T-Wave morphology in short QT syndrome.

BACKGROUND: Short QT syndrome (SQTS) is an inherited disorder characterized by a short QT interval and vulnerability to ventricular tachyarrhythmias. The diagnostic criteria for this syndrome are not well defined, since there is uncertainty about the lowest normal limits for the corrected QT (QTc) interval. OBJECTIVE: The aim of this study was to determine whether T-wave morphology parameters are abnormal in short QT subjects and whether those parameters can help in the diagnosis of SQTS. METHODS AND RESULTS: We describe three families (10 patients) with short QT intervals (QTc 310 +/- 32 ms). Seven subjects had suffered serious arrhythmic events and three were asymptomatic. T-wave morphology was assessed using the principal component analysis (PCA). QTc was significantly shorter and T-wave amplitude in lead V2 higher in the short QT subjects compared to healthy controls (n=149), (P < 0.001 for both). The total cosine of the angle between the main vectors of the QRS and T-wave loops (TCRT) was markedly abnormal among the symptomatic patients with short QT syndrome (n=7) (TCRT -0.14 +/- 0.55 vs 0.36 +/- 0.51, P=0.019). None of the three asymptomatic patients with short QT but without a history of arrhythmic events had an abnormally low TCRT. CONCLUSION: Our observations suggest that patients with a short QT interval and a history of arrhythmic events have abnormal T-wave loop parameters. These electrocardiogram (ECG) features may help in the diagnosis of SQTS in addition to the measurement of the duration of QT interval from the 12-lead ECG.

Family history and the risk of sudden cardiac death as a manifestation of an acute coronary event.

BACKGROUND: Observational studies have suggested that a parental history of sudden death increases one's risk of dying suddenly. This study tested the hypothesis that a family history of sudden cardiac death (SCD) is a risk factor for SCD caused by an acute coronary event. METHODS AND RESULTS: A retrospective case-control study included (1) consecutive victims of SCD (n=138) whose deaths were verified to be due to an acute coronary event without a history of prior myocardial infarction at medicolegal autopsy, (2) consecutive patients surviving an acute myocardial infarction (AMI; n=254), and (3) healthy control subjects (n=470). Family history of AMI and SCD among the first-degree relatives was ascertained in each study group. The incidence of SCD in the 1223 first-degree relatives of SCD victims was higher (5.2%) than that in the 2326 relatives of AMI survivors (3.3%; odds ration [OR] 1.6, 95% confidence interval [CI] 1.2 to 2.2, P<0.01) or the 3748 relatives of controls (OR 2.2; 95% CI 1.6 to 3.0, P<0.001). The history of SCD in 2 or more first-degree relatives was also higher (10.9%) among SCD victims than among AMI survivors (3.5%; OR 3.3, 95% CI 1.4 to 7.8, P<0.01) or controls (1.1%; OR 11.3, 95% CI 4.0 to 31.8, P<0.001). The family history of AMI did not differ between the SCD and AMI groups. Male gender and current smoking were the only coronary risk factors that were more prevalent among SCD victims than among AMI survivors (P<0.001 for both). CONCLUSIONS: Subjects with a family history of SCD have an increased risk of dying suddenly during an acute coronary event.

Functional significance of KCNH2 (HERG) K897T polymorphism for cardiac repolarization assessed by analysis of T-wave morphology.

BACKGROUND: Although KCNH2 (HERG) K897T polymorphism has been shown to be associated with the QT interval measured from 12-lead electrocardiogram (ECG), the functional significance of K897T polymorphism has been debated. The aim of this study was to test whether the K897T polymorphism of the KCNH2 (HERG) gene coding for the rapidly activating delayed rectifier K+ channel influences cardiac repolarization assessed by principal component analysis (PCA) of T-wave morphology. METHODS: Twelve-lead ECGs were digitized and T-wave morphology was analyzed with a PCA method in a population consisting of 228 healthy middle-aged subjects (121 women and 107 men). DNA samples were genotyped for the nucleotide 2690 A>C variation of the KCNH2 gene, corresponding to the KCNH2 K(lysine)897T(threonine) amino acid polymorphism. RESULTS: The allele frequencies were 0.86 (K) and 0.14 (T). The KCNH2 K897T polymorphism was associated with the total cosine R-to-T (TCRT), which reflects the wave front direction between depolarization and repolarization. TCRT was 0.421 in the genotype KK and 0.300 in the genotypes KT and TT (P = 0.04). The difference of TCRT was more marked between the KCNH2 K897T genotypes in women (P = 0.03) than in men (P = 0.52). CONCLUSIONS: The common K897T polymorphism of the cardiac potassium channel KCNH2 has functional significance for cardiac electrical properties. Subjects with a less common genotype, KT or TT, have smaller TCRT, which reflects dyssynchrony between depolarization and repolarization and is associated with an increased risk of cardiac mortality.