Quinidine-Induced Microvolt Electrocardiographic Alternans

Quinidine is a class Ia antiarrhythmic agent, but it seems also associated with an increased risk of ventricular arrhythmia and sudden death. This study aims to evaluate whether the possible risk of arrhythmia due to quinidine can be confirmed and tracked over time on electrocardiograms (ECGs) acquired on a healthy population before and within 24 hours after quinidine administration. The study population belongs to the "ECG Effects of Ranolazine, Dofetilide, Verapamil, and Quinidine in Healthy Subjects"database. The ECG analysis was performed through the enhanced correlation method (ECM) to quantify ECG alternans (ECGA), defined as beat-to-beat fluctuation of ECG wave morphology and recognized in the literature as an index of arrhythmia risk. ECM identified all forms of ECGA, thus not only T-wave alternans (TWA) as in its original formulation, but also P-wave alternans (PWA) and QRS-complex alternans (QRSA), quantified by amplitude and magnitude. The results showed that quinidine induced an increase in ECGA within 6 hours after administration, in accordance with its elimination half-life, and then returned to baseline (pre-dose) values. Depending on the ECGA form and quantification feature, the maximum increase was observed two to four times the baseline value. Furthermore, ECGA magnitude seemed to reveal transient changes better than amplitude, resulting in more post-dose time points, especially in the range 3.5-7 hours after quinidine administration, at which ECGA was statistically different than at the pre-dose time point. Thus, ECGA appears to disclose the higher risk of arrhythmia associated with quinidine.Clinical Relevance - The present study provides a contribution to guide therapy involving quinidine through the analysis of its proarrhythmic risk by electrocardiographic alternans.