Assessment of spatial heterogeneity of ventricular repolarization after multi-channel blocker drugs in healthy subjects. (June 2020)

• Record Type: Journal Article
• Authors: Corino, Valentina D.A.; Rivolta, Massimo W.; Mainardi, Luca T.; Sassi, Roberto
• Is Part Of: Computer methods and programs in biomedicine. Volume 189(2020)
• Publication Date: 2020-06
• Subjects: Calcium channel -- Dominant T-wave -- Human ether-à-go-go-related gene potassium channel -- Sodium channels -- Ventricular arrhythmias: ventricular repolarization; ECG electrocardiograms -- FDA US Food and Drugs Administration -- hERG human ether-à-go-go-related gene -- NSTEMI non-ST-elevation myocardial infarction -- QTc corrected QT interval -- TMP transmembrane potential; Medicine -- Computer programs -- Periodicals; Biology -- Computer programs -- Periodicals; Computers -- Periodicals; Medicine -- Periodicals; Médecine -- Logiciels -- Périodiques; Biologie -- Logiciels -- Périodiques; Biology -- Computer programs; Medicine -- Computer programs; Periodicals; Electronic journals; 610.28
• DOI: 10.1016/j.cmpb.2019.105291
• Languages: English
• ISSNs: 0169-2607

Abstract

Highlights: High torsadogenic drugs (dofetilide and quinidine) affected significantly the spatial heterogeneity of ventricular repolarization, as quantified by the V-index. The V-index has a potential in assessing drug arrhythmogenicity. Abstract: Background and Objectives: In contrast to potassium channel blockers, drugs affecting multiple channels seem to reduce torsadogenic risks. However, their effect on spatial heterogeneity of ventricular repolarization (SHVR) is still matter of investigation. Aim of this work is to assess the effect of four drugs blocking the human ether-à-go-go-related gene (hERG) potassium channel, alone or in combination with other ionic channel blocks, on SHVR, as estimated by the V-index on short triplicate 10 s ECG. Methods: The V-index is an estimate of the standard deviation of the repolarization times of the myocytes across the entire myocardium, obtained from multi-lead surface electrocardiograms. Twenty-two healthy subjects received a pure hERG potassium channel blocker (dofetilide) and 3 other drugs with additional varying degrees of sodium and calcium (L‐type) channel block (quinidine, ranolazine, and verapamil), as well as placebo. A one-way repeated-measures Friedman test was performed to compare the V-index over time. Results: Computer simulations and Bland-Altman analysis supported the reliability of the estimates of V-index on triplicate 10 s ECG. Ranolazine, verapamil and placebo did not affect the V-index. On the contrary, after quinidine and dofetilide administration, an increase of V-index from predose to its peak value was observed (ΔΔV-index values were 19 ms and 27 ms, respectively, p < 0.05). Conclusions: High torsadogenic drugs (dofetilide and quinidine) affected significantly the SHVR, as quantified by the V-index. The metric has therefore a potential in assessing drug arrhythmogenicity.