QTc prolongation following CV
In our study, during prolonged monitoring using 7-day Holter, we were able to demonstrate a significant number of patients with new significant QTc prolongation following CV. In 32 patients (35%), the median QTc reached new values ≥500 msec, and in 14 patients (16%) it even reached QTc ≥550 msec (baseline QTc was < 480 msec). Our observations are in line with previous case series and small studies.11,12 Houltz and colleagues had previously reported QTc prolongation up to a mean of 672 ± 26 ms in patients that, in fact, developed Torsade de pointes.13 In another study Choy and colleagues reported that QTc was prolonged from 405 ± 55 to 470 ± 67 ms following CV.3 These reports, however, included a relatively small number of patients (less than 10 patients in average) or included patients who were treated with new antiarrhythmic drug, such as Sotalol or Dofetilide. Notably, in our study, neither initiation of a new antiarrhythmic medication nor an increase in dose occurred.
The exact mechanisms of QTc prolongation following CV remains unclear. Possible causes include: 1) bradycardia - several studies demonstrated that lower heart rates following CV may prolong the QTc interval14, 2) increased drug toxicity - changes in the neuro-hormonal status, such as change in sympathetic nervous activity and ANP were reported following CV15, and can potentially modulate the sensitivity to antiarrhythmic drugs, 3) abrupt slowing of heart rates, following termination of fast ventricular rates, that may lead to QTc prolongation16, 4) ventricular repolarization remodeling during atrial fibrillation - QTc during SR following CV was reported to be significantly and transiently prolonged (although of limited magnitude, the prolongation was substantial (approximately 15%) in some individuals5), and 5) ion channels modification - in several previous studies17 an alterations in ion channels and several gene expressions in the atria and ventricle of patients with persistent AF were reported as leading to change in the QTc interval; In particular, the inward rectifier I(K1) channel, affecting the inward rectifier potassium current which regulates the terminal portion of phase 3 of the repolarization.18 Of note, in our study, we found that the magnitude of QTc prolongation was similar regardless of CV method, Midazolam use and regardless of the need to additional use/reloading of antiarrhythmic medication peri-cardioversion.