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Introduction: Repolarization heterogeneity (RH) is functionally linked to dispersion in refractoriness and to arrhythmogenicity. In the current study, we validate several proposed electrocardiogram (ECG) indices for RH: T-wave amplitude, -area, -complexity, and -symmetry ratio, QT dispersion, and the Tapex-end interval (the latter being an index of transmural dispersion of the repolarization (TDR)). Methods and Results: We used ECGSIM, a mathematical simulation model of ECG genesis in a human thorax, and varied global RH by increasing the standard deviation (SD) of the repolarization instants from 20 (default) to 70 msec in steps of 10 msec. T-wave amplitude, -area, -symmetry, and Tapex-end depended linearly on SD. T-wave amplitude increased from 275 ± 173 to 881 ± 456 μV, T-wave area from 34 × 103± 21 × 103 to 141 × 103± 58 × 103μV msec, T-wave symmetry decreased from 1.55 ± 0.11 to 1.06 ± 0.23, and Tapex-end increased from 84 ± 17 to 171 ± 52 msec. T-wave complexity increased initially but saturated at SD = 50 msec. QT dispersion increased modestly until SD = 40 msec and more rapidly for higher values of SD. TDR increased linearly with SD. Tapex-end increased linearly with TDR, but overestimated it. Conclusion: T-wave complexity did not discriminate between differences in larger RH values. QT dispersion had low sensitivity in the transitional zone between normal and abnormal RH. In conclusion, T-wave amplitude, -area, -symmetry, and, with some limitations, Tapex-end and T-wave complexity reliably reflect changes in RH. [ABSTRACT FROM AUTHOR]

Background and Aim: Previous studies have shown a relationship between schizophrenia and cannabis use. As both traits are substantially heritable, a shared genetic liability could explain the association. We use two recently developed genomics methods to investigate the genetic overlap between schizophrenia and cannabis use.Methods: Firstly, polygenic risk scores for schizophrenia were created based on summary statistics from the largest schizophrenia genome-wide association (GWA) meta-analysis to date. We analysed the association between these schizophrenia polygenic scores and multiple cannabis use phenotypes (lifetime use, regular use, age at initiation, and quantity and frequency of use) in a sample of 6,931 individuals. Secondly, we applied LD-score regression to the GWA summary statistics of schizophrenia and lifetime cannabis use to calculate the genome-wide genetic correlation.Results: Polygenic risk scores for schizophrenia were significantly (α<0.05) associated with five of the eight cannabis use phenotypes, including lifetime use, regular use, and quantity of use, with risk scores explaining up to 0.5% of the variance. Associations were not significant for age at initiation of use and two measures of frequency of use analyzed in lifetime users only, potentially because of reduced power due to a smaller sample size. The LD-score regression revealed a significant genetic correlation of rg=0.22 (SE=0.07, p=0.003) between schizophrenia and lifetime cannabis use.Conclusions: Common genetic variants underlying schizophrenia and lifetime cannabis use are partly overlapping. Individuals with a stronger genetic predisposition to schizophrenia are more likely to initiate cannabis use, use cannabis more regularly, and consume more cannabis over their lifetime. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To assess the effect of pulmonary valve replacement (PVR) on the repolarization of patients with tetralogy of Fallot. Background: Pulmonary valve regurgitation may cause right ventricular failure in adult patients with Fallot''s tetralogy. In these patients, prolonged depolarization and disturbed repolarization are associated with ventricular arrhythmias and sudden cardiac death. Methods: Thirty Fallot patients (age 32±9 years, 19 male) eligible for PVR were studied with cardiac magnetic resonance imaging (CMR) before and 6 months after PVR. Electrocardiograms obtained during initial and follow-up CMR were analyzed and occurrence of ventricular arrhythmias was studied. Results: Right ventricular end-diastolic volume (RV EDV) decreased from 322±87 to 215±57 ml after PVR (P <0.0001). The spatial QRS-T angle normalized from 117±34 to 100±35°, P =0.0004 (normal angle <105°). QT dispersion and T-wave complexity did not change significantly. T-wave amplitude decreased from 376±121 to 329±100 μV (P =0.01). T-wave area decreased from 43±15 to 38±13 μV s (P =0.02). Decreases in T-wave amplitude and area were most prominent in the right precordial leads overlying the RV. Three patients had sustained ventricular arrhythmias and one patient died suddenly. These patients had a QRS duration >160 ms. No severe ventricular arrhythmias were found in patients with a RV EDV <220 ml, QRS-T angle <100°, QT dispersion <60 ms or T-wave complexity <0.30. Conclusion: Normal repolarization indices may be associated with the absence of severe ventricular arrhythmias. PVR in Fallot patients with dilated right ventricles has a beneficial effect on electrocardiographic indices of repolarization heterogeneity. [Copyright &y& Elsevier]