Significance of QT dispersion in the long QT syndrome

The long QT syndrome (LQTS) has often been considered as a model to study the abnormalities of cardiac repolarization in humans because it represents a pure electrical disease with no evidence of cardiac structural abnormalities. The arrhythmogenic potential of prolonged ventricular repolarization has been extensively studied both in experimental models and at the clinical level in LQTS patients, and many studies pointed to the pathogenetic role of the dispersion of ventricular recovery times (i.e., dispersion of ventricular repolarization). In the last few years, a new critical knowledge has been achieved thanks to the molecular biology techniques that are unveiling the genetic bases of LQTS. Indeed, the understanding of the genes and mutations that may cause the LQTS opened the way to understanding the molecular determinants of the altered ventricular repolarization that can be found in LQTS patients. From the clinical standpoint, the traditional tools applied for the detection and quantification of the dispersion of ventricular repolarization (monophasic action potential, QT dispersion) showed their effectiveness but also their limitations. More recently, the availability of new algorithms and the development of powerful computerized supports allowed the evaluation of innovative techniques, which now represent possible attractive alternatives intended to quantify the degree of repolarization abnormalities in LQTS patients and possibly to noninvasively quantify the risk of cardiac events.     

"Benign" course and malignant clinical presentations of congenital long QT syndrome.

This report describes the "benign" clinical course of a congenital long QT syndrome (LQTS) simulated acute coronary event in an 85 year old woman who had a history of recurrent syncope accompanied by numerous severe traumatic events from childhood. Her daughter died suddenly. LQTS was diagnosed on the basis of characteristic ECG findings, including a permanently prolonged QT interval, typical dynamic T-wave changes, and runs of torsades de pointes. A permanent DDDR pacemaker was implanted. Eighteen months after implantation there have been no further complaints of dizziness or syncope.     

"Critical interval of the dispersion of refractoriness" in the pathogenesis of ventricular extrasystole in the long QT syndrome

The reentry mechanism (R.M.) has been demonstrated to be relevant in the genesis of experimental extrasystoles. The extrapolation of these observations to the ventricular extrasystoles (V.E.) observed in clinical situations is still debated. However, the V.E. related to the long QT syndromes have been commonly considered to be caused by R.M. In fact an abnormal prolongation of the repolarization time favors the dispersion of the myocardial recovery time. A critical lengthening of the QT interval has been observed by several Authors to underlie the appearance of V.E. That after a further critical prolongation of the QT the V.E. disappear, has not been so far described. We report a patient with long QT syndrome in whom the ECG demonstrated an extreme variability of the QT interval. The V.E. appeared only when the QT interval was greater than 580 msec, whereas they disappeared when the QT interval was greater than 660 msec. Thus, a critical interval of refractoriness dispersion (C.I.R.D.) between 580 and 660 msec was established. We suggest that in our case the V.E. were probably due to R.M., caused by regional lengthening of the repolarization; a further prolongation of repolarization time probably induced either an antegrade block in both limbs of the circuit or a retrograde block in the reentry pathway and consequently the abolition of R.M. The identification of a C.I.R.D. suggest a possible R.M. in the pathogenesis of clinical ventricular extrasystoles.     

短QT间期与短QT综合征

QT间期指体表心电图QRS波起点至T波终点的时间间隔,代表心室除极和复极的总时间,是心室电兴奋过程的标志.QT间期受心率影响大,生理状态下,心率快时QT间期短,心率慢时QT间期长.心率在60～100次/min时,QT间期的正常范围为0.44～0.32 s.影响心室电兴奋过程的各种生理和病理因素均可引起QT间期缩短.短QT指QT间期短于正常范围.     

The Effects of Intravenous Levofloxacin on the QT Interval and QT Dispersion

The QT dispersion (QT_d) is a non-invasive means of identifying those patients at an increased risk of developing sudden cardiac death (SCD). Although levofloxacin has a minimal effect on the QT_c interval, isolated reports of QT prolongation, polymorphic ventricular tachycardia with a normal QT interval and TdP have been reported. The purpose of this study was to examine the effect of intravenous levofloxacin on the QT interval and QT_d. Of the 50 patients who were deemed candidates to receive intravenous levofloxacin, 29 met the eligibility criteria and were enrolled in this study. A 12-lead ECG was performed before the initiation of levofloxacin (baseline), and on days 3 and 5. The QT^c _min, QT^c _max and the QT_d were calculated. Measurements where made by two independent observers blinded to the patients’ clinical status. The QT_d increased significantly on days 3 and 5 following the initiation of therapy [QT_d (baseline) 33.3 ± 20 ms, QT_d (day 3) 64.4 ± 31.3 ms (p = 0.023), QT_d (day 5) 66.8 ± 20.3 ms, (p = 0.008)]. The increase in the QT_d was significantly longer in men than women. Although women had a shorter baseline QT_d compared to men, this did not achieve statistical significance. Intravenous levofloxacin was found to significantly increase the QT_d, which was more pronounced in men compared to women. Its effect on the QT_d may increase the risk of developing a potentially fatal ventricular arrhythmia. Therefore, care must be taken when prescribing this medication to patients with a pre-existing risk of developing SCD.     

Automated versus Manual Measurement of the QT Interval and Corrected QT Interval

Background: The International Conference on Harmonization E14 Guideline specifies detailed assessment of QT interval or corrected QT interval prolongation when developing new drugs. We recently devised new software to precisely measure the QT interval. Methods and Results: The QT intervals of all leads for a selected single heart beat were compared between automated measurement with the new software from Fukuda Denshi and manual measurement. With both automated and manual measurement, QT intervals obtained by the tangent method were shorter than those obtained by the differential threshold method, but the extent of correction was smaller. QT interval data obtained by the differential threshold method were more similar to values obtained by visual measurement than were data obtained by the tangent method, but the extent of correction was larger. Variability was related to the T‐wave amplitude and to setting the baseline and tangent in the tangent method, while skeletal muscle potential noise affected the differential threshold method. Drift, low‐amplitude recordings, and T‐wave morphology were problems for both methods. Among the 12 leads, corrections were less frequent for leads II and V₃–V₆. Conclusion: We conclude that, for a thorough assessment of the QT/QTc interval, the tangent method or the differential threshold method appears to be suitable because of smaller interreader differences and better reproducibility. Correction of data should be done by readers who are experienced in measuring the QT interval. It is also important for electrocardiograms to have little noise and for a suitable heart rate and appropriate leads to be selected. Ann Noninvasive Electrocardiol 2011;16(2):156–164     

先天性长QT综合征的QT间期不均一性:诊断上的意义

目的 通过分析QTc间期在长QT综合征（longQTsyndrome,LQTS)家系患者中的分布状况,评估QTc值在诊断LQTS上的意义。方法 研究对象为KVLQT1和HERG基因突变形成的LQT1和LQT2基因型患者,研究24个LQTS家系中374个成员的QTc值,包括181个基因携带者（83个KVLQT1和98个HERG）和193个非基因携带者,基因携带者中男性88人,女性93人;非基因携带者中男性97人,女性96人。将QTc的分布制成图表并按基因型进行比较,计算QTc值诊断LQTS的敏感性和特异性97人,女性96人。将QTc患者的QTc范围为0.41-0.62s,非基因携带者为0.36-0.47s。当女性QTc≥0.48s,男性QTc≥0.47s时可诊断为LQTS,相反,当女性QTc≤0.41s,男性≤0.40s时可排除LQTS。QTc值在0.42s至0.46s之间者,需要进一步检查来确诊。结论 LQT1和LQT2基因携带者QTc值范围较宽,使QTc值正常和临界的基因携带者在诊断上较为困难,对这类患者诊断时应特别注意。     

Corrected QT variability in serial electrocardiograms in long QT syndrome: the importance of the maximum corrected QT for risk stratification.

OBJECTIVES: We evaluated the incremental prognostic information provided by multiple corrected QT (QTc) measurements on serial electrocardiograms (ECGs) in patients with the inherited long QT syndrome (LQTS). BACKGROUND: A baseline QTc of > or =500 ms has been shown to be associated with increased risk of cardiac events among LQTS patients. However, the value of QTc measurements on follow-up ECGs in risk assessment has not been determined. METHODS: The risk of a first LQTS-related cardiac event during adolescence was assessed in 375 patients enrolled in the International LQTS Registry for whom serial follow-up ECGs were recorded before age 10. RESULTS: The mean +/- SD difference between the minimum and maximum QTc values on serial ECGs recorded in study patients was 47 +/- 40 ms. The maximum QTc interval recorded before age 10 was the strongest predictor of cardiac events during adolescence (adjusted hazard ratio [HR] = 2.74; p < 0.001). Other follow-up QTc measures, including the baseline, the mean, and the most recent QTc interval recorded before age 10, were less significant risk factors. After adjusting for the maximum QTc value during follow-up, no significant association remained between the baseline QTc value and the risk of subsequent cardiac events (HR = 1.04; p = 0.91). CONCLUSIONS: In LQTS patients, there is a considerable variability in QTc measures in serial follow-up ECGs. The maximum QTc interval provides incremental prognostic information beyond the baseline measurement. We suggest that risk stratification in LQTS patients should include follow-up ECG data.     

QT dispersion and components of the QT interval in ischaemia and infarction.

OBJECTIVE--To evaluate changes in QT dispersion and components of the QT interval in patients admitted with unstable angina and acute myocardial infarction and to study the dynamics of these changes in patients with infarction. METHODS--Prospective study recording electrocardiograms at 50 mm/s in patients admitted with typical cardiac chest pain. Subsequent confirmation of acute myocardial infarction according to standard criteria. Single blind analysis for QT dispersion and QT components using a digitiser and simple computer program. Results are expressed as native QT dispersion, QTc dispersion, and the QT dispersion ratio defined as QT dispersion divided by cycle length and expressed as a percentage. RESULTS--QT dispersion, QTc dispersion, and QT dispersion ratio were all higher in patients with acute myocardial infarction than in those with unstable angina (mean (SD) 66 (18) ms, 75 (26) ms1/2, and 8.1 (2.4)% compared with 38 (13) ms, 39 (13) ms1/2, and 4.5 (1.7) % respectively). Dynamic changes in QTc dispersion were seen after acute infarction with significant differences in the QT components occurring between the different patient groups. Levels of QT dispersion (87 (15) ms), QTc dispersion (105 (17) ms1/2), and QT dispersion ratio (11.7 (0.8)%) in the four patients with ventricular fibrillation were significantly higher. Use of QT dispersion ratio gave a narrower confidence interval. CONCLUSION--QT dispersion is increased after myocardial infarction and levels are higher in patients with ventricular fibrillation. The changes in QT dispersion are dynamic and may reflect the changing pattern of underlying ventricular recovery of ventricular excitability, which is profoundly disturbed in the earliest phase of acute infarction. Expressing QT dispersion as a percentage of cycle length (QT dispersion ratio) rather than using standard rate correction may be superior in identifying patients who develop ventricular fibrillation.