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Quantitative T-wave morphology assessment from surface ECG is linked with cardiac events risk in genotype-positive KCNH2 mutation carriers with normal QTc values

Cortez, Daniel LU ; Zareba, Wojciech ; McNitt, Scott ; Polonsky, Bronislava ; Rosero, Spencer Z. and Platonov, Pyotr G. LU (2019) In Journal of Cardiovascular Electrophysiology 30(12). p.2907-2913
Abstract

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 +... (More)

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.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
cardiac events, long QT syndrome, T-wave vector magnitude
in
Journal of Cardiovascular Electrophysiology
volume
30
issue
12
pages
2907 - 2913
publisher
Wiley-Blackwell
external identifiers
  • scopus:85074089075
  • pmid:31579959
ISSN
1045-3873
DOI
10.1111/jce.14210
language
English
LU publication?
yes
id
8b7d4ce0-a4bc-443b-a22f-fa3ef7dd86ee
date added to LUP
2019-11-07 12:33:19
date last changed
2024-02-16 00:51:17
@article{8b7d4ce0-a4bc-443b-a22f-fa3ef7dd86ee,
  abstract     = {{<p>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 &lt; 460 ms in men and &lt;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 (TV6<sup>2</sup> + TII<sup>2</sup> + (0.5*TV2)<sup>2</sup>). 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 &lt;.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.</p>}},
  author       = {{Cortez, Daniel and Zareba, Wojciech and McNitt, Scott and Polonsky, Bronislava and Rosero, Spencer Z. and Platonov, Pyotr G.}},
  issn         = {{1045-3873}},
  keywords     = {{cardiac events; long QT syndrome; T-wave vector magnitude}},
  language     = {{eng}},
  month        = {{10}},
  number       = {{12}},
  pages        = {{2907--2913}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Journal of Cardiovascular Electrophysiology}},
  title        = {{Quantitative T-wave morphology assessment from surface ECG is linked with cardiac events risk in genotype-positive KCNH2 mutation carriers with normal QTc values}},
  url          = {{http://dx.doi.org/10.1111/jce.14210}},
  doi          = {{10.1111/jce.14210}},
  volume       = {{30}},
  year         = {{2019}},
}