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

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 + 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.

ArrhythmoGenoPharmacoTherapy

“…drugs (Chen et al, 2000;Mitcheson et al, 2000;Mehta et al, 2018) in connection with the pharmacotherapy of LQTS at genetic levels (Mehta et al, 2018;Yin et al, 2018;Cortez et al, 2019;Kerr et al, 2019). The voltage activated potassium channel (Kv11.1) is encoded by the humane-ether-a-go-go related gene (hERG), which predominantly contributes to the electrical activity of the myocardium (Vandenberg et al, 2012;Vasseur et al, 2019).…”

Vectorcardiography Findings Are Associated with Recurrent Ventricular Arrhythmias and Mortality in Patients with Heart Failure Treated with Implantable Cardioverter-Defibrillator Device

“…However, a cutoff level equivalent to the one in our study, for patients with narrow QRS, was identified: 0.24 mV [16]. A recent study showed that Twvm <0.30 mV conferred a threefold increased risk of cardiac events in females with long QT syndrome (genotype-positive KCNH2 with normal QTc values) [17]. More studies, however, have evaluated frontal T-wave amplitudes, as opposed to the possibly superior three-dimensional vector used in our study.…”

“…A reduced QRS vector mag nitude (QRSvm) predicts ventricular arrhythmia in se lected cohorts [13][14][15]. A reduced Twave vector magni tude (Twvm) is a marker for ventricular repolarization changes, and a lower Twvm value has been associated with an increased risk of cardiac events [16,17].…”