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Bupropion toxicity can cause cardiogenic shock, ventricular dysrhythmias, and death. Clinical and electrocardiographic factors associated with adverse cardiovascular events in bupropion toxicity have not been well-studied. This study aimed to identify factors associated with adverse cardiovascular events in adult patients with isolated bupropion exposures. This retrospective cohort study queried the National Poison Data System from 2019 through 2020. We included patients 20 years or older with acute or acute-on-chronic single-agent bupropion exposures evaluated in a healthcare facility. Exclusion criteria were confirmed non-exposure, withdrawal as a reason for exposure, lack of follow-up, documentation that exposure was probably not responsible for the effects, and missing data. The primary outcome was adverse cardiovascular events, defined as the presence of any of the following: vasopressor use, ventricular dysrhythmia, myocardial injury, or cardiac arrest. Independent variables were age, the intentionality of exposure, seizures, tachycardia, QRS widening, and QTc prolongation. Multivariable logistic regression was performed to test for independent associations between independent variables and adverse cardiovascular events. Of 4,640 patients included in the final analysis (56.7% female, 56.5% suspected suicidal intent), 68 (1.47%) experienced an adverse cardiovascular event. Age (odds ratio 1.03; 95% confidence intervals 1.02–1.05), single seizure (odds ratio 9.18; 95% confidence intervals 4.24–19.9) and complicated seizures (odds ratio 38.9; 95% confidence intervals 19.3–78.1), QRS widening (odds ratio 3.01; 95% confidence intervals 1.62–5.59), and QTc prolongation (odds ratio 1.76; 95% confidence intervals 1.00–3.10) were independently associated with adverse cardiovascular events. No patients with unintentional exposure experienced adverse cardiovascular events, prohibiting intentionality from inclusion in the regression model. In the post hoc subgroup analysis of intentional exposures, age, single and complicated seizures, and QRS widening remained independently associated with adverse cardiovascular events. Increasing age, seizures, QRS widening, and QTc prolongation were associated with adverse cardiovascular events in bupropion exposures. Adverse cardiovascular events did not occur in unintentional exposures. Further research is needed to develop screening tools and treatments for bupropion cardiotoxicity. [ABSTRACT FROM AUTHOR]

Psychotropic drugs such as antipsychotics may prolong the QTc interval, increasing the risk of torsades de pointes (TdP) and sudden cardiac death. To assess QTc prolongation by psychotropic drugs, an electrocardiogram (EKG) is usually recorded before and after starting treatment. Circadian variations in the QTc interval have been described but have not been adequately studied in patients taking psychotropic drugs. In psychiatric clinical practice, EKGs before and after treatment initiation are often compared, without considering the time of day at which the two EKGs are recorded. To determine whether there is a circadian change in the QTc interval in patients treated with psychotropic drugs, we evaluated the EKGs of a group of patients treated with psychotropic drugs (85% on antipsychotics) and the EKGs of a group of patients that were not treated with medications. In each group, we compared the EKGs recorded before 11:00 am with those recorded after 5:00 pm. The QTc value was significantly longer in the group treated with psychotropic drugs than in the group without drugs at both morning and evening evaluations (p ≤ 0.001). In each group, a statistically significant difference was found between the EKGs recorded before 11:00 a.m. and the EKGs recorded after 5:00 p.m. In patients treated with medications, the mean QTc in the morning was 453.3 ± 25.4 while the mean QTc in the afternoon was 428.4 ± 24.7 (p < 0.0001). In patients who were not receiving any medication, the morning mean QTc was 422.4 ± 22.6 while the mean afternoon QTc was 409.4 ± 19.6 (p = 0.002). These results suggest that a circadian variation in QTc is observed both in patients taking psychotropic drugs and in patients not taking medication. We conclude that any comparison of EKGs to test the effect on QTc of a medication, should be referred to EKGs recorded at the same time of day. [ABSTRACT FROM AUTHOR]

Prolonged corrected QT (QTc) interval is a hallmark of cirrhotic cardiomyopathy (CCM) and has been ascertained to predict mortality in cirrhosis. However, some critical issues remain to be addressed including unanimous cut-off, calculation approach and applicable population. A total of 274 patients with cirrhosis were included. The prolonged QTc interval over 440 ms according to adjusted Fridericia's formula was used to stratify enrolled subjects. Independent predictors of 3-year mortality were identified with Cox regression model. The Kaplan–Meier method was implemented to obtain survival curves. To reduce impact of selection bias and possible confounders, a propensity score matching (PSM) analysis was used. QTc > 440 ms was an independent risk factor in the entire cohort and PSM subset (HR 2.532, 95% CI 1.431–4.480, p=.001; HR 2.802, 95% CI 1.171–6.701, p=.021, respectively). Subgroup analysis showed that QTc > 440 ms was an independent predictor in cirrhotics with age ≤60 years (HR = 1.02, p=.035) and in the presence of ascites (HR = 1.01, p=.008). The prolonged QTc interval might help to identify patients with high-risk of all-cause mortality. [ABSTRACT FROM AUTHOR]

Background: Angiotensin receptor neprilysin inhibitor (ARNI, sacubitril/valsartan) reduces sudden death in heart failure with reduced ejection fraction (HFrEF). Corrected QT (QTc), T-wave peak to T-wave end interval (Tp-e) and Tp-e/QTc are electrocardiographic indices of ventricular repolarization heterogeneity. We aimed to assess the effects of switching from ramipril to ARNI on electrocardiographic indices of ventricular repolarization. Methods: A total of 48 patients with HFrEF (mean age: 63.3 ± 11.7 years; 36 males, 77.1% ischaemic etiology) were enrolled. All patients had New York Heart Association functional class II–III, left ventricular ejection fraction ≤35% and previously switched from ramipril to ARNI treatment. The standard 12-lead electrocardiograms on ramipril treatment and 1 month after ARNI treatment were analysed; heart rate, QTc, Tp-e and Tp-e/QTc were calculated. Minnesota Living with Heart Failure Questionnaire (MLWHFQ) scores and N-terminal pro-BNP (NT-proBNP) values were recorded. Results: QTc (415.2 ± 19.7 ms vs. 408.5 ± 20.8 ms, p = 0.022), Tp-e (100.7 ± 13.8 ms vs. 92.9 ± 12.1 ms, p < 0.001), Tp-e/QTc (0.242 ± 0.028 vs. 0.227 ± 0.029, p = 0.003) and heart rate (73.2 ± 4.7 bpm vs. 71.1 ± 4.9 bpm, p = 0.027) were reduced after ARNI. ARNI switch associated with improvement in MLWHFQ scores (32.4 ± 7.1 ms vs. 22.6 ± 7.0 ms, p < 0.001) and reduction of NT-proBNP (2457 ± 1879 pg/ml to 1377 ± 874 pg/ml, p < 0.001). Pearson's correlation analysis revealed moderate correlations of MLWHFQ score with Tp-e (r = 0.543, p = 0.001) and Tp-e/QTc (r = 0.556, p = 0.001). Conclusions: Switching from ramipril to ARNI favourably alters QTc, Tp-e and Tp-e/QTc in HFREF. ARNI reduces symptoms of HFREF assessed by MLWHFQ and lowers NT-proBNP levels. Reduction in Tp-e and Tp-e/QTc correlate with clinical improvement in patients with HFrEF. [ABSTRACT FROM AUTHOR]

Introduction: 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. Results: 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 < .0001; CI 2.22-10.74), two risk factors the OR was 6.922 (p < .0001; CI 2.94-16.28) and three or more risk factors, the OR was 13.997 (p < .0001; CI 5.649-34.68). Adding QTc > 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. Conclusions: Prolonged QTc was a risk factor for SCD and death even when controlling for typical risk factors. [ABSTRACT FROM AUTHOR]

The Qualitative Trajectory Calculus (QTC) is a qualitative spatio-temporal calculus for describing interactions between moving point objects. So far, it remained unclear whether QTC is useful for describing subtle differences, such as between the movements of different parts of a human body. We tested the applicability of QTC to detect differences in the gait patterns of children with or without Developmental Coordination Disorder (DCD). We found that using a combination of three markers (i.e. ankle, toe and trochanter), QTC can achieve a high classification accuracy (i.e. 83.3%) of classifying subjects correctly to either the DCD group or the control group. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the prevalence and longitudinal changes of prolonged QTc in DM patients admitted to our community hospital, and to determine, if any, its correlation with changes of left ventricular ejection fraction (LVEF).Methods: A retrospective chart review of patients with Type 1 (T1DM) and Type 2 (T2DM) with at least two admissions during a four-year period was performed to identify QTc interval, and LVEF, as measured on transthoracic echocardiogram. Changes in QTc and LVEF between patient hospital admissions were compared.Results: A prolonged QTc interval was found in 66.7% (n = 24) of type 1 and 51.3% (n = 154) type 2 diabetic patients. The QTc interval is progressively increased in both type 1 and type 2 diabetes during follow-up, although it did not reach statistical significance. A total of 62% patients (23 out 37 patients) had a reduction of LVEF during follow-up.Conclusion and Discussion: High prevalence of QTc prolongation was confirmed in hospitalized patients with in both T1DM and T2DM. Significant reduction of LVEF correlated with QTc prolongation over a mean of 17.3 months in T2DM patients, and may have implications for interventions. AbbreviationsCHF: Congestive heart failure LVEF: Left ventricular ejection fraction [ABSTRACT FROM PUBLISHER]

Aim: We aimed to investigate the QT dispersion and corrected QT (QTc) dispersion which are suggested as the signals of ventricular arrhythmias, in patients on maintenance CAPD and to evaluate the correlation between iron stores and these electrocardiographic parameters. Materials and method: Fifty-eight patients on maintenance CAPD and 19 healthy age- and sex-matched adults without cardiac disease were included. The PD patients were divided into two groups according to whether their computerized measurements of QTc dispersion were longer than 65 ms. Results: Although QT interval was statistically significantly shorter in control group (34 ± 28 vs. 43 ± 34 ms; p < 0.05), there was no significant difference in regards to the QTc, QT dispersion and QTc dispersion between two groups. PD patients with QTc dispersion longer than 65 ms had higher levels of serum ferritin ( p = 0.038) and transferrin saturation (TSAT; p = 0.022) than the others. QTc dispersion were positively correlated with ferritin ( r = 0.469, p < 0.01) and TSAT ( r = 0.430, p < 0.01) in CAPD patients. Conclusion: Although prolonged QTc, QT dispersion and QTc dispersion were suggested as the markers of ventricular arrhythmias we did not find any significant difference in regards to these parameters between control patients and CAPD patients. But the high body iron stores in these patients increase the risk of increased QT dispersion. The concern over iron overload in dialysis patients is not only because of its oxidative toxicity, but also its precipitation of arrhythmias, which may be measured by the surrogate marker of QTc dispersion. [ABSTRACT FROM AUTHOR]

Objective: Abnormalities observed in the electrocardiogram (ECG) after acute central nervous system (CNS) events have been reported. Our objective was to assess the incidence of heart rate-corrected QT interval (QTc) prolongation in patients admitted to the intensive care unit (ICU) after brain surgery. Methods: Admission standard 12-lead ECGs were analyzed blinded to patient data. The QT interval was measured and Bazzett's formula was used to obtain QTc. Prolonged QTc was defined as ≥450 ms. Results: We included 114 patients in the study. The mean age was 49&≤177;17 years. Brain neoplasm was the surgical indication in 90% of the patients. The mean QTc was 470&≤177;42 ms. Prolonged QTc was found in 71% patients. The heart rate-corrected QT interval was between 450 ms and 500 ms in 52% and .500 ms in 19% of the patients. The heart rate and concentration of serum glucose were higher in the prolonged QTc group. Only 7.5% of all patients had hypokalemia (≤3 mEq/l). In the prolonged QTc group 9.2% had hypokalemia compared to 3.2% in normal QTc patients (P 5 0.406). There were no significant associations between categories of QTc and the serum levels of creatinine, magnesium, calcium, sodium, or pH. Phenytoin and metoclopramide were not frequently used in patients with prolonged QTc. Discussion: This study supports our hypothesis that prolonged QTc is frequently observed after a brain surgery. Hypokalemia, hypocalcaemia, and drugs such as metoclopramide or phenytoin could not explain the high incidence of prolonged QTc. Brain injury during a surgical procedure may be one of the primary causes of QTc prolongation after neurosurgery. [ABSTRACT FROM AUTHOR]

This paper compares six commonly used QT correction models and three available parameter estimation methods using five indices for QTc evaluation based on real and simulated electrocardiograph (ECG) datasets. The results show that the golden section approach always finds the correction factor making QTc interval uncorrelated to heart rate for all six formulas. However, the correction formulas derived from mixed model sometimes fail to make QTc interval invariant of heart rate. The performance of an individual least-square regression method lies between the golden section iteration approach and the mixed model in terms of QTc–RR relationship. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine if multiple reef fish aggregation sites in the upper Florida Keys share characteristic geomorphic features. A commercial single-beam acoustic seabed classification system was used to map the seabed in the vicinity of reported or observed black grouper (Mycteroperca bonaci), mutton snapper (Lutjanus analis), and yellowtail snapper (L. chrysurus) aggregation sites. Results showed that drowned, margin-parallel, rocky ridges, known locally as outlier reefs, were features found in proximity to all of the mapped aggregation sites. In particular, three geomorphic characteristics were observed at most sites: a steep slope of the landward boundary of the upper slope terrace, an exposed outlier reef forming the seaward boundary of the upper slope terrace, and at least one other exposed outlier reef on the upper slope terrace. The results suggest that the acoustic-mapping technologies used herein could be valuable when considering the placement of marine reserves. [ABSTRACT FROM PUBLISHER]

This study studied the safety of fluticasone propionate/salmeterol combination (FSC) 100/50 HFA (2 inhalations of 50/25 mcg) twice daily, compared with fluticasone propionate (FP) 100 HFA (two inhalations of 50 mcg) twice daily, over a 12-week treatment period in subjects aged 4–11 years with persistent asthma. Of the 350 subjects randomized to receive double-blind treatment, 173 received FSC 100/50 HFA and 177 received FP 100 HFA. The two treatment groups were comparable in adverse events profiles, vital signs, asthma exacerbations, oropharyngeal examinations, clinical laboratory tests and urinary cortisol levels. The use of spacer did not meaningfully modify cortisol levels. The pre-specified analysis of 12-lead electrocardiograms (ECGs) identified abnormalities during screening as well as post-randomization in both study treatments, even though randomized subjects were without pre-existing cardiovascular disorders. An ad hoc analysis of the ECG data found no clinically relevant ECG abnormalities either prior to randomization or after randomization to study treatments. Thus, the ECG findings were false-positives related to details of the pre-specified analysis. This study highlights the importance of methodology when interpreting ECG data in a pediatric clinical trial. Overall, both FSC 100/50 HFA and FP 100 HFA were well-tolerated in children aged 4–11 years with persistent asthma. [ABSTRACT FROM AUTHOR]

We propose to use generalized additive models to fit the relationship between QT interval and RR (RR = 60/heart rate), and develop two new methods for correcting the QT for heart rate: the linear additive model and log-transformed linear additive model. The proposed methods are compared with six commonly used parametric models that were used in four clinical trial data sets and a simulated data set. The results show that the linear additive models provide the best fit for the vast majority of individual QT-RR profiles. Moreover, the QT correction formula derived from the linear additive model outperforms other correction methods. [ABSTRACT FROM AUTHOR]

The CYP2D6 gene is highly polymorphic, causing absent (poor metabolizers), decreased, normal or increased enzyme activity (extensive and ultrarapid metabolizers). The genetic polymorphism of the CYP2D6 influences plasma concentration of a wide variety of drugs metabolized in the liver by the cytochrome P450 (CYP) 2D6 enzyme, including antipsychotic drugs used for schizophrenia treatment. Additionally, CYP2D6 is involved in the metabolism of endogenous substrates in the brain, and reported to be located in regions such as the cortex, hippocampus and cerebellum, which are impaired in schizophrenia. Moreover, recently we have found that CYP2D6 poor metabolizers are under-represented in a case-control association study of schizophrenia. Furthermore, null CYP2D6 activity in healthy volunteers is associated with personality characteristics of social cognitive anxiety, which may bear some resemblance to milder forms of psychotic-like symptoms. In keeping with this, CYP2D6 may influence, not only variability to drug response, but also vulnerability to disease in schizophrenia patients. [ABSTRACT FROM AUTHOR]