Harmen H.M. Draisma

Normal limits of the spatial QRS-T angle and ventricular gradient in 12-lead electrocardiograms of young adults: dependence on sex and heart rate

BACKGROUND AND PURPOSE Normal limits of the spatial QRS-T angle and spatial ventricular gradient (SVG) are only available from Frank vectorcardiograms (VCGs) of male subjects. We determined normal limits for these variables derived from standard 12-lead electrocardiograms (ECGs) of 660 male and female students aged 18 to 29 years. METHODS A computer algorithm was used that constructed approximated VCG leads by inverse Dower matrix transformation of the 12-lead ECG and subsequently calculated the spatial QRS-T angle, SVG magnitude, and orientation. RESULTS In female subjects, the QRS-T angle was more acute (females, 66 degrees +/- 23 degrees; normal, 20 degrees-116 degrees; males, 80 degrees +/- 24 degrees; normal, 30 degrees-130 degrees; P < .001), and the SVG magnitude was smaller (females, 81 +/- 23 mV x ms; normal, 39-143 mV x ms; males, 110 +/- 29 mV x ms; normal, 59-187 mV x ms; P < .001) than in male subjects. The male SVG magnitude in our study was larger than that computed in Frank VCGs (79 +/- 28 mV.ms; P < .001). CONCLUSIONS The spatial QRS-T angle and SVG depend strongly on sex. Furthermore, normal limits of SVG derived from Frank VCGs differ markedly from those derived from VCGs synthesized from the standard ECG. As nowadays, VCGs are usually synthesized from the 12-lead ECG; normal limits derived from the standard ECG should preferably be used.

Validation of ECG Indices of Ventricular Repolarization Heterogeneity: A Computer Simulation Study

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)).

Reconstruction of standard 12-lead electrocardiograms from 12-lead electrocardiograms recorded with the Mason-Likar electrode configuration.

Electrocardiograms (ECGs) made with Mason-Likar electrode configuration (ML-ECGs) show well-known differences from standard 12-lead ECGs (Std-ECGs). We recorded, simultaneously, Std-ECGs and ML-ECGs in 180 subjects. Using these ECGs, 8 x 8 individual and general conversion matrices were created by linear regression, and standard ECGs were reconstructed from ML-ECGs using these matrices. The performance of the matrices was assessed by the root mean square differences between the original Std-ECGs and the reconstructed standard ECGs, by the differences in major ECG parameters, and by comparison of computer-generated diagnostic statements. As a result, we conclude that, based on the root mean square differences, reconstructions with 8 x 8 individual matrices perform significantly better than reconstructions with the group matrix and perform equally well with respect to the calculation of major electrocardiographic parameters, which gives an improved reliability of the QRS frontal axis and the maximal QRS and T amplitudes. Both types of matrices were able to reverse the underdiagnosis of inferior myocardial infarctions and the erroneous statements about the QRS frontal axis that arose in the ECGs that were made by using the Mason-Likar electrode positions.

RNA-Seq in 296 phased trios provides a high resolution map of genomic imprinting

Combining allelic analysis of RNA-Seq data with phased genotypes in family trios provides a powerful method to detect parent-of-origin biases in gene expression. We report findings in 296 family trios from two large studies: 165 lymphoblastoid cell lines from the 1000 Genomes Project, and 131 blood samples from the Genome of the Netherlands participants (GoNL). Based on parental haplotypes we identified >2.8 million transcribed heterozygous SNVs phased for parental origin, and developed a robust statistical framework for measuring allelic expression. We identified a total of 45 imprinted genes and one imprinted unannotated transcript, 17 of which have not previously been reported as showing parental expression bias. Multiple novel imprinted transcripts showing incomplete parental expression bias were located adjacent to known strongly imprinted genes. For example, PXDC1, a gene which lies adjacent to the paternally-expressed gene FAM50B, shows a 2:1 paternal expression bias. Other novel imprinted genes had promoter regions that coincide with sites of parentally-biased DNA methylation identified in blood from uniparental disomy (UPD) samples, thus providing independent validation of our results. Using the stranded nature of the RNA-Seq data in LCLs we identified multiple loci with overlapping sense/antisense transcripts, of which one is expressed paternally and the other maternally. Using a sliding window approach, we searched for imprinted expression across the entire genome, identifying a novel imprinted putative lncRNA in 13q21.2. Our methods and data provide a robust and high resolution map of imprinted gene expression in the human genome.