Introduction: Long QT syndrome (LQTS) mutation carriers have elevated the risk of cardiac events even in the absence of QTc prolongation; however, mutation penetrance in patients with normal QTc may be reflected in abnormal T-wave shape, particularly in KCNH2 mutation carriers. We aimed to assess whether the magnitude of a three-dimensional T-wave vector (TwVM) will identify KCNH2-mutation carriers with normal QTc at risk for cardiac events. Methods: Adult LQT2 patients with QTc < 460 ms in men and <470 ms in women (n = 113, age 42 ± 16 years, 43% male) were compared with genotype-negative family members (n = 1007). The TwVM was calculated using T-wave amplitudes in leads V6, II, and V2 as the square root of (TV62 + TII2 + (0.5*TV2)2). Cox regression analysis adjusted for gender and time-dependent beta-blocker use was performed to assess cardiac event (CE) risk, defined as syncope, aborted cardiac arrest, implantable cardioverter-defibrillator therapy, or sudden death. Results: Dichotomized by median of 0.30 mV, lower TwVM was associated with elevated CE risk compared to those with high TwVM (HR = 2.95, 95% CI, 1.25-6.98, P =.014) and also remained significant after including sex and time-dependent beta-blocker usage in the Cox regression analysis (HR = 2.64, 95% CI, 1.64-4.24, P <.001). However, these associations were found only in women but not in men who had low event rates. Conclusion: T-wave morphology quantified as repolarization vector magnitude using T-wave amplitudes retrieved from standard 12-lead electrocardiogram predicts cardiac events risk in LQT2 women and appears useful for risk stratification of KCNH2-mutation carriers without QTc prolongation.
Bibliographical noteFunding Information:
The study was performed with support from National Institutes of Health grant (No. HL-123483). Dr. Platonov was supported by the research grant from the Swedish Heart-Lung Foundation (grant no. 20150574) and scholarship grants from the Fulbright Commission, Maggie Stephens Foundation, Swedish Society of Medicine, (grant no. SLS-551761)and donation funds at Sk?ne University Hospital (Lund, Sweden) (grant no. 96332).
The study was performed with support from National Institutes of Health grant (No. HL‐123483). Dr. Platonov was supported by the research grant from the Swedish Heart‐Lung Foundation (grant no. 20150574) and scholarship grants from the Fulbright Commission, Maggie Stephens Foundation, Swedish Society of Medicine, (grant no. SLS‐551761)and donation funds at Skåne University Hospital (Lund, Sweden) (grant no. 96332).
- T-wave vector magnitude
- cardiac events
- long QT syndrome