Sex differences in ventricular repolarization during trigeminal nerve stimulation: insights into QT/RR hysteresis

Cardiac repolarization (i.e., QT interval) is inversely related to heart rate (HR). However, during diving-induced bradycardia, the QT response is delayed, a phenomenon known as QT/RR hysteresis, possibly due to autonomic coactivation. Although women exhibit longer QT intervals than men, sex differences in QT/RR hysteresis remain poorly explored. This study investigated sex differences in the relationship between QT interval and HR changes during trigeminal nerve stimulation (TGS), a controlled activation of diving bradycardia. Thirty-four healthy subjects (17 women, 22 ± 2 yr) underwent 2-min facial cooling in a semirecumbent position following a 5-min baseline. HR and blood pressure were continuously recorded, and the QT interval was analyzed using ECG Analysis software (LabChart, ADInstruments). TGS induced similar bradycardia in men and women (Δ-13 ± 1.6 vs. Δ-12 ± 1.8 beats/min; <i>P</i> = 0.918) and similar QT prolongation (Δ10 ± 2.1 vs. Δ11 ± 2.8 ms; <i>P</i> = 0.673). However, the QT-HR relationship was sex-dependent: women showed a stronger correlation (<i>r</i> = 0.87, <i>P</i> < 0.001 vs. <i>r</i> = 0.48, <i>P</i> = 0.05), a superior regression model (AIC = 102.9 vs. 121.3), and a consistent association after adjusting for bradycardia magnitude. In contrast, the QT-HR correlation in men was no longer significant after controlling for bradycardic response. At 15 s post-TGS onset, women showed significant bradycardia and QT prolongation, whereas QT changes in men were transient and not sustained. Similar results were observed during TGS offset. These findings highlight sex differences in QT/RR hysteresis during and after TGS, with women showing a more adaptive repolarization response, potentially conferring cardioprotective advantages during diving or aquatic activities.<b>NEW & NOTEWORTHY</b> QT interval response to diving-induced bradycardia is delayed, a phenomenon known as QT/RR hysteresis. This study reveals sex-specific differences in the QT-HR relationship during simulated diving: women exhibit faster QT adaptation than men, suggesting a more robust repolarization response. These findings provide new insights into the sex-dependent dynamics of cardiac repolarization under autonomic conflict, with potential implications for arrhythmia risk assessment and cardiovascular protection during diving or aquatic sports.