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Corrected QT Interval (corrected + qt_interval)
Selected AbstractsAn Evaluation of the Impact of Oral Magnesium Lactate on the Corrected QT Interval of Patients Receiving Sotalol or Dofetilide to Prevent Atrial or Ventricular Tachyarrhythmia RecurrenceANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 2 2006Brian F. McBride Pharm.D. Background: Intravenous magnesium reduces the QTc interval of patients receiving ibutilide. Whether oral magnesium can reduce the QTc interval associated with oral sotalol and dofetilide is not known. This study was undertaken to evaluate the impact of oral magnesium on the QTc interval and whether an inherent intracellular magnesium deficiency exists among patients with arrhythmias. Methods: Participants receiving sotalol or dofetilide for atrial or ventricular arrhythmias were randomized to receive magnesium l -lactate (504 mg elemental magnesium daily, Niche Pharmaceuticals, Roanoke, TX) or placebo for 48 hours. A 12-lead electrocardiogram (ECG) was obtained at baseline, 3 hours, and 51 hours after dosing to correspond to the Tmax after oral ingestion. The QTc interval was measured from the ECGs and compared between groups. Intracellular magnesium concentrations were determined by energy-dispersive x-ray analysis at baseline and 51 hours after dosing (Intracellular Diagnostics, Inc., Foster City, CA). Results: The QTc interval reductions from baseline were greater in the magnesium group than placebo at 3 and 51 hours (P = 0.015 and P < 0.001, respectively). Sixty-three percent of patients (regardless of experimental group) had baseline intracellular magnesium concentrations below the normal reference range of 33.9,41.9 mEq/IU, with an average level of 32.6 ± 2.2 mEq/IU. Conclusions: Oral magnesium l -lactate raises intracellular magnesium concentrations and lowers the QTc interval of patients receiving sotalol or dofetilide. [source] Patients with Metabolic Syndrome Have Prolonged Corrected QT Interval (QTc)CLINICAL CARDIOLOGY, Issue 12 2009Weiju Li MD Abstract Background Prolongation of corrected QT interval (QTc) increases morbidity and mortality and QTc has been found to be longer in patients with diabetes mellitus than in healthy controls. It is still inconclusive whether the metabolic syndrome results in QTc prolongation. Hypothesis We hypothesized that metabolic syndrome might contribute to risk of QTc prolongation. The hypothesis was tested in a large population. Methods A total of 5,815 individuals (men: 1,950, women: 3,865 aged 20,80 years) were enrolled. Metabolic syndrome was defined according to the revised third National Cholesterol Education Program Adult Treatment Panel (NCEP-ATP III). QTc was calculated by using Bazett and Fridericia equations and the corrected JT interval (JTc) was derived by subtracting the QRS duration from the QTcB. All individuals had physical examinations, electrocardiograms, echocardiography, and blood tests. Results Individuals with metabolic syndrome had longer QTcs and JTc than those without metabolic syndrome (439.84 ms versus 430.90 ms in men, 456.37 ms versus 445.12 ms in women, respectively, p < 0.001 using Bazett formula). The more the number of abnormal metabolic parameters they had, the longer the QTcs and JTc they had. Trend analysis indicated that QTcB, QTcF, and JTc were significantly correlated to the number of abnormal metabolic parameters both in men and in women. After being adjusted for conventional risk factors, QTcB, QTcF, and JTc remained negatively associated with serum potassium concentration and positively associated with interventricular septal thickness. Conclusions Metabolic syndrome is a risk factor for prolonged QTc, which may further increase cardiovascular morbidity and mortality in the subjects with metabolic syndrome. Copyright © 2009 Wiley Periodicals, Inc. [source] Prevalence and clinical relevance of corrected QT interval prolongation during methadone and buprenorphine treatment: a mortality assessment studyADDICTION, Issue 6 2009Katinka Anchersen ABSTRACT Aims To determine the prevalence of corrected QT interval (QTc) prolongation among patients in opioid maintenance treatment (OMT) and to investigate mortality potentially attributable to QTc prolongation in the Norwegian OMT programme. Participants and setting Two hundred OMT patients in Oslo were recruited to the QTc assessment study between October 2006 and August 2007. The Norwegian register of all patients receiving OMT in Norway (January 1997,December 2003) and the national death certificate register were used to assess mortality. Mortality records were examined for the 90 deaths that had occurred among 2382 patients with 6450 total years in OMT. Design and measures The QTc interval was assessed by electrocardiography (ECG). All ECGs were examined by the same cardiologist, who was blind to patient history and medication. Mortality was calculated by cross-matching the OMT register and the national death certificate register: deaths that were possibly attributable to QTc prolongation were divided by the number of patient-years in OMT. Findings In the QTc assessment sample (n = 200), 173 patients (86.5%) received methadone and 27 (13.5%) received buprenorphine. In the methadone group, 4.6% (n = 8) had a QTc above 500 milliseconds; 15% (n = 26) had a QTc interval above 470 milliseconds; and 28.9% (n = 50) had a QTc above 450 milliseconds. All patients receiving buprenorphine (n = 27) had QTc results <450 milliseconds. A positive dose-dependent association was identified between QTc length and dose of methadone, and all patients with a QTc above 500 milliseconds were taking methadone doses of 120 mg or more. OMT patient mortality, where QTc prolongation could not be excluded as the cause of death, was 0.06/100 patient-years. Only one death among 3850 OMT initiations occurred within the first month of treatment. Conclusion Of the methadone patients, 4.6% had QTc intervals above 500 milliseconds. The maximum mortality attributable to QTc prolongation was low: 0.06 per 100 patient-years. [source] Clinical Course and Risk Stratification of Patients Affected with the Jervell and Lange-Nielsen SyndromeJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 11 2006ILAN GOLDENBERG M.D. Introduction: Data regarding risk factors and clinical course of patients affected with Jervell and Lange-Nielsen syndrome (JLNS), an autosomal recesssive form of the congenital long-QT syndrome (LQTS), are limited to several reported cases and a retrospective analysis. Methods and Results: We prospectively followed-up 44 JLNS patients from the U.S. portion of the International LQTS Registry and compared their clinical course with 2,174 patients with the phenotypically determined dominant form of LQTS (Romano-Ward syndrome [RWS]) and a subgroup of 285 patients with type 1 LQTS (LQT1). Mean (±SD) corrected QT interval (QTc) in the JLNS, RWS, and LQT1 groups were 548 ± 73, 500 ± 48, and 502 ± 46 msec, respectively (P < 0.001). The cumulative rates of cardiac events from birth through age 40 among JLNS and RWS patients were 93% (mean [±SD] age: 5.0 ± 7.0 years) and 54% (mean [±SD] age: 14.2 ± 9.3 years), respectively (P < 0.001). The JLNS:RWS and JLNS:LQT1 adjusted hazard ratios (HR) for cardiac events were highest among patients with a baseline QTc ,550 msec (HR = 15.83 [P < 0.001] and 13.80 [P < 0.001], respectively). Among JLNS patients treated with beta-blockers, the cumulative probability of LQTS-related death was 35%; defibrillator therapy was associated with a 0% mortality rate during a mean (±SD) follow-up period of 4.9 ± 3.4 years. Conclusions: Patients with JLNS experience a high rate of cardiac and fatal events from early childhood despite medical therapy. Defibrillator therapy appears to improve outcome in this high-risk population, although longer follow-up is needed to establish its long-term efficacy. [source] Acute Effects of Low Doses of Red Wine on Cardiac Conduction and Repolarization in Young Healthy SubjectsALCOHOLISM, Issue 12 2009Matteo Cameli Background:, Moderate to high blood concentrations of ethanol have been shown to yield acute changes in cardiac electrophysiological properties, but the effect of low concentrations have never been assessed. The role of concomitant changes in clinical variables or cardiac dimensions is also still unknown. This study aimed at exploring the acute effects of low doses of ethanol, administered as Italian red wine, on conduction, depolarization, and repolarization electrocardiographic (ECG) intervals in a population of healthy subjects. Methods:, Forty healthy young volunteers drank a low quantity of red wine (5 ml/kg), and an equal volume of fruit juice in separate experiments. Heart rate, P-wave duration, PR interval, QRS duration, QT interval, corrected QT interval, QT dispersion, and corrected QT dispersion were assessed at baseline and after 60 minutes from challenge. Results:, Mean blood ethanol concentration after drinking was 0.48 ± 0.06 g/l. Compared to the control challenge, significant changes after red wine intake were observed in P-wave duration (from 101 ± 11 to 108 ± 14 milliseconds, p = 0.0006), PR interval (from 153 ± 15 to 167 ± 17 milliseconds, p < 0.0001), QT interval (from 346 ± 28 to 361 ± 24 milliseconds, p < 0.0001), and corrected QT interval (from 388 ± 24 to 402 ± 30 milliseconds, p = 0.0006). None of these changes showed correlations with modifications in clinical or echocardiographic variables. In multivariate analyses aimed at exploring predictors of ECG changes, none of the variables entered the final models. Conclusions:, Low doses of red wine acutely slow cardiac conduction and prolong repolarization in normal individuals. These changes are poorly predictable. The potential arrhythmogenic impact of these effects is worthy of exploration. [source] Post induction arrhythmia in a renal patient: an unexpected risk factorANAESTHESIA, Issue 4 2009A. Srivastava Summary A 44 year-old woman was anaesthetised for a transplant nephrectomy. About 10 min after induction of anaesthesia she had several runs of ventricular tachycardia followed by ventricular fibrillation requiring 30 s of cardiopulmonary resuscitation, after which she reverted to sinus rhythm. Review of her chest X-ray, suggested that the haemodialysis catheter (PermcathÔ) position may have precipitated this event. However, subsequent investigation found that she had toxic serum levels of sotalol, with a prolonged corrected QT interval on the electrocardiogram. She was started on sotalol while her renal graft was functioning well but it was not reviewed when the graft started to fail and she had to commence haemodialysis. This led to the accumulation of sotalol and explains her serum sotalol value of 7.1 mg.l,1 on the day of the event. Concentrations greater than 2.5 mg.l,1 are generally considered toxic. [source] Automatic Extraction of ECG Strips from Continuous 12-lead Holter Recordings for QT Analysis at Prescheduled versus Optimized Time PointsANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 2009Fabio Badilini Ph.D. Background: Continuous 12-lead ECG monitoring (Holter) in early-phase pharmaceutical studies is today widely used as an ideal platform to extract discrete ECGs for analysis. The extraction process is typically performed manually by trained readers using commercial Holter processing systems. Methods: Antares, a novel method for automatic 12-lead extraction from continuous Holter recordings applying minimal noise criteria and heart-rate stability conditions is presented. A set of 12-lead Holter recordings from healthy subjects administered with sotalol is used to compare ECG extractions at fixed time points with ECG extractions generated by Antares optimizing noise and heart rate inside 5 minute windows centered around each expected time point of interest. Results: Global, low- and high-frequency noise content of extracted ECGs was significantly reduced via optimized approach by Antares. Heart rate was also slightly reduced (from 69 ± 13 to 64 ± 13 bpm, P < 0.05). Similarly, the corrected QT interval from optimized extractions was significantly reduced (QTcB from 414 ± 32 to 402 ± 30 ms, P < 0.05). Using only baseline data, and after adjusting for intersubject variability, the standard deviation (SD) of QT intervals was highly reduced with optimized extraction (SD of QTcF from 11 ± 8 to 7 ± 2 ms, P < 0.05). Conclusions: Extraction of discrete 12-lead ECG strips from continuous Holter generates less noisy and more stable ECGs leading to more robust QTc data, thereby potentially facilitating the assessment of ECG effects on clinical trials. [source] Studies on the Acute Toxicity, Pharmacokinetics and Pharmacodynamics of Paliperidone Derivatives , Comparison to Paliperidone and Risperidone in Mice and RatsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2010Fengying Sun The i.g. LD50 and i.v. maximum tolerated doses of PD1, PD5 and PD6 were greater than those of paliperidone and risperidone in mice. Pharmacokinetic study showed that PDs were quickly metabolized to paliperidone to take effect in the treatment of schizophrenia in rats after i.g. administration. Only traces of the parent substances were found. Pharmacodynamic study showed that PDs significantly reduced MK-801-induced hyperlocomotion in mice. The electrocardiogram (ECG) was recorded at 0, 5, 10, 15, 20, 25, 30, 45 and 60 min. in anaesthetized rats after i.v. injection of 0.21, 0.59, 1.69 ,mol/kg drugs. Heart rate reduction had a linear relation with dose after i.v. injection of PDs, paliperidone and risperidone. No significant change in the ECG parameters was found in all groups after administration of the low dose. Although the reductions in heart rate and the corrected QT interval (QTc) were observed in all drugs at the high dose, PD5 and PD6 were associated with smaller effects on the ECG parameters than other compounds, including paliperidone and risperidone. Therefore, PD5 and PD6 could be potential candidates for the treatment of schizophrenia. [source] Patients with Metabolic Syndrome Have Prolonged Corrected QT Interval (QTc)CLINICAL CARDIOLOGY, Issue 12 2009Weiju Li MD Abstract Background Prolongation of corrected QT interval (QTc) increases morbidity and mortality and QTc has been found to be longer in patients with diabetes mellitus than in healthy controls. It is still inconclusive whether the metabolic syndrome results in QTc prolongation. Hypothesis We hypothesized that metabolic syndrome might contribute to risk of QTc prolongation. The hypothesis was tested in a large population. Methods A total of 5,815 individuals (men: 1,950, women: 3,865 aged 20,80 years) were enrolled. Metabolic syndrome was defined according to the revised third National Cholesterol Education Program Adult Treatment Panel (NCEP-ATP III). QTc was calculated by using Bazett and Fridericia equations and the corrected JT interval (JTc) was derived by subtracting the QRS duration from the QTcB. All individuals had physical examinations, electrocardiograms, echocardiography, and blood tests. Results Individuals with metabolic syndrome had longer QTcs and JTc than those without metabolic syndrome (439.84 ms versus 430.90 ms in men, 456.37 ms versus 445.12 ms in women, respectively, p < 0.001 using Bazett formula). The more the number of abnormal metabolic parameters they had, the longer the QTcs and JTc they had. Trend analysis indicated that QTcB, QTcF, and JTc were significantly correlated to the number of abnormal metabolic parameters both in men and in women. After being adjusted for conventional risk factors, QTcB, QTcF, and JTc remained negatively associated with serum potassium concentration and positively associated with interventricular septal thickness. Conclusions Metabolic syndrome is a risk factor for prolonged QTc, which may further increase cardiovascular morbidity and mortality in the subjects with metabolic syndrome. Copyright © 2009 Wiley Periodicals, Inc. [source] Video-Assisted Thoracoscopic Sympathectomy for Congenital Long QT SyndromesPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 4p1 2003JIANFENG LI LI, J., et al.: Video-Assisted Thoracoscopic Sympathectomy for Congenital Long QT Syndromes. The feasibility, safety, and effectiveness of video-assisted thoracoscopic sympathectomy (VATS) for congenital long QT syndrome were assessed in four patients who had frequent syncopal events before the surgeries. Under general anaesthesia, the pleural cavity was entered via two small incisions in the left third and fifth intercostal spaces at the mid-axillary line. The left thoracic sympathetic chain was identified and resected from T2-T5. The lower one third of the left stellate ganglion was also resected. VATS resulted in a significant shortening in corrected QT intervals (QTc) in three patients, the average QTc of the four patients immediately before and after VATS was538 ± 76and512 ± 57 ms, respectively(P = 0.047). The heart rate remained unchanged after the VATS (67 ± 4vs69 ± 4 beats/min, P > 0.05). There were no major perioperative complications apart from mild ptosis of the left upper eyelid in one patient who recovered in the following days. There was no recurrence in syncopal events after a 3-month follow-up. VATS is a safe and effective technique for left cardiac sympathectomy in patients with congenital long QT syndromes. (PACE 2003; 26[Pt. I]:870,873) [source] Hormone Replacement Therapy Shortens QT Dispersion in Healthy Postmenopausal WomenANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 3 2001Aylin Yildirir M.D. Background: The aim of the study was to investigate the effects of hormone replacement therapy (HRT) on myocardial repolarization characteristics in postmenopausal women without coronary artery disease. Methods: Fifty-one consecutive healthy postmenopausal women (age 48 ±; 5) with negative exercise stress testing were prospectively enrolled into the study. Standard 12-lead electrocardiograms were obtained to evaluate the effects of 6 months of HRT on QT intervals, corrected QT intervals (QTcmax and QTcmin), QT dispersion (QTd), and corrected QTd (QTcd). Hormone regimens were continuous 0.625 mg/day conjugated equine estrogen (CEE) plus 2.5 mg/day medroxyprogesterone acetate (MPA) or 0.625 mg/day CEE alone depending on the hysterectomy status. Results: Although not statistically significant, CEE alone or in combination with MPA increased QTmax and QTmin values. However, the increase in QTmin was greater than the increase in QTmax, which resulted in statistically significant shortening of QTd (P = 0.007 in CEE and P < 0.001 in CEE + MPA groups). There was a significant prolongation of QTcmin values after 6 months in patients assigned to the CEE group (P = 0.001). The QTcd values were significantly shortened by HRT with both regimens (for CEE group 49 ±; 13 ms vs 38 ±; 13 ms, P = 0.01; for CEE + MPA group 49 ±; 14 ms vs 36 ±; 13, P < 0.001). Conclusion: HRT significantly decreased the QTd and QTcd in postmenopausal women without coronary artery disease, independent of the addition of MPA to the regimen. This improvement in myocardial repolarization may be one of the mechanisms of the favorable effects of HRT on cardiovascular system. However, the clinical implications of the shortening of QTd in postmenopausal women with HRT must be clarified. A.N.E. 2001; 6(3):193,197 [source] Lamotrigine does not prolong QTc in a thorough QT/QTc study in healthy subjectsBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 3 2008Ruth Dixon WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Drugs that inhibit the human cardiac delayed rectifier potassium current may lead to prolongation of the cardiac QT interval and are associated with a fatal, polymorphic, ventricular tachycardia known as torsades de pointes. , Lamotrigine is indicated in the treatment of epilepsy and the prevention of mood episodes in patients with bipolar disorder. , Lamotrigine inhibits the human cardiac delayed rectifier potassium current in vitro, and it has been hypothesized that QT prolongation may contribute to the risk of sudden unexpected death in epilepsy patients. WHAT THIS STUDY ADDS , This is the first reported thorough QT/QTc study with lamotrigine conducted to International Conference on Harmonization guidelines. , The mean QTc interval was not prolonged by lamotrigine in healthy subjects, as assessed by the standard heart rate correction methods (Fridericia's and Bazett's). , The in vitro inhibition of the delayed rectifier potassium current does not translate into an effect on QT in man. AIM To characterize the effects of lamotrigine on QT interval in healthy subjects. METHODS Healthy subjects received a single oral dose of moxifloxacin (400 mg) or placebo in crossover design, followed by a dose-escalating regimen of lamotrigine (n = 76) over a 77-day period, or matched placebo (n = 76). Blood samples were taken for determination of moxifloxacin and lamotrigine concentrations and digital 12-lead ECGs were recorded. The relationships between individual QT values and respective individual moxifloxacin or lamotrigine concentrations were explored using population pharmacokinetic,pharmacodynamic (PK,PD) modelling. RESULTS Moxifloxacin was associated with a maximum mean increase from baseline in QTcF of 14.81 ms [90% confidence interval (CI) 13.50, 16.11] 2.5 h after dosing. Steady-state exposure to lamotrigine (50, 150 or 200 mg b.d.) was not associated with an increase in QTc interval. Small reductions in QTcF (maximum mean difference from placebo ,7.48 ms, 90% CI ,10.49, ,4.46) and small increases in heart rate (maximum mean difference from placebo 5.94 bpm, 90% CI 3.81, 8.06) were observed with lamotrigine 200 mg b.d. vs. placebo. No effect of lamotrigine on QRS duration or blood pressure was observed. No outliers with QTcF > 450 ms, or with an increase from baseline of >60 ms were observed in the lamotrigine group. PK,PD modelling indicated statistically significant decreases in individually corrected QT intervals for lamotrigine and statistically significant increases in individually corrected QT intervals for moxifloxacin over the concentration ranges studied. CONCLUSIONS Therapeutic doses of lamotrigine (50,200 mg b.d.) were not associated with QT prolongation in healthy subjects. [source] | ||||||||||||||||||||||