Serum Quinidine Concentrations and Effect on QT Dispersion and Interval

OBJECTIVE: To establish a relationship between serum quinidine concentrations (SQCs) and QT interval dispersion, compared with corresponding QT intervals, in order to identify a reason why many reports describe torsade de pointes as occurring at subtherapeutic concentrations. DESIGN: Retrospective study. SETTING: University teaching hospital. PARTICIPANTS: Eleven patients with atrial arrhythmias managed with quinidine therapy. MAIN OUTCOME MEASURES: Patients with subtherapeutic (<2 μg/mL) and therapeutic (2–5 μg/mL) SQCs with corresponding 12-lead electrocardiograms (ECGs) (25 mm/sec) and baseline ECG were evaluated for QT interval dispersion, calculated as the maximum minus the minimum QT interval on the 12-lead ECG. RESULTS: Mean ± SD subtherapeutic and therapeutic SQCs were 1.48 ± 0.39 μg/mL and 3.78 ± 0.88 μg/mL (p < 0.001). Baseline values for QT/QTc intervals were 376.4 ± 59.2/429.5 ± 57.3 msec. At subtherapeutic and therapeutic SQCs, mean QT/QTc intervals were 403.6 ± 59.9/450.5 ± 38.5 msec and 439.1 ± 48.9/472.4 ± 44.6 msec, respectively. Mean QT dispersion was 47 ± 16.2 msec at baseline, 98.2 ± 27.5 msec at subtherapeutic SQC, and 70.9 ± 33.9 msec at therapeutic SQCs (p = 0.001 for overall analysis; p < 0.001 for baseline vs. subtherapeutic concentrations; p = NS for therapeutic vs. subtherapeutic in post hoc comparison). CONCLUSIONS: Despite QT interval lengthening with increasing SQCs, QT dispersion was numerically greatest at subtherapeutic SQCs. Further study is required to determine the value of QT dispersion as a tool for identifying proarrhythmic risk with drugs that prolong the QT interval.