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Results for “QTc interval prolongation”

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PubMed1996

The role of ketoconazole in the QTc interval prolonging effects of H1-antihistamines in a guinea-pig model of arrhythmogenicity.

We have carried out experiments to re-evaluate the influence of ketoconazole (400 mg kg-1,p.o.) on the effects of ebastine, terfenadine and loratadine on the QTc interval in conscious guinea-pigs. Following a previously described protocol of oral drug administration, but using telemetric recording of the ECG, we have found that the prolongation of the QTc interval attributed to ebastine and terfenadine is in fact entirely due to ketoconazole, and that neither terfenadine, ebastine nor loratadine produce any additional effects on subsequent administration.

Animals↗
PubMed1996

[Prolonged QTc intervals in Parkinson's disease--relation to sudden death and autonomic dysfunction].

Sudden death has been reported in Parkinson's disease (PD), but the cause of death has not been fully clarified. A prolonged QT interval on the electrocardiogram (ECG) of patients without cardiac dysfunction is an independent risk factor for sudden death regardless of etiology. QT prolongation is believed to be related to cardiac autonomic dysfunction. We suspected that QTc intervals, as well as QT intervals, might be related to the clinical characteristics of PD and to the function of the autonomic nervous system in PD and also postulated a relationship between QTc prolongation and sudden death in PD. We investigated the QTc intervals on the ECGs of 48 PD patients (20 males 28 females) aged 64.5 +/- 9.4 years and 44 controls aged 60.0 +/- 8.2 years, and excluded patients with heart disease. QTc intervals were determined by using ECG-8210, ECAPS12 (Nihon-Kohden). The autonomic nervous system was evaluated by measuring CVR-R and performing orthostatic tests. Since the autonomic nervous system is considered to play an important role in the mechanism of diurnal blood pressure variation (DBPV), we assessed DBPV in 19 PD patients by determining blood pressure automatically every 30 minutes for 24 hours with an ambulatory blood pressure monitor (90202, Space Lab). QTc intervals were significantly longer in the PD patients (412 +/- 26 msec) than in the controls (401 +/- 14 msec) (p < 0.02, t-test). QTc prolongation was significantly correlated with severity according to Hoehn and Yahr stage (r = 0.509, p < 0.001), orthostatic hypotension, and decreased CVR-R ratio but not with duration of PD or treatment. The incidence of QTc prolongation was higher in the PD patients with non-dipper type DBPV than in those with the dipper type. Two of the PD patients died suddenly. Their QTc intervals a year before their death were 451 msec and 470 msec, respectively, suggesting that cardiac dysautonomia may have been involved in the cause of their death. These findings suggest that cardiac autonomic dysfunction is related to the severity of PD, and that it may predispose such patients to cardiac disorders including sudden cardiac death.

Adult↗
PubMed2006

QTc interval prolongation in children with Ulrich-Turner syndrome.

INTRODUCTION: The Ullrich-Turner-Syndrome (UTS) is the most commonly occurring sex chromosome abnormality in females. Cardiac malformations are well known, but no data exist on specific electrocardiogram (ECG) patterns in children and adolescents. A prolongation of the QT interval on the ECG has been correlated to an increased risk for sudden cardiac death, and medical treatment is warranted in patients with long QT syndrome (LQTS). Moreover, several drugs of common use are contraindicated in LQTS because of their effects on myocardial repolarization. METHODS: The ECG tracings of 86 UTS patients [mean age (+/-SD): 11.0+/-3.6 years; mean height-SD: -2.6+/-1.0] were analyzed and compared to age-matched control groups of 75 boys (mean age: 11.3+/-3.5 years; mean height-SD: -1.9+/-1.0) and 62 girls (mean age: 10.1+/-3.2 years; mean height-SD: -2.5+/-0.9) with short stature. RESULTS: Eighteen UTS patients (20.9%) had an abnormally prolonged QTc >0.45 s in contrast to only one control subject (0.9%). The QTc interval of UTS patients was significantly prolonged compared to that of the controls (p<0.01) and normal values. CONCLUSIONS: There is an increased prevalence of a long QT interval among UTS patients. This should be taken into account for the cardiovascular screening of such patients. Patients with UTS have an intrinsically prolonged QT interval and as such may be at higher risk for arrhythmias in the context of a QT-prolonging medication.

Body Mass Index↗
PubMed2000

Rank power of metrics used to assess QTc interval prolongation by clinical trial simulation.

Monte Carlo simulation was used to assess the type I error rate and rank order of power for six different metrics using linear mixed-effect models, including two variables recommended by the European Agency for the Evaluation of Medicinal Products (EMEA) in the analysis of QTc interval data. The metrics analyzed were maximal change in QTc interval from baseline, maximal QTc interval, area under the QTc interval-time curve (AUC), average QTc interval, maximal QTc interval with baseline QTc interval as covariate, and AUC with baseline QTc interval as covariate. Two dosing regimens were studied: multiple-dose oral and multiple-dose continuous intravenous infusion. Both regimens were designed to produce similar maximal plasma concentrations, albeit with the infusion regimen maintaining maximal plasma concentrations for a longer period of time. The ability of the metrics to detect a drug effect was examined, assuming drug effect followed either an Emax or linear model. All statistics had a type I error rate near the nominal value. Regardless of pharmacokinetic or pharmacodynamic model, AUC with baseline QTc interval as a covariate had greater power than any other metric examined. The simulations also suggest that mean QTc interval data not be used.

Administration, Oral↗
PubMed2006

Repolarization morphology in adult LQT2 carriers with borderline prolonged QTc interval.

BACKGROUND: At least 50% of LQT2 carriers have borderline QTc (0.42-0.47 s), and they present a diagnostic difficulty to clinicians evaluating patients suspected of having long QT syndrome (LQTS). OBJECTIVES: Because QTc in this borderline range is nondiagnostic, the purpose of this study was to investigate whether analysis of phenotypic features of T-wave morphology could help identify LQT2 carriers with normal or near-normal QTc-interval duration. METHODS: Standard 12-lead ECGs recorded without beta-blockers from LQT2 carriers (n = 90, 33 +/- 14 years, 61% female) and noncarriers (n = 69, 38 +/- 17 years, 58% female) were digitized. The following parameters were automatically measured: RR interval, QT/QTc, QT apex, T-wave amplitude, ascending (alpha(L)) and descending slopes (alpha(R)) of the T wave, and T-wave symmetry. We used a linear logistic regression model to identify the most relevant parameters for separating LQT2 carriers from noncarriers, within the overall population and among patients without overt QTc prolongation (390 </= QTc </= 470). RESULTS: Logistic regression selected three parameters: QT, RR interval, and alpha(L) in all models. In the overall population, the model provided 92.7% sensitivity and 90.0% specificity. In the group of patients without beta-blockers and near-normal QTc interval, 92.0% sensitivity (n = 46) and 81.4% specificity (n = 49) were achieved by the model including alpha(L.) CONCLUSION: Abnormal T-wave morphology is a phenotypic expression of LQT2, and its quantification could be used to identify patients with suspected LQTS who do not have overt QTc prolongation (QTc >470).

Action Potentials↗
PubMed2005

Absence of QTc-interval-prolonging or hemodynamic effects of a single dose of bitter-orange extract in healthy subjects.

STUDY OBJECTIVE: To evaluate the hemodynamic and electrocardiographic effects of a single dose of commercially available bitter-orange dried-fruit extract, which is increasingly being used in dietary supplements. DESIGN: Randomized, double-blind, placebo-controlled, crossover study. SETTING: University of Connecticut, Storrs Campus. SUBJECTS: Eighteen healthy volunteers aged 18 years or older. INTERVENTION: Subjects were given either placebo or bitter-orange dried-fruit extract (450 mg standardized to 27 mg of m- or p-synephrine) in phase 1. The opposite treatment was given during phase 2 after a washout period of at least 7 days. MEASUREMENTS AND MAIN RESULTS: The rate-corrected QT (QTc) interval and blood pressure were measured before dosing and at 1, 3, 5, and 8 hours after dosing. Mean+/-SD values of the maximum postdose values were compared between groups. Subjects receiving bitter-orange extract versus those receiving placebo had similar postdose QTc intervals (402+/-29 vs 403+/-24 msec, p=0.653), systolic blood pressure (114+/-10 vs 115+/-8 mm Hg, p=0.686) and diastolic blood pressure (68+/-9 vs 68+/-8, p=0.879). CONCLUSION: Bitter-orange dried-fruit extract standardized to m- or p-synephrine 27 mg did not significantly alter the QTc interval or blood pressure after a single dose was administered. Future studies are necessary to ensure the safety of this herbal product with multiple doses.

Adult↗
PubMed1999

The relation between QTc interval prolongation and diabetic complications. The EURODIAB IDDM Complication Study Group.

The prevalence of QT interval prolongation is higher in people with diabetes and its complications. Sudden death has been reported as a common cause of death in insulin-dependent diabetic patients affected by autonomic neuropathy. It has been postulated that QT prolongation predisposes to cardiac arrhythmias and sudden death. In this analysis the prevalence of QT interval prolongation and its relation with diabetic complications were evaluated in the EURODIAB IDDM Complications Study (3250 insulin-dependent diabetic patients attending 31 centres in 16 European countries). Five consecutive RR and QT intervals were measured with a ruler on the V5 lead of the resting ECG tracing and the QT interval corrected for the previous cardiac cycle length was calculated according to the Bazett's formula. The prevalence of an abnormally prolonged corrected QT was 16% in the whole population, 11% in males and 21 % in females (p < 0.001). The mean corrected QT was 0.412 s in males and 0.422 s in females (p < 0.001). Corrected QT duration was independently associated with age, HbA1c and blood pressure. Corrected QT was also correlated with ischaemic heart disease and nephropathy but this relation appeared to be stronger in males than in females. Male patients with neuropathy or impaired heart rate variability or both showed a higher mean adjusted corrected QT compared with male patients without this complication. The relation between corrected QT prolongation and autonomic neuropathy was not observed among females. In conclusion we have shown that corrected QT in insulin-dependent diabetic female patients is longer than in male patients, even in the absence of diabetic complications known to increase the risk of corrected QT prolongation.

Adult↗
PubMed2001

Prolonged QTc intervals on the electrocardiograms of hospitalized malnourished adults.

We investigated whether hospitalized malnourished adults would have longer QTc intervals on their electrocardiograms (ECGs) than non-malnourished adults. Seventy-five consecutive adults hospitalized in the Internal Medicine wards of our teaching hospital were prospectively studied. Main diagnoses, anthropometry, including body mass index (kg/m(2)), ECGs, and simultaneous serum levels of sodium, potassium, magnesium, phosphorus, and calcium were recorded. All QT intervals on ECGs were measured in a semiautomatic image analysis system; and QTc intervals were determined with the Bazett formula. Protein-energy malnutrition (PEM) was diagnosed with body mass index below 18.5 kg/m(2). There was no statistical difference between malnourished (n = 30) and non-malnourished (n = 45) with regard to age (40.7 +/- 18.9 y versus 41.4 +/- 16.2 y), male predominance (66.7% versus 80%), or associated diagnoses. Compared with non-malnourished, malnourished patients had higher percentages of positive C-reactive protein (66.7 versus 23.8%), lower serum levels of albumin (2.51 +/- 0.89 g/dL versus 3.41 +/- 0.74 g/dL) and potassium (3.64 +/- 0.65 mEq/L versus 4.12 +/- 0.65 mEq/L), and increased QTc lengths on ECGs (0.423 +/- 0.033 ms versus 0.396 +/- 0.031 ms). Malnourished adults hospitalized in general clinical wards are more likely to have longer QTc intervals on their ECGs, a phenomenon possibly linked to malnutrition and associated electrolyte disturbances.

Adult↗