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- Ntalla, Ioanna, et al.
(author)
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Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction
- 2020
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Journal article (peer-reviewed)abstract
- The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.
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2. |
- ter Haar, C. Cato, et al.
(author)
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Difference vectors to describe dynamics of the ST segment and the ventricular gradient in acute ischemia
- 2013
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In: Journal of Electrocardiology. - : Elsevier BV. - 1532-8430 .- 0022-0736. ; 46:4, s. 302-311
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Journal article (peer-reviewed)abstract
- Background: The ECG is important in the diagnosis and triage of the acute coronary syndrome (ACS), especially in the hyperacute phase, the "golden hours," during which myocardial salvage possibilities are largest. An important triaging decision to be taken is whether or not a patient requires primary PCI, for which, as mentioned in the guidelines, the presence of an ST elevation (STE) pattern in the ECG is a major criterion. However, preexisting non-zero ST amplitudes (diagnostic, but also non-diagnostic) can obscure or even preclude this diagnosis. Methods: In this study, we investigated the potential diagnostic possibilities of ischemia detection by means of changes in the ST vector, Delta ST, and changes in the VG (QRST integral) vector, Delta VG. We studied the vectorcardiograms (VCGs) synthesized of the ECGs of 84 patients who underwent elective PTCA. Mean +/- SD balloon occlusion times were 260 +/- 76 s. The ECG ischemia diagnosis (ST elevation, STE, or non-ST-elevation, NSTE), magnitudes and orientations of the ST and VG vectors, and the differences Delta ST and Delta VG with the baseline ECG were measured after 3 min of balloon occlusion. Results: Planar angles between the Delta ST and Delta VG vectors were 14.9 +/- 14.0 degrees. Linear regression of Delta VG on Delta ST yielded Delta VG = 324. Delta ST (r = 0.85; P < 0.0001, Delta ST in mV). We adopted Delta ST > 0.05 mV, and the corresponding Delta VG > 16.2 mV.ms as ischemia thresholds. The classical criteria characterized the ECGs of 46/84 (55%) patients after 3 min of occlusion as STE ECGs. Combined application of the Delta ST and Delta VG criteria identified 73/84 (87%) of the patients as ischemic. Conclusion: Differential diagnosis by Delta ST and Delta VG (requiring an earlier made non-ischemic baseline ECG) could dramatically improve ECG guided detection of patients who urgently require catheter intervention. (C) 2013 Elsevier Inc. All rights reserved.
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3. |
- Almer, Jakob, et al.
(author)
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Ischemic QRS prolongation as a biomarker of severe myocardial ischemia.
- 2016
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In: Journal of Electrocardiology. - : Elsevier BV. - 1532-8430 .- 0022-0736. ; 49:2, s. 139-147
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Journal article (peer-reviewed)abstract
- Previous studies have shown that QRS prolongation is a sign of depressed collateral flow and increased rate of myocardial cell death during coronary occlusion. The aims of this study were to evaluate ischemic QRS prolongation as a biomarker of severe ischemia by establishing the relationship between prolongation and collateral flow experimentally in a dog model, and test if the same pattern of ischemic QRS prolongation occurs in man.
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