QTc interval

azithromycin, there were no differences between the groups (data not shown). Patients in the fatal outcome group had a higher rate of a past history of diabetes melli- tus (DM) and cerebral vascular disease (CVD) (Table 2). Next, multiple logistic regression analysis of the clinical features of the pneumonia patients (30-day survivors group versus 30-day nonsurvivors group) was performed (Table 3). The odds ratios of age, CURB-65, PSI, lower albumin, QTc interval prolongation and past history of DM and CVD were significantly higher in the fatal out- come group. The odds ratio of QTc interval prolongation in the poor prognosis group (died within 30 days from admission) was 3.792 (95% CI = 1.100-13.071).

for known variants associated with prolonged QTc interval was not con- ducted due to the very transient nature of the presentation; however, it is possible that the patient was genetically predis- posed to prolonged QTc while under physiologic stress. Very-long-chain acyl- coenzyme A dehydrogenase (VLCAD) de fi ciency has been associated with prolonged QTc intervals, and the acyl- carnitine pro fi le did show evolving increases in some of the longer chain acylcarnitines when compared with the newborn screen (Table 3). However, these elevations are observed in much lower quantities than traditionally seen in VLCAD de fi ciency and would be an- ticipated for an individual with MCAD de fi ciency who is acutely catabolic, li-

One-way factorial ANOVA was used to assess the rela- tionship between severity score and plasma albuterol, and Fisher ’ s protected least significant difference (PLSD) post hoc test was used to assess any statistical signifi- cance. Linear regression was used for the relationship between continuous variables. Spearman rank correla- tion and Mann-Whitney tests were used to assess the relationship between the serum albuterol level and extrapulmonary effects (heart rate, QTc interval, serum potassium level and BSL), which did not exhibit Gaus- sian distributions. Statistical analyses were undertaken with Statview 5.0.1 (SAS Institute Australia Pty Ltd., NSW, Australia) and SPSS 15.0 for Windows (SPSS Australasia Pty. Ltd., Chatswood, NSW, Australia).

Material and Methods: Wistar rats of either sex were anaesthetised with urethane (1.5 g/kg) and electrocardiogram (ECG) was recorded by four channel physiological data acquisition system (BIOPAC). Rats were administered either with ondansetron and its enantiomers (R- and S-) in the dose of 3 mg/kg, i.v.) and ECG was recorded after the equilibrium period of 30 min. Amiodarone (25 mg/kg, i..v) was used as a standard drug. Results: (RS)-Ondansetron, (S)-ondansetron, and amiodarone produced significant prolongation of QTc interval. But, (R)-ondansetron did not prolonged QTc interval in rat ECG.

quantitative trait, believed to be influenced by several genetic and environmental factors. It is a strong prognostic indicator of cardiovascular mortality in patients with and without cardiac disease. More than 700 mutations have been described in 12 genes (LQT1-LQT12) involved in congenital long QT syndrome. However, the heritability (genetic contribution) of QTc interval in the general population cannot be adequately explained by these long QT syndrome genes. In order to further investigate the genetic architecture underlying QTc interval in the general population, genome-wide association studies, in which up to one million single nucleotide polymorphisms are assayed in thousands of individuals, are now being employed and have already led to the discovery of variants in seven novel loci and five loci that are known to cause congenital long or short QT syndrome. Here we show that a combined risk score using 11 of these loci explains about 10% of the heritability of QTc. Additional discovery of both common and rare variants will yield further etiological insight and accelerate clinical applications.

On the other hand, it is well known that concentration-effect relationships can differ between species, as result of for example differences in homeostatic processes, circadian variation, target expression and/or transduction mechanisms (31–34). Such dif- ferences need to be taken into account in the extrapolation of drug effects from pre-clinical species to humans, possibly by means of a system-specific translation function (34–36). In fact, the topic of interspecies scaling of drug-induced QTc interval prolongation was recently addressed in an extensive investiga- tion by Holzgrefe et al. (9). Their work however has not considered the role of pharmacokinetics and therefore a detailed and mean- ingful analysis of the PKPD relationship over a wide concentra- tion range was not possible. Specifically, a concentration-effect correlation was estimated by assuming a dose scaling factor and using the data obtained in a 1-h time interval around the Tmax, i.e., an empirical approach which disregards the differences in the pharmacokinetic profile of different compounds (14, 37).

Background: Arrhythmias commonly occur early in acute myocardial infarction and remain a common cause of sudden death in AMI. Magnesium has been implicated in the pathogenesis of acute myocardial infarction and its complication like arrhythmia. Magnesium improves myocardial metabolism, inhibits calcium accumulation and myocardial cell death. It improves vascular tone, peripheral vascular resistance, after load and cardiac output and reduces cardiac arrhythmias. The objective of this study to investigate the serum magnesium level and QTc interval prolongation in AMI and its correlation with arrhythmias.

A cross-sectional study was carried out in our institute. 100 willing subjects were randomly selected. The sample included both men and women. Even hypertensive subjects were included in the study. The subjects belonged to the age group of 20-45 years to avoid coexist- ing factors and diseases other than hyperten- sion. Alcoholics, smokers, tobacco chewerswere excluded. Those suffering from any active/ chronic infections, inflammations, neoplastic disorders, diabetes mellitus, thyroid disorders, liver disease were excluded from the study. Subjects taking drugs that may alter the QTc interval and/or CRP levels, and those taking antibiotics, anti-inflammatory, corticosteroids, postmenopausal hormone replacement therapy and subjects with CRP > 10 mg/dl were also excluded.

Long QT syndrome is one of the most important causes of arrhythmia that can cause syncopal attacks and even death in pediatrics. [1] Long QT syndrome is considered if QTc interval measured is ≥ 0.45 sec. [2] A standard 12-lead ECG tracing at 25 mm/sec paper speed at 10 mm/mV amplitude is generally adequate for accurate measurement of QT-interval duration. [3,4] Lead II is generally the best single lead for measuring QT interval because the T wave ending is usually discrete and the QT interval obtained from lead II has a good correlation with the maximal QT measured from the 12-lead ECG. [5]

BACKGROUND: Cirrhotic Cardiomyopathy is a relatively ill-characterized condition, which is often under-diagnosed due to absence of defined diagnostic criteria. ECG showing corrected QT Interval prolongation is the most suitable available option for diagnosis of this condition. OBJECTIVE: To determine the frequency of corrected QT interval prolongation in patients with liver cirrhosis. METHODOLOGY: Patients (n = 166) with confirmed cirrhosis, 30 years or older, presented in the outpatient and emergency department of medicine at Capital Hospital Islamabad between 1 Octo- ber 2011 and 30 September 2012, were enrolled in this cross-sectional study after taking consent. ECG was done using calibrated ECG machine, and the QT Interval was measured. Corrected QT was calculated using Bazett’s formula and a QTc of more than 0.44 seconds was considered as being prolonged. RESULTS: The mean age of the patients was 57.05 ± 12.03 years. The corrected QT In- terval varied from 337 ms to 560 ms. The mean QTc Interval was 429.92 ms ± 45.11. QTc was pro- longed in 41 out of 166 patients (24.7%). Frequency of QTc prolongation was 4.5% in Child Pugh Grade A, 23.2% in Child Pugh Grade B, and 32.0% in Child Pugh Grade C. Association of Child Pugh Scoring with QTc prolongation was determined and found to be statistically significant (P < 0.05). CONCLUSION: QTc interval was prolonged in 24.7% of cirrhotic patients in our study. There was a significant increase in frequency with worsening of Child Pugh Grade, thereby indicating an asso- ciation between QTc prolongation and the severity of cirrhosis.

PQTI was defined as a QTc interval ⱖ 460 milliseconds. Analysis was stratified by age, the distribution was made considering the activity of the CYP450 enzyme. A second EKG was performed in children with PQTI from group I after discontinuation of cisapride for 15 days. The same pediatric cardiologist blinded to both groups interpreted the EKG. A 24-hour Holter recording was performed in children with PQTI in both groups when PQTI was found.

In Low doses it will cause bradycardia by blocking prejunctional M1 receptor. shorten the PR interval on ECG by blocking muscarinic receptor in A-V node. Moderate dose cause tachycardia by blocking vagal slowing. In toxic doses cause intraventricular conduction disturbances due to local anesthetic action. Atropine block parasympathetic mediated coronary dilation. Blood pressure level is minimally affected by atropine.

Based on multiple epidemiological studies, compared to the non-diabetics of same sex and age, risk of developing cardiovascular disease is doubled in diabetics. The mortality due to cardiovascular diseases in type 2 DM is also increased. The doubled cardiovascular risk among diabetics remains even if the conventional risk factors for cardiovascular disease like hypertension, dyslipidemia, smoking, lack of physical activity are within normal limits. This suggests the presence of multiple other mechanism for the raised risk. Among the cardiovascular abnormalities, Ventricular instability which is manifested in QT abnormalities, is an important mechanism seen at higher rate in diabetics. The time needed for ventricular repolarization in an electrocardiogram is denoted by QT interval. By adjusting for heart rate this interval is termed as, the corrected QT interval(QTc). QTc is corrected in accordance with heart rate. The corrected QT (QTc) prolongation is nothing but the increased length of the QT interval indicating presence of a precursor of torsade de pointes, which is life-threatening ventricular dysrhythmia and ventricular fibrillation 1 . Morbidity and mortality is raised in people with QTc

The test is performed by the patient blowing into a mouthpiece connected to a modified sphygmomanometer and holds it at a pressure of 40 mm Hg for 15 seconds during which a continuous ECG is recorded. this test is performed 3 times with one minute interval between each.Patients with proliferative retinopathy should not undergo Valsalva because of the risk of retinal haemorrhage”[55].”The result of Valsalva test is expressed as the ratio of the longest R-R interval[55] after the manoeuvre(overshoot bradycardia following release) to the shortest R-R interval during the manoeuvre(tachycardia during the phase of strain),measured using a ruler from the electrocardiogram tracing..The mean of the three valsalva ratios is taken as the final value “[55

The infant in our study had 3 normal ECGs during his early life. However, continuous QTc monitoring demonstrated an acute and dramatic change that correlated with clinically relevant deterioration. Al- though determining causation and the exact mechanism of this phenomenon is impossible at this time, the QTc served as a noninvasive barometer of the health and stability of the patient ’ s ANS. Auto- nomic stressors are often cumulative and only result in clinical signi fi cance in an infant at critical times of autonomic or clinical vulnerability. The goal is to use the QTc to be able to detect these vul- nerable states in an attempt to intervene

RESULTS. We identified 52 newborns exposed to selective serotonin-reuptake inhibitor antidepressants in the immediate antepartum period and 52 matched control sub- jects. The mean QTc was significantly longer in the group of newborns exposed to antidepressants as compared with control subjects (409 ⫾ 42 vs 392 ⫾ 29 millisec- onds). Five (10%) newborns exposed to selective serotonin-reuptake inhibitor an- tidepressants had a markedly prolonged QTc interval ( ⬎ 460 milliseconds) compared with none of the unexposed newborns. The longest QTc interval observed among exposed newborns was 543 milliseconds. All of the drug-associated repolarization abnormalities normalized in subsequent electrocardiographic tracings.

This open-label randomized clinical trial included 50 American Society of Anesthesiologists physical status 1 or 2 patients aged 20–69 years who underwent elective lumbar spine surgery, including laminectomy, micro- scopic discectomy, microendoscopic discectomy, or spinal fusion, under general anesthesia between August 2016 and July 2017. The exclusion criteria included a medical history of ischemic heart disease, diabetes, asthma, preoperative electrocardiographic abnormalities, body mass index > 30 kg/m 2 , and preoperative medica- tions known to prolong the QTc interval, including β-adrenergic antagonists, antiarrhythmic agents, and anti- hypertensive medications such as calcium antagonists, angiotensin-converting enzyme inhibitors, and angioten- sin 2 receptor antagonists. None of the patients received any preanesthetic medication.

The baseline demographic and selected clinical para- meters on admission (day 0) for the two treatment groups were similar (Table 1). There was a difference in the mean ECG parameters before (day 0) and immedi- ately after (day 3) treatment, within each of the treat- ment groups (p<0.01). However, there were no significant differences between the ECG intervals in the two groups on days 3, or day 7 (Table 2). The proportion of subjects with bradycardia (defined as a ventricular rate below the normal for age), was significantly higher (p=0.03) in the artesunate-amodiaquine group (14.8%; 7/47), compared with the artemether-lumefantrine group (0/30). The mean age of subjects who developed brady- cardia (11.8 years) was significantly higher (p<0.001) than those who did not (6.3 years). Selected characteris- tics of subjects who developed bradycardia are shown (Table 3). The proportion of subjects with QTc interval change greater than 30 ms from baseline was also higher in the artesunate-amodiaquine group (31.9%; 15/47) compared with the artemether-lumefantrine group (20%; 6/30), but the difference was not statistically significant (OR, 1.9, 95% CI, 0.6-6.4, p=0.25), and this was not con- fined to older age groups. Selected characteristics of sub- jects with QTc increase more than 60 ms from baseline are shown (Table 4).

According to internationally accepted guidelines, the QTC interval was considered prolonged when higher than 440 ms for male patients, and higher than 460 ms for female patients [15]. The QT dispersion was considered prolonged when higher than 65 ms, according to other previously conducted studies [16]. Measurement of the Tpeak-Tend interval was conducted in DII, V2 and V5 leads. The Tpeak-Ted interval was obtained from the difference between QT interval and QT peak interval. The Tpeak-Tend interval was considered prolonged when greater than 100 ms, and the Tpeak-Tend dispersion was considered prolonged when higher than 20 ms, as suggested by otherstudies [17]. The ECG was performed by the same operator, and the aforementioned measurements were made by two independent observers.In case of disagreement on the values obtained, the measurements were repeated by a third observer with expertise in electrocardiographic analysis.

The QTc interval reflects the total time taken for ven- tricular myocardial depolarization and repolarization, and metabolic, morphological, functional and structural abnormalities of the myocardium may induce ventricu- lar myocardial membrane electrical destabilization and a subsequent increase in the QT interval. In an animal study, Lin et al. [31] observed that obese, insulin-resist- ant, 16 to 17-week-old rats developed cardiac hyper- trophy, exhibited defective inactivation of current, and presented altered electrophysiology characterized by a prolongation of QTc interval. This study suggests that defective calcium inactivation can cause prolongation of the QT interval in patients presented with insulin resist- ance. Type 2 diabetes is associated with a high prevalence of left ventricular hypertrophy [32], and left ventricular mass is a strong determinant of the QT interval in these patients [9]. Insulin resistance may be important in the development of left ventricular diastolic dysfunction and structure in patients with type 2 diabetes mellitus [33–35]. Insulin resistance and associated hyperinsuline- mia in type 2 diabetes can promote the development of a specific form of cardiomyopathy, which is also termed diabetic cardiomyopathy, manifested by left ventricular hypertrophy and diastolic dysfunction [36]. The myocar- dial triglyceride content is increased in type 2 diabetes patients with insulin resistance [37] and could contribute