P 1,3,4,5 and S1P 1,5 receptor modulators, respectively. • Fingolimod and siponimod induced AV block in the halothane-anesthetized guinea pigs. • S1P 1 in the hearts may be the target of fingolimod- and siponimod-induced AV block. • Fingolimod directly inhibited hERG current, which was not observed by

  9. 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

  10. Dynamic Properties of QT Intervals

    Czech Academy of Sciences Publication Activity Database

    Halámek, Josef; Jurák, Pavel; Vondra, Vlastimil; Lipoldová, J.; Leinveber, Pavel; Plachý, M.; Fráňa, P.; Kára, T.

    2009-01-01

    Roč. 36, - (2009), s. 517-520 ISSN 0276-6574 R&D Projects: GA ČR GA102/08/1129; GA MŠk ME09050 Institutional research plan: CEZ:AV0Z20650511 Keywords : QT Intervals * arrhythmia diagnosis Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering http://cinc.mit.edu/archives/2009/pdf/0517.pdf

  11. 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.

  12. 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.

  13. Increases of QT dispersion, corrected QT dispersion and QT interval in young healthy individuals during Ramadan fasting

    Directory of Open Access Journals (Sweden)

    Moradmand S

    2003-06-01

    Full Text Available Ramadan fasting is one of the most important religious duties of Muslims, that its effect on the heart has not been determined yet. Our objective was to evaluate the effect of Ramadan fasting on ventricular repolarization as assessed by QT interval, corrected QT interval, QT dispersion or corrected QT dispersion. Sixthy healthy subjects aged 20 to 35 years were dispersion included in this study. QT interval, corrected QT interval (QTc QT dispersion QTc dispersion, RR interval and QRS axis were measured in 12-lead surface electrocardiogram, once during fasting (10 to 11.5 hours of absolute fasting from food and liquid and another time, 15 tp 60 minutes after eating food at sunset, All of the subjects had been fasting 11 to 12 hours each day at least for 25 days during Ramadan. The study was performed at Amir Alam hospital in the year 2000. Maximal QT interval, mean QT interval and RR-interval, were longer during fasting (P<0.05, and both QT dispersion and QTc dispersion were increased (P<0.05. (QT dispersion: mean ±SD= 57.2±20.1 ms during fasting Vs 41.6±15.1 ms after meal, QTc dispersion=75.4±24.6 ms during fasting Vs 64.1±22.8 ms after meal. But mean QTc interval maximal QTc interval and QRS axis showed no significant difference. Prolongation of QT interval and RR interval during fasting, instead of no significant changes in corrected QT interval may primarily suggest that prolongation of RR-interval causes QTc interval not to have significant difference. But increases of QT dispersion and corrected QT dispersion (QTc dispersion during fasting -that are more reliable indicators of ventricular repolarization-support the idea that ventricular repolarization may be changed during Ramadan fasting. QT dispersion in cardiac patients is showed to increase from normal values of 30-40 to 64-138 ms, but in our study their increases did not reach critical value.

  14. 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...... intervals. Here, we evaluate variability of QT intervals in patients with a history of drug-induced long QT syndrome (dLQTS) and TdP in absence of a mutation in any of the major LQTS genes.......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...

  15. A Case of QT Prolongation Associated with Panhypopituitarism

    Directory of Open Access Journals (Sweden)

    Dilek Arpaci

    2013-01-01

    Full Text Available We describe a 37-year-old patient with panhypopituitarism who experienced symptoms and signs of hormonal insufficiency and QT prolongation on electrocardiogram without electrolyte disturbances. After hormonal (steroidal and thyroid replacement therapy electrocardiographic findings were normalized. Hormonal disorders should be considered as a cause of long QT intervals which may lead to torsade de pointes, even if plasma electrolyte levels are normal, because life-threatening arrhythmia is treatable by supplementation of the hormone that is lacking.

  16. Long-Term Haloperidol Treatment Prolongs QT Interval and Increases Expression of Sigma 1 and IP3 Receptors in Guinea Pig Hearts.

    Science.gov (United States)

    Stracina, Tibor; Slaninova, Iva; Polanska, Hana; Axmanova, Martina; Olejnickova, Veronika; Konecny, Petr; Masarik, Michal; Krizanova, Olga; Novakova, Marie

    2015-07-01

    Haloperidol is a neuroleptic drug used for a medication of various psychoses and deliria. Its administration is frequently accompanied by cardiovascular side effects, expressed as QT interval prolongation and occurrence of even lethal arrhythmias. Despite these side effects, haloperidol is still prescribed in Europe in clinical practice. Haloperidol binds to sigma receptors that are coupled with inositol 1,4,5-trisphosphate (IP3) receptors. Sigma receptors are expressed in various tissues, including heart muscle, and they modulate potassium channels. Together with IP3 receptors, sigma receptors are also involved in calcium handling in various tissues. Therefore, the present work aimed to study the effects of long-term haloperidol administration on the cardiac function. Haloperidol (2 mg/kg once a day) or vehiculum was administered by intraperitoneal injection to guinea pigs for 21 consecutive days. We measured the responsiveness of the hearts isolated from the haloperidol-treated animals to additional application of haloperidol. Expression of the sigma 1 receptor and IP3 receptors was studied by real time-PCR and immunohistochemical analyses. Haloperidol treatment caused the significant decrease in the relative heart rate and the prolongation of QT interval of the isolated hearts from the haloperidol-treated animals, compared to the hearts isolated from control animals. The expression of sigma 1 and IP3 type 1 and type 2 receptors was increased in both atria of the haloperidol-treated animals but not in ventricles. The modulation of sigma 1 and IP3 receptors may lead to altered calcium handling in cardiomyocytes and thus contribute to changed sensitivity of cardiac cells to arrhythmias.

  17. 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.

    Science.gov (United States)

    Elming, H; Holm, E; Jun, L; Torp-Pedersen, C; Køber, L; Kircshoff, M; Malik, M; Camm, J

    1998-09-01

    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. The QT interval was measured in all leads from a standard 12-lead ECG in a random sample 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 with a prolonged QT interval (430 ms or more) or prolonged QT interval dispersion (80 ms or more) were at higher risk of cardiovascular death and cardiac morbidity than subjects whose QT interval was less than 360 ms, or whose QT interval dispersion was less than 30 ms. Cardiovascular death relative risk ratios, adjusted for age, gender, myocardial infarct, angina pectoris, diabetes mellitus, arterial hypertension, smoking habits, serum cholesterol level, and heart rate were 2.9 for the QT interval (95% confidence interval 1.1-7.8) and 4.4 for QT interval dispersion (95% confidence interval 1.0-19-1). Fatal and non-fatal cardiac morbidity relative risk ratios were similar, at 2.7 (95% confidence interval 1.4-5.5) for the QT interval and 2.2 (95% confidence interval 1.1-4.0) for QT interval dispersion. Prolongation of the QT interval and QT interval dispersion independently affected the prognosis of cardiovascular mortality and cardiac fatal and non-fatal morbidity in a general population over 11 years.

  18. Pharmacometabolomic approach to predict QT prolongation in guinea pigs.

    Directory of Open Access Journals (Sweden)

    Jeonghyeon Park

    Full Text Available Drug-induced torsades de pointes (TdP, a life-threatening arrhythmia associated with prolongation of the QT interval, has been a significant reason for withdrawal of several medicines from the market. Prolongation of the QT interval is considered as the best biomarker for predicting the torsadogenic risk of a new chemical entity. Because of the difficulty assessing the risk for TdP during drug development, we evaluated the metabolic phenotype for predicting QT prolongation induced by sparfloxacin, and elucidated the metabolic pathway related to the QT prolongation. We performed electrocardiography analysis and liquid chromatography-mass spectroscopy-based metabolic profiling of plasma samples obtained from 15 guinea pigs after administration of sparfloxacin at doses of 33.3, 100, and 300 mg/kg. Principal component analysis and partial least squares modelling were conducted to select the metabolites that substantially contributed to the prediction of QT prolongation. QTc increased significantly with increasing dose (r = 0.93. From the PLS analysis, the key metabolites that showed the highest variable importance in the projection values (>1.5 were selected, identified, and used to determine the metabolic network. In particular, cytidine-5'-diphosphate (CDP, deoxycorticosterone, L-aspartic acid and stearic acid were found to be final metabolomic phenotypes for the prediction of QT prolongation. Metabolomic phenotypes for predicting drug-induced QT prolongation of sparfloxacin were developed and can be applied to cardiac toxicity screening of other drugs. In addition, this integrative pharmacometabolomic approach would serve as a good tool for predicting pharmacodynamic or toxicological effects caused by changes in dose.

  19. Sex Hormones and the QT Interval: A Review

    Science.gov (United States)

    Sedlak, Tara; Shufelt, Chrisandra; Iribarren, Carlos

    2012-01-01

    Abstract A prolonged QT interval is a marker for an increased risk of ventricular tachyarrhythmias. Both endogenous and exogenous sex hormones have been shown to affect the QT interval. Endogenous testosterone and progesterone shorten the action potential, and estrogen lengthens the QT interval. During a single menstrual cycle, progesterone levels, but not estrogen levels, have the dominant effect on ventricular repolarization in women. Studies of menopausal hormone therapy (MHT) in the form of estrogen-alone therapy (ET) and estrogen plus progesterone therapy (EPT) have suggested a counterbalancing effect of exogenous estrogen and progesterone on the QT. Specifically, ET lengthens the QT, whereas EPT has no effect. To date, there are no studies on oral contraception (OC) and the QT interval, and future research is needed. This review outlines the current literature on sex hormones and QT interval, including the endogenous effects of estrogen, progesterone, and testosterone and the exogenous effects of estrogen and progesterone therapy in the forms of MHT and hormone contraception. Further, we review the potential mechanisms and pathophysiology of sex hormones on the QT interval. PMID:22663191

  20. QT Interval in Pregnant and Non-pregnant Women

    Directory of Open Access Journals (Sweden)

    Majid Zamani

    2014-03-01

    Full Text Available Introduction: Prolongation of QT interval might result in dangerous cardiac arrhythmias, including Torsades de Pointes (TdP, consequently leading to syncope or death. A limited number of studies carried out in this respect to date have shown that QT interval might increase during pregnancy. On the other hand, it has been shown that each pregnancy might result in an increase in the risk of cardiac accidents in patients with long QT interval. Therefore, the present study was undertaken to compare QT intervals in pregnant and non-pregnant women. Methods: Pregnant women group consisted of 40 women in the second and third trimesters of pregnancy and the non-pregnant control group consisted of healthy women 18-35 years of age. All the patients underwent standard 12-lead electrocardiogram (ECG. The QT interval was measured for each patient at lead II. The mean corrected QT interval (QTc and QT dispersions (QTd were compared between the two groups. Results: Mean heart rates in the pregnant and non-pregnant groups were 98.55±14.09 and 72.53±13.17 beats/minutes (P<0.001. QTd and QTc means were in the normal range in both groups; however, these variables were 49.50±12.80 and 43.03±18.47 milliseconds in the pregnant group and 39.5±9.59 and 40.38±17.20 milliseconds in the control group, respectively (P<0.001. Conclusion: The QT interval was longer in pregnant women compared to non-pregnant women; however, it was in the normal range in both groups. Therefore, it is important to monitor and manage risk factors involved in prolongation of QT interval and prevent concurrence of these factors with pregnancy.

  1. Mutation of the Na+/K+-ATPase Atp1a1a.1 causes QT interval prolongation and bradycardia in zebrafish.

    Science.gov (United States)

    Pott, Alexander; Bock, Sarah; Berger, Ina M; Frese, Karen; Dahme, Tillman; Keßler, Mirjam; Rinné, Susanne; Decher, Niels; Just, Steffen; Rottbauer, Wolfgang

    2018-05-08

    The genetic underpinnings that orchestrate the vertebrate heart rate are not fully understood yet, but of high clinical importance, since diseases of cardiac impulse formation and propagation are common and severe human arrhythmias. To identify novel regulators of the vertebrate heart rate, we deciphered the pathogenesis of the bradycardia in the homozygous zebrafish mutant hiphop (hip) and identified a missense-mutation (N851K) in Na + /K + -ATPase α1-subunit (atp1a1a.1). N851K affects zebrafish Na + /K + -ATPase ion transport capacity, as revealed by in vitro pump current measurements. Inhibition of the Na + /K + -ATPase in vivo indicates that hip rather acts as a hypomorph than being a null allele. Consequently, reduced Na + /K + -ATPase function leads to prolonged QT interval and refractoriness in the hip mutant heart, as shown by electrocardiogram and in vivo electrical stimulation experiments. We here demonstrate for the first time that Na + /K + -ATPase plays an essential role in heart rate regulation by prolonging myocardial repolarization. Copyright © 2018. Published by Elsevier Ltd.

  2. 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...

  3. 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 (Cornelia); 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

  4. 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, 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.; Meyer zu Schwabedissen, Henriette; 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.; 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.; del Greco M, 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, 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 D.; 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 M.; 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

  5. 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.

  6. 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.

  7. Cardiovascular drugs inducing QT prolongation: facts and evidence.

    Science.gov (United States)

    Taira, Carlos A; Opezzo, Javier A W; Mayer, Marcos A; Höcht, Christian

    2010-01-01

    Acquired QT syndrome is mainly caused by the administration of drugs that prolong ventricular repolarization. On the other hand, the risk of drug-induced torsades de pointes is increased by numerous predisposing factors, such as genetic predisposition, female sex, hypokalemia and cardiac dysfunction. This adverse reaction is induced by different chemical compounds used for the treatment of a variety of pathologies, including arrhythmias. As it is known, antiarrhythmic agents and other cardiovascular drugs can prolong the QT interval, causing this adverse reaction. Of the 20 most commonly reported drugs, 10 were cardiovascular agents and these appeared in 348 of the reports (46%). Class Ia antiarrhythmic agents have frequently been linked to inducing arrhythmia, including torsades de pointes. Sotalol and amiodarone, class III antiarrhythmics, are known to prolong the QT interval by blocking I(Kr). Due to the severity of events caused by the therapeutic use of these drugs, in this work of revision the cardiovascular drugs that present this property and the factors and evidence will be mentioned.

  8. Acotiamide hydrochloride (Z-338), a new selective acetylcholinesterase inhibitor, enhances gastric motility without prolonging QT interval in dogs: comparison with cisapride, itopride, and mosapride.

    Science.gov (United States)

    Matsunaga, Yugo; Tanaka, Takao; Yoshinaga, Koji; Ueki, Shigeru; Hori, Yuko; Eta, Runa; Kawabata, Yoshihiro; Yoshii, Kazuyoshi; Yoshida, Kenji; Matsumura, Toshihiro; Furuta, Shigeru; Takei, Mineo; Tack, Jan; Itoh, Zen

    2011-03-01

    Acotiamide hydrochloride (acotiamide; N-[2-[bis(1-methylethyl) amino]ethyl]-2-[(2-hydroxy-4,5-dimethoxybenzoyl) amino] thiazole-4-carboxamide monohydrochloride trihydrate, Z-338) has been reported to improve meal-related symptoms of functional dyspepsia in clinical studies. Here, we examined the gastroprokinetic effects of acotiamide and its antiacetylcholinesterase activity as a possible mechanism of action in conscious dogs. Acotiamide increased postprandial gastric motor activity in conscious dogs with chronically implanted force transducers and, like itopride, mosapride, and cisapride, exhibited gastroprokinetic activity in these dogs. Furthermore, acotiamide improved clonidine-induced hypomotility and delayed gastric emptying. Acotiamide-enhanced postprandial gastroduodenal motility was suppressed completely by pretreatment with atropine, a muscarinic receptor antagonist. In in vitro studies, acotiamide enhanced acetylcholine- but not carbachol-induced contractile responses of guinea pig gastric antrum strips. Moreover, like itopride and neostigmine, acotiamide inhibited recombinant human and canine stomach-derived acetylcholinesterase (AChE) activity in vitro. The mode of the AChE inhibitory action of acotiamide was selective and reversible. Unlike itopride or mosapride, acotiamide showed no affinity for dopamine D(2) or serotonin 5-HT(4) receptors. With regard to cardiovascular side effects, unlike cisapride, acotiamide did not affect myocardial monophasic action potential duration, QT interval, or corrected QT interval in anesthetized dogs. These results suggest that acotiamide stimulates gastric motility in vivo by inhibiting AChE activity without affecting QT interval. Acotiamide thus represents a beneficial new drug for the treatment of functional dyspepsia involving gastric motility dysfunction, with differences from other prokinetic agents.

  9. 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 ... lower at day- and nighttime. Aging was associated with an increase of QT interval mainly at daytime and a significant shift of the T wave apex towards the end of the T wave. The circadian profile of ventricular repolarization is strongly related to the mean R-R interval, however, there are significant...

  10. Hyperglycemia and subsequent torsades de pointes with marked QT prolongation during refeeding.

    Science.gov (United States)

    Nakashima, Takashi; Kubota, Tomoki; Takasugi, Nobuhiro; Kitagawa, Yuichiro; Yoshida, Takahiro; Ushikoshi, Hiroaki; Kawasaki, Masanori; Nishigaki, Kazuhiko; Ogura, Shinji; Minatoguchi, Shinya

    2017-01-01

    A fatal cardiac complication can occasionally present in malnourished patients during refeeding; this is known as refeeding syndrome. However, to our knowledge, hyperglycemia preceding torsades de pointes with QT prolongation during refeeding has not been reported. In the present study, we present a case in which hyperglycemia preceded torsades de pointes with QT prolongation during refeeding. The aim of this study was to determine the possible mechanism underlying QT prolongation during refeeding and indicate how to prevent it. A 32-y-old severely malnourished woman (body mass index 14.57 kg/m 2 ) was admitted to the intensive care unit of our institution after resuscitation from cardiopulmonary arrest due to ventricular fibrillation. She was diagnosed with anorexia nervosa. Although no obvious electrolyte abnormalities were observed, her blood glucose level was 11 mg/dL. A 12-lead electrocardiogram at admission showed sinus rhythm with normal QT interval (QTc 0.448). Forty mL of 50% glucose (containing 20 g of glucose) was intravenously injected, followed by a drip infusion of glucose to maintain blood glucose level within normal range. After 9 h, the patient's blood glucose level increased to 569 mg/dL. However, after 38 h, an episode of marked QT prolongation (QTc 0.931) followed by torsades de pointes developed. Hyperglycemia during refeeding can present with QT prolongation; consequently, monitoring blood glucose levels may be useful in avoiding hyperglycemia, which can result in QT prolongation. Furthermore, additional monitoring of QT intervals using a 12-lead electrocardiogram should allow the early detection of QT prolongation when glucose solution is administered to a malnourished patient with (severe) hypoglycemia. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Long QT interval in Turner syndrome: a high prevalence of LQTS gene mutations

    DEFF Research Database (Denmark)

    Trolle, Christian

    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......QTc). The prevalence of mutations in genes related to Long QT syndrome (LQTS) was determined in females with TS 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 females with TS (414.0±25.5 ms...

  12. 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

  13. QT Prolongation Complicated with Torsades de Pointes in Prosthetic Mitral Valve Endocarditis: A Case Report

    Directory of Open Access Journals (Sweden)

    A. Tounsi

    2012-01-01

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

  14. 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

  15. The analysis of QT interval and repolarization morphology of the heart in chronic exposure to lead.

    Science.gov (United States)

    Kiełtucki, J; Dobrakowski, M; Pawlas, N; Średniawa, B; Boroń, M; Kasperczyk, S

    2017-10-01

    There are no common recommendations regarding electrocardiographic monitoring in occupationally exposed workers. Therefore, the present study was designed to investigate whether exposure to lead results in an increase of selected electrocardiography (ECG) pathologies, such as QT interval prolongation and repolarization disorders, in occupationally exposed workers. The study group included 180 workers occupationally exposed to lead compounds. The exposed group was divided according to the median of the mean blood lead level (PbB mean ) calculated based on a series of measurements performed during 5-year observation period (35 µg/dl) into two subgroups: low exposure (LE, PbB mean = 20.0-35.0 µg/dl) and high exposure (HE, PbB mean = 35.1-46.4 µg/dl). The control group consisted of 69 healthy workers without occupational exposure to lead. ECG evaluation included the analysis of heart rate (HR), QT interval and repolarization abnormalities. Mean QT interval was significantly greater in the exposed population than in the control group by 2%. In the HE group, mean QT interval was significantly greater than in the control group by 4% and significantly different from those noted in the LE group. Positive correlations between QT interval and lead exposure indices were also reported. Besides, there was a negative correlation between HR and blood lead level. Increased concentration of lead in the blood above 35 μg/dl is associated with the QT interval prolongation, which may trigger arrhythmias when combined with other abnormalities, such as long QT syndrome. Therefore, electrocardiographic evaluation should be a part of a routine monitoring of occupationally exposed populations.

  16. 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.

  17. Torsades de Pointes associated with QT prolongation after catheter ablation of paroxysmal atrial fibrillation

    Directory of Open Access Journals (Sweden)

    Yae Min Park

    2017-09-01

    Full Text Available A 79-year-old woman who underwent catheter ablation for paroxysmal atrial fibrillation presented with Torsades de Pointes (TdP. Aggravation of prolonged QT interval which is most likely due to neural modulation by catheter ablation, played major role in the initiation of TdP. The patient was successfully treated with isoproterenol during acute stage and discharged after stabilization without implantation of permanent pacemaker or implantable cardioverter defibrillator.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    BACKGROUND: The T(peak)T(end) (T(p)T(e)) interval is believed to reflect the transmural dispersion of repolarization. Accordingly, it should be a risk factor in long QT syndrome (LQTS). The aim of the study was to determine the effect of genotype on T(p)T(e) interval and test whether it was relat...

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    Trolle, Christian; Mortensen, Kristian H; Pedersen, Lisbeth N; Berglund, Agnethe; Jensen, Henrik K; Andersen, Niels H; Gravholt, Claus H

    2013-01-01

    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. 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. The mean hQTc in women with Turner syndrome (414.0 ± 25.5 ms) compared to controls (390.4 ± 17.8 ms) was prolonged (pTurner syndrome karyotypes (418.2 ± 24.8 vs. 407.6 ± 25.5 ms; p = 0.055). In women with Turner syndrome and a bQTc >432 ms, 7 had mutations in major Long QT syndrome genes (SCN5A and KCNH2) and one in a minor Long QT syndrome gene (KCNE2). 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. NCT00624949. https://register.clinicaltrials.gov/prs/app/action/SelectProtocol/sid/S0001FLI/selectaction/View/ts/3/uid/U000099E.

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

    Directory of Open Access Journals (Sweden)

    Christian Trolle

    Full Text Available 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.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.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.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.NCT00624949. https://register.clinicaltrials.gov/prs/app/action/SelectProtocol/sid/S0001FLI/selectaction/View/ts/3/uid/U000099E.

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

    African Journals Online (AJOL)

    Objective: 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). Materials and Methods: One‑hundred ten women (n = 55, for each group) with full‑term and single ...

  4. Cocaine Hydrolase Gene Transfer Demonstrates Cardiac Safety and Efficacy against Cocaine-Induced QT Prolongation in Mice

    OpenAIRE

    Murthy, Vishakantha; Reyes, Santiago; Geng, Liyi; Gao, Yang; Brimijoin, Stephen

    2016-01-01

    Cocaine addiction is associated with devastating medical consequences, including cardiotoxicity and risk-conferring prolongation of the QT interval. Viral gene transfer of cocaine hydrolase engineered from butyrylcholinesterase offers therapeutic promise for treatment-seeking drug users. Although previous preclinical studies have demonstrated benefits of this strategy without signs of toxicity, the specific cardiac safety and efficacy of engineered butyrylcholinesterase viral delivery remains...

  5. 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...

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

    International Nuclear Information System (INIS)

    Nozaki, Yumiko; Honda, Yayoi; Tsujimoto, Shinji; Watanabe, Hitoshi; Kunimatsu, Takeshi; Funabashi, Hitoshi

    2014-01-01

    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 + channel and Ca 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 Kr and I Ks blockers concentration-dependently prolonged corrected FPD (FPDc), whereas Ca 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 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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  8. 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

    Directory of Open Access Journals (Sweden)

    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

  9. [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].

    Science.gov (United States)

    Ceker, Zahit; Takmaz, Suna Akın; Baltaci, Bülent; Başar, Hülya

    2015-01-01

    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. 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 500mcg/kg followed by a 100mcg/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, 5min after esmolol and saline administration, 3min after the induction and 30s, 2min and 4min after intubation. 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) 30s after intubation. The risk of arrhythmia frequency was higher in the control group in the 4-min period following intubation (p=0.038). 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 enzyme inhibitors. These effects were prevented with esmolol (500mcg/kg bolus, followed by

  10. Psychotropic Pharmacotherapy Associated With QT Prolongation Among Veterans With Posttraumatic Stress Disorder.

    Science.gov (United States)

    Stock, Eileen M; Zeber, John E; McNeal, Catherine J; Banchs, Javier E; Copeland, Laurel A

    2018-04-01

    In 2012, the Food and Drug Administration issued Drug Safety Communications on several drugs associated with QT prolongation and fatal ventricular arrhythmias. Among these was citalopram, a selective serotonin reuptake inhibitor (SSRI) approved for depression and commonly used for posttraumatic stress disorder (PTSD). Evaluation of the risk for QT prolongation among other psychotropic drugs for individuals with PTSD remains limited. Explore psychotropic drugs associated with QT prolongation among veterans with PTSD. Patients in the Veterans Health Administration in 2006-2009 with PTSD and QT prolongation (176 cases) were matched 1:4 on age, gender, visit date and setting, and physical comorbidity. Classification trees assessed QT prolongation risk among prescribed medications (n=880). Receipt of any drug with known risk of QT prolongation varied by group (23% QT cases vs 15% control, prisks included ziprasidone (3% vs 1%, p=0.02) and buspirone (6% vs 2%, p=0.01). Increased risk was not observed for the SSRIs, citalopram and fluoxetine. Classification trees found that sotalol and amitriptyline carried greater risk among cardiac patients and methadone, especially if prescribed with quetiapine, among noncardiac patients. Per adjusted survival model, patients with QT prolongation were at increased risk for death (hazard ratio=1.60; 95% CI=1.04-2.44). Decision models are particularly advantageous when exploring nonlinear relationships or nonadditive interactions. These findings may potentially affect clinical decision-making concerning treatment for PTSD. For patients at higher risk of QT prolongation, antidepressants other than amitriptyline should be considered. Medications for comorbid conditions should also be closely monitored for heightened QT prolongation risk.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Evaluation of Tp-Te Interval and Tp-Te/QT Ratio in Patients with Coronary Slow Flow Tp-Te/QT Ratio and Coronary Slow Flow.

    Science.gov (United States)

    Tenekecioglu, Erhan; Karaagac, Kemal; Yontar, Osman Can; Agca, Fahriye Vatansever; Ozluk, Ozlem Arican; Tutuncu, Ahmet; Arslan, Burhan; Yilmaz, Mustafa

    2015-06-01

    Coronary slow flow (CSF) phenomenon is described by angiographically normal coronary arteries with delayed opacification of the distal vasculature. Several studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (Tp-Te) may correspond to the transmural dispersion of the repolarization and that increased Tp-Te interval and Tp-Te/QT ratio are associated with malignant ventricular arrhythmias. The aim of this study was to evaluate the ventricular repolarization by using Tp-Te interval and Tp-Te/QT ratio in patients with CSF. This study included 50 CSF patients (40 male, mean age 48.6±12.5 years) and 40 control individuals (23 male, mean age 47.8±12.5 years). Tp-Te interval and Tp-Te/QT ratio were measured from the 12-lead electrocardiogram. These parameters were compared in groups. Baseline characteristics of the study groups were comparable. In electrocardiographic parameters analysis, QT and corrected QT were similar in CSF patients compared to the controls (357±35.2 vs 362±38.0 milliseconds and 419±25.8 vs 430±44.2 milliseconds, all p value >0.05). Tp-Te interval, Tp-Te/QT and Tp-Te/QTc ratio were significantly higher in CSF patients (85±13.7 vs 74±9.9 milliseconds and 0.24±0.03 vs 0.20±0.02 and 0.20±0.03 vs 0.17±0.02 all p value ratio are prolonged in patients with CSF.

  13. 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.

  14. 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.

  15. Pharmacokinetics and effect on the corrected QT interval of single-dose escitalopram in healthy elderly compared with younger adults.

    Science.gov (United States)

    Chung, Hyewon; Kim, Anhye; Lim, Kyoung Soo; Park, Sang-In; Yu, Kyung-Sang; Yoon, Seo Hyun; Cho, Joo-Youn; Chung, Jae-Yong

    2017-01-01

    Escitalopram is the (S)-enantiomer of citalopram that has a potential QT prolonging effect. In this study, 12 healthy elderly individuals received a single oral dose of escitalopram (20 mg), and their pharmacokinetics and QT effect data were compared with data from 33 younger adults obtained in a previous study. Serial blood samples for pharmacokinetic analysis were collected and ECG was performed up to 48 h postdose. The elderly and younger adults showed similar pharmacokinetic profiles. The geometric mean ratios (90% confidence interval) of the elderly compared with the younger adults were 1.02 (0.89-1.17) and 1.01 (0.86-1.17) for the maximum plasma concentration and area under the concentration-time curve, respectively. The mean baseline-adjusted QT (dQT) time profiles were similar and the mean values of maximum dQT were not significantly different between the elderly and the younger adults. The linear mixed-effect model indicated a weak but positive relationship between the escitalopram concentration and dQT, with an estimated coefficient of concentration of 0.43-0.54. In conclusion, the pharmacokinetics and QT effect of a single dose of escitalopram observed in the elderly without comorbidities and younger adults were generally similar.

  16. Ciprofloxacin does not Prolong the QTc Interval : A Clinical Study in ICU Patients and Review of the Literature

    NARCIS (Netherlands)

    Heemskerk, Charlotte P.M.; Woldman, Evelien; Pereboom, Marieke; van der Hoeven, Ruud T M; Mantel-Teeuwisse, Aukje; Van Gemeren, Claudia; Becker, Matthijs Lambertus

    2017-01-01

    PURPOSE: Ciprofloxacin may prolong the QT interval and increase the risk of Torsade de Pointes (TdP). Intravenous administration of ciprofloxacin in patients with additional risks may elevate the risk of QTc interval prolongation. We prospectively assessed whether intravenous ciprofloxacin prolongs

  17. Prolonged QT Syndrome and Seizure Secondary to Alkaline Earth Metal Deficiency: A Case Report

    Directory of Open Access Journals (Sweden)

    A. McKinney

    2011-01-01

    Full Text Available Introduction. Alkaline earth metal deficiency is recognized as a cause of both seizure and long QT syndrome. Their deficiency can have significant repercussions on the function of cells, tissues, and organs of the body. An understanding of the role of electrolytes allows an appreciation of the significance of depleted levels on cell function. Case Report. A 65-year-old lady was admitted with symptoms of chest discomfort, vomiting, increased stoma output, and dizziness. Two days following admission she suffered a tonic-clonic seizure. ECG review demonstrated a prolonged QTc interval, raising the possibility of an underlying Torsades de Pointes as the precipitant. This was attributed to electrolyte disturbance arising as a result of multiple aetiologies. Discussion. This paper highlights the multisystem effects of electrolyte disturbance, with emphasis upon its role in precipitating cardiac arrhythmia and neurological symptoms.

  18. Mixed models for data from thorough QT studies: part 2. One-step assessment of conditional QT prolongation.

    Science.gov (United States)

    Schall, Robert

    2011-01-01

    We investigate mixed analysis of covariance models for the 'one-step' assessment of conditional QT prolongation. Initially, we consider three different covariance structures for the data, where between-treatment covariance of repeated measures is modelled respectively through random effects, random coefficients, and through a combination of random effects and random coefficients. In all three of those models, an unstructured covariance pattern is used to model within-treatment covariance. In a fourth model, proposed earlier in the literature, between-treatment covariance is modelled through random coefficients but the residuals are assumed to be independent identically distributed (i.i.d.). Finally, we consider a mixed model with saturated covariance structure. We investigate the precision and robustness of those models by fitting them to a large group of real data sets from thorough QT studies. Our findings suggest: (i) Point estimates of treatment contrasts from all five models are similar. (ii) The random coefficients model with i.i.d. residuals is not robust; the model potentially leads to both under- and overestimation of standard errors of treatment contrasts and therefore cannot be recommended for the analysis of conditional QT prolongation. (iii) The combined random effects/random coefficients model does not always converge; in the cases where it converges, its precision is generally inferior to the other models considered. (iv) Both the random effects and the random coefficients model are robust. (v) The random effects, the random coefficients, and the saturated model have similar precision and all three models are suitable for the one-step assessment of conditional QT prolongation. Copyright © 2010 John Wiley & Sons, Ltd.

  19. A thorough QT study to evaluate the QTc prolongation potential of two neuropsychiatric drugs, quetiapine and escitalopram, in healthy volunteers.

    Science.gov (United States)

    Kim, Anhye; Lim, Kyoung Soo; Lee, Howard; Chung, Hyewon; Yoon, Seo Hyun; Yu, Kyung-Sang; Cho, Joo-Youn; Jang, In-Jin; Chung, Jae-Yong

    2016-07-01

    Prolongation of the QT interval on an ECG is a surrogate marker for predicting the proarrhythmic potential of a drug under development. The aim of this study was to evaluate the QTc prolongation potential of two neuropsychiatric drugs, quetiapine immediate release (IR) and escitalopram, in healthy individuals. This was a randomized, open-label, 4×4 Williams crossover study, with four single-dose treatments [placebo, 400 mg moxifloxacin (positive control), 20 mg escitalopram, and 100 mg quetiapine IR], conducted in 40 healthy volunteers. Serial blood samples for pharmacokinetics and ECG were collected. Individually, RR-corrected QTc intervals (QTcI) and placebo-adjusted changes from baseline values of QTcI (ΔΔQTcI) were evaluated. Lower-bound values of the one-sided 95% confidence interval for ΔΔQTcI of moxifloxacin with more than 5 ms confirmed the sensitivity of the assay. The maximum upper bound 95% confidence interval for the ΔΔQTcI of quetiapine IR and escitalopram was 13.7 and 10.5 ms, with mean estimates of 10.2 and 6.9 ms, respectively. Peak effects of moxifloxacin and quetiapine IR on ΔΔQTcI were observed at approximately time to maximum concentration (Tmax), whereas that of escitalopram was observed 3 h after Tmax. The concentration-ΔΔQTcI relationships of quetiapine IR and escitalopram were relatively flat, as compared with that of moxifloxacin. The results demonstrated the validity of trial methodology and that quetiapine IR and escitalopram caused QT prolongation in healthy individuals. In addition, hysteresis of escitalopram-induced QTc prolongation. These results indicate that higher doses of these drugs could lead to greater QT prolongation in a dose-response manner.

  20. 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

  1. Risk factors for QTc interval prolongation

    NARCIS (Netherlands)

    Heemskerk, Charlotte P.M.; Pereboom, Marieke; van Stralen, Karlijn; Berger, Florine A.; van den Bemt, Patricia M.L.A.; Kuijper, Aaf F.M.; van der Hoeven, Ruud T M; Mantel-Teeuwisse, Aukje K.; Becker, Matthijs L

    2018-01-01

    Purpose: Prolongation of the QTc interval may result in Torsade de Pointes, a ventricular arrhythmia. Numerous risk factors for QTc interval prolongation have been described, including the use of certain drugs. In clinical practice, there is much debate about the management of the risks involved. In

  2. Giant T-U waves precede torsades de pointes in long QT syndrome: a systematic electrocardiographic analysis in patients with acquired and congenital QT prolongation

    NARCIS (Netherlands)

    Kirchhof, Paulus; Franz, Michael R.; Bardai, Abdennasser; Wilde, Arthur M.

    2009-01-01

    This study sought to identify electrocardiographic (ECG) criteria that are associated with initiation of torsades de pointes (TdP) in patients with acquired (a-) and congenital (c-) long QT syndrome (LQTS). Electrocardiographic criteria used as risk predictors for TdP commonly rely on a prolonged QT

  3. QT-interval effects of methadone, levomethadyl, and buprenorphine in a randomized trial.

    Science.gov (United States)

    Wedam, Erich F; Bigelow, George E; Johnson, Rolley E; Nuzzo, Paul A; Haigney, Mark C P

    2007-12-10

    Levomethadyl acetate, methadone hydrochloride, and buprenorphine hydrochloride are equally effective treatments for opioid dependence. Each blocks the human ether-a-go-go-related gene (hERG)-associated channel in vitro and represents a risk for QT prolongation. To compare the effects of 3 known hERG-associated channel blockers on the corrected QT (QTc), we conducted a randomized, controlled trial of opioid-addicted subjects. We analyzed 12-lead electrocardiograms collected at baseline and every 4 weeks from 165 opioid-addicted participants in a 17-week randomized double-blind clinical trial of equally effective doses of levomethadyl, methadone, and buprenorphine at a major referral center. Analyses were limited to the 154 patients with a normal baseline QTc = (QT/ radical R-R) who had at least 1 subsequent in-treatment electrocardiogram. Patients were randomized to receive treatment with levomethadyl, methadone, or buprenorphine (hereinafter, levomethadyl, methadone, and buprenorphine groups, respectively). The prespecified end points were a QTc greater than 470 milliseconds in men (or >490 milliseconds in women), or an increase from baseline in QTc greater than 60 milliseconds. Baseline QTc was similar in the 3 groups. The levomethadyl and methadone groups were significantly more likely to manifest a QTc greater than 470 or 490 milliseconds (28% for the levomethadyl group vs 23% for the methadone group vs 0% for the buprenorphine group; P methadone group [odds ratio, 8.4; 95% confidence interval, 1.9-36.4]) compared with the buprenorphine group (2% of subjects; P methadone remained fixed over at least 8 weeks, the QTc continued to increase progressively over time (P = .08 for the levomethadyl group, P = .01 for the methadone group). Buprenorphine is associated with less QTc prolongation than levomethadyl or methadone and may be a safe alternative.

  4. QT prolongation and sudden cardiac death risk in hypertrophic cardiomyopathy.

    Science.gov (United States)

    Patel, Salma I; Ackerman, Michael J; Shamoun, Fadi E; Geske, Jeffrey B; Ommen, Steve R; Love, William T; Cha, Stephen S; Bos, Johan M; Lester, Steven J

    2018-03-07

    Risk assessment for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) remains complex. The goal of this study was to assess electrocardiogram (ECG)-derived risk factors on SCD in a large HCM population Methods: Retrospective review of adults with HCM evaluated at Mayo Clinic, Rochester, MN from 1 December 2002 to 31 December 2012 was performed. Data inclusive of ECG and 24-hour ambulatory Holter monitor were assessed. SCD events were documented by ventricular fibrillation (VF) noted on implantable cardioverter defibrillator (ICD), or appropriate VT or VF-terminating ICD shock. Overall, 1615 patients (mean age 53.7 ± 15.2 years; 943 males, 58.4%) were assessed, with mean follow-up 2.46 years and 110 SCD events. Via logistic regression (n = 820), the odds of SCD increased with increasing number of conventional risk factors. With one risk factor the OR was 4.88 (p  450 to this logistic regression model had OR 1.722 (p = .04, CI 1.01-2.937) to predict SCD. QTc ≥ 450 was a significant predictor for death (HR 1.88, p = .021, CI 1.10-3.20). There was no correlation between sinus bradycardia, sinus tachycardia, first degree AV block, atrial fibrillation, left bundle branch block, right bundle branch block, premature atrial complexes, premature ventricular complexes, supraventricular tachycardia, PR interval, QRS interval and SCD. Prolonged QTc was a risk factor for SCD and death even when controlling for typical risk factors.

  5. Prolonged Tp-e Interval in Down Syndrome Patients with Congenitally Normal Hearts.

    Science.gov (United States)

    Kucuk, Mehmet; Karadeniz, Cem; Ozdemir, Rahmi; Meşe, Timur

    2018-03-25

    Heterogeneity of ventricular repolarization has been assessed by using the QT dispersion in Down syndrome (DS) patients with congenitally normal hearts. However, novel repolarization indexes, the Tp-e interval and Tp-e/QT ratio, have not previously been evaluated in these patients. The aim of this study was to evaluate the Tp-e interval and Tp-e/QT ratio in DS patients without congenital heart defects. Twelve-lead surface electrocardiograms of 160 DS patients and 110 age- and sex-matched healthy controls were used to evaluate and compare the Tp-e interval, Tp-e dispersion, and Tp-e/QT ratio. Heart rate, Tp-e interval, Tp-e dispersion, Tp-e/QT and Tp-e/QTc ratios were significantly higher in DS group than in the controls. Myocardial repolarization indexes in DS patients with congenitally normal hearts were found to be prolonged compared to those in normal controls. Further evaluation is warranted to reveal a relationship between prolonged repolarization indexes and arrhythmic events in these patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  6. 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

  7. Association between the physical activity and heart rate corrected-QT interval in older adults.

    Science.gov (United States)

    Michishita, Ryoma; Fukae, Chika; Mihara, Rikako; Ikenaga, Masahiro; Morimura, Kazuhiro; Takeda, Noriko; Yamada, Yosuke; Higaki, Yasuki; Tanaka, Hiroaki; Kiyonaga, Akira

    2015-07-01

    Increased physical activity can reduce the incidence of cardiovascular disease and the mortality rate. In contrast, a prolonged heart rate corrected-QT (QTc) interval is associated with an increased risk of arrhythmias, sudden cardiac death and coronary artery disease. The present cross-sectional study was designed to clarify the association between the physical activity level and the QTc interval in older adults. The participants included 586 older adults (267 men and 319 women, age 71.2 ± 4.7 years) without a history of cardiovascular disease, who were taking cardioactive drugs. Electrocardiography was recorded with a standard resting 12-lead electrocardiograph, while the QTc interval was calculated according to Hodges' formula. The physical activity level was assessed using a triaxial accelerometer. The participants were divided into four categories, which were defined equally quartile distributions of the QTc interval. After adjusting for age, body mass index, waist circumference and the number of steps, the time spent in inactivity was higher and the time spent in light physical activity was significantly lower in the longest QTc interval group than in the shortest QTc interval group in both sexes (P physical activities among the four groups in either sex. These results suggest that a decreased physical activity level, especially inactivity and light intensity physical activity, were associated with QTc interval in older adults. © 2014 Japan Geriatrics Society.

  8. Noninvasive cardiac activation imaging of ventricular arrhythmias during drug-induced QT prolongation in the rabbit heart.

    Science.gov (United States)

    Han, Chengzong; Pogwizd, Steven M; Killingsworth, Cheryl R; Zhou, Zhaoye; He, Bin

    2013-10-01

    Imaging myocardial activation from noninvasive body surface potentials promises to aid in both cardiovascular research and clinical medicine. To investigate the ability of a noninvasive 3-dimensional cardiac electrical imaging technique for characterizing the activation patterns of dynamically changing ventricular arrhythmias during drug-induced QT prolongation in rabbits. Simultaneous body surface potential mapping and 3-dimensional intracardiac mapping were performed in a closed-chest condition in 8 rabbits. Data analysis was performed on premature ventricular complexes, couplets, and torsades de pointes (TdP) induced during intravenous administration of clofilium and phenylephrine with combinations of various infusion rates. The drug infusion led to a significant increase in the QT interval (from 175 ± 7 to 274 ± 31 ms) and rate-corrected QT interval (from 183 ± 5 to 262 ± 21 ms) during the first dose cycle. All the ectopic beats initiated by a focal activation pattern. The initial beat of TdPs arose at the focal site, whereas the subsequent beats were due to focal activity from different sites or 2 competing focal sites. The imaged results captured the dynamic shift of activation patterns and were in good correlation with the simultaneous measurements, with a correlation coefficient of 0.65 ± 0.02 averaged over 111 ectopic beats. Sites of initial activation were localized to be ~5 mm from the directly measured initiation sites. The 3-dimensional cardiac electrical imaging technique could localize the origin of activation and image activation sequence of TdP during QT prolongation induced by clofilium and phenylephrine in rabbits. It offers the potential to noninvasively investigate the proarrhythmic effects of drug infusion and assess the mechanisms of arrhythmias on a beat-to-beat basis. © 2013 Heart Rhythm Society. All rights reserved.

  9. 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

    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...... athletic horses and to test for differences in the QT interval. ANIMALS: Ten Icelandic horses, 10 Arabian horses, 10 Thoroughbreds, 10 Standardbreds, six Coldblood trotters, 10 Warmbloods (dressage) and 10 Warmbloods (show jumping). All horses were geldings. METHODS: QT intervals were measured from resting...

  10. 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.

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

    Science.gov (United States)

    Gottlieb, Lisa A; Lubberding, Anniek; Larsen, Anders Peter; Thomsen, Morten B

    2017-01-01

    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 (QT 100 = QT/(RR/100) 1/2 ). Moreover, QT intervals were determined from complexes within the RR range of mean-RR ± 1% in the individual mouse (QT mean-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 cardiac deaths were observed. We find similar diurnal (light:dark) and circadian (darkness) rhythms of RR intervals in WT and KChIP2 -/- mice. Circadian rhythms in QT 100 intervals are present in both groups, but at physiological small amplitudes: 1.6 ± 0.2 and 1.0 ± 0.3 ms in WT and KChIP2 -/- , respectively (p = 0.15). A diurnal rhythm in QT 100 intervals was only found in WT mice. QT mean-RR intervals display clear diurnal and circadian rhythms in both WT and KChIP2 -/- . The amplitude of the circadian rhythm in QT mean-RR is 4.0 ± 0.3 and 3.1 ± 0.5 ms in WT and KChIP2 -/- , respectively (p = 0.16). In conclusion, KChIP2 expression does not appear to underlie the circadian rhythm in repolarization duration.

  12. 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.

  13. 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

    OBJECTIVES: This study sought to investigate whether prolongation of the heart rate-corrected QT (QTc) interval is a risk factor for sudden cardiac death in the general population. BACKGROUND: In developed countries, sudden cardiac death is a major cause of cardiovascular mortality. Prolongation...... of the QTc interval has been associated with ventricular arrhythmias, but in most population-based studies no consistent association was found between QTc prolongation and total or cardiovascular mortality. Only very few of these studies specifically addressed sudden cardiac death. METHODS: This study......). The association between a prolonged QTc interval and sudden cardiac death was estimated using Cox proportional hazards analysis. RESULTS: During an average follow-up period of 6.7 years (standard deviation, 2.3 years) 125 patients died of sudden cardiac death. An abnormally prolonged QTc interval (>450 ms in men...

  14. 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

  15. Erythromycin potentiates PR interval prolonging effect of verapamil in the rat: A pharmacodynamic drug interaction

    International Nuclear Information System (INIS)

    Dakhel, Yaman; Jamali, Fakhreddin

    2006-01-01

    Calcium channel blockers and macrolide antibiotics account for many drug interactions. Anecdotal reports suggest interactions between the two resulting in severe side effects. We studied the interaction between verapamil and erythromycin in the rat to see whether it occurs at the pharmacokinetics or pharmacodynamic level. Adult male Sprague-Dawley rats received doses of 1 mg/kg verapamil or 100 mg/kg erythromycin alone or in combination (n = 6/group). Serial blood samples (0-6 h) were taken for determination of the drug concentrations using HPLC. Electrocardiograms were recorded (0-6 h) through subcutaneously inserted lead II. Binding of the drugs to plasma proteins was studied using spiked plasma. Verapamil prolonged PR but not QT interval. Erythromycin prolonged QT but not PR interval. The combination resulted in a significant increase in PR interval prolongation and AV node blocks but did not further prolong QT interval. Pharmacokinetics and protein binding of neither drug were altered by the other. Our rat data confirm the anecdotal human case reports that combination of erythromycin and verapamil can result in potentiation of the cardiovascular response. The interaction appears to be at the pharmacodynamic rather than pharmacokinetic level hence may be extrapolated to other calcium channel antagonists

  16. Drug-Induced QTc Interval Prolongation: A Multicenter Study to Detect Drugs and Clinical Factors Involved in Every Day Practice.

    Science.gov (United States)

    Keller, Guillermo A; Alvarez, Paulino A; Ponte, Marcelo L; Belloso, Waldo H; Bagnes, Claudia; Sparanochia, Cecilia; Gonzalez, Claudio D; Villa Etchegoyen, M Cecilia; Diez, Roberto A; Di Girolamo, Guillermo

    2016-01-01

    The actual prevalence of drug induced QTc prolongation in clinical practice is unknown. Our objective was to determine the occurrence and characteristics of drug-induced QT prolongation in several common clinical practices. Additionally, a subgroup of patients treated with dextropropoxyphene of particular interest for the regulatory authority was analysed. Medical history and comorbidities predisposing to QT interval prolongation were registered for 1270 patient requiring medical assistance that involved drug administration. Three ionograms and ECGs were performed: baseline, intra- and after treatment; QT interval was corrected with Bazzet formula. Among patients, 9.9% presented QTc >450/470 ms, 3% QTc > 500 ms, 12.7% ΔQTc >30 ms and 5.2% ΔQTc >60 ms. QTc prolongation associated with congestive heart failure, ischemic cardiopathy, diabetes, renal failure, arrhythmias, hypothyroidism, and bradycardia. At univariate analysis, clarithromycin, haloperidol, tramadol, amiodarone, glyceryl trinitrate, amoxicillin + clavulanic acid, amoxicillin + sulbactam, ampicillin + sulbactam, fentanyl, piperacillin + tazobactam, and diazepam prolonged QTc. Prolongation remained significantly associated with furosemide, clarithromycin, glyceryl trinitrate and betalactamase inhibitors after multivariate analysis. QT interval prolongation in everyday practice is frequent, in association to clinical factors and drugs that can be easily identified for monitoring and prevention strategies.

  17. Optimisation of Embryonic and Larval ECG Measurement in Zebrafish for Quantifying the Effect of QT Prolonging Drugs

    Science.gov (United States)

    Dhillon, Sundeep Singh; Dóró, Éva; Magyary, István; Egginton, Stuart; Sík, Attila; Müller, Ferenc

    2013-01-01

    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. PMID:23579446

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

    Directory of Open Access Journals (Sweden)

    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.

  19. QT-RR relationships and suitable QT correction formulas for halothane-anesthetized dogs.

    Science.gov (United States)

    Tabo, Mitsuyasu; Nakamura, Mikiko; Kimura, Kazuya; Ito, Shigeo

    2006-10-01

    Several QT correction (QTc) formulas have been used for assessing the QT liability of drugs. However, they are known to under- and over-correct the QT interval and tend to be specific to species and experimental conditions. The purpose of this study was to determine a suitable formula for halothane-anesthetized dogs highly sensitive to drug-induced QT interval prolongation. Twenty dogs were anesthetized with 1.5% halothane and the relationship between the QT and RR intervals were obtained by changing the heart rate under atrial pacing conditions. The QT interval was corrected for the RR interval by applying 4 published formulas (Bazett, Fridericia, Van de Water, and Matsunaga); Fridericia's formula (QTcF = QT/RR(0.33)) showed the least slope and lowest R(2) value for the linear regression of QTc intervals against RR intervals, indicating that it dissociated changes in heart rate most effectively. An optimized formula (QTcX = QT/RR(0.3879)) is defined by analysis of covariance and represents a correction algorithm superior to Fridericia's formula. For both Fridericia's and the optimized formula, QT-prolonging drugs (d,l-sotalol, astemizole) showed QTc interval prolongation. A non-QT-prolonging drug (d,l-propranolol) failed to prolong the QTc interval. In addition, drug-induced changes in QTcF and QTcX intervals were highly correlated with those of the QT interval paced at a cycle length of 500 msec. These findings suggest that Fridericia's and the optimized formula, although the optimized is a little bit better, are suitable for correcting the QT interval in halothane-anesthetized dogs and help to evaluate the potential QT prolongation of drugs with high accuracy.

  20. 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...

  1. Evaluation of Tp-e interval and Tp-e/QT ratio in patients with non-dipper hypertension.

    Science.gov (United States)

    Demir, Mehmet; Uyan, Umut

    2014-01-01

    Non-dipper hypertension is associated with increased cardiovascular morbidity and mortality. Several studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (Tp-e) may correspond to the transmural dispersion of repolarization and that increased Tp-e interval and Tp-e/QT ratio are associated with malignant ventricular arrhythmias. The aim of this study was to evaluate ventricular repolarization by using Tp-e interval and Tp-e/QT ratio in patients with non-dipper hypertension. This study included 80 hypertensive patients. Hypertensive patients were divided into two groups: 50 dipper patients (29 male, mean age 51.5 ± 8 years) and 30 non-dipper patients (17 male, mean age 50.6 ± 5.4 years). Tp-e interval and Tp-e/QT ratio were measured from the 12-lead electrocardiogram. These parameters were compared between groups. No statistically significant difference was found between two groups in terms of basic characteristics. In electrocardiographic parameters analysis, QT dispersion (QTd) and corrected QTd were significantly increased in non-dipper patients compared to the dippers (39.4 ± 11.5 versus 27.3 ± 7.5 ms and 37.5 ± 9.5 versus 29.2 ± 6.5 ms, p = 0.001 and p = 0.01, respectively). Tp-e interval and Tp-e/QT ratio were also significantly higher in non-dipper patients (97.5 ± 11.2 versus 84.2 ± 8.3 ms and 0.23 ± 0.02 versus 0.17 ± 0.02, all p value ratio are prolonged in patients with non-dipper hypertension.

  2. New age- and sex-specific criteria for QT prolongation based on rate correction formulas that minimize bias at the upper normal limits.

    Science.gov (United States)

    Rautaharju, Pentti M; Mason, Jay W; Akiyama, Toshio

    2014-07-01

    Existing formulas for rate-corrected QT (QTc) commonly fail to properly adjust the upper normal limits which are more critical than the mean QTc for evaluation of prolonged QT. Age- and sex-related differences in QTc are also often overlooked. Our goal was to establish criteria for prolonged QTc using formulas that minimize QTc bias at the upper normal limits. Strict criteria were used in selecting a study group of 57,595 persons aged 5 to 89 years (54% women) and to exclude electrocardiograms (ECG) with possible disease-associated changes. Two QT rate adjustment formulas were identified which both minimized rate-dependency in the 98 th percentile limits: QTcmod, based on an electrophysiological model (QTcMod = QTx(120 + HR)/180)), and QTcLogLin, a power function of the RR interval with exponents 0.37 for men and 0.38 for women. QTc shortened in men during adolescence and QTcMod became 13 ms shorter than in women at age 20-29 years. The sex difference was maintained through adulthood although decreasing with age. The criteria established for prolonged QTc were: Age < 40 years, men 430 ms, women 440 ms; Age 40 to 69, men 440 ms, women 450 ms; Age ≥ 70 years, men 455 ms, and women 460 ms. Sex difference in QTc originates from shortened QT in adolescent males. Upper normal limits for QTc vary substantially by age and sex, and it is essential to use age- and sex-specific criteria for evaluation of QT prolongation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. Dynamic QT Interval Changes from Supine to Standing in Healthy Children.

    Science.gov (United States)

    Dionne, Audrey; Fournier, Anne; Dahdah, Nagib; Abrams, Dominic; Khairy, Paul; Abadir, Sylvia

    2018-01-01

    QT-interval variations in response to exercise-induced increases in heart rate have been reported in children and adults in the diagnosis of long QT syndrome (LQTS). A quick standing challenge has been proposed as an alternative provocative test in adults, with no pediatric data yet available. A standing test was performed in 100 healthy children (mean age, 9.7 ± 3.1 years) after 10 minutes in a supine position with continuous electrocardiographic recording. QT intervals were measured at baseline, at maximal heart rate, at maximal QT, and at each minute of a 5-minute recovery while standing. Measurements were taken in leads II/V 5 and were corrected for heart rate (QTc). On standing, the heart rate increased by 29 ± 10 beats per minute (bpm). The QT interval was similar at baseline and on standing (394 ± 34 ms vs 394 ± 34 ms; P = 1.0). However, QTc increased from 426 ± 21 to 509 ± 41 ms (P < 0.001). The 95th percentile for QTc at baseline and maximal heart rate was 457 ms and 563 ms, respectively. At 1 minute of recovery, the QT interval was shorter (375 ± 31 ms) compared with baseline (394 ± 34 ms; P < 0.001) and standing (394 ± 34 ms; P < 0.001). QTc reached baseline values after 1 minute of recovery and remained stable thereafter (423 ± 23 ms at 1 minute; 426 ± 22 ms at 5 minutes; P = 1.0). This first characterization of QTc changes on standing in children shows substantial alterations, which are greater than those seen in adults. Two-thirds of the children would have been misclassified as having LQTS by adult criteria, indicating the need to create child-specific standards. Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  4. The prevalence and significance of a short QT interval in 18,825 low-risk individuals including athletes.

    Science.gov (United States)

    Dhutia, Harshil; Malhotra, Aneil; Parpia, Sameer; Gabus, Vincent; Finocchiaro, Gherardo; Mellor, Greg; Merghani, Ahmed; Millar, Lynne; Narain, Rajay; Sheikh, Nabeel; Behr, Elijah R; Papadakis, Michael; Sharma, Sanjay

    2016-01-01

    The short QT syndrome is a cardiac channelopathy characterised by accelerated repolarisation which manifests as a short QT interval on the ECG. The definition of a short QT interval is debated, ranging from <390 to ≤320 ms, and its clinical significance in healthy young individuals is unknown. We assessed the prevalence and medium-term significance of an isolated short QT interval in a diverse young British population. Between 2005 and 2013, 18 825 apparently healthy people aged 14-35 years underwent cardiovascular evaluation with history, physical examination and ECG. QT intervals were measured by cardiologists using 4 recommended guidelines (Seattle 2013, Heart Rhythm Society 2013, European Society of Cardiology 2010 and American Heart Association 2009). The prevalence of a short QT interval was 0.1% (26 patients, ≤320 ms), 0.2% (44 patients, ≤330 ms), 7.9% (1478 patients, <380 ms), 15.8% (2973 patients, <390 ms). Male gender and Afro-Caribbean ethnicity had the strongest association with short QT intervals. Athletes had shorter QT intervals than non-athletes but athletic status did not predict short QT intervals. Individuals with short QT intervals ≤320 ms did not report syncope or a sinister family history, and during a follow-up period of 5.3±1.2 years, there were no deaths in this group. The prevalence of a short QT interval depends on the recommended cut-off value. Even at values ≤320 ms, there was an excellent medium-term prognosis among 14 people followed. We conclude that a definition of ≤320 ms is realistic to prevent overdiagnosis and excessive investigations. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  5. 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

    2017-01-01

    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...... cardiac deaths were observed. We find similar diurnal (light:dark) and circadian (darkness) rhythms of RR intervals in WT and KChIP2(-/-) mice. Circadian rhythms in QT100 intervals are present in both groups, but at physiological small amplitudes: 1.6 ± 0.2 and 1.0 ± 0.3 ms in WT and KChIP2......(-/-), respectively (p = 0.15). A diurnal rhythm in QT100 intervals was only found in WT mice. QTmean-RR intervals display clear diurnal and circadian rhythms in both WT and KChIP2(-/-). The amplitude of the circadian rhythm in QTmean-RR is 4.0 ± 0.3 and 3.1 ± 0.5 ms in WT and KChIP2(-/-), respectively (p = 0...

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

    Directory of Open Access Journals (Sweden)

    Daniel Medenwald

    Full Text Available 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.To determine the association between inflammation with an abnormally prolonged QT-time (APQT in men and women of the elderly general population.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.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.Our findings from cross-sectional analyses give evidence for an involvement of TNF-alpha in the pathology of APQT in women.

  7. QTc interval prolongation in children with Turner syndrome: the results of exercise testing and 24-h ECG.

    Science.gov (United States)

    Dalla Pozza, Robert; Bechtold, Susanne; Urschel, Simon; Netz, Heinrich; Schwarz, Hans-Peter

    2009-01-01

    Turner syndrome (TS) is the most common sex chromosome abnormality in females. Recently, a prolongation of the rate-corrected QT (QTc) interval in the electrocardiogram (ECG) of TS patients has been reported. A prolonged QTc interval has been correlated to an increased risk for sudden cardiac death, and medical treatment is warranted in patients with congenital long QT syndrome (LQTS). Additionally, several drugs of common use are contraindicated in LQTS because of their effects on myocardial repolarization. The importance of the QTc prolongation in TS patients is not known at present. Eighteen TS patients with a prolonged QTc interval (group 1) and 11 TS patients with a normal QTc interval (group 2) (mean age 12.6+/-3.1 vs. 11.8+/-2.1 years, respectively) were tested. The QTc interval was calculated during exercise testing and during 24-h ECG recordings. None of the patients experienced adverse cardiac events during the tests. The mean QTc interval decreased from 0.467 to 0.432 s in group 1 and from 0.432 to 0.412 s in group 2. During the 24-h ECG, the maximum QTc interval was significantly prolonged in group 1 (0.51 vs. 0.465 s, pinformation about the cardiac risk in the single TS patient with a prolonged QTc interval. This helps in counseling these girls, as clear therapeutic guidelines are currently lacking.

  8. 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...

  9. Multiple independent genetic factors at NOS1AP modulate the QT interval in a multi-ethnic population.

    Directory of Open Access Journals (Sweden)

    Dan E Arking

    Full Text Available Extremes of electrocardiographic QT interval are associated with increased risk for sudden cardiac death (SCD; thus, identification and characterization of genetic variants that modulate QT interval may elucidate the underlying etiology of SCD. Previous studies have revealed an association between a common genetic variant in NOS1AP and QT interval in populations of European ancestry, but this finding has not been extended to other ethnic populations. We sought to characterize the effects of NOS1AP genetic variants on QT interval in the multi-ethnic population-based Dallas Heart Study (DHS, n = 3,072. The SNP most strongly associated with QT interval in previous samples of European ancestry, rs16847548, was the most strongly associated in White (P = 0.005 and Black (P = 3.6 x 10(-5 participants, with the same direction of effect in Hispanics (P = 0.17, and further showed a significant SNP x sex-interaction (P = 0.03. A second SNP, rs16856785, uncorrelated with rs16847548, was also associated with QT interval in Blacks (P = 0.01, with qualitatively similar results in Whites and Hispanics. In a previously genotyped cohort of 14,107 White individuals drawn from the combined Atherosclerotic Risk in Communities (ARIC and Cardiovascular Health Study (CHS cohorts, we validated both the second locus at rs16856785 (P = 7.63 x 10(-8, as well as the sex-interaction with rs16847548 (P = 8.68 x 10(-6. These data extend the association of genetic variants in NOS1AP with QT interval to a Black population, with similar trends, though not statistically significant at P<0.05, in Hispanics. In addition, we identify a strong sex-interaction and the presence of a second independent site within NOS1AP associated with the QT interval. These results highlight the consistent and complex role of NOS1AP genetic variants in modulating QT interval.

  10. Assessment of cabozantinib treatment on QT interval in a phase 3 study in medullary thyroid cancer: evaluation of indirect QT effects mediated through treatment-induced changes in serum electrolytes.

    Science.gov (United States)

    Miles, Dale R; Lacy, Steven A; Wada, David R; Milwee, Steve; Yaron, Yifah; Nguyen, Linh T

    2017-08-01

    This study evaluated factors impacting QTc interval in a phase 3 trial of cabozantinib in progressive, metastatic, medullary thyroid cancer (MTC). Electrocardiogram (12-lead ECG) measurements were obtained at screening, and at pre-dose, and 2, 4, and 6 h post-dose on Days 1 and 29 in a phase 3 study in patients with MTC treated with cabozantinib (140 mg/day). Central tendency analyses were conducted on baseline-corrected QTc values. Linear and nonlinear mixed-effects models were used to evaluate potential factors affecting the QTc interval, including serum electrolytes, patient demographics, and cabozantinib concentration. Central tendency analysis showed that oral cabozantinib (140 mg/day) produced a 10-15 ms increase in delta-delta Fridericia corrected QT (∆∆QTcF) and delta-delta study-specific corrected QT (∆∆QTcS) on Day 29, but not on Day 1. Further analysis showed that QTcS provided a slightly more accurate QT correction than QTcF. Mixed-effects models evaluating serum electrolytes, age, sex, and cabozantinib concentration showed that decreased serum calcium and potassium could explain the majority of cabozantinib treatment-associated QTcS prolongation observed in this study. Cabozantinib treatment prolongs the ∆∆QTcF interval by 10-15 ms. There was the absence of a strong relationship between cabozantinib concentration and QTcS prolongation. Cabozantinib treatment effects on serum calcium and potassium best explain the QTcS prolongation observed in this study.

  11. 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.

  12. QT interval correction for drug-induced changes in body temperature during integrated cardiovascular safety assessment in regulatory toxicology studies in dogs: A case study.

    Science.gov (United States)

    El Amrani, Abdel-Ilah; El Amrani-Callens, Francine; Loriot, Stéphane; Singh, Pramila; Forster, Roy

    2016-01-01

    Cardiovascular safety assessment requires accurate evaluation of QT interval, which depends on the length of the cardiac cycle and also on core body temperature (BT). Increases in QT interval duration have been shown to be associated with decreases in BT in dogs. An example of altered QT interval duration associated with changes in body temperature observed during a 4-week regulatory toxicology study in dogs is presented. Four groups of Beagle dogs received the vehicle or test item once on Day 1, followed by a 4-week observation period. Electrocardiogram (ECG) parameters were continuously recorded on Days 1 and 26 by jacketed external telemetry (JET). Core body temperature (BT) was measured with a conventional rectal thermometer at appropriate time-points during the Day 1 recording period. Decreased BT was observed approximately 2h after treatment on Day 1, along with increased QT interval duration corrected according to the Van de Water formula (QTcV), but the effect was no longer observed after correction for changes in BT [QTcVcT=QTcV-14(37.5-BT)] according to the Van der Linde formula. No significant changes in QTcV were reported at the end of the observation period, on Day 26. The present study demonstrates that core body (rectal) temperature can easily be monitored at appropriate time-points during JET recording in regulatory toxicology studies in dogs, in order to correct QT interval duration values for treatment-related changes in BT. The successful application of the Van der Linde formula to correct QTc prolongation for changes in BT was demonstrated. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  13. QTc interval length and QT dispersion as predictors of mortality in patients with non-insulin-dependent diabetes

    DEFF Research Database (Denmark)

    Christensen, P K; Gall, M A; Major-Pedersen, A

    2000-01-01

    Patients with non-insulin-dependent diabetes (NIDDM) are at independent risk of cardiovascular death. The reason is only partially understood. The aim of our study was therefore to evaluate the impact of corrected QT interval length (QTc) and QT dispersion (QT-disp) on mortality in a cohort of 32....... Our study showed a high prevalence of QTc and QT-disp abnormalities and indicated that QTc-max but not QT-disp is an independent predictor of all cause and cardiovascular mortality in NIDDM patients.......-seven percent of the patients with PQTc died compared with 17% with normal QTc interval (pcause mortality; QTc-max (p....01), retinopathy (pcreatinine (p

  14. 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 r...... evaluation can serve as a guide for genotyping and can reduce the costs by suggesting which gene to start sequencing, but it is fiction that the ECG can replace genotyping....

  15. Long QT syndrome

    International Nuclear Information System (INIS)

    Contreras Z, Eduardo; Gomez M, Juan E; Zuluaga M, Sandra X.

    2008-01-01

    Long QT syndrome is a disease characterized by the electrocardiographic alteration in ventricular repolarization manifested by prolonged QT interval, secondary to prolonged ventricular repolarization. This makes these patients more vulnerable to very fast ventricular arrhythmias such as torsade des pointes or ventricular fibrillation. This syndrome is generally observed in young people and is associated with sudden death. It may appear as part of congenital LQTS (Jervell and Lange-Nielsen and Romano- Ward), or may be secondarily acquired due to metabolic or toxic alterations or to other pathophysiologic factors.

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

    Directory of Open Access Journals (Sweden)

    Yiyi Zhang

    2011-02-01

    Full Text Available 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.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.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.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.

  17. 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

    2011-02-28

    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. 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. 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). 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.

  18. Classification of the long-QT syndrome based on discriminant analysis of T-wave morphology

    DEFF Research Database (Denmark)

    Struijk, Johannes J.; Kanters, Jørgen K.; Andersen, M P

    2006-01-01

    The long QT syndrome (LQTS) is a genetic disorder, typically characterized by a prolonged QT interval in the ECG due to abnormal cardiac repolarization. LQTS may lead to syncopal episodes and sudden cardiac death. Various parameters based on T-wave morphology, as well as the QT interval itself ha...

  19. 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

    2017-11-01

    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.

  20. A case of hypoglycemiainduced QT prolongation leading to torsade de pointes and a review of pathophysiological mechanisms

    Directory of Open Access Journals (Sweden)

    Faris Hannoodi

    2017-06-01

    Full Text Available Torsades de pointes is a life-threatening cardiac arrhythmia. Occurrence of this arrhythmia as a result of hypoglycemia has not been reported in the literature. We describe an interesting case of an insulindependent diabetic patient presenting with torsades de pointes resulting from hypoglycemia. A 62-year-old male was admitted to the hospital following an episode of severe insulin-induced hypoglycemia and a cardiac arrest. He was found to unresponsive at home after taking insulin. His serum glucose was found to be 18. He was given juice initially to normalize his glucose and was then transferred by EMS to ER where he was given 5% dextrose infusion. Analysis of the LifeVest rhythm recording showed torsades de pointes that was terminated by defibrillation of the LifeVest. Several mechanisms are responsible for torsade, including QT interval prolongation, adrenalin secretion and calcium overload leading to intracellular calcium oscillations. These mechanisms are a trigger to torsade de pointes. Predisposing factors were present leading torsade to occur.

  1. 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

    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...

  2. Evaluation of Tp-E Interval and Tp-E/QT Ratio in Patients with Aortic Stenosis.

    Science.gov (United States)

    Yayla, Çağrı; Bilgin, Murat; Akboğa, Mehmet Kadri; Gayretli Yayla, Kadriye; Canpolat, Uğur; Dinç Asarcikli, Lale; Doğan, Mehmet; Turak, Osman; Çay, Serkan; Özeke, Özcan; Akyel, Ahmet; Yeter, Ekrem; Aydoğdu, Sinan

    2016-05-01

    The risk of syncope and sudden cardiac death due to ventricular arrhythmias increased in patients with aortic stenosis (AS). Recently, it was shown that Tp-e interval, Tp-e/QT, and Tp-e/QTc ratio can be novel indicators for prediction of ventricular arrhythmias and mortality. We aimed to investigate the association between AS and ventricular repolarization using Tp-e interval and Tp-e/QT ratio. Totally, 105 patients with AS and 60 control subjects were enrolled to this study. The severity of AS was defined by transthoracic echocardiographic examination. Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios were measured from the 12-lead electrocardiogram. Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios were significantly increased in parallel to the severity of AS (P ratio had significant positive correlation with mean aortic gradient (r = 0.192, P = 0.049). In multivariate logistic regression analysis, Tp-e/QTc ratio and left ventricular mass were found to be independent predictors of severe AS (P = 0.03 and P = 0.04, respectively). Our study showed that Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios were increased in patients with severe AS. Tp-e/QTc ratio and left ventricular mass were found as independent predictors of severe AS. © 2015 Wiley Periodicals, Inc.

  3. QT Interval Adaption to RR Interval Changes and Correlation Analysis between Heart Rate Variability and QT Interval Variability%QT间期对RR间期变化的响应及HRV与QTV的关联性分析

    Institute of Scientific and Technical Information of China (English)

    朱逸; 杨啸林; 彭屹

    2013-01-01

    体表心电图作为无创和连续的监测手段,在心脏安全评测方面具有重要而不可替代的位置.心电图中的间期时间序列包含着重要信息,其中以反映心动周期的RR间期序列,以及以QT间期为代表的反映心室复极化时程的间期序列,在临床上最为基础,相关的研究具有更为重要的意义.文中从应用基础研究的角度,就QT间期对于RR间期变化的响应,以及心率变异性(HRV)和QT间期变异性(QTV)关联性分析,分别介绍了其分析方法和研究进展,并且展望了可能的应用前景.%As a noninvasive and continuous monitoring method, surface electrocardiogram is significant in evaluating cardiac safety. The time interval series extracted from surface electrocardiogran contain important information. The RR and QT interval series, representing the cardiac cycle and the duration of ventricular repolarization, are with more research value. From the perspective of applied basic research, the methods and progress, concerning the QT interval adaption to RR interval changes and correlation analysis between heart rale variability (HRV) and QT interval variability (QTV) , were introduced here. And their potential applications were discussed as well.

  4. 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......-Nielsen syndrome (JLNS), Andersen syndrome (AS), and Timothy syndrome (TS). The genetics are further complicated by the occurrence of double and triple heterozygotes in LQTS and a considerable number of nonpathogenic rare polymorphisms in the involved genes. SQTS is a very rare condition, caused by mutations...

  5. QT interval and dispersion in drug-free anorexia nervosa adolescents: a case control study.

    Science.gov (United States)

    Bomba, Monica; Tremolizzo, Lucio; Corbetta, Fabiola; Nicosia, Franco; Lanfranconi, Francesca; Poggioli, Gianni; Goulene, Karine; Stramba-Badiale, Marco; Conti, Elisa; Neri, Francesca; Nacinovich, Renata

    2017-11-16

    Long QT values have been reported in patients with anorexia nervosa of the restricting type (ANr) potentially increasing the risk of fatal arrhythmia, especially if psychotropic drug treatment is required. Nevertheless, the previous studies on this topic are biased by drug exposure, long disease durations, and small sample sizes. This study is aimed at assessing QTc and QTcd values in ANr adolescents with recent onset and drug free, as compared to subjects affected by psychiatric disorders other than ANr. We evaluated QTc and its dispersion (QTcd) in a population of 77 drug-free ANr female adolescents and compared to an equal number of healthy controls (H-CTRL) and pathological controls (P-CTRL, mixed psychiatric disorders). The QT determination was performed on a standard simultaneous 12-lead ECG in blind by a single experienced investigator. QTc was calculated by the Bazett's formula and QTcd was determined as the difference between the maximum and minimum QTc intervals in different leads. Only for ANr patients, clinico-demographic data, hormones, and electrolytes were obtained. QTc was slightly reduced in ANr patients (27.7 ms, studies are needed to understand if the previously reported increase might be related to other associated chronic disorders, such as hormonal or electrolyte imbalance.

  6. Mechanisms, Risk Factors, and Management of Acquired Long QT Syndrome: A Comprehensive Review

    Directory of Open Access Journals (Sweden)

    Eleftherios M. Kallergis

    2012-01-01

    Full Text Available Long QT syndrome is characterized by prolongation of the corrected QT (QTc interval on the surface electrocardiogram and is associated with precipitation of torsade de pointes (TdP, a polymorphic ventricular tachycardia that may cause sudden death. Acquired long QT syndrome describes pathologic excessive prolongation of the QT interval, upon exposure to an environmental stressor, with reversion back to normal following removal of the stressor. The most common environmental stressor in acquired long QT syndrome is drug therapy. Acquired long QT syndrome is an important issue for clinicians and a significant public health problem concerning the large number of drugs with this adverse effect with a potentially fatal outcome, the large number of patients exposed to these drugs, and our inability to predict the risk for a given individual. In this paper, we focus on mechanisms underlying QT prolongation, risk factors for torsades de pointes and describe the short- and long-term treatment of acquired long QT syndrome.

  7. QT measurement and heart rate correction during hypoglycemia

    DEFF Research Database (Denmark)

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

    2010-01-01

    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......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...... prolongation at hypoglycemia for QTcB (42(6) ms; P measuring the QT interval has...

  8. Long QT syndrome and torsades de pointes complicating mitral valve replacement

    Directory of Open Access Journals (Sweden)

    Shegu Gilbert

    2016-09-01

    Full Text Available Severe QT interval prolongation >500 ms occurs in one quarter of cardiac surgical patients in the perioperative period while moderate prolongation occurs in most of them. Prolonged QT interval may be associated with torsades de pointes and lead to sudden cardiac death. Because of the high incidence of prolonged QT in cardiac surgery patients and its perioperative adverse outcomes, it is vital to identify it early and take necessary precautions. We report and discuss the catastrophic events and management of two patients with long QT syndrome complicating mitral valve replacement.

  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. Evaluation of Tp-e interval and Tp-e/QT ratio in patients with ankylosing spondylitis.

    Science.gov (United States)

    Acar, Gurkan; Yorgun, Hikmet; Inci, Mehmet Fatih; Akkoyun, Murat; Bakan, Betul; Nacar, Alper Bugra; Dirnak, Imran; Cetin, Gozde Yildirim; Bozoglan, Orhan

    2014-03-01

    Ankylosing spondylitis (AS) is a chronic multi-systemic inflammatory rheumatic disorder. Several studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (Tp-e) may correspond to the transmural dispersion of repolarization and that increased Tp-e interval and Tp-e/QT ratio are associated with malignant ventricular arrhythmias. The aim of this study was to evaluate ventricular repolarization by using Tp-e interval and Tp-e/QT ratio in patients with AS, and to assess the relation with inflammation. Sixty-two patients with AS and 50 controls were included. Tp-e interval and Tp-e/QT ratio were measured from a 12-lead electrocardiogram, and the Tp-e interval corrected for heart rate. The plasma level of high sensitive C-reactive protein (hsCRP) was measured. These parameters were compared between groups. In electrocardiographic parameters analysis, QT dispersion (QTd) and corrected QTd were significantly increased in AS patients compared to the controls (31.7 ± 9.6 vs 28.2 ± 7.4 and 35.8 ± 11.5 vs 30.6 ± 7.9 ms, P = 0.03 and P = 0.007, respectively). cTp-e interval and Tp-e/QT ratio were also significantly higher in AS patients (92.1 ± 10.2 vs 75.8 ± 8.4 and 0.22 ± 0.02 vs 0.19 ± 0.02 ms, all P values ratio were significantly correlated with hsCRP (r = 0.63, P ratio were increased in AS patients. These electrocardiographic ventricular repolarization indexes were significantly correlated with the plasma level of hsCRP.

  11. Congenital Short QT Syndrome

    Directory of Open Access Journals (Sweden)

    Lia Crotti

    2010-02-01

    Full Text Available The Short QT Syndrome is a recently described new genetic disorder, characterized by abnormally short QT interval, paroxysmal atrial fibrillation and life threatening ventricular arrhythmias. This autosomal dominant syndrome can afflict infants, children, or young adults; often a remarkable family background of cardiac sudden death is elucidated. At electrophysiological study, short atrial and ventricular refractory periods are found, with atrial fibrillation and polymorphic ventricular tachycardia easily induced by programmed electrical stimulation. Gain of function mutations in three genes encoding K+ channels have been identified, explaining the abbreviated repolarization seen in this condition: KCNH2 for Ikr (SQT1, KCNQ1 for Iks (SQT2 and KCNJ2 for Ik1 (SQT3. The currently suggested therapeutic strategy is an ICD implantation, although many concerns exist for asymptomatic patients, especially in pediatric age. Pharmacological treatment is still under evaluation; quinidine has shown to prolong QT and reduce the inducibility of ventricular arrhythmias, but awaits additional confirmatory clinical data.

  12. 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.

  13. Effects of atomoxetine on the QT interval in healthy CYP2D6 poor metabolizers

    Science.gov (United States)

    Loghin, Corina; Haber, Harry; Beasley, Charles M; Kothare, Prajakti A; Kauffman, Lynnette; April, John; Jin, Ling; Allen, Albert J; Mitchell, Malcolm I

    2013-01-01

    Aim The effects of atomoxetine (20 and 60 mg twice daily), 400 mg moxifloxacin and placebo on QTc in 131 healthy CYP2D6 poor metabolizer males were compared. Methods Atomoxetine doses were selected to result in plasma concentrations that approximated expected plasma concentrations at both the maximum recommended dose and at a supratherapeutic dose in CYP2D6 extensive metabolizers. Ten second electrocardiograms were obtained for time-matched baseline on days −2 and −1, three time points after dosing on day 1 for moxifloxacin and five time points on day 7 for atomoxetine and placebo. Maximum mean placebo-subtracted change from baseline model-corrected QT (QTcM) on day 7 was the primary endpoint. Results QTcM differences for atomoxetine 20 and 60 mg twice daily were 0.5 ms (upper bound of the one-sided 95% confidence interval 2.2 ms) and 4.2 ms (upper bound of the one-sided 95% confidence interval 6.0 ms), respectively. As plasma concentration of atomoxetine increased, a statistically significant increase in QTc was observed. The moxifloxacin difference from placebo met the a priori definition of non-inferiority. Maximum mean placebo-subtracted change from baseline QTcM for moxifloxacin was 4.8 ms and this difference was statistically significant. Moxifloxacin plasma concentrations were below the concentrations expected from the literature. However, the slope of the plasma concentration−QTc change observed was consistent with the literature. Conclusion Atomoxetine was not associated with a clinically significant change in QTc. However, a statistically significant increase in QTc was associated with increasing plasma concentrations. PMID:22803597

  14. PR Interval Prolongation and Cryptogenic Stroke: A Multicenter Retrospective Study.

    Science.gov (United States)

    Montalvo, Mayra; Tadi, Prasanna; Merkler, Alexander; Gialdini, Gino; Martin-Schild, Sheryl; Navalkele, Digvijaya; Samai, Alyana; Nouh, Amre; Hussain, Mohammad; Goldblatt, Steven; Hemendinger, Morgan; Chu, Antony; Song, Christopher; Kamel, Hooman; Furie, Karen L; Yaghi, Shadi

    2017-10-01

    Atrial dysfunction or "cardiopathy" has been recently proposed as a mechanism in cryptogenic stroke. A prolonged PR interval may reflect impaired atrial conduction and thus may be a biomarker of atrial cardiopathy. We aim to compare the prevalence of PR interval prolongation in patients with cryptogenic stroke (CS) when compared with known non-cryptogenic non-cardioembolic stroke (NCNCS) subtypes. We used prospective ischemic stroke databases of 3 comprehensive stroke centers to identify patients 18 years or older with a discharge diagnosis of ischemic non-cardioembolic stroke between December 1, 2013 and August 31, 2015. The main outcome was ischemic stroke subtype (CS versus NCNCS). We compared PR intervals as a continuous and categorical variable (PR interval prolongation and CS. We identified 644 patients with ischemic non-cardioembolic stroke (224 CS and 420 NCNCS). Patients with CS were more likely to have a PR of 200 milliseconds or greater when compared with those with NCNCS (23.2% versus 13.8%, P = .009). After adjusting for factors that were significant in univariate analyses, a PR of 200 milliseconds or greater was independently associated with CS (odds ratio [OR] 1.70, 95% CI 1.08-2.70). The association was more pronounced when excluding patients on atrioventricular nodal blocking agents (OR 2.64, 95% CI 1.44-4.83). A PR of 200 milliseconds or greater is associated with CS and may be a biomarker of atrial cardiopathy in the absence of atrial fibrillation. Prospective studies are needed to confirm this association. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  15. Relationship between Corrected-QT Intervals and Other ECG Characteristics with Methadone Dose in Methadone Maintenance Treatment (MMT Patients and Healthy Subjects: A Case- Control Study

    Directory of Open Access Journals (Sweden)

    Mina Akbari Rad

    2017-05-01

    Full Text Available Background In this study we assessed the relationship between corrected-QT intervals and other ECG characteristics with methadone dose and other parameters in MMT patients and healthy subjects. Methods This was a case-control study which was carried out on patients underwent MMT and healthy control group who had been referred to Ebne-Sina academic hospital, Mashhad during 2014 - 2015. At the time of the study, 40 patients who received MMT therapy for at least 6 months and 40 voluntary healthy subjects who matched on age and sex enrolled in the study. 12-lead ECG was performed for all the patients. Mean QT interval, PR interval and QRS duration in every 12 leads were documented for each patient in maximum. Results To evaluate the patients, we divided 80 patients into two groups: 40 patients under treatment with Methadone and 40 voluntary participants as control group. There were 20 males and 20 females in each group. Duration of addiction was 214.80 ± 126.99 months in MMT group. Significant differences were observed in PRi between the patient and control groups (P = 0.007, and also between methadone dose and PRi (r = 0.468, P = 0.038 in males. QTc prolongation was reported in 4 patients of addicted group (10%. All of the QTc prolongation patients were female (P = 0.037. There was significant relationship between PRi and weight (P = 0.015, addiction period (P = 0.011, methadone treatment period (P = 0.018 as well as methadone dosage (P = 0.14. Methadone cut off point of 65 mg had a significant relationship with systolic blood pressure (P = 0.002, diastolic blood pressure (P = 0.013, QTCi (P = 0.016 and QRS (P = 0.044; however, no significant relationship was reported with PRi (P = 0.451. Conclusions We found that there is no exact dosage of methadone in which the side effects such as TdP (Torsade de pointes or QTc prolongation can be predicted. Female gender and methadone dosage ≥ 65 mg were risk factors of our study for QTc prolongation which

  16. 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.

  17. 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.

  18. Congenital Short QT Syndrome

    Directory of Open Access Journals (Sweden)

    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.

  19. Testosterone-mediated upregulation of delayed rectifier potassium channel in cardiomyocytes causes abbreviation of QT intervals in rats.

    Science.gov (United States)

    Masuda, Kimiko; Takanari, Hiroki; Morishima, Masaki; Ma, FangFang; Wang, Yan; Takahashi, Naohiko; Ono, Katsushige

    2018-01-13

    Men have shorter rate-corrected QT intervals (QTc) than women, especially at the period of adolescence or later. The aim of this study was to elucidate the long-term effects of testosterone on cardiac excitability parameters including electrocardiogram (ECG) and potassium channel current. Testosterone shortened QT intervals in ECG in castrated male rats, not immediately after, but on day 2 or later. Expression of Kv7.1 (KCNQ1) mRNA was significantly upregulated by testosterone in cardiomyocytes of male and female rats. Short-term application of testosterone was without effect on delayed rectifier potassium channel current (I Ks ), whereas I Ks was significantly increased in cardiomyocytes treated with dihydrotestosterone for 24 h, which was mimicked by isoproterenol (24 h). Gene-selective inhibitors of a transcription factor SP1, mithramycin, abolished the effects of testosterone on Kv7.1. Testosterone increases Kv7.1-I Ks possibly through a pathway related to a transcription factor SP1, suggesting a genomic effect of testosterone as an active factor for cardiac excitability.

  20. Short QT syndrome

    Directory of Open Access Journals (Sweden)

    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.

  1. Interleukin-1β gene variants are associated with QTc interval prolongation following cardiac surgery: a prospective observational study.

    Science.gov (United States)

    Kertai, Miklos D; Ji, Yunqi; Li, Yi-Ju; Mathew, Joseph P; Daubert, James P; Podgoreanu, Mihai V

    2016-04-01

    We characterized cardiac surgery-induced dynamic changes of the corrected QT (QTc) interval and tested the hypothesis that genetic factors are associated with perioperative QTc prolongation independent of clinical and procedural factors. All study subjects were ascertained from a prospective study of patients who underwent elective cardiac surgery during August 1999 to April 2002. We defined a prolonged QTc interval as > 440 msec, measured from 24-hr pre- and postoperative 12-lead electrocardiograms. The association of 37 single nucleotide polymorphisms (SNPs) in 21 candidate genes -involved in modulating arrhythmia susceptibility pathways with postoperative QTc changes- was investigated in a two-stage design with a stage I cohort (n = 497) nested within a stage II cohort (n = 957). Empirical P values (Pemp) were obtained by permutation tests with 10,000 repeats. After adjusting for clinical and procedural risk factors, we selected four SNPs (P value range, 0.03-0.1) in stage I, which we then tested in the stage II cohort. Two functional SNPs in the pro-inflammatory cytokine interleukin-1β (IL1β), rs1143633 (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.53 to 0.95; Pemp = 0.02) and rs16944 (OR, 1.31; 95% CI, 1.01 to 1.70; Pemp = 0.04), remained independent predictors of postoperative QTc prolongation. The ability of a clinico-genetic model incorporating the two IL1B polymorphisms to classify patients at risk for developing prolonged postoperative QTc was superior to a clinical model alone, with a net reclassification improvement of 0.308 (P = 0.0003) and an integrated discrimination improvement of 0.02 (P = 0.000024). The results suggest a contribution of IL1β in modulating susceptibility to postoperative QTc prolongation after cardiac surgery.

  2. 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

  3. 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

    and moderate HF (New York Heart Association classes II to III) were compared to matched controls. Twenty patients had implantable cardiac defibrillators secondary to a history of ventricular tachycardia (VT). Two cardiologists blinded to diagnosis manually measured QT intervals. Beat-to-beat variability...

  4. Relationship between QT Interval Dispersion in acute stroke and stroke prognosis: A Systematic Review

    Science.gov (United States)

    Lederman, Yitzchok S.; Balucani, Clotilde; Lazar, Jason; Steinberg, Leah; Gugger, James; Levine, Steven R.

    2014-01-01

    Background QT dispersion (QTd) has been proposed as an indirect ECG measure of heterogeneity of ventricular repolarization. The predictive value of QTd in acute stroke remains controversial. We aimed to clarify the relationship between QTd and acute stroke and stroke prognosis. Methods A systematic review of the literature was performed using pre-specified medical subjects heading (MeSH) terms, Boolean logic and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Eligible studies (a) included ischemic or hemorrhagic stroke and (b) provided QTd measurements. Results Two independent reviewers identified 553 publications. Sixteen articles were included in the final analysis. There were a total of 888 stroke patients: 59% ischemic and 41% hemorrhagic. There was considerable heterogeneity in study design, stroke subtypes, ECG assessment-time, control groups and comparison groups. Nine studies reported a significant association between acute stroke and baseline QTd. Two studies reported that QTd increases are specifically related to hemorrhagic strokes, involvement of the insular cortex, right-side lesions, larger strokes, and increases in 3, 4-dihydroxyphenylethylene glycol in hemorrhagic stroke. Three studies reported QTd to be an independent predictor of stroke mortality. One study each reported increases in QTd in stroke patients who developed ventricular arrhythmias and cardiorespiratory compromise. Conclusions There are few well-designed studies and considerable variability in study design in addressing the significance of QTd in acute stroke. Available data suggest that stroke is likely to be associated with increased QTd. While some evidence suggests a possible prognostic role of QTd in stroke, larger and well-designed studies need to confirm these findings. PMID:25282188

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

    Directory of Open Access Journals (Sweden)

    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

  6. Electrophysiological mechanisms of long and short QT syndromes

    Directory of Open Access Journals (Sweden)

    Gary Tse

    2017-03-01

    Full Text Available The QT interval on the human electrocardiogram is normally in the order of 450 ms, and reflects the summated durations of action potential (AP depolarization and repolarization of ventricular myocytes. Both prolongation and shortening in the QT interval have been associated with ventricular tachy-arrhythmias, which predispose affected individuals to sudden cardiac death. In this article, the molecular determinants of the AP duration and the causes of long and short QT syndromes (LQTS and SQTS are explored. This is followed by a review of the recent advances on their arrhythmogenic mechanisms involving reentry and/or triggered activity based on experiments conducted in mouse models. Established and novel clinical risk markers based on the QT interval for the prediction of arrhythmic risk and cardiovascular mortality are presented here. It is concluded by a discussion on strategies for the future rational design of anti-arrhythmic agents.

  7. The congenital long QT syndrome Type 3: An update

    Directory of Open Access Journals (Sweden)

    Andrés Ricardo Pérez-Riera

    2018-01-01

    Full Text Available Congenital long QT syndrome type 3 (LQT3 is the third in frequency compared to the 15 forms known currently of congenital long QT syndrome (LQTS. Cardiac events are less frequent in LQT3 when compared with LQT1 and LQT2, but more likely to be lethal; the likelihood of dying during a cardiac event is 20% in families with an LQT3 mutation and 4% with either an LQT1 or an LQT2 mutation. LQT3 is consequence of mutation of gene SCN5A which codes for the Nav1.5 Na+ channel α-subunit and electrocardiographically characterized by a tendency to bradycardia related to age, prolonged QT/QTc interval (mean QTc value 478 ± 52 ms, accentuated QT dispersion consequence of prolonged ST segment, late onset of T wave and frequent prominent U wave because of longer repolarization of the M cell across left ventricular wall.

  8. A randomized, placebo-controlled, four-period crossover, definitive QT study of the effects of APF530 exposure, high-dose intravenous granisetron, and moxifloxacin on QTc prolongation

    Directory of Open Access Journals (Sweden)

    Mason JW

    2014-03-01

    Full Text Available Jay W Mason,1 Thomas E Moon,2 Erin O’Boyle,3 Albert Dietz41Department of Medicine, University of Utah, Salt Lake City, UT, 2Tarizona eHealth Services, Inc., San Carlos, CA, 3AP Pharma, Redwood City, CA, 4Spaulding Clinical Research, West Bend, WI, USABackground: Regulatory concern about potential QT-interval prolongation by serotonin-receptor antagonist antiemetics prompted product-label changes. The first-generation serotonin-receptor antagonist granisetron is available in oral (PO, intravenous (IV, and transdermal formulations. APF530 is a formulation that provides sustained release of granisetron when administered as a single subcutaneous (SC injection. The Phase I study reported here evaluated effects of APF530 on electrocardiographic intervals.Methods: This single-site, double-blind, placebo-controlled, four-period crossover trial randomized healthy men and women to receive varying sequences of APF530 1 g SC, granisetron 50 μg/kg IV, moxifloxacin 400 mg PO, and placebo. Subjects were assessed for 49 hours after each treatment. The primary objective was to evaluate differences between baseline-adjusted, heart rate-corrected QT-interval change using the Fridericia rate correction (dQTcF for APF530 1 g SC and placebo. Electrocardiograms were performed at various times throughout the assessment period. Pharmacokinetics and safety were evaluated.Results: The upper one-sided 95% confidence interval (CI for mean baseline-adjusted dQTcF at each post-dose time point between APF530 and placebo excluded 10 ms, indicating that APF530 1 g SC had no clinically significant effect on QTcF. Maximum observed QTcF change was 4.15 ms (90% CI, 0.94 to 7.36 at Hour 3. No clinically significant changes in other electrocardiogram intervals were observed. APF530 SC pharmacokinetics were as expected, with slow absorption (maximum plasma concentration 35.8 ng/mL, median time to maximum plasma concentration 11.1 hours and slow elimination (mean half-life 18.6 hours

  9. The effect of changes in core body temperature on the QT interval in beagle dogs: a previously ignored phenomenon, with a method for correction.

    Science.gov (United States)

    van der Linde, H J; Van Deuren, B; Teisman, A; Towart, R; Gallacher, D J

    2008-08-01

    Body core temperature (Tc) changes affect the QT interval, but correction for this has not been systematically investigated. It may be important to correct QT intervals for drug-induced changes in Tc. Anaesthetized beagle dogs were artificially cooled (34.2 degrees C) or warmed (42.1 degrees C). The relationship between corrected QT intervals (QTcV; QT interval corrected according to the Van de Water formula) and Tc was analysed. This relationship was also examined in conscious dogs where Tc was increased by exercise. When QTcV intervals were plotted against changes in Tc, linear correlations were observed in all individual dogs. The slopes did not significantly differ between cooling (-14.85+/-2.08) or heating (-13.12+/-3.46) protocols. We propose a correction formula to compensate for the influence of Tc changes and standardize the QTcV duration to 37.5 degrees C: QTcVcT (QTcV corrected for changes in core temperature)=QTcV-14 (37.5 - Tc). Furthermore, cooled dogs were re-warmed (from 34.2 to 40.0 degrees C) and marked QTcV shortening (-29%) was induced. After Tc correction, using the above formula, this decrease was abolished. In these re-warmed dogs, we observed significant increases in T-wave amplitude and in serum [K(+)] levels. No arrhythmias or increase in pro-arrhythmic biomarkers were observed. In exercising dogs, the above formula completely compensated QTcV for the temperature increase. This study shows the importance of correcting QTcV intervals for changes in Tc, to avoid misleading interpretations of apparent QTcV interval changes. We recommend that all ICH S7A, conscious animal safety studies should routinely measure core body temperature and correct QTcV appropriately, if body temperature and heart rate changes are observed.

  10. A randomized, placebo-controlled, four-period crossover, definitive QT study of the effects of APF530 exposure, high-dose intravenous granisetron, and moxifloxacin on QTc prolongation

    International Nuclear Information System (INIS)

    Mason, Jay W; Moon, Thomas E; O’Boyle, Erin; Dietz, Albert

    2014-01-01

    Regulatory concern about potential QT-interval prolongation by serotonin-receptor antagonist antiemetics prompted product-label changes. The first-generation serotonin-receptor antagonist granisetron is available in oral (PO), intravenous (IV), and transdermal formulations. APF530 is a formulation that provides sustained release of granisetron when administered as a single subcutaneous (SC) injection. The Phase I study reported here evaluated effects of APF530 on electrocardiographic intervals. This single-site, double-blind, placebo-controlled, four-period crossover trial randomized healthy men and women to receive varying sequences of APF530 1 g SC, granisetron 50 μg/kg IV, moxifloxacin 400 mg PO, and placebo. Subjects were assessed for 49 hours after each treatment. The primary objective was to evaluate differences between baseline-adjusted, heart rate-corrected QT-interval change using the Fridericia rate correction (dQTcF) for APF530 1 g SC and placebo. Electrocardiograms were performed at various times throughout the assessment period. Pharmacokinetics and safety were evaluated. The upper one-sided 95% confidence interval (CI) for mean baseline-adjusted dQTcF at each post-dose time point between APF530 and placebo excluded 10 ms, indicating that APF530 1 g SC had no clinically significant effect on QTcF. Maximum observed QTcF change was 4.15 ms (90% CI, 0.94 to 7.36) at Hour 3. No clinically significant changes in other electrocardiogram intervals were observed. APF530 SC pharmacokinetics were as expected, with slow absorption (maximum plasma concentration 35.8 ng/mL, median time to maximum plasma concentration 11.1 hours) and slow elimination (mean half-life 18.6 hours; systemic clearance 20.2 L/hour) of granisetron versus the expected early peak concentration and elimination of granisetron IV. APF530 SC was well tolerated. Adverse events, most commonly constipation and SC injection-site reactions, were generally mild and quickly resolved. APF530 1 g SC did

  11. 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.

  12. 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.

  13. 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

  14. Onset of decreased heart work is correlated with increased heart rate and shortened QT interval in high-carbohydrate fed overweight rats.

    Science.gov (United States)

    Durak, Aysegul; Olgar, Yusuf; Tuncay, Erkan; Karaomerlioglu, Irem; Kayki Mutlu, Gizem; Arioglu Inan, Ebru; Altan, Vecdi Melih; Turan, Belma

    2017-11-01

    Mechanical activity of the heart is adversely affected in metabolic syndrome (MetS) characterized by increased body mass and marked insulin resistance. Herein, we examined the effects of high carbohydrate intake on cardiac function abnormalities by evaluating in situ heart work, heart rate, and electrocardiograms (ECGs) in rats. MetS was induced in male Wistar rats by adding 32% sucrose to drinking water for 22-24 weeks and was confirmed by insulin resistance, increased body weight, increased blood glucose and serum insulin, and increased systolic and diastolic blood pressures in addition to significant loss of left ventricular integrity and increased connective tissue around myofibrils. Analysis of in situ ECG recordings showed a markedly shortened QT interval and decreased QRS amplitude with increased heart rate. We also observed increased oxidative stress and decreased antioxidant defense characterized by decreases in serum total thiol level and attenuated paraoxonase and arylesterase activities. Our data indicate that increased heart rate and a shortened QT interval concomitant with higher left ventricular developed pressure in response to β-adrenoreceptor stimulation as a result of less cyclic AMP release could be regarded as a natural compensation mechanism in overweight rats with MetS. In addition to the persistent insulin resistance and obesity associated with MetS, one should consider the decreased heart work, increased heart rate, and shortened QT interval associated with high carbohydrate intake, which may have more deleterious effects on the mammalian heart.

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

    Directory of Open Access Journals (Sweden)

    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

  16. Effects of energy drink consumption on corrected QT interval and heart rate variability in young obese Saudi male university students.

    Science.gov (United States)

    Alsunni, Ahmed; Majeed, Farrukh; Yar, Talay; AlRahim, Ahmed; Alhawaj, Ali Fouad; Alzaki, Muneer

    2015-01-01

    Consumption of energy drinks has adverse effects on the heart that might be potentiated in obese individuals. Since the incidence of obesity and use of energy drinks is high among Saudi youth, we used non-invasive tests to study hemodynamic changes produced by altered autonomic cardiac activ.ity following consumption of energy drinks in obese male students. This cross-sectional study was carried out at Department of Physiology, College of Medicine, University of Dammam, Saudi Arabia, over a one-year period from December 2013 to December 2014. In Saudi male university students we measured continuous ECG recordings and a one-minute deep breathing maneuver to measure the expiratory-to-inspiratory ratio, the mean heart rate range (MHRR), the mean percentage variability. (M%VHR) and the corrected QT interval (QTc) at 0, 30 and 60 minutes after consumption of energy drink. We enrolled 31 students (18 overweight/obese and 13 normal weights. QTc was significantly in.creased at 60 min as compared with the resting state in overweight/obese subjects (P=.006). Heart rate variability was significantly less in obese as compared with normal weight subjects at 60 minutes as indicated by E:I ratio, (P=.037), MHRR (P=.012), M%VHR (P=.040) after energy drink consumption. Significant increases in diastolic (P=.020) and mean arterial blood pressure (P=.024) were observed at 30 minutes in the obese group. Hemodynamic changes after intake of energy drinks in obese subjects indicate that obesity and energy drinks could synergistically induce harmful effects. This finding warrants efforts to caution the obese on intake of energy drinks and timely intervention to motivate changes in lifestyle.

  17. Obstructive sleep apnea is associated with increased QT corrected interval dispersion: the effects of continuous positive airway pressure.

    Science.gov (United States)

    Bilal, Nagihan; Dikmen, Nursel; Bozkus, Fulsen; Sungur, Aylin; Sarica, Selman; Orhan, Israfil; Samur, Anil

    2017-03-31

    Severe obstructive sleep apnea (OSA) is associated with increased QT corrected interval dispersion (QTcd) and continuous positive airway pressure (CPAP) is thought to improve this arrhythmogenic marker. The aim of the study was to determine the decrease of ratio of cardiovascular risk in patients with obstructive sleep apnea. The study included 65 patients with severe OSA who had an apnea-hypopnea index (AHI) score of >30. Each patient underwent 12-channel electrocardiogram (ECG) monitoring and polysomnography. Patients with an AHI score of <5 were used as the control group. The control group also underwent ECG monitoring and polysomnography testing. The QTcd levels of both groups were calculated. Three months after CPAP treatment, ECG recordings were obtained from the 65 patients with severe OSA again, and their QTcd values were calculated. There were 44 male and 21 female patients with severe OSA syndrome. The age, gender, body mass index, initial saturation, minimum saturation, average saturation, and desaturation index were determined in both groups. The QTc intervals of the OSA patients (62.48±16.29ms) were significantly higher (p=0.001) than those of the control group (29.72±6.30ms). There were statistically significant differences between the QTc values before and after the CPAP treatment, with pretreatment QTc intervals of 62.48±16.29ms and 3-month post-treatment values of 41.42±16.96ms (p=0.001). There was a positive and significant correlation between QTcd periods and the AHI and hypopnea index (HI) in OSA patients (p=0.001; r=0.71; p=0.001; r=0.679, respectively). CPAP treatment reduced the QTcd in patients with severe OSA. In addition, shortening the QTcd periods in patients with severe OSA may reduce their risk of arrhythmias and cardiovascular disease. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  18. Mouse models of long QT syndrome

    Science.gov (United States)

    Salama, Guy; London, Barry

    2007-01-01

    Congenital long QT syndrome is a rare inherited condition characterized by prolongation of action potential duration (APD) in cardiac myocytes, prolongation of the QT interval on the surface electrocardiogram (ECG), and an increased risk of syncope and sudden death due to ventricular tachyarrhythmias. Mutations of cardiac ion channel genes that affect repolarization cause the majority of the congenital cases. Despite detailed characterizations of the mutated ion channels at the molecular level, a complete understanding of the mechanisms by which individual mutations may lead to arrhythmias and sudden death requires study of the intact heart and its modulation by the autonomic nervous system. Here, we will review studies of molecularly engineered mice with mutations in the genes (a) known to cause long QT syndrome in humans and (b) specific to cardiac repolarization in the mouse. Our goal is to provide the reader with a comprehensive overview of mouse models with long QT syndrome and to emphasize the advantages and limitations of these models. PMID:17038432

  19. Conventional QT Variability Measurement vs. Template Matching Techniques: Comparison of Performance Using Simulated and Real ECG

    Science.gov (United States)

    Baumert, Mathias; Starc, Vito; Porta, Alberto

    2012-01-01

    Increased beat-to-beat variability in the QT interval (QTV) of ECG has been associated with increased risk for sudden cardiac death, but its measurement is technically challenging and currently not standardized. The aim of this study was to investigate the performance of commonly used beat-to-beat QT interval measurement algorithms. Three different methods (conventional, template stretching and template time shifting) were subjected to simulated data featuring typical ECG recording issues (broadband noise, baseline wander, amplitude modulation) and real short-term ECG of patients before and after infusion of sotalol, a QT interval prolonging drug. Among the three algorithms, the conventional algorithm was most susceptible to noise whereas the template time shifting algorithm showed superior overall performance on simulated and real ECG. None of the algorithms was able to detect increased beat-to-beat QT interval variability after sotalol infusion despite marked prolongation of the average QT interval. The QTV estimates of all three algorithms were inversely correlated with the amplitude of the T wave. In conclusion, template matching algorithms, in particular the time shifting algorithm, are recommended for beat-to-beat variability measurement of QT interval in body surface ECG. Recording noise, T wave amplitude and the beat-rejection strategy are important factors of QTV measurement and require further investigation. PMID:22860030

  20. Conventional QT variability measurement vs. template matching techniques: comparison of performance using simulated and real ECG.

    Directory of Open Access Journals (Sweden)

    Mathias Baumert

    Full Text Available Increased beat-to-beat variability in the QT interval (QTV of ECG has been associated with increased risk for sudden cardiac death, but its measurement is technically challenging and currently not standardized. The aim of this study was to investigate the performance of commonly used beat-to-beat QT interval measurement algorithms. Three different methods (conventional, template stretching and template time shifting were subjected to simulated data featuring typical ECG recording issues (broadband noise, baseline wander, amplitude modulation and real short-term ECG of patients before and after infusion of sotalol, a QT interval prolonging drug. Among the three algorithms, the conventional algorithm was most susceptible to noise whereas the template time shifting algorithm showed superior overall performance on simulated and real ECG. None of the algorithms was able to detect increased beat-to-beat QT interval variability after sotalol infusion despite marked prolongation of the average QT interval. The QTV estimates of all three algorithms were inversely correlated with the amplitude of the T wave. In conclusion, template matching algorithms, in particular the time shifting algorithm, are recommended for beat-to-beat variability measurement of QT interval in body surface ECG. Recording noise, T wave amplitude and the beat-rejection strategy are important factors of QTV measurement and require further investigation.

  1. Influence of gender and types of sports training on QT variables in young elite athletes.

    Science.gov (United States)

    Omiya, Kazuto; Sekizuka, Hiromitsu; Kida, Keisuke; Suzuki, Kengo; Akashi, Yoshihiro J; Ohba, Haruo; Musha, Haruki

    2014-01-01

    Influence of gender and sports training on QT variables such as QT interval and dispersion (QT dispersion: QTD) in young elite athletes were evaluated. Subjects included 104 male and 97 female Japanese elite athletes (mean age 21.6 years). Sports included basketball, fencing, gymnastics, judo, swimming, tennis, track and field and volleyball. Age-matched healthy non-athletes (32 men and 20 women) were enrolled as controls. QT measurements were manually obtained from a 12-lead resting electrocardiogram and QTD was calculated as the difference between the longest and shortest QT intervals. A corrected QT interval (QTc) was obtained using Bazett's formula. Subjects were divided into two groups; an endurance training group and a static training group on the basis of their training types. Maximum and minimum QTc were significantly longer in female athletes than in male athletes (max: 414.2 vs. 404.5 ms, min: 375.1 vs. 359.2 ms, pgender and different characteristics of sports training may affect QT variables even in young elite athletes. Vigorous static exercise training may independently prolong QT variables.

  2. Association of functional genetic variants of A-kinase anchoring protein 10 with QT interval length in full-term Polish newborns.

    Science.gov (United States)

    Łoniewska, Beata; Kaczmarczyk, Mariusz; Clark, Jeremy Simon; Gorący, Iwona; Horodnicka-Józwa, Anita; Ciechanowicz, Andrzej

    2015-03-16

    A-Kinase Anchoring Proteins (AKAPs) coordinate the specificity of protein kinase A signaling by localizing the kinase to subcellular sites. The 1936G (V646) AKAP10 allele has been associated in adults with low cholinergic/vagus nerve sensitivity, shortened PR intervals in ECG recording and in newborns with increased blood pressure and higher cholesterol cord blood concentration. The aim of the study was to answer the question of whether 1936A > G AKAP10 polymorphism is associated with the newborn electrocardiographic variables. Electrocardiograms were recorded from 114 consecutive healthy Polish newborns (55 females, 59 males), born after 37 gestational weeks to healthy women with uncomplicated pregnancies. All recordings were made between 3(rd) and 7(th) day of life to avoid QT variability. The heart rate per minute and duration of PR, QRS, RR and QT intervals were usually measured. The ECGs were evaluated independently by three observers. At birth, cord blood of neonates was obtained for isolation of genomic DNA. The distribution of anthropometric and electrocardiographic variables in our cohort approached normality (skewness G variant and QTc interval in Polish newborns.

  3. Hypothetical "anatomy" of Brugada phenomenon: "Long QT sine Long QT" syndrome implicating morphologically undefined specific "Brugada's myocells".

    Science.gov (United States)

    Stirbys, Petras

    2017-01-01

    The Brugada syndrome (BrS) is associated with increased risk of ventricular arrhythmias and sudden cardiac death. It generates genetically mediated arrhythmias posing a true pathophysiological challenge. In search of the similarities between BrS and long QT syndrome some novel insights are suggested. In patients with BrS the duration of QT interval is usually normal. Some investigators have found prolonged QT interval in the syndrome's natural course or the duration of QT segment have been extended by provocative tests unmasking BrS. Thus, BrS might be characterized as "long QT sine long QT" syndrome. The existence of two functional types of myocites is suspected. Regarding structure and function the majority of ventricular myocardium is probably mostly healthy. The rest of myocardium (preferably the subepicardium of right ventricular outflow tract) due to its genotypic peculiarities demonstrates no negative influence on ventricular performance until early adulthood is reached and/or other unstable preconditions are fulfilled (nocturnal time, fever, specific drugs, etc.). Based on published findings of positive outcomes, following the epicardial ablation of the right ventricular outflow tract region, a new hypothetical concept suggesting the presence of specific, genetically affected "Brugada's myocells" is proposed. These cells as a suitable arrhythmogenic substrate reside intramurally within the subepicardial region of the outflow tract of right ventricle. In the daytime these cells likely are dormant but at rest their nocturnal proarrhythmic behavior is activated occasionally. Presumptions regarding the pathophysiology of BrS might be the focus of further discussion.

  4. [Long QT syndrome. History, genetics, clinical symptoms, causes and therapy].

    Science.gov (United States)

    Krönauer, T; Friederich, P

    2015-08-01

    The long QT syndrome is caused by a change in cardiac repolarization due to functional ion channel defects. A differentiation is made between a congenital (cLQTS) and an acquired (aLQTS) form of the disease. The disease results in the name-giving prolongation of the QT interval in the electrocardiogram and represents a predisposition for cardiac arrhythmia and sudden cardiac death. This article summarizes the current knowledge on the history, pathophysiology, clinical symptoms and therapy of cLQTS and aLQTS. This knowledge of pathophysiological features of the symptoms allows the underlying anesthesiological approach for individualized perioperative concepts for patients suffering from LQTS to be derived.

  5. 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

  6. 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.

  7. Life Threatening Severe QTc Prolongation in Patient with Systemic Lupus Erythematosus due to Hydroxychloroquine

    Directory of Open Access Journals (Sweden)

    John P. O’Laughlin

    2016-01-01

    Full Text Available We present a case of a syncopal episode resulting from significant QT interval prolongation in a patient on hydroxychloroquine for the treatment of systemic lupus erythematosus and end stage renal disease. The patient had been treated with hydroxychloroquine for two years prior to presentation. After thorough workup for secondary causes of QT interval prolongation hydroxychloroquine was discontinued and the patient’s QT interval shortened. The patient was treated with mexiletine to prevent sudden ventricular arrhythmias, which was unique compared to other documented cases in which lidocaine was used. The patient was noted to have mild prolongation of the QT interval on electrocardiogram prior to initiation of hydroxychloroquine therapy which was exacerbated by its use and may have been caused due to toxicity from underlying renal failure.

  8. P6 Electroacupuncture Improved QTc Interval Prolongation by Upregulation of Connexin43 in Droperidol Treated Rats

    Directory of Open Access Journals (Sweden)

    Feng Zhao

    2014-01-01

    Full Text Available Aim. This study investigated the effect of P6 EA on droperidol-induced QTc interval prolongation and Cx43 expression in ventricular muscle of rats. Methods. Twenty-four rats were randomly divided into control group (C, droperidol group (D, or EA group (E. C group rats were injected with normal saline. D group rats were injected with droperidol 0.13 mg/kg. E group rats were pretreated with EA at left P6 acupoint for 30 min and then injected with droperidol (0.13 mg/kg. QTc intervals were recorded at lead II in ECG within 120 min. Cx43 expression was measured by RT-PCR and western blotting. Result. Droperidol significantly prolonged QTc intervals compared with controls at 5 min, 10 min, 15 min, and 30 min (P0.05. Conclusion. P6 EA could improve QTc interval prolongation induced by droperidol, which may relate to upregulation of Cx43 mRNA and protein. Antiemetic dose of droperidol had minor effects on Cx43 mRNA and protein expression at 120 min.

  9. 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

  10. Long QT syndrome unmasked in an adult subject presenting with excited delirium.

    Science.gov (United States)

    Bozeman, William P; Ali, Karim; Winslow, James E

    2013-02-01

    Excited delirium is increasingly recognized as a risk factor for sudden death, though the specific pathophysiology of these deaths is typically unclear. We describe a survivor of excited delirium that displayed a transient severe prolongation of the QT interval, suggesting unmasking of long QT syndrome as a possible mechanism of sudden death. A 30-year-old man was arrested by police for violent assaultive behavior. Officers at the scene noted confusion, nonsensical speech, sweating, and bizarre agitated behavior; he was transported to the Emergency Department for medical evaluation of possible excited delirium. His initial electrocardiogram revealed a markedly prolonged corrected QT interval of over 600 ms. Intravenous hydration and sodium bicarbonate were administered, with normalization of the QT; he was admitted and recovered uneventfully. We discuss the possible association between long QT syndrome and unexplained sudden deaths seen with excited delirium. Sodium bicarbonate may be considered when long QT syndrome is identified during or after agitated delirium, though its routine use cannot be recommended based on a case report. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Prolonged PR interval predicts clinical recurrence of atrial fibrillation after catheter ablation.

    Science.gov (United States)

    Park, Junbeom; Kim, Tae-Hoon; Lee, Jihei Sara; Park, Jin Kyu; Uhm, Jae Sun; Joung, Boyoung; Lee, Moon Hyoung; Pak, Hui-Nam

    2014-10-07

    A prolonged PR interval is known to be a poor prognostic factor in cardiovascular disease. The aim of this study was to investigate the association between PR interval and clinical outcome in patients undergoing radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF). We prospectively included 576 patients with AF (75.5% male, 57.8±11.6 years old, 68.8% paroxysmal AF) who underwent RFCA. We analyzed preprocedural sinus rhythm ECGs obtained in the absence of antiarrhythmic drug, and all enrolled patients were categorized into 4 groups based on the quartile values of the PR interval (166, 182, and 202 ms), and were analyzed according to the left atrium (LA) volume (CT; Computed tomography), LA voltage (NavX), and clinical outcome of AF ablation. Based on quartile value of PR interval, the highest quartile of PR interval (Q4; PR ≥202 ms) was oldest (PPR interval was a significant predictor of AF recurrence after RFCA of AF (HR=1.969, 95% CI 1.343 to 2.886, P=0.001). The PR interval was closely associated with advanced LA remodeling due to AF, and had a noninvasive significant predictive value of clinical recurrence of AF after RFCA. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  12. Flecainide provocation reveals concealed brugada syndrome in a long QT syndrome family with a novel L1786Q mutation in SCN5A

    DEFF Research Database (Denmark)

    Kanters, Jørgen K.; Yuan, Lei; Hedley, Paula L

    2014-01-01

    BACKGROUND: Mutations in SCN5A can result in both long QT type 3 (LQT3) and Brugada syndrome (BrS), and a few mutations have been found to have an overlapping phenotype. Long QT syndrome is characterized by prolonged QT interval, and a prerequisite for a BrS diagnosis is ST elevation in the right...... interval. The proband presented with an aborted cardiac arrest, and his mother died suddenly and unexpectedly at the age of 65. Flecainide treatment revealed coved ST elevation in all mutation carriers. Electrophysiological investigations of the mutant in HEK293 cells indicated a reduced peak current...

  13. Cardiovascular safety of tyrosine kinase inhibitors: Putting their “QT-phobia” in perspective

    Directory of Open Access Journals (Sweden)

    Rashmi Shah

    2016-10-01

    Full Text Available Many potentially valuable drugs, including protein kinase inhibitors (PKI, risk being dropped from further development, without exploration of their clinical benefits, if early studies show these drugs to inhibit hERG channel and therefore, to have a potential for prolonging ventricular repolarisation (QT interval. This QT-phobia results from a perceived possibility of the clinical risks of QT-related ventricular proarrhythmia, further aggravated by uncertainties surrounding the regulatory evaluation of the risk and either approvability or restrictive labelling of the drug concerned. In reality, QT interval prolongation per se is only an imperfect surrogate of the proarrhythmia risk which is much smaller than perceived and compared to their other cardiovascular and non-cardiovascular risks. PKI-induced clinical hepatotoxicity, also evaluated on the basis of surrogate markers (serum transaminases and bilirubin is another risk that far exceeds any risk arising from PKI-induced QT interval prolongation. This review of the currently approved 28 PKIs places the QT-phobia surrounding the development of PKIs in its perspective by juxta-positioning their potential to induce ventricular dysfunction, arterial thrombotic events and hepatotoxicity. Available evidence suggests that hERG channel may prove to be a valuable therapeutic target in oncology. Therefore, the development, approval and labelling of such vital oncology drugs requires careful assessment of their benefits and their risk/benefit generally, without being overtly consumed by their potential QT-liability, in terms of their more direct consequences on clinically relevant endpoints of morbidity, mortality and quality of life.

  14. Multi-channel System for Beat to Beat QT Interval Variability and its Use in Screening for Coronary Artery Disease and Cardiomyopathy

    Science.gov (United States)

    Starc, V.; Schlegel, T. T.; Arenare, B.; Greco, E. C.; DePalma, J. L.; Nunez, T.; Medina, R.; Jugo, D.; Rahman, M. A.; Delgado, R.

    2007-01-01

    We investigated the ability of beat-to-beat QT interval variability (QTV) and related parameters to differentiate healthy individuals from patients with obstructive coronary artery disease (CAD) and cardiomyopathy (CM). For this purpose we developed a PC-based ECG software program that in real time, acquires, analyzes and displays QTV in each of the eight independent channels that constitute the 12-lead conventional ECG. The system also analyzes and displays the QTV from QT interval signals that are derived from multiple channels and from singular value decomposition (SVD) to substantially reduce the effect of noise and other artifacts on the QTV results. It also provides other useful SVD-related parameters such as the normalized 3-dimensional volume of the T wave (nTV) = 100*(rho(sub 2)*rho(sub 3)rho(sub 1^2). Advanced high-fidelity 12-lead ECG tests (approx. 5-min supine) were first performed on a "training set" of 99 individuals: 33 with ischemic or dilated CM and low ejection fraction (EF less than 40%); 33 with catheterization-proven obstructive CAD but normal EF; and 33 age-/gender-matched healthy controls. All QTV parameters that were studied for their accuracy in detecting CM and CAD significantly differentiated both CM and CAD from controls (p less than 0.0001). Retrospective areas under the ROC curve (AUC) of SDNN-QTV, rmsSD-QTV, and QTV Index (QTVI) for CM vs. controls in the lead V5 were 0.85, 0.90, and 0.99, respectively, and those for CAD vs. controls in the lead II were 0.82, 0.82, and 0.89. Other advanced ECG parameters, such as HFQRS RAZ score, LF Lomb of RRV or QRS-T angle, differentiated both CM and CAD from controls less significantly, with the respective AUC values of 0.89, 0.88 and 0.98 for CM vs. controls, and 0.73, 0.71 and 0.80 for CAD vs. controls. QTV parameters (especially QTVI, which is QTV as indexed to RRV) were, diagnostically speaking, amongst the best performing of the advanced ECG techniques studied thus far.

  15. 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 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.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.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.

  16. 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

  17. Cardiac Events During Competitive, Recreational, and Daily Activities in Children and Adolescents With Long QT Syndrome.

    Science.gov (United States)

    Chambers, Kristina D; Beausejour Ladouceur, Virginie; Alexander, Mark E; Hylind, Robyn J; Bevilacqua, Laura; Mah, Douglas Y; Bezzerides, Vassilios; Triedman, John K; Walsh, Edward P; Abrams, Dominic J

    2017-09-21

    The 2005 Bethesda Conference Guidelines advise patients with long QT syndrome against competitive sports. We assessed cardiac event rates during competitive and recreational sports, and daily activities among treated long QT syndrome patients. Long QT syndrome patients aged ≥4 years treated with anti-adrenergic therapy were included. Demographics included mechanism of presentation, corrected QT interval pretreatment, symptom history, medication compliance, and administration of QT-prolonging medications. Corrected QT interval ≥550 ms or prior cardiac arrest defined high risk. Sports were categorized by cardiovascular demand per the 2005 Bethesda Conference Guidelines. Each was classified as recreational or competitive. One hundred seventy-two patients (90; 52% female) with median age 15.2 years (interquartile range 11.4, 19.4) were included. Evaluation was performed for family history (102; 59%), incidental finding (34; 20%), and symptoms (36; 21%). Median corrected QT interval was 474 ms (interquartile range 446, 496) and 14 patients (8%) were deemed high risk. Treatment included β-blockers (171; 99%), implantable cardioverter-defibrillator (27; 16%), left cardiac sympathetic denervation (7; 4%), and pacemaker (3; 2%). Sports participation was recreational (66; 38%) or competitive (106; 62%), with 92 (53%) exercising against the Bethesda Conference Guidelines. There were no cardiac events in competitive athletes and no deaths. There were 13 cardiac events in 9 previously symptomatic patients during either recreational exercise or activities of daily life. In this cohort of appropriately managed children with long QT syndrome, cardiac event rates were low and occurred during recreational but not competitive activities. This study further supports the need for increased assessment of arrhythmia risk during exercise in this patient population. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  18. Methadone, QTc prolongation and torsades de pointes: Current concepts, management and a hidden twist in the tale?

    Science.gov (United States)

    Mujtaba, Sobia; Romero, Jorge; Taub, Cynthia C

    2013-12-01

    Methadone is a drug that has found widespread utility in the management of opioid addiction and pain. Along with its popularity, methadone has also earned an infamous reputation for causing prolongation of the QT interval and an increased risk of torsades de pointes. In this article we will give a brief overview of the long QT syndromes, followed by an in-depth look at the current pathophysiologic mechanisms of methadone induced QT prolongation, a review of the existing literature and the current concepts regarding the prevention and management of methadone induced torsades de pointes. In addition, we explore the idea and implications of a genetic link between methadone induced prolongation of the QT interval and torsades de pointes.

  19. 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.

  20. QT and JT dispersion and cardiac performance in children with neonatal Bartter syndrome: a pilot study.

    Science.gov (United States)

    Hacihamdioglu, Duygu Ovunc; Fidanci, Kursat; Kilic, Ayhan; Gok, Faysal; Topaloglu, Rezan

    2013-10-01

    QT dispersion and JT dispersion are simple noninvasive arrhythmogenic markers that can be used to assess the homogeneity of cardiac repolarization. The aim of this study was to assess QT and JT dispersion and their relation with left ventricular systolic and diastolic functions in children with Bartter syndrome (BS). Nine neonatal patients with BS (median age 9.7 years) and 20 controls (median age 8 years) were investigated at rest. Both study and control subjects underwent electrocardiography (ECG) in which the interval between two R waves and QT intervals, corrected QT, QT dispersion, corrected QT dispersion, JT, corrected JT, JT dispersion and corrected JT dispersion were measured with 12-lead ECG. Two-dimensional, Doppler echocardiographic examinations were performed. Patients and controls did not differ for gender and for serum levels of potassium, magnesium, and calcium (p > 0.05). Both study and control subjects had normal echocardiographic examination and baseline myocardial performance indexes. The QT dispersion and JT dispersion were significantly prolonged in patients with BS compared to those of the controls {37.5 ms [interquartile range (IQR) 32.5-40] vs. 25.5 ms (IQR 20-30), respectively, p = 0.014 and 37.5 ms (IQR 27.5-40) vs. 22.5 ms (IQR 20-30), respectively, p = 0.003}. Elevated QT and JT dispersion during asymptomatic and normokalemic periods may be risk factors for the development of cardiac complications and arrhythmias in children with BS. In these patients the need for systematic cardiac screening and management protocol is extremely important for effective prevention.

  1. 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

  2. QT Adaptation and Intrinsic QT Variability in Congenital Long QT Syndrome.

    Science.gov (United States)

    Seethala, Srikanth; Singh, Prabhpreet; Shusterman, Vladimir; Ribe, Margareth; Haugaa, Kristina H; Němec, Jan

    2015-12-16

    Increased variability of QT interval (QTV) has been linked to arrhythmias in animal experiments and multiple clinical situations. Congenital long QT syndrome (LQTS), a pure repolarization disease, may provide important information on the relationship between delayed repolarization and QTV. Twenty-four-hour Holter monitor tracings from 78 genotyped congenital LQTS patients (52 females; 51 LQT1, 23 LQT2, 2 LQT5, 2 JLN, 27 symptomatic; age, 35.2±12.3 years) were evaluated with computer-assisted annotation of RR and QT intervals. Several models of RR-QT relationship were tested in all patients. A model assuming exponential decrease of past RR interval contributions to QT duration with 60-second time constant provided the best data fit. This model was used to calculate QTc and residual "intrinsic" QTV, which cannot be explained by heart rate change. The intrinsic QTV was higher in patients with long QTc (r=0.68; Padaptation to heart rate changes occurs with time constant ≈60 seconds, similar to results reported in control subjects. Intrinsic QTV correlates with the degree of repolarization delay and might reflect action potential instability observed in animal models of LQTS. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  3. 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. PMID:26926294

  4. A Síndrome do QT Longo Associada ao uso de Citalopram e Escitalopram / The Long QT Syndrome Associated to Citalopram and Escitalopram

    Directory of Open Access Journals (Sweden)

    Filipe Santos Falani

    2016-06-01

    benefit-risk should be evaluated before use. Citalopram is the selective inhibitor of serotonin reuptake most widely prescribed in the world as escitalopram is widely used in major depressive disorder. Escitalopram is also widely prescribed because of its mild and transient side effects. The Long QT syndrome occurs because of a change in the cardiac electrical system. A duration of the QT interval greater than 450ms in men and 460ms in women should be considered anomalous, with specific etiology. However, cardiac arrhythmias occur more frequently when QT is greater than 500ms. The primary mechanism of drug-induced long QT is the inhibition of the hERG potassium channel, particularly in those patients with the polymorphic variant. Conclusion: Despite the low prevalence of QT interval prolongation induced in second-generation antidepressant users, given its wide use by the population, a greater concern for electrocardiographic monitoring is required, especially when there are risk factors or signs of overdose.

  5. Pharmacokinetic–pharmacodynamic modelling of drug‐induced QTc interval prolongation in man: prediction from in vitro human ether‐à‐go‐go‐related gene binding and functional inhibition assays and conscious dog studies

    Science.gov (United States)

    Dubois, V F S; Casarotto, E; Danhof, M

    2016-01-01

    Background and Purpose Functional measures of human ether‐à‐go‐go‐related gene (hERG; Kv11.1) channel inhibition have been prioritized as an in vitro screening tool for candidate molecules. However, it is unclear how these results can be translated to humans. Here, we explore how data on drug binding and functional inhibition in vitro relate to QT prolongation in vivo. Using cisapride, sotalol and moxifloxacin as paradigm compounds, we assessed the relationship between drug concentrations, binding, functional measures and in vivo effects in preclinical species and humans. Experimental Approach Pharmacokinetic–pharmacodynamic modelling was used to characterize the drug effects in hERG functional patch clamp, hERG radio‐labelled dofetilide displacement experiments and QT interval in conscious dogs. Data were analysed in parallel to identify potential correlations between pharmacological activity in vitro and in vivo. Key Results An Emax model could not be used due to large variability in the functional patch clamp assay. Dofetilide displacement revealed that binding curves are unrelated to the in vivo potency estimates for QTc prolongation in dogs and humans. Mean in vitro potency estimates ranged from 99.9 nM for cisapride to 1030 μM for moxifloxacin. Conclusions and Implications The lack of standardized protocols for in vitro assays leads to significant differences in experimental conditions, making the assessment of in vitro–in vivo correlations unreliable. Identification of an accurate safety window during the screening of candidate molecules requires a quantitative framework that disentangles system‐ from drug‐specific properties under physiological conditions, enabling translation of the results to humans. Similar considerations will be relevant for the comprehensive in vitro pro‐arrhythmia assay initiative. PMID:27427789

  6. Acquired Long QT Syndrome and Torsade de Pointes Associated with HIV Infection

    Directory of Open Access Journals (Sweden)

    Alexander Shimabukuro-Vornhagen

    2010-01-01

    Full Text Available Here, we report the case of an HIV infected patient that was treated for pneumonia with a macrolid antibiotic. The patient experienced a prolongation of the already pathologic QTc interval resulting in repeated torsades de pointes necessitating CPR and implantation of an AICD. This case exemplifies that torsades de pointes due to acquired long QT syndrome is a serious and potentially fatal complication in HIV-positive patients.

  7. 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 maintenance...

  8. 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.

  9. 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!.

  10. The effects of thioridazine on the QTc interval — cardiovascular ...

    African Journals Online (AJOL)

    Background. Thioridazine has long been used as a first-line antipsychotic in South Africa without any apparent problems. Recently the American Food and Drug Administration (FDA) and Novartis have warned of potentially lethal arrhythmias that may result from the use of thioridazine. Abnormal QT-interval prolongation on ...

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

    DEFF Research Database (Denmark)

    Elliott, Anja; Mørk, Thibault Johan; 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 prolonged...

  12. 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.

  13. 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

  14. Determinants of torsades de pointes in older patients with drug-associated long QT syndrome: a case-control study.

    Science.gov (United States)

    Goutelle, Sylvain; Sidolle, Elodie; Ducher, Michel; Caron, Jacques; Timour, Quadiri; Nony, Patrice; Gouraud, Aurore

    2014-08-01

    Many elderly patients are routinely exposed to drugs that may prolong the cardiac QT interval and cause Torsades de pointes (TdP). However, predictors of TdP in patients with drug-associated long QT syndrome (LQTS) are not fully understood, especially in the geriatric population. The objective of this study was to identify risk factors of TdP in elderly patients with drug-associated LQTS. In this retrospective, case-control study, documented reports of drug-associated LQTS plus TdP (n = 125) and LQTS without TdP (n = 81) in patients ≥65 years of age were retrieved from the French Pharmacovigilance Database over a 10-year period. Available clinical, biological, and drug therapy data were compared in the two groups and logistic regression was performed to identify significant predictors of TdP. The uncorrected QT interval was significantly longer in patients with TdP than in patients without TdP (577 ± 79 vs. 519 ± 68 ms; p = 0.0001). The number of drugs with a known risk of TdP administered to each patient was not a predictor of arrhythmia, nor was female gender. Logistic regression analysis identified the uncorrected QT interval as the only significant predictor of TdP. The receiver operating characteristic curve analysis was characterized by an area under the curve of 0.77 (95 % confidence interval 0.64-0.88) and a QT cutoff of 550 ms. The uncorrected QT interval was significantly associated with the probability of TdP in elderly patients with acquired, drug-associated LQTS.

  15. Predicting QRS and PR interval prolongations in humans using nonclinical data.

    Science.gov (United States)

    Bergenholm, L; Parkinson, J; Mettetal, J; Evans, N D; Chappell, M J; Collins, T

    2017-10-01

    Risk of cardiac conduction slowing (QRS/PR prolongations) is assessed prior to clinical trials using in vitro and in vivo studies. Understanding the quantitative translation of these studies to the clinical situation enables improved risk assessment in the nonclinical phase. Four compounds that prolong QRS and/or PR (AZD1305, flecainide, quinidine and verapamil) were characterized using in vitro (sodium/calcium channels), in vivo (guinea pigs/dogs) and clinical data. Concentration-matched translational relationships were developed based on in vitro and in vivo modelling, and the in vitro to clinical translation of AZD1305 was quantified using an in vitro model. Meaningful (10%) human QRS/PR effects correlated with low levels of in vitro Na v 1.5 block (3-7%) and Ca v 1.2 binding (13-21%) for all compounds. The in vitro model developed using AZD1305 successfully predicted QRS/PR effects for the remaining drugs. Meaningful QRS/PR changes in humans correlated with small effects in guinea pigs and dogs (QRS 2.3-4.6% and PR 2.3-10%), suggesting that worst-case human effects can be predicted by assuming four times greater effects at the same concentration from dog/guinea pig data. Small changes in vitro and in vivo consistently translated to meaningful PR/QRS changes in humans across compounds. Assuming broad applicability of these approaches to assess cardiovascular safety risk for non-arrhythmic drugs, this study provides a means of predicting human QRS/PR effects of new drugs from effects observed in nonclinical studies. © 2017 The British Pharmacological Society.

  16. 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.

  17. 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!

  18. 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....

  19. 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.

  20. Methadone, QTc prolongation and torsades de pointes: Current concepts, management and a hidden twist in the tale?

    OpenAIRE

    Mujtaba, Sobia; Romero, Jorge; Taub, Cynthia C.

    2013-01-01

    Methadone is a drug that has found widespread utility in the management of opioid addiction and pain. Along with its popularity, methadone has also earned an infamous reputation for causing prolongation of the QT interval and an increased risk of torsades de pointes.

  1. 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.

  2. Gene-specific paradoxical QT responses during rapid eye movement sleep in women with congenital long QT syndrome

    Czech Academy of Sciences Publication Activity Database

    Lanfranchi, P. A.; Ackerman, M. J.; Kára, T.; Shamsuzzaman, A. S.; Wolk, R.; Jurák, Pavel; Amin, R.; Somers, V. K.

    2010-01-01

    Roč. 7, č. 8 (2010), s. 1067-1074 ISSN 1547-5271 R&D Projects: GA MZd NS10098; GA MZd NS10099 Institutional research plan: CEZ:AV0Z20650511 Keywords : autonomic nervous system * heart rate * long QT syndrome * QT interval * sex * sleep Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 4.246, year: 2010

  3. [Long QT syndrome and polymorphic ventricular tachycardia due to hypopituitarism. Report of one case].

    Science.gov (United States)

    García-Castro, José Miguel; García-Martín, Antonia; Guirao-Arrabal, Emilio; Carrillo-Alascio, Pedro Luis

    2017-07-01

    Symptoms of hypopituitarism are usually chronic and nonspecific, but rarely the disease can have acute and life threatening manifestations. We report a 53 years old female with a pituitary adenoma that was admitted to our hospital because of syncope. The electrocardiogram showed sinus bradycardia with a prolonged QT interval. Frequent runs of non-sustained polymorphic ventricular tachycardia were noted on telemetry. The patient had a history of severe acute headaches in the previous days and laboratory tests revealed severe secondary hypothyroidism, adrenal insufficiency and a decrease in pituitary hormones. A magnetic resonance imaging of the head showed changes in the size and contrast enhancement of the adenoma. A diagnosis of hypopituitarism secondary to pituitary apoplexy was made and treatment with hydrocortisone and, subsequently, levothyroxine was started. Hormonal disorders such as hypothyroidism, adrenal insufficiency or hypopituitarism should be considered as unusual causes for reversible cardiomyopathy, long QT syndrome and ventricular arrhythmias.

  4. 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.

  5. Prevalence of long QT syndrome and other cardiac defects in deaf-mute children

    International Nuclear Information System (INIS)

    Niaz, A.; Rizvi, S.F.U.; Khurram, D.

    2011-01-01

    Background: Long QT syndrome is considered a fatal disease because of its association with ventricular arrhythmias and sudden cardiac death. Objectives of study were to determine the prevalence of long QT syndrome and other heart diseases, in deaf-mute children. Methods: A Cross-sectional descriptive study was conducted at Cholistan special education centre and Cardiology department, Sheikh Zayed hospital Rahim Yar Khan, Pakistan in September 2006. A total of 104 congenitally deaf-mute children were assessed. Height, weight and blood pressure measured, 12-lead electrocardiogram done and QTc calculated using Bazette's formula. Children with prolonged QTc underwent 24-hour ambulatory ECG recording. All were auscultated following complete protocol. A child with murmur was further evaluated with colour Doppler echocardiography. Audiometry was performed on all the children and the result interpreted according to WHO recommendations. Diagnosis of LQTS was based on Revised Schwartz criteria. Results: Out of 104 children, 62 were male with mean age 11.89 yrs. The average systolic and diastolic BP was 97/67 mmHg. Average height was 126 Cm. All children had moderate to severe bilateral sensorineural hearing loss (40-80 dB). One child had associated Patent Ductus Arteriosis. Fifteen had an innocent murmur. Prevalence of congenital heart disease was found to be 0.1/1000. Four children had QT interval more than 440 mSec, (range 0.46-0.47 mSec.). Both genders were equally affected. Three children had high probability of LQTS and one had intermediate probability. Screening of family of these 4 patients showed prolonged QT interval in the sibling of one patient. Conclusion: Our study highlights the significant prevalence of Jervell Lange-Nielsen Syndrome in Pakistani deaf-mute children, which may be associated to the high level of consanguinity in this region. Awareness of this syndrome among health care providers is needed as timely diagnosis and subsequent treatment may prevent

  6. Prediction of Thorough QT study results using action potential simulations based on ion channel screens.

    Science.gov (United States)

    Mirams, Gary R; Davies, Mark R; Brough, Stephen J; Bridgland-Taylor, Matthew H; Cui, Yi; Gavaghan, David J; Abi-Gerges, Najah

    2014-01-01

    Detection of drug-induced pro-arrhythmic risk is a primary concern for pharmaceutical companies and regulators. Increased risk is linked to prolongation of the QT interval on the body surface ECG. Recent studies have shown that multiple ion channel interactions can be required to predict changes in ventricular repolarisation and therefore QT intervals. In this study we attempt to predict the result of the human clinical Thorough QT (TQT) study, using multiple ion channel screening which is available early in drug development. Ion current reduction was measured, in the presence of marketed drugs which have had a TQT study, for channels encoded by hERG, CaV1.2, NaV1.5, KCNQ1/MinK, and Kv4.3/KChIP2.2. The screen was performed on two platforms - IonWorks Quattro (all 5 channels, 34 compounds), and IonWorks Barracuda (hERG & CaV1.2, 26 compounds). Concentration-effect curves were fitted to the resulting data, and used to calculate a percentage reduction in each current at a given concentration. Action potential simulations were then performed using the ten Tusscher and Panfilov (2006), Grandi et al. (2010) and O'Hara et al. (2011) human ventricular action potential models, pacing at 1Hz and running to steady state, for a range of concentrations. We compared simulated action potential duration predictions with the QT prolongation observed in the TQT studies. At the estimated concentrations, simulations tended to underestimate any observed QT prolongation. When considering a wider range of concentrations, and conventional patch clamp rather than screening data for hERG, prolongation of ≥5ms was predicted with up to 79% sensitivity and 100% specificity. This study provides a proof-of-principle for the prediction of human TQT study results using data available early in drug development. We highlight a number of areas that need refinement to improve the method's predictive power, but the results suggest that such approaches will provide a useful tool in cardiac safety

  7. 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.

  8. Elevation of QT dispersion after obesity drug sibutramine.

    Science.gov (United States)

    Yalcin, Ahmet A; Yavuz, Bunyamin; Ertugrul, Derun T; Algul, Beyza; Yilmaz, Hamiyet; Deveci, Onur S; Kucukazman, Metin; Ata, Naim; Demirel, Gokhan; Dal, Kursat; Tutal, Emre

    2010-11-01

    QT dispersion (QTd) is an arrhythmia parameter that can be used to assess homogeneity of cardiac repolarization. An antiobesity drug sibutramine is linked with several cardiovascular adverse events, including arrhythmias. Previous studies showed that sibutramine may prolong the QT interval and may be associated with cardiac arrest. The aim of this study was to evaluate the effect of sibutramine on QTd. The study group consisted of 65 consecutive patients with obesity. All patients were to receive 15 mg of sibutramine once a day in addition to standard care for lifestyle change. Twelve-lead ECG was performed before the onset of the medication and after 16 weeks of treatment. QTd was calculated. Three individuals were withdrawn from the study because of the adverse effects of sibutramine. Sixty-two patients with obesity were recruited into the study. All patients were women (62, 100%). Body weight (106.3 ± 15.0 kg vs. 101.6 ± 16.9 kg, P sibutramine treatment. The increase in QTd was not correlated with the decrease in body weight. There was no correlation between QTd and any conditions such as diabetes or hypertension. This study has shown an elevation in QTd, which may lead to cardiac arrhythmias, after sibutramine treatment. Molecular mechanisms may play role in increasing QTd. Further randomized studies are needed to clarify cardiac adverse events of the sibutramine.

  9. 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!

  10. QT dynamics during treatment with sertindole

    DEFF Research Database (Denmark)

    Nielsen, Jimmi; Wang, Fan; Graff, Claus

    2015-01-01

    be revealed by dynamic measures of the QT interval such as the ratio of QT variability to heart rate variability (variability ratio [VR]). The aim of this study was to investigate the effect of sertindole on QT dynamics. METHODS: QTc and the VR were assessed in an observational study using 24-hour Holter...... monitoring at baseline and after 3 weeks of treatment with sertindole 16 mg. The VR was calculated by dividing the standard deviation of QT intervals with the standard deviation of heart rates. Outcome measures were compared using paired t-test. RESULTS: A total of 18 patients participated in the study, two...... 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...

  11. Analytic study in patients presenting to a tertiary care hospital regarding the artemether-lumefantrine induced qtc interval changes in ECG

    International Nuclear Information System (INIS)

    Badshah, A.; Haider, I.

    2017-01-01

    Malaria is one of the most common causes of morbidity and mortality in our part of the world. Artemether-Lumefantrine (AL) Combination therapy is widely used for the treatment of malaria both in outpatients and inpatients hospital settings. Some of the previous anti-malarial were associated with prolongation of QT/sub c/ interval. Similar query was raised about AL therapy. This study was conducted to determine the risk of QT/sub c/ interval prolongation in ECG of patients with Falciparum malaria using oral Artemether-Lumefantrine (AL) combination therapy. Methods: The venue of this analytical, quasi-experimental study was Medical Unit A, Khyber Teaching Hospital Peshawar, spanning 1st August 2015 to 31st July 2016. The study sample included male and female patients, having Plasmodium falciparum rings in their peripheral smear. These patients were treated with oral Artemether- Lumefantrine (AL) combination for 3 consecutive days in recommended doses. Electrocardiography (ECG) profile before and after 72 hours' treatment with AL was noted for discernable QT/sub c/ interval changes. The calculated prolongation of the QT/sub c/ interval between these two study points was analyzed using Paired samples t-test. The statistically significant P value for this study was 0.05. SPSS version 23 was used for statistical analysis. Results: Amongst 200 cases, the QT/sub c/ interval was noted to be normal before the start of the treatment in all. There was no significant prolongation of QT/sub c/ interval following the treatment (p-value= 0.119) in the treated patients. It appears that cardiotoxicity is a remote adverse effect of AL combination therapy and that its use is safe in patients with Falciparum malaria. Conclusion: It can thus be concluded that AL is a safe drug combination for the treatment of falciparum malaria with negligible cardiotoxic adverse effects. (author)

  12. 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

  13. Screening of Long Q-T Syndrome in Patients with Congenital Sensorineural Hearing Loss (Jervell and Lange Neilesen Syndrome: Prevention of Fatal Events

    Directory of Open Access Journals (Sweden)

    Farid Matin

    2001-01-01

    Full Text Available Objective:The idiopathic long Q-T syndrome is an infrequently occurring disorder in which affected individuals have an unusual electrocardiographic repolarization abnormality presenting as syncope or loss of consciousness related to ventricular tachycardia or fibrillation. Congenital long Q-T prolongation can be associated with congenital deafness in an autosomal recessive manner (Jervell and Lange-Nielsen syndrome. The purpose of this stuff was to screen this electrocardiographic abnormality in deaf-mute school children in our population, which has not been yet performed. Materials & Methods:  Of 1190 patients with hearing loss, 779 had congenital sensorineural deafness (CSD, aged 13±3.8 years (4-24, 63% female and 37% male. The family history of deafness was as follows: Cardiac axis deviation was found in 56 (7% patients. Electrical conduction abnormalities were found in 12 (15% patients, Wolff-Parkinson-White syndrome, sinus bradycardia, and sinus arrhythmia were found in 2 (0.25%, 4 (0.5%, and 3 (0.38% patients, respectively. The Q-T interval, and Q-Tc duration were 312.6±28.9 ms (200-500 ms, median 320 ms, and 383.6±29.3 ms (232-527 ms, median 413ms, respectively. Long Q-T syndrome was found in 4 (0.5% patients (3F and 1M. Results: Two of these 4 patients had total deafness and 2 had profound hearing loss. None of the patients with mild deafness had Q-T prolongation. Only one of these patients was symptomatic, and had been treated as a case of epilepsy for several years. Conclusion: This data supports the presence of long Q-T syndrome in patients with sensorineural hearing loss in our population, so routine electrocardiographic screening of anyone with congenital deafness is warranted to prevent subsequent associated cardiac arrhythmias and sudden cardiac death.

  14. Computational Cardiac Modeling Reveals Mechanisms of Ventricular Arrhythmogenesis in Long QT Syndrome Type 8: CACNA1C R858H Mutation Linked to Ventricular Fibrillation

    Directory of Open Access Journals (Sweden)

    Jieyun Bai

    2017-10-01

    Full Text Available Functional analysis of the L-type calcium channel has shown that the CACNA1C R858H mutation associated with severe QT interval prolongation may lead to ventricular fibrillation (VF. This study investigated multiple potential mechanisms by which the CACNA1C R858H mutation facilitates and perpetuates VF. The Ten Tusscher-Panfilov (TP06 human ventricular cell models incorporating the experimental data on the kinetic properties of L-type calcium channels were integrated into one-dimensional (1D fiber, 2D sheet, and 3D ventricular models to investigate the pro-arrhythmic effects of CACNA1C mutations by quantifying changes in intracellular calcium handling, action potential profiles, action potential duration restitution (APDR curves, dispersion of repolarization (DOR, QT interval and spiral wave dynamics. R858H “mutant” L-type calcium current (ICaL augmented sarcoplasmic reticulum calcium content, leading to the development of afterdepolarizations at the single cell level and focal activities at the tissue level. It also produced inhomogeneous APD prolongation, causing QT prolongation and repolarization dispersion amplification, rendering R858H “mutant” tissue more vulnerable to the induction of reentry compared with other conditions. In conclusion, altered ICaL due to the CACNA1C R858H mutation increases arrhythmia risk due to afterdepolarizations and increased tissue vulnerability to unidirectional conduction block. However, the observed reentry is not due to afterdepolarizations (not present in our model, but rather to a novel blocking mechanism.

  15. A high-risk patient with long-QT syndrome with no response to cardioselective beta-blockers.

    Science.gov (United States)

    Toyota, Naoki; Miyazaki, Aya; Sakaguchi, Heima; Shimizu, Wataru; Ohuchi, Hideo

    2015-09-01

    We present a case of a high-risk 19-year-old female with long-QT syndrome (LQTS) with compound mutations. She had a history of aborted cardiac arrest and syncope and had received treatment with propranolol for 15 years. However, because she developed adult-onset asthma we tried to switch propranolol, a nonselective beta-blocker, to beta-1-cardioselective agents, bisoprolol and metoprolol. These resulted in both a markedly prolonged corrected QT interval and the development of LQTS-associated arrhythmias. Eventually, propranolol was reinitiated at a higher dose with the addition of verapamil, and she has had no further cardiac or asthmatic events for 5 years.

  16. Prolonged QRS Widening After Aripiprazole Overdose.

    Science.gov (United States)

    Mazer-Amirshahi, Maryann; Porter, Robert; Dewey, Kayla

    2018-05-05

    Aripiprazole is an atypical antipsychotic with a long half-life. Overdose can result in protracted somnolence and cardiac disturbances, particularly QT interval prolongation. This is a single case report of a 14-year-old boy who took an overdose of aripiprazole and developed QRS widening. A 14-year-old boy intentionally ingested 20 tablets of aripiprazole (5 mg). He was brought to the emergency department when his ingestion was discovered. The patient's vital signs were as follows: temperature, 37.7°C; heart rate, 108 beats/min; blood pressure, 138/98 mm Hg; and respirations, 16 breaths/min. Activated charcoal was administered within 90 minutes of ingestion. Initial electrocardiogram (EKG) showed sinus tachycardia, with a QRS of 138 ms and QT interval of 444 ms. QRS duration was 90 ms on an EKG performed 3 months earlier. A bolus of sodium bicarbonate was administered, and the patient was transferred to the pediatric intensive care unit. Repeat EKG demonstrated a QRS of 156 ms, and a sodium bicarbonate infusion was initiated. The patient continued to have QRS prolongation for the next 8 days, reaching a peak of 172 ms 3 days postingestion. Despite aggressive treatment with sodium bicarbonate, there was persistent QRS prolongation; however, the patient did not have any dysrhythmias and remained hemodynamically stable. The patient was discharged 9 days postingestion when the QRS duration normalized to 82 ms. Genetic testing revealed that the patient was a CYP2D6 poor metabolizer. This case suggests that aripiprazole toxicity may possibly be associated with QRS prolongation without associated dysrhythmias or cardiovascular compromise. In addition, toxicity may be prolonged in patients who are CYP2D6 poor metabolizers.

  17. New in vitro model for proarrhythmia safety screening: IKs inhibition potentiates the QTc prolonging effect of IKr inhibitors in isolated guinea pig hearts.

    Science.gov (United States)

    Kui, Péter; Orosz, Szabolcs; Takács, Hedvig; Sarusi, Annamária; Csík, Norbert; Rárosi, Ferenc; Csekő, Csongor; Varró, András; Papp, Julius Gy; Forster, Tamás; Farkas, Attila S; Farkas, András

    2016-01-01

    Preclinical in vivo QT measurement as a proarrhythmia essay is expensive and not reliable enough. The aim of the present study was to develop a sensitive, cost-effective, Langendorff perfused guinea pig heart model for proarrhythmia safety screening. Low concentrations of dofetilide and cisapride (inhibitors of the rapid delayed rectifier potassium current, IKr) were tested alone and co-perfused with HMR-1556 (inhibitor of the slow delayed rectifier potassium current, IKs) in Langendorff perfused guinea pig hearts. The electrocardiographic rate corrected QT (QTc) interval, the Tpeak-Tend interval and the beat-to-beat variability and instability (BVI) of the QT interval were determined in sinus rhythm. Dofetilide and HMR-1556 alone or co-perfused, prolonged the QTc interval by 20±2%, 10±1% and 55±10%, respectively. Similarly, cisapride and HMR-1556 alone or co-perfused, prolonged the QTc interval by 11±3%, 11±4% and 38±6%, respectively. Catecholamine-induced fast heart rate abolished the QTc prolonging effects of the IKr inhibitors, but augmented the QTc prolongation during IKs inhibition. None of the drug perfusions increased significantly the Tpeak-Tend interval and the sinus BVI of the QT interval. IKs inhibition increased the QTc prolonging effect of IKr inhibitors in a super-additive (synergistic) manner, and the QTc interval was superior to other proarrhythmia biomarkers measured in sinus rhythm in isolated guinea pig hearts. The effect of catecholamines on the QTc facilitated differentiation between IKr and IKs inhibitors. Thus, QTc measurement in Langendorff perfused guinea pig hearts with pharmacologically attenuated repolarization reserve and periodic catecholamine perfusion seems to be suitable for preclinical proarrhythmia screening. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. 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.

  19. 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 conduc...

  20. Prolonged interval between neoadjuvant chemoradiotherapy and esophagectomy does not benefit the outcome in esophageal cancer: a systematic review and meta-analysis.

    Science.gov (United States)

    Tie, H; He, F; Shen, J; Zhang, B; Ye, M; Chen, B; Wu, Q

    2018-01-01

    Whether a prolonged interval between neoadjuvant chemoradiotherapy (nCRT) and esophagectomy could benefits conditions such as rectal cancer, still remains unknown. We therefore performed the current study to evaluate the influence of the interval between nCRT and esophagectomy on the clinical outcomes in patients with esophageal cancer. PubMed and Embase were searched to identify eligible cohort studies. The primary outcome was five-year overall survival (OS), and secondary outcomes included the incidence of anastomotic complications, perioperative mortality, pathologic complete response (pCR) rate, positive circumferential resection margin (CRM) rate, and R0 resection rate. A random-effects model was used for all meta-analyses irrespective of heterogeneity. Ten cohort studies with 2383 patients were included. Overall, the pooled estimate revealed that the prolonged interval has no impact on five-year OS (odds ratio (OR) 0.87, 95% CI 0.66 to 1.14, P = 0.30), with low heterogeneity (PH = 0.78, I2 = 0%). However, it was associated with an increased risk of anastomotic complication (OR 1.71, 95% CI 1.15 to 2.54, P = 0.008), with no effect on perioperative mortality (OR 1.20, 95% CI 0.79 to 1.83, P = 0.40). Additionally, the prolonged interval failed to increase the pCR rate (OR 1.02, 95% CI 0.78 to 1.33, P = 0.89). Even worse, it was correlated with a decreased R0 resection rate (OR 0.60, 95% CI 0.41 to 0.88, P = 0.009) and increased positive CRM rate (OR 2.20, 95% CI 1.44 to 3.36, P < 0.001). This study suggests that the prolonged interval between nCRT and esophagectomy fails to result in better outcomes, and in fact, could worsen clinical outcomes, with increasing anastomotic complications, and undermine resection completeness. However, this conclusion should be treated with caution because of the limitations of retrospective cohort study and substantial clinical heterogeneity. (The study was registered at PRESPERO as CRD42016048210). © The Authors

  1. Menopause, hormone replacement and RR and QT modulation during sleep

    Czech Academy of Sciences Publication Activity Database

    Lanfranchi, P. A.; Gosselin, N.; Kára, T.; Jurák, Pavel; Somers, V. K.; Denesle, R.; Petit, D.; Carrier, J.; Nadeau, R.; Montplaisir, J.

    2005-01-01

    Roč. 6, č. 6 (2005), s. 561-566 ISSN 1389-9457 R&D Projects: GA ČR(CZ) GA102/05/0402 Keywords : Sleep * Menopause * RR interval * QT interval * Gender * Hormones Subject RIV: FS - Medical Facilities ; Equipment Impact factor: 2.711, year: 2005

  2. Acquired long QT syndrome and Torsades de Poin

    Directory of Open Access Journals (Sweden)

    Ahmet Seyfeddin Gurbuz

    2016-09-01

    Full Text Available Acetylcholinesterase inhibitors are group of drugs commonly used in Alzheimer disease and have beneficial effects on treatment. Although they have many known side effects, cardiovascular side effects are rarely seen. We present a 84 year old female who was admitted to emergency service due to repetitive syncope episodes while taking donepezil. Her electrocardiogram showed QT prolongation and on follow-up a Torsades de Pointes episode occurred. Patient was discharged with normal corrected QT time after removal of donepezil.

  3. Prognostic implications of mutation-specific QTc standard deviation in congenital long QT syndrome

    NARCIS (Netherlands)

    Mathias, Andrew; Moss, Arthur J.; Lopes, Coeli M.; Barsheshet, Alon; McNitt, Scott; Zareba, Wojciech; Robinson, Jennifer L.; Locati, Emanuela H.; Ackerman, Michael J.; Benhorin, Jesaia; Kaufman, Elizabeth S.; Platonov, Pyotr G.; Qi, Ming; Shimizu, Wataru; Towbin, Jeffrey A.; Michael Vincent, G.; Wilde, Arthur A. M.; Zhang, Li; Goldenberg, Ilan

    2013-01-01

    Individual corrected QT interval (QTc) may vary widely among carriers of the same long QT syndrome (LQTS) mutation. Currently, neither the mechanism nor the implications of this variable penetrance are well understood. To hypothesize that the assessment of QTc variance in patients with congenital

  4. A Prolonged Time Interval Between Trauma and Prophylactic Radiation Therapy Significantly Increases the Risk of Heterotopic Ossification

    Energy Technology Data Exchange (ETDEWEB)

    Mourad, Waleed F., E-mail: Waleed246@gmail.com [Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS (United States); Department of Radiation Oncology, Beth Israel Medical Center, New York, NY (Israel); Packianathan, Satyaseelan [Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS (United States); Shourbaji, Rania A. [Department of Epidemiology and Biostatistics, Jackson State University, Jackson, MS (United States); Zhang Zhen; Graves, Mathew [Department of Orthopedic Surgery, University of Mississippi Medical Center, Jackson, MS (United States); Khan, Majid A. [Department of Radiology, University of Mississippi Medical Center, Jackson, MS (United States); Baird, Michael C. [Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS (United States); Russell, George [Department of Orthopedic Surgery, University of Mississippi Medical Center, Jackson, MS (United States); Vijayakumar, Srinivasan [Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS (United States)

    2012-03-01

    Purpose: To ascertain whether the time from injury to prophylactic radiation therapy (RT) influences the rate of heterotopic ossification (HO) after operative treatment of displaced acetabular fractures. Methods and Materials: This is a single-institution, retrospective analysis of patients referred for RT for the prevention of HO. Between January 2000 and January 2009, 585 patients with displaced acetabular fractures were treated surgically followed by RT for HO prevention. We analyzed the effect of time from injury on prevention of HO by RT. In all patients, 700 cGy was prescribed in a single fraction and delivered within 72 hours postsurgery. The patients were stratified into five groups according to time interval (in days) from the date of their accident to the date of RT: Groups A {<=}3, B {<=}7, C {<=}14, D {<=}21, and E >21days. Results: Of the 585 patients with displaced acetabular fractures treated with RT, (18%) 106 patients developed HO within the irradiated field. The risk of HO after RT increased from 10% for RT delivered {<=}3 days to 92% for treatment delivered >21 days after the initial injury. Wilcoxon test showed a significant correlation between the risk of HO and the length of time from injury to RT (p < 0.0001). Chi-square test and multiple logistic regression analysis showed no significant association between all other factors and the risk of HO (race, gender, cause and type of fracture, surgical approach, or the use of indomethacin). Conclusions: Our data suggest that there is higher incidence and risk of HO if prophylactic RT is significantly delayed after a displaced acetabular fracture. Thus, RT should be administered as early as clinically possible after the trauma. Patients undergoing RT >3 weeks from their displaced acetabular fracture should be informed of the higher risk (>90%) of developing HO despite prophylaxis.

  5. 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...

  6. Computational Analysis of the Mode of Action of Disopyramide and Quinidine on hERG-Linked Short QT Syndrome in Human Ventricles

    Directory of Open Access Journals (Sweden)

    Dominic G. Whittaker

    2017-10-01

    Full Text Available The short QT syndrome (SQTS is a rare cardiac disorder associated with arrhythmias and sudden death. Gain-of-function mutations to potassium channels mediating the rapid delayed rectifier current, IKr, underlie SQTS variant 1 (SQT1, in which treatment with Na+ and K+ channel blocking class Ia anti-arrhythmic agents has demonstrated some efficacy. This study used computational modeling to gain mechanistic insights into the actions of two such drugs, disopyramide and quinidine, in the setting of SQT1. The O'Hara-Rudy (ORd human ventricle model was modified to incorporate a Markov chain formulation of IKr describing wild type (WT and SQT1 mutant conditions. Effects of multi-channel block by disopyramide and quinidine, including binding kinetics and altered potency of IKr/hERG channel block in SQT1 and state-dependent block of sodium channels, were simulated on action potential and multicellular tissue models. A one-dimensional (1D transmural ventricular strand model was used to assess prolongation of the QT interval, effective refractory period (ERP, and re-entry wavelength (WL by both drugs. Dynamics of re-entrant excitation waves were investigated using a 3D human left ventricular wedge model. In the setting of SQT1, disopyramide, and quinidine both produced a dose-dependent prolongation in (i the QT interval, which was primarily due to IKr block, and (ii the ERP, which was mediated by a synergistic combination of IKr and INa block. Over the same range of concentrations quinidine was more effective in restoring the QT interval, due to more potent block of IKr. Both drugs demonstrated an anti-arrhythmic increase in the WL of re-entrant circuits. In the 3D wedge, disopyramide and quinidine at clinically-relevant concentrations decreased the dominant frequency of re-entrant excitations and exhibited anti-fibrillatory effects; preventing formation of multiple, chaotic wavelets which developed in SQT1, and could terminate arrhythmias. This

  7. The effect of additional carbohydrate supplements for 7 days after prolonged interval exercise on exercise performance and energy metabolism during submaximal exercise in team-sports athletes.

    Science.gov (United States)

    Park, Hun-Young; Kim, Jisu; Park, Miyoung; Chung, Nana; Lim, Kiwon

    2018-03-30

    The purpose of our study was to determine the effectiveness of carbohydrate loading by additional carbohydrate supplements for 7 days after prolonged interval exercise on exercise performance and energy metabolism during submaximal exercise in team-sports athletes. Twenty male team-sports athletes (14 soccer and 6 rugby players) volunteered to participate in the study and were equally divided into the experimental group (EXP, n=10) performing additional carbohydrate supplementation for 7 days after prolonged interval exercise until blood glucose level reaches 50 mg/dL or less and the control group (CON, n=10). Then, maximal oxygen consumption (VO2max) and minute ventilation (VE), oxygen consumption (VO2), carbon dioxide excretion (VCO2), respiratory exchange ratio (RER), blood glucose level, and blood lactate level were measured in all team-sports players during submaximal exercise corresponding to 70% VO2max before and after intervention. There was no significant interaction in all parameters, but team-sports players in the EXP presented more improved VO2max (CON vs EXP = vs 5.3% vs 6.3%), VE (CON vs EXP = vs 3.8% vs 6.6%), VO2 (CON vs EXP = vs 8.5% vs 9.9%), VCO2 (CON vs EXP = vs 2.8% vs 4.0%), blood glucose level (CON vs EXP = vs -12.9% vs -7.6%), and blood lactate level (CON vs EXP = -18.2% vs -25%) compared to those in the CON. These findings showed that additional carbohydrate supplementation conducted in our study is not effective in exercise performance and energy metabolism during submaximal exercise. ©2018 The Korean Society for Exercise Nutrition.

  8. The effect of additional carbohydrate supplements for 7 days after prolonged interval exercise on exercise performance and energy metabolism during submaximal exercise in team-sports athletes

    Science.gov (United States)

    Park, Hun-Young; Kim, Jisu; Park, Miyoung; Chung, Nana; Lim, Kiwon

    2018-01-01

    [Purpose] The purpose of our study was to determine the effectiveness of carbohydrate loading by additional carbohydrate supplements for 7 days after prolonged interval exercise on exercise performance and energy metabolism during submaximal exercise in team-sports athletes. [Methods] Twenty male team-sports athletes (14 soccer and 6 rugby players) volunteered to participate in the study and were equally divided into the experimental group (EXP, n=10) performing additional carbohydrate supplementation for 7 days after prolonged interval exercise until blood glucose level reaches 50 mg/dL or less and the control group (CON, n=10). Then, maximal oxygen consumption (VO2max) and minute ventilation (VE), oxygen consumption (VO2), carbon dioxide excretion (VCO2), respiratory exchange ratio (RER), blood glucose level, and blood lactate level were measured in all team-sports players during submaximal exercise corresponding to 70% VO2max before and after intervention. [Results] There was no significant interaction in all parameters, but team-sports players in the EXP presented more improved VO2max (CON vs EXP = vs 5.3% vs 6.3%), VE (CON vs EXP = vs 3.8% vs 6.6%), VO2 (CON vs EXP = vs 8.5% vs 9.9%), VCO2 (CON vs EXP = vs 2.8% vs 4.0%), blood glucose level (CON vs EXP = vs -12.9% vs -7.6%), and blood lactate level (CON vs EXP = -18.2% vs -25%) compared to those in the CON. [Conclusion] These findings showed that additional carbohydrate supplementation conducted in our study is not effective in exercise performance and energy metabolism during submaximal exercise. PMID:29673243

  9. Left ventricular epicardial activation increases transmural dispersion of repolarization in healthy, long QT, and dilated cardiomyopathy dogs.

    Science.gov (United States)

    Bai, Rong; Lü, Jiagao; Pu, Jun; Liu, Nian; Zhou, Qiang; Ruan, Yanfei; Niu, Huiyan; Zhang, Cuntai; Wang, Lin; Kam, Ruth

    2005-10-01

    Benefits of cardiac resynchronization therapy (CRT) are well established. However, less is understood concerning its effects on myocardial repolarization and the potential proarrhythmic risk. Healthy dogs (n = 8) were compared to a long QT interval (LQT) model (n = 8, induced by cesium chloride, CsCl) and a dilated cardiomyopathy with congestive heart failure (DCM-CHF, induced by rapid ventricular pacing, n = 5). Monophasic action potential (MAP) recordings were obtained from the subendocardium, midmyocardium, subepicardium, and the transmural dispersion of repolarization (TDR) was calculated. The QT interval and the interval from the peak to the end of the T wave (T(p-e)) were measured. All these characteristics were compared during left ventricular epicardial (LV-Epi), right ventricular endocardial (RV-Endo), and biventricular (Bi-V) pacing. In healthy dogs, TDR prolonged to 37.54 ms for Bi-V pacing and to 47.16 ms for LV-Epi pacing as compared to 26.75 ms for RV-Endo pacing (P canine models in addition to their intrinsic transmural heterogeneity in the intact heart. This mechanism may contribute to the development of malignant ventricular arrhythmias, such as torsades de pointes (TdP) in congestive heart failure (CHF) patients treated with CRT.

  10. 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.

  11. Marked QTc prolongation and Torsades de Pointes in patients with chronic inflammatory arthritis

    Directory of Open Access Journals (Sweden)

    Pietro Enea Lazzerini

    2016-09-01

    Full Text Available Mounting evidence indicates that in chronic inflammatory arthritis (CIA, QTc prolongation is frequent and correlates with systemic inflammatory activation. Notably, basic studies demonstrated that inflammatory cytokines induce profound changes in potassium and calcium channels resulting in a prolonging effect on cardiomyocyte action potential duration (APD, thus on the QT interval on the electrocardiogram. Moreover, it has been demonstrated that in RA patients the risk of SCD is significantly increased when compared to non-RA subjects. Conversely, to date no data are available about Torsades de Pointes (TdP prevalence in CIA, and the few case reported considered CIA only an incidental concomitant disease, not contributing factor to TdP development.We report three patients with active CIA developing marked QTc prolongation, in two cases complicated with TdP degenerating to cardiac arrest. In these patients, a blood sample was obtained within 24h from TdP/marked QTc prolongation occurrence and levels of IL-6, TNF-alpha and IL-1 were evaluated. In all three cases, IL-6 was markedly elevated, ~10 to 100 times more than reference values. Moreover, one patient also showed high circulating levels of TNF-alpha and IL-1. In conclusion, active CIA may represent a currently overlooked QT-prolonging risk factor, potentially contributing in the presence of other classical risk factors to TdP occurrence. In particular, a relevant role may be played by elevated circulating IL-6 levels via direct electrophysiological effects on the heart. This observation should be carefully kept in mind, particularly when recognizable risk factors are already present and/or the addition of QT-prolonging drugs is required.

  12. 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.

  13. Cross-platform software development with Qt

    CERN Multimedia

    CERN. Geneva

    2018-01-01

    Overview of the Qt framework, new features of Qt 5.10 and preview of the Qt roadmap Introduction of the Qt framework as well as the new features and improvements of Qt 5.10. Showcase the different Qt UI technologies such as Widgets and Qml, overview of the automation suite and preview of the new features to come in Qt Creator. Elaborating on the Qt 3D offering and preview of the Qt roadmap. Presenting use cases of Qt integration in the medical and automation sectors. About the speaker Ionut is a serial entrepreneur, now working as Qt Adviser for The Qt Company. He studied biomedical engineering in Montreal, Canada and worked for 4 years as a Senior Software Developer at a software company in the life science and medical imaging area. He founded two interactive media companies, one in Montreal, Canada and another one in Berlin, Germany. Ionut has also more than 10 years of experience in the digital signage industry. He has been working with the Qt framework since 2006 and is a huge fan of it.   &...

  14. Measure of the QT-RR Dynamic Coupling in Patients with the Long QT Syndrome

    Czech Academy of Sciences Publication Activity Database

    Halámek, Josef; Couderc, J. P.; Jurák, Pavel; Vondra, Vlastimil; Zareba, W.; Viščor, Ivo; Leinveber, P.

    2012-01-01

    Roč. 17, č. 4 (2012), s. 323-330 ISSN 1082-720X R&D Projects: GA MŠk ME09050 Institutional support: RVO:68081731 Keywords : Long QT syndrome * Dynamic QT-RR coupling * Holter recording * QT adaptation * QT parameters Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.084, year: 2012

  15. Congenital short QT syndrome and implantable cardioverter defibrillator treatment: inherent risk for inappropriate shock delivery.

    Science.gov (United States)

    Schimpf, Rainer; Wolpert, Christian; Bianchi, Francesca; Giustetto, Carla; Gaita, Florenzo; Bauersfeld, Urs; Borggrefe, Martin

    2003-12-01

    A congenital short QT interval constitutes a new primary electrical abnormality associated with syncope and/or sudden cardiac death. We report on the initial use of implantable cardioverter defibrillator (ICD) therapy in patients with inherited short QT interval and discuss sensing abnormalities and detection issues. In five consecutive patients from two unrelated European families who had structurally normal hearts, excessively shortened QT intervals, and a strong positive family history of sudden cardiac death, ICDs were placed for primary and secondary prevention. Mean QT intervals were 252 +/- 13 ms (QTc 287 +/- 13 ms). Despite normal sensing behavior during intraoperative and postoperative device testing, 3 of 5 patients experienced inappropriate shock therapies for T wave oversensing 30 +/- 26 days after implantation. Programming lower sensitivities and decay delays prevented further inappropriate discharges. The congenital short QT syndrome constitutes a new clinical entity with an increased risk for sudden cardiac death. Currently, ICD treatment is the only therapeutic option. In patients with short QT interval and implanted ICD, increased risk for inappropriate therapy is inherent due to the detection of short-coupled and prominent T waves. Careful testing of ICD function and adaptation of sensing levels and decay delays without sacrificing correct arrhythmia detection are essential.

  16. 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.

  17. Oxaliplatin-induced acquired long QT syndrome with torsades de pointes and myocardial injury in a patient with dilated cardiomyopathy and rectal cancer

    Directory of Open Access Journals (Sweden)

    Rei-Yeuh Chang

    2013-08-01

    Full Text Available A 67-year-old woman presented with a history of dilated cardiomyopathy with congestive heart failure since 2003, who subsequently developed lower rectal cancer (adenocarcinoma with liver, bone, and lymph node metastasis. Abdominoperineal resection and hepatectomy were performed. The patient received two rounds of intravenous chemotherapy, including 12 and six courses of FOLFOX4 (5-fluorouracil, leucovorin, and oxaliplatin; 85 mg/m2 per cycle. She underwent a third round of intravenous FOLFOX4 because of tumor progression. During the 21st course of FOLFOX4 regimen, the patient developed ST segment depression in lead II and prolongation of QT interval with polymorphic ventricular tachycardia, torsades de pointes right after the start of oxaliplatin infusion. Immediate defibrillation and cardiopulmonary resuscitation were administered, and the patient regained spontaneous circulation and consciousness. Twelve-lead electrocardiogram showed ST segment elevation in III, aVF, and ST segment depression in V4–6 after resuscitation. To our knowledge, prolongation of QT interval with torsades de pointes and coronary spasm with myocardial injury that were stabilized in one patient following oxaliplatin infusion has not been reported. We present a patient with these rare complications.

  18. Congestive Heart Failure Leads to Prolongation of the PR Interval and Atrioventricular Junction Enlargement and Ion Channel Remodelling in the Rabbit

    Science.gov (United States)

    Nikolaidou, Theodora; Cai, Xue J.; Stephenson, Robert S.; Yanni, Joseph; Lowe, Tristan; Atkinson, Andrew J.; Jones, Caroline B.; Sardar, Rida; Corno, Antonio F.; Dobrzynski, Halina; Withers, Philip J.; Jarvis, Jonathan C.; Hart, George; Boyett, Mark R.

    2015-01-01

    Heart failure is a major killer worldwide. Atrioventricular conduction block is common in heart failure; it is associated with worse outcomes and can lead to syncope and bradycardic death. We examine the effect of heart failure on anatomical and ion channel remodelling in the rabbit atrioventricular junction (AVJ). Heart failure was induced in New Zealand rabbits by disruption of the aortic valve and banding of the abdominal aorta resulting in volume and pressure overload. Laser micro-dissection and real-time polymerase chain reaction (RT-PCR) were employed to investigate the effects of heart failure on ion channel remodelling in four regions of the rabbit AVJ and in septal tissues. Investigation of the AVJ anatomy was performed using micro-computed tomography (micro-CT). Heart failure animals developed first degree heart block. Heart failure caused ventricular myocardial volume increase with a 35% elongation of the AVJ. There was downregulation of HCN1 and Cx43 mRNA transcripts across all regions and downregulation of Cav1.3 in the transitional tissue. Cx40 mRNA was significantly downregulated in the atrial septum and AVJ tissues but not in the ventricular septum. mRNA abundance for ANP, CLCN2 and Navβ1 was increased with heart failure; Nav1.1 was increased in the inferior nodal extension/compact node area. Heart failure in the rabbit leads to prolongation of the PR interval and this is accompanied by downregulation of HCN1, Cav1.3, Cx40 and Cx43 mRNAs and anatomical enlargement of the entire heart and AVJ. PMID:26509807

  19. Congestive Heart Failure Leads to Prolongation of the PR Interval and Atrioventricular Junction Enlargement and Ion Channel Remodelling in the Rabbit.

    Directory of Open Access Journals (Sweden)

    Theodora Nikolaidou

    Full Text Available Heart failure is a major killer worldwide. Atrioventricular conduction block is common in heart failure; it is associated with worse outcomes and can lead to syncope and bradycardic death. We examine the effect of heart failure on anatomical and ion channel remodelling in the rabbit atrioventricular junction (AVJ. Heart failure was induced in New Zealand rabbits by disruption of the aortic valve and banding of the abdominal aorta resulting in volume and pressure overload. Laser micro-dissection and real-time polymerase chain reaction (RT-PCR were employed to investigate the effects of heart failure on ion channel remodelling in four regions of the rabbit AVJ and in septal tissues. Investigation of the AVJ anatomy was performed using micro-computed tomography (micro-CT. Heart failure animals developed first degree heart block. Heart failure caused ventricular myocardial volume increase with a 35% elongation of the AVJ. There was downregulation of HCN1 and Cx43 mRNA transcripts across all regions and downregulation of Cav1.3 in the transitional tissue. Cx40 mRNA was significantly downregulated in the atrial septum and AVJ tissues but not in the ventricular septum. mRNA abundance for ANP, CLCN2 and Navβ1 was increased with heart failure; Nav1.1 was increased in the inferior nodal extension/compact node area. Heart failure in the rabbit leads to prolongation of the PR interval and this is accompanied by downregulation of HCN1, Cav1.3, Cx40 and Cx43 mRNAs and anatomical enlargement of the entire heart and AVJ.

  20. Diclofenac prolongs repolarization in ventricular muscle with impaired repolarization reserve.

    Directory of Open Access Journals (Sweden)

    Attila Kristóf

    Full Text Available BACKGROUND: The aim of the present work was to characterize the electrophysiological effects of the non-steroidal anti-inflammatory drug diclofenac and to study the possible proarrhythmic potency of the drug in ventricular muscle. METHODS: Ion currents were recorded using voltage clamp technique in canine single ventricular cells and action potentials were obtained from canine ventricular preparations using microelectrodes. The proarrhythmic potency of the drug was investigated in an anaesthetized rabbit proarrhythmia model. RESULTS: Action potentials were slightly lengthened in ventricular muscle but were shortened in Purkinje fibers by diclofenac (20 µM. The maximum upstroke velocity was decreased in both preparations. Larger repolarization prolongation was observed when repolarization reserve was impaired by previous BaCl(2 application. Diclofenac (3 mg/kg did not prolong while dofetilide (25 µg/kg significantly lengthened the QT(c interval in anaesthetized rabbits. The addition of diclofenac following reduction of repolarization reserve by dofetilide further prolonged QT(c. Diclofenac alone did not induce Torsades de Pointes ventricular tachycardia (TdP while TdP incidence following dofetilide was 20%. However, the combination of diclofenac and dofetilide significantly increased TdP incidence (62%. In single ventricular cells diclofenac (30 µM decreased the amplitude of rapid (I(Kr and slow (I(Ks delayed rectifier currents thereby attenuating repolarization reserve. L-type calcium current (I(Ca was slightly diminished, but the transient outward (I(to and inward rectifier (I(K1 potassium currents were not influenced. CONCLUSIONS: Diclofenac at therapeutic concentrations and even at high dose does not prolong repolarization markedly and does not increase the risk of arrhythmia in normal heart. However, high dose diclofenac treatment may lengthen repolarization and enhance proarrhythmic risk in hearts with reduced repolarization reserve.

  1. 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.

  2. [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. Copyright © 2013 SEP y SEPB. Published by Elsevier España. All rights reserved.

  3. Sex-selective QT prolongation during rapid eye movement sleep

    Czech Academy of Sciences Publication Activity Database

    Lanfranchi, P.; Shamsuzzaman, A. S.; Ackerman, M. J.; Kára, T.; Jurák, Pavel; Wolk, R.; Somers, V.

    2002-01-01

    Roč. 106, č. 12 (2002), s. 1488 - 1492 ISSN 0009-7322 R&D Projects: GA ČR GA102/95/0467; GA ČR GA102/02/1339 Institutional research plan: CEZ:AV0Z2065902 Keywords : sleep * sex * nervous system Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 10.255, year: 2002

  4. 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

  5. Evaluation of QT and P wave dispersion and mean platelet volume among inflammatory bowel disease patients.

    Science.gov (United States)

    Dogan, Yuksel; Soylu, Aliye; Eren, Gulay A; Poturoglu, Sule; Dolapcioglu, Can; Sonmez, Kenan; Duman, Habibe; Sevindir, Isa

    2011-01-01

    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. 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. 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). 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 with IBD. No significant difference was found in the QT

  6. 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, penergy 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.

  7. Диспластические синдромы и фенотипы в оценке изменений интервала QT при малых аномалиях сердца

    Directory of Open Access Journals (Sweden)

    А. В. Ягода

    2011-01-01

    Full Text Available To assess relation of dysplastic syndromes and phenotypes to pathological QT interval in patients with minor cardiac anomalies, 128 patients aged 18–35 years were examined. A statistically significant increase in the prevalence of QT interval disorder was found. Pathological QT interval without clinical features was observed more frequently. Correlations were revealed between the QT interval disorder and myxomatous mitral valve prolapse, phenotype similar to Marfan syndrome, and benign joints hypermobility.

  8. Long QT Syndrome: A Clinical Entity Resembling Epilepsy

    Directory of Open Access Journals (Sweden)

    Mehmet Güney Şenol

    2008-06-01

    Full Text Available Scientific BACKGROUND: Long QT Syndrome (LQTS is a cardiac repolarization defect, characterized by lengthened QT interval in the ECG. It can cause syncope due to rapid, polimorphic ventricular tachycardia known as Torsades de Pointes (TdP or it may cause sudden cardiac death. This clinical entity is frequently mistaken for epilepsy. CASE: In this report, a 24-year old male patient with congenital LQTS is presented. The patient was originally followed-up for epilepsy. During the evaluation process his loss of consciousness attacks were linked with ventricular tachycardia -TdP- periods and thus a diagnosis of LQTS was reached. When cardiac arrest ocurred in this patient, "stellate ganglion blockage” was performed. CONCLUSION: One must bear LQTS in mind in all patients with suspicious-looking syncope attacks and it must not be forgotten that early diagnosis and timely therapy will save the life of the individual

  9. Palbociclib has no clinically relevant effect on the QTc interval in patients with advanced breast cancer.

    Science.gov (United States)

    Durairaj, Chandrasekar; Ruiz-Garcia, Ana; Gauthier, Eric R; Huang, Xin; Lu, Dongrui R; Hoffman, Justin T; Finn, Richard S; Joy, Anil A; Ettl, Johannes; Rugo, Hope S; Zheng, Jenny; Wilner, Keith D; Wang, Diane D

    2018-03-01

    The aim of this study was to assess the potential effects of palbociclib in combination with letrozole on QTc. PALOMA-2, a phase 3, randomized, double-blind, placebo-controlled trial, compared palbociclib plus letrozole with placebo plus letrozole in postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. The study included a QTc evaluation substudy carried out as a definitive QT interval prolongation assessment for palbociclib. Time-matched triplicate ECGs were performed at 0, 2, 4, 6, and 8 h at baseline (Day 0) and on Cycle 1 Day 14. Additional ECGs were collected from all patients for safety monitoring. The QT interval was corrected for heart rate using Fridericia's correction (QTcF), Bazett's correction (QTcB), and a study-specific correction factor (QTcS). In total, 666 patients were randomized 2 : 1 to palbociclib plus letrozole or placebo plus letrozole. Of these, 125 patients were enrolled in the QTc evaluation substudy. No patients in the palbociclib plus letrozole arm of the substudy (N=77) had a maximum postbaseline QTcS or QTcF value of ≥ 480 ms, or a maximum increase from clock time-matched baseline for QTcS or QTcF values of ≥ 60 ms. The upper bounds of the one-sided 95% confidence interval for the mean change from time-matched baseline for QTcS, QTcF, and QTcB at all time points and at steady-state Cmax following repeated administration of 125 mg palbociclib were less than 10 ms. Palbociclib, when administered with letrozole at the recommended therapeutic dosing regimen, did not prolong the QT interval to a clinically relevant extent.

  10. 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.

  11. Acute effects of smoking on QT dispersion in healthy males

    Directory of Open Access Journals (Sweden)

    Mohammad Ali Akbarzadeh

    2014-03-01

    Full Text Available 800x600 BACKGROUND: Cigarette smoking increases the risk of ventricular fibrillation and sudden cardiac death (SCD. QT dispersion (QTD is an important predictor of cardiac arrhythmia. The aim of this study was to assess the acute effect of smoking a single standard cigarette containing 1.7 mg nicotine on QT interval and QTD in healthy smokers and nonsmokers. METHODS: The study sample population consisted of 40 healthy male hospital staff, including 20 smokers and 20 nonsmokers. They were asked to refrain from smoking at least 6 h before attending the study. A 12-lead surface electrocardiogram (ECG, recorded at paper speed of 50 mm/s, was obtained from all participants before and 10 min after smoking of a single complete cigarette. QT interval, corrected QT interval, QTD, and corrected QT dispersion (QTcD were measured before and after smoking. RESULTS: Smokers and nonsmokers did not have any significant differences in heart rate (HR (before smoking = 67.35 ± 5.14 vs. 67.70 ± 5.07, after smoking = 76.70 ± 6.50 vs. 76.85 ± 6.50, respectively, QTD (before smoking = 37.75 ± 7.16 vs. 39.15 ± 6.55, after smoking = 44.75 ± 11.97 vs. 45.50 ± 9.58, respectively, and QTcD (before smoking = 39.85 ± 7.40 vs. 41.55 ± 6.57, after smoking = 50.70 ± 14.31 vs. 51.50 ± 11.71, respectively. However, after smoking a single cigarette, HR, mean QTD, and QTcD significantly increased (all had P value <0.001 in comparison to the measures before smoking. CONCLUSION: Smoking of a single complete cigarette in both smokers and nonsmokers results in significant QTD increase, which can cause arrhythmia and SCD.   Keywords: Cardiac, Death, Electrocardiography, Smoking, Sudden  Normal 0 false false false EN-US X-NONE FA MicrosoftInternetExplorer4

  12. Association Between ACE Gene Polymorphism and QT Dispersion in Patients with Acute Myocardial Infarction.

    Science.gov (United States)

    Karahan, Zulkuf; Ugurlu, Murat; Ucaman, Berzal; Veysel Ulug, Ali; Kaya, Ilyas; Cevik, Kemal; Sahin Adiyaman, Mehmet; Oztürk, Onder; Iyem, Hikmet; Ozdemir, Ferit

    2016-01-01

    Angiotensin converting enzyme (ACE) gene polymorphism is associated with high renin-angiotensin system causing myocardial fibrosis and ventricular repolarization abnormality. Based on these findings, this study was designed to determine the association between ACE gene insertion/deletion (I/D) polymorphism and QT dispersion after acute myocardial infarction (MI). The study included 108 patients with acute MI. Blood samples were obtained from all the patients for genomic DNA analysis. ECGs were recorded at baseline and at the end of a 6-month follow up. The OT dispersion was manually calculated. The mean age of the patients was 57.5 ±9.9 years (ranging from 36 to 70). The patients with DD genotype showed longer QT dispersion than patients with II or DI genotype at the baseline, while at the end of the six-month follow up the patients with DI genotype showed longer QT dispersion than patients with DD or II genotypes. However, the magnitude of the QT dispersion prolongation was higher in patients carrying the ACE D allele than patients who were not carrying it, at baseline and at the end of six-month follow up (52.5 ±2.6 msn vs. 47.5±2.1 msn at baseline, 57±3.2 msn vs. 53±2.6 msn in months, P: 0.428 and P: 0.613, respectively). Carriers of the D allele of ACE gene I/D polymorphism may be associated with QT dispersion prolongation in patients with MI.An interaction of QT dispersion and ACE gene polymorphism may be associated with an elevation of serum type I-C terminal pro-collagen concentration, possibly leading to myocardial fibrosis, and increased action potential duration.

  13. 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...... and TdP could be a more general problem associated with the use of these drugs. The aims of this study were to evaluate the association between different opioids and the QTc among patients and measure hERG activity under influence by opioids in vitro. METHODS: One hundred chronic nonmalignant pain...... 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...

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

    African Journals Online (AJOL)

    2015-12-20

    Dec 20, 2015 ... different electrical impulse speeds in different ventricular ... the control were enrolled in this study. All women ..... disorders. J Hum Hypertens 2004;18:707‑12. 5. Voss A, Malberg H, Schumann A, Wessel N, Walther T, Stepan H, et al. Baroreflex sensitivity, heart rate, and blood pressure variability in normal.

  15. The human Nav1.5 F1486 deletion associated with long QT syndrome leads to impaired sodium channel inactivation and reduced lidocaine sensitivity

    Science.gov (United States)

    Song, Weihua; Xiao, Yucheng; Chen, Hanying; Ashpole, Nicole M; Piekarz, Andrew D; Ma, Peilin; Hudmon, Andy; Cummins, Theodore R; Shou, Weinian

    2012-01-01

    The deletion of phenylalanine 1486 (F1486del) in the human cardiac voltage-gated sodium channel (hNav1.5) is associated with fatal long QT (LQT) syndrome. In this study we determined how F1486del impairs the functional properties of hNav1.5 and alters action potential firing in heterologous expression systems (human embryonic kidney (HEK) 293 cells) and their native cardiomyocyte background. Cells expressing hNav1.5-F1486del exhibited a loss-of-function alteration, reflected by an 80% reduction of peak current density, and several gain-of-function alterations, including reduced channel inactivation, enlarged window current, substantial augmentation of persistent late sodium current and an increase in ramp current. We also observed substantial action potential duration (APD) prolongation and prominent early afterdepolarizations (EADs) in neonatal cardiomyocytes expressing the F1486del channels, as well as in computer simulations of myocyte activity. In addition, lidocaine sensitivity was dramatically reduced, which probably contributed to the poor therapeutic outcome observed in the patient carrying the hNav1.5-F1486del mutation. Therefore, despite the significant reduction in peak current density, the F1486del mutation also leads to substantial gain-of-function alterations that are sufficient to cause APD prolongation and EADs, the predominant characteristic of LQTs. These data demonstrate that hNav1.5 mutations can have complex functional consequences and highlight the importance of identifying the specific molecular defect when evaluating potential treatments for individuals with prolonged QT intervals. PMID:22826127

  16. Electrocardiographic Abnormalities and QTc Interval in Patients Undergoing Hemodialysis.

    Directory of Open Access Journals (Sweden)

    Yuxin Nie

    abnormalities were found in this group. In multiple regression analyses, serum Ca2+ concentration before HD and LAD were independent variables of QTc interval prolongation. UA, ferritin, and interventricular septum were independent variables of ΔQTc.Prolonged QT interval is very common in HD patients and is associated with several risk factors. An appropriate concentration of dialysate electrolytes should be chosen depending on patients' clinical conditions.

  17. Contractility Dispersion in Long QT Syndrome

    Directory of Open Access Journals (Sweden)

    MH Nikoo

    2009-09-01

    Full Text Available Background: Previous studies, using M mode echocardiography, provided unexpected evidence of a mechanical alteration in patients with long QT syndrome. The aim of this study was to evaluate entire left ventricular (LV wall motion characteristics in patients with long QT syndrome using tissue Doppler imaging. Methods: We enrolled 17 patients with congenital long QT syndrome [11 female and 6 male], aged 21 to 45 years. 10 subjects without cardiac disease were also selected as a control group. Two-dimensional tissue Doppler imaging (TDI recording of the LV was obtained from the basal and mid-segments from apical four-chamber, two-chamber, and long-axis views. ‘Myocardial Contraction Duration’ [MCD] was defined as the time from start of R wave on ECG to end of S wave on TDI. MCD was measured in the six LV wall positions: septal, anteroseptal, lateral, inferior, posterior and anterior positions.Results: LV contractility dispersion was significantly greater in long QT syndrome patients compared to control group [0.051 ± 0.011 vs. 0.016 ± 0.06; P < 0.001]. Conclusion: Our study evaluated left ventricular dispersion of contractility duration in patients with long QT syndrome. This mechanical dispersion may be a reflection of the inhomogeneity of repolarisation in the long QT syndrome.

  18. 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)....

  19. Lack of an Effect of Standard and Supratherapeutic Doses of Linezolid on QTc Interval Prolongation▿†

    Science.gov (United States)

    Damle, Bharat; LaBadie, Robert R.; Cuozzo, Cheryl; Alvey, Christine; Choo, Heng Wee; Riley, Steve; Kirby, Deborah

    2011-01-01

    A double-blind, placebo-controlled, four-way crossover study was conducted in 40 subjects to assess the effect of linezolid on corrected QT (QTc) interval prolongation. Time-matched, placebo-corrected QT intervals were determined predose and at 0.5, 1 (end of infusion), 2, 4, 8, 12, and 24 h after intravenous dosing of linezolid 600 and 1,200 mg. Oral moxifloxacin at 400 mg was used as an active control. The pharmacokinetic profile of linezolid was also evaluated. At each time point, the upper bound of the 90% confidence interval (CI) for placebo-corrected QTcF values (i.e., QTc values adjusted for ventricular rate using the correction methods of Fridericia) for linezolid 600 and 1,200-mg doses were 5 ms, indicating that the study was adequately sensitive to assess QTc prolongation. The pharmacokinetic profile of linezolid at 600 mg was consistent with previous observations. Systemic exposure to linezolid increased in a slightly more than dose-proportional manner at supratherapeutic doses, but the degree of nonlinearity was small. At a supratherapeutic single dose of 1,200 mg of linezolid, no treatment-related increase in adverse events was seen compared to 600 mg of linezolid, and no clinically meaningful effects on vital signs and safety laboratory evaluations were noted. PMID:21709083

  20. Two markers in predicting the cardiovascular events in patients with polycystic ovary syndrome: increased P-wave and QT dispersion.

    Science.gov (United States)

    Akdag, S; Cim, N; Yildizhan, R; Akyol, A; Ozturk, F; Babat, N

    2015-09-01

    Polycystic ovary syndrome (PCOS) is a prevalent disease with many potential long-term cardiovascular risks. P-wave dispersion (Pdis) and QT dispersion (QTdis) have been shown to be noninvasive electrocardiographic predictors for development of cardiac arrhythmias. In this study we aimed to search Pdis and QTdis parameters in patients with PCOS. The study included 82 patients with PCOS and 74 age- and sex-matched healthy controls. Baseline 12-lead electrocardiographic and transthoracic echocardiographic measurements were evaluated. P-wave maximum duration (Pmax), P-wave minimum duration (Pmin), Pdis, QT interval, heart rate-corrected QT dispersion and QTdis were calculated by two cardiologists. Patients wirh PCOS had significantly higher QT dispersion (49.5 ± 14.1 vs. 37.9 ± 12.6 ms, p PCOS patients.

  1. Dispersion of repolarization and refractoriness are determinants of arrhythmia phenotype in transgenic mice with long QT.

    Science.gov (United States)

    London, Barry; Baker, Linda C; Petkova-Kirova, Polina; Nerbonne, Jeanne M; Choi, Bum-Rak; Salama, Guy

    2007-01-01

    Enhanced dispersion of repolarization (DR) and refractoriness may be a unifying mechanism central to arrhythmia genesis in the long QT (LQT) syndrome. The role of DR in promoting arrhythmias was investigated in several strains of molecularly engineered mice: (a) Kv4.2 dominant negative transgenic (Kv4.2DN) that lacks the fast component of the transient outward current, I(to,f), have action potential (AP) and QT prolongation, but no spontaneous arrhythmias, (b) Kv1.4 targeted mice (Kv1.4-/-) that lack the slow component of I(to) (I(to,s)), have no QT prolongation and no spontaneous arrhythmias, and (c) double transgenic (Kv4.2DN x Kv1.4-/-) mice that lack both I(to,f) and I(to,s), have AP and QT prolongation, and spontaneous ventricular tachyarrhythmias. Hearts were perfused, stained with di-4-ANEPPS and optically mapped. Activation patterns and conduction velocities were similar between the strains but AP duration at 75% recovery (APD75) was longer in Kv4.2DN (28.0 +/- 2.5 ms, P mice than controls (20.3 +/- 1.0 ms, n = 5). Dispersion of refractoriness between apex and base was markedly reduced in Kv4.2DN (0.3 +/- 0.5 ms, n = 6, P mice compared with controls (10 +/- 2 ms, n = 5). A premature pulse elicited ventricular tachycardia (VT) in Kv1.4-/- (n = 4/5) and Kv4.2DN x Kv1.4-/- hearts (n = 5/5) but not Kv4.2DN hearts (n = 0/6). Voltage-clamp recordings showed that I(to,f) was 30% greater in myocytes from the apex than base which may account for the absence of DR in Kv4.2DN mice. Thus, dispersion of repolarization (DR) appears to be an important determinant of arrhythmia vulnerability.

  2. 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.

  3. 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.

  4. 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

  5. QT/RR Coupling and Gender Differences

    Czech Academy of Sciences Publication Activity Database

    Halámek, Josef; Jurák, Pavel; Lipoldová, J.; Leinveber, Pavel

    2010-01-01

    Roč. 37, - (2010), s. 365-368 ISSN 0276-6574 R&D Projects: GA ČR GA102/08/1129 Institutional research plan: CEZ:AV0Z20650511 Keywords : THEW * QT/RR model * EXPDC Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering http://cinc.mit.edu/archives/2010/pdf/0365.pdf

  6. Effect of PR interval prolongation on long-term outcomes in patients with left bundle branch block vs non-left bundle branch block morphologies undergoing cardiac resynchronization therapy.

    Science.gov (United States)

    Rickard, John; Karim, Mohammad; Baranowski, Bryan; Cantillon, Daniel; Spragg, David; Tang, W H Wilson; Niebauer, Mark; Grimm, Richard; Trulock, Kevin; Wilkoff, Bruce; Varma, Niraj

    2017-10-01

    Although the influence of QRS duration (QRSd) and/or bundle branch block morphology on outcomes of cardiac resynchronization therapy (CRT) have been well studied, the effect of PR interval remains uncertain. The purpose of this study was to evaluate the impact of PR prolongation (PRp) before CRT on long-term outcomes, specifically taking into account bundle branch block morphology and QRSd. We extracted clinical data on consecutive patients undergoing CRT. Multivariate models were constructed to analyze the effect of PRp (≥200 ms) on the combined endpoint of death, heart transplant, or left ventricular assist device. Kaplan-Meier curves were constructed stratifying patients based on bundle branch block and QRSd (dichotomized by 150 ms). Of the 472 patients who met inclusion criteria, 197 (41.7%) had PR interval ≥200 ms. During follow-up (mean 5.1 ± 2.6 years) there were 214 endpoints, of which 109 (23.1%) occurred in patients with PRp. In multivariate analysis, PRp was independently associated with worsened outcomes (hazard ratio 1.34, 95% confidence interval 1.01-1.77, P = .04). When stratified by bundle branch block morphology, PRp was significantly associated with worsened outcomes (log-rank P <.001) in patients with LBBB but not in those with non-LBBB (log-rank P = .55). Among patients with LBBB, stratified by QRSd, patients without PRp had improved outcomes compared to those with PRp independent of QRSd (log-rank P <.001). PRp is an independent predictor of impaired long-term outcome after CRT among patients with LBBB but not in non-LBBB patients. Notably, among LBBB patients, PRp is a more important predictor than QRSd in assessing long-term outcomes. Copyright © 2017. Published by Elsevier Inc.

  7. Effects of Single Dose Energy Drink on QT and P-Wave Dispersion

    Directory of Open Access Journals (Sweden)

    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.

  8. Arrhythmia phenotype in mouse models of human long QT.

    Science.gov (United States)

    Salama, Guy; Baker, Linda; Wolk, Robert; Barhanin, Jacques; London, Barry

    2009-03-01

    Enhanced dispersion of repolarization (DR) was proposed as a unifying mechanism, central to arrhythmia genesis in the long QT (LQT) syndrome. In mammalian hearts, K(+) channels are heterogeneously expressed across the ventricles resulting in 'intrinsic' DR that may worsen in long QT. DR was shown to be central to the arrhythmia phenotype of transgenic mice with LQT caused by loss of function of the dominant mouse K(+) currents. Here, we investigated the arrhythmia phenotype of mice with targeted deletions of KCNE1 and KCNH2 genes which encode for minK/IsK and Merg1 (mouse homolog of human ERG) proteins resulting in loss of function of I(Ks) and I(Kr), respectively. Both currents are important human K(+) currents associated with LQT5 and LQT2. Loss of minK, a protein subunit that interacts with KvLQT1, results in a marked reduction of I(Ks) giving rise to the Jervell and Lange-Nielsen syndrome and the reduced KCNH2 gene reduces MERG and I(Kr). Hearts were perfused, stained with di-4-ANEPPS and optically mapped to compare action potential durations (APDs) and arrhythmia phenotype in homozygous minK (minK(-/-)) and heterozygous Merg1 (Merg(+/-)) deletions and littermate control mice. MinK(-/-) mice has similar APDs and no arrhythmias (n = 4). Merg(+/-) mice had prolonged APDs (from 20 +/- 6 to 32 +/- 9 ms at the base, p mice (60% vs. 10%). A comparison of mouse models of LQT based on K(+) channel mutations important to human and mouse repolarization emphasizes DR as a major determinant of arrhythmia vulnerability.

  9. 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.

  10. In Vitro and In Silico Risk Assessment in Acquired Long QT Syndrome: The Devil Is in the Details.

    Science.gov (United States)

    Lee, William; Windley, Monique J; Vandenberg, Jamie I; Hill, Adam P

    2017-01-01

    Acquired long QT syndrome, mostly as a result of drug block of the Kv11. 1 potassium channel in the heart, is characterized by delayed cardiac myocyte repolarization, prolongation of the T interval on the ECG, syncope and sudden cardiac death due to the polymorphic ventricular arrhythmia Torsade de Pointes (TdP). In recent years, efforts are underway through the Comprehensive in vitro proarrhythmic assay (CiPA) initiative, to develop better tests for this drug induced arrhythmia based in part on in silico simulations of pharmacological disruption of repolarization. However, drug binding to Kv11.1 is more complex than a simple binary molecular reaction, meaning simple steady state measures of potency are poor surrogates for risk. As a result, there is a plethora of mechanistic detail describing the drug/Kv11.1 interaction-such as drug binding kinetics, state preference, temperature dependence and trapping-that needs to be considered when developing in silico models for risk prediction. In addition to this, other factors, such as multichannel pharmacological profile and the nature of the ventricular cell models used in simulations also need to be considered in the search for the optimum in silico approach. Here we consider how much of mechanistic detail needs to be included for in silico models to accurately predict risk and further, how much of this detail can be retrieved from protocols that are practical to implement in high throughout screens as part of next generation of preclinical in silico drug screening approaches?

  11. Effects of Single Dose Energy Drink on QT and P-Wave Dispersion

    OpenAIRE

    Arınç, Hüseyin; Sarli, Bahadir; Baktir, Ahmet Oguz; Yolcu, Mustafa; Ozyildirim, Serhan; Kayardi, Mahmut; Cosgun, Mehmet; Erguzel, Nuri; Gunduz, Huseyin; Uyan, Cihangir

    2013-01-01

    Objective: 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 tho...

  12. Quinsy tonsillectomy or interval tonsillectomy - a prospective ...

    African Journals Online (AJOL)

    Fifty-one patients with peritonsillar abscesses were randomised to undergo either quinsy tonsillectomy (aT) or interval tonsillectomy (IT), and the two groups were compared. The QT group lost fewer (10,3 v. 17,9) working days and less blood during the operation (158,6 ml v. 205,7 ml); haemostasis was easier and the ...

  13. Heart rate variability and QT dispersion study in brain death patients and comatose patients with normal brainstem function

    International Nuclear Information System (INIS)

    Vakilian, A.R.; Iranmanesh, F.; Nadimi, A.E.; Kahnali, J.A.

    2011-01-01

    To compare heart rate variability (HRV) and QT dispersion in comatose patients with normal brainstem function and with brain death. Fourteen brain death patients with clinical signs of imminent brain death and 15 comatose patients were examined by neurologist in intensive care unit. HRV, RR interval and QT dispersion on ECG were assessed for 24 hours in both groups. Independent t-test and chi-square test were used for statistical analysis to determine significance which was set at p < 0.05. According to Holter findings, mean of standard deviation of RR-interval in the comatose and brain death groups was 48.33 and 35 respectively (p = 0.045). Mean of covariance coefficient of RR-interval was 0.065 in the comatose group and 0.043 in the brain deaths (p = 0.006). QT dispersion was not significant difference in two groups. HRV and RR-interval analysis appeared as an early finding for the diagnosis of brainstem death in comparison to comatose patients with normal brainstem function. QT dispersion had not significant in this regard. (author)

  14. Enhanced basal late sodium current appears to underlie the age-related prolongation of action potential duration in guinea pig ventricular myocytes.

    Science.gov (United States)

    Song, Yejia; Belardinelli, Luiz

    2017-12-14

    Aging hearts have prolonged QT interval and are vulnerable to oxidative stress. Because the QT interval indirectly reflects the action potential duration (APD), we examined the hypotheses that 1) the APD of ventricular myocytes increases with age; 2) the age-related prolongation of APD is due to an enhancement of basal late Na + current (I NaL ); 3) inhibition of I NaL may protect aging hearts from arrhythmogenic effects of hydrogen peroxide (H 2 O 2 ). Experiments were performed on ventricular myocytes isolated from one-month (young) and one-year (old) guinea pigs (GPs). The APD of myocytes from old GPs was significantly longer than that from young GPs and was shortened by the I NaL inhibitors GS967 and tetrodotoxin. The magnitude of I NaL was significantly larger in myocytes from old than from young GPs. The CaMKII inhibitors KN-93 and AIP and the Na V 1.5-channel blocker MTSEA blocked the I NaL . There were no significant differences between myocytes from young and old GPs in L-type Ca 2+ current and the rapidly- and slowly-activating delayed rectifier K + currents, although the inward rectifier K + current was slightly decreased in myocytes from old GPs. H 2 O 2 induced more early afterdepolarizations in myocytes from old than from young GPs. The effect of H 2 O 2 was attenuated by GS967. The results suggest that 1) the APD of myocytes from old GPs is prolonged, 2) a CaMKII-mediated increase in Na V 1.5-channel I NaL is responsible for the prolongation of APD, and 3) Inhibition of I NaL may be beneficial for maintaining electrical stability under oxidative stress in myocytes of old GPs.

  15. Prognostic implications of mutation-specific QTc standard deviation in congenital long QT syndrome.

    Science.gov (United States)

    Mathias, Andrew; Moss, Arthur J; Lopes, Coeli M; Barsheshet, Alon; McNitt, Scott; Zareba, Wojciech; Robinson, Jennifer L; Locati, Emanuela H; Ackerman, Michael J; Benhorin, Jesaia; Kaufman, Elizabeth S; Platonov, Pyotr G; Qi, Ming; Shimizu, Wataru; Towbin, Jeffrey A; Michael Vincent, G; Wilde, Arthur A M; Zhang, Li; Goldenberg, Ilan

    2013-05-01

    Individual corrected QT interval (QTc) may vary widely among carriers of the same long QT syndrome (LQTS) mutation. Currently, neither the mechanism nor the implications of this variable penetrance are well understood. To hypothesize that the assessment of QTc variance in patients with congenital LQTS who carry the same mutation provides incremental prognostic information on the patient-specific QTc. The study population comprised 1206 patients with LQTS with 95 different mutations and ≥ 5 individuals who carry the same mutation. Multivariate Cox proportional hazards regression analysis was used to assess the effect of mutation-specific standard deviation of QTc (QTcSD) on the risk of cardiac events (comprising syncope, aborted cardiac arrest, and sudden cardiac death) from birth through age 40 years in the total population and by genotype. Assessment of mutation-specific QTcSD showed large differences among carriers of the same mutations (median QTcSD 45 ms). Multivariate analysis showed that each 20 ms increment in QTcSD was associated with a significant 33% (P = .002) increase in the risk of cardiac events after adjustment for the patient-specific QTc duration and the family effect on QTc. The risk associated with QTcSD was pronounced among patients with long QT syndrome type 1 (hazard ratio 1.55 per 20 ms increment; P<.001), whereas among patients with long QT syndrome type 2, the risk associated with QTcSD was not statistically significant (hazard ratio 0.99; P = .95; P value for QTcSD-by-genotype interaction = .002). Our findings suggest that mutations with a wider variation in QTc duration are associated with increased risk of cardiac events. These findings appear to be genotype-specific, with a pronounced effect among patients with the long QT syndrome type 1 genotype. Copyright © 2013. Published by Elsevier Inc.

  16. Heritability of Tpeak-Tend Interval and T-wave Amplitude: A Twin Study

    DEFF Research Database (Denmark)

    Haarmark, Christian; Kyvik, Kirsten O; Vedel-Larsen, Esben

    2011-01-01

    BACKGROUND: -Tpeak-Tend interval (TpTe) and T-wave amplitude (Tamp) carry diagnostic and prognostic information regarding cardiac morbidity and mortality. Heart rate and QT interval are known to be heritable traits. The heritability of T-wave morphology parameters such as TpTe and Tamp is unknown...... interval, QTpeak and QTend interval) were measured and averaged over three consecutive beats in lead V5. TpTe was calculated as the QTend and QTpeak interval difference. Heritability was assessed using structural equation models adjusting for age, gender and BMI. All models were reducible to a model...... of additive genetics and unique environment. All variables had considerable genetic components. Adjusted heritability estimates were: TpTe 46%, Tamp lead V1 34%, Tamp lead V5 47%, RR interval 55%, QT interval 67% and QTcB 42%. CONCLUSIONS: -RR interval, QT-interval, T-wave amplitude and Tpeak-Tend interval...

  17. Thorough QT (TQT) studies: concordance with torsadogenesis and an evolving cardiac safety testing paradigm.

    Science.gov (United States)

    Wiśniowska, Barbara; Tylutki, Zofia; Polak, Sebastian

    2017-10-01

    Since 2005, when the International Conference on Harmonisation (ICH) E14 guideline was adopted, no drug has been withdrawn because of QTc prolongation or torsade de pointes arrhythmia. There are, however, costs associated with this success. In addition to the time and money invested, thorough QT (TQT) studies have limited the efficiency of the drug development pipeline. In this paper, we discuss the relevance of TQT trials as a tool for proarrhythmic risk prediction as a part of the debate regarding their usefulness. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. The clinical factors′ prediction of increased intradialytic qt dispersion on the electrocardiograms of chronic hemodialysis patients

    Directory of Open Access Journals (Sweden)

    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.

  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. 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...... circadian variation using mean values of QTdisp 12, QTdisp 6, or QTdisp 2 obtained every hour, every 2, or every 4 hours, except in QTdisp 6, which demonstrated a significant circadian variation (P ... a significant circadian variation in QTdisp 12 and QTdisp 6 (P circadian variation was seen in QTdisp 2. A subdivision into 10-year age groups revealed that subjects at age >50 years had a significant circadian variation in QTdisp 12 and QTdisp 6, but not in QTdisp 2. Only in males...

  1. The Static and Dynamic QT/RR Coupling and QT Parameters

    Czech Academy of Sciences Publication Activity Database

    Halámek, Josef; Jurák, Pavel; Villa, M.; Fráňa, P.; Novák, M.; Lipoldová, J.; Leinveber, P.; Vondra, Vlastimil; Somers, V. K.; Kára, T.

    2008-01-01

    Roč. 6, č. 1 (2008), s. 533 ISSN 1556-7451. [World Congress on Heart Disease /14./. 26.07.2008-29.07.2008, Toronto] Institutional research plan: CEZ:AV0Z20650511 Keywords : QT parameters Subject RIV: FA - Cardiovascular Disease s incl. Cardiotharic Surgery

  2. Solving the TTC 2013 Flowgraphs 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 Flowgraphs Transformation Case. It solves all four tasks, and it has won the best efficiency award for this case.

  3. Single Doses up to 800 mg of E-52862 Do Not Prolong the QTc Interval--A Retrospective Validation by Pharmacokinetic-Pharmacodynamic Modelling of Electrocardiography Data Utilising the Effects of a Meal on QTc to Demonstrate ECG Assay Sensitivity.

    Science.gov (United States)

    Täubel, Jörg; Ferber, Georg; Lorch, Ulrike; Wang, Duolao; Sust, Mariano; Camm, A John

    2015-01-01

    E-52862 is a Sigma-1 receptor antagonist (S1RA) currently under investigation as a potential analgesic medicine. We successfully applied a concentration-effect model retrospectively to a four-way crossover Phase I single ascending dose study and utilized the QTc shortening effects of a meal to demonstrate assay sensitivity by establishing the time course effects from baseline in all four periods, independently from any potential drug effects. Thirty two healthy male and female subjects were included in four treatment periods to receive single ascending doses of 500 mg, 600 mg or 800 mg of E-52862 or placebo. PK was linear over the dose range investigated and doses up to 600 mg were well tolerated. The baseline electrocardiography (ECG) measurements on Day-1 were time-matched with ECG and pharmacokinetic (PK) samples on Day 1 (dosing day). In this conventional mean change to time-matched placebo analysis, the largest time-matched difference to placebo QTcI was 1.44 ms (90% CI: -4.04, 6.93 ms) for 500 mg; -0.39 ms (90% CI: -3.91, 3.13 ms) for 600 mg and 1.32 ms (90% CI: -1.89, 4.53 ms) for 800 mg of E-52862, thereby showing the absence of any QTc prolonging effect at the doses tested. In addition concentration-effect models, one based on the placebo corrected change from baseline and one for the change of QTcI from average baseline with time as fixed effect were fitted to the data confirming the results of the time course analysis. The sensitivity of this study to detect small changes in the QTc interval was confirmed by demonstrating a shortening of QTcF of -8.1 (90% CI: -10.4, -5.9) one hour and -7.2 (90% CI: -9.4, -5.0) three hours after a standardised meal. EU Clinical Trials Register EudraCT 2010 020343 13.

  4. Analysis of the potential effect of ponatinib on the QTc interval in patients with refractory hematological malignancies.

    Science.gov (United States)

    Sonnichsen, Daryl; Dorer, David J; Cortes, Jorge; Talpaz, Moshe; Deininger, Michael W; Shah, Neil P; Kantarjian, Hagop M; Bixby, Dale; Mauro, Michael J; Flinn, Ian W; Litwin, Jeffrey; Turner, Christopher D; Haluska, Frank G

    2013-06-01

    Cardiac dysfunction, particularly QT interval prolongation, has been observed with tyrosine kinase inhibitors approved to treat chronic myeloid leukemia. This study examines the effects of ponatinib on cardiac repolarization in patients with refractory hematological malignancies enrolled in a phase 1 trial. Electrocardiograms (ECGs) were collected at 3 dose levels (30, 45, and 60 mg) at 6 time points. Electrocardiographic parameters, including QTc interval, were measured, and 11 morphological analyses were conducted. Central tendency analyses of ECG parameters were performed using time-point and time-averaged approaches. All patients with at least 2 baseline ECGs and 1 on-treatment ECG were included in the analyses. Patients with paired ECGs and plasma samples were included in the pharmacokinetic/pharmacodynamic analysis to examine the relationship between ponatinib plasma concentration and change from baseline in QT intervals. Thirty-nine patients at the 30-, 45-, and 60-mg dose levels were included in the central tendency and morphological analyses. There was no significant effect on cardiac repolarization, as evidenced by non-clinically significant mean QTcF changes from baseline of -10.9, -3.6, and -5.0 ms for the 30-, 45-, and 60-mg dose levels, respectively. The morphological analysis revealed 2 patients with atrial fibrillation and 2 with T wave inversion. Seventy-five patients were included in the pharmacokinetic/pharmacodynamic analysis across all dose levels. The slope of the relationship for QTcF versus plasma ponatinib concentration was not positive (-0.0171), indicating no exposure-effect relationship. Ponatinib is associated with a low risk of QTc prolongation in patients with refractory hematological malignancies.

  5. Qt based control system software for Low Energy Accelerator Facility

    International Nuclear Information System (INIS)

    Basu, A.; Singh, S.; Nagraju, S.B.V.; Gupta, S.; Singh, P.

    2012-01-01

    Qt based control system software for Low Energy Accelerating Facility (LEAF) is operational at Bhabha Atomic Research Centre (BARC), Trombay, Mumbai. LEAF is a 50 keV negative ion electrostatic accelerator based on SNICS ion source. Control system uses Nokia Trolltech's QT 4.x API for control system software. Ni 6008 USB based multifunction cards has been used for control and read back field equipments such as power supplies, pumps, valves etc. Control system architecture is designed to be client server. Qt is chosen for its excellent GUI capability and platform independent nature. Control system follows client server architecture. The paper will describe the control system. (author)

  6. In Vitro and In Silico Risk Assessment in Acquired Long QT Syndrome: The Devil Is in the Details

    Directory of Open Access Journals (Sweden)

    William Lee

    2017-11-01

    Full Text Available Acquired long QT syndrome, mostly as a result of drug block of the Kv11. 1 potassium channel in the heart, is characterized by delayed cardiac myocyte repolarization, prolongation of the T interval on the ECG, syncope and sudden cardiac death due to the polymorphic ventricular arrhythmia Torsade de Pointes (TdP. In recent years, efforts are underway through the Comprehensive in vitro proarrhythmic assay (CiPA initiative, to develop better tests for this drug induced arrhythmia based in part on in silico simulations of pharmacological disruption of repolarization. However, drug binding to Kv11.1 is more complex than a simple binary molecular reaction, meaning simple steady state measures of potency are poor surrogates for risk. As a result, there is a plethora of mechanistic detail describing the drug/Kv11.1 interaction—such as drug binding kinetics, state preference, temperature dependence and trapping—that needs to be considered when developing in silico models for risk prediction. In addition to this, other factors, such as multichannel pharmacological profile and the nature of the ventricular cell models used in simulations also need to be considered in the search for the optimum in silico approach. Here we consider how much of mechanistic detail needs to be included for in silico models to accurately predict risk and further, how much of this detail can be retrieved from protocols that are practical to implement in high throughout screens as part of next generation of preclinical in silico drug screening approaches?

  7. Prevalence and spectrum of large deletions or duplications in the major long QT syndrome-susceptibility genes and implications for long QT syndrome genetic testing.

    Science.gov (United States)

    Tester, David J; Benton, Amber J; Train, Laura; Deal, Barbara; Baudhuin, Linnea M; Ackerman, Michael J

    2010-10-15

    Long QT syndrome (LQTS) is a cardiac channelopathy associated with syncope, seizures, and sudden death. Approximately 75% of LQTS is due to mutations in genes encoding for 3 cardiac ion channel α-subunits (LQT1 to LQT3). However, traditional mutational analyses have limited detection capabilities for atypical mutations such as large gene rearrangements. We set out to determine the prevalence and spectrum of large deletions/duplications in the major LQTS-susceptibility genes in unrelated patients who were mutation negative after point mutation analysis of LQT1- to LQT12-susceptibility genes. Forty-two unrelated, clinically strong LQTS patients were analyzed using multiplex ligation-dependent probe amplification, a quantitative fluorescent technique for detecting multiple exon deletions and duplications. The SALSA multiplex ligation-dependent probe amplification LQTS kit from MRC-Holland was used to analyze the 3 major LQTS-associated genes, KCNQ1, KCNH2, and SCN5A, and the 2 minor genes, KCNE1 and KCNE2. Overall, 2 gene rearrangements were found in 2 of 42 unrelated patients (4.8%, confidence interval 1.7 to 11). A deletion of KCNQ1 exon 3 was identified in a 10-year-old Caucasian boy with a corrected QT duration of 660 ms, a personal history of exercise-induced syncope, and a family history of syncope. A deletion of KCNQ1 exon 7 was identified in a 17-year-old Caucasian girl with a corrected QT duration of 480 ms, a personal history of exercise-induced syncope, and a family history of sudden cardiac death. In conclusion, because nearly 5% of patients with genetically elusive LQTS had large genomic rearrangements involving the canonical LQTS-susceptibility genes, reflex genetic testing to investigate genomic rearrangements may be of clinical value. Copyright © 2010 Elsevier Inc. All rights reserved.

  8. The effect of thrombolytic therapy on QT dispersion in acute ...

    African Journals Online (AJOL)

    2013-07-02

    Jul 2, 2013 ... intraventricular conduction defect or atrial fibrillation were excluded from the study. .... detection and their benign characteristics. In some series including .... Glancy JM, Garratt CJ, Woods KL, de Bono DP. QT dispersion and ...

  9. Patients with Long QT Syndrome Due to Impaired hERG-encoded Kv11.1 Potassium Channel Have Exaggerated Endocrine Pancreatic and Incretin Function Associated with Reactive Hypoglycemia

    DEFF Research Database (Denmark)

    Hyltén-Cavallius, Louise; Iepsen, Eva W; Wewer Albrechtsen, Nicolai J

    2017-01-01

    Background -Loss-of-function mutations in hERG (encoding the Kv11.1 voltage-gated potassium channel) cause long QT syndrome (LQT2) due to prolonged cardiac repolarization. However, Kv11.1 is also present in pancreatic α and β cells and intestinal L and K cells, secreting glucagon, insulin, and th...

  10. Histone Deacetylase Inhibitors Prolong Cardiac Repolarization through Transcriptional Mechanisms.

    Science.gov (United States)

    Spence, Stan; Deurinck, Mark; Ju, Haisong; Traebert, Martin; McLean, LeeAnne; Marlowe, Jennifer; Emotte, Corinne; Tritto, Elaine; Tseng, Min; Shultz, Michael; Friedrichs, Gregory S

    2016-09-01

    Histone deacetylase (HDAC) inhibitors are an emerging class of anticancer agents that modify gene expression by altering the acetylation status of lysine residues of histone proteins, thereby inducing transcription, cell cycle arrest, differentiation, and cell death or apoptosis of cancer cells. In the clinical setting, treatment with HDAC inhibitors has been associated with delayed cardiac repolarization and in rare instances a lethal ventricular tachyarrhythmia known as torsades de pointes. The mechanism(s) of HDAC inhibitor-induced effects on cardiac repolarization is unknown. We demonstrate that administration of structurally diverse HDAC inhibitors to dogs causes delayed but persistent increases in the heart rate corrected QT interval (QTc), an in vivo measure of cardiac repolarization, at timepoints far removed from the Tmax for parent drug and metabolites. Transcriptional profiling of ventricular myocardium from dogs treated with various HDAC inhibitors demonstrated effects on genes involved in protein trafficking, scaffolding and insertion of various ion channels into the cell membrane as well as genes for specific ion channel subunits involved in cardiac repolarization. Extensive in vitro ion channel profiling of various structural classes of HDAC inhibitors (and their major metabolites) by binding and acute patch clamp assays failed to show any consistent correlations with direct ion channel blockade. Drug-induced rescue of an intracellular trafficking-deficient mutant potassium ion channel, hERG (G601S), and decreased maturation (glycosylation) of wild-type hERG expressed by CHO cells in vitro correlated with prolongation of QTc intervals observed in vivo The results suggest that HDAC inhibitor-induced prolongation of cardiac repolarization may be mediated in part by transcriptional changes of genes required for ion channel trafficking and localization to the sarcolemma. These data have broad implications for the development of these drug classes and

  11. The Jervell and Lange-Nielsen syndrome; atrial pacing combined with ß-blocker therapy, a favorable approach in young high-risk patients with long QT syndrome?

    Science.gov (United States)

    Früh, Andreas; Siem, Geir; Holmström, Henrik; Døhlen, Gaute; Haugaa, Kristina H

    2016-11-01

    Patients with Jervell and Lange-Nielsen syndrome (JLNS) exhibit severe phenotypes that are characterized by congenital deafness, very long QT intervals, and high risk of life-threatening arrhythmias. Current treatment strategies include high doses of beta-blocker medication, left cardiac sympathetic denervation, and ICD placement, which is challenging in young children. The purpose of this study was to evaluate the safety and effect of pacing in addition to beta-blocker treatment in children with JLNS. All genetically confirmed patients with JLNS born since 1999 in Norway were included in the study. Data on history of long QT syndrome-related symptoms, QT interval, and beta-blocker and pacemaker treatment were recorded. A total of 9 patients with QT intervals ranging from 510 to 660 ms were identified. Eight patients developed long QT syndrome-related symptoms, and 1 patient died before diagnosis. The survivors received beta-blocker medication. Seven patients also received a pacemaker; 1 had a ventricular lead and 6 had atrial leads. The patient with the ventricular lead died during follow-up. The 6 patients with atrial leads survived without events at a mean follow-up of 6.9 years after pacemaker implantation. Two patients received prophylactic upgrade to a 2-chamber ICD. No arrhythmic events occurred in 6 very young JLNS patients who received atrial pacing in combination with increased doses of beta-blockers during 7-year follow-up. If confirmed in additional patients, this treatment strategy may prevent life-threatening arrhythmias in this high-risk patient group and may act as a bridge to insertion of a 2-chamber ICD when left cardiac sympathetic denervation is not available. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  12. 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

    BACKGROUND AND OBJECTIVE: The T-peak to T-end (TpTe) interval has been suggested as an index of transmural dispersion and as a marker of drug-induced abnormal repolarization. In this study, we investigate the relation between TpTe and the QT interval. METHODS: Electrocardiograms (ECGs) from five...

  13. Evaluasi Elektrokardiogram Interval QTc dan JTc pada Penderita Malaria Vivaks yang Diberikan Dihidroartemisinin-Piperakuin dan Primakuin

    Directory of Open Access Journals (Sweden)

    Jason Sriwijaya

    2016-03-01

    . One of the side effects that must be put into caution is the prolongation ofventricular repolarization, which can lead to the development of ventricular arrhythmia known as Torsadede Pointes (TdP. This study used  ‘before and after’ design and was aimed to find out whether there was asignificant difference of QTc and JTc interval of vivax malaria patients pre and post DHA-PPQ and Primaquin(PQ dose. The ECG record of DHA-PPQ and PQ, respectively, 24 and 14 subjects. QT and JT intervalsare affected by heart rate, thus, both of them have to be corrected according to the heart rate using twoformulas, i.e.: Bazett (QTcB, JTcB and Fridericia (QTcF, JTcF formulas. The results showed significant QTcFprolongations of 14.42 ms predose and 20.53 ms postdose on D3 DHA-PPQ treatment compared to thebaseline value, whereas prolongations of JT interval were 13.43 ms found on D3 postdose. The results aftergiven PQ showed mean difference of QTcB compared to the baseline value was 19.42 ms. The result for JTcFinterval after given PQ, showed mean difference of prolongations compared to the baseline value was 16.50ms, which was statistically significant. Key words: dihydroartemisinin-piperaquine, primaquine vivax malaria, Torsade de Pointes, QTcinterval,JTc interval

  14. Genotype-Phenotype Aspects of Type 2 Long QT Syndrome

    NARCIS (Netherlands)

    Shimizu, Wataru; Moss, Arthur J.; Wilde, Arthur A. M.; Towbin, Jeffrey A.; Ackerman, Michael J.; January, Craig T.; Tester, David J.; Zareba, Wojciech; Robinson, Jennifer L.; Qi, Ming; Vincent, G. Michael; Kaufman, Elizabeth S.; Hofman, Nynke; Noda, Takashi; Kamakura, Shiro; Miyamoto, Yoshihiro; Shah, Samit; Amin, Vinit; Goldenberg, Ilan; Andrews, Mark L.; McNitt, Scott

    2009-01-01

    Objectives The purpose of this study was to investigate the effect of location, coding type, and topology of KCNH2(hERG) mutations on clinical phenotype in type 2 long QT syndrome (LQTS). Background Previous studies were limited by population size in their ability to examine phenotypic effect of

  15. The role of CAV3 in long-QT syndrome

    DEFF Research Database (Denmark)

    Hedley, Paula L; Kanters, Jørgen K.; Dembic, Maja

    2013-01-01

    Mutations in CAV3, coding for caveolin-3, the major constituent scaffolding protein of cardiac caveolae, have been associated with skeletal muscle disease, cardiomyopathy, and most recently long-QT syndrome (LQTS) and sudden infant death syndrome. We examined the occurrence of CAV3 mutations...

  16. Commentary on: ?Levofloxacin?Induced QTc Prolongation Depends on the Time of Drug Administration?

    OpenAIRE

    Garnett, C; Johannesen, L

    2016-01-01

    Circadian variations in the corrected QT (QTc) interval have been documented in clinical trials. Animal models show circadian variations in expression of the cardiac ion channels that are necessary to maintain the heart's electrophysiological properties. Can these diurnal rhythms in QTc affect the ability of a drug to delay cardiac repolarization?

  17. Effects of valsartan and nebivolol on blood pressure, QT dispersion and left ventricular hypertrophy in hypertensive patients

    Directory of Open Access Journals (Sweden)

    Luminita Lăţea

    2010-06-01

    Full Text Available Objectives: The aim of this study was to analyze the antihypertensiveeffect of Valsartan and Nebivolol and their effects on QT dispersion and left ventricular hypertrophy (LVH in the treatment of naive hypertensive patients.Methods: A prospective study with a six-month follow-up was conducted on hypertensive patients with LVH and mild/ moderate essential hypertension. The patients were randomly assigned to Valsartan (80 to 160 mg/day or Nebivolol (5 to 10 mg/day groups. The study group consistedof 108 patients, 55 in the Valsartan group and 53 in the Nebivolol group.Results: The range of mean systolic blood pressure (SBP varied from 152±17 (baseline to 132±17 mmHg (follow-up in the Valsartan group (p<0.001; from 146±13 to 125±14 mmHg in the Nebivolol group (p<0.001. The decrease in mean diastolic blood pressure (DBP was 9.5±2.5 mmHg in the Valsartan group and 12.3±5.0 mmHg in the Nebivolol group. A significant reduction in QT and corrected QT (Bazett’s formula dispersion was observed in both groups, with a slightly higher reduction in the Valsartan group. Echocardiography showed a decreasein the left ventricle mass (LVM indices (p<0.05 in both groups with a greater reduction in the Valsartan group.Conclusion: Valsartan treatment was as effective as Nebivolol in reducing the 24 hour- SBP after a 6 month treatment. Nebivolol treatment proved to be superior to Valsartan in reducing DBP. Both therapies were effective in reducing the LVH; Valsartan proved to be superior to Nebivolol in reducing the QT interval indexes in relation to blood pressure and LVM reduction.

  18. Magnitude of increase in QTc interval after initiation of dofetilide in patients with persistent atrial fibrillation is associated with increased rates of pharmacological cardioversion and long-term freedom from recurrent atrial fibrillation.

    Science.gov (United States)

    Huang, Henry D; Waks, Jonathan W; Steinhaus, Daniel A; Zimetbaum, Peter

    2016-07-01

    Dofetilide is a class III antiarrhythmic drug approved for the treatment of atrial fibrillation (AF). Dofetilide-induced corrected QT (QTc) interval prolongation is a surrogate for the degree of drug effect, but the relationships between drug-induced QTc interval prolongation, pharmacological cardioversion (PCV), and freedom from recurrent AF are unclear. The purpose of this study was to assess associations between QTc interval change during dofetilide initiation and PCV and long-term AF recurrence. We performed retrospective analyses of a prospective cohort of patients with AF admitted for dofetilide initiation between 2001 and 2014. Clinical characteristics and electrocardiographic variables were assessed. We evaluated outcomes of successful PCV in patients with persistent AF and time to recurrence of AF in patients with paroxysmal and persistent AF. During the study, 243 patients with persistent AF and 176 patients with paroxysmal AF initiated dofetilide. PCV occurred in 93/243 (41.7%) patients with persistent AF. After multivariable adjustment, QTc interval change was associated with PCV (adjusted odds ratio 1.21; P = .003 per 10-ms QTc increase). Inhospital QTc interval change was associated with long-term freedom from AF in patients with persistent AF (adjusted hazard ratio 0.92; P = .011 at 4 years per 10-ms QTc increase), but not in patients with paroxysmal AF. In patients with persistent AF, PCV was also associated with long-term freedom from recurrent AF (adjusted hazard ratio 0.62; P = .009 at 4 years). The magnitude of QTc interval prolongation during dofetilide initiation is an independent predictor of successful PCV and long-term freedom from arrhythmia in patients with persistent AF. QTc interval change had no association with AF recurrence in patients with paroxysmal AF, suggesting that different mechanisms of arrhythmogenesis may be operant in different AF types. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  19. The effects of thioridazine on the QTc interval - cardiovascular safety in a South African setting

    Directory of Open Access Journals (Sweden)

    Cathlene Seller

    2005-09-01

    Full Text Available Background. Thioridazine has long been used as a first-line antipsychotic in South Africa without any apparent problems. Recently the American Food and Drug Administration (FDA and Novartis have warned of potentially lethal arrhythmias that may result from the use of thioridazine. Abnormal QT-interval prolongation on the electrocardiogram (ECG seems to be the most reliable indicator of risk of arrhythmias, such as torsade de pointes and ventricular fibrillation. Objective. The purpose of this study was to determine whether these warnings are of clinical relevance in a setting where there are already a limited number of antipsychotics available. Method. Thirty hospitalised subjects who required switching from a high-potency to a low-potency antipsychotic were included. All subjects were commenced on thioridazine 300 mg per day and had an ECG 1 week after initiation and 48 hours after each dose adjustment. QTc was determined using Bazett’s formula. Results. Thioridazine induced a significant increase (p = 0.0001 in QTc interval from baseline values of 400.6 (± 27.3 milliseconds to 429.1 (± 44.2 milliseconds. The QTc interval increased to above 450 milliseconds in 7 subjects (23% and thioridazine was discontinued in 2 subjects because of a QTc interval greater or equal to 500 milliseconds. Conclusion. Thioridazine caused a significant, although asymptomatic, increase in QTc interval in almost one-quarter of subjects who received the medication as second-line treatment. Thioridazine should no longer be used as a first-line treatment and if used it should be accompanied by regular ECG monitoring.

  20. Rehabilitating drug-induced long-QT promoters: in-silico design of hERG-neutral cisapride analogues with retained pharmacological activity.

    Science.gov (United States)

    Durdagi, Serdar; Randall, Trevor; Duff, Henry J; Chamberlin, Adam; Noskov, Sergei Y

    2014-03-08

    The human ether-a-go-go related gene 1 (hERG1), which codes for a potassium ion channel, is a key element in the cardiac delayed rectified potassium current, IKr, and plays an important role in the normal repolarization of the heart's action potential. Many approved drugs have been withdrawn from the market due to their prolongation of the QT interval. Most of these drugs have high potencies for their principal targets and are often irreplaceable, thus "rehabilitation" studies for decreasing their high hERG1 blocking affinities, while keeping them active at the binding sites of their targets, have been proposed to enable these drugs to re-enter the market. In this proof-of-principle study, we focus on cisapride, a gastroprokinetic agent withdrawn from the market due to its high hERG1 blocking affinity. Here we tested an a priori strategy to predict a compound's cardiotoxicity using de novo drug design with molecular docking and Molecular Dynamics (MD) simulations to generate a strategy for the rehabilitation of cisapride. We focused on two key receptors, a target interaction with the (adenosine) receptor and an off-target interaction with hERG1 channels. An analysis of the fragment interactions of cisapride at human A2A adenosine receptors and hERG1 central cavities helped us to identify the key chemical groups responsible for the drug activity and hERG1 blockade. A set of cisapride derivatives with reduced cardiotoxicity was then proposed using an in-silico two-tier approach. This set was compared against a large dataset of commercially available cisapride analogs and derivatives. An interaction decomposition of cisapride and cisapride derivatives allowed for the identification of key active scaffolds and functional groups that may be responsible for the unwanted blockade of hERG1.

  1. Qt-sovelluksen kehittäminen Symbian-alustalle

    OpenAIRE

    Väyrynen, Jani

    2012-01-01

    Työn tavoitteena on kehittää toimiva Qt-sovellus Symbian-alustalle, joka toimii valvontakamerana. Työssä käsitellään Symbian-kehitysalustaa, sekä tutustutaan Qt-ohjelmointiin Symbian-alustalle. Tässä työssä kehitetään QVideoVahti -sovellusta, jonka tarkoituksena on tehdä älypuhelimesta langaton ”valvontakamera”. Sovelluksen päätoimintana on lähettää älypuhelimen tallentamia kuvia FTP-palvelimelle verkkoyhteyttä käyttäen. Sovelluksen muita toimintoja ovat muun muassa liikkeentunnistus, j...

  2. Qt based GUI system for EPICS control systems

    International Nuclear Information System (INIS)

    Rhyder, A.; Fernandes, R.N.; Starritt, A.

    2012-01-01

    The Qt-based GUI system developed at the Australian Synchrotron for use on EPICS control systems has recently been enhanced to including support for imaging, plotting, user login, logging and configuration recipes. Plans are also being made to broaden its appeal within the wider EPICS community by expanding the range of development options and adding support for EPICS V4. Current features include graphical and non-graphical application development as well as simple 'code-free' GUI design. Additional features will allow developers to let the GUI system handle its own data using Qt-based EPICS-aware classes or, as an alternative, use other control systems data such as PSI's CAFE. (author)

  3. Clinical Aspects of Type 3 Long-QT Syndrome

    DEFF Research Database (Denmark)

    Wilde, Arthur A M; Moss, Arthur J; Kaufman, Elizabeth S

    2016-01-01

    BACKGROUND: -Risk stratification in patients with type 3 long QT syndrome (LQT3) by clinical and genetic characteristics and effectiveness of ß-blocker therapy have not been studied previously in a large LQT3 population. METHODS: -The study population included 406 LQT3 patients with 51 different......-blocker therapy reduces this risk in females, but efficacy in males could not be conclusively determined due to low number of events....

  4. 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

    electrocardiograms from 173 529 primary care patients aged 50-90 years were collected during 2001-11. The Framingham formula was used for heart rate-correction of the QT interval. Data on medication, comorbidity, and outcomes were retrieved from administrative registries. During a median follow-up period of 6......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...

  5. 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)....

  6. Childhood cancer and factors related to prolonged diagnostic intervals

    DEFF Research Database (Denmark)

    Ahrensberg, J M; Olesen, F; Hansen, R P

    2013-01-01

    overleveringen til hospitalet var af betydning for hvor lang tid, der går fra lægesøgning til diagnose. Metode: Dansk populations-baseret studie. Data for 550 børn cancer diagnose (jan 2007-dec 2010) blev indsamlet vha spørgeskemaer til forældre (response-rate=69%) and praktiserende læger...... barnets symptomer som vage og ukarakteristiske i 25,4%; som alvorlige, men ikke cancer-relaterede i 50,0%; og som alarm symptom i 19,0% af tilfælde. Symptom tolkningen varierede med cancertype (p

  7. Evaluation of Electrocardiographic T-Peak to T-End Interval in Patients with Cardiac Syndrome X

    Directory of Open Access Journals (Sweden)

    Ozgur Kaplan

    2016-04-01

    Full Text Available Aim: The relationship between metabolic syndrome X (MSX and atrial arrhythmia such as atrial fibrillation (AF has been shown in previous studies. The aim of this study was to evaluate ventricular repolarization by using Tp-e interval and Tp-e/QT ratio in patients with cardiac syndrome X (CSX.Material and Method: A total of 65 consecutive subjects were included in the present study. Diagnostic coronary angiography was performed on patients who had a positive stress test and suspected myocardial scintigraphy or coronary artery disease (CAD. 35 patients who were diagnosed as having CSX (Group I and 30 patients with normal coronary angiograms (Group II were included in this study. QT parameters, Tp-e intervals, and Tp-e/QT ratio were measured from the 12-lead electrocardiogram. Results: The Tp-e interval (83.4 ± 6 vs. 75 ± 5, p

  8. In silico cardiac risk assessment in patients with long QT syndrome

    DEFF Research Database (Denmark)

    Hoefen, Ryan; Reumann, Matthias; Goldenberg, Ilan

    2012-01-01

    The study was designed to assess the ability of computer-simulated electrocardiography parameters to predict clinical outcomes and to risk-stratify patients with long QT syndrome type 1 (LQT1).......The study was designed to assess the ability of computer-simulated electrocardiography parameters to predict clinical outcomes and to risk-stratify patients with long QT syndrome type 1 (LQT1)....

  9. Effects of conventional vs high-dose rocuronium on the QTc interval during anesthesia induction and intubation in patients undergoing coronary artery surgery: a randomized, double-blind, parallel trial

    Science.gov (United States)

    Öztürk, T.; Ağdanlı, D.; Bayturan, Ö.; Çıkrıkcı, C.; Keleş, G.T.

    2015-01-01

    Myocardial ischemia, as well as the induction agents used in anesthesia, may cause corrected QT interval (QTc) prolongation. The objective of this randomized, double-blind trial was to determine the effects of high- vs conventional-dose bolus rocuronium on QTc duration and the incidence of dysrhythmias following anesthesia induction and intubation. Fifty patients about to undergo coronary artery surgery were randomly allocated to receive conventional-dose (0.6 mg/kg, group C, n=25) or high-dose (1.2 mg/kg, group H, n=25) rocuronium after induction with etomidate and fentanyl. QTc, heart rate, and mean arterial pressure were recorded before induction (T0), after induction (T1), after rocuronium (just before laryngoscopy; T2), 2 min after intubation (T3), and 5 min after intubation (T4). The occurrence of dysrhythmias was recorded. In both groups, QTc was significantly longer at T3 than at baseline [475 vs 429 ms in group C (P=0.001), and 459 vs 434 ms in group H (P=0.005)]. The incidence of dysrhythmias in group C (28%) and in group H (24%) was similar. The QTc after high-dose rocuronium was not significantly longer than after conventional-dose rocuronium in patients about to undergo coronary artery surgery who were induced with etomidate and fentanyl. In both groups, compared with baseline, QTc was most prolonged at 2 min after intubation, suggesting that QTc prolongation may be due to the nociceptive stimulus of intubation. PMID:25714880

  10. Hybrid integrated circuit for charge-to-time interval conversion

    Energy Technology Data Exchange (ETDEWEB)

    Basiladze, S.G.; Dotsenko, Yu.Yu.; Man' yakov, P.K.; Fedorchenko, S.N. (Joint Inst. for Nuclear Research, Dubna (USSR))

    The hybrid integrated circuit for charge-to time interval conversion with nanosecond input fast response is described. The circuit can be used in energy measuring channels, time-to-digital converters and in the modified variant in amplitude-to-digital converters. The converter described consists of a buffer amplifier, a linear transmission circuit, a direct current source and a unit of time interval separation. The buffer amplifier represents a current follower providing low input and high output resistances by the current feedback. It is concluded that the described converter excelled the QT100B circuit analogous to it in a number of parameters especially, in thermostability.

  11. EPICS-QT based graphical user interface for accelerator control

    International Nuclear Information System (INIS)

    Basu, A.; Singh, S.K.; Rosily, Sherry; Bhagwat, P.V.

    2016-01-01

    Particle accelerators and many industrial complex systems, require a robust and efficient control for its proper operation to achieve required beam quality, safety of its sub component and all working personnel. This control is executed via a graphical user interface through which an operator interacts with the accelerator to achieve the desired state of the machine and its output. Experimental Physics and Industrial Control System (EPICS) is a widely used control system framework in the field of accelerator control. It acts as a middle layer between field devices and graphic user interface used by the operator. Field devices can also be made EPICS compliant by using EPICS based software in that. On the other hand Qt is a C++ framework which is widely used for creating very professional looking and user friendly graphical component. In Low Energy High Intensity Proton Accelerator (LEHIPA), which is the first stage of the three stage Accelerator Driven System (ADS) program taken by Bhabha Atomic Research Centre (BARC), it is decided that EPICS will be used for controlling the accelerator and Qt will be used for developing the various Graphic User Interface (GUI) for operation and diagnostics. This paper discuss the work carried out to achieve this goal in LEHIPA

  12. Spectrum of pathogenic mutations and associated polymorphisms in a cohort of 44 unrelated patients with long QT syndrome.

    Science.gov (United States)

    Millat, G; Chevalier, P; Restier-Miron, L; Da Costa, A; Bouvagnet, P; Kugener, B; Fayol, L; Gonzàlez Armengod, C; Oddou, B; Chanavat, V; Froidefond, E; Perraudin, R; Rousson, R; Rodriguez-Lafrasse, C

    2006-09-01

    Long QT syndrome (LQTS) is a rare and clinically heterogeneous inherited disorder characterized by a long QT interval on the electrocardiogram, increased risk of syncope and sudden death caused by arrhythmias. This syndrome is mostly caused by mutations in genes encoding various cardiac ion channels. The clinical heterogeneity is usually attributed to variable penetrance. One of the reasons for this variability in expression could be the coexistence of common single nucleotide polymorphisms (SNPs) on LQTS-causing genes and/or unknown genes. Some synonymous and nonsynonymous exonic SNPs identified in LQTS-causing genes may have an effect on the cardiac repolarization process and modulate the clinical expression of a latent LQTS pathogenic mutation. We report the molecular pattern of 44 unrelated patients with LQTS using denaturing high-performance liquid chromatography analysis of the KCNQ1, KCNH2, SCN5A, KCNE1 and KCNE2 genes. Forty-five disease-causing mutations (including 24 novel ones) were identified in this cohort. Most of our patients (84%) showed complex molecular pattern with one mutation (and even two for four patients) associated with several SNPs located in several LQTS genes.

  13. 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.

  14. [Pathophysiology of prolonged hypokinesia].

    Science.gov (United States)

    Kovalenko, E A

    1976-01-01

    Hypokinesia is an important problem in modern medicine. In the pathogenetic effect of prolonged hypokinesia the main etiological factor is diminished motor activity; of major importance are disorders in the energy and plastic metabolism which affect the muscle system; the contributing factors are cardiovascular deconditioning and orthostatic intolerance. This is attributed to a decreased oxygen supply and eliminated hydrostatic influences during a prolonged recumbency. Blood redistribution in the vascular bed is related to the Gauer-Henry reflex and subsequent changes in the fluid-electrolyte balance. Decreased load on the bone system induces changes in the protein-phosphate-calcium metabolism, diminished bone density and increased calcium content in the blood and urine. Changes in the calcium metabolism are systemic. The activity of the higher nervous system and reflex functions is lowered. Changes in the function of the autonomic nervous system which include a noticeable decline of its adaptive-trophic role as a result of the decrease of afferent and efferent impulsation are of great importance. Changes in the hormonal function involve a peculiar stress-reaction which develops at an early stage of hypokinesia as a response to an unusual situation. Prolonged hypokinesia may result in a disturbed function of the pituitary-adrenal system. It is assumed that prolonged hypokinesia may induce a specific disease of hypokinesia during which man cannot lead a normal mode of life and work.

  15. Design of MPPT Controller Monitoring Software Based on QT Framework

    Science.gov (United States)

    Meng, X. Z.; Lu, P. G.

    2017-10-01

    The MPPT controller was a hardware device for tracking the maximum power point of solar photovoltaic array. Multiple controllers could be working as networking mode by specific communicating protocol. In this article, based on C++ GUI programming with Qt frame, we designed one sort of desktop application for monitoring and analyzing operational parameter of MPPT controller. The type of communicating protocol for building network was Modbus protocol which using Remote Terminal Unit mode and The desktop application of host computer was connected with all the controllers in the network through RS485 communication or ZigBee wireless communication. Using this application, user could monitor the parameter of controller wherever they were by internet.

  16. ShelXle: a Qt graphical user interface for SHELXL.

    Science.gov (United States)

    Hübschle, Christian B; Sheldrick, George M; Dittrich, Birger

    2011-12-01

    ShelXle is a graphical user interface for SHELXL [Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122], currently the most widely used program for small-molecule structure refinement. It combines an editor with syntax highlighting for the SHELXL-associated .ins (input) and .res (output) files with an interactive graphical display for visualization of a three-dimensional structure including the electron density (F(o)) and difference density (F(o)-F(c)) maps. Special features of ShelXle include intuitive atom (re-)naming, a strongly coupled editor, structure visualization in various mono and stereo modes, and a novel way of displaying disorder extending over special positions. ShelXle is completely compatible with all features of SHELXL and is written entirely in C++ using the Qt4 and FFTW libraries. It is available at no cost for Windows, Linux and Mac-OS X and as source code.

  17. Modern high strength QT, TM and duplex-stainless steels

    International Nuclear Information System (INIS)

    Bocquet, P.; Luxenburger, G.; Porter, D.; Ericsson, C.

    2003-01-01

    Pressure vessels are commonly manufactured with normalised steel grades with a yield strength up to 355 MPa or with austenitic stainless steels when corrosion as to be considered. From three decades, modern steels with higher mechanical properties - up to yield strength of 960 Mpa - are available and largely used for other applications where weight saving is of major importance as per off-shore, bridges, cranes, shipbuilding, line pipes.. The paper presents these modern steel's families - TMCP (Thermo Mechanically Controlled Process), QT (Quenched and Tempered) and Duplex (austeno-ferritic) stainless - in comparison with the normalised and austenitic steel grades. The following aspects are presented: the main mechanical properties (tensile and Charpy) as per the requirements of the standards for pressure equipment; some examples of use of these modern steels in the industry are given; the limitations of the forming conditions are considered; the weldability aspects and welds properties are developed; the interest of the PWHT (Post Weld Heat Treatment) is discussed. (orig.)

  18. 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.

  19. 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.

  20. 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 

  1. Management of prolonged pregnancy

    International Nuclear Information System (INIS)

    Iqbal, S.

    2004-01-01

    Objective: To compare two strategies for management of prolonged pregnancy (= or >294 days) i.e. induction (intervention) versus expectant management (non-intervention) and evaluate the associated feto-maternal risks. Subjects and Methods: One hundred cases of uncomplicated prolonged gestation were selected. The gestational age was confirmed by ultrasound in first trimester. One group (50 patients) was managed by intervention i.e. induction of labour (group A) and other group (50 patients) by non-intervention i.e. expectant management (group B). In group A intervention was done at 42 weeks. In expectant group, the methods of monitoring were fetal kick charting recorded daily by the patient, and ultrasound for amniotic fluid index. The biophysical profile score and NST (non stress test) were performed once a week till 42 weeks and then twice weekly. Results: The frequency of prolonged pregnancy was found to be 10.9%. There was no significant difference in the number of spontaneous vaginal deliveries between the two groups. The rate of LSCS (lower segment caesarean section) was higher in intervention group ( 30% versus 18% ). The neonatal depression at birth was more in group B ( 10% versus 4%) and at 5 minutes almost same between two groups (4% versus 2%). There were 11 cases of meconium aspiration syndrome, leading to one neonatal death. Among nine perinatal deaths two were neonatal deaths. Seven cases of intrauterine deaths in which antepartum deaths occurred because of non compliance of patients. No cause could be detected for the other three fetuses. Conclusion: There was increased LSCS rate in group A. However in expectant group B perinatal mortality was about twice more as compared to intervention group. Active early intervention at 42 weeks is warranted to reduce perinatal morbidity and mortality. (author)

  2. 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.

  3. 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.

  4. 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.

  5. Modern high strength QT, TM and duplex-stainless steels

    Energy Technology Data Exchange (ETDEWEB)

    Bocquet, P. [Industeel (France); Luxenburger, G. [Aktiengesellschaft der Dillinger Huettenwerke, Dillingen/Saar (Germany); Porter, D. [Rautaruukki (Finland); Ericsson, C. [Avesta Polarit (Sweden)

    2003-07-01

    Pressure vessels are commonly manufactured with normalised steel grades with a yield strength up to 355 MPa or with austenitic stainless steels when corrosion as to be considered. From three decades, modern steels with higher mechanical properties - up to yield strength of 960 Mpa - are available and largely used for other applications where weight saving is of major importance as per off-shore, bridges, cranes, shipbuilding, line pipes.. The paper presents these modern steel's families - TMCP (Thermo Mechanically Controlled Process), QT (Quenched and Tempered) and Duplex (austeno-ferritic) stainless - in comparison with the normalised and austenitic steel grades. The following aspects are presented: the main mechanical properties (tensile and Charpy) as per the requirements of the standards for pressure equipment; some examples of use of these modern steels in the industry are given; the limitations of the forming conditions are considered; the weldability aspects and welds properties are developed; the interest of the PWHT (Post Weld Heat Treatment) is discussed. (orig.)

  6. 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...

  7. Interval selection with machine-dependent intervals

    OpenAIRE

    Bohmova K.; Disser Y.; Mihalak M.; Widmayer P.

    2013-01-01

    We study an offline interval scheduling problem where every job has exactly one associated interval on every machine. To schedule a set of jobs, exactly one of the intervals associated with each job must be selected, and the intervals selected on the same machine must not intersect.We show that deciding whether all jobs can be scheduled is NP-complete already in various simple cases. In particular, by showing the NP-completeness for the case when all the intervals associated with the same job...

  8. 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 pregnancy only during the supine position (p pregnancy in all physiological states (p pregnancy in all states (p pregnancy is associated with substantial changes in 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.

  9. Role of sarcoplasmic reticulum calcium in development of secondary calcium rise and early afterdepolarizations in long QT syndrome rabbit model.

    Directory of Open Access Journals (Sweden)

    Po-Cheng Chang

    Full Text Available L-type calcium current reactivation plays an important role in development of early afterdepolarizations (EADs and torsades de pointes (TdP. Secondary intracellular calcium (Cai rise is associated with initiation of EADs.To test whether inhibition of sarcoplasmic reticulum (SR Ca2+ cycling suppresses secondary Cai rise and genesis of EADs.Langendorff perfusion and dual voltage and Cai optical mapping were conducted in 10 rabbit hearts. Atrioventricular block (AVB was created by radiofrequency ablation. After baseline studies, E4031, SR Ca2+ cycling inhibitors (ryanodine plus thapsigargin and nifedipine were then administrated subsequently, and the protocols were repeated.At baseline, there was no spontaneous or pacing-induced TdP. After E4031 administration, action potential duration (APD was significantly prolonged and the amplitude of secondary Cai rise was enhanced, and 7 (70% rabbits developed spontaneous or pacing-induced TdP. In the presence of ryanodine plus thapsigargin, TdP inducibility was significantly reduced (2 hearts, 20%, p = 0.03. Although APD was significantly prolonged (from 298 ± 30 ms to 457 ± 75 ms at pacing cycle length of 1000 m, p = 0.007 by ryanodine plus thapsigargin, the secondary Cai rise was suppressed (from 8.8 ± 2.6% to 1.2 ± 0.9%, p = 0.02. Nifedipine inhibited TdP inducibility in all rabbit hearts.In this AVB and long QT rabbit model, inhibition of SR Ca2+ cycyling reduces the inducibility of TdP. The mechanism might be suppression of secondary Cai rise and genesis of EADs.

  10. Calmodulin is essential for cardiac IKS channel gating and assembly: impaired function in long-QT mutations

    DEFF Research Database (Denmark)

    Shamgar, Liora; Ma, Lijuan; Schmitt, Nicole

    2006-01-01

    The slow IKS K+ channel plays a major role in repolarizing the cardiac action potential and consists of the assembly of KCNQ1 and KCNE1 subunits. Mutations in either KCNQ1 or KCNE1 genes produce the long-QT syndrome, a life-threatening ventricular arrhythmia. Here, we show that long-QT mutations ...

  11. Relation between the behaviors of P-wave and QT dispersions in elderly patients with heart failure

    Directory of Open Access Journals (Sweden)

    Szlejf Cláudia

    2002-01-01

    Full Text Available OBJECTIVE: To assess the relation between P-wave and QT dispersions in elderly patients with heart failure. METHODS: Forty-seven elderly patients (75.6±6 years with stable heart failure in NYHA functional classes II or III and with ejection fractions of 37±6% underwent body surface mapping to analyze P-wave and QT dispersions. The degree of correlation between P-wave and QT dispersions was assessed, and P-wave dispersion values in patients with QT dispersion greater than and smaller than 100 ms were compared. RESULTS: The mean values of P-wave and QT dispersions were 54±14 ms and 68±27 ms, respectively. The correlation between the 2 variables was R=0.41 (p=0.04. In patients with QT dispersion values > 100 ms, P-wave dispersion was significantly greater than in those with QT dispersion values < 100 ms (58±16 vs 53±12 ms, p=0.04 . CONCLUSION: Our results suggest that, in elderly patients with heart failure, a correlation between the values of P-wave and QT dispersions exists. These findings may have etiopathogenic, pathophysiologic, prognostic, and therapeutic implications, which should be investigated in other studies.

  12. Electrocardiographic PR prolongation and atrial fibrillation risk: a meta-analysis of prospective cohort studies.

    Science.gov (United States)

    Cheng, Min; Lu, Xiangfeng; Huang, Jianfeng; Zhang, Shu; Gu, Dongfeng

    2015-01-01

    Electrocardiographic PR interval prolongation is considered a benign condition, but recent studies have challenged the notion by demonstrating that prolonged PR interval is associated with an increased risk of atrial fibrillation (AF). The purpose of this study was to perform a meta-analysis of prospective cohort studies to evaluate the evidence supporting an association of prolonged PR interval with AF incidence. We searched the MEDLINE and EMBASE database (from inception to May 2014) supplemented by manual searches of references of relevant retrieved articles. Prospective cohort studies were included with hazard ratio (HR) of prolonged PR interval for incident AF. The search strategy yielded 6 cohort studies meeting eligibility criteria. A total of 328,932 participants were included, with 14,191 participants suffering from AF during follow-up. Pooled HRs of prolonged PR interval for incident AF was 1.30 (95% CI: 1.13 to 1.49) using random-effect model (I(2) = 30%). There was a significant difference of combined HRs between studies with and without adjustment for taking of AV nodal blocking agents in subgroup analysis. Sensitivity analysis supported the robustness of the results. Prolonged PR interval is not a totally benign condition but an independent risk factor for AF incidence. The mechanisms underlying the association of prolonged PR interval with AF incidence need further research. © 2014 Wiley Periodicals, Inc.

  13. Collaborative development of the EPICS Qt framework Phase I Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Mayssat, Robert E. [Lyncean Technologies, Inc., Palo Alto, CA (United States)

    2015-01-15

    At Lyncean, a private company spun-off from technology developed at the SLAC National Lab, we have been using EPICS for over a decade. EPICS is ubiquitous on our flagship product – the Compact Light Source. EPICS is not only used to control our laser and accelerator systems, but also to control our x-ray beamlines. The goal of this SBIR is for Lyncean Technologies to spearhead a worldwide collaborative effort for the development of control system tools for EPICS using the Qt framework, a C++-based coding environment that could serve as a competitive alternative to the Java-based Control System Studio (CSS). This grant's Phase I, not unlike a feasibility study, is designed for planning and scoping the preparatory work needed for Phase II or other funding opportunities. The three main objectives of this Phase I are (1) to become better acquainted with the existing EPICS Qt software and Qt framework in order to evaluate the best options for ongoing development, (2) to demonstrate that our engineers can lead the EPICS community and jump-start the Qt collaboration, and (3) to identify a scope for our future work with solicited feedback from the EPICS community. This Phase I report includes key technical findings. It clarifies the differences between the two apparently-competing EPICS Qt implementations, caQtDM and the QE Framework; it explains how to create python-bindings, and compares Qt graphical libraries. But this report is also a personal story that narrates the birth of a collaboration. Starting a collaboration is not the work of a single individual, but the work of many. Therefore this report is also an attempt to publicly give credit to many who supported the effort. The main take-away from this grant is the successful birth of an EPICS Qt collaboration, seeded with existing software from the PSI and the Australian Synchrotron. But a lot more needs to be done for the collaboration founders' vision to be realized, and for the collaboration to reach

  14. Short QTc Interval in Males with Klinefelter Syndrome-Influence of CAG Repeat Length, Body Composition, and Testosterone Replacement Therapy

    DEFF Research Database (Denmark)

    Jørgensen, Inger Norlyk; Skakkebaek, Anne; Andersen, Niels Holmark

    2015-01-01

    BackgroundKlinefelter syndrome (KS) is a sex chromosomal aneuploidy (47,XXY) affecting 1/660 males. Based on findings in Turner syndrome, we hypothesized that electrocardiogram (ECG) abnormalities would be present in males with KS. ObjectiveTo investigate ECGs in males with KS and compare...... syndrome was determined in participants with a QTc ... interval comparable to controls. No mutations in genes related to short QT syndrome were found. ConclusionWe found short QTc interval in males with KS, with further shortening of the QTc interval by T. These results suggest that genes on the X chromosome could be involved in regulation of the QTc interval...

  15. 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

  16. 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

    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 ...... the approach has not been tested in this setting....

  17. 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...

  18. 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...

  19. Convex Interval Games

    NARCIS (Netherlands)

    Alparslan-Gok, S.Z.; Brânzei, R.; Tijs, S.H.

    2008-01-01

    In this paper, convex interval games are introduced and some characterizations are given. Some economic situations leading to convex interval games are discussed. The Weber set and the Shapley value are defined for a suitable class of interval games and their relations with the interval core for

  20. Effects of conventional vs high-dose rocuronium on the QTc interval during anesthesia induction and intubation in patients undergoing coronary artery surgery: a randomized, double-blind, parallel trial

    Directory of Open Access Journals (Sweden)

    T. Öztürk

    2015-04-01

    Full Text Available Myocardial ischemia, as well as the induction agents used in anesthesia, may cause corrected QT interval (QTc prolongation. The objective of this randomized, double-blind trial was to determine the effects of high- vs conventional-dose bolus rocuronium on QTc duration and the incidence of dysrhythmias following anesthesia induction and intubation. Fifty patients about to undergo coronary artery surgery were randomly allocated to receive conventional-dose (0.6 mg/kg, group C, n=25 or high-dose (1.2 mg/kg, group H, n=25 rocuronium after induction with etomidate and fentanyl. QTc, heart rate, and mean arterial pressure were recorded before induction (T0, after induction (T1, after rocuronium (just before laryngoscopy; T2, 2 min after intubation (T3, and 5 min after intubation (T4. The occurrence of dysrhythmias was recorded. In both groups, QTc was significantly longer at T3 than at baseline [475 vs 429 ms in group C (P=0.001, and 459 vs 434 ms in group H (P=0.005]. The incidence of dysrhythmias in group C (28% and in group H (24% was similar. The QTc after high-dose rocuronium was not significantly longer than after conventional-dose rocuronium in patients about to undergo coronary artery surgery who were induced with etomidate and fentanyl. In both groups, compared with baseline, QTc was most prolonged at 2 min after intubation, suggesting that QTc prolongation may be due to the nociceptive stimulus of intubation.

  1. Phenotype guided characterization and molecular analysis of Indian patients with long QT syndromes

    Directory of Open Access Journals (Sweden)

    Bijal Vyas

    2016-01-01

    Conclusions: This study in a cohort of Asian Indian patients highlights the mutation spectrum of common Long QT syndromes. The clinical utility for prevention of unexplained sudden cardiac deaths is an important sequel to identification of the mutation in at-risk family members.

  2. Glucose ingestion causes cardiac repolarization disturbances in type 1 long QT syndrome patients and healthy subjects

    DEFF Research Database (Denmark)

    Hyltén-Cavallius, Louise; Iepsen, Eva W; Christiansen, Michael

    2017-01-01

    BACKGROUND: Both hypoglycemia and severe hyperglycemia constitute known risk factors for cardiac repolarization changes potentially leading to malignant arrhythmias. Patients with loss of function mutations in KCNQ1 are characterized by long QT syndrome (LQTS) and may be at increased risk...

  3. Pregnancy and the risk of torsades de pointes in congenital long-QT syndrome

    NARCIS (Netherlands)

    Meregalli, P. G.; Westendorp, I. C. D.; Tan, H. L.; Elsman, P.; Kok, W. E. M.; Wilde, A. A. M.

    2008-01-01

    Patients with congenital long-QT syndrome (LQTS) are at increased risk of ventricular arrhythmias during stressful situations. Large-scale studies have pointed out that affected individuals are particularly at risk in the period following pregnancy (post-partum). This is recognised especially for

  4. High distress in parents whose children undergo predictive testing for long QT syndrome

    NARCIS (Netherlands)

    Grosfeld, FJM; Wilde, AAM; van den Bout, J; van Langen, IM; van Tintelen, JP; ten Kroode, HFJ

    2005-01-01

    Objectives: To assess the psychological effect of predictive testing in parents of children at risk for long QT syndrome (LQTS) in a prospective study. Methods: After their child was clinically screened by electrocardiography and blood was taken for DNA analysis, and shortly after delivery of the

  5. 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, and...

  6. Prenatal diagnosis of long QT syndrome with the superior vena cava-aorta Doppler approach.

    Science.gov (United States)

    Chabaneix, Julie; Andelfinger, Gregor; Fournier, Anne; Fouron, Jean-Claude; Raboisson, Marie-Josée

    2012-10-01

    We describe a fetus at 36 weeks with long QT syndrome presenting with variable types of atrioventricular blocks, ventricular premature beats, and torsades de pointes. All these diagnoses were made with the superior vena cava-aorta Doppler approach and confirmed with postnatal electrocardiography. Copyright © 2012 Mosby, Inc. All rights reserved.

  7. Refinement and fracture mechanisms of as-cast QT700-6 alloy by alloying method

    Directory of Open Access Journals (Sweden)

    Min-qiang Gao

    2017-01-01

    Full Text Available The as-cast QT700-6 alloy was synthesized with addition of a certain amount of copper, nickel, niobium and stannum elements by alloying method in a medium frequency induction furnace, aiming at improving its strength and toughness. Microstructures of the as-cast QT700-6 alloy were observed using a scanning-electron microscope (SEM and the mechanical properties were investigated using a universal tensile test machine. Results indicate that the ratio of pearlite/ferrite is about 9:1 and the graphite size is less than 40 μm in diameter in the as-cast QT700-6 alloy. The predominant refinement mechanism is attributed to the formation of niobium carbides, which increases the heterogeneous nucleus and hinders the growth of graphite. Meanwhile, niobium carbides also exist around the grain boundaries, which improve the strength of the ductile iron. The tensile strength and elongation of the as-cast QT700-6 alloy reach over 700 MPa and 6%, respectively, when the addition amount of niobium is 0.8%. The addition of copper and nickel elements contributed to the decrease of eutectoid transformation temperature, resulting in the decrease of pearlite lamellar spacing (about 248 nm, which is also beneficial to enhancing the tensile strength. The main fracture mechanism is cleavage fracture with the appearance of a small amount of dimples.

  8. Perioperative considerations in a newly described subtype of congenital long QT syndrome.

    Science.gov (United States)

    Joseph-Reynolds, Ann; Auden, Steve; Sobczyzk, Walter

    1997-05-01

    An infant with a newly-described subtype of congenital long QT syndrome is presented, along with her perioperative management on three separate occasions. During each anaesthetic characteristic arrhythmias occurred. The available literature and rational approaches to these high risk patients are reviewed. 1997 Blackwell Science Ltd.

  9. Identification of a Kir3.4 Mutation in Congenital Long QT Syndrome

    DEFF Research Database (Denmark)

    Yang, Yanzong; Yang, Yiqing; Liang, Bo

    2010-01-01

    Congenital long QT syndrome (LQTS) is a hereditary disorder that leads to sudden cardiac death secondary to fatal cardiac arrhythmias. Although many genes for LQTS have been described, the etiology remains unknown in 30%-40% of cases. In the present study, a large Chinese family (four generations...

  10. Safe drug use in long QT syndrome and Brugada syndrome: comparison of website statistics

    NARCIS (Netherlands)

    Postema, Pieter G.; Neville, Jon; de Jong, Jonas S. S. G.; Romero, Klaus; Wilde, Arthur A. M.; Woosley, Raymond L.

    2013-01-01

    We sought to obtain insights into the efficacy of two websites, www.QTdrugs.org and www.BrugadaDrugs.org, that have the intention to prevent fatal arrhythmias due to unsafe drug use in Long QT syndrome and Brugada syndrome. Prospective web-use statistical analysis combined with online surveys were

  11. Prolongation of islet allograft survival

    International Nuclear Information System (INIS)

    Lacy, P.E.; Davie, J.M.; Finke, E.H.; Scharp, D.W.

    1979-01-01

    Pretreatment of donor rats with irradiation and silica followed by in vitro culture of the islets for 1 to 2 days prolonged survival of allografts across a minor histocompatibility barrier if hand-picked, clean islets were used for transplantation. Pretreatment of donor rats with irradiation and silica in conjunction with a single injection of antilymphocyte serum (ALS) into the recipient produced a prolongation of survival of hand-picked islets transplanted across a major histocompatibility barrier

  12. Genetic influence on prolonged gestation

    DEFF Research Database (Denmark)

    Laursen, Maja; Bille, Camilla; Olesen, Annette Wind

    2004-01-01

    OBJECTIVE: The purpose of this study was to test a possible genetic component to prolonged gestation. STUDY DESIGN: The gestational duration of single, first pregnancies by both female and male twins was obtained by linking the Danish Twin Registry, The Danish Civil Registration System, and the D...... factors. CONCLUSION: Maternal genes influence prolonged gestation. However, a substantial paternal genetic influence through the fetus was not found....

  13. Long QT Syndrome–Associated Mutations in Intrauterine Fetal Death

    Science.gov (United States)

    Crotti, Lia; Tester, David J.; White, Wendy M.; Bartos, Daniel C.; Insolia, Roberto; Besana, Alessandra; Kunic, Jennifer D.; Will, Melissa L.; Velasco, Ellyn J.; Bair, Jennifer J.; Ghidoni, Alice; Cetin, Irene; Van Dyke, Daniel L.; Wick, Myra J.; Brost, Brian; Delisle, Brian P.; Facchinetti, Fabio; George, Alfred L.; Schwartz, Peter J.; Ackerman, Michael J.

    2013-01-01

    Importance Intrauterine fetal death or stillbirth occurs in approximately 1 out of every 160 pregnancies and accounts for 50% of all perinatal deaths. Postmortem evaluation fails to elucidate an underlying cause in many cases. Long QT syndrome (LQTS) may contribute to this problem. Objective To determine the spectrum and prevalence of mutations in the 3 most common LQTS susceptible genes (KCNQ1, KCNH2, and SCN5A) for a cohort of unexplained cases. Design, Setting, and Patients In this case series, retrospective postmortem genetic testing was conducted on a convenience sample of 91 unexplained intrauterine fetal deaths (mean [SD] estimated gestational age at fetal death, 26.3 [8.7] weeks) that were collected from 2006-2012 by the Mayo Clinic, Rochester, Minnesota, or the Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. More than 1300 ostensibly healthy individuals served as controls. In addition, publicly available exome databases were assessed for the general population frequency of identified genetic variants. Main Outcomes and Measures Comprehensive mutational analyses of KCNQ1 (KV7.1, LQTS type 1), KCNH2 (HERG/KV11.1, LQTS type 2), and SCN5A (NaV1.5, LQTS type 3) were performed using denaturing high-performance liquid chromatography and direct DNA sequencing on genomic DNA extracted from decedent tissue. Functional analyses of novel mutations were performed using heterologous expression and patch-clamp recording. Results The 3 putative LQTS susceptibility missense mutations (KCNQ1, p.A283T; KCNQ1, p.R397W; and KCNH2[1b], p.R25W), with a heterozygous frequency of less than 0.05% in more than 10000 publicly available exomes and absent in more than 1000 ethnically similar control patients, were discovered in 3 intrauterine fetal deaths (3.3% [95% CI, 0.68%-9.3%]). Both KV7.1-A283T (16-week male) and KV7.1-R397W (16-week female) mutations were associated with marked KV7.1 loss-of-function consistent with in utero LQTS type 1, whereas the HERG1b-R25W mutation

  14. UrQt: an efficient software for the Unsupervised Quality trimming of NGS data.

    Science.gov (United States)

    Modolo, Laurent; Lerat, Emmanuelle

    2015-04-29

    Quality control is a necessary step of any Next Generation Sequencing analysis. Although customary, this step still requires manual interventions to empirically choose tuning parameters according to various quality statistics. Moreover, current quality control procedures that provide a "good quality" data set, are not optimal and discard many informative nucleotides. To address these drawbacks, we present a new quality control method, implemented in UrQt software, for Unsupervised Quality trimming of Next Generation Sequencing reads. Our trimming procedure relies on a well-defined probabilistic framework to detect the best segmentation between two segments of unreliable nucleotides, framing a segment of informative nucleotides. Our software only requires one user-friendly parameter to define the minimal quality threshold (phred score) to consider a nucleotide to be informative, which is independent of both the experiment and the quality of the data. This procedure is implemented in C++ in an efficient and parallelized software with a low memory footprint. We tested the performances of UrQt compared to the best-known trimming programs, on seven RNA and DNA sequencing experiments and demonstrated its optimality in the resulting tradeoff between the number of trimmed nucleotides and the quality objective. By finding the best segmentation to delimit a segment of good quality nucleotides, UrQt greatly increases the number of reads and of nucleotides that can be retained for a given quality objective. UrQt source files, binary executables for different operating systems and documentation are freely available (under the GPLv3) at the following address: https://lbbe.univ-lyon1.fr/-UrQt-.html .

  15. P-wave and QT dispersion in patients with conversion disorder

    Directory of Open Access Journals (Sweden)

    Izci F

    2015-03-01

    Full Text Available Filiz Izci,1 Hilal Hocagil,2 Servet Izci,3 Vedat Izci,4 Merve Iris Koc,5 Rezzan Deniz Acar3 1Department of Psychiatry, Istanbul Bilim University, Sisli Florence Nightingale Hospital; 2Department of Emergency, Faculty of Medicine Hospital Zonguldak Bulent Ecevit University, Zonguldak, Turkey; 3Department of Cardiology, Kosuyolu High Specialization Training and Research Hospital, Istanbul, Turkey; 4Department of Emergency, Kartal Training and Research Hospital, Istanbul, Turkey; 5Department of Psychiatry, Erenköy Training and Research Hospital for Psychiatry, Istanbul, Turkey Objective: 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.Patients and methods: 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.Results: 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, P<0.001 and Beck Depression Scale scores (11.24±6.15 and 6.58±5.69, respectively, P<0.01 were significantly higher in CD patients. P-wave dispersion measurements did not show any significant differences between conversion 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

  16. Levofloxacin-Induced QTc Prolongation Depends on the Time of Drug Administration

    NARCIS (Netherlands)

    Kervezee, L; Gotta, V; Stevens, J; Birkhoff, W; Kamerling, Imc; Danhof, M; Meijer, J H; Burggraaf, J

    2016-01-01

    Understanding the factors influencing a drug's potential to prolong the QTc interval on an electrocardiogram is essential for the correct evaluation of its safety profile. To explore the effect of dosing time on drug-induced QTc prolongation, a randomized, crossover, clinical trial was conducted in

  17. Overlapping LQT1 and LQT2 phenotype in a patient with long QT syndrome associated with loss-of-function variations in KCNQ1 and KCNH2

    DEFF Research Database (Denmark)

    Cordeiro, Jonathan M; Perez, Guillermo J; Schmitt, Nicole

    2010-01-01

    . The proband (MMRL0362), a 32-year-old female, exhibited multiple ventricular extrasystoles and one syncope. Her ECG (QT interval corrected for heart rate (QTc) = 518ms) showed an LQT2 morphology in leads V4-V6 and LQT1 morphology in leads V1-V2. Genomic DNA was isolated from lymphocytes. All exons and intron...... borders of 7 LQTS susceptibility genes were amplified and sequenced. Variations were detected predicting a novel missense mutation (V110I) in KCNQ1, as well as a common polymorphism in KCNH2 (K897T). We expressed wild-type (WT) or V110I Kv7.1 channels in CHO-K1 cells cotransfected with KCNE1 and performed.......15 mV for K897T and WT, respectively; p loss-of-function mutation in KCNQ1 and a loss-of-function polymorphism in KCNH2. Our results suggest...

  18. Programming with Intervals

    Science.gov (United States)

    Matsakis, Nicholas D.; Gross, Thomas R.

    Intervals are a new, higher-level primitive for parallel programming with which programmers directly construct the program schedule. Programs using intervals can be statically analyzed to ensure that they do not deadlock or contain data races. In this paper, we demonstrate the flexibility of intervals by showing how to use them to emulate common parallel control-flow constructs like barriers and signals, as well as higher-level patterns such as bounded-buffer producer-consumer. We have implemented intervals as a publicly available library for Java and Scala.

  19. Potassium dynamics are attenuated in hyperkalemia and a determinant of QT adaptation in exercising hemodialysis patients

    DEFF Research Database (Denmark)

    Tran, Cao Thach; Bundgaard, Henning; Ladefoged, Søren Daustrand

    2013-01-01

    Disturbances in plasma potassium concentration (pK) are well known risk factors for the development of cardiac arrhythmia. The aims of the present study were to evaluate the effect of hemodialysis on exercise pK dynamics and QT hysteresis, and whether QT hysteresis is associated with the p......K decrease following exercise. Twenty-two end-stage renal disease patients exercised on a cycle ergometer with incremental work load before and after hemodialysis. ECG was recorded and pK was measured during exercise and recovery. During exercise, pK increased from 5.1 ± 0.2 to 6.1 ± 0.2 mM (mean ± SE; P...

  20. Integral type operators from normal weighted Bloch spaces to QT,S spaces

    Directory of Open Access Journals (Sweden)

    Yongyi GU

    2016-08-01

    Full Text Available Operator theory is an important research content of the analytic function space theory. The discussion of simultaneous operator and function space is an effective way to study operator and function space. Assuming that  is an analytic self map on the unit disk Δ, and the normal weighted bloch space μ-B is a Banach space on the unit disk Δ, defining a composition operator C∶C(f=f on μ-B for all f∈μ-B, integral type operator JhC and CJh are generalized by integral operator and composition operator. The boundeness and compactness of the integral type operator JhC acting from normal weighted Bloch spaces to QT,S spaces are discussed, as well as the boundeness of the integral type operators CJh acting from normal weighted Bloch spaces to QT,S spaces. The related sufficient and necessary conditions are given.

  1. Atrioventricular junction (AVJ) motion tracking: a software tool with ITK/VTK/Qt.

    Science.gov (United States)

    Pengdong Xiao; Shuang Leng; Xiaodan Zhao; Hua Zou; Ru San Tan; Wong, Philip; Liang Zhong

    2016-08-01

    The quantitative measurement of the Atrioventricular Junction (AVJ) motion is an important index for ventricular functions of one cardiac cycle including systole and diastole. In this paper, a software tool that can conduct AVJ motion tracking from cardiovascular magnetic resonance (CMR) images is presented by using Insight Segmentation and Registration Toolkit (ITK), The Visualization Toolkit (VTK) and Qt. The software tool is written in C++ by using Visual Studio Community 2013 integrated development environment (IDE) containing both an editor and a Microsoft complier. The software package has been successfully implemented. From the software engineering practice, it is concluded that ITK, VTK, and Qt are very handy software systems to implement automatic image analysis functions for CMR images such as quantitative measure of motion by visual tracking.

  2. Prolonged unexplained fatigue in paediatrics

    NARCIS (Netherlands)

    Bakker, R.J.

    2010-01-01

    Prolonged Unexplained Fatigue in Paediatrics. Fatigue, as the result of mental or physical exertion, will disappear after rest, drinks and food. Fatigue as a symptom of illness will recover with the recovering of the illness. But when fatigue is ongoing for a long time, and not the result of

  3. Physiology Of Prolonged Bed Rest

    Science.gov (United States)

    Greenleaf, John E.

    1991-01-01

    Report describes physiological effects of prolonged bed rest. Rest for periods of 24 hours or longer deconditions body to some extent; healing proceeds simultaneously with deconditioning. Report provides details on shifts in fluid electrolytes and loss of lean body mass, which comprises everything in body besides fat - that is, water, muscle, and bone. Based on published research.

  4. KCNQ1 Long QT syndrome patients have hyperinsulinemia and symptomatic hypoglycemia

    DEFF Research Database (Denmark)

    Torekov, Signe S; Iepsen, Eva; Christiansen, Michael

    2014-01-01

    Patients with loss-of-function mutations in KCNQ1 have KCNQ1 long QT syndrome (LQTS). KCNQ1 encodes a voltage-gated K+ channel located in both cardiomyocytes and pancreatic b-cells. Inhibition of KCNQ1 in b-cells increases insulin secretion. Therefore KCNQ1 LQTS patients may exhibit increased...... min (low potassium after an oral glucose challenge, suggesting that KCNQ1...

  5. Massive Boson Production at Small qT in Soft-Collinear Effective Theory

    Science.gov (United States)

    Becher, Thomas; Neubert, Matthias; Wilhelm, Daniel

    2013-01-01

    We study the differential cross sections for electroweak gauge-boson and Higgs production at small and very small transverse-momentum qT. Large logarithms are resummed using soft-collinear effective theory. The collinear anomaly generates a non-perturbative scale q*, which protects the processes from receiving large long-distance hadronic contributions. A numerical comparison of our predictions with data on the transverse-momentum distribution in Z-boson production at the Tevatron and LHC is given.

  6. RD50 Prolongation Request 2018

    CERN Document Server

    Casse, Gianluigi

    2018-01-01

    With this document, we request the prolongation of the CERN RD50 research program for 5 years. A very brief historical review of the RD50 research program since the RD50 project approval by the Research Board in the year 2002 is presented and the biggest RD50 achievements are highlighted. The present composition of the collaboration, its organizational structure, and the research methodology are described. The role of RD50 in the present various upgrade and research programs of the LHC Experiments community is given and the overall work plan explained. Finally, a detailed 5-years work program with precise milestones and deliverables for the various research activities is presented. We conclude with our prolongation request towards the LHCC.

  7. Electrophysiological safety of sertindole in dogs with normal and remodeled hearts

    DEFF Research Database (Denmark)

    Thomsen, Morten Bækgaard; Volders, Paul G A; Stengl, Milan

    2003-01-01

    Inhibition of the potassium current IKr and QT prolongation are associated with drug-induced torsades de pointes arrhythmias (TdP) and sudden cardiac death. We investigated the cardiac electrophysiological effects of sertindole, an antipsychotic drug reported to prolong the QT interval...

  8. Mechanistic Basis for Type 2 Long QT Syndrome Caused by KCNH2 Mutations that Disrupt Conserved Arginine Residue in the Voltage Sensor

    Science.gov (United States)

    McBride, Christie M.; Smith, Ashley M.; Smith, Jennifer L.; Reloj, Allison R.; Velasco, Ellyn J.; Powell, Jonathan; Elayi, Claude S.; Bartos, Daniel C.; Burgess, Don E.

    2013-01-01

    KCNH2 encodes the Kv11.1 channel, which conducts the rapidly activating delayed rectifier K+ current (IKr) in the heart. KCNH2 mutations cause type 2 long QT syndrome (LQT2), which increases the risk for life-threatening ventricular arrhythmias. LQT2 mutations are predicted to prolong the cardiac action potential (AP) by reducing IKr during repolarization. Kv11.1 contains several conserved basic amino acids in the fourth transmembrane segment (S4) of the voltage sensor that are important for normal channel trafficking and gating. This study sought to determine the mechanism(s) by which LQT2 mutations at conserved arginine residues in S4 (R531Q, R531W or R534L) alter Kv11.1 function. Western blot analyses of HEK293 cells transiently expressing R531Q, R531W or R534L suggested that only R534L inhibited Kv11.1 trafficking. Voltage-clamping experiments showed that R531Q or R531W dramatically altered Kv11.1 current (IKv11.1) activation, inactivation, recovery from inactivation and deactivation. Coexpression of wild type (to mimic the patients’ genotypes) mostly corrected the changes in IKv11.1 activation and inactivation, but deactivation kinetics were still faster. Computational simulations using a human ventricular AP model showed that accelerating deactivation rates was sufficient to prolong the AP, but these effects were minimal compared to simply reducing IKr. These are the first data to demonstrate that coexpressing wild type can correct activation and inactivation dysfunction caused by mutations at a critical voltage-sensing residue in Kv11.1. We conclude that some Kv11.1 mutations might accelerate deactivation to cause LQT2 but that the ventricular AP duration is much more sensitive to mutations that decrease IKr. This likely explains why most LQT2 mutations are nonsense or trafficking-deficient. PMID:23546015

  9. Mechanistic basis for type 2 long QT syndrome caused by KCNH2 mutations that disrupt conserved arginine residues in the voltage sensor.

    Science.gov (United States)

    McBride, Christie M; Smith, Ashley M; Smith, Jennifer L; Reloj, Allison R; Velasco, Ellyn J; Powell, Jonathan; Elayi, Claude S; Bartos, Daniel C; Burgess, Don E; Delisle, Brian P

    2013-05-01

    KCNH2 encodes the Kv11.1 channel, which conducts the rapidly activating delayed rectifier K+ current (I Kr) in the heart. KCNH2 mutations cause type 2 long QT syndrome (LQT2), which increases the risk for life-threatening ventricular arrhythmias. LQT2 mutations are predicted to prolong the cardiac action potential (AP) by reducing I Kr during repolarization. Kv11.1 contains several conserved basic amino acids in the fourth transmembrane segment (S4) of the voltage sensor that are important for normal channel trafficking and gating. This study sought to determine the mechanism(s) by which LQT2 mutations at conserved arginine residues in S4 (R531Q, R531W or R534L) alter Kv11.1 function. Western blot analyses of HEK293 cells transiently expressing R531Q, R531W or R534L suggested that only R534L inhibited Kv11.1 trafficking. Voltage-clamping experiments showed that R531Q or R531W dramatically altered Kv11.1 current (I Kv11.1) activation, inactivation, recovery from inactivation and deactivation. Coexpression of wild type (to mimic the patients' genotypes) mostly corrected the changes in I Kv11.1 activation and inactivation, but deactivation kinetics were still faster. Computational simulations using a human ventricular AP model showed that accelerating deactivation rates was sufficient to prolong the AP, but these effects were minimal compared to simply reducing I Kr. These are the first data to demonstrate that coexpressing wild type can correct activation and inactivation dysfunction caused by mutations at a critical voltage-sensing residue in Kv11.1. We conclude that some Kv11.1 mutations might accelerate deactivation to cause LQT2 but that the ventricular AP duration is much more sensitive to mutations that decrease I Kr. This likely explains why most LQT2 mutations are nonsense or trafficking-deficient.

  10. Pharmacological activation of Kv11.1 in transgenic long QT-1 rabbits

    DEFF Research Database (Denmark)

    Bentzen, Bo Hjorth; Bahrke, Sophia; Wu, Kezhong

    2011-01-01

    Transgenic rabbits expressing pore mutants of K(V)7.1 display a long QT syndrome 1 (LQT1) phenotype. Recently, NS1643 has been described to increase I(Kr).We hypothesized that NS1643 would shorten the action potential duration (APD(90)) in LQT1 rabbits. Transgenic LQT1 rabbits were compared...... with littermate control (LMC) rabbits. In vivo electrocardiogram studies in sedated animals were performed at baseline and during 45 minutes of intravenous infusion of NS1643 or vehicle in a crossover design. Ex vivo monophasic action potentials were recorded from Langendorff-perfused hearts at baseline...

  11. Overconfidence in Interval Estimates

    Science.gov (United States)

    Soll, Jack B.; Klayman, Joshua

    2004-01-01

    Judges were asked to make numerical estimates (e.g., "In what year was the first flight of a hot air balloon?"). Judges provided high and low estimates such that they were X% sure that the correct answer lay between them. They exhibited substantial overconfidence: The correct answer fell inside their intervals much less than X% of the time. This…

  12. Biophysical characterization of the short QT mutation hERG-N588K reveals a mixed gain-and loss-of-function

    DEFF Research Database (Denmark)

    Grunnet, M.; Diness, T.G.; Hansen, R.S.

    2008-01-01

    The short QT syndrome is a newly discovered pro-arrhythmic condition, which may cause ventricular fibrillation and sudden death. Short QT can originate from the apparent gain-of-function mutation N588K in the hERG potassium channel that conducts repolarising I(Kr) current. The present study...

  13. Adrenal and extra-adrenal pheochromocytomas presenting as life-threatening ventricular arrhythmias: Report of three cases

    Directory of Open Access Journals (Sweden)

    Sai Satish Oruganti

    2016-05-01

    Full Text Available Pheochromocytoma patients can rarely have prolonged QT interval in the ECG. We report three cases of pheochromocytoma in females presenting with ventricular arrhythmia; two had torsades de pointes and a third patient had frequent VPCs and nonsustained ventricular tachycardia. All the patients were treated with surgical removal of the tumor with complete relief of symptoms and normalization of QT interval.

  14. Impacto do uso de psicotrópicos na dispersão do intervalo QT em pacientes adultos

    Directory of Open Access Journals (Sweden)

    Bruno de Queiroz Claudio

    2014-06-01

    Full Text Available Fundamento: A dispersão do intervalo QT induzida por fármacos tem sido associada a arritmias ventriculares potencialmente fatais. Pouco se conhece sobre o uso de psicotrópicos, isolados ou em combinação com outros fármacos, na dispersão do QT. Objetivo: Avaliar o impacto do uso psicotrópicos na dispersão do intervalo QT em pacientes adultos. Métodos: Estudo de coorte observacional, envolvendo 161 pacientes hospitalizados em um departamento de emergência de hospital terciário, estratificados em usuários e não usuários de psicotrópicos. Dados demográficos, clínicos, laboratoriais e de fármacos em uso foram coletados à admissão, bem como o eletrocardiograma de 12 derivações, com a mensuração do intervalo e da dispersão do QT. Resultados: A dispersão do intervalo QT foi significativamente maior no grupo de usuário de psicotrópicos comparado ao grupo não usuário (69,25 ± 25,5 ms vs. 57,08 ± 23,4 ms; p = 0,002. O intervalo QT corrigido pela fórmula de Bazzett também se mostrou maior no grupo de usuário de psicotrópicos, com significância estatística (439,79 ± 31,14 ms vs. 427,71 ± 28,42 ms; p = 0,011. A análise por regressão linear mostrou associação positiva entre o número absoluto de psicotrópicos utilizados e a dispersão do intervalo QT, com r = 0,341 e p < 0,001. Conclusão: Na população amostral estudada, o uso de psicotrópicos se mostrou associado ao aumento da dispersão do intervalo QT, e esse incremento se acentuou em função do maior número de psicotrópicos utilizados.

  15. Applications of interval computations

    CERN Document Server

    Kreinovich, Vladik

    1996-01-01

    Primary Audience for the Book • Specialists in numerical computations who are interested in algorithms with automatic result verification. • Engineers, scientists, and practitioners who desire results with automatic verification and who would therefore benefit from the experience of suc­ cessful applications. • Students in applied mathematics and computer science who want to learn these methods. Goal Of the Book This book contains surveys of applications of interval computations, i. e. , appli­ cations of numerical methods with automatic result verification, that were pre­ sented at an international workshop on the subject in EI Paso, Texas, February 23-25, 1995. The purpose of this book is to disseminate detailed and surveyed information about existing and potential applications of this new growing field. Brief Description of the Papers At the most fundamental level, interval arithmetic operations work with sets: The result of a single arithmetic operation is the set of all possible results as the o...

  16. Prolonged Intermittent Renal Replacement Therapy.

    Science.gov (United States)

    Edrees, Fahad; Li, Tingting; Vijayan, Anitha

    2016-05-01

    Prolonged intermittent renal replacement therapy (PIRRT) is becoming an increasingly popular alternative to continuous renal replacement therapy in critically ill patients with acute kidney injury. There are significant practice variations in the provision of PIRRT across institutions, with respect to prescription, technology, and delivery of therapy. Clinical trials have generally demonstrated that PIRRT is non-inferior to continuous renal replacement therapy regarding patient outcomes. PIRRT offers cost-effective renal replacement therapy along with other advantages such as early patient mobilization and decreased nursing time. However, due to lack of standardization of the procedure, PIRRT still poses significant challenges, especially pertaining to appropriate drug dosing. Future guidelines and clinical trials should work toward developing consensus definitions for PIRRT and ensure optimal delivery of therapy. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  17. Clinical characteristics in genetically distinct forms of the congenital long QT syndrome

    International Nuclear Information System (INIS)

    Kawahara, Yosuke; Sawayama, Toshitami; Samukawa, Masanobu; Nezuo, Shoso; Tanaka, Junji; Suetsuna, Ryoji; Kamiyama, Norio

    1998-01-01

    The clinical characteristics in genetically distinct forms of the congenital long QT syndrome (LQTs) were examined on the balance of bilateral sympathetic nerves, and ECG findings. The subjects (mean: 19.4 years old) were three genetically distinct forms of LQTs, including 3 patients in A-family (the high risk family with sudden death), 2 patients in B-family and 3 patients in C-family. All patients met the standard diagnostic criteria according to Schwartz. As the index of the balance of bilateral sympathetic nerves, the dissociation of Tl and MIBG uptake (D) was examined and the radioactivity ratio (the A/L ratio) of anteroseptal wall to posterolateral wall was calculated. The T-wave patterns of ECG and the situation at syncope were examined. In A-family, all 3 patients showed the lowered A/L ratio, D(+), and similar T-wave patterns in ECG. The syndrome developed at exercise, and their QTc extended at exercise. In B-family, all 2 patients showed normal A/L ratio and long T-wave at QT onset, and their QTc shortened at exercise. All patients had developed syncope at rest. In C-family, all 3 patients showed a little decrease of A/L ratio and similar T-wave patterns. Their QTc extended at exercise. These results suggest that the characteristics of the sympathetic nerve balance, ECG wave patterns and the syndrome may depend on each family. (K.H.)

  18. First International Symposium on Long QT Syndrome through the Internet, April 2004

    Directory of Open Access Journals (Sweden)

    Sergio Dubner

    2004-07-01

    Full Text Available With the First Virtual Symposium on Long QT Syndrome already finished; which was held over the month of April, 2004 as an educational activity of the International Society for Holter and Noninvasive Electrocardiology (ISHNE, and completely through the Internet; we, the Presidents of the Scientific and Steering Committees, Sergio Dubner, Edgardo Schapachnik and Andrés Ricardo Pérez Riera, are wondering gladly surprised, which may have been the main causes of such a huge success as we have reached, and the enormous interest arisen. Just to have an idea of the dimension achieved, data obtained from http://www.a9.com (an Amazon.com site or with the traditional search engine Google, prove that the first reply when you request information about long QT Syndrome is the access site of the Symposium. We believe that the response to this question may be summarized in one word: REALIZATION. The best definition for success is realization. The huge motivation in each one of us made the difference. We worked with a cohesive group, like a team, aware of the unparalleled and great opportunity Prof. Arthur Moss had initially assigned to Sergio Dubner and Edgardo Schapachnik, an invitation that the latter extended to Andrés Ricardo Pérez Riera.

  19. Visi—A VTK- and QT-Based Open-Source Project for Scientific Data Visualization

    Science.gov (United States)

    Li, Yiming; Chen, Cheng-Kai

    2009-03-01

    In this paper, we present an open-source project, Visi for high-dimensional engineering and scientific data visualization. Visi is with state-of-the-art interactive user interface and graphics kernels based upon Qt (a cross-platform GUI toolkit) and VTK (an object-oriented visualization library). For an initialization of Visi, a preliminary window will be activated by Qt, and the kernel of VTK is simultaneously embedded into the window, where the graphics resources are allocated. Representation of visualization is through an interactive interface so that the data will be rendered according to user's preference. The developed framework possesses high flexibility and extensibility for advanced functions (e.g., object combination, etc) and further applications. Application of Visi to data visualization in various fields, such as protein structure in bioinformatics, 3D semiconductor transistor, and interconnect of very-large scale integration (VLSI) layout is also illustrated to show the performance of Visi. The developed open-source project is available in our project website on the internet [1].

  20. QTc-prolonging drugs and hospitalizations for cardiac arrhythmias

    DEFF Research Database (Denmark)

    De Bruin, Marie L; Hoes, Arno W; Leufkens, Hubert G M

    2003-01-01

    Cardiac arrhythmia as an adverse effect of noncardiac drugs has been an issue of growing importance during the past few years. In this population-based study, we evaluated the risk for serious cardiac arrhythmias during the use of several noncardiac QTc-prolonging drugs in day-to-day practice......, and subsequently focused on several specific groups of patients who could be extremely vulnerable for drug-induced arrhythmias. We performed a case-control study in which patients (cases), hospitalized for nonatrial cardiac arrhythmias from 1987 to 1998, were compared with their matched controls regarding current...... use of QTc-prolonging drugs. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariate conditional logistic regression, adjusting for potential confounding factors. Data were obtained from the PHARMO record linkage system. We identified 501 cases, 39 of whom used QTc...

  1. The effects of sodium bicarbonate during prolonged cardiopulmonary resuscitation.

    Science.gov (United States)

    Weng, Yi-Ming; Wu, Shih-Hao; Li, Wen-Cheng; Kuo, Chan-Wei; Chen, Shou-Yen; Chen, Jih-Chang

    2013-03-01

    This study was performed to determine the effects of sodium bicarbonate injection during prolonged cardiopulmonary resuscitation (for >15 minutes). The retrospective cohort study consisted of adult patients who presented to the emergency department (ED) with the diagnosis of cardiac arrest in 2009. Data were retrieved from the institutional database. A total of 92 patients were enrolled in the study. Patients were divided into 2 groups based on whether they were treated (group1, n = 30) or not treated (group 2, n = 62) with sodium bicarbonate. There were no significant differences in demographic characteristics between groups. The median time interval between the administration of CPR and sodium bicarbonate injection was 36.0 minutes (IQR: 30.5-41.8 minutes). The median amount of bicarbonate injection was 100.2 mEq (IQR: 66.8-104.4). Patients who received a sodium bicarbonate injection during prolonged CPR had a higher percentage of return of spontaneous circulation, but not statistical significant (ROSC, 40.0% vs. 32.3%; P = .465). Sustained ROSC was achieved by 2 (6.7%) patients in the sodium bicarbonate treatment group, with no survival to discharge. No significant differences in vital signs after ROSC were detected between the 2 groups (heart rate, P = .124; systolic blood pressure, P = .094). Sodium bicarbonate injection during prolonged CPR was not associated with ROSC after adjust for variables by regression analysis (Table 3; P = .615; odds ratio, 1.270; 95% confidence interval: 0.501-3.219) The administration of sodium bicarbonate during prolonged CPR did not significantly improve the rate of ROSC in out-of-hospital cardiac arrest. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Prolonged pregnancy: Methods, Causal Determinants and Outcome

    DEFF Research Database (Denmark)

    Olesen, Annette Wind

    Summary Prolonged pregnancy, defined as a pregnancy with a gestational length of 294 days or more, is a frequent condition. It is associated with an increased risk of fetal and maternal complications. Little is known about the aetiology of prolonged pregnancy. The aims of the thesis were 1......) to study the incidence of prolonged pregnancy as a function of methods for determining gestational age; 2) to determine the risk of obstetrical and fetal complications in prolonged pregnancy; 3) to validate the self-reported gestational age in the National Birth Cohort; 4) to determine whether...... the risk of recurrence of prolonged pregnancy as a function of change in male partner and social conditions (IV). The National Birth Cohort provided data for the study on prenatal risk indicators of prolonged pregnancy in a follow-up design (V). The self-reported gestational ages from this database...

  3. Surveillance test interval optimization

    International Nuclear Information System (INIS)

    Cepin, M.; Mavko, B.

    1995-01-01

    Technical specifications have been developed on the bases of deterministic analyses, engineering judgment, and expert opinion. This paper introduces our risk-based approach to surveillance test interval (STI) optimization. This approach consists of three main levels. The first level is the component level, which serves as a rough estimation of the optimal STI and can be calculated analytically by a differentiating equation for mean unavailability. The second and third levels give more representative results. They take into account the results of probabilistic risk assessment (PRA) calculated by a personal computer (PC) based code and are based on system unavailability at the system level and on core damage frequency at the plant level

  4. Detecting drug-induced prolongation of the QRS complex: New insights for cardiac safety assessment

    Energy Technology Data Exchange (ETDEWEB)

    Cros, C., E-mail: caroline.cros@hotmail.co.uk [Safety Pharmacology, Global Safety Assessment, Safety Assessment UK, AstraZeneca R and D, Alderley Park, Macclesfield, SK10 4TG (United Kingdom); Skinner, M., E-mail: Matthew.Skinner@astrazeneca.com [Safety Pharmacology, Global Safety Assessment, Safety Assessment UK, AstraZeneca R and D, Alderley Park, Macclesfield, SK10 4TG (United Kingdom); Moors, J. [Safety Pharmacology, Global Safety Assessment, Safety Assessment UK, AstraZeneca R and D, Alderley Park, Macclesfield, SK10 4TG (United Kingdom); Lainee, P. [Sanofi-Aventis R and D, 371, rue du Pr Joseph Blayac, 34184 Montpellier Cedex 04 (France); Valentin, J.P. [Safety Pharmacology, Global Safety Assessment, Safety Assessment UK, AstraZeneca R and D, Alderley Park, Macclesfield, SK10 4TG (United Kingdom)

    2012-12-01

    Background: Drugs slowing the conduction of the cardiac action potential and prolonging QRS complex duration by blocking the sodium current (I{sub Na}) may carry pro-arrhythmic risks. Due to the frequency-dependent block of I{sub Na}, this study assesses whether activity-related spontaneous increases in heart rate (HR) occurring during standard dog telemetry studies can be used to optimise the detection of class I antiarrhythmic-induced QRS prolongation. Methods: Telemetered dogs were orally dosed with quinidine (class Ia), mexiletine (class Ib) or flecainide (class Ic). QRS duration was determined standardly (5 beats averaged at rest) but also prior to and at the plateau of each acute increase in HR (3 beats averaged at steady state), and averaged over 1 h period from 1 h pre-dose to 5 h post-dose. Results: Compared to time-matched vehicle, at rest, only quinidine and flecainide induced increases in QRS duration (E{sub max} 13% and 20% respectively, P < 0.01–0.001) whereas mexiletine had no effect. Importantly, the increase in QRS duration was enhanced at peak HR with an additional effect of + 0.7 ± 0.5 ms (quinidine, NS), + 1.8 ± 0.8 ms (mexiletine, P < 0.05) and + 2.8 ± 0.8 ms (flecainide, P < 0.01) (calculated as QRS at basal HR-QRS at high HR). Conclusion: Electrocardiogram recordings during elevated HR, not considered during routine analysis optimised for detecting QT prolongation, can be used to sensitise the detection of QRS prolongation. This could prove useful when borderline QRS effects are detected. Analysing during acute increases in HR could also be useful for detecting drug-induced effects on other aspects of cardiac function. -- Highlights: ► We aimed to improve detection of drug-induced QRS prolongation in safety screening. ► We used telemetered dogs to test class I antiarrhythmics at low and high heart rate. ► At low heart rate only quinidine and flecainide induced an increase in QRS duration. ► At high heart rate the effects of two

  5. Detecting drug-induced prolongation of the QRS complex: New insights for cardiac safety assessment

    International Nuclear Information System (INIS)

    Cros, C.; Skinner, M.; Moors, J.; Lainee, P.; Valentin, J.P.

    2012-01-01

    Background: Drugs slowing the conduction of the cardiac action potential and prolonging QRS complex duration by blocking the sodium current (I Na ) may carry pro-arrhythmic risks. Due to the frequency-dependent block of I Na , this study assesses whether activity-related spontaneous increases in heart rate (HR) occurring during standard dog telemetry studies can be used to optimise the detection of class I antiarrhythmic-induced QRS prolongation. Methods: Telemetered dogs were orally dosed with quinidine (class Ia), mexiletine (class Ib) or flecainide (class Ic). QRS duration was determined standardly (5 beats averaged at rest) but also prior to and at the plateau of each acute increase in HR (3 beats averaged at steady state), and averaged over 1 h period from 1 h pre-dose to 5 h post-dose. Results: Compared to time-matched vehicle, at rest, only quinidine and flecainide induced increases in QRS duration (E max 13% and 20% respectively, P < 0.01–0.001) whereas mexiletine had no effect. Importantly, the increase in QRS duration was enhanced at peak HR with an additional effect of + 0.7 ± 0.5 ms (quinidine, NS), + 1.8 ± 0.8 ms (mexiletine, P < 0.05) and + 2.8 ± 0.8 ms (flecainide, P < 0.01) (calculated as QRS at basal HR-QRS at high HR). Conclusion: Electrocardiogram recordings during elevated HR, not considered during routine analysis optimised for detecting QT prolongation, can be used to sensitise the detection of QRS prolongation. This could prove useful when borderline QRS effects are detected. Analysing during acute increases in HR could also be useful for detecting drug-induced effects on other aspects of cardiac function. -- Highlights: ► We aimed to improve detection of drug-induced QRS prolongation in safety screening. ► We used telemetered dogs to test class I antiarrhythmics at low and high heart rate. ► At low heart rate only quinidine and flecainide induced an increase in QRS duration. ► At high heart rate the effects of two out of three

  6. Distribution of Eight QT-Prolonging Drugs and Their Main Metabolites Between Postmortem Cardiac Tissue and Blood Reveals Potential Pitfalls in Toxicological Interpretation

    DEFF Research Database (Denmark)

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

    2018-01-01

    significantly higher compared to femoral and cardiac blood concentrations, with two exceptions. The median cardiac tissue-to-femoral blood concentration ratio (Kb) ranged from 2.2 (venlafaxine) to 15 (nortriptyline). The inter-individual fold difference between the minimum and maximum Kb ranged from 2.6-fold (Z......-hydroxynortriptyline) to 61 (venlafaxine). For 12 compounds, postmortem redistribution appeared to be minimal, whereas four compounds displayed some degree of postmortem redistribution. Citalopram and quetiapine were selected for in-depth analysis of the relation between the toxicological interpretation and femoral blood...

  7. Chaos on the interval

    CERN Document Server

    Ruette, Sylvie

    2017-01-01

    The aim of this book is to survey the relations between the various kinds of chaos and related notions for continuous interval maps from a topological point of view. The papers on this topic are numerous and widely scattered in the literature; some of them are little known, difficult to find, or originally published in Russian, Ukrainian, or Chinese. Dynamical systems given by the iteration of a continuous map on an interval have been broadly studied because they are simple but nevertheless exhibit complex behaviors. They also allow numerical simulations, which enabled the discovery of some chaotic phenomena. Moreover, the "most interesting" part of some higher-dimensional systems can be of lower dimension, which allows, in some cases, boiling it down to systems in dimension one. Some of the more recent developments such as distributional chaos, the relation between entropy and Li-Yorke chaos, sequence entropy, and maps with infinitely many branches are presented in book form for the first time. The author gi...

  8. Interventricular dispersion in repolarization causes bifid T waves in dogs with dofetilide-induced long QT syndrome

    NARCIS (Netherlands)

    Meijborg, Veronique M F; Chauveau, Samuel; Janse, Michiel J; Anyukhovsky, Evgeny P; Danilo, Peter R; Rosen, Michael R; Opthof, Tobias; Coronel, Ruben

    BACKGROUND: Long QT2 (LQT2) syndrome is characterized by bifid (or notched) T waves, whose mechanism is not understood. OBJECTIVE: The purpose of this study was to test whether increased interventricular dispersion of repolarization induces bifid T waves. METHODS: We simultaneously recorded surface

  9. Interventricular dispersion in repolarization causes bifid T waves in dogs with dofetilide-induced long QT syndrome

    NARCIS (Netherlands)

    Meijborg, Veronique M. F.; Chauveau, Samuel; Janse, Michiel J.; Anyukhovsky, Evgeny P.; Danilo, Peter R.; Rosen, Michael R.; Opthof, Tobias; Coronel, Ruben

    2015-01-01

    Long QT2 (LQT2) syndrome is characterized by bifid (or notched) T waves, whose mechanism is not understood. The purpose of this study was to test whether increased interventricular dispersion of repolarization induces bifid T waves. We simultaneously recorded surface ECG and unipolar electrograms at

  10. The Importance of the Family History in Caring for Families With Long QT Syndrome and Dilated Cardiomyopathy

    NARCIS (Netherlands)

    Ruiter, J.S.; Berkenbosch-Nieuwhof, K.; van den Berg, M.P.; van Dijk, R.; Middel, B.; van Tintelen, J.P.

    In potentially inherited cardiac diseases, the family history is of great importance. We looked at the way cardiologists take a family history in patients with idiopathic dilated cardiomyopathy (DCM) or long QT syndrome (LQTS) and whether this led to screening of relatives or other follow-up. We

  11. Diagnostic criteria for congenital long QT syndrome in the era of molecular genetics: Do we need a scoring system?

    NARCIS (Netherlands)

    Hofman, Nynke; Wilde, Arthur A.M.; Kääb, Stefan; Van Langen, Irene M.; Tanck, Michael W.T.; Mannens, Marcel M.A.M.; Hinterseer, Martin; Beckmann, Britt-Maria; Tan, Hanno L.

    2007-01-01

    Aims: Previously published diagnostic systems, based on ECG analysis and clinical parameters (Schwartz criteria and Keating criteria), have been used to estimate the probability of inherited long QT syndrome (LQTS). Nowadays, a certain diagnosis can often be made by DNA testing. We aimed to

  12. The QT dispersion and QTc dispersion in patients presenting with acute neurological events and its impact on early prognosis

    Directory of Open Access Journals (Sweden)

    Kailash Kumar Rahar

    2016-01-01

    Full Text Available Aims: To find out and investigate whether the QT dispersion and QTc dispersion is related to type and prognosis of the acute stroke in patients presenting within 24 h of the onset of stroke. Settings and Design: This was a observational study conducted at Mahatma Gandhi Hospital, Dr. SN. Medical College, Jodhpur, during January 2014 to January 2015. Subjects and Methods: The patients presented within 24 h of onset of acute stroke (hemorrhagic, infarction, or transient ischemic event were included in the study. The stroke was confirmed by computed tomography scan and magnetic resonance imaging. Patients with (i altered sensorium because of metabolic, infective, seizures, trauma, or tumor; (ii prior history of cardiovascular disease, electrocardiographic abnormalities' because of dyselectrolytemia; and (iii and patients who were on drugs (antiarrhythmic drugs, antipsychotic drugs, erythromycin, theophylline, etc., which known to cause electrocardiogram changes, were excluded from the study. National Institute of Health Stroke Score (NIHSS was calculated at the time of admission and Modified Rankin Scale (MRS at the time of discharge. Fifty age- and sex-matched healthy controls included. Statistical Analysis Used: Student's t-test, ANOVA, and area under curve for sensitivity and specificity for the test. Results: We included 52 patients (male/female: 27/25 and 50 controls (26/24. The mean age of patients was 63.17 ± 08.90 years. Of total patients, infarct was found in 32 (61.53%, hemorrhage in 18 (34.61%, transient ischemic attack (TIA in 1 (1.9%, and subarachnoid hemorrhage in 1 (1.9% patient. The QT dispersion and QTc dispersion were significantly higher in cases as compare to controls. (87.30 ± 24.42 vs. 49.60 ± 08.79 ms; P < 0.001 and (97.53 ± 27.36 vs. 56.28 ± 09.86 ms; P < 0.001. Among various types of stroke, the mean QT dispersion and QTc dispersion were maximum and significantly higher in hemorrhagic stroke as compared to infarct and

  13. Interval methods: An introduction

    DEFF Research Database (Denmark)

    Achenie, L.E.K.; Kreinovich, V.; Madsen, Kaj

    2006-01-01

    This chapter contains selected papers presented at the Minisymposium on Interval Methods of the PARA'04 Workshop '' State-of-the-Art in Scientific Computing ''. The emphasis of the workshop was on high-performance computing (HPC). The ongoing development of ever more advanced computers provides...... the potential for solving increasingly difficult computational problems. However, given the complexity of modern computer architectures, the task of realizing this potential needs careful attention. A main concern of HPC is the development of software that optimizes the performance of a given computer....... An important characteristic of the computer performance in scientific computing is the accuracy of the Computation results. Often, we can estimate this accuracy by using traditional statistical techniques. However, in many practical situations, we do not know the probability distributions of different...

  14. Multichannel interval timer

    International Nuclear Information System (INIS)

    Turko, B.T.

    1983-10-01

    A CAMAC based modular multichannel interval timer is described. The timer comprises twelve high resolution time digitizers with a common start enabling twelve independent stop inputs. Ten time ranges from 2.5 μs to 1.3 μs can be preset. Time can be read out in twelve 24-bit words either via CAMAC Crate Controller or an external FIFO register. LSB time calibration is 78.125 ps. An additional word reads out the operational status of twelve stop channels. The system consists of two modules. The analog module contains a reference clock and 13 analog time stretchers. The digital module contains counters, logic and interface circuits. The timer has an excellent differential linearity, thermal stability and crosstalk free performance

  15. Experimenting with musical intervals

    Science.gov (United States)

    Lo Presto, Michael C.

    2003-07-01

    When two tuning forks of different frequency are sounded simultaneously the result is a complex wave with a repetition frequency that is the fundamental of the harmonic series to which both frequencies belong. The ear perceives this 'musical interval' as a single musical pitch with a sound quality produced by the harmonic spectrum responsible for the waveform. This waveform can be captured and displayed with data collection hardware and software. The fundamental frequency can then be calculated and compared with what would be expected from the frequencies of the tuning forks. Also, graphing software can be used to determine equations for the waveforms and predict their shapes. This experiment could be used in an introductory physics or musical acoustics course as a practical lesson in superposition of waves, basic Fourier series and the relationship between some of the ear's subjective perceptions of sound and the physical properties of the waves that cause them.

  16. Early diastolic time intervals during hypertensive pregnancy.

    Science.gov (United States)

    Spinelli, L; Ferro, G; Nappi, C; Farace, M J; Talarico, G; Cinquegrana, G; Condorelli, M

    1987-10-01

    Early diastolic time intervals have been assessed by means of the echopolycardiographic method in 17 pregnant women who developed hypertension during pregnancy (HP) and in 14 normal pregnant women (N). Systolic time intervals (STI), stroke volume (SV), ejection fraction (EF), and mean velocity of myocardial fiber shortening (VCF) were also evaluated. Recordings were performed in the left lateral decubitus (LLD) and then in the supine decubitus (SD). In LLD, isovolumic relaxation period (IRP) was prolonged in the hypertensive pregnant women compared with normal pregnant women (HP 51 +/- 12.5 ms, N 32.4 +/- 15 ms p less than 0.05), whereas time of the mitral valve maximum opening (DE) was not different in the groups. There was no difference in SV, EF, and mean VCF, whereas STI showed only a significant (p less than 0.05) lengthening of pre-ejection period (PEP) in HP. When the subjects shifted from the left lateral to the supine decubitus position, left ventricular ejection time index (LVETi) and SV decreased significantly (p less than 0.05) in both normotensive hypertensive pregnant women. IRP and PEP lengthened significantly (p less than 0.05) only in normals, whereas they were unchanged in HP. DE time did not vary in either group. In conclusion, hypertension superimposed on pregnancy induces lengthening of IRP, as well as of PEP, and minimizes the effects of the postural changes in preload on the above-mentioned time intervals.

  17. Prenatal risk indicators of a prolonged pregnancy

    DEFF Research Database (Denmark)

    Olesen, Annette Wind; Westergaard, Jes Grabow; Olsen, Jørn

    2006-01-01

    BACKGROUND: Few prenatal risk factors of prolonged pregnancy, a pregnancy of 42 weeks or more, are known. The objective was to examine whether sociodemographic, reproductive, toxicologic, or medical health conditions were associated with the risk of prolonged pregnancy. METHODS: Data from...

  18. [Brain function recovery after prolonged posttraumatic coma].

    Science.gov (United States)

    Klimash, A V; Zhanaidarov, Z S

    2016-01-01

    To explore the characteristics of brain function recovery in patients after prolonged posttraumatic coma and with long-unconscious states. Eighty-seven patients after prolonged posttraumatic coma were followed-up for two years. An analysis of a clinical/neurological picture after a prolonged episode of coma was based on the dynamics of vital functions, neurological status and patient's reactions to external stimuli. Based on the dynamics of the clinical/neurological picture that shows the recovery of functions of the certain brain areas, three stages of brain function recovery after a prolonged episode of coma were singled out: brain stem areas, diencephalic areas and telencephalic areas. These functional/anatomic areas of brain function recovery after prolonged coma were compared to the present classifications.

  19. 9. Nuclear power plant service life prolongation

    International Nuclear Information System (INIS)

    Evropin, S.V.

    1998-01-01

    The problem of prolongation of nuclear power plant service life duration is discussed. A schematic diagram of the program developed in the course of activities dealing with NPP service time prolongation is shown and analyzed in details. It is shown that the basic moment when determining the strategy for NPP service time prolongation is the positive confirmation of the agreement between the NPP safety provisions and modern safety requirements. The other very important aspect of the problem is engineering substantiation of the measures assuring the reactor operation prolongation. The conclusion is made that available methods of recovering reactor materials properties, main components repair and replacement, the modern techniques for nondestructive testing of metals and NPP pipelines, as well as the developed approaches to reactor facility safety improvements make the prolongation of the Russian NPP service lifetimes possible from engineering viewpoint and economically desirable

  20. Dissection of a Quantitative Trait Locus for PR Interval Duration Identifies Tnni3k as a Novel Modulator of Cardiac Conduction

    NARCIS (Netherlands)

    Lodder, Elisabeth M.; Scicluna, Brendon P.; Milano, Annalisa; Sun, Albert Y.; Tang, Hao; Remme, Carol Ann; Moerland, Perry D.; Tanck, Michael W. T.; Pitt, Geoffrey S.; Marchuk, Douglas A.; Bezzina, Connie R.

    2012-01-01

    Atrio-ventricular conduction disease is a common feature in Mendelian rhythm disorders associated with sudden cardiac death and is characterized by prolongation of the PR interval on the surface electrocardiogram (ECG). Prolongation of the PR interval is also a strong predictor of atrial

  1. Transient Outward K+ Current (Ito) Underlies the Right Ventricular Initiation of Polymorphic Ventricular Tachycardia in a Transgenic Rabbit Model of Long-QT Syndrome Type 1.

    Science.gov (United States)

    Choi, Bum-Rak; Li, Weiyan; Terentyev, Dmitry; Kabakov, Anatoli Y; Zhong, Mingwang; Rees, Colin M; Terentyeva, Radmila; Kim, Tae Yun; Qu, Zhilin; Peng, Xuwen; Karma, Alain; Koren, Gideon

    2018-06-01

    Sudden death in long-QT syndrome type 1 (LQT1), an inherited disease caused by loss-of-function mutations in KCNQ1, is triggered by early afterdepolarizations (EADs) that initiate polymorphic ventricular tachycardia (pVT). We investigated ionic mechanisms that underlie pVT in LQT1 using a transgenic rabbit model of LQT1. Optical mapping, cellular patch clamping, and computer modeling were used to elucidate the mechanisms of EADs in transgenic LQT1 rabbits. The results showed that shorter action potential duration in the right ventricle (RV) was associated with focal activity during pVT initiation. RV cardiomyocytes demonstrated higher incidence of EADs under 50 nmol/L isoproterenol. Voltage-clamp studies revealed that the transient outward potassium current (I to ) magnitude was 28% greater in RV associated with KChiP2 but with no differences in terms of calcium-cycling kinetics and other sarcolemmal currents. Perfusing with the I to blocker 4-aminopyridine changed the initial focal sites of pVT from the RV to the left ventricle, corroborating the role of I to in pVT initiation. Computer modeling showed that EADs occur preferentially in the RV because of the larger conductance of the slow-inactivating component of I to , which repolarizes the membrane potential sufficiently rapidly to allow reactivation of I Ca,L before I Kr has had sufficient time to activate. I to heterogeneity creates both triggers and an arrhythmogenic substrate in LQT1. In the absence of I Ks , I to interactions with I Ca,L and I Kr promote EADs in the RV while prolonging action potential duration in the left ventricle. This heterogeneity of action potential enhances dispersion of refractoriness and facilitates conduction blocks that initiate pVTs. © 2018 American Heart Association, Inc.

  2. Toward Personalized Medicine: Using Cardiomyocytes Differentiated From Urine-Derived Pluripotent Stem Cells to Recapitulate Electrophysiological Characteristics of Type 2 Long QT Syndrome.

    Science.gov (United States)

    Jouni, Mariam; Si-Tayeb, Karim; Es-Salah-Lamoureux, Zeineb; Latypova, Xenia; Champon, Benoite; Caillaud, Amandine; Rungoat, Anais; Charpentier, Flavien; Loussouarn, Gildas; Baró, Isabelle; Zibara, Kazem; Lemarchand, Patricia; Gaborit, Nathalie

    2015-09-01

    Human genetically inherited cardiac diseases have been studied mainly in heterologous systems or animal models, independent of patients' genetic backgrounds. Because sources of human cardiomyocytes (CMs) are extremely limited, the use of urine samples to generate induced pluripotent stem cell-derived CMs would be a noninvasive method to identify cardiac dysfunctions that lead to pathologies within patients' specific genetic backgrounds. The objective was to validate the use of CMs differentiated from urine-derived human induced pluripotent stem (UhiPS) cells as a new cellular model for studying patients' specific arrhythmia mechanisms. Cells obtained from urine samples of a patient with long QT syndrome who harbored the HERG A561P gene mutation and his asymptomatic noncarrier mother were reprogrammed using the episomal-based method. UhiPS cells were then differentiated into CMs using the matrix sandwich method.UhiPS-CMs showed proper expression of atrial and ventricular myofilament proteins and ion channels. They were electrically functional, with nodal-, atrial- and ventricular-like action potentials recorded using high-throughput optical and patch-clamp techniques. Comparison of HERG expression from the patient's UhiPS-CMs to the mother's UhiPS-CMs showed that the mutation led to a trafficking defect that resulted in reduced delayed rectifier K(+) current (IKr). This phenotype gave rise to action potential prolongation and arrhythmias. UhiPS cells from patients carrying ion channel mutations can be used as novel tools to differentiate functional CMs that recapitulate cardiac arrhythmia phenotypes. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  3. Characteristics of PR interval as predictor for atrial fibrillation: association with biomarkers and outcomes.

    Science.gov (United States)

    Schumacher, Katja; Dagres, Nikolaos; Hindricks, Gerhard; Husser, Daniela; Bollmann, Andreas; Kornej, Jelena

    2017-10-01

    The PR interval may be considered as a simple and easily obtainable predictor for adverse events, including atrial fibrillation (AF), pacemaker implantation, and mortality. Interestingly, both high and low extremes of the PR duration are associated with AF risk. However, the results regarding PR prolongation as a risk factor for AF are inconsistent. Some studies have analyzed the impact of P duration (as a part of the PR interval) and demonstrated that the P-duration contributes to the length of PR interval and adverse outcomes. The PR prolongation could be considered as a marker for cardiovascular degenerative aging caused by myocardial fibrosis and vascular inflammation. Furthermore, due to PR prolongation chronically raised intra-atrial pressure and consequential neuro-hormonal activation predispose systemic vascular endothelial dysfunction and explain the associations with adverse vascular events. In this review, we discuss the association between biomarkers with PR interval in AF.

  4. Diclofenac Prolongs Repolarization in Ventricular Muscle with Impaired Repolarization Reserve

    Science.gov (United States)

    Kristóf, Attila; Husti, Zoltán; Koncz, István; Kohajda, Zsófia; Szél, Tamás; Juhász, Viktor; Biliczki, Péter; Jost, Norbert; Baczkó, István; Papp, Julius Gy; Varró, András; Virág, László

    2012-01-01

    Background The aim of the present work was to characterize the electrophysiological effects of the non-steroidal anti-inflammatory drug diclofenac and to study the possible proarrhythmic potency of the drug in ventricular muscle. Methods Ion currents were recorded using voltage clamp technique in canine single ventricular cells and action potentials were obtained from canine ventricular preparations using microelectrodes. The proarrhythmic potency of the drug was investigated in an anaesthetized rabbit proarrhythmia model. Results Action potentials were slightly lengthened in ventricular muscle but were shortened in Purkinje fibers by diclofenac (20 µM). The maximum upstroke velocity was decreased in both preparations. Larger repolarization prolongation was observed when repolarization reserve was impaired by previous BaCl2 application. Diclofenac (3 mg/kg) did not prolong while dofetilide (25 µg/kg) significantly lengthened the QTc interval in anaesthetized rabbits. The addition of diclofenac following reduction of repolarization reserve by dofetilide further prolonged QTc. Diclofenac alone did not induce Torsades de Pointes ventricular tachycardia (TdP) while TdP incidence following dofetilide was 20%. However, the combination of diclofenac and dofetilide significantly increased TdP incidence (62%). In single ventricular cells diclofenac (30 µM) decreased the amplitude of rapid (IKr) and slow (IKs) delayed rectifier currents thereby attenuating repolarization reserve. L-type calcium current (ICa) was slightly diminished, but the transient outward (Ito) and inward rectifier (IK1) potassium currents were not influenced. Conclusions Diclofenac at therapeutic concentrations and even at high dose does not prolong repolarization markedly and does not increase the risk of arrhythmia in normal heart. However, high dose diclofenac treatment may lengthen repolarization and enhance proarrhythmic risk in hearts with reduced repolarization reserve. PMID:23300901

  5. Historical space weather monitoring of prolonged aurora activities in Japan and in China

    Science.gov (United States)

    Kataoka, Ryuho; Isobe, Hiroaki; Hayakawa, Hisashi; Tamazawa, Harufumi; Kawamura, Akito Davis; Miyahara, Hiroko; Iwahashi, Kiyomi; Yamamoto, Kazuaki; Takei, Masako; Terashima, Tsuneyo; Suzuki, Hidehiko; Fujiwara, Yasunori; Nakamura, Takuji

    2017-02-01

    Great magnetic storms are recorded as aurora sightings in historical documents. The earliest known example of "prolonged" aurora sightings, with aurora persistent for two or more nights within a 7 day interval at low latitudes, in Japan was documented on 21-23 February 1204 in Meigetsuki, when a big sunspot was also recorded in China. We have searched for prolonged events over the 600 year interval since 620 in Japan based on the catalogue of Kanda and over the 700 year interval since 581 in China based on the catalogues of Tamazawa et al. (2017) and Hayakawa et al. (2015). Before the Meigetsuki event, a significant fraction of the 200 possible aurora sightings in Sòng dynasty (960-1279) of China was detected at least twice within a 7 day interval and sometimes recurred with approximately the solar rotation period of 27 days. The majority of prolonged aurora activity events occurred around the maximum phase of solar cycles rather than around the minimum, as estimated from the 14C analysis of tree rings. They were not reported during the Oort Minimum (1010-1050). We hypothesize that the prolonged aurora sightings are associated with great magnetic storms resulting from multiple coronal mass ejections from the same active region. The historical documents therefore provide useful information to support estimation of great magnetic storm frequency, which are often associated with power outages and other societal concerns.

  6. Prolonged CT urography in duplex kidney.

    Science.gov (United States)

    Gong, Honghan; Gao, Lei; Dai, Xi-Jian; Zhou, Fuqing; Zhang, Ning; Zeng, Xianjun; Jiang, Jian; He, Laichang

    2016-05-13

    Duplex kidney is a common anomaly that is frequently associated with multiple complications. Typical computed tomography urography (CTU) includes four phases (unenhanced, arterial, parenchymal and excretory) and has been suggested to considerably aid in the duplex kidney diagnosi. Unfortunately, regarding duplex kidney with prolonged dilatation, the affected parenchyma and tortuous ureters demonstrate a lack of or delayed excretory opacification. We used prolonged-delay CTU, which consists of another prolonged-delay phase (1- to 72-h delay; mean delay: 24 h) to opacify the duplicated ureters and affected parenchyma. Seventeen patients (9 males and 8 females; age range: 2.5-56 y; mean age: 40.4 y) with duplex kidney were included in this study. Unenhanced scans did not find typical characteristics of duplex kidney, except for irregular perirenal morphology. Duplex kidney could not be confirmed on typical four-phase CTU, whereas it could be easily diagnosed in axial and CT-3D reconstruction using prolonged CTU (prolonged-delay phase). Between January 2005 and October 2010, in this review board-approved study (with waived informed consent), 17 patients (9 males and 8 females; age range: 2.5 ~ 56 y; mean age: 40.4 y) with suspicious duplex kidney underwent prolonged CTU to opacify the duplicated ureters and confirm the diagnosis. Our results suggest the validity of prolonged CTU to aid in the evaluation of the function of the affected parenchyma and in the demonstration of urinary tract malformations.

  7. Licence prolongations of US nuclear power plants

    International Nuclear Information System (INIS)

    2004-04-01

    Licences of US nuclear reactors were initially attributed for a 40 years duration. However, the vast majority of the reactors can benefit of a licence prolongation for a period of 20 years maximum. This article recalls first the procedure to follow for the licence prolongation demands (safety analysis, components aging, environmental impact statement), and then it makes a status of the accepted prolongations, of the demands under examination, and of the demands that should be presented in the next 5 years. (J.S.)

  8. Prolonged delirium misdiagnosed as a mood disorder.

    Science.gov (United States)

    Cao, Fei; Salem, Haitham; Nagpal, Caesa; Teixeira, Antonio L

    2017-01-01

    Delirium can be conceptualized as an acute decline in cognitive function that typically lasts from hours to a few days. Prolonged delirium can also affect patients with multiple predisposing and/or precipitating factors. In clinical practice, prolonged delirium is often unrecognized, and can be misdiagnosed as other psychiatric disorders. We describe a case of a 59-year-old male presenting with behavioral and cognitive symptoms that was first misdiagnosed as a mood disorder in a general hospital setting. After prolonged delirium due to multiple factors was confirmed, the patient was treated accordingly with symptomatic management. He evolved with progressive improvement of his clinical status. Early diagnosis and management of prolonged delirium are important to improve patient prognosis and avoid iatrogenic measures.

  9. Prolonged parenteral nutrition after neonatal gastrointestinal surgery

    DEFF Research Database (Denmark)

    Estmann, Anne; Qvist, Niels; Husby, Steffen

    2002-01-01

    to diagnosis and clinical course. METHODOLOGY: This study reviews the clinical course of infants with gastrointestinal disease (gastroschisis, intestinal atresia, omphalocele, volvulus, Hirschsprung's disease and necrotizing enterocolitis) with a prolonged need for parenteral nutrition in the Western part...

  10. Prolonged Pregnancy: Methods, Causal Determinants and Outcome

    DEFF Research Database (Denmark)

    Olesen, Annette Wind

    ) to study the incidence of prolonged pregnancy as a function of methods for determining gestational age; 2) to determine the risk of obstetrical and fetal complications in prolonged pregnancy; 3) to validate the self-reported gestational age in the National Birth Cohort; 4) to determine whether...... an ultrasound scan in the first or second trimester, or menstrual history was best at predicting the day of delivery; 5) to study the risk of recurrence of prolonged pregnancy as a function of change in male partner, social status and municipality; and 6) to detect prenatal risk indicators of prolonged...... of perinatal and obstetrical complications was high in post-term delivery compared to term delivery (OR between 1.2 and 3.1). The risk of perinatal death (OR=1.36 (1.08-1.72)) was also higher in the post-term group (I). The self-reported gestational ages in the National Birth Cohort correlated well with data...

  11. The Power of Phase I Studies to Detect Clinical Relevant QTc Prolongation: A Resampling Simulation Study

    Directory of Open Access Journals (Sweden)

    Georg Ferber

    2015-01-01

    Full Text Available Concentration-effect (CE models applied to early clinical QT data from healthy subjects are described in the latest E14 Q&A document as promising analysis to characterise QTc prolongation. The challenges faced if one attempts to replace a TQT study by thorough ECG assessments in Phase I based on CE models are the assurance to obtain sufficient power and the establishment of a substitute for the positive control to show assay sensitivity providing protection against false negatives. To demonstrate that CE models in small studies can reliably predict the absence of an effect on QTc, we investigated the role of some key design features in the power of the analysis. Specifically, the form of the CE model, inclusion of subjects on placebo, and sparse sampling on the performance and power of this analysis were investigated. In this study, the simulations conducted by subsampling subjects from 3 different TQT studies showed that CE model with a treatment effect can be used to exclude small QTc effects. The number of placebo subjects was also shown to increase the power to detect an inactive drug preventing false positives while an effect can be underestimated if time points around tmax are missed.

  12. QTc prolongation in Black diabetic subjects with cardiac autonomic ...

    African Journals Online (AJOL)

    ed QT (QTc) in diabetic individuals with cardiac auto- .... standing compared to the R-R at the 15th beat (30:15) was calculated. Abnormal .... tion between QTc and age (Pearson's univariate analysis r=0.080 ..... Diagnosis and management of.

  13. Epidemiology of symptomatic drug-induced long QT syndrome and Torsade de Pointes in Germany.

    Science.gov (United States)

    Sarganas, Giselle; Garbe, Edeltraut; Klimpel, Andreas; Hering, Rolf C; Bronder, Elisabeth; Haverkamp, Wilhelm

    2014-01-01

    Drug-induced long QT syndrome (diLQTS) leading to Torsade de Pointes (TdP) is a potentially lethal condition, which has led to several post-marketing drug withdrawals in the past decade. The true incidence of diLQTS/TdP is largely unknown. One explanation is under-reporting of this potentially life-threatening adverse event by physicians and other medical staff to pharmacovigilance agencies. To gain more insight into the incidence of diLQTS and TdP, the Berlin Pharmacovigilance Center (PVZ-FAKOS) has actively and prospectively identified patients who developed this particular type of drug-induced adverse event. Here, the basic characteristics of the affected patients are summarized and suspected drugs are discussed. Furthermore, an extrapolation of the Berlin incidence rates to the German Standard Population is presented. Using a Berlin-wide network of 51 collaborating hospitals (>180 clinical departments), adult patients presenting with long QT syndrome (LQTS/TdP) between 2008 and 2011 were identified by active surveillance of these hospitals. Drug exposures as well as other possible risk factors were obtained from the patient's files and in a face-to-face interview with the patient. One-hundred and seventy patients of possible LQTS/TdP were reported to the Pharmacovigilance Center of whom 58 cases were confirmed in a thorough validation process. The majority (66%) of these cases were female and 60% had developed LQTS/TdP in the outpatient setting. Thirty-five (60%) of 58 confirmed cases were assessed as drug-related based on a standardized causality assessment applying the criteria of the World Health Organization. Drugs assessed as related in more than two cases were metoclopramide, amiodarone, melperone, citalopram, and levomethadone. The age-standardized incidence of diLQTS/TdP in Berlin was estimated to be 2.5 per million per year for males and 4.0 per million per year for females. While European annual reporting rates based on spontaneous reports suggest an

  14. Change and dispersion of QT interval during treatment with quetiapine extended release versus aripiprazole in children and adolescents with first-episode psychosis

    DEFF Research Database (Denmark)

    Jensen, Karsten Gjessing; Gärtner, Stefan; Correll, Christoph U.

    2018-01-01

    was correlated to higher QTcH change in the quetiapine ER group. The HR increased significantly with quetiapine ER (+ 11.0 ± 14.2 bpm, p bpm, p = 0.643). QTd did not significantly change with quetiapine ER or aripiprazole. Conclusion: QTcH and HR increased...

  15. Performance Evaluation of MMA7260QT and ADXL345 on Self Balancing Robot

    Directory of Open Access Journals (Sweden)

    Djoko Purwanto

    2013-03-01

    Full Text Available A Self Balancing Robot (SBR controller needs to detect platform inclination. For this purpose, an accelerometer is used. From various types of accelerometer, we can divide into digital and analog ones. The problem is how to select the right type for the SBR.This paper evaluates the performance of the ADXL345 and the MMA7260QT. The Arduino is used to read data from the sensor and send it to PC for plotting. Both sensors use the lowest sensitivity. The sensors are evaluated with three criteria, i.e. stationary, dynamical response and collaborating with ITG3200 3-axis gyroscope for Kalman Filter fusion. For stationary criterion, the ADXL345 is better than the other sensor for all stationary position. For dynamical response, both sensors suffer from the noise due to acceleration of the platform. The sensors do not only sense the gravity but also the acceleration of the platform when it is moved. But the noise level for the ADXL345 is lower than the other. Using Kalman Filter makes both sensors show good performance for a SBR application. If three criteria are combined with hardware aspect, then the authors recommend using the ADXL345. Besides, it has several useful features to handle abrupt acceleration.

  16. Reconstruction of action potential of repolarization in patients with congenital long-QT syndrome

    International Nuclear Information System (INIS)

    Kandori, Akihiko; Shimizu, Wataru; Yokokawa, Miki; Kamakura, Shiro; Miyatake, Kunio; Murakami, Masahiro; Miyashita, Tsuyoshi; Ogata, Kuniomi; Tsukada, Keiji

    2004-01-01

    A method for reconstructing an action potential during the repolarization period was developed. This method uses a current distribution-plotted as a current-arrow map (CAM)-calculated using magnetocardiogram (MCG) signals. The current arrows are summarized during the QRS complex period and subtracted during the ST-T wave period in order to reconstruct the action-potential waveform. To ensure the similarity between a real action potential and the reconstructed action potential using CAM, a monophasic action potential (MAP) and an MCG of the same patient with type-I long-QT syndrome were measured. Although the MAP had one notch that was associated with early afterdepolarization (EAD), the reconstructed action potential had two large and small notches. The small notch timing agreed with the occurrence of the EAD in the MAP. On the other hand, the initiation time of an abnormal current distribution coincides with the appearance timing of the first large notch, and its end time coincides with that of the second small notch. These results suggest that a simple reconstruction method using a CAM based on MCG data can provide a similar action-potential waveform to a MAP waveform without having to introduce a catheter

  17. Levofloxacin?Induced QTc Prolongation Depends on the Time of Drug Administration

    OpenAIRE

    Kervezee, L; Gotta, V; Stevens, J; Birkhoff, W; Kamerling, IMC; Danhof, M; Meijer, JH; Burggraaf, J

    2016-01-01

    Understanding the factors influencing a drug's potential to prolong the QTc interval on an electrocardiogram is essential for the correct evaluation of its safety profile. To explore the effect of dosing time on drug-induced QTc prolongation, a randomized, crossover, clinical trial was conducted in which 12 healthy male subjects received levofloxacin at 02:00, 06:00, 10:00, 14:00, 18:00, and 22:00. Using a pharmacokinetic-pharmacodynamic (PK-PD) modeling approach to account for variations in ...

  18. Predictive factors for oropharyngeal dysphagia after prolonged orotracheal intubation.

    Science.gov (United States)

    Oliveira, Ana Carolina Martins de; Friche, Amélia Augusta de Lima; Salomão, Marina Silva; Bougo, Graziela Chamarelli; Vicente, Laélia Cristina Caseiro

    2017-09-13

    Lesions in the oral cavity, pharynx and larynx due to endotracheal intubation can cause reduction in the local motility and sensitivity, impairing the swallowing process, resulting in oropharyngeal dysphagia. To verify the predictive factors for the development of oropharyngeal dysphagia and the risk of aspiration in patients with prolonged orotracheal intubation admitted to an intensive care unit. This is an observational, analytical, cross-sectional and retrospective data collection study of 181 electronic medical records of patients submitted to prolonged orotracheal intubation. Data on age; gender; underlying disease; associated comorbidities; time and reason for orotracheal intubation; Glasgow scale on the day of the Speech Therapist assessment; comprehension; vocal quality; presence and severity of dysphagia; risk of bronchoaspiration; and the suggested oral route were collected. The data were analyzed through logistic regression. The level of significance was set at 5%, with a 95% Confidence Interval. The prevalence of dysphagia in this study was 35.9% and the risk of aspiration was 24.9%. As the age increased, the altered vocal quality and the degree of voice impairment increased the risk of the presence of dysphagia by 5-; 45.4- and 6.7-fold, respectively, and of aspiration by 6-; 36.4- and 4.8-fold. The increase in the time of orotracheal intubation increased the risk of aspiration by 5.5-fold. Patients submitted to prolonged intubation who have risk factors associated with dysphagia and aspiration should be submitted to an early speech-language/audiology assessment and receive appropriate and timely treatment. The recognition of these predictive factors by the entire multidisciplinary team can minimize the possibility of clinical complications inherent to the risk of dysphagia and aspiration in extubated patients. Copyright © 2017. Published by Elsevier Editora Ltda.

  19. Effect of prolonged exposure to low antigen concentration for sensitization

    International Nuclear Information System (INIS)

    Och, Francois M.M. van; Vandebriel, Rob J.; Jong, Wim H. de; Loveren, Henk van

    2003-01-01

    The local lymph node assay (LLNA) is an assay in mice to identify potential allergens. Compounds that do not induce a stimulation index (SI)≥3 are not considered sensitizers. Of the chemicals that do, the SI of 3 is used as a benchmark, and indicates the sensitizing potency of a chemical. Compared to the exposure duration of the LLNA (3 days), real life exposure often lasts for months or years. We therefore investigated whether prolonged exposure to sensitizers at concentrations that do not induce a SI≥3 in the LLNA, were able to surpass this threshold. Mice were treated for 2 months at 7-day intervals with a range of concentrations of the known allergens ethyl-p-aminobenzoate (benzocaine, BENZ), 2,4-dinitrochlorobenzene (DNCB), and tetramethyl thiuram disulfide (TMTD). Both proliferative activity and cytokine production were established at day 60. Neither BENZ nor TMTD showed a significant increase in the proliferation rate compared to vehicle controls. Only DNCB at concentrations originally above the EC 3 a significant increase in proliferation was seen after prolonged exposure. No significant effect on IFN-γ and IL-4 production was observed for all three compounds compared. These findings indicate that for classification of sensitizers the shorter exposure period employed in the standard LLNA is sufficient, and longer periods of exposure have no bearing on this classification

  20. New Heterogeneous Clustering Protocol for Prolonging Wireless Sensor Networks Lifetime

    Directory of Open Access Journals (Sweden)

    Md. Golam Rashed

    2014-06-01

    Full Text Available Clustering in wireless sensor networks is one of the crucial methods for increasing of network lifetime. The network characteristics of existing classical clustering protocols for wireless sensor network are homogeneous. Clustering protocols fail to maintain the stability of the system, especially when nodes are heterogeneous. We have seen that the behavior of Heterogeneous-Hierarchical Energy Aware Routing Protocol (H-HEARP becomes very unstable once the first node dies, especially in the presence of node heterogeneity. In this paper we assume a new clustering protocol whose network characteristics is heterogeneous for prolonging of network lifetime. The computer simulation results demonstrate that the proposed clustering algorithm outperforms than other clustering algorithms in terms of the time interval before the death of the first node (we refer to as stability period. The simulation results also show the high performance of the proposed clustering algorithm for higher values of extra energy brought by more powerful nodes.

  1. Interval stability for complex systems

    Science.gov (United States)

    Klinshov, Vladimir V.; Kirillov, Sergey; Kurths, Jürgen; Nekorkin, Vladimir I.

    2018-04-01

    Stability of dynamical systems against strong perturbations is an important problem of nonlinear dynamics relevant to many applications in various areas. Here, we develop a novel concept of interval stability, referring to the behavior of the perturbed system during a finite time interval. Based on this concept, we suggest new measures of stability, namely interval basin stability (IBS) and interval stability threshold (IST). IBS characterizes the likelihood that the perturbed system returns to the stable regime (attractor) in a given time. IST provides the minimal magnitude of the perturbation capable to disrupt the stable regime for a given interval of time. The suggested measures provide important information about the system susceptibility to external perturbations which may be useful for practical applications. Moreover, from a theoretical viewpoint the interval stability measures are shown to bridge the gap between linear and asymptotic stability. We also suggest numerical algorithms for quantification of the interval stability characteristics and demonstrate their potential for several dynamical systems of various nature, such as power grids and neural networks.

  2. BAG3-related myopathy, polyneuropathy and cardiomyopathy with long QT syndrome.

    Science.gov (United States)

    Kostera-Pruszczyk, Anna; Suszek, Małgorzata; Płoski, Rafał; Franaszczyk, Maria; Potulska-Chromik, Anna; Pruszczyk, Piotr; Sadurska, Elżbieta; Karolczak, Justyna; Kamińska, Anna M; Rędowicz, Maria Jolanta

    2015-12-01

    BAG3 belongs to BAG family of molecular chaperone regulators interacting with HSP70 and anti-apoptotic protein Bcl-2. It is ubiquitously expressed with strong expression in skeletal and cardiac muscle, and is involved in a panoply of cellular processes. Mutations in BAG3 and aberrations in its expression cause fulminant myopathies, presenting with progressive limb and axial muscle weakness, and respiratory insufficiency and neuropathy. Herein, we report a sporadic case of a 15-years old girl with symptoms of myopathy, demyelinating polyneuropathy and asymptomatic long QT syndrome. Genetic testing demonstrated heterozygous mutation Pro209Leu (c.626C > T) in exon 3 of BAG3 gene causing severe myopathy and neuropathy, often associated with restrictive cardiomyopathy. We did not find a mutation in any known LQT syndrome genes. Analysis of muscle biopsy revealed profound disintegration of Z-discs with extensive accumulation of granular debris and large inclusions within fibers. We demonstrated profound alterations in BAG3 distribution as the protein localized to long filamentous structures present across the fibers that were positively stained not only for α-actinin but also for desmin and filamin indicating that those disintegrated Z-disc regions contained also other sarcomeric proteins. The mutation caused a decrease in the content of BAG3 and HSP70, and also of α-actinin desmin, filamin and fast myosin heavy chain, confirming its severe effect on the muscle fiber morphology and thus function. We provide further evidence that BAG3 is associated with Z-disc maintenance, and the Pro209Leu mutation may occur worldwide. We also provide a summary of cases associated with this mutation reported so far.

  3. In silico investigation of the short QT syndrome, using human ventricle models incorporating electromechanical coupling

    Directory of Open Access Journals (Sweden)

    Ismail eAdeniran

    2013-07-01

    Full Text Available Introduction Genetic forms of the Short QT Syndrome (SQTS arise due to cardiac ion channel mutations leading to accelerated ventricular repolarisation, arrhythmias and sudden cardiac death. Results from experimental and simulation studies suggest that changes to refractoriness and tissue vulnerability produce a substrate favourable to re-entry. Potential electromechanical consequences of the SQTS are less well understood. The aim of this study was to utilize electromechanically coupled human ventricle models to explore electromechanical consequences of the SQTS. Methods and results: The Rice et al. mechanical model was coupled to the ten Tusscher et al. ventricular cell model. Previously validated K+ channel formulations for SQT variants 1 and 3 were incorporated. Functional effects of the SQTS mutations on transients, sarcomere length shortening and contractile force at the single cell level were evaluated with and without the consideration of stretch activated channel current (Isac. Without Isac, the SQTS mutations produced dramatic reductions in the amplitude of transients, sarcomere length shortening and contractile force. When Isac was incorporated, there was a considerable attenuation of the effects of SQTS-associated action potential shortening on Ca2+ transients, sarcomere shortening and contractile force. Single cell models were then incorporated into 3D human ventricular tissue models. The timing of maximum deformation was delayed in the SQTS setting compared to control. Conclusion: The incorporation of Isac appears to be an important consideration in modelling functional effects of SQT 1 and 3 mutations on cardiac electro-mechanical coupling. Whilst there is little evidence of profoundly impaired cardiac contractile function in SQTS patients, our 3D simulations correlate qualitatively with reported evidence for dissociation between ventricular repolarization and the end of mechanical systole.

  4. Implantable cardioverter-defibrillator explantation for overdiagnosed or overtreated congenital long QT syndrome.

    Science.gov (United States)

    Gaba, Prakriti; Bos, J Martijn; Cannon, Bryan C; Cha, Yong-Mei; Friedman, Paul A; Asirvatham, Samuel J; Ackerman, Michael J

    2016-04-01

    Primary treatment of long QT syndrome (LQTS) currently consists of beta-blocker therapy, although an implantable cardioverter-defibrillator (ICD) is considered for high-risk patients. However, both overdiagnosis and overtreatment must be avoided because their sequelae can be significant. The purpose of this study was to evaluate the prevalence and details of ICD explants in a cohort of patients from a tertiary genetic heart rhythm clinic for a previously rendered diagnosis of LQTS. Overall, 1227 consecutive patients were included in the study. All patients had been referred to the Mayo Clinic for evaluation of possible LQTS and subsequently were either diagnosed with LQTS or dismissed as normal. Further stratification of patients was conducted to assess how many patients had an ICD and how many had a subsequent ICD explant. In total, 170 patients (14%) had an ICD, including 157 of 670 patients (23%) with confirmed LQTS and 13 of 557 patients (2%) who did not have LQTS. Among these, 12 of 1227 (1%) had the ICD removed: 7 of 157 LQTS patients (4.5%) compared to 5 of 14 non-LQTS patients (36%). Before explant, 5 of 12 patients (42%) experienced inappropriate shocks, ranging from 2 to as many as 54 shocks. In addition, 4 had a device-related infection, and 9 had device malfunction (including lead dysfunction or fracture). None of these patients had a breakthrough cardiac event since removal of their ICD during 5.5 ± 3.5 years of follow-up. Implications of overdiagnosis and overtreatment are profound because unnecessary ICD placement can be associated with infection, malfunction, inappropriate shocks, and subsequent anxiety. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  5. SALIVARY ANTIMICROBIAL PROTEIN RESPONSE TO PROLONGED RUNNING

    Directory of Open Access Journals (Sweden)

    Suzanne Schneider

    2013-01-01

    Full Text Available Prolonged exercise may compromise immunity through a reduction of salivary antimicrobial proteins (AMPs. Salivary IgA (IgA has been extensively studied, but little is known about the effect of acute, prolonged exercise on AMPs including lysozyme (Lys and lactoferrin (Lac. Objective: To determine the effect of a 50-km trail race on salivary cortisol (Cort, IgA, Lys, and Lac. Methods: 14 subjects: (6 females, 8 males completed a 50km ultramarathon. Saliva was collected pre, immediately after (post and 1.5 hrs post race ( 1.5. Results: Lac concentration was higher at 1.5 hrs post race compared to post exercise (p0.05. IgA concentration, secretion rate, and IgA/Osm were lower 1.5 hrs post compared to pre race (p<0.05. Cort concentration was higher at post compared to 1.5 (p<0.05, but was unaltered from pre race levels. Subjects finished in 7.81 ± 1.2 hrs. Saliva flow rate did not differ between time points. Saliva Osm increased at post (p<0.05 compared to pre race. Conclusions: The intensity could have been too low to alter Lys and Lac secretion rates and thus, may not be as sensitive as IgA to changes in response to prolonged running. Results expand our understanding of the mucosal immune system and may have implications for predicting illness after prolonged running.

  6. Prolonged displacement may compromise resilience in Eritrean ...

    African Journals Online (AJOL)

    Objective: to assess the impact of prolonged displacement on the resilience of Eritrean mothers. Methods: an adapted SOC scale (short form) was administered. Complementary qualitative data were gathered from study participants' spontaneous reactions to and commentaries on the SOC scale. Results: Displaced ...

  7. Prolonged Cholestatic Jaundice Associated With Flurbiprofen.

    Science.gov (United States)

    Dogan, Serkan; Celikbilek, Mehmet; Demirkan, Kutay; Yilmaz, Semih; Deniz, Kemal; Gursoy, Sebnem; Yucesoy, Mehmet

    2014-08-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely consumed drugs throughout the world for pain relief. Although the adverse effects of NSAIDs to the liver are well known, flurbiprofen-induced liver cholestasis is extremely rare. Herein, we present a patient with prolonged icterus that is associated with the use of flurbiprofen without causing ductopenia. © The Author(s) 2013.

  8. Hippocampal Abnormalities after Prolonged Febrile Convulsions

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2003-11-01

    Full Text Available Hippocampal volume and T2 relaxation times were determined in an MRI study of 14 children with prolonged febrile convulsions (PFC who were investigated, 1 within 5 days of a PFC, and 2 at follow-up 4-8 months after the acute study, at the Institute of Child Health, University College, and Great Ormond Street Hospital, London, UK.

  9. Acute Right Ventricular Dysfunction Complicating Prolonged ...

    African Journals Online (AJOL)

    We report a case of transient right ventricular dysfunction associated with prolonged cardiac tamponade, an unusual complication of uncertain etiology. We believe that in this case dynamic coronary flow restriction resulted in ischemic injury and stunning of the right ventricle. Other possible causes are briefly reviewed. Right ...

  10. A novel KCNQ1 nonsense variant in the isoform-specific first exon causes both jervell and Lange-Nielsen syndrome 1 and long QT syndrome 1: a case report.

    Science.gov (United States)

    Nishimura, Motoi; Ueda, Marehiko; Ebata, Ryota; Utsuno, Emi; Ishii, Takuma; Matsushita, Kazuyuki; Ohara, Osamu; Shimojo, Naoki; Kobayashi, Yoshio; Nomura, Fumio

    2017-06-08

    According to previous KCNQ1 (potassium channel, voltage gated, KQT-like subfamily, member 1) gene screening studies, missense variants, but not nonsense or frame-shift variants, cause the majority of long QT syndrome (LQTS; Romano-Ward syndrome [RWS]) 1 cases. Several missense variants are reported to cause RWS by a dominant-negative mechanism, and some KCNQ1 variants can cause both Jervell and Lange-Nielsen Syndrome (JLNS; in an autosomal recessive manner) and LQTS1 (in an autosomal dominant manner), while other KCNQ1 variants cause only JLNS. The human KCNQ1 gene is known to have two transcript isoforms (kidney isoform and pancreas isoform), and both isoforms can form a functional cardiac potassium channel. Here, we report a novel nonsense KCNQ1 variant causing not only JLNS, but also significant QTc prolongation identical to RWS in an autosomal dominant manner. Our case study supports that haploinsufficiency in the KCNQ1 gene is causative of significant QTc prolongation identical to RWS. Interestingly, the nonsense variant (NM_000218.2:c.115G > T [p.Glu39X]) locates in exon 1a of KCNQ1, which is a kidney-isoform specific exon. The variant is located closer to the N-terminus than previously identified nonsense or frame-shift variants. To the best of our knowledge, this is the first report showing that a nonsense variant in exon 1a of KCNQ1, which is the kidney-isoform specific exon, causes JLNS. Our findings may be informative to the genetic pathogenesis of RWS and JLNS caused by KCNQ1 variants.

  11. Calving interval and survival breeding values as measure of cow fertility in a pasture based production system with seasonal calving

    NARCIS (Netherlands)

    Olori, V.; Meuwissen, T.H.E.; Veerkamp, R.F.

    2001-01-01

    In a grass-based production system with seasonal calving, fertility is of major economic importance. A delay in conception due to poor fertility prolongs intercalving interval and causes a shift in calving pattern, which can lead to culling. Calving interval (CIV) information is readily available

  12. Licence prolongations of US nuclear power plants; Les prolongations de licence des centrales nucleaires americaines

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2004-04-01

    Licences of US nuclear reactors were initially attributed for a 40 years duration. However, the vast majority of the reactors can benefit of a licence prolongation for a period of 20 years maximum. This article recalls first the procedure to follow for the licence prolongation demands (safety analysis, components aging, environmental impact statement), and then it makes a status of the accepted prolongations, of the demands under examination, and of the demands that should be presented in the next 5 years. (J.S.)

  13. Complex aberrant splicing in the induced pluripotent stem cell-derived cardiomyocytes from a patient with long-QT syndrome carrying KCNQ1-A344Aspl mutation.

    Science.gov (United States)

    Wuriyanghai, Yimin; Makiyama, Takeru; Sasaki, Kenichi; Kamakura, Tsukasa; Yamamoto, Yuta; Hayano, Mamoru; Harita, Takeshi; Nishiuchi, Suguru; Chen, Jiarong; Kohjitani, Hirohiko; Hirose, Sayako; Yokoi, Fumika; Gao, Jingshan; Chonabayashi, Kazuhisa; Watanabe, Ken; Ohno, Seiko; Yoshida, Yoshinori; Kimura, Takeshi; Horie, Minoru

    2018-05-29

    Long-QT syndrome type 1 (LQT1) is caused by mutations in KCNQ1, which encodes the α-subunit of the slow delayed rectifier potassium current (I Ks ) channel. We previously reported that a synonymous mutation, c.1032G>A, p.A344Aspl in KCNQ1 is most commonly identified in the genotyped LQT1 Japanese patients, and the aberrant splicing was analyzed in the lymphocytes isolated from patients' blood samples. However, the mechanisms underlying the observed processes in human cardiomyocytes remains unclear. To establish and analyze patient-specific human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) model carrying KCNQ1-A344Aspl. We generated hiPSCs from the peripheral blood mononuclear cells obtained from an LQT1 patient carrying KCNQ1-A344Aspl. Using the differentiated cardiomyocytes, we analyzed splicing variants and performed electrophysiological studies. We identified seven aberrant RNA variants in A344Aspl-hiPSC-CMs, more complex compared with those in the peripheral lymphocytes. Multi-electrode array analysis revealed that 1 μM isoproterenol significantly prolonged the duration of corrected field potential in A344Aspl-hiPSC-CMs, compared with that in the controls. Additionally, 100 nM E-4031, I Kr blocker, was shown to induce early afterdepolarization-like waveforms in A344Aspl-hiPSC-CMs. Action potential durations (APDs) did not significantly differ between the hiPSC-CM groups. After administrating 500 nM isoproterenol, APDs of A344Aspl-hiPSC-CMs were significantly longer than those of the controls. ML277 and phenylboronic acid, I Ks activators, ameliorated the APDs of hiPSC-CMs. We identified complex aberrant mRNA variants in the A344Aspl-hiPSC-CM model, and successfully recapitulated the clinical phenotypes of the patient with concealed LQT1. This model allows the investigation of the underlying mechanisms and development of novel therapies. Copyright © 2018. Published by Elsevier Inc.

  14. Implementación de un editor gráfico de circuitos eléctricos con Qt

    OpenAIRE

    Martínez Muñoz, León Alberto

    2011-01-01

    Desarrollo de un Editor de Esquemas Eléctricos bajo el lenguaje de programación Qt que permite diseñar circuitos eléctricos para su posterior interpretación con un simulador de redes PLC. El Editor de Esquemas Eléctricos permita dibujar sobre un área de diseño un esquema eléctrico. El usuario dispone de cualquier componente eléctrico que pueda ser encontrado en una vivienda. Permite modificar los parámetros de cada componente utilizando los diferentes menús que ofrece la aplicación y expor...

  15. Grading of Emphysema Is Indispensable for Predicting Prolonged Air Leak After Lung Lobectomy.

    Science.gov (United States)

    Murakami, Junichi; Ueda, Kazuhiro; Tanaka, Toshiki; Kobayashi, Taiga; Hamano, Kimikazu

    2018-04-01

    The aim of this study was to assess the utility of quantitative computed tomography-based grading of emphysema for predicting prolonged air leak after thoracoscopic lobectomy. A consecutive series of 284 patients undergoing thoracoscopic lobectomy for lung cancer was retrospectively reviewed. Prolonged air leak was defined as air leaks lasting 7 days or longer. The grade of emphysema (emphysema index) was defined by the proportion of the emphysematous lung volume (less than -910 HU) to the total lung volume (-600 to -1,024 HU) by a computer-assisted histogram analysis of whole-lung computed tomography scans. The mean length of chest tube drainage was 1.5 days. Fifteen patients (5.3%) presented with prolonged air leak. According to a receiver-operating characteristics curve analysis, the emphysema index was the best predictor of prolonged air leak, with an area under the curve of 0.85 (95% confidence interval: 0.73 to 0.98). An emphysema index of 35% or greater was the best cutoff value for predicting prolonged air leak, with a negative predictive value of 0.99. The emphysema index was the only significant predictor for the length of postoperative chest tube drainage among conventional variables, including the pulmonary function and resected lobe, in both univariate and multivariate analyses. Prolonged air leak resulted in an increased duration of hospitalization (p leak that adversely influences early postoperative outcomes. We must take new measures against prolonged air leak in quantitative computed tomography-based high-risk patients. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  16. Use of a novel transfer function to reduce repolarization interval hysteresis

    Czech Academy of Sciences Publication Activity Database

    Halámek, Josef; Jurák, Pavel; Bunch, T.J.; Lipoldová, J.; Novák, M.; Vondra, Vlastimil; Leinveber, Pavel; Plachý, M.; Kára, T.; Villa, M.; Fráňa, P.; Souček, M.; Somers, V. K.; Asirvatham, S.J.

    2010-01-01

    Roč. 29, č. 1 (2010), s. 23-32 ISSN 1383-875X R&D Projects: GA ČR GA102/08/1129 Institutional research plan: CEZ:AV0Z20650511 Keywords : QT hysteresis * QT/RR coupling * Transfer function * Long QT syndrome Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.228, year: 2010

  17. Landiolol suppression of electrical storm of torsades de pointes in patients with congenital long-QT syndrome type 2 and myocardial ischemia

    Directory of Open Access Journals (Sweden)

    Ryota Kitajima, MD

    2017-10-01

    Full Text Available A 76-year-old man who had been diagnosed with long-QT syndrome type 2 had frequent syncopal attacks. The electrocardiogram was monitored, and frequent torsades de pointes (TdP was detected despite administration of conventional medications: oral propranolol, verapamil, intravenous magnesium sulfate, verapamil, and lidocaine. In contrast, 2 μg/kg/min landiolol could completely suppress TdP. Subsequently, an implantable cardioverter defibrillator was placed, and he was diagnosed with silent myocardial ischemia using myocardial perfusion scintigraphy and coronary angiography. This is the first case report wherein landiolol effectively suppressed TdP due to long-QT syndrome with silent myocardial ischemia.

  18. Generalized Confidence Intervals and Fiducial Intervals for Some Epidemiological Measures

    Directory of Open Access Journals (Sweden)

    Ionut Bebu

    2016-06-01

    Full Text Available For binary outcome data from epidemiological studies, this article investigates the interval estimation of several measures of interest in the absence or presence of categorical covariates. When covariates are present, the logistic regression model as well as the log-binomial model are investigated. The measures considered include the common odds ratio (OR from several studies, the number needed to treat (NNT, and the prevalence ratio. For each parameter, confidence intervals are constructed using the concepts of generalized pivotal quantities and fiducial quantities. Numerical results show that the confidence intervals so obtained exhibit satisfactory performance in terms of maintaining the coverage probabilities even when the sample sizes are not large. An appealing feature of the proposed solutions is that they are not based on maximization of the likelihood, and hence are free from convergence issues associated with the numerical calculation of the maximum likelihood estimators, especially in the context of the log-binomial model. The results are illustrated with a number of examples. The overall conclusion is that the proposed methodologies based on generalized pivotal quantities and fiducial quantities provide an accurate and unified approach for the interval estimation of the various epidemiological measures in the context of binary outcome data with or without covariates.

  19. Severe bradycardia and prolonged hypotension in ciguatera.

    Science.gov (United States)

    Chan, Thomas Yan Keung

    2013-06-01

    Ciguatera results when ciguatoxin-contaminated coral reef fish from tropical or subtropical waters are consumed. The clinical features that present in affected persons are mainly gastrointestinal, neurological, general, and much less commonly, cardiovascular. We report the case of a 50-year-old man who developed the characteristic combination of acute gastrointestinal and neurological symptoms after the consumption of an unidentified coral reef fish head. In addition to those symptoms, he developed dizziness, severe bradycardia (46 bpm) and prolonged hypotension, which required the administration of intravenous atropine and over three days of intravenous fluid replacement with dopamine infusion. Patients with ciguatera can develop severe bradycardia and prolonged hypotension. Physicians should recognise the possible cardiovascular complications of ciguatera and promptly initiate treatment with intravenous atropine, intravenous fluid replacement and inotropic therapy if such complications are observed.

  20. Haemostatic reference intervals in pregnancy

    DEFF Research Database (Denmark)

    Szecsi, Pal Bela; Jørgensen, Maja; Klajnbard, Anna

    2010-01-01

    largely unchanged during pregnancy, delivery, and postpartum and were within non-pregnant reference intervals. However, levels of fibrinogen, D-dimer, and coagulation factors VII, VIII, and IX increased markedly. Protein S activity decreased substantially, while free protein S decreased slightly and total......Haemostatic reference intervals are generally based on samples from non-pregnant women. Thus, they may not be relevant to pregnant women, a problem that may hinder accurate diagnosis and treatment of haemostatic disorders during pregnancy. In this study, we establish gestational age......-20, 21-28, 29-34, 35-42, at active labor, and on postpartum days 1 and 2. Reference intervals for each gestational period using only the uncomplicated pregnancies were calculated in all 391 women for activated partial thromboplastin time (aPTT), fibrinogen, fibrin D-dimer, antithrombin, free protein S...

  1. Variation in Definition of Prolonged Mechanical Ventilation.

    Science.gov (United States)

    Rose, Louise; McGinlay, Michael; Amin, Reshma; Burns, Karen Ea; Connolly, Bronwen; Hart, Nicholas; Jouvet, Philippe; Katz, Sherri; Leasa, David; Mawdsley, Cathy; McAuley, Danny F; Schultz, Marcus J; Blackwood, Bronagh

    2017-10-01

    Consistency of definitional criteria for terminology applied to describe subject cohorts receiving mechanical ventilation within ICU and post-acute care settings is important for understanding prevalence, risk stratification, effectiveness of interventions, and projections for resource allocation. Our objective was to quantify the application and definition of terms for prolonged mechanical ventilation. We conducted a scoping review of studies (all designs except single-case study) reporting a study population (adult and pediatric) using the term prolonged mechanical ventilation or a synonym. We screened 5,331 references, reviewed 539 full-text references, and excluded 120. Of the 419 studies (representing 38 countries) meeting inclusion criteria, 297 (71%) reported data on a heterogeneous subject cohort, and 66 (16%) included surgical subjects only (46 of those 66, 70% cardiac surgery). Other studies described COPD (16, 4%), trauma (22, 5%), neuromuscular (17, 4%), and sepsis (1, 0.2%) cohorts. A total of 741 terms were used to refer to the 419 study cohorts. The most common terms were: prolonged mechanical ventilation (253, 60%), admission to specialized unit (107, 26%), and long-term mechanical ventilation (79, 19%). Some authors (282, 67%) defined their cohorts based on duration of mechanical ventilation, with 154 studies (55%) using this as the sole criterion. We identified 37 different durations of ventilation ranging from 5 h to 1 y, with > 21 d being the most common (28 of 282, 7%). For studies describing a surgical cohort, minimum ventilation duration required for inclusion was ≥ 24 h for 20 of 66 studies (30%). More than half of all studies (237, 57%) did not provide a reason/rationale for definitional criteria used, with only 28 studies (7%) referring to a consensus definition. We conclude that substantial variation exists in the terminology and definitional criteria for cohorts of subjects receiving prolonged mechanical ventilation. Standardization of

  2. Prolonged Exposure: a Rapid Treatment for Phobias

    Science.gov (United States)

    Watson, J. P.; Gaind, R.; Marks, I. M.

    1971-01-01

    Ten adult patients with long-standing specific phobias were treated by prolonged continuous exposure to their phobic objects in fantasy and reality without avoidance. All patients were greatly helped by four to five hours' treatment in two or three sessions, and all improved more after practice than after imaginal sessions. The treatment method is more economical and efficient than other methods described so far. PMID:5539135

  3. Inverse Interval Matrix: A Survey

    Czech Academy of Sciences Publication Activity Database

    Rohn, Jiří; Farhadsefat, R.

    2011-01-01

    Roč. 22, - (2011), s. 704-719 E-ISSN 1081-3810 R&D Projects: GA ČR GA201/09/1957; GA ČR GC201/08/J020 Institutional research plan: CEZ:AV0Z10300504 Keywords : interval matrix * inverse interval matrix * NP-hardness * enclosure * unit midpoint * inverse sign stability * nonnegative invertibility * absolute value equation * algorithm Subject RIV: BA - General Mathematics Impact factor: 0.808, year: 2010 http://www.math.technion.ac.il/iic/ ela / ela -articles/articles/vol22_pp704-719.pdf

  4. Haemostatic reference intervals in pregnancy

    DEFF Research Database (Denmark)

    Szecsi, Pal Bela; Jørgensen, Maja; Klajnbard, Anna

    2010-01-01

    Haemostatic reference intervals are generally based on samples from non-pregnant women. Thus, they may not be relevant to pregnant women, a problem that may hinder accurate diagnosis and treatment of haemostatic disorders during pregnancy. In this study, we establish gestational age-specific refe......Haemostatic reference intervals are generally based on samples from non-pregnant women. Thus, they may not be relevant to pregnant women, a problem that may hinder accurate diagnosis and treatment of haemostatic disorders during pregnancy. In this study, we establish gestational age......-specific reference intervals for coagulation tests during normal pregnancy. Eight hundred one women with expected normal pregnancies were included in the study. Of these women, 391 had no complications during pregnancy, vaginal delivery, or postpartum period. Plasma samples were obtained at gestational weeks 13......-20, 21-28, 29-34, 35-42, at active labor, and on postpartum days 1 and 2. Reference intervals for each gestational period using only the uncomplicated pregnancies were calculated in all 391 women for activated partial thromboplastin time (aPTT), fibrinogen, fibrin D-dimer, antithrombin, free protein S...

  5. Robust misinterpretation of confidence intervals

    NARCIS (Netherlands)

    Hoekstra, Rink; Morey, Richard; Rouder, Jeffrey N.; Wagenmakers, Eric-Jan

    2014-01-01

    Null hypothesis significance testing (NHST) is undoubtedly the most common inferential technique used to justify claims in the social sciences. However, even staunch defenders of NHST agree that its outcomes are often misinterpreted. Confidence intervals (CIs) have frequently been proposed as a more

  6. Interval matrices: Regularity generates singularity

    Czech Academy of Sciences Publication Activity Database

    Rohn, Jiří; Shary, S.P.

    2018-01-01

    Roč. 540, 1 March (2018), s. 149-159 ISSN 0024-3795 Institutional support: RVO:67985807 Keywords : interval matrix * regularity * singularity * P-matrix * absolute value equation * diagonally singilarizable matrix Subject RIV: BA - General Mathematics Impact factor: 0.973, year: 2016

  7. Chaotic dynamics from interspike intervals

    DEFF Research Database (Denmark)

    Pavlov, A N; Sosnovtseva, Olga; Mosekilde, Erik

    2001-01-01

    Considering two different mathematical models describing chaotic spiking phenomena, namely, an integrate-and-fire and a threshold-crossing model, we discuss the problem of extracting dynamics from interspike intervals (ISIs) and show that the possibilities of computing the largest Lyapunov expone...

  8. The in vivo study on the radiobiologic effect of prolonged delivery time to tumor control in C57BL mice implanted with Lewis lung cancer

    International Nuclear Information System (INIS)

    Wang, Xin; Xiong, Xiao-Peng; Lu, Jiade; Zhu, Guo-Pei; He, Shao-Qin; Hu, Chao-Su; Ying, Hong-Mei

    2011-01-01

    High-precision radiation therapy techniques such as IMRT or sterotactic radiosurgery, delivers more complex treatment fields than conventional techniques. The increased complexity causes longer dose delivery times for each fraction. The purpose of this work is to explore the radiobiologic effect of prolonged fraction delivery time on tumor response and survival in vivo. 1-cm-diameter Lewis lung cancer tumors growing in the legs of C57BL mice were used. To evaluate effect of dose delivery prolongation, 18 Gy was divided into different subfractions. 48 mice were randomized into 6 groups: the normal control group, the single fraction with 18 Gy group, the two subfractions with 30 min interval group, the seven subfractions with 5 min interval group, the two subfractions with 60 min interval group and the seven subfractions with 10 min interval group. The tumor growth tendency, the tumor growth delay and the mice survival time were analyzed. The tumor growth delay of groups with prolonged delivery time was shorter than the group with single fraction of 18 Gy (P < 0.05). The tumor grow delay of groups with prolonged delivery time 30 min was longer than that of groups with prolonged delivery time 60 min P < 0.05). There was no significant difference between groups with same delivery time (P > 0.05). Compared to the group with single fraction of 18 Gy, the groups with prolonged delivery time shorten the mice survival time while there was no significant difference between the groups with prolonged delivery time 30 min and the groups with prolonged delivery time 60 min. The prolonged delivery time with same radiation dose shorten the tumor growth delay and survival time in the mice implanted with Lewis lung cancer. The anti-tumor effect decreased with elongation of the total interfractional time

  9. Prolonged labour as indication for emergency caesarean section

    DEFF Research Database (Denmark)

    Maaløe, Nanna; Sorensen, B L; Onesmo, R

    2012-01-01

    To audit the quality of obstetric management preceding emergency caesarean sections for prolonged labour.......To audit the quality of obstetric management preceding emergency caesarean sections for prolonged labour....

  10. Can parents adjust to the idea that their child is at risk for a sudden death?: Psychological impact of risk for Long QT Syndrome

    NARCIS (Netherlands)

    Hendriks, Karin S. W. H.; Grosfeld, F. J. M.; van Tintelen, J. P.; van Langen, I. M.; Wilde, A. A. M.; van den Bout, J.; ten Kroode, H. F. J.

    2005-01-01

    Can a parent adjust to the idea that its child is at risk for a sudden death? This question is raised by a diagnostic procedure in which children were tested for an inherited Long QT Syndrome (LQTS). This potentially life-threatening but treatable cardiac arrhythmia syndrome may cause sudden death,

  11. Can parents adjust to the idea that their child is at risk for a sudden death? : Psychological impact of risk for Long QT Syndrome

    NARCIS (Netherlands)

    Hendriks, Karin S. W. H.; Grosfeld, FJM; van Tintelen, JP; van Langen, IM; Wilde, AAM; van den Bout, J; ten Kroode, HFJ

    2005-01-01

    Can a parent adjust to the idea that its child is at risk for a sudden death? This question is raised by a diagnostic procedure in which children were tested for an inherited Long QT Syndrome (LQTS). This potentially life-threatening but treatable cardiac arrhythmia syndrome may cause sudden death,

  12. Mutations in conserved amino acids in the KCNQ1 channel and risk of cardiac events in type-1 long-QT syndrome

    DEFF Research Database (Denmark)

    Jons, Christian; Moss, Arthur J; Lopes, Coeli M

    2009-01-01

    BACKGROUND: Type-1 long-QT syndrome (LQT1) is caused by mutations in the KCNQ1 gene. The purpose of this study was to investigate whether KCNQ1 mutations in highly conserved amino acid residues within the voltage-gated potassium channel family are associated with an increased risk of cardiac even...

  13. Long QT 1 mutation KCNQ1A344V increases local anesthetic sensitivity of the slowly activating delayed rectifier potassium current

    DEFF Research Database (Denmark)

    Siebrands, Cornelia C; Binder, Stephan; Eckhoff, Ulrike

    2006-01-01

    BACKGROUND: Anesthesia in patients with long QT syndrome (LQTS) is a matter of concern. Congenital LQTS is most frequently caused by mutations in KCNQ1 (Kv7.1), whereas drug-induced LQTS is a consequence of HERG (human ether-a-go-go-related gene) channel inhibition. The aim of this study was to i...

  14. Laryngotracheal Injury following Prolonged Endotracheal Intubation

    Directory of Open Access Journals (Sweden)

    J. Mehdizadeh

    2006-07-01

    Full Text Available Background: Prolonged endotracheal intubation is a growing method for supporting ventilation in patients who require intensive care. Despite considerable advancement in endotracheal intubation, this method still has some complications; the most important is laryngo-tracheal injuries. Methods: Over a 2-year period, this retrospective study was conducted on 57 patients with history of prolonged intubation who were referred to the ENT Department of Amir Alam Hospital. For each patient, a complete evaluation including history, physical examination, and direct laryngoscopy and bronchoscopy was done under general anesthesia. Results: Fifty-seven patients (44 male; mean age, 23.014.7 years were studied. Mean intubation period was 15.88 days. The most common presenting symptom was dyspnea (62%. Head trauma was responsible for most cases of intubation (72.4%. The most common types of tracheal and laryngeal lesions were tracheal (56.9% and subglottic (55.2% stenosis, respectively. Mean length of tracheal stenosis was 0.810.83 cm. There was a statistically significant relationship between length of tracheal stenosis and intubation period (P=0.0001 but no relation was observed between tracheal stenosis and age, sex, and etiology of intubation (All P=NS. Among the glottic lesions, inter- arytenoids adhesion was the most common lesion (25.9%. No statistically significant relation was found between glottic and subglottic lesions and age, sex and intubation period (all P=NS. Length of stenosis and intubation period was significantly greater in tracheal/ subglottic lesions than those in glottic/ supraglottic lesions (all P=NS. Conclusion: After prolonged endotracheal intubation, laryngo-tracheal lesions had no relation with patient’s age, sex, and cause of intubation.There was direct relation between length of tracheal stenosis and intubation period. Glottic lesions were more commonly observed in head trauma patients. Lesion length and intubation

  15. Risk management of QTc-prolongation in patients receiving haloperidol: an epidemiological study in a University hospital in Belgium.

    Science.gov (United States)

    Vandael, Eline; Vandenberk, Bert; Vandenberghe, Joris; Spriet, Isabel; Willems, Rik; Foulon, Veerle

    2016-04-01

    Many drugs, including haloperidol, are linked with a risk of QTc-prolongation, which can lead to Torsade de Pointes and sudden cardiac death. To investigate the prevalence of concomitant risk factors for QTc-prolongation in patients treated with haloperidol, and the use of safety measures to minimize this risk. University Hospitals of Leuven, Belgium. Methods A retrospective epidemiological study was performed. On 15 consecutive Mondays, all patients with a prescription for haloperidol were included. A risk score for QTc-prolongation, inspired by the pro-QTc score of Haugaa et al., was calculated based on gender, comorbidities, lab results and concomitant QTc-prolonging drugs (each factor counting for one point). Available electrocardiograms before and during the treatment of haloperidol were registered. Management of the risk of QTc-prolongation. Two hundred twenty-two patients were included (59.0 % men, median age 77 years) of whom 26.6 % had a risk score of ≥4 (known to significantly increase the mortality). Overall, 24.3 % received haloperidol in combination with other drugs with a known risk of Torsade de Pointes. Half of the patients had an electrocardiogram in the week before the start of haloperidol; only in one-third a follow-up electrocardiogram during haloperidol treatment was performed. Of the patients with a moderately (n = 41) or severely (n = 14) prolonged QTc-interval before haloperidol, 48.8 % and 42.9 % respectively had a follow-up electrocardiogram. In patients with a risk score ≥4, significantly more electrocardiograms were taken before starting haloperidol (p = 0.020). Although many patients had risk factors for QTc-prolongation (including the use of other QTc-prolonging drugs) or had a prolonged QTc on a baseline electrocardiogram, follow-up safety measures were limited. Persistent efforts should be taken to develop decision support systems to manage this risk.

  16. Interval timing in genetically modified mice: a simple paradigm.

    Science.gov (United States)

    Balci, F; Papachristos, E B; Gallistel, C R; Brunner, D; Gibson, J; Shumyatsky, G P

    2008-04-01

    We describe a behavioral screen for the quantitative study of interval timing and interval memory in mice. Mice learn to switch from a short-latency feeding station to a long-latency station when the short latency has passed without a feeding. The psychometric function is the cumulative distribution of switch latencies. Its median measures timing accuracy and its interquartile interval measures timing precision. Next, using this behavioral paradigm, we have examined mice with a gene knockout of the receptor for gastrin-releasing peptide that show enhanced (i.e. prolonged) freezing in fear conditioning. We have tested the hypothesis that the mutants freeze longer because they are more uncertain than wild types about when to expect the electric shock. The knockouts however show normal accuracy and precision in timing, so we have rejected this alternative hypothesis. Last, we conduct the pharmacological validation of our behavioral screen using d-amphetamine and methamphetamine. We suggest including the analysis of interval timing and temporal memory in tests of genetically modified mice for learning and memory and argue that our paradigm allows this to be done simply and efficiently.

  17. Topical Drug Formulations for Prolonged Corneal Anesthesia

    Science.gov (United States)

    Wang, Liqiang; Shankarappa, Sahadev A.; Tong, Rong; Ciolino, Joseph B.; Tsui, Jonathan H.; Chiang, Homer H.; Kohane, Daniel S.

    2013-01-01

    Purpose Ocular local anesthetics (OLA’s) currently used in routine clinical practice for corneal anesthesia are short acting and their ability to delay corneal healing makes them unsuitable for long-term use. In this study, we examined the effect on the duration of corneal anesthesia of the site-1 sodium channel blocker tetrodotoxin (TTX), applied with either proparacaine or the chemical permeation enhancer OTAB. The effect of test solutions on corneal healing was also studied. Methods Solutions of TTX, proparacaine, and OTAB, singly or in combination were applied topically to the rat cornea. The blink response, an indirect measure of corneal sensitivity, was recorded using a Cochet-Bonnet esthesiometer, and the duration of corneal anesthesia calculated. The effect of test compounds on the rate of corneal epithelialization was studied in vivo following corneal debridement. Results Combination of TTX and proparacaine resulted in corneal anesthesia that was 8–10 times longer in duration than that from either drug administered alone, while OTAB did not prolong anesthesia. The rate of corneal healing was moderately delayed following co-administration of TTX and proparacaine. Conclusion Co-administration of TTX and proparacaine significantly prolonged corneal anesthesia but in view of delayed corneal re-epithelialization, caution is suggested in use of the combination. PMID:23615270

  18. Characterization of Myocardial Repolarization Reserve in Adolescent Females With Anorexia Nervosa.

    Science.gov (United States)

    Padfield, Gareth J; Escudero, Carolina A; DeSouza, Astrid M; Steinberg, Christian; Gibbs, Karen; Puyat, Joseph H; Lam, Pei Yoong; Sanatani, Shubhayan; Sherwin, Elizabeth; Potts, James E; Sandor, George; Krahn, Andrew D

    2016-02-09

    Patients with anorexia nervosa exhibit abnormal myocardial repolarization and are susceptible to sudden cardiac death. Exercise testing is useful in unmasking QT prolongation in disorders associated with abnormal repolarization. We characterized QT adaptation during exercise in anorexia. Sixty-one adolescent female patients with anorexia nervosa and 45 age- and sex-matched healthy volunteers performed symptom-limited cycle ergometry during 12-lead ECG monitoring. Changes in the QT interval during exercise were measured, and QT/RR-interval slopes were determined by using mixed-effects regression modeling. Patients had significantly lower body mass index than controls; however, resting heart rates and QT/QTc intervals were similar at baseline. Patients had shorter exercise times (13.7±4.5 versus 20.6±4.5 minutes; Panorexia nervosa. © 2016 American Heart Association, Inc.

  19. Statistical intervals a guide for practitioners

    CERN Document Server

    Hahn, Gerald J

    2011-01-01

    Presents a detailed exposition of statistical intervals and emphasizes applications in industry. The discussion differentiates at an elementary level among different kinds of statistical intervals and gives instruction with numerous examples and simple math on how to construct such intervals from sample data. This includes confidence intervals to contain a population percentile, confidence intervals on probability of meeting specified threshold value, and prediction intervals to include observation in a future sample. Also has an appendix containing computer subroutines for nonparametric stati

  20. QT/RR hysteresis as a function of RR excitation – implications for risk

    Czech Academy of Sciences Publication Activity Database

    Halámek, Josef; Jurák, Pavel; Somers, V. K.; Nykodým, J.; Leinveber, P.; Fráňa, P.; Eisenberger, M.; Kára, T.

    2005-01-01

    Roč. 4, č. 1 (2005), s. 98 [World Congress on Heart Disease - New Trends in Research, Diagnosis and Treatment /12./. 16.07.2005-19.07.2005, Vancouver] Institutional research plan: CEZ:AV0Z20650511 Keywords : ventricular repolarization * RR intervals Subject RIV: FA - Cardiovascular Disease s incl. Cardiotharic Surgery

  1. Generation of human induced pluripotent stem cell line from a patient with a long QT syndrome type 2

    Directory of Open Access Journals (Sweden)

    Azra Fatima

    2016-03-01

    Full Text Available We report here the generation of human iPS cell line UKKi009-A from dermal fibroblasts of a patient carrying heterozygous mutation c.3035-3045delTCCCTCGATGC, p.Leu1012Pro (fs*55 in KCNH2 gene leading to long QT syndrome type 2 (LQT2. We used the Sleeping Beauty transposon-based plasmids expressing OSKM along with microRNAs 307/367 to reprogram the fibroblasts. The iPS cells possess pluripotent stem cell characteristics and differentiate to cell lineages of all three germ layers. This cell line can serve as a source for in vitro modeling of LQT2. This cell line is distributed by the European Collection of Authenticated Cell Cultures (ECACC.

  2. Dijets at large rapidity intervals

    CERN Document Server

    Pope, B G

    2001-01-01

    Inclusive diet production at large pseudorapidity intervals ( Delta eta ) between the two jets has been suggested as a regime for observing BFKL dynamics. We have measured the dijet cross section for large Delta eta in pp collisions at square root s = 1800 and 630 GeV using the DOE detector. The partonic cross section increases strongly with the size of Delta eta . The observed growth is even stronger than expected on the basis of BFKL resummation in the leading logarithmic approximation. The growth of the partonic cross section can be accommodated with an effective BFKL intercept of alpha /sub BFKL/(20 GeV) = 1.65 +or- 0.07.

  3. Variational collocation on finite intervals

    International Nuclear Information System (INIS)

    Amore, Paolo; Cervantes, Mayra; Fernandez, Francisco M

    2007-01-01

    In this paper, we study a set of functions, defined on an interval of finite width, which are orthogonal and which reduce to the sinc functions when the appropriate limit is taken. We show that these functions can be used within a variational approach to obtain accurate results for a variety of problems. We have applied them to the interpolation of functions on finite domains and to the solution of the Schroedinger equation, and we have compared the performance of the present approach with others

  4. Electrocardiogram PR Interval Is a Surrogate Marker to Predict New Occurrence of Atrial Fibrillation in Patients with Frequent Premature Atrial Contractions.

    Science.gov (United States)

    Chun, Kwang Jin; Hwang, Jin Kyung; Choi, So Ra; Park, Seung-Jung; On, Young Keun; Kim, June Soo; Park, Kyoung-Min

    2016-04-01

    The clinical significance of prolonged PR interval has not been evaluated in patients with frequent premature atrial contractions (PACs). We investigated whether prolonged PR interval could predict new occurrence of atrial fibrillation (AF) in patients with frequent PACs. We retrospectively analyzed 684 patients with frequent PACs (> 100 PACs/day) who performed repeated 24-hour Holter monitoring. Prolonged PR interval was defined as longer than 200 msec. Among 684 patients, 626 patients had normal PR intervals (group A) and 58 patients had prolonged PR intervals (group B). After a mean follow-up of 59.3 months, 14 patients (24.1%) in group B developed AF compared to 50 patients (8.0%) in group A (P PR interval (hazard ratio [HR], 1.950; 95% CI, 1.029-3.698; P = 0.041), age (HR, 1.033; 95% CI, 1.006-1.060; P = 0.015), and left atrial (LA) dimension (HR, 1.061; 95% CI, 1.012-1.112; P = 0.015) were associated with AF occurrence. Prolonged PR interval, advanced age, and enlarged LA dimension are independent risk factors of AF occurrence in patients with frequent PACs.

  5. Role of PR-Interval In Predicting the Occurrence of Atrial Fibrillation

    DEFF Research Database (Denmark)

    Bidstrup, Signe Brøker; Salling Olesen, Morten; Hastrup Svendsen, Jesper

    2013-01-01

    The identification of individuals at high risk of developing atrial fibrillation (AF) is important to prevent potentially lethal and invalidating complications of this arrhythmia. Recently, several studies have investigated the association between PR-interval and the risk of AF and have tested...... the value of PR-interval in personalized risk scores for AF. However, the results of these studies are generally conflicting. When looking for an association between a prolonged PR-interval (first-degree atrioventricular [AV] block vs. normal PR-interval) and an increased risk of AF, not all studies were...... able to find a consistent and statistically significant association. In two recent studies, however, the investigators were able to show an increased risk of AF for individuals with PR-intervals in the short range compared with individuals in the middle range. The existence of a true U...

  6. Prolonged toxicity from Kambo cleansing ritual.

    Science.gov (United States)

    Li, Kai; Horng, Howard; Lynch, Kara; Smollin, Craig G

    2018-04-02

    Kambo cleanse is a purification, cleansing ritual traditionally performed by South American shaman to confer luck and health to hunters. We report a patient who presented to the emergency department with prolonged symptoms of vomiting, flushing, facial swelling, altered mental status, and agitation requiring chemical restraints, 22 h after a Kambo cleanse. The patient was found with four small, circular, superficial burns to the ankle at the site where the resin was introduced. The cleanse consists of rubbing resin obtained from the secretions of the giant leaf frog (Phyllomedusa bicolor) into superficial wounds to produce intense gastrointestinal symptoms followed by a sensation of increased stamina and strength. The cleanse is now being increasingly performed in Europe and USA.

  7. Bywalled plasma formation in vacuum prolonged channels

    International Nuclear Information System (INIS)

    Korenev, S.A.; Rubin, N.B.

    1982-01-01

    To produce homogeneous along the channel length plasma the application of incomplete rate-in surface dielectric discharge for generating the bywalled plasma in prolonged cylindrical channels at a pressure of the residual gas of P approximately 10 -5 Torr is proposed. Experimental set-up consisted of a pulse voltage generator and a plasma channel. The plasma channel was a coaxial system of three tubes inserted into each other. The first outer tube is made of a stainless steel, the second - of a dielectric material, the third - of smallsized stainless steel greed. It is demonstrated that the plasma being formed in the process is sufficiently homogeneous by concentration of the components, by the channel length and azimuth. The length of the experimental channel under investigation was 1.6 m, its diameter amounted 0.05 m. The maximum concentration of electron component was 10 17 m -3

  8. Neurohumoral responses during prolonged exercise in humans

    DEFF Research Database (Denmark)

    Nybo, Lars; Nielsen, Bodil; Blomstrand, Eva

    2003-01-01

    This study examined neurohumoral alterations during prolonged exercise with and without hyperthermia. The cerebral oxygen-to-carbohydrate uptake ratio (O2/CHO = arteriovenous oxygen difference divided by arteriovenous glucose difference plus one-half lactate), the cerebral balances of dopamine......, and the metabolic precursor of serotonin, tryptophan, were evaluated in eight endurance-trained subjects during exercise randomized to be with or without hyperthermia. The core temperature stabilized at 37.9 +/- 0.1 degrees C (mean +/- SE) in the control trial, whereas it increased to 39.7 +/- 0.2 degrees C...... in the hyperthermic trial, with a concomitant increase in perceived exertion (P exercise trials. Both the arterial and jugular venous dopamine levels...

  9. Prolonged grieving after abortion: a descriptive study.

    Science.gov (United States)

    Brown, D; Elkins, T E; Larson, D B

    1993-01-01

    Although flawed by methodological problems, the research literature tends to provide support for the assumption that induced abortion in the 1st trimester is not accompanied by enduring negative psychological sequelae. In cases where such sequelae are reported, the morbidity is attributed to a pre-existing psychiatric condition or circumstances precipitating the choice of abortion. However, detailed descriptive letters from 45 women prepared in response to a request by a pastor of an upper-middle-class Protestant congregation in Florida indicate that prolonged grieving after abortion may be more widespread phenomenon than previously believed. Letter writers ranged in age from 25-60 years; 75% were unmarried at the time of the procedure and 29% aborted before the legalization of abortion in the US. The most frequently cited long-term sequela, especially among those who felt coerced to abort, was a continued feeling of guilt. Fantasies about the aborted fetus was the next most frequently mentioned experience. Half of the letter writers referred to their abortions, as "murder" and 44% voiced regret about their decision to abort. Other long-term effects included depression (44%), feelings of loss (31%), shame (27%), and phobic responses to infants (13%). For 42% of these women, the adverse psychological effects of abortion endured over 10 years. Since letter-writers came from a self-selected population group with a known bias against abortion and only negative experiences were solicited, these experiences must be regarded as subjectives and anecdotal. However, they draw attention to the need for methodologically sound studies of a possible prolonged grief syndrome among a small percentage of women who have abortions, especially when coercion is involved.

  10. Effects of parenteral administration of enrofloxacin on electrocardiographic parameters in hospitalized dogs

    Directory of Open Access Journals (Sweden)

    Carlos Fernando Agudelo Ramírez

    2012-01-01

    Full Text Available The effect of enrofloxacin on the QT interval of the electrocardiogram was studied in 30 hospitalized dogs. The experimental group (n = 15 received enrofloxacin parenterally (subcutaneously at a dose of 5 mg/kg twice daily and amoxicillin-clavulanate intravenously at a dose of 22 mg/kg three times daily. The control group (n = 15 received only amoxicillin-clavulanate. Electrocardiography was carried out for 5 min once daily for 6 days. The QT interval was corrected by four different formulae. No differences were found between the two groups or within each group for the duration of the study. On the last day of the study the average QT interval for the control and experimental groups was 213.2 ms and 202.9 ms, respectively. Enrofloxacin did not cause prolongation of the QT or corrected QT intervals. We can conclude that the parenteral administration of enrofloxacin in non-cardiac dogs does not adversely affect the electrocardiographic indicators (no prolongation of the QT or corrected QT interval and does not induce ventricular arrhythmias. Parenteral use of enrofloxacin is thus safe and effective in non-cardiac dogs.

  11. Prolonged thromboprophylaxis with low molecular weight heparin for abdominal or pelvic surgery

    DEFF Research Database (Denmark)

    Rasmussen, Morten Schnack; Jørgensen, Lars Nannestad; Wille-Jørgensen, Peer

    2009-01-01

    BACKGROUND: Major abdominal and pelvic surgery carries a high risk of venous thromboembolism (VTE). The efficacy of thromboprophylaxis with low-molecular weight heparin (LMWH) administered during the in-hospital period is well documented, but the optimal duration of thromboprophylaxis after surgery...... evaluating prolonged thromboprophylaxis with LMWH as compared to control or placebo. 133 studies were found in the searches, of which only 4 were found eligible for inclusion, and 129 were excluded. The incidence of overall VTE after major abdominal or pelvic surgery was 14.3% (95% confidence interval 11...... significant reduction of even the incidence of symptomatic VTE from 1.7% (95% CI 0.8% - 3.4%) in the control group to 0.2 % (95% CI 0.0% - 1.2%) in patients receiving prolonged thromboprophylaxis, Peto Odds ratio 0.22 (95% CI 0.06 -0.80), P = 0.02. The respective incidence of bleeding in the control and LMWH...

  12. In vivo effects of the IKr agonist NS3623 on cardiac electrophysiology of the guinea pig

    DEFF Research Database (Denmark)

    Hansen, Rie Schultz; Olesen, Søren-Peter; Rønn, Lars Christian B

    2008-01-01

    to examining the in vivo effects of NS3623. Injection of 30 mg/kg NS3623 shortened the corrected QT interval by 25 +/- 4% in anaesthetized guinea pigs. Accordingly, 50 mg/kg of NS3623 shortened the QT interval by 30 +/- 6% in conscious guinea pigs. Finally, pharmacologically induced QT prolongation by a h......ERG channel antagonist (0.15 mg/kg E-4031) could be reverted by injection of NS3623 (50 mg/kg) in conscious guinea pigs. In conclusion, the present in vivo study demonstrates that injection of the hERG channel agonist NS3623 results in shortening of the QTc interval as well as reversal of a pharmacologically...... induced QT prolongation in both anaesthetized and conscious guinea pigs....

  13. Some Characterizations of Convex Interval Games

    NARCIS (Netherlands)

    Brânzei, R.; Tijs, S.H.; Alparslan-Gok, S.Z.

    2008-01-01

    This paper focuses on new characterizations of convex interval games using the notions of exactness and superadditivity. We also relate big boss interval games with concave interval games and obtain characterizations of big boss interval games in terms of exactness and subadditivity.

  14. False sense of safety by daily QTc interval monitoring during methadone IVPCA titration in a patient with chronic pain

    Directory of Open Access Journals (Sweden)

    Miranda-Grajales H

    2013-05-01

    Full Text Available Hector Miranda-Grajales, Joy Hao, Ricardo A CrucianiDepartment of Pain Medicine and Palliative Care, Beth Israel Medical Center, New York, NY, USAAbstract: It has been proposed that some deaths attributed to methadone are related to prolongation of the QTc interval; however, there are no clear recommendations on electrocardiogram (ECG monitoring in patients undergoing intravenous methadone infusion. This is a report on a patient receiving methadone intravenous patient-controlled analgesia titration for the treatment of chronic pain. Initially, her daily ECGs showed QTc intervals within normal limits; however, she experienced a rapid increase in QTc interval from 317 ms to 784 ms within a 24-hour period after methadone had been discontinued for excessive sedation. QTc interval greater than 500 ms is considered to be high risk for the fatal arrhythmia Torsades de Pointes. Daily ECGs did not detect a gradual increase in the QTc interval that would have alerted the medical staff of the need to decrease or stop the methadone before reaching a prolonged QTc interval associated with cardiotoxicity. In selected cases where aggressive methadone titration is required, more intensive monitoring, such as telemetry or ECG determinations every 12 hours, might help detect changes in QTc interval duration that might otherwise be missed by daily ECG determinations.Keywords: methadone, QTc prolongation, opioids, opioid side effects, IVPCA methadone

  15. Assessment of Interspecies Differences in Drug-Induced QTc Interval Prolongation in Cynomolgus Monkeys, Dogs and Humans.

    NARCIS (Netherlands)

    Dubois, V.F.S.; Witte, de W.E.A.; Visser, S.A.; Danhof, M.; Della, Pasqua O.

    2016-01-01

    BACKGROUND AND PURPOSE The selection of the most suitable animal species and subsequent translation of the concentration-effect relationship to humans are critical steps for accurate assessment of the pro-arrhythmic risk of candidate molecules. The objective of this investigation was to assess

  16. The Presence or Absence of QTc Prolongation in Buprenorphine-Naloxone Among Youth with Opioid Dependence

    Science.gov (United States)

    Poole, Sabrina A.; Pecoraro, Anna; Subramaniam, Geetha; Woody, George; Vetter, Victoria L

    2015-01-01

    Objective To evaluate buprenorphine-naloxone effects on the QTc in youth with opioid dependence. Buprenorphine is a partial agonist that is an effective treatment for opioid dependence. Compared to methadone it has a lower risk of QTc prolongation in adults but is less well studied in youth. It may also reduce the risk for torsades de pointes (TdP) an uncommon variant of polymorphic ventricular tachycardia, that can result in syncope, ventricular fibrillation, and sudden death. Methods Secondary analysis of ECG data from 95 subjects who participated in a multi-site trial for youth with opioid dependence. Subjects were randomized to a 2-week (DETOX), or a 12-week course of buprenorphine-naloxone (BUP). 12-lead ECGs were done at baseline, weeks 4 and 12, and QTc intervals were hand measured and calculated using Bazett's formula. Increases > 60 milliseconds (ms) were considered clinically significant, and readings > 450 ms (males) and 470 ms (females) indicated a prolonged QTc. Results Mean QTc intervals were higher for BUP than DETOX participants at baseline, week 4, and week 12 (p = 0.045), and females had longer mean QTc intervals than males (p DETOX patients. Minimal changes in the QTc were seen at 4 and 12-weeks in a few patients in both groups. There was no evidence that buprenorphine-naloxone alone increased the QTc to a level that increased the risk for TdP. PMID:26690291

  17. Presence or Absence of QTc Prolongation in Buprenorphine-Naloxone Among Youth With Opioid Dependence.

    Science.gov (United States)

    Poole, Sabrina A; Pecoraro, Anna; Subramaniam, Geetha; Woody, George; Vetter, Victoria L

    2016-01-01

    The aim of the study was to evaluate buprenorphine-naloxone effects on the QTc in youth with opioid dependence. Buprenorphine is a partial agonist that is an effective treatment for opioid dependence. Compared with methadone, it has a lower risk of QTc prolongation in adults, but is less studied in the youth. It may also reduce the risk of torsades de pointes (TdP)--an uncommon variant of polymorphic ventricular tachycardia--that can result in syncope, ventricular fibrillation, and sudden death. Secondary analysis of the electrocardiogram data from 95 individuals who participated in a multisite trial for youth with opioid dependence. The participants were randomized to a 2-week (DETOX) or a 12-week course of buprenorphine-naloxone (BUP). At baseline, 12-lead electrocardiograms were done at weeks 4 and 12, and QTc intervals were hand-measured and calculated using Bazett formula. Increases above 60 milliseconds were considered clinically significant, and readings above 450 milliseconds (in men) and 470 milliseconds (in women) indicated a prolonged QTc. Mean QTc intervals were higher for BUP than for DETOX participants at baseline, week 4, and week 12 (P = 0.045), and women had longer mean QTc intervals than men (P DETOX patients. Minimal changes in the QTc were seen at 4 and 12 weeks in a few patients in both groups. There was no evidence that buprenorphine-naloxone alone increased the QTc to a level that increased the risk for TdP.

  18. Does UTI cause prolonged jaundice in otherwise well infants?

    Science.gov (United States)

    Chowdhury, Tanzila; Kisat, Hamudi; Tullus, Kjell

    2015-07-01

    The symptoms of urinary tract infections in infants are very non-specific and have historically included prolonged hyperbilirubinaemia. We studied the results of routine urine samples in 319 infants with prolonged jaundice. Convincing findings of UTI was not found in any of these children even if one of them was treated with antibiotics after four consecutive urine cultures with different bacteria. A urine culture might thus not be an appropriate investigation in a child with prolonged jaundice without any other symptoms of UTI. • The symptoms of UTI in infancy are very non-specific. • Old studies suggest that prolonged hyperbilirubinaemia is one such symptom; more modern studies give more conflicting results. What is New: • Our study could not confirm that children with prolonged jaundice have an increased risk of UTI. • Routine urine testing is thus not needed in otherwise healthy infants with prolonged jaundice.

  19. Prolonged response without prolonged chemotherapy: a lesson from PCV chemotherapy in low-grade gliomas

    Science.gov (United States)

    Peyre, Matthieu; Cartalat-Carel, Stéphanie; Meyronet, David; Ricard, Damien; Jouvet, Anne; Pallud, Johan; Mokhtari, Karima; Guyotat, Jacques; Jouanneau, Emmanuel; Sunyach, Marie-Pierre; Frappaz, Didier; Honnorat, Jérôme; Ducray, François

    2010-01-01

    Previous studies with temozolomide suggest that a prolonged duration of chemotherapy is important for treating low-grade gliomas (LGGs). PCV (procarbazine, CCNU, vincristine) chemotherapy has demonstrated efficacy in treating LGGs, but this therapy cannot be used for a prolonged period because of the cumulative toxicity. The aim of the present study was to evaluate the impact of first-line PCV chemotherapy on LGGs growth kinetics. The mean tumor diameter (MTD) of 21 LGGs was measured on serial magnetic resonance images before (n=13), during, and after PCV onset (n=21). During PCV treatment, a decrease in the MTD was observed in all patients. After PCV discontinuation, an ongoing decrease in MTD was observed in 20 of the 21 patients. Median duration of the MTD decrease was 3.4 years (range, 0.8–7.7) after PCV onset and 2.7 years (range, 0–7) after the end of PCV treatment with 60% of LGGs, demonstrating an ongoing and prolonged (>2 years) response despite chemotherapy no longer being administered. According to McDonald's criteria, the rates of partial and minor responses were 5% and 38% at the end of PCV but 38% and 42% at the time of maximal MTD decrease, which occurred after a median period of 3.4 years after PCV onset. These results challenge the idea that a prolonged duration of chemotherapy is necessary for treating LGGs and raise the issue of understanding the mechanisms involved in the persistent tumor volume decrease once chemotherapy is terminated. PMID:20488959

  20. Fermionic covariant prolongation structure theory for supernonlinear evolution equation

    International Nuclear Information System (INIS)

    Cheng Jipeng; Wang Shikun; Wu Ke; Zhao Weizhong

    2010-01-01

    We investigate the superprincipal bundle and its associated superbundle. The super(nonlinear)connection on the superfiber bundle is constructed. Then by means of the connection theory, we establish the fermionic covariant prolongation structure theory of the supernonlinear evolution equation. In this geometry theory, the fermionic covariant fundamental equations determining the prolongation structure are presented. As an example, the supernonlinear Schroedinger equation is analyzed in the framework of this fermionic covariant prolongation structure theory. We obtain its Lax pairs and Baecklund transformation.

  1. Robust misinterpretation of confidence intervals.

    Science.gov (United States)

    Hoekstra, Rink; Morey, Richard D; Rouder, Jeffrey N; Wagenmakers, Eric-Jan

    2014-10-01

    Null hypothesis significance testing (NHST) is undoubtedly the most common inferential technique used to justify claims in the social sciences. However, even staunch defenders of NHST agree that its outcomes are often misinterpreted. Confidence intervals (CIs) have frequently been proposed as a more useful alternative to NHST, and their use is strongly encouraged in the APA Manual. Nevertheless, little is known about how researchers interpret CIs. In this study, 120 researchers and 442 students-all in the field of psychology-were asked to assess the truth value of six particular statements involving different interpretations of a CI. Although all six statements were false, both researchers and students endorsed, on average, more than three statements, indicating a gross misunderstanding of CIs. Self-declared experience with statistics was not related to researchers' performance, and, even more surprisingly, researchers hardly outperformed the students, even though the students had not received any education on statistical inference whatsoever. Our findings suggest that many researchers do not know the correct interpretation of a CI. The misunderstandings surrounding p-values and CIs are particularly unfortunate because they constitute the main tools by which psychologists draw conclusions from data.

  2. The in vivo study on the radiobiologic effect of prolonged delivery time to tumor control in C57BL mice implanted with Lewis lung cancer

    Directory of Open Access Journals (Sweden)

    Zhu Guo-Pei

    2011-01-01

    Full Text Available Abstract Background High-precision radiation therapy techniques such as IMRT or sterotactic radiosurgery, delivers more complex treatment fields than conventional techniques. The increased complexity causes longer dose delivery times for each fraction. The purpose of this work is to explore the radiobiologic effect of prolonged fraction delivery time on tumor response and survival in vivo. Methods 1-cm-diameter Lewis lung cancer tumors growing in the legs of C57BL mice were used. To evaluate effect of dose delivery prolongation, 18 Gy was divided into different subfractions. 48 mice were randomized into 6 groups: the normal control group, the single fraction with 18 Gy group, the two subfractions with 30 min interval group, the seven subfractions with 5 min interval group, the two subfractions with 60 min interval group and the seven subfractions with 10 min interval group. The tumor growth tendency, the tumor growth delay and the mice survival time were analyzed. Results The tumor growth delay of groups with prolonged delivery time was shorter than the group with single fraction of 18 Gy (P 0.05. Compared to the group with single fraction of 18 Gy, the groups with prolonged delivery time shorten the mice survival time while there was no significant difference between the groups with prolonged delivery time 30 min and the groups with prolonged delivery time 60 min. Conclusions The prolonged delivery time with same radiation dose shorten the tumor growth delay and survival time in the mice implanted with Lewis lung cancer. The anti-tumor effect decreased with elongation of the total interfractional time.

  3. Carbohydrate Dependence During Prolonged, Intense Endurance Exercise.

    Science.gov (United States)

    Hawley, John A; Leckey, Jill J

    2015-11-01

    A major goal of training to improve the performance of prolonged, continuous, endurance events lasting up to 3 h is to promote a range of physiological and metabolic adaptations that permit an athlete to work at both higher absolute and relative power outputs/speeds and delay the onset of fatigue (i.e., a decline in exercise intensity). To meet these goals, competitive endurance athletes undertake a prodigious volume of training, with a large proportion performed at intensities that are close to or faster than race pace and highly dependent on carbohydrate (CHO)-based fuels to sustain rates of muscle energy production [i.e., match rates of adenosine triphosphate (ATP) hydrolysis with rates of resynthesis]. Consequently, to sustain muscle energy reserves and meet the daily demands of training sessions, competitive athletes freely select CHO-rich diets. Despite renewed interest in high-fat, low-CHO diets for endurance sport, fat-rich diets do not improve training capacity or performance, but directly impair rates of muscle glycogenolysis and energy flux, limiting high-intensity ATP production. When highly trained athletes compete in endurance events lasting up to 3 h, CHO-, not fat-based fuels are the predominant fuel for the working muscles and CHO, not fat, availability becomes rate limiting for performance.

  4. Prolonged disengagement from distractors near the hands

    Directory of Open Access Journals (Sweden)

    Daniel B Vatterott

    2013-08-01

    Full Text Available Because items near our hands are often more important than items far from our hands, the brain processes visual items near our hands differently than items far from our hands. Multiple experiments have attributed this processing difference to spatial attention, but the exact mechanism behind how spatial attention near our hands changes is still under investigation. The current experiments sought to differentiate between two of the proposed mechanisms: a prioritization of the space near the hands and a prolonged disengagement of spatial attention near the hands. To differentiate between these two accounts, we used the additional singleton paradigm in which observers searched for a shape singleton among homogenously shaped distractors. On half the trials, one of the distractors was a different color. Both the prioritization and disengagement accounts predict differently colored distractors near the hands will slow target responses more than differently colored distractors far from the hands, but the prioritization account also predicts faster responses to targets near the hands than far from the hands. The disengagement account does not make this prediction, because attention does not need to be disengaged when the target appears near the hand. We found support for the disengagement account: Salient distractors near the hands slowed responses more than those far from the hands, yet observers did not respond faster to targets near the hands.

  5. Using the confidence interval confidently.

    Science.gov (United States)

    Hazra, Avijit

    2017-10-01

    Biomedical research is seldom done with entire populations but rather with samples drawn from a population. Although we work with samples, our goal is to describe and draw inferences regarding the underlying population. It is possible to use a sample statistic and estimates of error in the sample to get a fair idea of the population parameter, not as a single value, but as a range of values. This range is the confidence interval (CI) which is estimated on the basis of a desired confidence level. Calculation of the CI of a sample statistic takes the general form: CI = Point estimate ± Margin of error, where the margin of error is given by the product of a critical value (z) derived from the standard normal curve and the standard error of point estimate. Calculation of the standard error varies depending on whether the sample statistic of interest is a mean, proportion, odds ratio (OR), and so on. The factors affecting the width of the CI include the desired confidence level, the sample size and the variability in the sample. Although the 95% CI is most often used in biomedical research, a CI can be calculated for any level of confidence. A 99% CI will be wider than 95% CI for the same sample. Conflict between clinical importance and statistical significance is an important issue in biomedical research. Clinical importance is best inferred by looking at the effect size, that is how much is the actual change or difference. However, statistical significance in terms of P only suggests whether there is any difference in probability terms. Use of the CI supplements the P value by providing an estimate of actual clinical effect. Of late, clinical trials are being designed specifically as superiority, non-inferiority or equivalence studies. The conclusions from these alternative trial designs are based on CI values rather than the P value from intergroup comparison.

  6. Direct Interval Forecasting of Wind Power

    DEFF Research Database (Denmark)

    Wan, Can; Xu, Zhao; Pinson, Pierre

    2013-01-01

    This letter proposes a novel approach to directly formulate the prediction intervals of wind power generation based on extreme learning machine and particle swarm optimization, where prediction intervals are generated through direct optimization of both the coverage probability and sharpness...

  7. A note on birth interval distributions

    International Nuclear Information System (INIS)

    Shrestha, G.

    1989-08-01

    A considerable amount of work has been done regarding the birth interval analysis in mathematical demography. This paper is prepared with the intention of reviewing some probability models related to interlive birth intervals proposed by different researchers. (author). 14 refs

  8. Cardiac time intervals by tissue Doppler imaging M-mode echocardiography

    DEFF Research Database (Denmark)

    Biering-Sørensen, Tor

    2016-01-01

    for myocardial myocytes to achieve an LV pressure equal to that of aorta increases, resulting in a prolongation of the isovolumic contraction time (IVCT). Furthermore, the ability of myocardial myocytes to maintain the LV pressure decreases, resulting in reduction in the ejection time (ET). As LV diastolic...... of whether the LV is suffering from impaired systolic or diastolic function. A novel method of evaluating the cardiac time intervals has recently evolved. Using tissue Doppler imaging (TDI) M-mode through the mitral valve (MV) to estimate the cardiac time intervals may be an improved method reflecting global...

  9. Optimal Data Interval for Estimating Advertising Response

    OpenAIRE

    Gerard J. Tellis; Philip Hans Franses

    2006-01-01

    The abundance of highly disaggregate data (e.g., at five-second intervals) raises the question of the optimal data interval to estimate advertising carryover. The literature assumes that (1) the optimal data interval is the interpurchase time, (2) too disaggregate data causes a disaggregation bias, and (3) recovery of true parameters requires assumption of the underlying advertising process. In contrast, we show that (1) the optimal data interval is what we call , (2) too disaggregate data do...

  10. An Adequate First Order Logic of Intervals

    DEFF Research Database (Denmark)

    Chaochen, Zhou; Hansen, Michael Reichhardt

    1998-01-01

    This paper introduces left and right neighbourhoods as primitive interval modalities to define other unary and binary modalities of intervals in a first order logic with interval length. A complete first order logic for the neighbourhood modalities is presented. It is demonstrated how the logic can...... support formal specification and verification of liveness and fairness, and also of various notions of real analysis....

  11. Consistency and refinement for Interval Markov Chains

    DEFF Research Database (Denmark)

    Delahaye, Benoit; Larsen, Kim Guldstrand; Legay, Axel

    2012-01-01

    Interval Markov Chains (IMC), or Markov Chains with probability intervals in the transition matrix, are the base of a classic specification theory for probabilistic systems [18]. The standard semantics of IMCs assigns to a specification the set of all Markov Chains that satisfy its interval...

  12. Multivariate interval-censored survival data

    DEFF Research Database (Denmark)

    Hougaard, Philip

    2014-01-01

    Interval censoring means that an event time is only known to lie in an interval (L,R], with L the last examination time before the event, and R the first after. In the univariate case, parametric models are easily fitted, whereas for non-parametric models, the mass is placed on some intervals, de...

  13. Prolonged Screen Viewing Times and Sociodemographic Factors among Pregnant Women: A Cross-Sectional Survey in China.

    Science.gov (United States)

    Xu, Xianglong; Liu, Dengyuan; Rao, Yunshuang; Zeng, Huan; Zhang, Fan; Wang, Lu; Xie, Yaojie; Sharma, Manoj; Zhao, Yong

    2018-02-27

    Objectives: This study aimed to assess the prevalence of prolonged television, computer, and mobile phone viewing times and examined related sociodemographic factors among Chinese pregnant women. Methods: In this study, a cross-sectional survey was implemented among 2400 Chinese pregnant women in 16 hospitals of 5 provinces from June to August in 2015, and the response rate of 97.76%. We excluded women with serious complications and cognitive disorders. The women were asked about their television, computer, and mobile phone viewing during pregnancy. Prolonged television watching or computer viewing was defined as spending more than two hours on television or computer viewing per day. Prolonged mobile phone viewing was watching more than one hour on mobile phone per day. Results: Among 2345 pregnant women, about 25.1% reported prolonged television viewing, 20.6% reported prolonged computer viewing, and 62.6% reported prolonged mobile phone viewing. Pregnant women with long mobile phone viewing times were likely have long TV (Estimate = 0.080, Standard Error ( SE ) = 0.016, p women with long TV (Estimate = 0.134, SE = 0.027, p women with long TV viewing times were less likely to have long computer viewing times (Estimate = -0.032, SE = 0.015, p = 0.035), and pregnant women with long computer viewing times were less likely have long TV viewing times (Estimate = -0.059, SE = 0.028, p = 0.035). Pregnant women in their second pregnancy had lower prolonged computer viewing times than those in their first pregnancy (Odds Ratio (OR) 0.56, 95% Confidence Interval (CI) 0.42-0.74). Pregnant women in their second pregnancy were more likely have longer prolonged mobile phone viewing times than those in their first pregnancy ( OR 1.25, 95% CI 1.01-1.55). Conclusions: The high prevalence rate of prolonged TV, computer, and mobile phone viewing times was common for pregnant women in their first and second pregnancy. This study preliminarily explored the relationship between

  14. Prolonged Screen Viewing Times and Sociodemographic Factors among Pregnant Women: A Cross-Sectional Survey in China

    Directory of Open Access Journals (Sweden)

    Xianglong Xu

    2018-02-01

    Full Text Available Objectives: This study aimed to assess the prevalence of prolonged television, computer, and mobile phone viewing times and examined related sociodemographic factors among Chinese pregnant women. Methods: In this study, a cross-sectional survey was implemented among 2400 Chinese pregnant women in 16 hospitals of 5 provinces from June to August in 2015, and the response rate of 97.76%. We excluded women with serious complications and cognitive disorders. The women were asked about their television, computer, and mobile phone viewing during pregnancy. Prolonged television watching or computer viewing was defined as spending more than two hours on television or computer viewing per day. Prolonged mobile phone viewing was watching more than one hour on mobile phone per day. Results: Among 2345 pregnant women, about 25.1% reported prolonged television viewing, 20.6% reported prolonged computer viewing, and 62.6% reported prolonged mobile phone viewing. Pregnant women with long mobile phone viewing times were likely have long TV (Estimate = 0.080, Standard Error (SE = 0.016, p < 0.001 and computer viewing times (Estimate = 0.053, SE = 0.022, p = 0.015. Pregnant women with long TV (Estimate = 0.134, SE = 0.027, p < 0.001 and long computer viewing times (Estimate = 0.049, SE = 0.020, p = 0.015 were likely have long mobile phone viewing times. Pregnant women with long TV viewing times were less likely to have long computer viewing times (Estimate = −0.032, SE = 0.015, p = 0.035, and pregnant women with long computer viewing times were less likely have long TV viewing times (Estimate = −0.059, SE = 0.028, p = 0.035. Pregnant women in their second pregnancy had lower prolonged computer viewing times than those in their first pregnancy (Odds Ratio (OR 0.56, 95% Confidence Interval (CI 0.42–0.74. Pregnant women in their second pregnancy were more likely have longer prolonged mobile phone viewing times than those in their first pregnancy (OR 1.25, 95

  15. Cryo-EM Structure of a KCNQ1/CaM Complex Reveals Insights into Congenital Long QT Syndrome.

    Science.gov (United States)

    Sun, Ji; MacKinnon, Roderick

    2017-06-01

    KCNQ1 is the pore-forming subunit of cardiac slow-delayed rectifier potassium (I Ks ) channels. Mutations in the kcnq1 gene are the leading cause of congenital long QT syndrome (LQTS). Here, we present the cryoelectron microscopy (cryo-EM) structure of a KCNQ1/calmodulin (CaM) complex. The conformation corresponds to an "uncoupled," PIP 2 -free state of KCNQ1, with activated voltage sensors and a closed pore. Unique structural features within the S4-S5 linker permit uncoupling of the voltage sensor from the pore in the absence of PIP 2 . CaM contacts the KCNQ1 voltage sensor through a specific interface involving a residue on CaM that is mutated in a form of inherited LQTS. Using an electrophysiological assay, we find that this mutation on CaM shifts the KCNQ1 voltage-activation curve. This study describes one physiological form of KCNQ1, depolarized voltage sensors with a closed pore in the absence of PIP 2 , and reveals a regulatory interaction between CaM and KCNQ1 that may explain CaM-mediated LQTS. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. The importance of the family history in caring for families with long QT syndrome and dilated cardiomyopathy.

    Science.gov (United States)

    Ruiter, Jolien S; Berkenbosch-Nieuwhof, Karin; van den Berg, Maarten P; van Dijk, Rene; Middel, Berrie; van Tintelen, J Peter

    2010-03-01

    In potentially inherited cardiac diseases, the family history is of great importance. We looked at the way cardiologists take a family history in patients with idiopathic dilated cardiomyopathy (DCM) or long QT syndrome (LQTS) and whether this led to screening of relatives or other follow-up. We performed retrospective cross-sectional analyses of adult index patients with DCM or LQTS in a general hospital (GH) or a University Medical Center (UMC). We identified 82 index patients with DCM (34 GH; 48 UMC) and 20 with LQTS (all UMC) between 1996 and 2005. Mean follow-up was 58 months. A family history was recorded in 90% of both LQTS and DCM patients most of the cases restricted to first-degree family members. The genetic aspects, counseling and screening of family members was discussed significantly more often with LQTS than DCM patients (all P family members, DNA analysis and referral) was performed significantly more often in LQTS than DCM patients. Cardiologists in the UMC referred DCM index patients for genetic counseling more often than those in the GH (25% vs. 6%; P familial. Since early recognition and treatment may reduce morbidity and mortality we recommend cardiologists take a more thorough family history and always consider referring to a clinical genetics department in such index patients. (c) 2010 Wiley-Liss, Inc.

  17. Electrical PR Interval Variation Predicts New Occurrence of Atrial Fibrillation in Patients With Frequent Premature Atrial Contractions.

    Science.gov (United States)

    Chun, Kwang Jin; Hwang, Jin Kyung; Park, Seung-Jung; On, Young Keun; Kim, June Soo; Park, Kyoung-Min

    2016-04-01

    Atrial fibrillation (AF) is associated with the autonomic nervous system (ANS), and fluctuation of autonomic tone is more prominent in patients with AF. As autonomic tone affects the heart rate (HR), and there is an inverse relationship between HR and PR interval, PR interval variation could be greater in patients with AF than in those without AF. The purpose of this study was to investigate the correlation between PR interval variation and new-onset AF in patients with frequent PACs.We retrospectively enrolled 207 patients with frequent PACs who underwent electrocardiographs at least 4 times during the follow-up period. The PR variation was calculated by subtracting the minimum PR interval from the maximum PR interval. The outcomes were new occurrence of AF and all-cause mortality during the follow-up period.During a median follow-up of 8.3 years, 24 patients (11.6%) developed new-onset AF. Univariate analysis showed that prolonged PR interval (PR interval > 200 ms, P = 0.021), long PR variation (PR variation > 36.5 ms, P = 0.018), and PR variation (P = 0.004) as a continuous variable were associated with an increased risk of AF. Cox regression analysis showed that prolonged PR interval (hazard ratio = 3.321, 95% CI 1.064-10.362, P = 0.039) and PR variation (hazard ratio = 1.013, 95% CI 1.002-1.024, P = 0.022) were independent predictors for new-onset AF. However, PR variation and prolonged PR interval were not associated with all-cause mortality (P = 0.465 and 0.774, respectively).PR interval variation and prolonged PR interval are independent risk factors for new-onset AF in patients with frequent PACs. However we were unable to determine a cut-off value of PR interval variation for new-onset AF.

  18. Probability Distribution for Flowing Interval Spacing

    International Nuclear Information System (INIS)

    Kuzio, S.

    2001-01-01

    The purpose of this analysis is to develop a probability distribution for flowing interval spacing. A flowing interval is defined as a fractured zone that transmits flow in the Saturated Zone (SZ), as identified through borehole flow meter surveys (Figure 1). This analysis uses the term ''flowing interval spacing'' as opposed to fractured spacing, which is typically used in the literature. The term fracture spacing was not used in this analysis because the data used identify a zone (or a flowing interval) that contains fluid-conducting fractures but does not distinguish how many or which fractures comprise the flowing interval. The flowing interval spacing is measured between the midpoints of each flowing interval. Fracture spacing within the SZ is defined as the spacing between fractures, with no regard to which fractures are carrying flow. The Development Plan associated with this analysis is entitled, ''Probability Distribution for Flowing Interval Spacing'', (CRWMS M and O 2000a). The parameter from this analysis may be used in the TSPA SR/LA Saturated Zone Flow and Transport Work Direction and Planning Documents: (1) ''Abstraction of Matrix Diffusion for SZ Flow and Transport Analyses'' (CRWMS M and O 1999a) and (2) ''Incorporation of Heterogeneity in SZ Flow and Transport Analyses'', (CRWMS M and O 1999b). A limitation of this analysis is that the probability distribution of flowing interval spacing may underestimate the effect of incorporating matrix diffusion processes in the SZ transport model because of the possible overestimation of the flowing interval spacing. Larger flowing interval spacing results in a decrease in the matrix diffusion processes. This analysis may overestimate the flowing interval spacing because the number of fractures that contribute to a flowing interval cannot be determined from the data. Because each flowing interval probably has more than one fracture contributing to a flowing interval, the true flowing interval spacing could be

  19. Levo-α-acetylmethadol (LAAM induced QTc-prolongation - results from a controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Wieneke H

    2009-01-01

    Full Text Available Abstract Background Due to potential proarrhythmic side-effects levo-α-Acetylmethadol (LAAM is currently not available in EU countries as maintenance drug in the treatment of opiate addiction. However, recent studies and meta-analyses underline the clinical advantages of LAAM with respect to the reduction of heroin use. Thus a reappraisal of LAAM has been demanded. The aim of the present study was to evaluate the relative impact of LAAM on QTc-interval, as a measure of pro-arrhythmic risk, in comparison to methadone, the current standard in substitution therapy. Methods ECG recordings were analysed within a randomized, controlled clinical trial evaluating the efficacy and tolerability of maintenance treatment with LAAM compared with racemic methadone. Recordings were done at two points: 1 during a run-in period with all patients on methadone and 2 24 weeks after randomisation into methadone or LAAM treatment group. These ECG recordings were analysed with respect to QTc-values and QTc-dispersion. Mean values as well as individual changes compared to baseline parameters were evaluated. QTc-intervals were classified according to CPMP-guidelines. Results Complete ECG data sets could be obtained in 53 patients (31 LAAM-group, 22 methadone-group. No clinical cardiac complications were observed in either group. After 24 weeks, patients receiving LAAM showed a significant increase in QTc-interval (0.409 s ± 0.022 s versus 0.418 s ± 0.028 s, p = 0.046, whereas no significant changes could be observed in patients remaining on methadone. There was no statistically significant change in QTc-dispersion in either group. More patients with borderline prolonged and prolonged QTc-intervals were observed in the LAAM than in the methadone treatment group (n = 7 vs. n = 1; p = 0.1. Conclusions In this controlled trial LAAM induced QTc-prolongation in a higher degree than methadone. Given reports of severe arrhythmic events, careful ECG-monitoring is recommended

  20. Correct Bayesian and frequentist intervals are similar

    International Nuclear Information System (INIS)

    Atwood, C.L.

    1986-01-01

    This paper argues that Bayesians and frequentists will normally reach numerically similar conclusions, when dealing with vague data or sparse data. It is shown that both statistical methodologies can deal reasonably with vague data. With sparse data, in many important practical cases Bayesian interval estimates and frequentist confidence intervals are approximately equal, although with discrete data the frequentist intervals are somewhat longer. This is not to say that the two methodologies are equally easy to use: The construction of a frequentist confidence interval may require new theoretical development. Bayesians methods typically require numerical integration, perhaps over many variables. Also, Bayesian can easily fall into the trap of over-optimism about their amount of prior knowledge. But in cases where both intervals are found correctly, the two intervals are usually not very different. (orig.)