QTc Prolongation (qtc + prolongation)

Distribution by Scientific Domains

Selected Abstracts

QTc-interval abnormalities in a forensic population

Sobhi Girgis
Background,Antipsychotic drugs have been linked to sudden death among psychiatric patients, with a suggestion that prolongation of the QT-interval detectable on a standard electrocardiogram may be linked to fatal cardiac arrhythmias in these circumstances. Patients in secure forensic psychiatric facilities may be particularly likely to be on high-dose antipsychotic medication, and yet, as far as the authors are aware, no study of QT-intervals among such patients has been reported. Aim,To investigate the prevalence of QT-interval abnormalities and associated known risk factors for fatal cardiac arrhythmias in a sample of forensic patients. Method,Participants had a 12-lead electrocardiogram taken at 50 mm/s. Information was collected on their age, gender, psychiatric diagnosis, history of cardiovascular, liver and kidney diseases, and smoking, on all medications and on history of seclusion over the previous 12 months. Analysis was carried out using binary logistic regression. Results,Lower rates of QT-interval abnormalities than might be expected for this population were found. It was also found that a high dose of antipsychotics was associated with QTc prolongation (Adjusted OR = 9.5, 95% CI 2.6,34.2), a result consistent with previous literature. Conclusion,Forensic patients need not be at increased risk of QTc abnormality provided risk factors are properly managed. A high dose of antipsychotic medication increases the risk of QTc prolongation. Copyright 2007 John Wiley & Sons, Ltd. [source]

Effect of insulin infusion on electrocardiographic findings following acute myocardial infarction: importance of glycaemic control

R. M. Gan
Abstract Aims, To determine the effects of insulin infusion and blood glucose levels during acute myocardial infarction (AMI) on electrocardiographic (ECG) features of myocardial electrical activity. Methods, ECGs at admission and 24 h were examined in a randomized study of insulin infusion vs. routine care for AMI patients with diabetes or hyperglycaemia. Results were analysed according to treatment allocation and also according to average blood glucose level. Results, ECG characteristics were similar at admission in both groups. Patients allocated to conventional treatment had prolongation of the QT interval (QTc) after 24 h but those receiving infused insulin did not. In patients with a mean blood glucose in the first 24 h > 8.0 mmol/l, new ECG conduction abnormalities were significantly more common than in patients with mean blood glucose , 8.0 mmol/l (15.0% vs. 6.0%, P < 0.05). Conclusions, Prevention of QTc prolongation by administration of insulin may reflect a protective effect on metabolic and electrical activity in threatened myocardial tissue. Abnormalities of cardiac electrical conduction may also be influenced by blood glucose. [source]

Prevalence and clinical relevance of corrected QT interval prolongation during methadone and buprenorphine treatment: a mortality assessment study

ADDICTION, Issue 6 2009
Katinka 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]

Cardiac side effects of psychiatric drugs,

Paul Mackin
Abstract This review describes the common effects of psychotropic drugs on the cardiovascular system and offers guidance for practical management. Selected reports from the literature describing common side effects associated with psychotropic drugs are reviewed, and suggestions for further reading are given throughout the text. Orthostatic hypotension is the most common adverse autonomic side effect of antipsychotic drugs. Among the atypical antipsychotics the risk of orthostatic hypotension is highest with clozapine and among the conventional drugs the risk is highest with low potency agents. Rarely, orthostatic hypotension may result in neurocardiogenic syncope. QTc prolongation can occur with all antipsychotics but an increased risk is seen with pimozide, thioridazine, sertindole and zotepine. QTc prolongation is a marker of arrhythmic risk. Torsade de pointe, a specific arrhythmia, may lead to syncope, dizziness or ventricular fibrillation and sudden death. Heart muscle disease presents most commonly in the elderly as chronic heart failure, but myocarditis and cardiomyopathy, although relatively rare, are devastating, but potentially reversible complications of psychotropic drug therapy have been particularly linked to clozapine treatment. Patients with severe mental illness (SMI) are a ,high risk' population with regard to cardiovascular morbidity and mortality. It is probable that many patients accumulate an excess of ,traditional' risk factors for the development of cardiovascular disease, but other mechanisms including psychotropic drugs may also be influential in increasing risk in this vulnerable group. These risks need to be seen in the context of the undoubted therapeutic efficacy of the psychotropic armamentarium and the relief that these drugs bring to those suffering from mental disorder. Copyright 2007 John Wiley & Sons, Ltd. [source]

QTc prolongation and liver disease , As good as PELD score?

Gaurav Arora MD
No abstract is available for this article. [source]

Targeting tumor metabolism with 2-deoxyglucose in patients with castrate-resistant prostate cancer and advanced malignancies

THE PROSTATE, Issue 13 2010
Mark Stein
Abstract BACKGROUND A profound difference between cancer and normal tissues is the preferential utilization of glycolysis by cancer cells. To translate this paradigm in the clinic, we completed a phase I study of 2-deoxyglucose (2DG), and assessed 2DG uptake with fluorodeoxyglucose (FDG) positron emission tomography (PET) and the autophagy substrate p62 as a marker of 2DG resistance. METHODS Patients received 2DG orally on days 1,14 of a 21-day cycle in cohorts of three in a dose-escalating manner. Correlative assessments included PET scans at baseline and day 2 and p62 protein in peripheral blood mononuclear cells as a potential marker of 2DG resistance. RESULTS The dose of 45,mg/kg was defined as the recommended phase II dose, secondary to dose-limiting toxicity of grade 3 asymptomatic QTc prolongation at a dose of 60,mg/kg. PK evaluation of 2DG revealed linear pharmacokinetics with Cmax 45,g/ml (277,M), 73.7,g/ml (449,M), and 122,g/ml (744,M) in dose levels 30, 45, and 60,mg/kg, respectively. Five of eight patients assessed with FDG-PET scanning demonstrated decreased FDG uptake by day 2 of therapy, suggesting competition of 2DG with FDG. Five of six patients assessed for p62 had a decrease in p62 at 24,hr. CONCLUSIONS These data support the safety of 2DG, defined 2DG PK, demonstrated the effect of 2DG on FDG-PET imaging, and demonstrated the feasibility of assessment of p62 as an autophagic resistance marker. These data support future studies of 2DG alone or in combination with approaches to abrogate autophagy. Prostate 70: 1388,1394, 2010. 2010 Wiley-Liss, Inc. [source]

Influence of promethazine on cardiac repolarisation: a double-blind, midazolam-controlled study

ANAESTHESIA, Issue 6 2009
R. Owczuk
Summary Drugs used in anaesthesia may provoke torsadogenic changes in cardiac repolarisation. The aim of this study was to assess the effect of promethazine on the parameters of ventricular repolarisation: QTc interval and transmural dispersion of repolarisation. Forty patients were randomly allocated to receive promethazine (25 mg) or midazolam (2.5 mg). Changes in the ECG and arterial blood pressure were recorded. Correction of QT interval was calculated using Bazett's formula and Fridericia's correction; transmural dispersion of repolarisation was determined as Tpeak,Tend time. Significant prolongation of QT interval, corrected with both formulae, was detected in patients receiving promethazine, while no change in the QTc value was observed in the midazolam group. There were no significant differences in Tpeak,Tend time either between or within the groups. In conclusion, promethazine induces significant QTc prolongation but the lack of influence on transmural dispersion of repolarisation makes the risk of its torsadogenic action very low. [source]

A Bizarre Electrocardiographic Pattern Due to Chronic Lithium Therapy

Mehmet Kayrak M.D.
Cardiotoxicity that results from lithium overdose is uncommon and electrocardiographic (ECG) changes are rarely reported. However, some authors have specifically reported the occurrence of ischemic ECG changes due to a lithium overdose. This article describes a case that is demonstrating ECG changes that mimic inferior myocardial infarction during the course of chronic lithium treatment and showing QTc prolongation in this patient. The patients' ECG changes were partially recovered after hemodialysis. Ann Noninvasive Electrocardiol 2010;15(3):289,292 [source]

Correction for QT/RR Hysteresis in the Assessment of Drug-Induced QTc Changes,Cardiac Safety of Gadobutrol

M.D., Marek Malik Ph.D.
Background: The so-called thorough QT/QTc (TQT) studies required for every new pharmaceutical compound are negative if upper single-sided 95% confidence interval (CI) of placebo and baseline corrected QTc prolongation is <10 ms. This tight requirement has many methodological implications. If the investigated drug has a fast action and ECGs cannot be obtained at stable heart rates, QT/RR hysteresis correction is needed. Methods: This was used in a TQT study of gadobutrol. The TQT study was a randomized double-blind five-times crossover study of three doses of gadobutrol (0.1, 0.3, and 0.5 mmol/kg) that was placebo and positive effect controlled (moxifloxacin 400 mg). The study enrolled 50 healthy subjects with data of all periods. QT/RR hysteresis was assessed from prestudy exercise test ECGs. Among others, comparisons were made between population heart rate correction without hysteresis considerations and combined population heart rate and hysteresis correction. Results: The highest heart rate increase (placebo and baseline controlled) of 13.1 beats per minute (90% CI 9.9,16.4) occurred 1 minute after the administration of the highest dose of gadobutrol. Without hysteresis consideration, the highest ,,QTc were 9.91 ms (90% CI 8.01,11.81) while with hysteresis correction, these values were 7.62 ms (90% CI 6.37,8.87), thus turning a marginally positive TQT study into a negative finding. Conclusion: Hence, omitting hysteresis correction from episodes of fast heart rate changes may lead to incorrect conclusions. Despite substantial rate acceleration, accurate hysteresis correction confirms that gadobutrol does not have any effects on cardiac repolarization that would be within the limits of regulatory relevance. [source]

The Measurement of the QT and QTc on the Neonatal and Infant Electrocardiogram: A Comprehensive Reliability Assessment

B.S., Robert M. Gow M.B.
Background: An electrocardiogram has been proposed to screen for prolonged QT interval that may predispose infants to sudden death in the first year of life. Understanding the reliability of QT interval measurement will inform the design of a screening program. Methods: Three pediatric cardiologists measured the QT/RR intervals on 60 infant electrocardiograms (median age 46 days), from leads II, V5 and V6 on three separate occasions, 7 days apart, according to a standard protocol. The QTc was corrected by Bazett's (QTcB), Fridericia's (QTCFrid), and Hodges' (QTcH) formulae. Intraobserver and interobserver reliability were assessed by intraclass correlation coefficients (ICC), limits of agreement and repeatability coefficients for single, average of two and average of three measures. Agreement for QTc prolongation (> 440 msec) was assessed by kappa coefficients. Results: QT interval intraobserver ICC was 0.86 and repeatability coefficient was 25.9 msec; interobserver ICC increased from 0.88 for single observations to 0.94 for the average of 3 measurements and repeatability coefficients decreased from 22.5 to 16.7 msec. For QTcB, intraobserver ICC was 0.67, and repeatability was 39.6 msec. Best interobserver reliability for QTcB was for the average of three measurements (ICC 0.83, reproducibility coefficient 25.8 msec), with further improvement for QTcH (ICC 0.92, reproducibility coefficient 16.69 msec). Maximum interobserver kappa for prolonged QTc was 0.77. Misclassification around specific cut points occurs because of the repeatability coefficients. Conclusions: Uncorrected QT measures are more reliable than QTcB and QTCFrid. An average of three independent measures provides the most reliable QT and QTc measurements, with QTcH better than QTcB. [source]

Cardiac monitoring of patients receiving arsenic trioxide therapy

Dilip Unnikrishnan
Summary Arsenic trioxide (ATO) is approved for the treatment of acute promyelocytic leukaemia and is under investigation for other malignancies. We report the cardiac findings in 18 patients with haematologic malignancies treated with ATO and assess the role of cardiac factors in fluid retention syndrome observed during ATO therapy. Based on initial observations in 10 patients treated with ATO, cardiac functions in the subsequent eight patients were evaluated prospectively. Evaluation included pre- and during-treatment electrocardiograms, Holter monitoring, echocardiograms, multigated acquisition scan and cardiac stress tests if indicated. All eight patients developed fluid retention during ATO, evidenced by pulmonary congestion, oedema and pleural/pericardial effusions. No cardiac factors were identified that contributed to fluid retention. Six patients had prolonged corrected QT (QTc) compared with baseline, three developed ventricular tachycardia. Sinus tachycardia, ventricular premature contractions, and non-sustained ventricular/supraventricular tachycardia were seen during ATO treatment. Fluid retention and cardiac events did not correlate with the dose or total amount of ATO or prior anthracycline therapy. In summary, fluid overload during ATO therapy does not appear to be cardiac in origin but appears to be drug-related, and may reflect cytokine-induced capillary leak. QTc prolongation, transient arrhythmias and clinically significant arrhythmias were seen with therapeutic doses of ATO. [source]

Dexrazoxane protects the heart from acute doxorubicin-induced QT prolongation: a key role for IKs

J Ducroq
Introduction:, Doxorubicin, an anthracycline widely used in the treatment of a broad range of tumours, causes acute QT prolongation. Dexrazoxane has been shown to prevent the QT prolongation induced by another anthracycline, epirubicin, but has not yet been reported to prevent that induced by doxorubicin. Thus, the present study was designed to test whether the acute QT effects induced by doxorubicin could be blocked by dexrazoxane and to explore the mechanism. Results were compared with those obtained with a reference human ether-a-go-go (hERG) channel blocker, moxifloxacin. Methods:, The effects of moxifloxacin (100 M) and doxorubicin (30 M), with or without dexrazoxane (from 3 to 30 M), have been evaluated on the QTc interval in guinea-pig isolated hearts and on IKr (rapid component of the delayed rectifier current) and IKs (slow component of the delayed rectifier current) currents stably expressed in human embryonic kidney 293 cells. Results:, Moxifloxacin (100 M), a potent hERG blocker, prolonged QTc by 22%, and this effect was not prevented by dexrazoxane. Doxorubicin (30 M) also prolonged QTc by 13%, did not significantly block hERG channels and specifically inhibited IKs (IC50: 4.78 M). Dexrazoxane significantly reduced the doxorubicin-induced QTc prolongation and prevented doxorubicin-induced inhibition of IKs. Conclusion and implications:, Doxorubicin acutely prolonged the QT interval in guinea-pig heart by selective IKs blockade. This effect was prevented by dexrazoxane. This result is important because it illustrates the danger of neglecting IKs in favour of hERG screening alone, for early preclinical testing for possible induction of torsade de pointes. This article is part of a themed section on QT safety. To view this issue visit http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2010 [source]

Patients with Metabolic Syndrome Have Prolonged Corrected QT Interval (QTc)

Weiju 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]