Sex influences on ventricular repolarization duration in normal subjects and in type 1, 2 and 3 long QT syndrome patients: Different effect in acquired and congenital type 2 LQTS.

To evaluate the interaction between sex and rate corrected QT interval (QTc) duration in normal subjects after drug-induced QT prolongation and in LQTS patients. Semi-automated measurements were performed on 875 digital ECGs (200 normal subjects off drugs (100 females), 200 normal subjects on Moxifloxacin (100 females), 259 LQT1 patients (161 females), 183 LQT2 patients (100 females) and 33 LQT3 patients (15 females)). A sex specific coefficient was calculated in each group and was used to calculate group specific corrected QT intervals (QTci). The mean sex difference (female minus male) in QTci interval duration was 17 ms 95%CI(12.7; 21.3) in normal subjects, 19 ms (14.5; 23.5) on Moxifloxacin, and 13 ms (4.8; 21.2) in LQT1 patients. The mean difference was 2 ms (-7.9; 11.9) in LQT2 and - 5 ms (-32.2; 22.2) in LQT3 patients (p = 0.0067 for the group and sex interaction). In the subgroup of patients above 15 years and without beta blocker treatment, the sex effect (female minus male) on QTci interval duration was 17 ms (4.1; 29.9) in LQT1 patients. QTc duration was not different between sex in LQT2 and in LQT3 patients (mean difference - 3 ms (-21.6; 15.6) and 12 ms (-28.4; 52.4), respectively) (p = 0.0191 for group and sex interaction). The interaction between sex and QTc interval is preserved in type 1 LQTS and drug-induced QTc prolongation but blurred in type 2 LQTS. Further experimental studies are warranted to better understand the interaction of sexual hormones with malfunctioning KCNH2 encoded repolarizing potassium channel.

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