Quanti cation of ventricular repolarization heterogeneity during moxi oxacin or sotalol administration using Vindex

Drug-induced alterations of ventricular heterogeneity must be limited to avoid induction of lethal ventricular arrhythmias. In here, a new parameter called V-index, able to measure the standard deviation of myocites' repolarization times, was evaluated after moxi6oxacin and sotalol administration. The two drugs are known to provide different alteration of the QT interval length ranging from subtle (moxi6oxacin) to evident (sotalol). In fact, while the former is employed as active-comparator in thorough QT studies, the latter might induce torsades de pointes. 24 h Holter ECGs of 39 (sotalol) and 68 (moxi6oxacin) healthy subjects were retrospectively analyzed. The recordings were performed after infusion of the drugs and after the placebo (moxi6oxacin) or at baseline (sotalol). The corrected QT interval (QTc) was included as well in the study, for a direct comparison. In both populations, V -index and QTc increased along with the drugs' serum concentration and were statistically different from values in the placebo arm or at baseline (p < 0.05). With sotalol, the maximum value of V-index occurred, on average, after 5.64 h from the infusion, whereas for QTc after about 4.27 h. The two metrics displayed evident changes (V-index: 27.79 ms ± 4.89 ms versus 60.13 ms ± 18.52 ms; QT corrected: 387.07 ms ± 19.84 ms versus 437.76 ± 32.05 ms; p < 0.05). Regarding moxi6oxacin, maximum values were reached, on average, 5.01 h after administration for V-index (30.70 ms ± 8.32 ms versus 40.48 ms ± 7.61 ms; p < 0.05), and 4.37 h for QTc (404.29 ms ± 29.05 ms versus 426.77 ± 36.67 ms; p < 0.05). They were statistically different from baseline values. With both drugs, the maximal percent variation after administration was higher for V-index than Institute of Physics and Engineering in Medicine 0967-3334/15/040803+9$33.00 © 2015 Institute of Physics and Engineering in Medicine Printed in the UK Physiol. Meas. 36 (2015) 803–811 doi:10.1088/0967-3334/36/4/803

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