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. 2023 Jan;28(1):e13015.
doi: 10.1111/anec.13015. Epub 2022 Nov 7.

The diagnostic role of T wave morphology biomarkers in congenital and acquired long QT syndrome: A systematic review

Daniel T Tardo  1   2   3 , Matthew Peck  1 , Rajesh N Subbiah  1   2   4 , Jamie I Vandenberg  1   4 , Adam P Hill  1   4
Affiliations

The diagnostic role of T wave morphology biomarkers in congenital and acquired long QT syndrome: A systematic review

Daniel T Tardo et al. Ann Noninvasive Electrocardiol. 2023 Jan.

Abstract

Introduction: QTc prolongation is key in diagnosing long QT syndrome (LQTS), however 25%-50% with congenital LQTS (cLQTS) demonstrate a normal resting QTc. T wave morphology (TWM) can distinguish cLQTS subtypes but its role in acquired LQTS (aLQTS) is unclear.

Methods: Electronic databases were searched using the terms "LQTS," "long QT syndrome," "QTc prolongation," "prolonged QT," and "T wave," "T wave morphology," "T wave pattern," "T wave biomarkers." Whole text articles assessing TWM, independent of QTc, were included.

Results: Seventeen studies met criteria. TWM measurements included T-wave amplitude, duration, magnitude, Tpeak-Tend, QTpeak, left and right slope, center of gravity (COG), sigmoidal and polynomial classifiers, repolarizing integral, morphology combination score (MCS) and principal component analysis (PCA); and vectorcardiographic biomarkers. cLQTS were distinguished from controls by sigmoidal and polynomial classifiers, MCS, QTpeak, Tpeak-Tend, left slope; and COG x axis. MCS detected aLQTS more significantly than QTc. Flatness, asymmetry and notching, J-Tpeak; and Tpeak-Tend correlated with QTc in aLQTS. Multichannel block in aLQTS was identified by early repolarization (ERD30% ) and late repolarization (LRD30% ), with ERD reflecting hERG-specific blockade. Cardiac events were predicted in cLQTS by T wave flatness, notching, and inversion in leads II and V5 , left slope in lead V6 ; and COG last 25% in lead I. T wave right slope in lead I and T-roundness achieved this in aLQTS.

Conclusion: Numerous TWM biomarkers which supplement QTc assessment were identified. Their diagnostic capabilities include differentiation of genotypes, identification of concealed LQTS, differentiating aLQTS from cLQTS; and determining multichannel versus hERG channel blockade.

Keywords: ECG biomarkers; LQTS; T wave morphology; acquired long QT syndrome; congenital long QT syndrome; sudden cardiac death.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Summary of search results. TdP, Torsades de pointes
FIGURE 2
FIGURE 2
Selected T wave morphology analysis techniques. (a) ECG time intervals indicating specific T wave parameters, including Tpeak‐Tend interval (ms), T duration (ms), and T amplitude (mV). (bi) Application of sigmoidal classifiers demonstrated using Boltzmann sigmoidal functions: Upslope (red dotted line), downslope (red bold dotted line), and switch (red dashed line), as adapted from Immanuel et al. (2016). (bii) T wave fitting of the repolarizing integral (RI), derived from three Hill parameters: n (red bold slope), V max (red horizontal arrow), K m (red vertical arrow) as adapted from Kanters et al. (2004). (c) T wave features applied by the novel, proprietary T wave program, including T wave area, T wave right and left (mV/s), COG (x/y) of T wave; and COG of first and last 25% of T wave (ms) as adapted from Sugrue et al. (2016). (d) T wave architectural patterns
FIGURE 3
FIGURE 3
Vectorcardiographic biomarkers including (a) QRS‐T angle (dark blue dotted line), ventricular gradient (green dashed line), maximum magnitude of the T vector (derived from the QRS loop [dark red solid line], and T wave loop [light blue dashed line]); (b) and 30% early (ERD30%, blue solid line) and late (LRD30%, red solid line) repolarization of the T wave loop as adapted from Vicente et al. (2015).
See this image and copyright information in PMC

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