Assessment of Spatial Heterogeneity of Ventricular Repolarization after Quinidine in Healthy Subjects

Abstract

When spatial heterogeneity of ventricular repolarization (SHVR) increases, vulnerability to ventricular arrhythmias, including lethal ones, has also been observed to increase. Drug-induced multi-ion-channel blocks may increase SHVR. Aim of this study is to non-invasively assess whether quinidine, a strong hERG potassium channel blocker with weaker effects on calcium and late sodium currents, increases SHVR. We analyzed data from 21 healthy subjects that received both the drug and a placebo and underwent to 12 leads Holter monitoring. From the recording, three 10-s ECGs were extracted at each of 16 predefined time-points. SHVR was assessed by the Vindex, which evaluates the standard deviation of the repolarization times from multi-lead ECG recordings. At any time point, a value of V-index was computed for each of the three 10s ECGs and averaged if the difference in the mean RR of the 10s ECGs was lower than 50 ms. The Vindex did not change after the placebo (V-index pre-dose = 29.2 ± 9.9 ms vs. V-index post-dose1h = 26.7 ± 10.3, ns), whereas, after quinidine, it significantly increased one hour post-dose (V-index pre-dose = 29.5 ± 10.2 ms vs. Vindex post-dose1h = 46.5 ± 33.8 ms, p = 0.01). Quinidine had its maximum effect on the V-index 2.5 h after dose (V-index post-dose2.5h = 53.6 ± 39.6 ms).

Theoretical and Empirical Estimates of V-index Variability

“…Among the indexes developed in the last decades [1], the V-index is meant to assess the spatial heterogeneity of the ventricular repolarization (SHVR) from the surface ECG [2]. The index was proven to detect: i) pathological condi-tions such as those in patients suffering from Chagas disease [3] or in patients with symptoms suggestive of non-ST-elevation myocardial infarction [4]; and ii) effects of administration of pro-arrhythmic drugs [5,6].…”