Electrical behavior of T-Wave polarity alternans in patients with congenital long QT syndrome

Filho, Fernando E. S. Cruz; Maia, Ivan G.; Fagundes, Márcio; Barbosa, Rosa; Alves, Pedro Nascimento; Sá, Roberto; Boghossian, Silvia Helena Cardoso; Ribeiro, José Carlos

doi:10.1016/s0735-1097(00)00694-x

Cited by 31 publications

(4 citation statements)

References 32 publications

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“…The Ca 2+ channel blocker verapamil reduced these alternans, suggesting an involvement of intracellular Ca 2+ deregulation in this phenomenon. Previous studies had shown that patients with long QT syndrome can exhibit T-wave alternans during sinus tachycardia (Cruz Filho et al, 2000; Viskin et al, 2004). …”

Section: Models For the Lqt3 Syndromementioning

confidence: 98%

Mouse Models of SCN5A-Related Cardiac Arrhythmias

Derangeon¹,

Montnach²,

Baró³

et al. 2012

Front. Physio.

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Mutations of SCN5A gene, which encodes the α-subunit of the voltage-gated Na+ channel NaV1.5, underlie hereditary cardiac arrhythmic syndromes such as the type 3 long QT syndrome, cardiac conduction diseases, the Brugada syndrome, the sick sinus syndrome, a trial standstill, and numerous overlap syndromes. Patch-clamp studies in heterologous expression systems have provided important information to understand the genotype-phenotype relationships of these diseases. However, they could not clarify how SCN5A mutations can be responsible for such a large spectrum of diseases, for the late age of onset or the progressiveness of some of these diseases and for the overlapping syndromes. Genetically modified mice rapidly appeared as promising tools for understanding the pathophysiological mechanisms of cardiac SCN5A-related arrhythmic syndromes and several mouse models have been established. This review presents the results obtained on these models that, for most of them, recapitulate the clinical phenotypes of the patients. This includes two models knocked out for Nav1.5 β1 and β3 auxiliary subunits that are also discussed. Despite their own limitations that we point out, the mouse models still appear as powerful tools to elucidate the pathophysiological mechanisms of SCN5A-related diseases and offer the opportunity to investigate the secondary cellular consequences of SCN5A mutations such as the expression remodeling of other genes. This points out the potential role of these genes in the overall human phenotype. Finally, they constitute useful tools for addressing the role of genetic and environmental modifiers on cardiac electrical activity.

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Section: Models For the Lqt3 Syndromementioning

confidence: 98%

Mouse Models of SCN5A-Related Cardiac Arrhythmias

Derangeon¹,

Montnach²,

Baró³

et al. 2012

Front. Physio.

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“…Macroscopic TWA has frequently been reported in patients with LQTS: 2.5% in standard 12‐lead ECGs 8 and 45% in ambulatory ECGs. 15 Macroscopic TWA is not only the diagnostic criteria for LQTS but also a risk marker for cardiac events. 8 Due to the process of spatially discordant repolarization alternans, in which adjacent myocytes begin alternating in opposing phases, the presence of TWA in patients with LQTS can predispose to Tdp.…”

Section: Discussionmentioning

confidence: 99%

T‐Wave Alternans Measured by 24‐Hour Ambulatory Recordings Rather Than Exercise Stress Tests as a Risk Stratification Marker in Patients With Long QT Syndrome

Yang,

Luo,

et al. 2024

JAHA

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Background Few small‐sample studies have quantified the T‐wave alternans (TWA) value by 24‐hour ambulatory recordings or exercise stress tests in patients with long QT syndrome (LQTS). The cutoff point of TWA ≥47 μV was based on patients with myocardial infarction. In our study, we aimed to (1) evaluate the association of TWA with life‐threatening arrhythmic events (LAEs); (2) compare the predictive model of LAEs according to the TWA value measured by 24‐hour ambulatory recordings and exercise stress tests; and (3) propose a cutoff point for the high risk of LAEs in patients with LQTS. Methods and Results The study cohort included 110 patients with LQTS referred to our hospital, and the primary outcome was LAEs. Thirty‐one patients with LQTS (31/110 [28.2%]) developed LAEs during the following 24 (12–47) months. Peak TWA value quantified from 12 leads by 24‐hour ambulatory recordings in patients with LQTS with LAEs (LQTS–LAEs group) was significantly higher than LQTS without LAEs (LQTS–non‐LAEs group) (64.0 [42.0–86.0] μV versus 43.0 [36.0–53.0] μV; P <0.01). There was no statistical difference in TWA value measured by exercise stress tests between the 2 groups (69.0 [54.5–127.5] μV versus 68.5 [53.3–99.8] μV; P =0.871). The new cutoff point of the peak TWA value measured by 24‐hour ambulatory recordings was 55.5 μV, with a sensitivity of 75.0% and a specificity of 78.6%. A univariate Cox regression analysis revealed that TWA value ≥55.5 μV was a strong predictor of LAEs (hazard ratio [HR], 4.5 [2.1–9.6]; P <0.001]. A multivariate Cox regression analysis indicated that TWA value ≥55.5 μV remained significant (HR, 2.7 [1.1–6.8]; P =0.034). Conclusions Peak TWA measured by 24‐hour ambulatory recordings was a more favorable risk stratification marker than exercise stress tests for patients with LQTS.

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“…Macrovoltage TWA has been shown to precede episodes of polymorphic ventricular tachycardia in patients with LQTS (Schwartz et al, 1975), and the presence of macrovoltage TWA at rest seems to be an adverse prognostic factor (Cruz Filho et al, 2000; Fujimoto et al, 1999; Motoyasu et al, 1992; Shimizu et al, 1996). In another study, μV-TWA was only infrequently found and no significant differences were detectable comparing patients with or without LQTS (Kaufman et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Nicorandil normalizes prolonged repolarisation in the first transgenic rabbit model with Long-QT syndrome 1 both in vitro and in vivo

Biermann¹,

Wu²,

Odening³

et al. 2011

European Journal of Pharmacology

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Transgenic rabbits expressing loss-of-function pore mutants of the human gene KCNQ1 (K v LQT1-Y315S) have a Long QT-Syndrome 1 (LQT1) phenotype. We evaluated for the first time the effect of nicorandil, an opener of ATP-sensitive potassium channels, and of isoproterenol on cardiac action potential duration and heart rate dependent dispersion of repolarisation in transgenic LQT1 rabbits.In vivo LQT1 and littermate control were subjected to transvenous electrophysiological studies; in vitro monophasic action potentials were recorded from explanted Langendorff-perfused hearts.In vivo ventricular effective refractory periods (VERP) at the right ventricular base were significantly prolonged in LQT1 as compared to littermate control, resulting in a more pronounced VERP dispersion in LQT1. This difference in VERP dispersion between LQT1 and littermate control disappeared after infusion of nicorandil. In vitro, mean action potential durations (APD 75 and APD90) of LQT1 were significantly prolonged compared to littermate control at baseline. Nicorandil decreased APD 75 and APD 90 in LQT1 and littermate control at all stimulated heart rates. After adding nicorandil, the APD 90 at all hearts rates and the APD75 at high heart rates were no longer different. Dispersion of repolarisation (ΔAPD 75 and ΔAPD 90 ) was heart rate dependently decreased after nicorandil at all tested stimulation cycle lengths only in LQT1.We demonstrated phenotypic differences of LQT1 and littermate control in vivo and in vitro. Nicorandil 20 μmol/l improved repolarisation abnormalities and heterogeneities in transgenic LQT1 rabbits.

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Electrical behavior of T-Wave polarity alternans in patients with congenital long QT syndrome

Abstract: The TWPA was dependent on the cardiac CL; there was loss of the LncQT/CL and an increase in the QT interval variability. Like other biological variables, T-wave polarity alternans has a higher density during the morning.

Cited by 31 publications

References 32 publications

Mouse Models of SCN5A-Related Cardiac Arrhythmias

Mouse Models of SCN5A-Related Cardiac Arrhythmias

T‐Wave Alternans Measured by 24‐Hour Ambulatory Recordings Rather Than Exercise Stress Tests as a Risk Stratification Marker in Patients With Long QT Syndrome

Nicorandil normalizes prolonged repolarisation in the first transgenic rabbit model with Long-QT syndrome 1 both in vitro and in vivo

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