Spectrum of ST-T-wave patterns and repolarization parameters in congenital long-QT syndrome: ECG findings identify genotypes.

LDS Hospital, Salt Lake City, Utah 84103, USA.
Circulation (Impact Factor: 14.95). 01/2001; 102(23):2849-55. DOI: 10.1161/01.CIR.102.23.2849
Source: PubMed

ABSTRACT Congenital long-QT syndrome (LQTS) is caused by mutations of genes encoding the slow component of the delayed rectifier current (LQT1, LQT5), the rapid component of the delayed rectifier current (LQT2, LQT6), or the Na(+) current (LQT3), resulting in ST-T-wave abnormalities on the ECG. This study evaluated the spectrum of ST-T-wave patterns and repolarization parameters by genotype and determined whether genotype could be identified by ECG.
ECGs of 284 gene carriers were studied to determine ST-T-wave patterns, and repolarization parameters were quantified. Genotypes were identified by individual ECG versus family-grouped ECG analysis in separate studies using ECGs of 146 gene carriers from 29 families and 233 members of 127 families undergoing molecular genotyping, respectively. Ten typical ST-T patterns (4 LQT1, 4 LQT2, and 2 LQT3) were present in 88% of LQT1 and LQT2 carriers and in 65% of LQT3 carriers. Repolarization parameters also differed by genotype. A combination of quantified repolarization parameters identified genotype with sensitivity/specificity of 85%/70% for LQT1, 83%/94% for LQT2, and 47%/63% for LQT3. Typical patterns in family-grouped ECGs best identified the genotype, being correct in 56 of 56 (21 LQT1, 33 LQT2, and 2 LQT3) families with mutation results.
Typical ST-T-wave patterns are present in the majority of genotyped LQTS patients and can be used to identify LQT1, LQT2, and possibly LQT3 genotypes. Family-grouped ECG analysis improves genotype identification accuracy. This approach can simplify genetic screening by targeting the gene for initial study. The multiple ST-T patterns in each genotype raise questions regarding the pathophysiology and regulation of repolarization in LQTS.

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    • "Unfortunately no medical records could be obtained. ECGs of the mother showed prolonged QTc (471-499 ms) with subtle bifid T waves in most of 12-leads, an ECG pattern typically seen in LQT2.[15] [17] [19] The proband's father had an IRBBB, borderline QTc (456-463 ms) with an atypical T wave morphology. Unlike their daughter, they had no structural cardiovascular abnormalities. "
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    ABSTRACT: Objective Patients with inherited long QT syndrome (LQTS) are prone to torsade de pointes and sudden death (SD). Identifying affected individuals is important for SD prevention. This study aimed to determine the cause and genotype-phenotype characteristics of LQTS in a large Omani family. Methods Upon LQTS diagnosis of a 5-year-old girl (proband), targeted mutation screening was performed based on the gene-specific ECG pattern identified in her mother. ECG-guided family genotyping was conducted for identifying additional affected individuals. Results ECGs of the proband demonstrated 2:1 AV block, incomplete right bundle branch block (IRBBB) and markedly prolonged QTc (571-638 ms) with bizarre T waves. Cardiac imaging revealed dilatation of the ascending aorta and pulmonary artery, and left ventricular non-compaction. Her parents were first cousins. Both showed mild QT prolongation, with the mother presenting a LQT2 T wave pattern and the father IRBBB. Targeted KCNH2 screening identified a novel homozygous frameshift mutation p.T1019Pfs × 38 in the proband within 72-hour. Family genotyping uncovered 3 concealed LQT2 and confirmed 11 members showing LQT2 ECG patterns as heterozygous mutation carriers. All heterozygous carriers were asymptomatic, with 71% showing normal to borderline prolonged QTc (458 ± 33 ms, range 409-522 ms). Conclusion p.T1019Pfs × 38, a novel KCNH2 mutation, has been identified in a large LQTS family in Oman. Consanguineous marriages resulted in a homozygous with severe LQTS. ECG-guided phenotyping and genotyping achieved a high efficiency. Genetic testing is essential in identifying concealed LQTS. Further investigation is warranted to determine if there is a causative relationship between homozygous p.T1019Pfs × 38 and cardiovascular anomaly.
    07/2014; 4. DOI:10.1016/j.ijchv.2014.06.001
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    • "Using T peak –T end and QT interval dispersion in the same population, Yamaguchi et al. (2003) opined that the former rather than the latter better predicts TdP. Zhang et al. (2000) showed that typical ST–T wave patterns are found in most genotyped long QT syndrome. These patterns may be used to identify LQT1, LQT2, and possibly LQT3 genotypes. "
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    ABSTRACT: A recent publication asserted that even low-dose risperidone may induce corrected QT (QTc) interval prolongation up to 500 ms without drug-induced IKr blockade. We seek to better understand the complexity of any link between risperidone-induced/associated QTc interval prolongation and torsade de pointes (TdP). The objective of this study is to systematically analyze all available case reports of risperidone, QTc interval prolongation, and/or TdP. We identify case reports using PubMed, Medline, EMBASE, and Cochrane. Of the 15 cases found, nine were adult women (ages 31, 33, 34, 37, 47, "elderly", 77, 84, and 87 years) and one was a teenager. There were four men (ages 28, 29, 29, and 46 years) and one preadolescent boy. Besides risperidone administration or overdose, traditional risk factors for QTc interval prolongation and TdP included female sex (n = 10), older age (n = 4), heart disease (n = 3), hypokalemia (n = 2), bradycardia (n = 1), liver disease (n = 1), QTc interval prolonging drugs other than risperidone (n = 8), and metabolic inhibitors (n = 2). TdP occurred in four cases. Six patients died, and three deaths were probably related to TdP. Risperidone (when properly prescribed in patients free of other risk factors for QTc interval prolongation and TdP) is a relatively safe drug. Conventional statistics can neither predict the individual patient who will experience TdP nor determine the relationship of drug dose to QTc interval prolongation and TdP. Narrative medicine using a case report format appears to be an alternative and valuable additional approach to advance our understanding of this relationship and to reduce risks.
    Psychopharmacology 06/2013; DOI:10.1007/s00213-013-3192-8 · 3.99 Impact Factor
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    • "The diagnostic criteria for LQTS are better defined than those of SQTS, in part because LQTS was identified first. There are some genotype-specific correlations that characterize the three most common variants of congenital LQTS (LQT1, LQT2, and LQT3): i.e. peculiar T-wave morphology, different factors triggering syncope, varying efficiencies of anti-arrhythmic drugs and different risks for SCD (Zareba, 2006; Zhang et al., 2000). As illustrated in Fig. 4, ECGs of LQT1 and LQT2 patients have often broad-based, prolonged or low amplitude T waves. "
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    ABSTRACT: Channelopathies are diseases caused by dysfunctional ion channels, due to either genetic or acquired pathological factors. Inherited cardiac arrhythmic syndromes are among the most studied human disorders involving ion channels. Since seminal observations made in 1995, thousands of mutations have been found in many of the different genes that code for cardiac ion channel subunits and proteins that regulate the cardiac ion channels. The main phenotypes observed in patients carrying these mutations are congenital long QT syndrome (LQTS), Brugada syndrome (BrS), catecholaminergic polymorphic ventricular tachycardia (CPVT), short QT syndrome (SQTS) and variable types of conduction defects (CD). The goal of this review is to present an update of the main genetic and molecular mechanisms, as well as the associated phenotypes of cardiac channelopathies as of 2012.
    Gene 12/2012; 517(1). DOI:10.1016/j.gene.2012.12.061 · 2.08 Impact Factor
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