Determinants of cardiac repolarization and risk for ventricular arrhythmias during mild therapeutic hypothermia.

Purpose: We aimed to investigate the factors that modulate the extent of QTc prolongation and potential arrhythmogenic consequences during mild therapeutic hypothermia (MTH).

Methods: We studied 205 patients after out-of-hospital cardiac arrest (131 underwent MTH). QTc was measured at baseline, 3h, 6h, 12h, 24h (end of hypothermia), 48h and 72h, and ventricular arrhythmias quantified.

Results: During MTH, the QTc interval increased progressively peaking at 12h (mean increase 42ms, 95% CI 30-55). There was a strong gender effect (P<0.001) and a significant gender-by-MTH interaction (P=0.004). At 12h, the QTc interval was markedly longer in women as compared with men (mean difference 50ms [95% CI 27-73]. Anoxic brain injury (P=0.002) was also positively associated with QTc prolongation. The risk for ventricular arrhythmic events was not higher with MTH compared with no hypothermia (incidence rate ratio 0.57, 95% CI 0.32-1.02, P=0.06). However, typical cases of Torsade de pointes occurred in association with AV block and LQT2.

Conclusion: QTc prolongation during MTH is strongly affected by female gender and moderately by concomitant anoxic brain injury. Although the overall risk for ventricular arrhythmias is not greater with MTH, Torsade de pointes may develop when other contributing factors coexist.