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- Diamant, Ulla-Britt, 1955-, et al.
(författare)
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Electrophysiological phenotype in the LQTS mutations Y111C and R518X in the KCNQ1 gene
- 2013
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Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 115:10, s. 1423-1432
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Tidskriftsartikel (refereegranskat)abstract
- Long QT syndrome is the prototypical disorder of ventricular repolarization (VR), and a genotype-phenotype relation is postulated. Furthermore, although increased VR heterogeneity (dispersion) may be important in the arrhythmogenicity in long QT syndrome, this hypothesis has not been evaluated in humans and cannot be tested by conventional electrocardiography. In contrast, vectorcardiography allows assessment of VR heterogeneity and is more sensitive to VR alterations than electrocardiography. Therefore, vectorcardiography was used to compare the electrophysiological phenotypes of two mutations in the LQT1 gene with different in vitro biophysical properties, and with LQT2 mutation carriers and healthy control subjects. We included 99 LQT1 gene mutation carriers (57 Y111C, 42 R518X) and 19 LQT2 gene mutation carriers. Potassium channel function is in vitro most severely impaired in Y111C. The control group consisted of 121 healthy subjects. QRS, QT, and T-peak to T-end (Tp-e) intervals, measures of the QRS vector and T vector and their relationship, and T-loop morphology parameters were compared at rest. Apart from a longer heart rate-corrected QT interval (QT heart rate corrected according to Bazett) in Y111C mutation carriers, there were no significant differences between the two LQT1 mutations. No signs of increased VR heterogeneity were observed among the LQT1 and LQT2 mutation carriers. QT heart rate corrected according to Bazett and Tp-e were longer, and the Tp-e-to-QT ratio greater in LQT2 than in LQT1 and the control group. In conclusion, there was a marked discrepancy between in vitro potassium channel function and in vivo electrophysiological properties in these two LQT1 mutations. Together with previous observations of the relatively low risk for clinical events in Y111C mutation carriers, our results indicate need for cautiousness in predicting in vivo electrophysiological properties and the propensity for clinical events based on in vitro assessment of ion channel function alone.
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| 2. |
- Vahedi, Farzad, et al.
(författare)
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Effect of heart rate on ventricular repolarization in healthy individuals applying vectorcardiographic T vector and T vector loop analysis.
- 2011
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Ingår i: Annals of Noninvasive Electrocardiology. - : John Wiley & Sons. - 1542-474X .- 1082-720X. ; 16:3, s. 287-294
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Tidskriftsartikel (refereegranskat)abstract
- Background: Ventricular repolarization (VR) is strongly influenced by heart rate (HR) and autonomic nervous activity, both of which also are important for arrhythmogenesis. Their relative influence on VR is difficult to separate, but might be crucial for understanding while some but not other individuals are at risk for life-threatening arrhythmias at a certain HR. This study was therefore designed to assess the “pure” effect of HR increase by atrial pacing on the ventricular gradient (VG) and other vectorcardiographically (VCG) derived VR parameters during an otherwise unchanged condition. Methods: In 19 patients with structurally normal hearts, a protocol with stepwise increased atrial pacing was performed after successful arrhythmia ablation. Conduction intervals were measured on averaged three-dimensional (3D) QRST complexes. In addition, various VCG parameters were measured from the QRS and T vectors as well as from the T loop. All measurements were performed after at least 3 minutes of rate adaptation of VR. Results: VR changes at HR from 80 to 120 bpm were assessed. The QRS and QT intervals, VG, QRSarea, Tarea, and Tamplitude were markedly rate dependent. In contrast, the Tp-e/QT ratio was rate independent as well as the T-loop morphology parameters Tavplan and Teigenvalue describing the bulginess and circularity of the loop. Conclusions: In healthy individuals, the response to increased HR within the specified range suggests a decreased heterogeneity of depolarization instants, action potential morphology, and consequently of the global VR.
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| 3. |
- Vahedi, Farzad, et al.
(författare)
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Instability of repolarization in LQTS mutation carriers compared to healthy control subjects assessed by vectorcardiography
- 2013
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Ingår i: Heart Rhythm. - : Elsevier BV. - 1547-5271 .- 1556-3871. ; 10:8, s. 1169-1175
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Potassium channel dysfunction in congenital and acquired forms of long QT syndrome types 1 and 2 (LQT1 and LQT2) increases the beat-to-beat variability of the (IT interval. OBJECTIVE To study about the little known variability (instability) of other aspects of ventricular repolarization (VR) in humans by using vectorcardiography. METHODS Beat-to-beat analysis was performed regarding vectorcardiography derived RR, QRS, and QT intervals, as well as T vector- and T vector loop-based parameters during 1-minute recordings of uninterrupted sinus rhythm at rest in 41 adult LQT1 (n = 31) and LQT2 (n = 10) mutation carriers and 41 age- and sex-matched control subjects. The short-term variability for each parameter, describing the mean orthogonal distance to the line of identity on the Poincare plot, was calculated. RESULTS Mutation carriers showed significantly larger (by a factor 2) instability in most VR parameters compared to controls despite higher instantaneous heart rate variability (STVRR) in the control group. The longer the (IT interval, the greater was its instability, and the instability of VR dispersion measures. CONCLUSIONS A greater instability of most aspects of VR already at rest seems to be a salient feature in both LQT1 and LQT2, which might pave the way for early afterdepolarizations and torsades de pointes ventricular tachycardia. In contrast, no signs of increased VR dispersion per se were observed in mutation carriers.
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| 4. |
- Vahedi, Farzad, et al.
(författare)
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Vectorcardiography analysis of the repolarization response to pharmacologically induced autonomic nervous system modulation in healthy subjects
- 2012
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Ingår i: Journal of Applied Physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 113:3, s. 368-376
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Tidskriftsartikel (refereegranskat)abstract
- Vahedi F, Odenstedt J, Hartford M, Gilljam T, Bergfeldt L. Vectorcardiography analysis of the repolarization response to pharmacologically induced autonomic nervous system modulation in healthy subjects. J Appl Physiol 113: 368-376, 2012. First published May 10, 2012; doi:10.1152/japplphysiol.01190.2011.-Autonomic nervous system activity is essential for regulation of ventricular repolarization (VR) and plays an important role in several arrhythmogenic conditions. This study in 31 healthy adult subjects (16 men, 15 women) evaluated the VR response to pharmacologically modulated autonomic nervous system activity applying vectorcardiography (VCG) analysis. During continuous VCG recording, 0.01-0.1 mu g.kg(-1).min(-1) isoprenaline (Iso) was infused at an increasing flow rate until three targeted heart rates (HR) were reached. After Iso washout, one intravenous bolus of 0.04 mg/kg atropine was given followed by an intravenous bolus of 0.2 mg/kg propranolol. A 5-min steady-state VCG recording was analyzed for each of the seven phases (including baseline 1 and 2). Furthermore, during the first 4 min following atropine, six periods of 10-s VCG were selected for subanalysis to evaluate the time course of change. The analysis included QRS, QT, and T-peak to T-end intervals, measures of the QRS and T vectors and their relation, as well as T-loop morphology parameters. By increasing HR, Iso infusion decreased HR dependent parameters reflecting total heterogeneity of VR (T area) and action potential morphology (ventricular gradient). In contrast, Iso prolonged QT HR corrected according to Bazett and increased the T-peak to T-end-to-QT ratio to levels observed in arrhythmogenic conditions. HR acceleration after atropine was accompanied by a transient paradoxical QT prolongation and delayed HR adaptation of T area and ventricular gradient. In addition to the expected HR adaptation, the VR response to beta-adrenoceptor stimulation with Iso and to muscarinic receptor blockade with atropine thus included alterations previously observed in congenital and acquired long QT syndromes, demonstrating substantial overlap between physiological and pathophysiological electrophysiology. ILDSKOV JA, 1976, AMERICAN HEART JOURNAL, V92, P210
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