Analysis of 24-h Rhythm in Ventricular Repolarization Identifies QT Diurnality As a Novel Clinical Parameter Associated with Previous Ventricular Arrhythmias in Heart Failure Patients

Cardiac repolarization abnormalities are among the major causes of ventricular arrhythmias and sudden cardiac death. In humans, cardiac repolarization duration has a 24-h rhythm. Animal studies show that this rhythm is regulated by 24-h rhythms in ion channel function and that disruption of this rhythm leads to ventricular arrhythmias. We hypothesized that 24-h rhythms in QT duration can be used as a predictor for sudden cardiac death and are associated with ventricular arrhythmias. Secondly, we assessed a possible mechanistic explanation by studying the putative role of hERG channel dysfunction. In 2 retrospective studies, measures of the 24-h variation in the QT and QTc intervals (QT and QTc diurnality, QTd and QTcd, respectively) have been derived from Holter analyses and compared between groups: 1) 39 post-infarct patients with systolic heart failure (CHF: < 35%), of which 14 with, and 25 without a history of ventricular arrhythmias and 2) five patients with proven (LQTS2) and 16 with potential (Sotalol-induced) hERG channel dysfunction vs. 22 controls. QTd was two-fold higher in CHF patients with a history of ventricular arrhythmias (38 ± 15 ms) compared to CHF patients without VT (16 ± 9 ms, = 0.001). QTd was significantly increased in LQT2 patients (43 ± 24 ms) or those treated with Sotalol (30 ± 10 ms) compared to controls (21 ± 8 ms, < 0.05 for both). QT diurnality presents a novel clinical parameter of repolarization that can be derived from Holter registrations and may be useful for identification of patients at risk for ventricular arrhythmias.