Gender differences in the long QT syndrome: Effects of β-adrenoceptor blockade

Background: Gender differences have been reported in patients with the congenital long QT syndrome (LQTS). We analyzed whether electrocardiographic differences existed in females, males, girls and boys in response to β-adrenoceptor blockade. Methods: 12-lead ECGs before and during β-adrenoceptor blockade were collected in 87 genotyped LQTS patients (48 women, 14 men, 12 girls and 13 boys). Up to three QTc intervals were determined in each lead of the ECG. V4 was used for QT/QTc analysis. Difference between longest and shortest QT interval was taken as a measure for dispersion of QT intervals. Results: (1) Adult males had the greatest shortening of the QTc interval upon treatment with β-adrenoceptor blockade. During treatment, adult males with LQTS₁ (mutation in the KCNQ1 gene, affecting I_Ks current) were found to have shorter QTc intervals than adult females; this difference did not exist in LQTS₂ patients (mutation in the HERG gene, affecting I_Kr current). (2) Female LQTS₂ patients had a 50% larger dispersion than female LQTS₁ patients both before and during treatment. (3) Adult male LQTS₁ patients constitute the only patient group with a marked decrease in QTc intervals and dispersion associated with a 100% efficacy of treatment in response to β-adrenoceptor blockade. Conclusions: These findings indicate that, in addition to underlying differences in repolarization between men and women, cardiac electrophysiological responses to β-adrenoceptor blockade can be modulated by gender-related factors.