title: Quantification of ventricular repolarization heterogeneity during moxifloxacin or sotalol administration using [Formula: see text]-index.
abstract: Drug-induced alterations of ventricular heterogeneity must be limited to avoid induction of lethal ventricular arrhythmias. In here, a new parameter called [Formula: see text]-index, able to measure the standard deviation of myocites' repolarization times, was evaluated after moxifloxacin and sotalol administration. The two drugs are known to provide different alteration of the QT interval length ranging from subtle (moxifloxacin) 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 (moxifloxacin) healthy subjects were retrospectively analyzed. The recordings were performed after infusion of the drugs and after the placebo (moxifloxacin) or at baseline (sotalol). The corrected QT interval (QTc) was included as well in the study, for a direct comparison. In both populations, [Formula: see text]-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 [Formula: see text]-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 ([Formula: see text]-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 moxifloxacin, maximum values were reached, on average, 5.01 h after administration for [Formula: see text]-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 [Formula: see text]-index than QTc (moxifloxacin: 34.56% ± 24.60% versus 5.56% ± 2.98% ; sotalol: 114.77% ± 33.15% versus 12.13% ± 2.85% ; p < 0.05).The study suggests that the standard deviation of the ventricular repolarization times, as quantified by the [Formula: see text]-index, might be an effective measure of spatial heterogeneity.
authors: Dipartimento di Informatica, Università degli Studi di Milano, Via Bramante 65, 26013 Crema, Italy.
authors: M W
authors: MW
authors: Rivolta
authors: L T
authors: LT
authors: Mainardi
authors: R
authors: R
authors: Sassi
mesh_terms: D002317:Cardiovascular Agents / Q000097:blood / Q000494:pharmacology*; D004562:Electrocardiography / Q000379:methods*; D024841:Fluoroquinolones / Q000097:blood / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D000077266:Moxifloxacin; D015990:Placebo Effect; D012189:Retrospective Studies; D012815:Signal Processing, Computer-Assisted; D013015:Sotalol / Q000097:blood / Q000494:pharmacology*; D016276:Ventricular Function / Q000187:drug effects* / Q000502:physiology
chemical_list: D002317:Cardiovascular Agents; D024841:Fluoroquinolones; D013015:Sotalol; D000077266:Moxifloxacin