Long QT syndrome (LQTS) mutation carriers have higher risk of cardiac events than unaffected family members even in the absence of QTc prolongation. Changes in T wave morphology may reflect penetrance of LQTS mutations. We aimed to assess whether T-wave morphology may improve risk stratification of LQT2 mutation carriers with normal QTc interval.
LQT2-mutation carriers with QTc<460 ms in men and <470 ms in women (n=154) were compared with unaffected family members (n=1007). Baseline ECGs recorded at age ≥18 years underwent blinded assessment. Flat, notched or negative T-waves in leads II or V5 were considered ’abnormal’. Cox regression analysis was performed to assess the association between T-wave morphology, the presence of mutations in the pore region of KCNH2 and the risk of cardiac events defined as syncope, aborted cardiac arrest, defibrillator therapy or sudden cardiac death. Gender-specific associations were estimated using interactions terms.
LQT2 female carriers with abnormal T-wave morphology had significantly higher risk of cardiac events compared to LQT2 female carriers with normal T waves (HR=3.31; 95% CI: 1.68–6.52; p=0.001) whereas this association was not significant in males. LQT2 males with pore location of mutations has significantly higher risk of cardiac events than non-pore location males (HR=6.01; 95%CI: 1.50–24.08; p=0.011) whereas no such association was found in females.